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Parkinson’s disease

Parkinson’s disease
Classification and external resources
Two sketches (one from the front and one from the right side) of a man, with an expressionless face. He is stooped forward and is presumably having difficulty walking.
Illustration of Parkinson’s disease by William Richard Gowers, which was first published in A Manual of Diseases of the Nervous System (1886)
ICD-10 G20, F02.3
ICD-9 332
OMIM 168600 556500
DiseasesDB 9651
MedlinePlus 000755
eMedicine neuro/304 neuro/635 in young
pmr/99 rehab
GeneReviews Parkinson Disease Overview

Parkinson’s disease (also known as Parkinson disease, Parkinson’s, idiopathic parkinsonism, primary parkinsonism, PD, or paralysis agitans) is a degenerative disorder of the central nervous system. It results from the death of dopamine-generating cells in the substantia nigra, a region of the midbrain; the cause of cell-death is unknown. Early in the course of the disease, the most obvious symptoms are movement-related, including shaking, rigidity, slowness of movement and difficulty with walking and gait. Later, cognitive and behavioural problems may arise, with dementia commonly occurring in the advanced stages of the disease. Other symptoms include sensory, sleep and emotional problems. PD is more common in the elderly with most cases occurring after the age of 50.

The main motor symptoms are collectively called parkinsonism, or a “parkinsonian syndrome”. Parkinson’s disease is often defined as a parkinsonian syndrome that is idiopathic (having no known cause), although some atypical cases have a genetic origin. Many risk and protective factors have been investigated: the clearest evidence is for an increased risk of PD in people exposed to certain pesticides and a reduced risk in tobacco smokers. The pathology of the disease is characterized by the accumulation of a protein called alpha-synuclein into inclusions called Lewy bodies in neurons, and from insufficient formation and activity of dopamine produced in certain neurons within parts of the midbrain. Diagnosis of typical cases is mainly based on symptoms, with tests such as neuroimaging being used for confirmation.

Modern treatments are effective at managing the early motor symptoms of the disease, mainly through the use of levodopa and dopamine agonists. As the disease progresses and dopamine neurons continue to be lost, a point eventually arrives at which these drugs become ineffective at treating the symptoms and at the same time produce a complication called dyskinesia, marked by involuntary writhing movements. Diet and some forms of rehabilitation have shown some effectiveness at alleviating symptoms. Surgery and deep brain stimulation have been used to reduce motor symptoms as a last resort in severe cases where drugs are ineffective. Research directions include a search of new animal models of the disease and investigations of the potential usefulness of gene therapy, stem cell transplants and neuroprotective agents. Medications to treat non-movement-related symptoms of PD, such as sleep disturbances and emotional problems, also exist.

The disease is named after the English doctor James Parkinson, who published the first detailed description in An Essay on the Shaking Palsy in 1817. Several major organizations promote research and improvement of quality of life of those with the disease and their families. Public awareness campaigns include Parkinson’s disease day on the birthday of James Parkinson, April 11, and the use of a red tulip as the symbol of the disease. People with parkinsonism who have enhanced the public’s awareness include Michael J. Fox and Muhammad Ali.



The term parkinsonism is used for a motor syndrome whose main symptoms are tremor at rest, stiffness, slowing of movement and postural instability. Parkinsonian syndromes can be divided into four subtypes according to their origin: primary or idiopathic, secondary or acquired, hereditary parkinsonism, and parkinson plus syndromes or multiple system degeneration.[1] Parkinson’s disease is the most common form of parkinsonism and is usually defined as “primary” parkinsonism, meaning parkinsonism with no external identifiable cause.[2][3] In recent years several genes that are directly related to some cases of Parkinson’s disease have been discovered. As much as this can go against the definition of Parkinson’s disease as an idiopathic illness, genetic parkinsonism disorders with a similar clinical course to PD are generally included under the Parkinson’s disease label. The terms “familial Parkinson’s disease” and “sporadic Parkinson’s disease” can be used to differentiate genetic from truly idiopathic forms of the disease.[4]

PD is usually classified as a movement disorder, although it also gives rise to several non-motor types of symptoms such as sensory deficits,[5] cognitive difficulties or sleep problems. Parkinson plus diseases are primary parkinsonisms which present additional features.[2] They include multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and dementia with Lewy bodies.[2]

In terms of pathophysiology, PD is considered a synucleinopathy due to an abnormal accumulation of alpha-synuclein protein in the brain in the form of Lewy bodies, as opposed to other diseases such as Alzheimer’s disease where the brain accumulates tau protein in the form of neurofibrillary tangles.[6] Nevertheless, there is clinical and pathological overlap between tauopathies and synucleinopathies. The most typical symptom of Alzheimer’s disease, dementia, occurs in advanced stages of PD, while it is common to find neurofibrillary tangles in brains affected by PD.[6]

Dementia with Lewy bodies (DLB) is another synucleinopathy that has similarities with PD, and especially with the subset of PD cases with dementia. However the relationship between PD and DLB is complex and still has to be clarified.[7] They may represent parts of a continuum or they may be separate diseases.[7]

Signs and symptoms

First line of text is "Catherine Metzger" Second line of text is "13 Octobre 1869" (October 13th of 1869; in French).

Handwriting of a person affected by PD in Lectures on the diseases of the nervous system by Charcot (1879). The original description of the text states “The strokes forming the letters are very irregular and sinuous, whilst the irregularities and sinuosities are of a very limited width. (…) the down-strokes are all, with the exception of the first letter, made with comparative firmness and are, in fact, nearly normal — the finer up-strokes, on the contrary, are all tremulous in appearance (…).”

Parkinson’s disease affects movement, producing motor symptoms.[1] Non-motor symptoms, which include autonomic dysfunction, neuropsychiatric problems (mood, cognition, behavior or thought alterations), and sensory and sleep difficulties, are also common.[1]


Black and white picture of male with PD stooping forward as he walks. He is viewed from the left side and there is a chair behind him.

A man with Parkinson’s disease displaying a flexed walking posture pictured in 1892. Photo appeared in Nouvelle Iconographie de la Salpètrière, vol. 5.

Further information: Parkinsonian gait

Four motor symptoms are considered cardinal in PD: tremor, rigidity, slowness of movement, and postural instability.[1]

Tremor is the most apparent and well-known symptom.[1] It is the most common; though around 30% of individuals with PD do not have tremor at disease onset, most develop it as the disease progresses.[1] It is usually a rest tremor: maximal when the limb is at rest and disappearing with voluntary movement and sleep.[1] It affects to a greater extent the most distal part of the limb and at onset typically appears in only a single arm or leg, becoming bilateral later.[1] Frequency of PD tremor is between 4 and 6 hertz (cycles per second). A feature of tremor is “pill-rolling”, a term used to describe the tendency of the index finger of the hand to get into contact with the thumb and perform together a circular movement.[1][8] The term derives from the similarity between the movement in PD patients and the earlier pharmaceutical technique of manually making pills.[8]

Bradykinesia (slowness of movement) is another characteristic feature of PD, and is associated with difficulties along the whole course of the movement process, from planning to initiation and finally execution of a movement.[1] Performance of sequential and simultaneous movement is hindered.[1] Bradykinesia is the most disabling symptom in the early stages of the disease.[2] Initial manifestations are problems when performing daily tasks which require fine motor control such as writing, sewing or getting dressed.[1] Clinical evaluation is based in similar tasks such as alternating movements between both hands or both feet.[2] Bradykinesia is not equal for all movements or times. It is modified by the activity or emotional state of the subject, to the point that some patients are barely able to walk yet can still ride a bicycle.[1] Generally patients have less difficulty when some sort of external cue is provided.[1][9]

Rigidity is stiffness and resistance to limb movement caused by increased muscle tone, an excessive and continuous contraction of muscles.[1] In parkinsonism the rigidity can be uniform (lead-pipe rigidity) or ratchety (cogwheel rigidity).[1][2][10][11] The combination of tremor and increased tone is considered to be at the origin of cogwheel rigidity.[12] Rigidity may be associated with joint pain; such pain being a frequent initial manifestation of the disease.[1] In early stages of Parkinson’s disease, rigidity is often asymmetrical and it tends to affect the neck and shoulder muscles prior to the muscles of the face and extremities.[13] With the progression of the disease, rigidity typically affects the whole body and reduces the ability to move.

Postural instability is typical in the late stages of the disease, leading to impaired balance and frequent falls, and secondarily to bone fractures.[1] Instability is often absent in the initial stages, especially in younger people.[2] Up to 40% of the patients may experience falls and around 10% may have falls weekly, with number of falls being related to the severity of PD.[1]

Other recognized motor signs and symptoms include gait and posture disturbances such as festination (rapid shuffling steps and a forward-flexed posture when walking),[1] speech and swallowing disturbances including voice disorders,[14] mask-like face expression or small handwriting, although the range of possible motor problems that can appear is large.[1]


Parkinson’s disease can cause neuropsychiatric disturbances which can range from mild to severe. This includes disorders of speech, cognition, mood, behaviour, and thought.[1]

Cognitive disturbances can occur in the initial stages of the disease and sometimes prior to diagnosis, and increase in prevalence with duration of the disease.[1][15] The most common cognitive deficit in affected individuals is executive dysfunction, which can include problems with planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting relevant sensory information. Fluctuations in attention and slowed cognitive speed are among other cognitive difficulties. Memory is affected, specifically in recalling learned information. Nevertheless, improvement appears when recall is aided by cues. Visuospatial difficulties are also part of the disease, seen for example when the individual is asked to perform tests of facial recognition and perception of the orientation of drawn lines.[15]

A person with PD has two to six times the risk of suffering dementia compared to the general population.[1][15] The prevalence of dementia increases with duration of the disease.[15] Dementia is associated with a reduced quality of life in people with PD and their caregivers, increased mortality, and a higher probability of needing nursing home care.[15]

Behavior and mood alterations are more common in PD without cognitive impairment than in the general population, and are usually present in PD with dementia. The most frequent mood difficulties are depression, apathy and anxiety.[1] Impulse control behaviors such as medication overuse and craving, binge eating, hypersexuality, or pathological gambling can appear in PD and have been related to the medications used to manage the disease.[1][16] Psychotic symptoms—hallucinations or delusions—occur in 4% of patients, and it is assumed that the main precipitant of psychotic phenomena in Parkinson’s disease is dopaminergic excess secondary to treatment; it therefore becomes more common with increasing age and levodopa intake.[17][18]


In addition to cognitive and motor symptoms, PD can impair other body functions. Sleep problems are a feature of the disease and can be worsened by medications.[1] Symptoms can manifest in daytime drowsiness, disturbances in REM sleep, or insomnia.[1] Alterations in the autonomic nervous system can lead to orthostatic hypotension (low blood pressure upon standing), oily skin and excessive sweating, urinary incontinence and altered sexual function.[1] Constipation and gastric dysmotility can be severe enough to cause discomfort and even endanger health.[19] PD is related to several eye and vision abnormalities such as decreased blink rate, dry eyes, deficient ocular pursuit (eye tracking) and saccadic movements (fast automatic movements of both eyes in the same direction), difficulties in directing gaze upward, and blurred or double vision.[1][20] Changes in perception may include an impaired sense of smell, sensation of pain and paresthesia (skin tingling and numbness).[1] All of these symptoms can occur years before diagnosis of the disease.[1]


PDB rendering of Parkin (ligase)

Most people with Parkinson’s disease have idiopathic Parkinson’s disease (having no specific known cause). A small proportion of cases, however, can be attributed to known genetic factors. Other factors have been associated with the risk of developing PD, but no causal relationship has been proven.

PD traditionally has been considered a non-genetic disorder; however, around 15% of individuals with PD have a first-degree relative who has the disease.[2] At least 5% of people are now known to have forms of the disease that occur because of a mutation of one of several specific genes.[21]

Mutations in specific genes have been conclusively shown to cause PD. These genes code for alpha-synuclein (SNCA), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2 or dardarin), PTEN-induced putative kinase 1 (PINK1), DJ-1 and ATP13A2.[4][21] In most cases, people with these mutations will develop PD. With the exception of LRRK2, however, they account for only a small minority of cases of PD.[4] The most extensively studied PD-related genes are SNCA and LRRK2. Mutations in genes including SNCA, LRRK2 and glucocerebrosidase (GBA) have been found to be risk factors for sporadic PD. Mutations in GBA are known to cause Gaucher’s disease.[21] Genome-wide association studies, which search for mutated alleles with low penetrance in sporadic cases, have now yielded many positive results.[22]

The role of the SNCA gene is important in PD because the alpha-synuclein protein is the main component of Lewy bodies.[21] Missense mutations of the gene (in which a single nucleotide is changed), and duplications and triplications of the locus containing it have been found in different groups with familial PD.[21] Missense mutations are rare.[21] On the other hand, multiplications of the SNCA locus account for around 2% of familial cases.[21] Multiplications have been found in asymptomatic carriers, which indicate that penetrance is incomplete or age-dependent.[21]

The LRRK2 gene (PARK8) encodes for a protein called dardarin. The name dardarin was taken from a Basque word for tremor, because this gene was first identified in families from England and the north of Spain.[4] Mutations in LRRK2 are the most common known cause of familial and sporadic PD, accounting for approximately 5% of individuals with a family history of the disease and 3% of sporadic cases.[4][21] There are many different mutations described in LRRK2, however unequivocal proof of causation only exists for a small number.[21]


Several brain cells stained in blue. The largest one, a neurone, with an approximately circular form, has a brown circular body inside it. The brown body is about 40% the diameter of the cell in which it appears.

A Lewy body (stained brown) in a brain cell of the substantia nigra in Parkinson’s disease. The brown colour is positive immunohistochemistry staining for alpha-synuclein.

Anatomical pathology

The basal ganglia, a group of “brain structures” innervated by the dopaminergic system, are the most seriously affected brain areas in PD.[23] The main pathological characteristic of PD is cell death in the substantia nigra and, more specifically, the ventral (front) part of the pars compacta, affecting up to 70% of the cells by the time death occurs.[4]

Macroscopic alterations can be noticed on cut surfaces of the brainstem, where neuronal loss can be inferred from a reduction of melanin pigmentation in the substantia nigra and locus coeruleus.[24] The histopathology (microscopic anatomy) of the substantia nigra and several other brain regions shows neuronal loss and Lewy bodies in many of the remaining nerve cells. Neuronal loss is accompanied by death of astrocytes (star-shaped glial cells) and activation of the microglia (another type of glial cell). Lewy bodies are a key pathological feature of PD.[24]


Composite of three images, one in top row (described in caption as A), two in second row (described in caption as B). Top shows a mid-line sagittal plane of the brainstem and cerebellum. There are three circles superimposed along the brainstem and an arrow linking them from bottom to top and continuing upward and forward towards the frontal lobes of the brain. A line of text accompanies each circle: lower is "1. Dorsal Motor X Nucleus", middle is "2. Gain Setting Nuclei" and upper is "3. Substantia Nigra/Amygdala". A fourth line of text above the others says "4. ...". The two images at the bottom of the composite are magnetic resonance imaging (MRI) scans, one saggital and the other transverse, centred at the same brain coordinates (x=-1, y=-36, z=-49). A colored blob marking volume reduction covers most of the brainstem.

A. Schematic initial progression of Lewy body deposits in the first stages of Parkinson’s disease, as proposed by Braak and colleagues
B. Localization of the area of significant brain volume reduction in initial PD compared with a group of participants without the disease in a neuroimaging study, which concluded that brain stem damage may be the first identifiable stage of PD neuropathology[25]

The primary symptoms of Parkinson’s disease result from greatly reduced activity of dopamine-secreting cells caused by cell death in the pars compacta region of the substantia nigra.[23]

There are five major pathways in the brain connecting other brain areas with the basal ganglia. These are known as the motor, oculo-motor, associative, limbic and orbitofrontal circuits, with names indicating the main projection area of each circuit.[23] All of them are affected in PD, and their disruption explains many of the symptoms of the disease since these circuits are involved in a wide variety of functions including movement, attention and learning.[23] Scientifically, the motor circuit has been examined the most intensively.[23]

A particular conceptual model of the motor circuit and its alteration with PD has been of great influence since 1980, although some limitations have been pointed out which have led to modifications.[23] In this model, the basal ganglia normally exert a constant inhibitory influence on a wide range of motor systems, preventing them from becoming active at inappropriate times. When a decision is made to perform a particular action, inhibition is reduced for the required motor system, thereby releasing it for activation. Dopamine acts to facilitate this release of inhibition, so high levels of dopamine function tend to promote motor activity, while low levels of dopamine function, such as occur in PD, demand greater exertions of effort for any given movement. Thus the net effect of dopamine depletion is to produce hypokinesia, an overall reduction in motor output.[23] Drugs that are used to treat PD, conversely, may produce excessive dopamine activity, allowing motor systems to be activated at inappropriate times and thereby producing dyskinesias.[23]

 Brain cell death

There is speculation of several mechanisms by which the brain cells could be lost.[26] One mechanism consists of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. This insoluble protein accumulates inside neurones forming inclusions called Lewy bodies.[4][27] According to the Braak staging, a classification of the disease based on pathological findings, Lewy bodies first appear in the olfactory bulb, medulla oblongata and pontine tegmentum, with individuals at this stage being asymptomatic. As the disease progresses, Lewy bodies later develop in the substantia nigra, areas of the midbrain and basal forebrain, and in a last step the neocortex.[4] These brain sites are the main places of neuronal degeneration in PD; however, Lewy bodies may not cause cell death and they may be protective.[26][27] In patients with dementia, a generalized presence of Lewy bodies is common in cortical areas. Neurofibrillary tangles and senile plaques, characteristic of Alzheimer’s disease, are not common unless the person is demented.[24]

Other cell-death mechanisms include proteosomal and lysosomal system dysfunction and reduced mitochondrial activity.[26] Iron accumulation in the substantia nigra is typically observed in conjunction with the protein inclusions. It may be related to oxidative stress, protein aggregation and neuronal death, but the mechanisms are not fully understood.[28]


Sagittal PET scan at the level of the striatum. Hottest areas are the cortical grey matter and the striatum.

Fludeoxyglucose (18F) (FDG)] PET scan of a healthy brain. Hotter areas reflect higher glucose uptake. A decreased activity in the basal ganglia can aid in diagnosing Parkinson’s disease.

A physician will diagnose Parkinson’s disease from the medical history and a neurological examination.[1] There is no lab test that will clearly identify the disease, but brain scans are sometimes used to rule out disorders that could give rise to similar symptoms. Patients may be given levodopa and resulting relief of motor impairment tends to confirm diagnosis. The finding of Lewy bodies in the midbrain on autopsy is usually considered proof that the patient suffered from Parkinson’s disease. The progress of the illness over time may reveal it is not Parkinson’s disease, and some authorities recommend that the diagnosis be periodically reviewed.[1][29]

Other causes that can secondarily produce a parkinsonian syndrome are Alzheimer’s disease, multiple cerebral infarction and drug-induced parkinsonism.[29] Parkinson plus syndromes such as progressive supranuclear palsy and multiple system atrophy must be ruled out.[1] Anti-Parkinson’s medications are typically less effective at controlling symptoms in Parkinson plus syndromes.[1] Faster progression rates, early cognitive dysfunction or postural instability, minimal tremor or symmetry at onset may indicate a Parkinson plus disease rather than PD itself.[30] Genetic forms are usually classified as PD, although the terms familial Parkinson’s disease and familial parkinsonism are used for disease entities with an autosomal dominant or recessive pattern of inheritance.[2]

Medical organizations have created diagnostic criteria to ease and standardize the diagnostic process, especially in the early stages of the disease. The most widely known criteria come from the UK Parkinson’s Disease Society Brain Bank and the US National Institute of Neurological Disorders and Stroke.[1] The PD Society Brain Bank criteria require slowness of movement (bradykinesia) plus either rigidity, resting tremor, or postural instability. Other possible causes for these symptoms need to be ruled out. Finally, three or more of the following features are required during onset or evolution: unilateral onset, tremor at rest, progression in time, asymmetry of motor symptoms, response to levodopa for at least five years, clinical course of at least ten years and appearance of dyskinesias induced by the intake of excessive levodopa.[1] Accuracy of diagnostic criteria evaluated at autopsy is 75–90%, with specialists such as neurologists having the highest rates.[1]

Computed tomography (CT) and magnetic resonance imaging (MRI) brain scans of people with PD usually appear normal.[31] These techniques are nevertheless useful to rule out other diseases that can be secondary causes of parkinsonism, such as basal ganglia tumors, vascular pathology and hydrocephalus.[31] A specific technique of MRI, diffusion MRI, has been reported to be useful at discriminating between typical and atypical parkinsonism, although its exact diagnostic value is still under investigation.[31] Dopaminergic function in the basal ganglia can be measured with different PET and SPECT radiotracers. Examples are ioflupane (123I) (trade name DaTSCAN) and iometopane (Dopascan) for SPECT or fludeoxyglucose (18F) for PET.[31] A pattern of reduced dopaminergic activity in the basal ganglia can aid in diagnosing PD.[31]



There is no cure for Parkinson’s disease, but medications, surgery and multidisciplinary management can provide relief from the symptoms. The main families of drugs useful for treating motor symptoms are levodopa (usually combined with a dopa decarboxylase inhibitor or COMT inhibitor), dopamine agonists and MAO-B inhibitors.[32] The stage of the disease determines which group is most useful. Two stages are usually distinguished: an initial stage in which the individual with PD has already developed some disability for which he needs pharmacological treatment, then a second stage in which an individual develops motor complications related to levodopa usage.[32] Treatment in the initial stage aims for an optimal tradeoff between good symptom control and side-effects resulting from enhancement of dopaminergic function. The start of levodopa (or L-DOPA) treatment may be delayed by using other medications such as MAO-B inhibitors and dopamine agonists, in the hope of delaying the onset of dyskinesias.[32] In the second stage the aim is to reduce symptoms while controlling fluctuations of the response to medication. Sudden withdrawals from medication or overuse have to be managed.[32] When medications are not enough to control symptoms, surgery and deep brain stimulation can be of use.[33] In the final stages of the disease, palliative care is provided to enhance quality of life.[34]


Levodopa has been the most widely used treatment for over 30 years.[32] L-DOPA is converted into dopamine in the dopaminergic neurons by dopa decarboxylase.[32] Since motor symptoms are produced by a lack of dopamine in the substantia nigra, the administration of L-DOPA temporarily diminishes the motor symptoms.[32]

Only 5–10% of L-DOPA crosses the blood-brain barrier. The remainder is often metabolized to dopamine elsewhere, causing a variety of side effects including nausea, dyskinesias and joint stiffness.[32] Carbidopa and benserazide are peripheral dopa decarboxylase inhibitors,[32] which help to prevent the metabolism of L-DOPA before it reaches the dopaminergic neurons, therefore reducing side effects and increasing bioavailability. They are generally given as combination preparations with levodopa.[32] Existing preparations are carbidopa/levodopa (co-careldopa) and benserazide/levodopa (co-beneldopa). Levodopa has been related to dopamine dysregulation syndrome, which is a compulsive overuse of the medication, and punding.[16] There are controlled release versions of levodopa in the form intravenous and intestinal infusions that spread out the effect of the medication. These slow-release levodopa preparations have not shown an increased control of motor symptoms or motor complications when compared to immediate release preparations.[32][35]

Tolcapone inhibits the COMT enzyme, which degrades dopamine, thereby prolonging the effects of levodopa.[32] It has been used to complement levodopa; however, its usefulness is limited by possible side effects such as liver damage.[32] A similarly effective drug, entacapone, has not been shown to cause significant alterations of liver function.[32] Licensed preparations of entacapone contain entacapone alone or in combination with carbidopa and levodopa.[32]

Levodopa preparations lead in the long term to the development of motor complications characterized by involuntary movements called dyskinesias and fluctuations in the response to medication.[32] When this occurs a person with PD can change from phases with good response to medication and few symptoms (“on” state), to phases with no response to medication and significant motor symptoms (“off” state).[32] For this reason, levodopa doses are kept as low as possible while maintaining functionality.[32] Delaying the initiation of therapy with levodopa by using alternatives (dopamine agonists and MAO-B inhibitors) is common practice.[32] A former strategy to reduce motor complications was to withdraw L-DOPA medication for some time. This is discouraged now, since it can bring dangerous side effects such as neuroleptic malignant syndrome.[32] Most people with PD will eventually need levodopa and later develop motor side effects.[32]

 Dopamine agonists

Several dopamine agonists that bind to dopaminergic post-synaptic receptors in the brain have similar effects to levodopa.[32] These were initially used for individuals experiencing on-off fluctuations and dyskinesias as a complementary therapy to levodopa; they are now mainly used on their own as an initial therapy for motor symptoms with the aim of delaying motor complications.[32][36] When used in late PD they are useful at reducing the off periods.[32] Dopamine agonists include bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine and lisuride.

Dopamine agonists produce significant, although usually mild, side effects including drowsiness, hallucinations, insomnia, nausea and constipation.[32] Sometimes side effects appear even at a minimal clinically effective dose, leading the physician to search for a different drug.[32] Compared with levodopa, dopamine agonists may delay motor complications of medication use but are less effective at controlling symptoms.[32] Nevertheless, they are usually effective enough to manage symptoms in the initial years.[2] They tend to be more expensive than levodopa.[2] Dyskinesias due to dopamine agonists are rare in younger people who have PD, but along with other side effects, become more common with age at onset.[2] Thus dopamine agonists are the preferred initial treatment for earlier onset, as opposed to levodopa in later onset.[2] Agonists have been related to a impulse control disorders (such as compulsive sexual activity and eating, and pathological gambling and shopping) even more strongly than levodopa.[16]

Apomorphine, a non-orally administered dopamine agonist, may be used to reduce off periods and dyskinesia in late PD.[32] It is administered by intermittent injections or continuous subcutaneous infusions.[32] Since secondary effects such as confusion and hallucinations are common, individuals receiving apomorphine treatment should be closely monitored.[32] Two dopamine agonists that are administered through skin patches (lisuride and rotigotine) have been recently found to be useful for patients in initial stages and preliminary positive results has been published on the control of off states in patients in the advanced state.[35]

 MAO-B inhibitors

MAO-B inhibitors (selegiline and rasagiline) increase the level of dopamine in the basal ganglia by blocking its metabolism. They inhibit monoamine oxidase-B (MAO-B) which breaks down dopamine secreted by the dopaminergic neurons. The reduction in MAO-B activity results in increased L-DOPA in the striatum.[32] Like dopamine agonists, MAO-B inhibitors used as monotherapy improve motor symptoms and delay the need for levodopa in early disease, but produce more adverse effects and are less effective than levodopa. There are few studies of their effectiveness in the advanced stage, although results suggest that they are useful to reduce fluctuations between on and off periods.[32] An initial study indicated that selegiline in combination with levodopa increased the risk of death, but this was later disproven.[32]

 Other drugs

Other drugs such as amantadine and anticholinergics may be useful as treatment of motor symptoms. However, the evidence supporting them lacks quality, so they are not first choice treatments.[32] In addition to motor symptoms, PD is accompanied by a diverse range of symptoms. A number of drugs have been used to treat some of these problems.[37] Examples are the use of clozapine for psychosis, cholinesterase inhibitors for dementia, and modafinil for daytime sleepiness.[37][38] A 2010 meta-analysis found that non-steroidal anti-inflammatory drugs (apart from acetaminophen and aspirin), have been associated with at least a 15 percent (higher in long-term and regular users) reduction of incidence of the development of Parkinson’s disease.[39]

Surgery and deep brain stimulation

Placement of an electrode into the brain. The head is stabilised in a frame for stereotactic surgery.

Treating motor symptoms with surgery was once a common practice, but since the discovery of levodopa, the number of operations declined.[40] Studies in the past few decades have led to great improvements in surgical techniques, so that surgery is again being used in people with advanced PD for whom drug therapy is no longer sufficient.[40] Surgery for PD can be divided in two main groups: lesional and deep brain stimulation (DBS). Target areas for DBS or lesions include the thalamus, the globus pallidus or the subthalamic nucleus.[40] Deep brain stimulation (DBS) is the most commonly used surgical treatment. It involves the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain. DBS is recommended for people who have PD who suffer from motor fluctuations and tremor inadequately controlled by medication, or to those who are intolerant to medication, as long as they do not have severe neuropsychiatric problems.[33] Other, less common, surgical therapies involve the formation of lesions in specific subcortical areas (a technique known as pallidotomy in the case of the lesion being produced in the globus pallidus).[40]


There is some evidence that speech or mobility problems can improve with rehabilitation, although studies are scarce and of low quality.[41][42] Regular physical exercise with or without physiotherapy can be beneficial to maintain and improve mobility, flexibility, strength, gait speed, and quality of life.[42] However, when an exercise program is performed under the supervision of a physiotherapist, there are more improvements in motor symptoms, mental and emotional functions, daily living activities, and quality of life compared to a self-supervised exercise program at home.[43] In terms of improving flexibility and range of motion for patients experiencing rigidity, generalized relaxation techniques such as gentle rocking have been found to decrease excessive muscle tension. Other effective techniques to promote relaxation include slow rotational movements of the extremities and trunk, rhythmic initiation, diaphragmatic breathing, and meditation techniques.[44] As for gait and addressing the challenges associated with the disease such as hypokinesia (slowness of movement), shuffling and decreased arm swing; physiotherapists have a variety of strategies to improve functional mobility and safety. Areas of interest with respect to gait during rehabilitation programs focus on but are not limited to improving gait speed, base of support, stride length, trunk and arm swing movement. Strategies include utilizing assistive equipment (pole walking and treadmill walking), verbal cueing (manual, visual and auditory), exercises (marching and PNF patterns) and altering environments (surfaces, inputs, open vs. closed).[45] Strengthening exercises have shown improvements in strength and motor function for patients with primary muscular weakness and weakness related to inactivity with mild to moderate Parkinson’s disease. However, reports show a significant interaction between strength and the time the medications was taken. Therefore, it is recommended that patients should perform exercises 45 minutes to one hour after medications, when the patient is at their best.[46] Also, due to the forward flexed posture, and respiratory dysfunctions in advanced Parkinson’s disease, deep diaphragmatic breathing exercises are beneficial in improving chest wall mobility and vital capacity.[47] Exercise may improve constipation.[19]

One of the most widely practiced treatments for speech disorders associated with Parkinson’s disease is the Lee Silverman voice treatment (LSVT).[41][48] Speech therapy and specifically LSVT may improve speech.[41] Occupational therapy (OT) aims to promote health and quality of life by helping people with the disease to participate in as many of their daily living activities as possible.[41] There have been few studies on the effectiveness of OT and their quality is poor, although there is some indication that it may improve motor skills and quality of life for the duration of the therapy.[41][49]


Muscles and nerves that control the digestive process may be affected by PD, resulting in constipation and gastroparesis (food remaining in the stomach for a longer period of time than normal).[19] A balanced diet, based on periodical nutritional assessments, is recommended and should be designed to avoid weight loss or gain and minimize consequences of gastrointestinal dysfunction.[19] As the disease advances, swallowing difficulties (dysphagia) may appear. In such cases it may be helpful to use thickening agents for liquid intake and an upright posture when eating, both measures reducing the risk of choking. Gastrostomy to deliver food directly into the stomach is possible in severe cases.[19]

Levodopa and proteins use the same transportation system in the intestine and the blood-brain barrier, thereby competing for access.[19] When they are taken together, this results in a reduced effectiveness of the drug.[19] Therefore, when levodopa is introduced, excessive protein consumption is discouraged and well balanced Mediterranean diet is recommended. In advanced stages, additional intake of low-protein products such as bread or pasta is recommended for similar reasons.[19] To minimize interaction with proteins, levodopa should be taken 30 minutes before meals.[19] At the same time, regimens for PD restrict proteins during breakfast and lunch, allowing protein intake in the evening.[19]

Palliative care

Palliative care is often required in the final stages of the disease when all other treatment strategies have become ineffective. The aim of palliative care is to maximize the quality of life for the person with the disease and those surrounding him or her. Some central issues of palliative care are: care in the community while adequate care can be given there, reducing or withdrawing drug intake to reduce drug side effects, preventing pressure ulcers by management of pressure areas of inactive patients, and facilitating end-of-life decisions for the patient as well as involved friends and relatives.[34]

 Other treatments

Repetitive transcranial magnetic stimulation temporarily improves levodopa-induced dyskinesias.[50] Its usefulness in PD is an open research topic,[51] although recent studies have shown no effect by rTMS.[52] Several nutrients have been proposed as possible treatments; however there is no evidence that vitamins or food additives improve symptoms.[53] There is no evidence to substantiate that acupuncture and practice of Qigong, or T’ai chi, have any effect on the course of the disease or symptoms. Further research on the viability of Tai chi for balance or motor skills are necessary.[54][55][56] Fava beans and velvet beans are natural sources of levodopa and are eaten by many people with PD. While they have shown some effectiveness in clinical trials,[57] their intake is not free of risks. Life-threatening adverse reactions have been described, such as the neuroleptic malignant syndrome.[58][59]



Global burden of Parkinson’s disease, measured in disability-adjusted life yearsper 100,000 inhabitants in 2004

  no data
  < 5
  > 80

PD invariably progresses with time. The Hoehn and Yahr scale, which defines five stages of progression, is commonly used to estimate the progress of the disease.

Motor symptoms, if not treated, advance aggressively in the early stages of the disease and more slowly later. Untreated, individuals are expected to lose independent ambulation after an average of eight years and be bedridden after ten years.[60] However, it is uncommon to find untreated people nowadays. Medication has improved the prognosis of motor symptoms, while at the same time it is a new source of disability because of the undesired effects of levodopa after years of use.[60] In people taking levodopa, the progression time of symptoms to a stage of high dependency from caregivers may be over 15 years.[60] However, it is hard to predict what course the disease will take for a given individual.[60] Age is the best predictor of disease progression.[26] The rate of motor decline is greater in those with less impairment at the time of diagnosis, while cognitive impairment is more frequent in those who are over 70 years of age at symptom onset.[26]

Since current therapies improve motor symptoms, disability at present is mainly related to non-motor features of the disease.[26] Nevertheless, the relationship between disease progression and disability is not linear. Disability is initially related to motor symptoms.[60] As the disease advances, disability is more related to motor symptoms that do not respond adequately to medication, such as swallowing/speech difficulties, and gait/balance problems; and also to motor complications, which appear in up to 50% of individuals after 5 years of levodopa usage.[60] Finally, after ten years most people with the disease have autonomic disturbances, sleep problems, mood alterations and cognitive decline.[60] All of these symptoms, especially cognitive decline, greatly increase disability.[26][60]

The life expectancy of people with PD is reduced.[60] Mortality ratios are around twice those of unaffected people.[60] Cognitive decline and dementia, old age at onset, a more advanced disease state and presence of swallowing problems are all mortality risk factors. On the other hand a disease pattern mainly characterized by tremor as opposed to rigidity predicts an improved survival.[60] Death from aspiration pneumonia is twice as common in individuals with PD as in the healthy population.[60]


PD is the second most common neurodegenerative disorder after Alzheimer’s disease.[61] The prevalence (proportion in a population at a given time) of PD is about 0.3% of the whole population in industrialized countries. PD is more common in the elderly and prevalence rises from 1% in those over 60 years of age to 4% of the population over 80.[61] The mean age of onset is around 60 years, although 5–10% of cases, classified as young onset, begin between the ages of 20 and 50.[2] PD may be less prevalent in those of African and Asian ancestry, although this finding is disputed.[61] Some studies have proposed that it is more common in men than women, but others failed to detect any differences between the two sexes.[61] The incidence of PD is between 8 and 18 per 100,000 person–years.[61]

Many risk factors and protective factors have been proposed, sometimes in relation to theories concerning possible mechanisms of the disease, however none have been conclusively related to PD by empirical evidence. When epidemiological studies have been carried out in order to test the relationship between a given factor and PD, they have often been flawed and their results have in some cases been contradictory.[61] The most frequently replicated relationships are an increased risk of PD in those exposed to pesticides, and a reduced risk in smokers.[61]

 Risk factors

U.S. Army helicopter spraying Agent Orange over Vietnamese agricultural land during the Vietnam war. Agent Orange has been associated with PD.

Injections of the synthetic neurotoxin MPTP produce a range of symptoms similar to those of PD as well as selective damage to the dopaminergic neurons in the substantia nigra. This observation has led to theorizing that exposure to some environmental toxins may increase the risk of having PD.[61] Exposure to toxins that have been consistently related to the disease can double the risk of PD, and include certain pesticides, such as rotenone or paraquat, and herbicides, such as Agent Orange.[61][62][63] Indirect measures of exposure, such as living in rural environments, have been found to increase the risk of PD.[63] Heavy metals exposure has been proposed to be a risk factor, through possible accumulation in the substantia nigra; however, studies on the issue have been inconclusive.[61]

Protective factors

Smoking has been related to a reduced risk of having PD. Smokers’ risk of having PD may be reduced down to a third when compared to non-smokers.[61] The basis for this effect is not known, but possibilities include an effect of nicotine as a dopamine stimulant.[61] Tobacco smoke contains compounds that act as MAO inhibitors that also might contribute to this effect.[64] Caffeine consumption also protects against PD.[65] Antioxidants, such as vitamins C and D, have been proposed to protect against the disease but results of studies have been contradictory and no positive effect has been proven.[61] The results regarding fat and fatty acids have been contradictory, with various studies reporting protective effects, risk-enhancing effects or no effects.[61] Finally there have been preliminary indications of a possible protective role of estrogens and anti-inflammatory drugs.[61]



A 1893 photograph of Jean-Martin Charcot, who made important contributions to the understanding of the disease and proposed its current name honoring James Parkinson

Several early sources, including an Egyptian papyrus, an Ayurvedic medical treatise, the Bible, or Galen‘s writings, describe symptoms resembling those of PD.[66] After Galen there are no references unambiguously related to PD until the 17th century.[66] In the 17th and 18th centuries, several authors wrote about elements of the disease, including Sylvius, Gaubius, Hunter and Chomel.[66][67][68]

In 1817 an English doctor, James Parkinson, published his essay reporting six cases of paralysis agitans.[69] An Essay on the Shaking Palsy described the characteristic resting tremor, abnormal posture and gait, paralysis and diminished muscle strength, and the way that the disease progresses over time.[69][70] Early neurologists who made further additions to the knowledge of the disease include Trousseau, Gowers, Kinnier Wilson and Erb, and most notably Jean-Martin Charcot, whose studies between 1868 and 1881 were a landmark in the understanding of the disease.[69] Among other advances, he made the distinction between rigidity, weakness and bradykinesia.[69] He also championed the renaming of the disease in honor of James Parkinson.[69]

In 1912 Frederic Lewy described microscopic particles in affected brains, later named “Lewy bodies“.[69] In 1919 Konstantin Tretiakoff reported that the substantia nigra was the main cerebral structure affected, but this finding was not widely accepted until it was confirmed by further studies published by Rolf Hassler in 1938.[69] The underlying biochemical changes in the brain were identified in the 1950s, due largely to the work of Arvid Carlsson on the neurotransmitter dopamine and its role on PD.[71] In 1997, alpha-synuclein was found to be the main component of Lewy bodies.[27]

Anticholinergics and surgery (lesioning of the corticospinal pathway or some of the basal ganglia structures) were the only treatments until the arrival of levodopa, which reduced their use dramatically.[67][72] Levodopa was first synthesized in 1911 by Casimir Funk, but it received little attention until the mid 20th century.[71] It entered clinical practice in 1967 and brought about a revolution in the management of PD.[71][73] By the late 1980s deep brain stimulation emerged as a possible treatment.[74]

Research directions


There is little prospect of dramatic new PD treatments expected in a short time frame.[75] Currently active research directions include the search for new animal models of the disease and studies of the potential usefulness of gene therapy, stem cell transplants and neuroprotective agents.[26]

Animal models

PD is not known to occur naturally in any species other than humans, although animal models which show some features of the disease are used in research. The appearance of parkinsonian symptoms in a group of drug addicts in the early 1980s who consumed a contaminated batch of the synthetic opiate MPPP led to the discovery of the chemical MPTP as an agent that causes a parkinsonian syndrome in non-human primates as well as in humans.[76] Other predominant toxin-based models employ the insecticide rotenone, the herbicide paraquat and the fungicide maneb.[77] Models based on toxins are most commonly used in primates. Transgenic rodent models that replicate various aspects of PD have been developed.[78]

 Gene therapy

Gene therapy involves the use of a non-infectious virus to shuttle a gene into a part of the brain. The gene used leads to the production of an enzyme that helps to manage PD symptoms or protects the brain from further damage.[26][79] In 2010 there were four clinical trials using gene therapy in PD.[26] There have not been important adverse effects in these trials although the clinical usefulness of gene therapy is still unknown.[26] One of these reported positive results in 2011.[80]

Neuroprotective treatments

While several chemical compounds such as GDNF (chemical structure pictured) have been proposed as neuroprotectors in PD, none have proven efficacy.

Investigations on neuroprotection are at the forefront of PD research. Several molecules have been proposed as potential treatments.[26] However, none of them have been conclusively demonstrated to reduce degeneration.[26] Agents currently under investigation include anti-apoptotics (omigapil, CEP-1347), antiglutamatergics, monoamine oxidase inhibitors (selegiline, rasagiline), promitochondrials (coenzyme Q10, creatine), calcium channel blockers (isradipine) and growth factors (GDNF).[26] Preclinical research also targets alpha-synuclein.[75]

 Neural transplantation

Since early in the 1980s, fetal, porcine, carotid or retinal tissues have been used in cell transplants, in which dissociated cells are injected into the substantia nigra in the hope that they will incorporate themselves into the brain in a way that replaces the dopamine-producing cells that have been lost.[26] Although there was initial evidence of mesencephalic dopamine-producing cell transplants being beneficial, double-blind trials to date indicate that cell transplants produce no long-term benefit.[26] An additional significant problem was the excess release of dopamine by the transplanted tissue, leading to dystonias.[81] Stem cell transplants are a recent research target, because stem cells are easy to manipulate and stem cells transplanted into the brains of rodents and monkeys have been found to survive and reduce behavioral abnormalities.[26][82] Nevertheless, use of fetal stem cells is controversial.[26] It has been proposed that effective treatments may be developed in a less controversial way by use of induced pluripotent stem cells taken from adults.[26]

Society and culture

Muhammad Ali at the age of 64 in 2006. He has shown signs of parkinsonism since the age of 38.


The costs of PD to society are high, but difficult to calculate exactly due to methodological difficulties in research and differences between countries.[83] The annual cost in the UK is estimated to be between 449 million and 3.3 billion pounds, while the cost per patient per year in the US is probably around $10,000 and the total burden around 23 billion dollars.[83] The largest share of direct cost comes from inpatient care and nursing homes, while the share coming from medications is substantially lower.[83] Indirect costs are high, due to reduced productivity and the burden on caregivers.[83] In addition to economic costs, PD reduces quality of life of those with the disease and their caregivers.[83]


April 11, the birthday of James Parkinson, has been designated as the world’s Parkinson’s disease day.[69][84] A red tulip was chosen by several international organizations as the symbol of the disease in 2005: it represents the James Parkinson Tulip cultivar, registered in 1981 by a Dutch horticulturalist.[84] Advocacy organizations on the disease include the National Parkinson Foundation, which has provided more than $155 million in care, research and support services since 1982,[85] Parkinson’s Disease Foundation, which has provided more than $90 million for research and $37 million for education and advocacy programs since its founding in 1957 by William Black;[86][87] the American Parkinson Disease Association, founded in 1961;[88] and the European Parkinson’s Disease Association, founded in 1992.[89]

Notable cases

Among the many famous people with PD, one who has greatly increased the public awareness of the disease is the actor Michael J. Fox. Fox was diagnosed in 1991 when he was 30, but kept his condition secret from the public for seven years.[90] He has written two autobiographic books in which his fight against the disease plays a major role,[91] and appeared before the United States Congress without medication to illustrate the effects of the disease.[91] The Michael J. Fox Foundation aims to develop a cure for Parkinson’s disease. In recent years it has been the major Parkinson’s fundraiser in the US, providing 140 million dollars in research funding between 2001 and 2008.[91] Fox’s work led him to be named one of the 100 people “whose power, talent or moral example is transforming the world” in 2007 by Time magazine,[90] and he received an honorary doctorate in medicine from Karolinska Institutet for his contributions to research in Parkinson’s disease.[92] Another foundation that supports Parkinson’s research was established by professional cyclist Davis Phinney.[93] The Davis Phinney Foundation strives to improve the lives of those living with Parkinson’s disease by providing them with information and tools.[94] Muhammad Ali has been called the “world’s most famous Parkinson’s patient”.[95] He was 42 at diagnosis although he already showed signs of Parkinson’s when he was 38.[96] Nevertheless, whether he has PD or a parkinsonian syndrome caused by boxing is still an open question.


Penyakit Parkinson

Penyakit Parkinson
Klasifikasi dan sumber daya eksternal

Two sketches (one from the front and one from the right side) of a man, with an expressionless face. He is stooped forward and is presumably having difficulty walking.

Ilustrasi penyakit Parkinson oleh William Richard Gowers, yang pertama kali diterbitkan dalam A Manual Penyakit pada Sistem Saraf (1886)
ICD-10 G20, F02.3
ICD-9 332
OMIM 168600 556500
DiseasesDB 9651
MedlinePlus 000755
eMedicine neuro/304 neuro/635 di muda
pmr/99 rehabilitasi
Penyakit Parkinson GeneReviews Ikhtisar

Penyakit Parkinson (juga dikenal sebagai penyakit Parkinson, Parkinson, parkinson idiopatik, parkinson primer, PD, atau agitans kelumpuhan) adalah gangguan degeneratif sistem saraf pusat. Ini hasil dari kematian dopamin-menghasilkan sel-sel di substansia nigra, sebuah wilayah otak tengah, penyebab kematian sel tidak diketahui. Di awal perjalanan penyakit, gejala yang paling jelas adalah gerakan-terkait, termasuk gemetar, kekakuan, lambatnya gerakan dan kesulitan dengan berjalan dan kiprah. Kemudian, kognitif dan masalah perilaku mungkin timbul, dengan demensia sering terjadi pada tahap lanjut dari penyakit. Gejala lain termasuk sensorik, tidur dan masalah emosional. PD adalah lebih umum pada orang tua dengan sebagian besar kasus terjadi setelah usia 50.

Gejala motor utama secara kolektif disebut parkinson, atau “sindrom parkinsonian”. Penyakit Parkinson sering didefinisikan sebagai sindrom parkinsonian yang idiopatik (tidak memiliki diketahui penyebabnya), meskipun beberapa kasus atipikal memiliki asal-usul genetik. Banyak risiko dan faktor pelindung telah diselidiki: bukti yang paling jelas adalah untuk peningkatan risiko PD pada orang terpapar pestisida tertentu dan mengurangi risiko pada perokok tembakau. Patologi penyakit ini ditandai oleh akumulasi protein yang disebut alpha-synuclein menjadi inklusi disebut badan Lewy di neuron, dan dari pembentukan cukup dan aktivitas dopamin diproduksi di neuron tertentu dalam bagian otak tengah. Diagnosis kasus khas adalah terutama didasarkan pada gejala, dengan tes seperti neuroimaging digunakan untuk konfirmasi.

Pengobatan modern efektif mengelola gejala motor awal penyakit, terutama melalui penggunaan levodopa dan dopamin agonis. Sebagai penyakit berlangsung dan neuron dopamin terus hilang, titik akhirnya tiba di mana obat ini menjadi tidak efektif untuk mengobati gejala dan pada saat yang sama menghasilkan komplikasi yang disebut tardive, ditandai oleh gerakan menggeliat disengaja. Diet dan beberapa bentuk rehabilitasi telah menunjukkan efektivitas beberapa di mengurangi gejala. Bedah dan stimulasi otak dalam telah digunakan untuk mengurangi gejala motor sebagai pilihan terakhir pada kasus yang berat di mana obat tidak efektif. Arah penelitian memasukan sebuah pencarian dari model hewan baru dari penyakit dan penyelidikan dari kegunaan potensi terapi gen, transplantasi stem sel dan agen saraf. Obat untuk mengobati non-gerakan-gejala terkait dari PD, seperti gangguan tidur dan masalah emosional, juga ada.

Penyakit ini dinamai setelah doctor dari Inggris James Parkinson, yang menerbitkan deskripsi rinci pertama di Sebuah Esai tentang Cerebral Gemetar pada tahun 1817. Beberapa organisasi besar mempromosikan penelitian dan peningkatan kualitas hidup dari orang-orang dengan penyakit dan keluarga mereka. Kampanye kesadaran publik termasuk hari penyakit Parkinson pada ulang tahun James Parkinson, 11 April, dan penggunaan tulip merah sebagai simbol dari penyakit. Orang dengan parkinson yang telah meningkatkan kesadaran masyarakat termasuk Michael J. Fox dan Muhammad Ali.

1 Klasifikasi
2 Tanda dan gejala
2.1 motor
Neuropsikiatrik 2.2
Lainnya 2,3
3 Penyebab
4 Patologi
4.1 Anatomi Patologi
4.2 Patofisiologi
4.3 Otak kematian sel
5 Diagnosis
6 Manajemen
6.1 Levodopa
6.2 Dopamin agonis
6.3 MAO-B inhibitor
6.4 Obat lain
6,5 Bedah dan stimulasi otak dalam
6.6 Rehabilitasi
6,7 Diet
6.8 Perawatan paliatif
6.9 Lain perawatan
7 Prognosis
8 Epidemiologi
8.1 Faktor risiko
8.2 Perlindungan faktor
9 Sejarah
10 Penelitian arah
10.1 Hewan Model
10.2 Terapi gen
10,3 neuroprotektif perawatan
10,4 Neural transplantasi
11 Masyarakat dan budaya
11.1 Biaya
11.2 Advokasi
11.3 Terkemuka kasus
12 Referensi
13 Pranala luar

Para parkinsonisme Istilah digunakan untuk sindrom bermotor yang utama gejala tremor saat istirahat, kekakuan, memperlambat gerak dan instabilitas postural. Sindrom parkinsonian dapat dibagi menjadi empat subtipe menurut asal mereka: primer atau idiopatik, sekunder atau diperoleh, parkinson turun-temurun, dan ditambah parkinson sindrom atau degenerasi sistem multi [1] penyakit Parkinson adalah bentuk paling umum dari parkinson dan biasanya didefinisikan sebagai. “primer” parkinson, parkinsonism berarti tanpa penyebab yang dapat diidentifikasikan eksternal [2] [3]. Dalam beberapa tahun terakhir beberapa gen yang secara langsung berkaitan dengan beberapa kasus penyakit Parkinson telah ditemukan. Sebanyak ini bisa menentang definisi penyakit Parkinson sebagai penyakit idiopatik, gangguan parkinson genetik dengan perjalanan klinis yang sama dengan PD umumnya termasuk dalam label penyakit Parkinson. Istilah “penyakit Parkinson kekeluargaan” dan “penyakit Parkinson sporadis yang” dapat digunakan untuk membedakan genetik dari bentuk yang benar-benar idiopatik penyakit. [4]

PD biasanya diklasifikasikan sebagai gangguan gerakan, meskipun juga menimbulkan beberapa non-motor jenis gejala seperti defisit sensorik, [5] kognitif kesulitan atau masalah tidur. Ditambah penyakit Parkinson parkinsonisms primer yang hadir fitur tambahan. [2] Mereka termasuk atrofi sistem multi, palsy supranuclear progresif, degenerasi corticobasal dan demensia dengan badan Lewy. [2]

Dalam hal patofisiologi, PD dianggap sebagai synucleinopathy karena adanya akumulasi abnormal dari alfa-synuclein protein dalam otak dalam bentuk badan Lewy, sebagai lawan dari penyakit lain seperti penyakit Alzheimer mana otak terakumulasi protein tau dalam bentuk neurofibrillary kusut [6]. Namun demikian, ada tumpang tindih klinis dan patologis antara tauopathies dan synucleinopathies. Gejala yang paling khas, demensia penyakit Alzheimer, terjadi pada tahap lanjut dari PD, sementara itu adalah umum untuk menemukan kusut neurofibrillary di otak terpengaruh oleh PD. [6]

Demensia dengan badan Lewy (DLB) synucleinopathy lain yang memiliki kesamaan dengan PD, dan terutama dengan subset kasus PD dengan demensia. Namun hubungan antara PD dan DLB adalah kompleks dan masih harus diklarifikasi. [7] Mereka mungkin merupakan bagian dari kontinum atau mereka mungkin penyakit yang terpisah. [7]

Tanda dan gejala

Tulisan tangan seseorang yang dipengaruhi oleh PD dalam Ceramah pada penyakit pada sistem saraf oleh Charcot (1879). Deskripsi asli dari teks menyatakan “Para stroke membentuk huruf sangat tidak teratur dan berliku-liku, sedangkan penyimpangan dan sinuosities adalah dengan lebar sangat terbatas. (…) Down-stroke semua, dengan pengecualian huruf pertama , dibuat dengan ketegasan komparatif dan, pada kenyataannya, hampir normal – lebih halus up-stroke, sebaliknya, semua gemetar dalam penampilan (…).”
Artikel utama: Tanda dan gejala penyakit Parkinson
Penyakit Parkinson mempengaruhi gerakan, menghasilkan gejala motor [1] Non-motor gejala, yang termasuk disfungsi otonom, masalah neuropsikiatri (suasana hati, kognisi, perilaku atau pikiran perubahan), dan kesulitan sensorik dan tidur, juga umum. [1].


Seorang pria dengan penyakit Parkinson menampilkan menekuk postur berjalan digambarkan pada tahun 1892. Foto muncul di Nouvelle Iconographie de la Salpetriere, vol. 5.
Informasi lebih lanjut: Parkinsonian kiprah
Empat gejala motor dianggap kardinal di PD:. Tremor, kekakuan, lambatnya gerakan, dan instabilitas postural [1]

Tremor adalah gejala yang paling jelas dan terkenal [1] Ini adalah yang paling umum;. Meskipun sekitar 30% dari individu dengan PD tidak memiliki tremor saat onset penyakit, yang paling berkembang sebagai penyakit berlangsung [1] Hal ini biasanya. getaran istirahat: maksimal saat ekstremitas berada pada istirahat dan menghilang dengan gerakan sukarela dan tidur [1] Ini mempengaruhi untuk sebagian besar bagian paling distal ekstremitas dan saat onset biasanya hanya muncul di lengan tunggal atau kaki, menjadi bilateral. kemudian [1]. Frekuensi getaran PD adalah antara 4 dan 6 hertz (siklus per detik). Sebuah fitur getaran adalah “pil-rolling”, sebuah istilah yang digunakan untuk menggambarkan kecenderungan jari telunjuk dari tangan untuk mendapatkan ke dalam kontak dengan ibu jari dan melakukan bersama-sama gerakan melingkar [1] [8]. Istilah ini berasal dari kesamaan antara gerakan pada pasien PD dan teknik sebelumnya farmasi secara manual membuat pil. [8]

Bradykinesia (lambatnya gerakan) adalah fitur lain karakteristik dari PD, dan berhubungan dengan kesulitan sepanjang perjalanan seluruh proses gerakan, mulai dari perencanaan sampai inisiasi dan akhirnya pelaksanaan gerakan [1] Kinerja gerakan sekuensial dan simultan terhalang.. [1] bradykinesia adalah gejala yang paling melumpuhkan pada tahap awal penyakit ini. [2] manifestasi awal masalah ketika melakukan tugas sehari-hari yang memerlukan kontrol motorik halus seperti menulis, menjahit atau berpakaian [1] evaluasi klinis. yang berbasis di tugas-tugas serupa seperti bergantian gerakan antara kedua tangan atau kedua kaki [2] bradykinesia tidak sama untuk semua gerakan atau kali.. Hal ini dimodifikasi oleh aktivitas atau keadaan emosi subjek, ke titik bahwa beberapa pasien yang hampir tidak bisa berjalan namun masih bisa naik sepeda [1]. Umumnya pasien mengalami sedikit kesulitan ketika beberapa jenis isyarat eksternal disediakan. [1 ] [9]

Kekakuan adalah kekakuan dan ketahanan terhadap gerakan anggota tubuh yang disebabkan oleh nada otot meningkat, kontraksi berlebihan dan terus menerus otot [1] Dalam parkinsonisme kekakuan dapat seragam (timbal-pipa kekakuan) atau ratchety (kekakuan cogwheel).. [1] [2 ] [10] [11] Kombinasi tremor dan peningkatan nada dianggap di asal kekakuan cogwheel [12] Kekakuan mungkin berhubungan dengan nyeri sendi;. sakit seperti menjadi manifestasi awal dari penyakit yang sering [1]. Pada tahap awal penyakit Parkinson, kekakuan seringkali asimetris dan cenderung mempengaruhi otot leher dan bahu sebelum otot-otot wajah dan ekstremitas [13] Dengan perkembangan penyakit, kekakuan biasanya mempengaruhi seluruh tubuh dan mengurangi. kemampuan untuk bergerak.

Instabilitas postural adalah khas dalam tahap akhir dari penyakit, yang menyebabkan gangguan keseimbangan dan jatuh sering, dan sekunder untuk patah tulang [1]. Ketidakstabilan ini sering absen pada tahap awal, terutama pada orang muda. [2] Sampai dengan 40% dari pasien mungkin mengalami jatuh dan sekitar 10% mungkin telah jatuh mingguan, dengan jumlah yang jatuh berhubungan dengan keparahan dari PD [1].

Tanda-tanda motor lain diakui dan gejala termasuk gangguan gaya berjalan dan postur seperti festination (langkah mengocok cepat dan postur tubuh ke depan tertekuk ketika berjalan), [1] berbicara dan gangguan menelan termasuk gangguan suara, [14] seperti topeng ekspresi wajah atau tulisan tangan kecil , meskipun berbagai masalah motorik yang mungkin yang dapat muncul adalah besar [1].

Penyakit Parkinson dapat menyebabkan gangguan neuropsikiatri yang bisa berkisar dari ringan sampai parah. Ini termasuk gangguan berbicara, kognisi, mood, perilaku, dan pikiran [1].

Gangguan kognitif dapat terjadi pada tahap awal penyakit dan kadang-kadang sebelum diagnosis, dan peningkatan prevalensi dengan durasi penyakit [1] [15]. Defisit kognitif yang paling umum pada individu yang terkena adalah disfungsi eksekutif, yang dapat mencakup masalah dengan perencanaan, fleksibilitas kognitif, berpikir abstrak, akuisisi aturan, memulai tindakan yang tepat dan tindakan tidak pantas menghambat, dan memilih informasi sensorik relevan. Fluktuasi perhatian dan memperlambat kecepatan kognitif antara kesulitan kognitif lainnya. Memori dipengaruhi, khususnya dalam mengingat informasi yang dipelajari. Namun demikian, perbaikan muncul ketika mengingat dibantu oleh isyarat. Kesulitan visuospatial juga merupakan bagian dari penyakit, dilihat misalnya ketika individu diminta untuk melakukan tes pengenalan wajah dan persepsi orientasi garis yang ditarik [15].

Seseorang dengan PD memiliki dua sampai enam kali risiko menderita demensia dibandingkan dengan populasi umum [1] [15]. Prevalensi demensia meningkat dengan durasi penyakit. [15] Demensia dikaitkan dengan berkurangnya kualitas hidup di orang dengan PD dan pengasuh mereka, meningkatnya kematian, dan probabilitas yang lebih tinggi membutuhkan perawatan di rumah. [15]

Perubahan perilaku dan suasana hati lebih sering terjadi pada PD tanpa gangguan kognitif dibandingkan pada populasi umum, dan biasanya hadir dalam PD dengan demensia. Kesulitan suasana hati yang paling sering adalah depresi, apatis dan kecemasan. [1] perilaku kontrol impuls seperti obat-obatan dan keinginan berlebihan, makan pesta, hypersexuality, atau judi patologis dapat muncul di PD dan telah terkait dengan obat yang digunakan untuk mengelola penyakit ini. [1] [16] psikotik gejala-halusinasi atau delusi-terjadi pada 4% pasien, dan diasumsikan bahwa tergesa-gesa utama fenomena psikotik pada penyakit Parkinson adalah kelebihan dopaminergik sekunder untuk pengobatan; karena itu menjadi lebih umum dengan bertambahnya usia dan asupan levodopa [17]. [18]

Selain gejala kognitif dan motor, PD dapat merusak fungsi tubuh lainnya. Masalah tidur adalah fitur dari penyakit dan dapat diperburuk oleh obat [1] Gejala. Dapat terwujud dalam rasa kantuk di siang hari, gangguan dalam tidur REM, atau insomnia. [1] Perubahan dalam sistem saraf otonom dapat menyebabkan hipotensi ortostatik (darah rendah tekanan terhadap berdiri), kulit berminyak dan berkeringat berlebihan, inkontinensia urin dan fungsi seksual diubah [1]. Sembelit dan dismotilitas lambung dapat cukup parah untuk menyebabkan ketidaknyamanan dan bahkan membahayakan kesehatan [19]. PD adalah terkait dengan beberapa mata dan kelainan visi seperti sebagai penurunan tingkat berkedip, mata kering, mata mengejar kekurangan (pelacakan mata) dan gerakan saccadic (gerakan otomatis cepat dari kedua mata di arah yang sama), kesulitan dalam mengarahkan pandangannya ke atas, dan penglihatan kabur atau ganda [1]. [20] Perubahan dalam persepsi mungkin termasuk rasa gangguan penciuman, sensasi rasa sakit dan paresthesia (kesemutan dan mati rasa kulit) [1]. Semua gejala ini dapat terjadi tahun sebelum diagnosis penyakit. [1]


PDB rendering Parkin (ligase)
Kebanyakan orang dengan penyakit Parkinson memiliki penyakit Parkinson idiopatik (tidak memiliki diketahui penyebabnya yang spesifik). Sebagian kecil kasus, bagaimanapun, dapat dikaitkan dengan faktor genetik dikenal. Faktor lain telah dikaitkan dengan risiko pengembangan PD, tetapi tidak ada hubungan kausal telah terbukti.

PD tradisional telah dianggap sebagai gangguan non-genetik;. Namun, sekitar 15% dari individu dengan PD memiliki kerabat tingkat pertama yang memiliki penyakit [2] Setidaknya 5% dari orang kini diketahui memiliki bentuk penyakit yang terjadi karena mutasi dari salah satu gen yang spesifik. [21]

Mutasi pada gen-gen tertentu telah meyakinkan terbukti menyebabkan PD. Ini kode gen untuk alfa-synuclein (SPMB), Parkin (PRKN), leusin kaya kinase mengulang 2 (LRRK2 atau dardarin), PTEN-diinduksi kinase putatif 1 (PINK1), DJ-1 dan ATP13A2. [4] [21] Dalam kebanyakan kasus, orang dengan mutasi ini akan mengembangkan PD. Dengan pengecualian LRRK2, bagaimanapun, mereka account hanya minoritas kecil dari kasus PD [4] PD-terkait paling ekstensif dipelajari gen SPMB dan LRRK2.. Mutasi pada gen termasuk SPMB, LRRK2 dan glucocerebrosidase (GBA) telah ditemukan menjadi faktor risiko untuk PD sporadis. Mutasi di GBA diketahui menyebabkan penyakit Gaucher. [21] Genome-wide studi hubungan, yang mencari alel bermutasi dengan penetrasi yang rendah dalam kasus-kasus sporadis, kini telah menghasilkan banyak hasil positif. [22]

Peran dari gen SPMB adalah penting dalam PD karena protein alpha-synuclein adalah komponen utama dari badan Lewy. [21] mutasi missense gen (di mana nukleotida tunggal berubah), dan duplikasi dan triplications dari lokus yang berisi itu telah ditemukan dalam kelompok-kelompok yang berbeda dengan PD keluarga [21] missense mutasi jarang terjadi.. [21] Di sisi lain, perkalian dari account lokus SPMB untuk sekitar 2% dari kasus keluarga. [21] perkalian telah ditemukan di asimtomatik operator, yang menunjukkan bahwa penetrasi tidak lengkap atau usia tergantung. [21]

Gen LRRK2 (PARK8) mengkode untuk protein yang disebut dardarin. Nama dardarin diambil dari kata Basque untuk tremor, karena gen ini pertama kali diidentifikasi pada keluarga dari Inggris dan bagian utara Spanyol [4]. Mutasi di LRRK2 adalah penyebab paling umum dikenal PD keluarga dan sporadis, akuntansi untuk sekitar 5 % dari individu dengan riwayat keluarga penyakit dan 3% dari kasus sporadis. [4] [21] Ada banyak mutasi yang berbeda dijelaskan dalam LRRK2, namun bukti tegas dari sebab-akibat hanya ada untuk sejumlah kecil. [21]


Sebuah tubuh Lewy (coklat patri) dalam sel otak substantia nigra dalam penyakit Parkinson. Warna coklat adalah pewarnaan imunohistokimia positif untuk alfa-synuclein.

patologi anatomi
Ganglia basal, sebuah kelompok “struktur otak” diinervasi oleh sistem dopaminergik, adalah yang paling serius terkena dampak area otak di PD [23]. Karakteristik patologis utama dari PD adalah kematian sel dalam substantia nigra dan, lebih khusus, ventral (depan) bagian dari pars compacta, yang mempengaruhi hingga 70% dari kematian sel dengan waktu terjadi. [4]

Perubahan makroskopik dapat melihat pada permukaan dipotong dari batang otak, di mana hilangnya neuron dapat disimpulkan dari pengurangan pigmentasi melanin dalam substantia nigra dan lokus coeruleus [24]. Para histopatologi (anatomi mikroskopik) dari substantia nigra dan beberapa daerah otak lainnya menunjukkan hilangnya neuron dan badan Lewy dalam banyak sel-sel saraf yang tersisa. Hilangnya neuron disertai dengan kematian astrosit (berbentuk bintang sel-sel glial) dan aktivasi dari mikroglia (jenis lain dari sel glial). Badan Lewy adalah fitur kunci dari PD patologis. [24]


A. Skema awal perkembangan deposito tubuh Lewy pada tahap pertama penyakit Parkinson, seperti yang diusulkan oleh Braak dan rekan
B. Lokalisasi wilayah volume otak penurunan yang signifikan di PD awal dibandingkan dengan kelompok peserta tanpa penyakit dalam studi neuroimaging, yang menyimpulkan bahwa kerusakan batang otak mungkin tahap pertama diidentifikasi PD neuropatologi [25]
Gejala utama hasil penyakit Parkinson dari kegiatan sangat mengurangi sel mensekresi dopamin yang disebabkan oleh kematian sel di daerah pars compacta dari substantia nigra. [23]

Ada lima jalur utama di otak yang menghubungkan daerah otak lainnya dengan ganglia basal. Ini dikenal sebagai motor, oculo-motor, sirkuit asosiatif, limbik dan orbitofrontal, dengan nama yang menunjukkan area proyeksi utama dari setiap sirkuit [23]. Semua dari mereka yang terkena di PD, dan gangguan mereka menjelaskan banyak gejala penyakit sejak sirkuit ini terlibat dalam berbagai fungsi termasuk gerakan, perhatian dan belajar. [23] Secara ilmiah, sirkuit motor telah diperiksa paling intensif [23].

Sebuah model konseptual tertentu dari sirkuit motor dan perubahan dengan PD telah pengaruh besar sejak tahun 1980, meskipun beberapa keterbatasan telah menunjukkan yang telah menyebabkan modifikasi. [23] Dalam model ini, ganglia basal biasanya memberikan pengaruh penghambatan konstan pada berbagai sistem motor, mencegah mereka dari menjadi aktif pada waktu yang tidak tepat. Ketika keputusan dibuat untuk melakukan suatu tindakan tertentu, penghambatan berkurang untuk sistem motor yang diperlukan, sehingga melepaskannya untuk aktivasi. Dopamin bertindak untuk memfasilitasi pelepasan inhibisi, tingkat begitu tinggi fungsi dopamin cenderung mempromosikan aktivitas motorik, sementara tingkat rendah fungsi dopamin, seperti yang terjadi pada PD, permintaan pengerahan tenaga lebih besar dari upaya untuk setiap gerakan yang diberikan. Jadi efek bersih dari deplesi dopamin adalah untuk menghasilkan hypokinesia, pengurangan secara keseluruhan dalam output bermotor [23]. Obat yang digunakan untuk mengobati PD, sebaliknya, bisa menghasilkan aktivitas dopamin berlebihan, yang memungkinkan sistem motor yang akan diaktifkan pada saat yang tidak tepat dan dengan demikian menghasilkan dyskinesias [23].

 Kematian otak sel
Ada spekulasi beberapa mekanisme dimana sel-sel otak bisa hilang [26]. Salah satu mekanisme terdiri dari akumulasi abnormal dari protein alfa-synuclein terikat ubiquitin dalam sel yang rusak. Protein ini tidak larut terakumulasi di dalam neuron membentuk inklusi disebut Lewy tubuh [4]. [27] Menurut pementasan Braak, klasifikasi penyakit berdasarkan temuan patologis, badan Lewy pertama kali muncul di olfactory bulb, medulla oblongata dan pons tegmentum, dengan individu pada tahap ini menjadi asimtomatik. Sebagai penyakit berlangsung, badan Lewy kemudian berkembang di substantia nigra, area otak tengah dan otak depan basal, dan langkah terakhir neokorteks [4] Situs-situs otak adalah tempat utama degenerasi saraf di PD,. Namun, badan Lewy mungkin tidak menyebabkan kematian sel dan mereka mungkin menjadi pelindung [26]. [27] Pada pasien dengan demensia, kehadiran umum dari badan Lewy yang umum di daerah kortikal. Kusut neurofibrillary dan plak pikun, karakteristik penyakit Alzheimer, yang tidak umum kecuali orang itu gila. [24]

Lain-sel mati Mekanisme ini termasuk disfungsi sistem proteosomal dan lisosomal dan aktivitas mitokondria berkurang [26]. Besi akumulasi dalam substantia nigra biasanya diamati dalam hubungannya dengan inklusi protein. Ini mungkin berhubungan dengan stres oksidatif, agregasi protein dan kematian neuronal, tetapi mekanisme tidak sepenuhnya dipahami [28].


Fludeoxyglucose (18F) (FDG)] PET scan otak yang sehat. Daerah panas mencerminkan penyerapan glukosa yang lebih tinggi. Sebuah penurunan aktivitas di ganglia basal dapat membantu dalam mendiagnosa penyakit Parkinson.
Seorang dokter akan mendiagnosa penyakit Parkinson dari riwayat medis dan pemeriksaan neurologis [1]. Tidak ada tes laboratorium yang jelas akan mengidentifikasi penyakit, tetapi pemindaian otak kadang-kadang digunakan untuk mengesampingkan gangguan yang dapat menimbulkan gejala yang sama. Pasien dapat diberikan levodopa dan lega yang dihasilkan dari gangguan motorik cenderung untuk mengkonfirmasikan diagnosis. Temuan badan Lewy di otak tengah pada otopsi biasanya dianggap bukti bahwa pasien menderita penyakit Parkinson. Kemajuan dari penyakit dari waktu ke waktu dapat mengungkapkan itu bukan penyakit Parkinson, dan beberapa pihak berwenang merekomendasikan bahwa diagnosis secara periodik terakhir [1] [29].

Penyebab lain yang secara sekunder dapat menghasilkan sindrom parkinsonian adalah penyakit Alzheimer, infark serebral ganda dan obat-induced parkinson. [29] Parkinson ditambah sindrom seperti palsy supranuclear progresif dan atrofi sistem multi harus dikesampingkan [1] obat anti-Parkinson. biasanya kurang efektif mengendalikan gejala di Parkinson ditambah sindrom [1]. angka kemajuan lebih cepat, disfungsi kognitif awal atau instabilitas postural, tremor minimal atau simetri saat onset mungkin mengindikasikan penyakit Parkinson ditambah ketimbang PD itu sendiri. [30] bentuk genetik biasanya diklasifikasikan sebagai PD, meskipun istilah penyakit Parkinson keluarga dan parkinson kekeluargaan yang digunakan untuk entitas penyakit dengan pola dominan atau resesif autosomal dari warisan. [2]

Organisasi medis telah menciptakan kriteria diagnostik untuk kemudahan dan standarisasi proses diagnostik, terutama pada tahap awal penyakit ini. Kriteria yang paling banyak dikenal berasal dari Otak Masyarakat Bank Parkinson Inggris Penyakit dan US National Institute of Neurological Gangguan dan Stroke [1]. Kriteria PD Otak Bank Masyarakat membutuhkan lambatnya gerakan (bradykinesia) plus kekakuan, tremor istirahat, atau postural ketidakstabilan. Kemungkinan penyebab lain untuk gejala ini harus dikesampingkan. Akhirnya, tiga atau lebih dari fitur berikut diperlukan saat onset atau evolusi: onset sepihak, tremor saat istirahat, kemajuan dalam waktu, asimetri gejala motorik, respon terhadap levodopa setidaknya selama lima tahun, perjalanan klinis setidaknya sepuluh tahun dan penampilan dari dyskinesias diinduksi oleh asupan levodopa berlebihan [1] Akurasi kriteria diagnostik dievaluasi pada otopsi adalah 75-90%, dengan spesialis seperti ahli saraf memiliki tingkat tertinggi.. [1]

Computed tomography (CT) dan magnetic resonance imaging scan otak (MRI) dari orang-orang dengan PD biasanya tampak normal. [31] Teknik-teknik ini tetap berguna untuk menyingkirkan penyakit lain yang dapat menyebabkan parkinson sekunder, seperti tumor basal ganglia, vaskular patologi dan hidrosefalus [31]. Sebuah teknik khusus dari MRI, difusi MRI, telah dilaporkan berguna untuk membedakan antara parkinson khas dan atipikal, meskipun nilai yang tepat diagnostik masih dalam penyelidikan. [31] fungsi dopaminergik di ganglia basal dapat diukur dengan PET dan SPECT radiotracers yang berbeda. Contohnya adalah ioflupane (123I) (nama dagang DaTSCAN) dan iometopane (Dopascan) untuk SPECT atau fludeoxyglucose (18F) untuk PET. [31] Sebuah pola aktivitas dopaminergik berkurang di ganglia basal dapat membantu dalam mendiagnosa PD. [31]

Artikel utama: Pengobatan penyakit Parkinson
Tidak ada obat untuk penyakit Parkinson, tetapi obat-obatan, operasi dan manajemen multidisiplin dapat memberikan bantuan dari gejala. Keluarga utama dari obat yang berguna untuk mengobati gejala motor levodopa (biasanya dikombinasikan dengan inhibitor dekarboksilase dopa atau inhibitor COMT), agonis dopamin dan MAO-B inhibitor [32]. Tahap penyakit menentukan kelompok mana yang paling berguna. Dua tahap biasanya dibedakan:. Tahap awal di mana individu dengan PD telah mengembangkan beberapa cacat yang dia butuhkan pengobatan farmakologis, maka tahap kedua di mana seorang individu mengembangkan komplikasi motorik yang berhubungan dengan penggunaan levodopa [32] Pengobatan di awal tahap bertujuan untuk tradeoff yang optimal antara kontrol gejala yang baik dan efek samping yang dihasilkan dari peningkatan fungsi dopaminergik. Awal levodopa (atau L-dopa) pengobatan mungkin tertunda dengan menggunakan obat lain seperti MAO-B inhibitor dan agonis dopamin, dengan harapan menunda timbulnya dyskinesias [32] Pada tahap kedua. Tujuannya adalah untuk mengurangi gejala sambil mengontrol fluktuasi dari respon terhadap pengobatan. Penarikan mendadak dari obat atau berlebihan harus dikelola [32]. Bila obat tidak cukup untuk mengontrol gejala, operasi dan stimulasi otak dalam dapat berguna. [33] Pada tahap akhir dari penyakit, perawatan paliatif diberikan untuk meningkatkan kualitas hidup [34].

Levodopa telah menjadi pengobatan yang paling banyak digunakan untuk lebih dari 30 tahun [32]. L-dopa diubah menjadi dopamin di neuron dopaminergik oleh dopa dekarboksilase. [32] Karena gejala motor yang diproduksi oleh kurangnya dopamin dalam substansia nigra, yang administrasi L-dopa sementara mengurangi gejala motor. [32]

Hanya 5-10% L-dopa melintasi penghalang darah-otak. Sisanya sering dimetabolisme untuk dopamin di tempat lain, menyebabkan berbagai efek samping termasuk mual, diskinesia dan kekakuan sendi [32]. Carbidopa dan benserazide adalah inhibitor dekarboksilase dopa perifer, [32] yang membantu mencegah metabolisme L-dopa sebelum mencapai neuron dopaminergik, sehingga mengurangi efek samping dan meningkatkan bioavailabilitas. Mereka umumnya diberikan sebagai persiapan kombinasi dengan levodopa [32] persiapan yang ada. Yang carbidopa / levodopa (co-careldopa) dan benserazide / levodopa (co-beneldopa). Levodopa telah terkait dengan sindrom disregulasi dopamin, yang merupakan berlebihan kompulsif obat, dan punding [16]. Ada versi rilis dikendalikan dari levodopa dalam bentuk infus intravena dan usus yang menyebar efek obat. Ini lambat-release persiapan levodopa belum menunjukkan peningkatan kontrol gejala motor atau komplikasi motor ketika dibandingkan dengan persiapan segera dibebaskan. [32] [35]

Tolcapone menghambat enzim COMT, yang menurunkan dopamin, sehingga memperpanjang efek levodopa [32] ini telah digunakan untuk melengkapi levodopa;.. Namun, kegunaannya dibatasi oleh efek samping yang mungkin seperti kerusakan hati [32] Sebuah obat sama efektif , entacapone, belum terbukti menyebabkan perubahan yang signifikan dari fungsi hati [32] persiapan Berlisensi dari entacapone mengandung entacapone sendiri atau dalam kombinasi dengan carbidopa dan levodopa.. [32]

Persiapan levodopa memimpin dalam jangka panjang untuk pengembangan komplikasi motorik ditandai dengan gerakan tak terkendali yang disebut dyskinesias dan fluktuasi dalam respon terhadap pengobatan [32]. Ketika ini terjadi orang dengan PD dapat berubah dari fase dengan respon yang baik terhadap obat dan beberapa gejala ( “pada” negara), untuk fase dengan tidak ada respon terhadap pengobatan dan gejala motor yang signifikan (“off” negara) [32] Untuk alasan ini,. dosis levodopa yang dijaga serendah mungkin dengan tetap menjaga fungsi [32] Menunda inisiasi. terapi dengan levodopa dengan menggunakan alternatif (agonis dopamin dan MAO-B inhibitor) adalah praktek yang umum. [32] Sebuah strategi mantan untuk mengurangi komplikasi motor untuk menarik L-dopa obat untuk beberapa waktu. Ini tidak disarankan sekarang, karena dapat membawa efek samping yang berbahaya seperti sindrom neuroleptik ganas. [32] Kebanyakan orang dengan PD akhirnya akan membutuhkan levodopa dan kemudian mengembangkan efek samping motorik. [32]

 agonis Dopamin
Beberapa agonis dopamin yang mengikat pasca-sinaptik dopaminergik reseptor di otak memiliki efek yang sama terhadap levodopa [32] ini pada awalnya digunakan untuk individu mengalami on-off fluktuasi dan diskinesia sebagai terapi komplementer untuk levodopa,. Mereka sekarang terutama digunakan pada mereka sendiri sebagai terapi awal untuk gejala motor dengan tujuan menunda komplikasi bermotor [32]. [36] Ketika digunakan di PD an mereka berguna untuk mengurangi periode off. [32] agonis Dopamin termasuk bromokriptin, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine dan lisuride.

Agonis dopamin menghasilkan signifikan, meskipun biasanya ringan, efek samping termasuk rasa kantuk, halusinasi, mual insomnia, dan sembelit. [32] Kadang-kadang efek samping muncul bahkan pada dosis klinis efektif minim, menyebabkan dokter untuk mencari obat yang berbeda. [32] Dibandingkan dengan levodopa, agonis dopamin dapat menunda komplikasi motor menggunakan obat tetapi kurang efektif mengendalikan gejala [32] Meskipun demikian, mereka biasanya cukup efektif untuk mengelola gejala pada tahun-tahun awal.. [2] Mereka cenderung lebih mahal daripada levodopa [2]. dyskinesias akibat agonis dopamin jarang pada orang muda yang memiliki PD, namun seiring dengan efek samping lainnya, menjadi lebih umum dengan usia saat onset [2] Jadi. agonis dopamin adalah pengobatan awal yang lebih disukai untuk onset awal, sebagai lawan terhadap levodopa dalam onset kemudian [2]. Agonis telah terkait dengan gangguan impuls kontrol (seperti aktivitas seksual kompulsif dan makan, dan judi patologis dan belanja) bahkan lebih kuat dari levodopa. [16]

Apomorphine, suatu agonis dopamin non-oral, dapat digunakan untuk mengurangi off periode dan tardive di PD-an [32]. Hal ini dikelola oleh suntikan subkutan intermiten atau kontinu infus [32]. Karena efek sekunder seperti kebingungan dan halusinasi yang umum , individu-individu yang menerima pengobatan apomorphine harus diawasi secara ketat. [32] Dua agonis dopamin yang diberikan melalui patch kulit (lisuride dan rotigotine) telah baru-baru ini ditemukan bermanfaat bagi pasien dalam tahap awal dan hasil positif awal telah dipublikasikan pada kontrol mematikan negara pada pasien di negara maju [35].

MAO-B inhibitor
MAO-B inhibitor (selegiline dan rasagiline) meningkatkan tingkat dopamin di ganglia basal dengan menghalangi metabolisme. Mereka menghambat monoamin oksidase-B (MAO-B) yang memecah dopamin disekresikan oleh neuron dopaminergik. Pengurangan MAO-B hasil kegiatan dalam peningkatan L-dopa di striatum [32] Seperti agonis dopamin, MAO-B inhibitor yang digunakan sebagai monoterapi memperbaiki gejala motorik dan menunda kebutuhan untuk levodopa pada penyakit awal, tetapi menghasilkan efek yang lebih merugikan dan. kurang efektif daripada levodopa. Ada beberapa studi efektivitas mereka dalam stadium lanjut, meskipun hasil menunjukkan bahwa mereka berguna untuk mengurangi fluktuasi antara on dan off periode [32]. Sebuah studi awal mengindikasikan bahwa selegiline dalam kombinasi dengan levodopa meningkatkan risiko kematian, tapi ini kemudian disproven. [32]

 Obat lain
Obat lain seperti amantadine dan antikolinergik mungkin berguna sebagai pengobatan gejala motor. Namun, bukti mendukung mereka tidak memiliki kualitas, sehingga mereka tidak pengobatan pilihan pertama. [32] Selain gejala motor, PD disertai dengan beragam gejala. Sejumlah obat telah digunakan untuk mengobati beberapa masalah [37]. Contohnya adalah penggunaan clozapine untuk psikosis, cholinesterase inhibitor untuk demensia, dan modafinil untuk kantuk di siang hari. [37] [38] Sebuah meta-analisis 2010 menemukan bahwa non-steroid anti-inflammatory drugs (selain asetaminofen dan aspirin), telah dihubungkan dengan setidaknya 15 persen (lebih tinggi dalam jangka panjang dan pengguna biasa) pengurangan kejadian perkembangan penyakit Parkinson. [39]

PD adalah gangguan neurodegeneratif kedua yang paling umum setelah penyakit Alzheimer [61]. Prevalensi (proporsi dalam populasi pada suatu waktu tertentu) dari PD adalah sekitar 0,3% dari seluruh penduduk di negara-negara industri. PD lebih umum pada lansia dan prevalensi meningkat dari 1% pada mereka yang 60 tahun lebih dari usia sampai 4% dari populasi lebih dari 80 [61]. Rata-rata usia onset adalah sekitar 60 tahun, meskipun 5-10% dari kasus, diklasifikasikan sebagai onset muda, mulai antara usia 20 dan 50 [2]. PD mungkin kurang lazim dalam orang-orang keturunan Afrika dan Asia, meskipun temuan ini diperdebatkan. [61] Beberapa penelitian telah mengusulkan bahwa itu adalah lebih umum pada laki-laki daripada perempuan, tetapi yang lain gagal untuk mendeteksi perbedaan antara kedua jenis kelamin. [61] Insiden PD adalah antara 8 dan 18 per 100.000 orang-tahun [61].

Banyak faktor risiko dan faktor pelindung telah diusulkan, kadang-kadang dalam kaitannya dengan teori-teori tentang kemungkinan mekanisme penyakit ini, namun belum ada yang meyakinkan terkait dengan PD oleh bukti empiris. Ketika studi epidemiologis telah dilakukan dalam rangka untuk menguji hubungan antara faktor yang diberikan dan PD, mereka sering telah cacat dan hasil mereka dalam beberapa kasus telah bertentangan [61]. Hubungan yang paling sering ditiru adalah peningkatan risiko PD di mereka yang terpapar pestisida, dan mengurangi risiko pada perokok [61].

 Faktor risiko

US Army helikopter penyemprotan Agen Oranye atas tanah pertanian Vietnam selama perang Vietnam. Agen Oranye telah dikaitkan dengan PD.

Suntikan dari MPTP neurotoksin sintetik menghasilkan berbagai gejala mirip dengan PD serta kerusakan selektif ke neuron dopaminergik di substansia nigra. Pengamatan ini telah menyebabkan teori bahwa paparan terhadap beberapa racun lingkungan dapat meningkatkan risiko memiliki PD. [61] Paparan racun yang telah secara konsisten terkait dengan penyakit ini dapat melipatgandakan risiko PD, dan termasuk pestisida tertentu, seperti rotenone atau parakuat, dan herbisida, seperti Agent Orange [61]. [62] [63] langkah-langkah tidak langsung paparan, seperti tinggal di lingkungan pedesaan, telah ditemukan untuk meningkatkan risiko PD. [63] logam berat telah diusulkan paparan menjadi faktor risiko, melalui akumulasi mungkin dalam substantia nigra;. Namun, studi tentang masalah ini telah meyakinkan [61]

Faktor pelindung
Merokok telah dikaitkan dengan penurunan risiko memiliki PD. Risiko perokok memiliki PD dapat dikurangi turun ke ketiga ketika dibandingkan non-perokok [61]. Dasar untuk efek ini tidak diketahui, tetapi kemungkinan mencakup efek dari nikotin sebagai stimulan dopamin. [61] Asap tembakau mengandung senyawa yang bertindak sebagai inhibitor MAO yang mungkin juga berkontribusi terhadap efek ini [64] konsumsi Kafein juga melindungi terhadap PD. [65] Antioksidan, seperti vitamin C dan D, telah diusulkan untuk melindungi terhadap penyakit, tetapi hasil penelitian telah. bertentangan dan tidak ada efek positif telah terbukti. [61] Hasil mengenai asam lemak dan lemak telah bertentangan, dengan berbagai penelitian melaporkan efek protektif, risiko-meningkatkan efek atau tanpa efek. [61] Akhirnya ada indikasi awal dari suatu kemungkinan peran protektif estrogen dan anti-inflamasi [61].


Sebuah foto dari 1893 Jean-Martin Charcot, yang membuat kontribusi penting untuk memahami penyakit dan diusulkan namanya sekarang menghormati James Parkinson

Sumber-sumber awal Beberapa, termasuk papirus Mesir, sebuah risalah medis Ayurvedic, Alkitab, atau tulisan Galen, menggambarkan gejala menyerupai orang-orang PD [66]. Setelah Galen tidak ada referensi jelas terkait dengan PD sampai abad ke-17. [66] Dalam abad 17 dan 18, beberapa penulis menulis tentang unsur-unsur dari penyakit, termasuk Sylvius, Gaubius, Hunter dan Chomel. [66] [67] [68]

Pada 1817 seorang dokter Inggris, James Parkinson, menerbitkan esainya melaporkan enam kasus agitans kelumpuhan. [69] Sebuah Esai tentang Cerebral Sambil menggambarkan karakteristik tremor istirahat, postur abnormal dan kiprah, kelumpuhan dan kekuatan otot berkurang, dan cara yang Penyakit berlangsung dari waktu ke waktu. [69] [70] ahli saraf Awal yang membuat penambahan lebih lanjut untuk pengetahuan tentang penyakit ini termasuk Trousseau, Gowers, Kinnier Wilson dan Erb, dan terutama Jean-Martin Charcot, yang penelitiannya antara 1868 dan 1881 adalah tengara dalam pemahaman penyakit ini [69] Di antara kemajuan lain., dia membuat perbedaan antara kekakuan, kelemahan dan bradykinesia. [69] Ia juga memperjuangkan penggantian nama penyakit untuk menghormati James Parkinson. [69]

Pada tahun 1912 Frederic Lewy dijelaskan partikel mikroskopis dalam otak yang terkena, kemudian dinamai “badan Lewy” [69] Pada tahun 1919 melaporkan bahwa Konstantin Tretiakoff substantia nigra adalah struktur otak utama yang terkena dampak, namun temuan ini tidak diterima secara luas sampai dikonfirmasi oleh lebih lanjut. studi yang diterbitkan oleh Rolf Hassler tahun 1938 [69]. Perubahan biokimia yang mendasari di otak diidentifikasi pada tahun 1950, terutama disebabkan oleh Arvid Carlsson pekerjaan pada neurotransmitter dopamin dan perannya di PD. [71] Pada tahun 1997, alfa- synuclein ditemukan menjadi komponen utama dari badan Lewy. [27]

Antikolinergik dan pembedahan (lesioning dari jalur kortikospinalis atau beberapa struktur basal ganglia) adalah pengobatan hanya sampai kedatangan levodopa, yang mengurangi penggunaan mereka secara dramatis [67] [72]. Levodopa pertama kali disintesis pada tahun 1911 oleh Casimir Funk, namun itu mendapat sedikit perhatian sampai pertengahan abad ke-20 [71] Ini masuk praktek klinis pada tahun 1967 dan membawa sebuah revolusi dalam manajemen PD [71] [73]. Dengan stimulasi otak 1980-an yang mendalam muncul sebagai pengobatan mungkin.. [ 74]

Penelitian arah

Ada sedikit prospek dramatis perawatan PD baru yang diharapkan dalam jangka waktu yang singkat [75] arah penelitian Saat ini aktif meliputi mencari model hewan baru dari penyakit dan studi tentang manfaat potensi terapi gen, transplantasi stem sel dan agen saraf.. [26]

Hewan model
PD tidak diketahui terjadi secara alami dalam spesies selain manusia, meskipun model hewan yang menunjukkan beberapa fitur penyakit yang digunakan dalam penelitian. Munculnya gejala parkinsonian dalam kelompok pecandu narkoba di awal 1980-an yang mengkonsumsi terkontaminasi batch dari candu sintetis MPPP menyebabkan penemuan MPTP kimia sebagai agen yang menyebabkan sindrom parkinsonian dalam primata non-manusia serta manusia [76]. Lain dominan racun model berbasis mempekerjakan rotenone insektisida, herbisida paraquat dan fungisida maneb [77]. Model didasarkan pada racun yang paling sering digunakan pada primata. Hewan model transgenik yang meniru berbagai aspek dari PD telah dikembangkan. [78]

 Terapi gen
Terapi gen melibatkan penggunaan virus tidak menular untuk antar-jemput gen menjadi bagian dari otak. Gen yang digunakan menyebabkan produksi enzim yang membantu untuk mengelola gejala PD atau melindungi otak dari kerusakan lebih lanjut [26]. [79] Pada tahun 2010 ada empat uji klinis menggunakan terapi gen pada PD. [26] belum ada efek samping penting dalam ujicoba tersebut meskipun kegunaan klinis terapi gen masih belum diketahui [26] Salah satu hasil positif yang dilaporkan pada tahun 2011.. [80]

Perawatan saraf

Sementara beberapa senyawa kimia seperti GDNF (struktur kimia digambarkan) telah diusulkan sebagai neuroprotectors di PD, belum terbukti kemanjurannya.

Investigasi pada pelindung saraf berada di garis depan PD penelitian. Beberapa molekul telah diusulkan sebagai perawatan potensial. [26] Namun, tidak satupun dari mereka telah meyakinkan menunjukkan untuk mengurangi degenerasi [26]. Agen saat ini sedang diselidiki termasuk anti-apoptotics (omigapil, CEP-1347), antiglutamatergics, inhibitor monoamine oxidase ( selegiline, rasagiline), promitochondrials (koenzim Q10, creatine), calcium channel blockers (isradipine) dan faktor pertumbuhan (GDNF) [26] Penelitian praklinis juga menargetkan alpha-synuclein.. [75]

 Neural transplantasi
Sejak awal 1980-an, janin, babi, jaringan karotis atau retina telah digunakan dalam transplantasi sel, di mana sel terdisosiasi yang disuntikkan ke dalam substantia nigra dengan harapan bahwa mereka akan menggabungkan diri ke otak dengan cara yang menggantikan dopamin- memproduksi sel-sel yang telah hilang [26]. Meskipun ada bukti awal yang memproduksi dopamin mesensefalik transplantasi sel yang menguntungkan, double-blind uji coba sampai saat ini menunjukkan bahwa transplantasi sel tidak menghasilkan manfaat jangka panjang. [26] Sebuah masalah yang signifikan tambahan pelepasan dopamin kelebihan oleh jaringan transplantasi, menyebabkan distonia [81]. Transplantasi sel induk adalah target penelitian terbaru, karena sel-sel induk yang mudah untuk memanipulasi dan sel induk yang ditransplantasikan ke dalam otak tikus dan monyet telah ditemukan untuk bertahan hidup dan mengurangi kelainan perilaku [26] [82]. Namun demikian, penggunaan sel induk janin kontroversial. [26] Telah diusulkan bahwa perawatan yang efektif dapat dikembangkan dalam cara yang kurang kontroversial oleh penggunaan sel induk pluripotent yang diambil dari orang dewasa. [ 26]

Masyarakat dan budaya

Muhammad Ali pada usia 64 pada tahun 2006. Dia telah menunjukkan tanda-tanda parkinson sejak usia 38.

Biaya PD untuk masyarakat yang tinggi, tetapi sulit untuk menghitung persis karena kesulitan metodologis dalam penelitian dan perbedaan antara negara-negara [83]. Biaya tahunan di Inggris diperkirakan antara 449 juta dan 3.3 miliar pounds, sedangkan biaya per pasien per tahun di AS mungkin sekitar $ 10.000 dan total beban sekitar 23 miliar dolar [83]. Bagian terbesar dari biaya langsung berasal dari rawat inap dan panti jompo, sedangkan pangsa datang dari obat secara substansial lebih rendah. [83] Tidak Langsung biaya tinggi, karena produktivitas berkurang dan beban pada pengasuh [83] Di samping biaya ekonomi, PD mengurangi kualitas hidup dari orang-orang dengan penyakit dan pengasuh mereka.. [83]

April 11, ulang tahun James Parkinson, telah ditunjuk sebagai hari penyakit dunia Parkinson [69] [84] Sebuah bunga tulip merah dipilih oleh beberapa organisasi internasional sebagai simbol penyakit pada tahun 2005:. Itu merupakan kultivar James Tulip Parkinson , terdaftar pada tahun 1981 oleh seorang holtikultura Belanda [84] organisasi Advokasi pada penyakit termasuk National Parkinson Foundation, yang telah memberikan lebih dari $ 155,000,000 dalam pelayanan perawatan, penelitian dan dukungan sejak 1982., [85] Penyakit Yayasan Parkinson, yang telah memberikan lebih dari $ 90 juta untuk penelitian dan $ 37.000.000 untuk program pendidikan dan advokasi sejak didirikan pada tahun 1957 oleh William Hitam; [86] [87] American Parkinson Penyakit Asosiasi, didirikan pada tahun 1961; [88] dan Parkinson Eropa Penyakit Asosiasi, didirikan pada tahun 1992 [89].

Terkemuka kasus
Artikel utama: Daftar orang didiagnosis dengan penyakit Parkinson
Di antara banyak orang terkenal dengan PD, orang yang telah sangat meningkatkan kesadaran masyarakat dari penyakit adalah aktor Michael J. Fox. Fox didiagnosis pada tahun 1991 ketika ia berumur 30, tapi kondisinya dirahasiakan dari publik selama tujuh tahun [90] Ia telah menulis dua buku yg berhubungan dgn riwayat hidup sendiri di mana perjuangannya melawan penyakit tersebut memainkan peran utama, [91]. Dan muncul sebelum Kongres Amerika Serikat tanpa obat untuk menggambarkan efek dari penyakit [91]. Michael J. Fox Foundation bertujuan untuk mengembangkan obat untuk penyakit Parkinson. Dalam beberapa tahun terakhir ini telah menjadi penggalang dana utama Parkinson di Amerika Serikat, menyediakan 140 juta dolar dalam pendanaan penelitian antara 2001 dan 2008 [91]. Kerja Fox membuatnya menjadi nama salah satu dari 100 orang “yang kekuasaannya, bakat atau contoh moral mengubah dunia “pada tahun 2007 oleh majalah Time, [90] dan ia menerima gelar doktor kehormatan dalam kedokteran dari Karolinska Institutet atas kontribusi untuk penelitian dalam penyakit Parkinson [92]. lain yayasan yang mendukung riset Parkinson didirikan oleh pengendara sepeda profesional Davis Phinney. [93] Para Davis Phinney Yayasan berusaha untuk memperbaiki kehidupan mereka yang hidup dengan penyakit Parkinson dengan menyediakan mereka dengan informasi dan alat-alat [94]. Muhammad Ali telah disebut “pasien yang paling terkenal di dunia Parkinson” itu. [95] Dia adalah 42 pada Diagnosis meskipun dia sudah menunjukkan tanda-tanda Parkinson ketika ia 38. [96] Namun demikian, apakah ia telah PD atau sindrom parkinsonian disebabkan oleh tinju masih merupakan pertanyaan terbuka


The end @ copyright Dr Iwan suwandy 2011

The Mysterious Black Death(Plague Pes or Anthrax Disease)











The Driwan’s  Cybermuseum

 The Mysterious Black Death


Ilustrasi dari Black Death dari Alkitab Toggenburg (1411)
The Black Death adalah salah satu pandemi yang paling menghancurkan dalam sejarah manusia, memuncak di Eropa antara 1348 dan 1350. Dari beberapa teori yang bersaing, penjelasan yang dominan untuk Black Death adalah teori wabah, yang atribut wabah ke Yersinia pestis bakteri. Pemikiran telah dimulai di Cina, perjalanan sepanjang Jalan Sutra dan mencapai Krimea oleh 1346. Dari sana, mungkin dibawa oleh kutu tikus Oriental hidup di tikus hitam yang penumpang reguler pada kapal dagang, menyebar di seluruh Mediterania dan Eropa.

The Black Death diperkirakan telah membunuh 30-60 persen dari populasi Eropa, [1] mengurangi populasi dunia diperkirakan dari 450 juta untuk antara 350 dan 375 juta di abad ke-14. Setelah wabah menciptakan serangkaian pergolakan agama, sosial dan ekonomi, yang memiliki efek mendalam pada sejarah Eropa. Butuh waktu 150 tahun bagi penduduk Eropa untuk memulihkan. Wabah kembali pada berbagai waktu, membunuh lebih banyak orang, sampai meninggalkan Eropa di abad 19.

1 Ikhtisar
1.1 Penamaan
2 Migrasi
2.1 Populasi dalam krisis
2.2 Infeksi dan migrasi
2.3 Eropa wabah
2,4 wabah Timur Tengah
3 Gejala
4 Penyebab
4.1 Wabah
4.2 Alternatif penjelasan
4,3 bukti DNA
5 Konsekuensi
5.1 Kambuh
5.2 Dalam budaya
6 Lihat juga
7 Referensi
8 Bacaan lebih lanjut
9 Pranala luar


Terinspirasi oleh Black Death, The Dance of Death, sebuah alegori tentang universalitas kematian, merupakan motif lukisan umum dalam periode akhir abad pertengahan.
Ada tiga wabah utama dari wabah. Wabah dari Justinian pada abad 6 dan 7 adalah serangan pertama yang diketahui pada catatan, dan menandai pola tegas tercatat pertama wabah pes. Dari uraian sejarah, sebanyak 40 persen dari penduduk Konstantinopel meninggal karena wabah. Perkiraan modern menunjukkan setengah dari penduduk Eropa dihapuskan sebelum wabah menghilang di 700s [2] Setelah 750, penyakit epidemi besar tidak muncul lagi di Eropa sampai Black Death abad 14.. [3] Ketiga Pandemi melanda China di tahun 1890-an dan hancur India tetapi itu terbatas pada wabah yang terbatas di barat. [4]

The Black Death berasal di atau dekat Cina dan menyebar dengan cara Jalan Sutera atau dengan kapal. [4] Ini mungkin telah mengurangi populasi dunia diperkirakan dari 450 juta untuk antara 350 dan 375 juta pada 1400. [5]

Wabah diperkirakan telah kembali pada interval dengan virulensi yang bervariasi dan mortalitas sampai abad ke-18 [6] Setelah kembali di 1603, misalnya, wabah membunuh 38.000 London. [7]. Penting lain abad ke-17 wabah adalah Wabah Italia (1629-1631), Wabah Besar Seville (1647-1652), Wabah Besar London (1665-1666), [8] dan Wabah Besar Wina (1679). Ada beberapa kontroversi mengenai identitas dari penyakit, tetapi dalam bentuk virulen, setelah Wabah Besar Marseille pada 1720-1722, [9] Wabah Besar 1738 (yang menghantam Eropa Timur), dan wabah Rusia 1770 – 1772, tampaknya secara bertahap menghilang dari Eropa. Dengan awal abad ke 19, ancaman wabah telah berkurang, tapi itu cepat digantikan oleh penyakit baru. Kolera Asiatik adalah yang pertama dari pandemi kolera beberapa menyapu Asia dan Eropa selama abad 19 dan 20 [10].

Letusan abad ke-14 dari Black Death memiliki efek drastis terhadap populasi Eropa, tidak dapat ditarik kembali mengubah struktur sosial. Itu, boleh dibilang, sebuah pukulan serius terhadap Gereja Katolik, dan mengakibatkan penganiayaan luas minoritas seperti Yahudi, orang asing, pengemis, dan penderita kusta. Ketidakpastian kelangsungan hidup sehari-hari telah dilihat sebagai menciptakan suasana umum morbiditas, mempengaruhi orang untuk “hidup untuk saat ini”, seperti yang digambarkan oleh Giovanni Boccaccio dalam The Decameron (1353) [11].

Abad Pertengahan orang yang disebut bencana abad ke-14 baik “Sampar Agung” ‘atau “Wabah Besar” [12] Penulis kontemporer wabah disebut acara sebagai “Mortalitas Besar”.. Sejarah Swedia dan Denmark abad ke-16 menggambarkan peristiwa sebagai “hitam” untuk pertama kalinya, tidak menggambarkan tanda tahap akhir dari penyakit, di mana kulit penderita akan menghitamkan karena perdarahan subepidermal dan ekstremitas akan gelap dengan gangren , tetapi lebih cenderung untuk merujuk pada hitam dalam arti murung atau yang mengerikan dan untuk menunjukkan terribleness dan kesuraman dari peristiwa [13] Para dokter Jerman dan medis penulis Justus Hecker. menyarankan bahwa kesalahan penerjemahan dari mors atra Latin (yang mengerikan, atau hitam, kematian) telah terjadi di Skandinavia ketika ia menggambarkan bencana di 1832 [12] dalam bukunya “Der Tod im Schwarze vierzehnten Jahrhundert”. Pekerjaan itu diterjemahkan ke dalam bahasa Inggris pada tahun berikutnya, dan dengan epidemi kolera yang terjadi pada waktu itu, “The Black Death di abad 14″ mendapat perhatian luas dan istilah Schwarzer Tod dan Kematian Hitam menjadi lebih banyak digunakan dalam berbahasa Jerman dan Inggris dunia, masing-masing.

Artikel utama: migrasi Black Death
Populasi dalam krisis
Di Eropa, Warm Period Abad Pertengahan berakhir kadang menjelang akhir abad ke-13, membawa “Little Ice Age” [14] dan musim dingin yang lebih keras dengan hasil panen berkurang. Di Eropa Utara, inovasi teknologi baru seperti bajak berat dan sistem tiga-lapangan tidak efektif dalam membersihkan ladang baru untuk panen karena mereka di Mediterania karena utara telah miskin, seperti tanah liat tanah [12]. Kekurangan Makanan dan cepat menggembungkan harga adalah kenyataan hidup sebanyak satu abad sebelum wabah. Gandum, gandum, rumput kering dan akibatnya ternak, semua dalam pasokan pendek. Kelangkaan mereka mengakibatkan malnutrisi, yang meningkatkan kerentanan terhadap infeksi karena sistem kekebalan yang melemah. Tingkat kesuburan tinggi secara konsisten, pada 5 anak / wanita atau lebih di seluruh Eropa, mengakibatkan tingkat pertumbuhan penduduk yang tinggi dan memberikan kontribusi kepada kekurangan pangan. Pada musim gugur 1314, hujan lebat mulai turun, yang merupakan awal dari beberapa tahun musim dingin dan basah [12] panen sudah lemah dari utara menderita dan kelaparan yang terjadi tujuh tahun.. Pada tahun-tahun 1315-1317 sebuah bencana kelaparan, yang dikenal sebagai Kelaparan Besar, melanda sebagian besar Eropa Barat Utara. Itu bisa dibilang yang terburuk dalam sejarah Eropa, mungkin mengurangi populasi lebih dari 10 persen. [12]

Infeksi dan migrasi


Penyebaran kematian hitam di Eropa (1346-1353)
Wabah penyakit, umumnya diduga disebabkan oleh Yersinia pestis, yang enzootic (biasa hadir) dalam populasi kutu dibawa oleh hewan pengerat tanah, termasuk marmut, di berbagai daerah termasuk Asia Tengah, Kurdistan, Asia Barat, India Utara dan Uganda. [15 ] Nestorian kuburan dating ke 1338-9 dekat Danau Issyk Kul di Kyrgizstan harus mengacu pada prasasti dan investigasi wabah terbaru oleh arkeolog Rusia yang Chwolson menunjukkan angka kejadian yang tinggi dan diperkirakan oleh banyak ahli epidemiologi untuk menandai wabah epidemi, dari mana mereka bisa mudah telah menyebar ke China dan India [16] Pada bulan Oktober 2010, genetika medis menegaskan bahwa wabah berasal dari Cina. [4] Di Cina, Mongol abad ke-13 penaklukan menyebabkan penurunan dalam pertanian dan perdagangan.. Namun, pemulihan ekonomi telah diamati pada awal abad ke-14. Pada frekuensi tinggi 1330-an bencana alam dan wabah penyakit menyebabkan kelaparan luas yang dimulai pada 1331 dengan wabah mematikan tiba segera setelah [17]. Populasi menurun dari sekitar 120-60000000. [18] abad ke-14 wabah menewaskan sekitar 25 juta China memperkirakan dan Asia lainnya selama 15 tahun sebelum memasuki Konstantinopel pada tahun 1347. [19]

Penyakit ini mungkin memiliki perjalanan sepanjang Jalan Sutra dengan tentara Mongol dan pedagang atau bisa datang melalui kapal [20] Pada akhir 1346 laporan wabah telah mencapai pelabuhan Eropa:. “India depopulasi, Tartar, Mesopotamia, Suriah , Armenia ditutupi dengan mayat “. [21]

Wabah dilaporkan pertama kali diperkenalkan ke Eropa di kota perdagangan Caffa di Krimea pada tahun 1347. Setelah pengepungan yang berlarut-larut, di mana pasukan Mongol di bawah Jani Beg adalah menderita penyakit ini, mereka terlempar mayat-mayat yang terinfeksi selama tembok kota untuk menginfeksi penduduk. Para pedagang Genoa melarikan diri, mengambil wabah dengan kapal ke Sisilia dan selatan Eropa, dari mana ia menyebar utara [22] Apakah atau tidak hipotesis ini adalah akurat, jelas bahwa beberapa kondisi yang ada seperti perang, kelaparan, dan cuaca berkontribusi. dengan tingkat keparahan dari Black Death.

Eropa wabah
Ada tampaknya telah beberapa perkenalan ke Eropa. It mencapai Sisilia pada Oktober 1347 yang dibawa oleh dua belas kapal Genoa, [23] di mana ia dengan cepat tersebar di seluruh pulau. Kapal dari Caffa mencapai Genoa dan Venesia di Januari 1348 tetapi wabah itu di Pisa beberapa minggu kemudian bahwa adalah titik masuk ke bagian utara Italia. Menjelang akhir Januari salah satu kapal diusir dari Italia tiba di Marseilles. [24]

Dari Italia penyakit menyebar di seluruh Eropa barat laut, mencolok Perancis, Spanyol, Portugal dan Inggris pada bulan Juni 1348, lalu berbalik dan menyebar ke timur melalui Jerman dan Skandinavia 1348-1350. Saat itu diperkenalkan di Norwegia pada 1349 ketika sebuah kapal mendarat di Askøy, kemudian mulai menyebar ke Bjørgvin (modern Bergen) tetapi tidak pernah mencapai Islandia [25]. Akhirnya menyebar ke utara-barat Rusia di 1351. Wabah terhindar dari beberapa bagian Eropa, termasuk Kerajaan Polandia dan bagian terisolasi dari Belgia dan Belanda [kutipan diperlukan].

Timur Tengah wabah
Wabah melanda berbagai negara di Timur Tengah selama pandemi, yang menyebabkan depopulasi serius dan perubahan permanen dalam struktur ekonomi dan sosial. Seperti menyebar ke Eropa Barat, penyakit ini juga memasuki wilayah tersebut dari Rusia selatan. Dengan musim gugur 1347, wabah mencapai Alexandria di Mesir, mungkin melalui perdagangan pelabuhan dengan Konstantinopel, dan pelabuhan di Laut Hitam. Selama 1347, penyakit yang ditempuh ke arah timur ke Gaza, dan utara di sepanjang pantai timur ke kota-kota di Lebanon, Suriah dan Palestina, termasuk Ashkelon, Acre, Yerusalem, Sidon, Damaskus, Homs, dan Aleppo. Pada 1348-49, penyakit mencapai Antiokhia. Penduduk kota melarikan diri ke utara, sebagian besar dari mereka meninggal selama perjalanan, tetapi infeksi telah menyebar ke orang-orang di Asia Kecil.

Mekkah menjadi terinfeksi pada 1349. Pada tahun yang sama, catatan menunjukkan kota Mawsil (Mosul) mengalami epidemi besar, dan kota Baghdad mengalami putaran kedua penyakit. Pada 1351, Yaman mengalami pecahnya wabah. Hal ini bertepatan dengan kembalinya Raja Mujahid Yaman dari penjara di Kairo. Partainya telah membawa penyakit dengan mereka dari Mesir.


Buboes dalam korban wabah

Sebuah adegan menunjukkan bhikkhu, rusak oleh wabah penyakit, yang diberkati oleh seorang imam. Inggris, 1360-1375
Rekening kontemporer dari wabah sering bervariasi atau tidak tepat. Gejala yang paling sering dicatat adalah munculnya buboes (atau gavocciolos) di selangkangan, leher dan ketiak, yang mengalir nanah dan berdarah ketika dibuka [26] deskripsi Boccaccio adalah grafis.:

“Pada laki-laki dan perempuan sama-sama pertama kali dikhianati sendiri oleh munculnya tumor tertentu di paha atau ketiak, beberapa di antaranya tumbuh sebagai besar sebagai apel umum, orang lain sebagai telur … Dari dua kata bagian dari tubuh ini mematikan gavocciolo segera mulai menyebarkan dan menyebarkan dirinya sendiri ke segala arah acuh tak acuh, setelah mana bentuk penyakit mulai berubah, bintik hitam atau marah membuat penampilan mereka dalam banyak kasus di lengan atau paha atau di tempat lain, sekarang sedikit dan besar, sekarang menit dan banyak. Sebagai gavocciolo telah dan masih merupakan tanda kematian mendekati sempurna, seperti juga yang bintik-bintik pada siapapun mereka menunjukkan diri mereka sendiri “[27].

Ziegler komentar bahwa detail-satunya medis yang dipertanyakan adalah kemaksuman mendekati kematian, seolah-olah pembuangan bubo, pemulihan adalah mungkin. [28]

Ini diikuti dengan demam akut dan muntah darah. Kebanyakan korban meninggal dalam waktu dua sampai tujuh hari setelah infeksi. David Herlihy mengidentifikasi tanda lain potensi wabah: bintik-bintik dan ruam [29] yang dapat menjadi hasil dari gigitan kutu.

Beberapa account, seperti Louis Heyligen, seorang musisi di Avignon yang meninggal wabah di 1348, mencatat bentuk yang berbeda dari penyakit yang menginfeksi paru-paru dan menyebabkan masalah pernapasan [26] dan yang diidentifikasi dengan wabah pneumonia.

“Dikatakan bahwa wabah itu mengambil tiga bentuk Pada orang pertama menderita infeksi paru-paru, yang menyebabkan kesulitan bernapas.. Siapapun yang ini korupsi atau kontaminasi sampai batas tertentu tidak dapat melarikan diri tetapi akan mati dalam waktu dua hari. Bentuk lain .. di mana bisul meletus di bawah ketiak, … bentuk ketiga di mana orang dari kedua jenis kelamin diserang di selangkangan “[30]..

Artikel utama: Teori Black Death
Pengetahuan medis telah mengalami stagnasi selama Abad Pertengahan dan akun paling otoritatif pada saat itu berasal dari Fakultas Kedokteran di Paris dalam sebuah laporan kepada Raja Prancis, yang menyalahkan langit-konjungsi planet-planet di tiga 1345, yang menyebabkan “besar wabah penyakit di udara “[31]. Laporan ini menjadi yang pertama dan paling luas beredar dari serangkaian” traktat wabah “yang berusaha untuk memberikan nasihat kepada penderita. Bahwa wabah itu disebabkan oleh udara yang buruk menjadi teori yang paling diterima secara luas. Adalah penting untuk menyadari bahwa wabah kata tidak memiliki makna khusus saat ini. Namun terulangnya wabah selama Abad Pertengahan memberinya reputasi yang unik dan nama telah menjadi istilah medis.

Pentingnya kebersihan hanya diakui dalam abad kesembilan belas dan sampai saat itu adalah umum bahwa jalan-jalan kotor, dengan binatang hidup dari segala macam sekitar dan kutu kutu manusia dan berlimpah. Setiap penyakit menular akan menyebar dengan mudah dalam kondisi seperti itu. Salah satu perkembangan sebagai hasil dari Black Death adalah pembentukan ide karantina di Dubrovnik di 1377 setelah wabah terus [kutipan diperlukan].



Yersinia pestis dilihat di 200x pembesaran. Bakteri ini, dibawa dan disebarkan oleh kutu, umumnya dianggap telah menjadi penyebab jutaan kematian. [32]
Penjelasan yang dominan untuk Black Death adalah teori wabah, yang atribut wabah untuk Yersinia pestis, juga bertanggung jawab untuk epidemi yang dimulai di China selatan pada tahun 1865, akhirnya menyebar ke India. Penyelidikan patogen yang menyebabkan wabah abad ke-19 dimulai oleh tim ilmuwan yang mengunjungi Hong Kong pada tahun 1894, di antaranya adalah Alexandre Yersin, setelah yang patogen itu bernama Yersinia pestis. [33] Mekanisme dimana Y. pestis biasanya ditularkan didirikan pada tahun 1898 oleh Paul-Louis Simond dan ditemukan untuk melibatkan gigitan kutu yang telah menjadi terhalang midguts dengan mereplikasi Y. pestis beberapa hari setelah makan pada sebuah host yang terinfeksi. Penyumbatan ini menyebabkan kelaparan dan perilaku makan agresif oleh kutu, yang berulang kali mencoba untuk menghapus penyumbatan mereka dengan regurgitasi, mengakibatkan ribuan wabah bakteri yang memerah ke situs makan, menginfeksi host. Mekanisme penyakit pes itu juga tergantung pada dua populasi tikus – satu resisten terhadap penyakit, yang bertindak sebagai tuan rumah, menjaga penyakit endemik, dan yang kedua yang kurang perlawanan. Ketika populasi kedua meninggal, kutu pindah ke host lain, termasuk orang-orang, sehingga menciptakan suatu epidemi manusia. [33]

Sejarawan Francis Aidan Gasquet, yang telah menulis tentang ‘Sampar Agung’ pada tahun 1893 [34] dan menyarankan bahwa “akan muncul menjadi beberapa bentuk dari wabah pes Timur atau biasa” mampu mengadopsi epidemiologi penyakit pes untuk Black Death untuk edisi kedua tahun 1908, melibatkan tikus dan kutu dalam proses, dan penafsirannya secara luas diterima untuk epidemi kuno dan abad pertengahan lainnya, seperti wabah Justinian yang lazim di Kekaisaran Romawi Timur 541-700 AD. [33]

Wabah pes modern memiliki tingkat kematian 30 sampai 75 persen dan gejala termasuk demam 38-41 ° C (101-105 ° F), sakit kepala, nyeri sendi sakit, mual dan muntah, dan perasaan umum malaise. Jika tidak diobati, dari mereka yang kontrak penyakit pes, 80 persen meninggal dalam waktu delapan hari [35] wabah pneumonia. Memiliki tingkat kematian 90 sampai 95 persen. Gejalanya meliputi demam, batuk, dan darah-biruan dahak. Sebagai penyakit berlangsung, dahak menjadi merah dan terang mengalir bebas. Wabah septicemia adalah yang paling umum dari tiga bentuk, dengan tingkat mortalitas mendekati 100 persen. Gejala demam tinggi dan bercak kulit ungu (purpura akibat koagulasi intravaskular diseminata). Dalam kasus wabah pneumonia dan khususnya septicemia kemajuan penyakit ini begitu cepat sehingga sering ada akan ada waktu untuk pengembangan pembesaran kelenjar getah bening yang tercatat sebagai buboes [36].

“Banyak sarjana modern menerima bahwa mematikan dari Black Death berasal dari kombinasi wabah pes dan pneumonia dengan penyakit lain dan memperingatkan bahwa setiap menyebutkan sejarah ‘hama’ bukan wabah pes tentu … Dalam studi nya wabah 15thC, Ann Carmichael menyatakan bahwa cacing, cacar, demam dan disentri jelas disertai penyakit pes “[37].

Alternatif penjelasan
Penafsiran ini pertama kali secara signifikan ditantang oleh karya bakteriologi Inggris JFD Shrewsbury pada tahun 1970, yang mencatat bahwa tingkat kematian dilaporkan di daerah pedesaan selama pandemi abad ke-14 tidak konsisten dengan penyakit pes modern, memimpin dia untuk menyimpulkan bahwa rekening kontemporer berlebihan . [33] Pada tahun 1984 ahli zoologi Graham Twigg menghasilkan karya besar pertama untuk langsung menantang teori penyakit pes, dan keraguan tentang identitas Black Death telah diambil oleh sejumlah penulis, termasuk Samuel K. Cohn, Jr (2002), David Herlihy (1997), dan Susan Scott dan Christopher Duncan (2001) [33].

Hal ini diakui bahwa account epidemiologi wabah adalah sebagai penting sebagai identifikasi gejala, namun para peneliti terhambat oleh kurangnya statistik yang dapat diandalkan dari periode ini. Pekerjaan yang paling telah dilakukan pada penyebaran wabah di Inggris, dan bahkan perkiraan populasi keseluruhan di awal bervariasi oleh lebih dari 100% karena tidak ada sensus dilakukan antara Kitab Domesday dan 1377. [38] Perkiraan korban wabah biasanya diekstrapolasi dari angka untuk para ulama.

Selain berdebat bahwa populasi tikus tidak cukup untuk account untuk pandemi penyakit pes, skeptis dari titik wabah pes teori bahwa gejala Black Death tidak unik (dan bisa dibilang dalam beberapa rekening mungkin berbeda dari wabah pes); yang transferensi melalui kutu barang itu mungkin penting marjinal dan bahwa tes DNA mungkin cacat dan belum pernah diulang di tempat lain, meskipun sampel yang luas dari kuburan massal lainnya [33] argumen lainnya termasuk:. kurangnya rekening kematian tikus sebelum wabah wabah antara abad 14 dan 17, suhu yang terlalu dingin di Eropa Utara untuk kelangsungan hidup kutu, bahwa, meskipun sistem transportasi primitif, penyebaran Black Death jauh lebih cepat daripada Bubonic plague modern, yang tingkat mortalitas dari Black Death tampaknya sangat tinggi, bahwa, selama wabah pes modern sebagian besar endemik sebagai penyakit pedesaan, Black Death melanda tanpa pandang bulu daerah perkotaan dan pedesaan; bahwa pola Black Death, dengan wabah besar di daerah yang sama yang dipisahkan oleh antara 5 dan 15 tahun, berbeda dari wabah pes yang modern, yang sering menjadi endemik selama beberapa dekade, melebar sampai pada dasar tahunan. [33]

Walløe mengeluh bahwa semua penulis “menerima begitu saja bahwa infeksi Model Simond itu, tikus hitam → kutu tikus → manusia, yang dikembangkan untuk menjelaskan penyebaran wabah di India, adalah satu-satunya cara epidemi infeksi pestis Yersinia dapat menyebar” , sementara menunjuk ke kemungkinan lainnya. [39]

Anthrax kulit lesi
Berbagai alternatif ke Y. pestis telah diajukan. Twigg menyarankan bahwa penyebabnya adalah bentuk antraks dan NF penyanyi (2001) berpikir itu mungkin telah menjadi kombinasi anthrax dan pandemi lainnya. Scott dan Duncan berpendapat bahwa pandemi adalah bentuk penyakit menular yang mencirikan sebagai wabah hemoragik mirip dengan Ebola. Barney arkeolog Sloane berpendapat bahwa ada bukti yang cukup dari kepunahan sejumlah besar tikus dalam catatan arkeologi abad pertengahan di tepi laut London dan bahwa wabah itu menyebar terlalu cepat untuk mendukung tesis bahwa Y. pestis adalah menyebar dari kutu pada tikus dan berpendapat transmisi yang pasti orang ke orang [40] [41]. Namun, ada solusi alternatif tunggal telah mencapai penerimaan luas. [33] Banyak sarjana berdebat untuk Y. pestis sebagai agen utama dari pandemi, menunjukkan bahwa perusahaan luas dan gejala dapat dijelaskan oleh kombinasi dari wabah pes dengan penyakit lain, termasuk infeksi tifus, cacar dan pernapasan. Selain infeksi pes, orang lain titik untuk septicemia tambahan (tipe “keracunan darah”) dan pneumonia (sebuah wabah udara yang menyerang paru-paru sebelum seluruh tubuh) bentuk wabah, yang memperpanjang durasi wabah seluruh musim dan membantu menjelaskan tingkat kematian yang tinggi dan gejala dicatat tambahan [26].

Bukti DNA
Pada bulan Oktober 2010 akses terbuka jurnal ilmiah PLoS Pathogens menerbitkan sebuah makalah oleh tim multinasional yang melakukan penyelidikan baru ke dalam peran Yersinia pestis di Black Death berikut identifikasi diperdebatkan oleh Drancourt & Raoult pada tahun 1998 [42]. Survei mereka diuji untuk tanda tangan DNA dan protein spesifik untuk Y. pestis dalam kerangka manusia dari kuburan massal secara luas didistribusikan di utara, tengah dan selatan Eropa yang dikaitkan arkeologis dengan Black Death dan resurgences berikutnya. Para penulis menyimpulkan bahwa penelitian baru ini, bersama dengan analisis terlebih dahulu dari bagian selatan Perancis dan Jerman

Pembakaran Yahudi selama wabah Black Death, 1349
“… Mengakhiri perdebatan mengenai etiologi dari Black Death, dan jelas menunjukkan bahwa Y. pestis adalah agen penyebab wabah epidemi yang menghancurkan Eropa selama Abad Pertengahan.” [43]
Studi ini juga menemukan bahwa ada dua clades sebelumnya tidak diketahui namun terkait (cabang genetik) dari Y. pestis genom dikaitkan dengan kuburan massal abad pertengahan. Ini clades (yang dianggap punah) ditemukan merupakan nenek moyang isolat modern dari yang modern Y. pestis strain orientalis dan medievalis, menunjukkan bahwa wabah mungkin telah masuk ke Eropa dalam dua gelombang. Survei dari pit wabah tetap di Prancis dan Inggris menunjukkan bahwa varian pertama kali memasuki Eropa melalui pelabuhan Marseille sekitar November 1347 dan menyebar melalui Prancis selama dua tahun ke depan, akhirnya mencapai Inggris pada musim semi 1349, di mana ia menyebar melalui negara dalam tiga epidemi. Survei dari pit wabah tetap dari kota Belanda Bergen op Zoom menunjukkan bahwa genotipe Y. pestis bertanggung jawab atas pandemi yang menyebar melalui Negara Rendah dari 1350 berbeda dari yang ditemukan di Inggris dan Perancis, yang menyiratkan bahwa Bergen op Zoom (dan mungkin lainnya bagian selatan Belanda) tidak secara langsung terinfeksi dari Inggris atau Perancis pada 1349 dan menyarankan bahwa gelombang kedua wabah, yang berbeda dari mereka di Inggris dan Perancis, mungkin telah dibawa ke Low Countries dari Norwegia, kota-kota Hanseatic atau situs lain . [43]

Hasil studi Haensch telah sejak dikonfirmasi dan diubah. Berdasarkan bukti genetik yang berasal dari korban Black Death di situs pemakaman Smithfield Timur di Inggris, Schuenemann et al. pada 2011 lebih lanjut menyimpulkan “bahwa Black Death di Eropa abad pertengahan disebabkan oleh Y. pestis varian yang mungkin tidak ada lagi.” [44] Sebuah studi yang dipublikasikan di Nature pada bulan Oktober 2011 sequencing genom Y. pestis dari para korban wabah penyakit dan menunjukkan bahwa strain yang menyebabkan Black Death adalah nenek moyang strain paling modern penyakit. [45]

Artikel utama: Konsekuensi dari Black Death
Angka korban tewas bervariasi menurut daerah dan dari sumber ke sumber sebagai penelitian baru dan penemuan datang ke cahaya. Ini diperkirakan menewaskan sekitar 75 juta-200 juta orang di abad ke-14 [46] [47] [48] Menurut sejarawan abad pertengahan Philip Daileader pada tahun 2007.:

Sebuah adegan menunjukkan Yahudi dibakar hidup-hidup selama periode Black Death, Liber Chronicarum.
Kecenderungan dari penelitian baru-baru ini menunjuk ke angka yang lebih seperti 45 persen menjadi 50 persen dari penduduk Eropa meninggal selama periode empat tahun. Ada cukup banyak variasi geografis. Di Mediterania Eropa, bidang-bidang seperti Italia, selatan Perancis dan Spanyol, di mana wabah berlari selama sekitar empat tahun berturut-turut, itu mungkin lebih dekat ke 75 persen menjadi 80 persen dari populasi. Di Jerman dan Inggris … itu mungkin lebih dekat ke 20 persen. [49]

Perkiraan yang paling banyak diterima untuk Timur Tengah, termasuk Irak, Iran dan Suriah, selama waktu ini, adalah untuk tingkat kematian sekitar sepertiga. [50] The Black Death membunuh sekitar 40% dari populasi Mesir. [51] Setengah dari penduduk Paris dari 100.000 orang meninggal. Di Italia, populasi Florence berkurang dari 110.000 atau 120.000 penduduk tahun 1338 menjadi 50.000 pada 1351. Setidaknya 60 persen dari Hamburg dan populasi Bremen tewas. [52] Sebelum 1350, ada sekitar 170.000 pemukiman di Jerman, dan ini berkurang hampir 40.000 dengan 1450 [53] Pada 1348, wabah menyebar begitu cepat. Bahwa sebelum dokter atau otoritas pemerintah punya waktu untuk merenungkan asal-usulnya, sekitar sepertiga dari penduduk Eropa yang sudah tewas. Di kota-kota padat, tidak jarang sebanyak 50 persen dari populasi untuk mati. Eropa yang tinggal di daerah terpencil mengalami kurang, sedangkan rahib dan pendeta yang terutama terpukul karena mereka peduli untuk korban Black Death. [54]

Flagellants dipraktekkan pembekuan daging sebagai penitensi
Karena penyembuh abad ke-14 berada di kerugian untuk menjelaskan penyebab, Eropa berpaling ke kekuatan astrologi, gempa bumi, dan keracunan sumur oleh orang Yahudi sebagai alasan mungkin untuk munculnya wabah tersebut. [12] Pemerintah Eropa telah ada respon yang jelas terhadap krisis karena tidak ada yang tahu penyebabnya atau bagaimana itu menyebar. Mekanisme infeksi dan penularan penyakit sedikit dipahami dalam abad ke-14, banyak orang percaya hanya murka Allah bisa memproduksi layar mengerikan tersebut. Ada banyak serangan terhadap komunitas Yahudi [55] Pada Agustus 1349, komunitas Yahudi dari Mainz dan Cologne dibasmi.. Pada bulan Februari tahun yang sama, warga Strasbourg 2.000 orang Yahudi dibunuh [55] Pada 1351, 60 besar dan 150 komunitas Yahudi yang lebih kecil hancur.. [56] Ikhwanul dari Flagellants, gerakan kata ke nomor sampai dengan 800.000, mencapai puncaknya popularitas [57].

Sebuah epidemik wabah meninggal setelah beberapa bulan karena tidak memiliki tuan rumah di mana bakteri dapat bertahan hidup. Namun itu tidak berarti bahwa tidak ada suatu tempat beberapa infeksi yang masih hidup, di tempat tikus atau kutu atau hangat, yang bertindak sebagai reservoir sehingga cepat atau lambat pecah lagi. [58]

Wabah berulang kali kembali menghantui Eropa dan Mediterania sepanjang 14 sampai 17 abad [59]. Menurut Biraben, wabah itu ada di suatu tempat di Eropa setiap tahun antara 1346 dan 1671. [60] Para Pandemi Kedua terutama luas di berikut tahun: 1360-1363, 1374, 1400, 1438-1439, 1456-1457, 1464-1466, 1481-1485, 1500-1503, 1518-1531, 1544-1548, 1563-1566, 1573-1588, 1596-1599; 1602-1611, 1623-1640, 1644-1654;. dan 1664-1667 [61] Menurut Geoffrey Parker, “Perancis saja kehilangan hampir satu juta orang untuk wabah epidemi di 1628-31.” [62]

Di Inggris, dalam ketiadaan angka sensus, sejarawan mengusulkan berbagai pra-insiden jumlah penduduk dari setinggi 7 juta untuk serendah 4 juta pada 1300, [63] dan pasca-insiden populasi angka serendah 2 juta [64] Pada akhir 1350. Black Death mereda, tapi tidak pernah benar-benar mati di Inggris. Selama beberapa ratus tahun berikutnya, ada wabah lebih lanjut dalam 1361-62, 1369, 1379-83, 1389-93, dan sepanjang paruh pertama abad ke-15 [65]. Sebuah wabah di 1471 mengambil sebanyak 10-15 persen dari populasi, sementara tingkat kematian wabah 1479-1480 bisa setinggi 20 persen [66]. Wabah yang paling umum di Tudor dan Stuart Inggris tampaknya telah dimulai pada tahun 1498, 1535, 1543, 1563, 1589, 1603, 1625, dan 1636, dan berakhir dengan Wabah Besar London pada tahun 1665. [67]

Wabah Kerusuhan di Moskow pada 1771. Selama wabah kota, antara 50.000 dan 100.000 meninggal (1 / 6 sampai 1 / 3 dari populasi nya).
Pada 1466, mungkin 40.000 orang meninggal dari wabah di Paris [68] Selama abad 16 dan 17, wabah mengunjungi Paris selama hampir satu tahun dari tiga.. [69] The Black Death melanda Eropa selama tiga tahun sebelum melanjutkan ke Rusia , dimana penyakit hit di suatu tempat sekali setiap lima atau enam tahun 1350-1490 [70] Wabah epidemi melanda London pada 1563, 1593, 1603, 1625, 1636, dan 1665, [71] mengurangi populasi 10 hingga 30%. selama tahun-tahun [72] Lebih dari 10% penduduk Amsterdam meninggal. di 1623-1625, dan sekali lagi pada 1635-1636, 1655 dan 1664. [73] Ada dua puluh dua wabah wabah di Venesia antara 1361 dan 1528. [74 ] Tulah dari 1576-1577 menewaskan 50.000 di Venice, hampir sepertiga dari penduduk [75] Akhir wabah di pusat Eropa termasuk Italia Wabah 1629-1631, yang berhubungan dengan gerakan pasukan selama Perang Tiga Puluh Tahun ‘,. dan Wabah Besar Wina pada tahun 1679. Lebih dari 60 persen penduduk Norwegia meninggal 1348-1350. [76] Wabah terakhir dilanda wabah Oslo pada 1654 [77].

Pada paruh pertama abad ke-17 mengklaim beberapa wabah 1.730.000 korban di Italia, atau sekitar 14% dari populasi [78] Pada 1656. Wabah membunuh sekitar setengah dari 300.000 Naples ‘penduduk. [79] Lebih dari 1.250.000 kematian akibat kejadian ekstrim wabah di Spanyol abad ke-17. [80] Para wabah 1649 mungkin mengurangi populasi Sevilla dengan setengah [81] Pada 1709-1713., epidemi wabah yang mengikuti Perang Besar Utara (1700-1721, Swedia v Rusia dan sekutu). [82] menewaskan sekitar 100.000 di Swedia, [83] dan 300.000 di Prusia [81]. Tulah membunuh dua-pertiga dari penduduk Helsinki, [84] dan mengklaim sepertiga dari populasi Stockholm. [85 epidemi besar terakhir] Eropa terjadi pada tahun 1720 di Marseilles. [76]

Distribusi di seluruh dunia terinfeksi wabah hewan 1998
The Black Death melanda sebagian besar dunia Islam [86]. Wabah hadir dalam setidaknya satu lokasi di dunia Islam hampir setiap tahun antara tahun 1500 dan 1850. [87] Wabah berulang kali melanda kota-kota Afrika Utara. Aljazair kehilangan 30,000-50,000 untuk wabah di 1620-21, dan sekali lagi pada 1654-57,, 1665 1691, dan 1740-42 [88]. Wabah tetap menjadi peristiwa besar dalam masyarakat Utsmani sampai kuartal kedua abad ke-19. Antara 1701 dan 1750, 37 epidemi wabah yang lebih besar dan lebih kecil tercatat di Konstantinopel, dan 31 antara 1751 dan 1800 [89]. Baghdad telah menderita parah dari kunjungan wabah, dan kadang-kadang dua-pertiga dari penduduknya telah musnah. [ 90]

Para Pandemi Ketiga (1855-1959) dimulai di Cina pada pertengahan abad ke-19, wabah menyebar ke semua benua yang dihuni dan membunuh 10 juta orang di India saja. [91]

Dari 1944 hingga 1993, 362 kasus wabah manusia yang dilaporkan di Amerika Serikat, sekitar 90 persen dari terjadi di empat negara bagian barat;. Arizona, California, Colorado, dan New Mexico [92] Wabah dikonfirmasi di Amerika Serikat dari sembilan negara Barat selama 1995 [93].

Bakteri wabah dapat mengembangkan resistensi obat dan sekali lagi menjadi ancaman kesehatan utama. Kemampuan untuk melawan banyak antibiotik digunakan untuk melawan wabah telah ditemukan sejauh ini hanya dalam satu kasus penyakit di Madagaskar, pada tahun 1995. [94]

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Artikel utama: Black Death dalam budaya Abad Pertengahan

Pieter Bruegel The Triumph of Death (c. 1562) mencerminkan pergolakan sosial dan teror yang diikuti wabah yang menghancurkan Eropa Abad Pertengahan
The Black Death memiliki dampak yang mendalam pada seni dan sastra di seluruh generasi yang mengalaminya. Sebagian besar manifestasi yang paling berguna dari Black Death dalam literatur, para ahli sejarah, berasal dari rekening sejarah nya. Beberapa penulis sejarah adalah penulis terkenal, filsuf dan penguasa seperti Boccaccio dan Petrarch. Tulisan-tulisan mereka, bagaimanapun, tidak mencapai mayoritas penduduk Eropa. Petrarch pekerjaan itu dibaca terutama oleh bangsawan kaya dan pedagang negara-kota Italia. Dia menulis ratusan surat dan puisi vernakular, dan diteruskan kepada generasi berikutnya interpretasi direvisi cinta santun [95]. Ada satu penyanyi, menulis dalam gaya lirik panjang keluar dari fashion, yang aktif dalam 1348.






Illustration of the Black Death from the Toggenburg Bible (1411)

The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350. Of several competing theories, the dominant explanation for the Black Death is the plague theory, which attributes the outbreak to the bacterium Yersinia pestis. Thought to have started in China, it travelled along the Silk Road and reached the Crimea by 1346. From there, probably carried by Oriental rat fleas living on the black rats that were regular passengers on merchant ships, it spread throughout the Mediterranean and Europe.

The Black Death is estimated to have killed 30–60 percent of Europe’s population,[1] reducing the world’s population from an estimated 450 million to between 350 and 375 million in the 14th century. The aftermath of the plague created a series of religious, social and economic upheavals, which had profound effects on the course of European history. It took 150 years for Europe’s population to recover. The plague returned at various times, killing more people, until it left Europe in the 19th century.



Inspired by the Black Death, The Dance of Death, an allegory on the universality of death, is a common painting motif in the late medieval period.

There have been three major outbreaks of plague. The Plague of Justinian in the 6th and 7th centuries is the first known attack on record, and marks the first firmly recorded pattern of bubonic plague. From historical descriptions, as much as 40 percent of the population of Constantinople died from the plague. Modern estimates suggest half of Europe’s population was wiped out before the plague disappeared in the 700s.[2] After 750, major epidemic diseases did not appear again in Europe until the Black Death of the 14th century.[3] The Third Pandemic hit China in the 1890s and devastated India but was confined to limited outbreaks in the west.[4]

The Black Death originated in or near China and spread by way of the Silk Road or by ship.[4] It may have reduced the world’s population from an estimated 450 million to between 350 and 375 million in 1400.[5]

The plague is thought to have returned at intervals with varying virulence and mortality until the 18th century.[6] On its return in 1603, for example, the plague killed 38,000 Londoners.[7] Other notable 17th-century outbreaks were the Italian Plague (1629–1631), the Great Plague of Seville (1647–1652), the Great Plague of London (1665–1666),[8] and the Great Plague of Vienna (1679). There is some controversy over the identity of the disease, but in its virulent form, after the Great Plague of Marseille in 1720–1722,[9] the Great Plague of 1738 (which hit Eastern Europe), and the Russian plague of 1770-1772, it seems to have gradually disappeared from Europe. By the early 19th century, the threat of plague had diminished, but it was quickly replaced by a new disease. The Asiatic cholera was the first of several cholera pandemics to sweep through Asia and Europe during the 19th and 20th centuries.[10]

The 14th century eruption of the Black Death had a drastic effect on Europe’s population, irrevocably changing the social structure. It was, arguably, a serious blow to the Catholic Church, and resulted in widespread persecution of minorities such as Jews, foreigners, beggars, and lepers. The uncertainty of daily survival has been seen as creating a general mood of morbidity, influencing people to “live for the moment”, as illustrated by Giovanni Boccaccio in The Decameron (1353).[11]


Medieval people called the catastrophe of the 14th century either the “Great Pestilence”‘ or the “Great Plague”.[12] Writers contemporary to the plague referred to the event as the “Great Mortality”. Swedish and Danish chronicles of the 16th century described the events as “black” for the first time, not to describe the late-stage sign of the disease, in which the sufferer’s skin would blacken due to subepidermal hemorrhages and the extremities would darken with gangrene, but more likely to refer to black in the sense of glum or dreadful and to denote the terribleness and gloom of the events.[13] The German physician and medical writer Justus Hecker suggested that a mistranslation of the Latin atra mors (terrible, or black, death) had occurred in Scandinavia when he described the catastrophe in 1832[12] in his publication “Der schwarze Tod im vierzehnten Jahrhundert”. The work was translated into English the following year, and with the cholera epidemic happening at that time, “The Black Death in the 14th century” gained widespread attention and the terms Schwarzer Tod and Black Death became more widely used in the German and English speaking worlds, respectively.


Main article: Black Death migration

Populations in crisis

In Europe, the Medieval Warm Period ended sometime towards the end of the 13th century, bringing the “Little Ice Age[14] and harsher winters with reduced harvests. In Northern Europe, new technological innovations such as the heavy plough and the three-field system were not as effective in clearing new fields for harvest as they were in the Mediterranean because the north had poor, clay-like soil.[12] Food shortages and rapidly inflating prices were a fact of life for as much as a century before the plague. Wheat, oats, hay and consequently livestock, were all in short supply. Their scarcity resulted in malnutrition, which increases susceptibility to infections due to weakened immunity. Consistently high fertility rates, at 5 children/woman or more throughout Europe, resulted in high population growth rates and contributed to food shortages. In the autumn of 1314, heavy rains began to fall, which were the start of several years of cold and wet winters.[12] The already weak harvests of the north suffered and the seven-year famine ensued. In the years 1315 to 1317 a catastrophic famine, known as the Great Famine, struck much of North West Europe. It was arguably the worst in European history, perhaps reducing the population by more than 10 percent.[12]

Infection and migration

Spread of the black death in Europe (1346–53)

The plague disease, generally thought to be caused by Yersinia pestis, is enzootic (commonly present) in populations of fleas carried by ground rodents, including marmots, in various areas including Central Asia, Kurdistan, Western Asia, Northern India and Uganda.[15] Nestorian graves dating to 1338-9 near Lake Issyk Kul in Kyrgizstan have inscriptions referring to plague and recent investigations by the Russian archeologist Chwolson show a high incidence rate and are thought by many epidemiologists to mark the outbreak of the epidemic, from which they could easily have spread to China and India.[16] In October 2010, medical geneticists confirmed that the plague came from China.[4] In China, the 13th century Mongol conquest caused a decline in farming and trading. However, economic recovery had been observed in the beginning of the 14th century. In 1330s high frequency of natural disaster and plague led to widespread famine starting in 1331 with deadly plague arriving soon after.[17] The population dropped from approximately 120 to 60 million.[18] The 14th-century plague killed an estimated 25 million Chinese and other Asians during the 15 years before it entered Constantinople in 1347.[19]

The disease may have travelled along the Silk Road with Mongol armies and traders or it could have come via ship.[20] By the end of 1346 reports of plague had reached the seaports of Europe: “India was depopulated, Tartary, Mesopotamia, Syria, Armenia were covered with dead bodies”.[21]

Plague was reportedly first introduced to Europe at the trading city of Caffa in the Crimea in 1347. After a protracted siege, during which the Mongol army under Jani Beg was suffering the disease, they catapulted the infected corpses over the city walls to infect the inhabitants. The Genoese traders fled, taking the plague by ship into Sicily and the south of Europe, whence it spread north.[22] Whether or not this hypothesis is accurate, it is clear that several existing conditions such as war, famine, and weather contributed to the severity of the Black Death.

European outbreak

There appear to have been several introductions into Europe. It reached Sicily in October 1347 carried by twelve Genoese galleys,[23] where it rapidly spread all over the island. Galleys from Caffa reached Genoa and Venice in January 1348 but it was the outbreak in Pisa a few weeks later that was the entry point to northern Italy. Towards the end of January one of the galleys expelled from Italy arrived in Marseilles.[24]

From Italy the disease spread northwest across Europe, striking France, Spain, Portugal and England by June 1348, then turned and spread east through Germany and Scandinavia from 1348 to 1350. It was introduced in Norway in 1349 when a ship landed at Askøy, then proceeded to spread to Bjørgvin (modern Bergen) but never reached Iceland.[25] Finally it spread to north-western Russia in 1351. The plague spared some parts of Europe, including the Kingdom of Poland and isolated parts of Belgium and the Netherlands.[citation needed]

Middle Eastern outbreak

The plague struck various countries in the Middle East during the pandemic, leading to serious depopulation and permanent change in both economic and social structures. As it spread to western Europe, the disease also entered the region from southern Russia. By autumn 1347, the plague reached Alexandria in Egypt, probably through the port’s trade with Constantinople, and ports on the Black Sea. During 1347, the disease travelled eastward to Gaza, and north along the eastern coast to cities in Lebanon, Syria and Palestine, including Ashkelon, Acre, Jerusalem, Sidon, Damascus, Homs, and Aleppo. In 1348–49, the disease reached Antioch. The city’s residents fled to the north, most of them dying during the journey, but the infection had been spread to the people of Asia Minor.

Mecca became infected in 1349. During the same year, records show the city of Mawsil (Mosul) suffered a massive epidemic, and the city of Baghdad experienced a second round of the disease. In 1351, Yemen experienced an outbreak of the plague. This coincided with the return of King Mujahid of Yemen from imprisonment in Cairo. His party may have brought the disease with them from Egypt.


Buboes in a victim of plague

A scene showing monks, disfigured by the plague, being blessed by a priest. England, 1360–75

Contemporary accounts of the plague are often varied or imprecise. The most commonly noted symptom was the appearance of buboes (or gavocciolos) in the groin, the neck and armpits, which oozed pus and bled when opened.[26] Boccaccio’s description is graphic:

“In men and women alike it first betrayed itself by the emergence of certain tumours in the groin or armpits, some of which grew as large as a common apple, others as an egg…From the two said parts of the body this deadly gavocciolo soon began to propagate and spread itself in all directions indifferently; after which the form of the malady began to change, black spots or livid making their appearance in many cases on the arm or the thigh or elsewhere, now few and large, now minute and numerous. As the gavocciolo had been and still was an infallible token of approaching death, such also were these spots on whomsoever they showed themselves.”[27]

Ziegler comments that the only medical detail that is questionable is the infallibility of approaching death, as if the bubo discharges, recovery is possible.[28]

This was followed by acute fever and vomiting of blood. Most victims died within two to seven days after infection. David Herlihy identifies another potential sign of the plague: freckle-like spots and rashes[29] which could be the result of flea-bites.

Some accounts, like that of Louis Heyligen, a musician in Avignon who died of the plague in 1348, noted a distinct form of the disease which infected the lungs and led to respiratory problems[26] and which is identified with pneumonic plague.

“It is said that the plague takes three forms. In the first people suffer an infection of the lungs, which leads to breathing difficulties. Whoever has this corruption or contamination to any extent cannot escape but will die within two days. Another form…in which boils erupt under the armpits,…a third form in which people of both sexes are attacked in the groin.”[30]


Medical knowledge had stagnated during the Middle Ages and the most authoritative account at the time came from the Medical Faculty in Paris in a report to the King of France, which blamed the heavens—a conjunction of three planets in 1345, which caused a “great pestilence in the air”.[31] This report became the first and most widely circulated of a series of “plague tracts” which sought to give advice to sufferers. That the plague was caused by bad air became the most widely accepted theory. It is important to realise that the word plague had no special significance at this time. But the recurrence of outbreaks during the Middle Ages gave it a unique reputation and the name has become the medical term.

The importance of hygiene was only recognised in the nineteenth century and until then it was common that the streets were filthy, with live animals of all sorts around and human fleas and ticks abounding. Any transmissible disease will spread easily in such conditions. One development as a result of the Black Death was the establishment of the idea of quarantine in Dubrovnik in 1377 after continuing outbreaks.[citation needed]


Yersinia pestis seen at 200x magnification. This bacterium, carried and spread by fleas, is generally thought to have been the cause of millions of deaths.[32]

The dominant explanation for the Black Death is the plague theory, which attributes the outbreak to Yersinia pestis, also responsible for an epidemic that began in southern China in 1865, eventually spreading to India. The investigation of the pathogen that caused the 19th-century plague was begun by teams of scientists who visited Hong Kong in 1894, among whom was Alexandre Yersin, after whom the pathogen was named Yersinia pestis.[33] The mechanism by which Y. pestis was usually transmitted was established in 1898 by Paul-Louis Simond and was found to involve the bites of fleas whose midguts had become obstructed by replicating Y. pestis several days after feeding on an infected host. This blockage results in starvation and aggressive feeding behaviour by the fleas, which repeatedly attempt to clear their blockage by regurgitation, resulting in thousands of plague bacteria being flushed into the feeding site, infecting the host. The bubonic plague mechanism was also dependent on two populations of rodents — one resistant to the disease, who act as hosts, keeping the disease endemic, and a second who lack resistance. When the second population dies, the fleas move on to other hosts, including people, thus creating a human epidemic.[33]

The historian Francis Aidan Gasquet, who had written about the ‘Great Pestilence’ in 1893[34] and suggested that “it would appear to be some form of the ordinary Eastern or bubonic plague” was able to adopt the epidemiology of the bubonic plague for the Black Death for the second edition in 1908, implicating rats and fleas in the process, and his interpretation was widely accepted for other ancient and medieval epidemics, such as the Justinian plague that was prevalent in the Eastern Roman Empire from 541 to 700 AD.[33]

The modern bubonic plague has a mortality rate of 30 to 75 percent and symptoms including fever of 38–41 °C (101–105 °F), headaches, painful aching joints, nausea and vomiting, and a general feeling of malaise. If untreated, of those that contract the bubonic plague, 80 percent die within eight days.[35] Pneumonic plague has mortality rate of 90 to 95 percent. Symptoms include fever, cough, and blood-tinged sputum. As the disease progresses, sputum becomes free flowing and bright red. Septicemic plague is the least common of the three forms, with a mortality rate close to 100 percent. Symptoms are high fevers and purple skin patches (purpura due to disseminated intravascular coagulation). In cases of pneumonic and particularly septicemic plague the progress of the disease is so rapid that there would often be no time for the development of the enlarged lymph nodes that were noted as buboes.[36]

“Many modern scholars accept that the lethality of the Black Death stemmed from the combination of bubonic and pneumonic plague with other diseases and warn that every historical mention of ‘pest’ was not necessarily bubonic plague…In her study of 15thC outbreaks, Ann Carmichael states that worms, the pox, fevers and dysentery clearly accompanied bubonic plague.”[37]

Alternative explanations

This interpretation was first significantly challenged by the work of British bacteriologist J. F. D. Shrewsbury in 1970, who noted that the reported rates of mortality in rural areas during the 14th century pandemic were inconsistent with the modern bubonic plague, leading him to conclude that contemporary accounts were exaggerations.[33] In 1984 zoologist Graham Twigg produced the first major work to directly challenge the bubonic plague theory, and his doubts about the identity of the Black Death have been taken up by a number of authors, including Samuel K. Cohn, Jr. (2002), David Herlihy (1997), and Susan Scott and Christopher Duncan (2001).[33]

It is recognised that an epidemiological account of the plague is as important as an identification of symptoms, but researchers are hampered by the lack of reliable statistics from this period. Most work has been done on the spread of the plague in England, and even estimates of overall population at the start vary by over 100% as no census was undertaken between the Domesday Book and 1377.[38] Estimates of plague victims are usually extrapolated from figures for the clergy.

In addition to arguing that the rat population was insufficient to account for a bubonic plague pandemic, sceptics of the bubonic plague theory point out that the symptoms of the Black Death are not unique (and arguably in some accounts may differ from bubonic plague); that transference via fleas in goods was likely to be of marginal significance and that the DNA testing may be flawed and have not been repeated elsewhere, despite extensive samples from other mass graves.[33] Other arguments include: the lack of accounts of the death of rats before outbreaks of plague between the 14th and 17th centuries; temperatures that are too cold in Northern Europe for the survival of fleas; that, despite primitive transport systems, the spread of the Black Death was much faster than modern Bubonic plague; that mortality rates of the Black Death appear to be very high; that, while modern bubonic plague is largely endemic as a rural disease, the Black Death indiscriminately struck urban and rural areas; that the pattern of the Black Death, with major outbreaks in the same areas separated by between 5 and 15 years, differs from modern Bubonic plague, which often becomes endemic for decades, flaring up on an annual basis.[33]

Walløe complains that all of these authors “take it for granted that Simond’s infection model, black rat → rat flea → human, which was developed to explain the spread of plague in India, is the only way an epidemic of Yersinia pestis infection could spread”, whilst pointing to several other possibilities.[39]

Anthrax skin lesion

A variety of alternatives to the Y. pestis have been put forward. Twigg suggested that the cause was a form of anthrax and N. F. Cantor (2001) thought it may have been a combination of anthrax and other pandemics. Scott and Duncan have argued that the pandemic was a form of infectious disease that characterise as hemorrhagic plague similar to Ebola. Archaeologist Barney Sloane has argued that there are insufficient evidence of the extinction of large number of rats in the archaeological record of the medieval waterfront in London and that the plague spread too quickly to support the thesis that the Y. pestis was spread from fleas on rats and argues that transmission must have been person to person.[40][41] However, no single alternative solution has achieved widespread acceptance.[33] Many scholars arguing for the Y. pestis as the major agent of the pandemic, suggest that its extent and symptoms can be explained by a combination of bubonic plague with other diseases, including typhus, smallpox and respiratory infections. In addition to the bubonic infection, others point to additional septicemic (a type of “blood poisoning”) and pneumonic (an airborne plague that attacks the lungs before the rest of the body) forms of the plague, which lengthen the duration of outbreaks throughout the seasons and help account for its high mortality rate and additional recorded symptoms.[26]

DNA evidence

In October 2010 the open-access scientific journal PLoS Pathogens published a paper by a multinational team who undertook a new investigation into the role of Yersinia pestis in the Black Death following the disputed identification by Drancourt & Raoult in 1998.[42] Their surveys tested for DNA and protein signatures specific for Y. pestis in human skeletons from widely distributed mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. The authors concluded that this new research, together with prior analyses from the south of France and Germany

Burning of Jews during the Black Death epidemic, 1349

“…ends the debate about the etiology of the Black Death, and unambiguously demonstrates that Y. pestis was the causative agent of the epidemic plague that devastated Europe during the Middle Ages.”[43]

The study also found that there were two previously unknown but related clades (genetic branches) of the Y. pestis genome associated with medieval mass graves. These clades (which are thought to be extinct) were found to be ancestral to modern isolates of the modern Y. pestis strains Orientalis and Medievalis, suggesting that the plague may have entered Europe in two waves. Surveys of plague pit remains in France and England indicate that the first variant entered Europe through the port of Marseille around November 1347 and spread through France over the next two years, eventually reaching England in the spring of 1349, where it spread through the country in three epidemics. Surveys of plague pit remains from the Dutch town of Bergen op Zoom showed that the Y. pestis genotype responsible for the pandemic that spread through the Low Countries from 1350 differed from that found in Britain and France, implying that Bergen op Zoom (and possibly other parts of the southern Netherlands) was not directly infected from England or France in 1349 and suggesting that a second wave of plague, different from those in Britain and France, may have been carried to the Low Countries from Norway, the Hanseatic cities or another site.[43]

The results of the Haensch study have since been confirmed and amended. Based on genetic evidence derived from Black Death victims in the East Smithfield burial site in England, Schuenemann et al. in 2011 further conclude “that the Black Death in medieval Europe was caused by a variant of Y. pestis that may no longer exist.”[44] A study published in Nature in October 2011 sequenced the genome of Y. pestis from plague victims and indicated that the strain which caused the Black Death is ancestral to most modern strains of the disease.[45]


Figures for the death toll vary widely by area and from source to source as new research and discoveries come to light. It killed an estimated 75 million–200 million people in the 14th century.[46][47][48] According to medieval historian Philip Daileader in 2007:

A scene showing Jews being burned alive during the period of Black Death, Liber Chronicarum.

The trend of recent research is pointing to a figure more like 45 percent to 50 percent of the European population dying during a four-year period. There is a fair amount of geographic variation. In Mediterranean Europe, areas such as Italy, the south of France and Spain, where plague ran for about four years consecutively, it was probably closer to 75 percent to 80 percent of the population. In Germany and England … it was probably closer to 20 percent.[49]

The most widely accepted estimate for the Middle East, including Iraq, Iran and Syria, during this time, is for a death rate of about a third.[50] The Black Death killed about 40% of Egypt’s population.[51] Half of Paris’s population of 100,000 people died. In Italy, Florence‘s population was reduced from 110,000 or 120,000 inhabitants in 1338 to 50,000 in 1351. At least 60 percent of Hamburg‘s and Bremen‘s population perished.[52] Before 1350, there were about 170,000 settlements in Germany, and this was reduced by nearly 40,000 by 1450.[53] In 1348, the plague spread so rapidly that before any physicians or government authorities had time to reflect upon its origins, about a third of the European population already perished. In crowded cities, it was not uncommon for as much as 50 percent of the population to die. Europeans living in isolated areas suffered less, whereas monks and priests were especially hard hit since they cared for the Black Death’s victims.[54]

Flagellants practised mortification of the flesh as a penance

Because 14th century healers were at a loss to explain the cause, Europeans turned to astrological forces, earthquakes, and the poisoning of wells by Jews as possible reasons for the plague’s emergence.[12] The governments of Europe had no apparent response to the crisis because no one knew its cause or how it spread. The mechanism of infection and transmission of diseases was little understood in the 14th century; many people believed only God’s anger could produce such horrific displays. There were many attacks against Jewish communities.[55] In August 1349, the Jewish communities of Mainz and Cologne were exterminated. In February of that same year, the citizens of Strasbourg murdered 2,000 Jews.[55] By 1351, 60 major and 150 smaller Jewish communities were destroyed.[56] The Brotherhood of the Flagellants, a movement said to number up to 800,000, reached its peak of popularity.[57]


An epidemic of plague dies out after a few months because it has no host in which the bacteria can survive. However that does not mean that there is not somewhere some surviving infection, in a rodent or flea or warm place, that acts as a reservoir so that sooner or later it breaks out again.[58]

The plague repeatedly returned to haunt Europe and the Mediterranean throughout the 14th to 17th centuries.[59] According to Biraben, plague was present somewhere in Europe in every year between 1346 and 1671.[60] The Second Pandemic was particularly widespread in the following years: 1360–1363; 1374; 1400; 1438–1439; 1456–1457; 1464–1466; 1481–1485; 1500–1503; 1518–1531; 1544–1548; 1563–1566; 1573–1588; 1596–1599; 1602–1611; 1623–1640; 1644–1654; and 1664–1667.[61] According to Geoffrey Parker, “France alone lost almost a million people to plague in the epidemic of 1628–31.”[62]

In England, in the absence of census figures, historians propose a range of pre-incident population figures from as high as 7 million to as low as 4 million in 1300,[63] and a post-incident population figure as low as 2 million.[64] By the end of 1350 the Black Death subsided, but it never really died out in England. Over the next few hundred years, there were further outbreaks in 1361–62, 1369, 1379–83, 1389–93, and throughout the first half of the 15th century.[65] An outbreak in 1471 took as much as 10-15 percent of the population, while the death rate of the plague of 1479-80 could have been as high as 20 percent.[66] The most general outbreaks in Tudor and Stuart England seem to have begun in 1498, 1535, 1543, 1563, 1589, 1603, 1625, and 1636, and ended with the Great Plague of London in 1665.[67]

Plague Riot in Moscow in 1771. During the course of the city’s plague, between 50,000 and 100,000 died (1/6 to 1/3 of its population).

In 1466, perhaps 40,000 people died of plague in Paris.[68] During the 16th and 17th centuries, plague visited Paris for almost one year out of three.[69] The Black Death ravaged Europe for three years before it continued on into Russia, where the disease hit somewhere once every five or six years from 1350 to 1490.[70] Plague epidemics ravaged London in 1563, 1593, 1603, 1625, 1636, and 1665,[71] reducing its population by 10 to 30% during those years.[72] Over 10% of Amsterdam‘s population died in 1623–1625, and again in 1635–1636, 1655, and 1664.[73] There were twenty-two outbreaks of plague in Venice between 1361 and 1528.[74] The plague of 1576-1577 killed 50,000 in Venice, almost a third of the population.[75] Late outbreaks in central Europe included the Italian Plague of 1629–1631, which is associated with troop movements during the Thirty Years’ War, and the Great Plague of Vienna in 1679. Over 60 percent of Norway’s population died from 1348 to 1350.[76] The last plague outbreak ravaged Oslo in 1654.[77]

In the first half of the 17th century a plague claimed some 1,730,000 victims in Italy, or about 14% of the population.[78] In 1656 the plague killed about half of Naples‘ 300,000 inhabitants.[79] More than 1,250,000 deaths resulted from the extreme incidence of plague in 17th century Spain.[80] The plague of 1649 probably reduced the population of Seville by half.[81] In 1709–1713, a plague epidemic that followed the Great Northern War (1700–1721, Sweden v. Russia and allies)[82] killed about 100,000 in Sweden,[83] and 300,000 in Prussia.[81] The plague killed two-thirds of the inhabitants of Helsinki,[84] and claimed a third of Stockholm‘s population.[85] Europe’s last major epidemic occurred in 1720 in Marseilles.[76]

Worldwide distribution of plague-infected animals 1998

The Black Death ravaged much of the Islamic world.[86] Plague was present in at least one location in the Islamic world virtually every year between 1500 and 1850.[87] Plague repeatedly struck the cities of North Africa. Algiers lost 30,000–50,000 to plague in 1620–21, and again in 1654–57, 1665, 1691, and 1740–42.[88] Plague remained a major event in Ottoman society until the second quarter of the 19th century. Between 1701 and 1750, 37 larger and smaller plague epidemics were recorded in Constantinople, and 31 between 1751 and 1800.[89] Baghdad has suffered severely from visitations of the plague, and sometimes two-thirds of its population has been wiped out.[90]

The Third Pandemic (1855–1959) started in China in the middle of the 19th century, spreading plague to all inhabited continents and killing 10 million people in India alone.[91]

From 1944 through 1993, 362 cases of human plague were reported in the United States; approximately 90 percent of these occurred in four western states; Arizona, California, Colorado, and New Mexico.[92] Plague was confirmed in the United States from nine western states during 1995.[93]

The plague bacterium could develop drug-resistance and again become a major health threat. The ability to resist many of the antibiotics used against plague has been found so far in only a single case of the disease in Madagascar, in 1995.[94]

In culture

Pieter Bruegel‘s The Triumph of Death (c. 1562) reflects the social upheaval and terror that followed the plague which devastated medieval Europe

The Black Death had a profound impact on art and literature throughout the generation that experienced it. Much of the most useful manifestations of the Black Death in literature, to historians, comes from the accounts of its chroniclers. Some of these chroniclers were famous writers, philosophers and rulers such as Boccaccio and Petrarch. Their writings, however, did not reach the majority of the European population. Petrarch’s work was read mainly by wealthy nobles and merchants of Italian city-states. He wrote hundreds of letters and vernacular poetry, and passed on to later generations a revised interpretation of courtly love.[95] There was one troubadour, writing in the lyric style long out of fashion, who was active in 1348. Peire Lunel de Montech composed the sorrowful sirventes “Meravilhar no·s devo pas las gens” during the height of the plague in Toulouse.

They died by the hundreds, both day and night, and all were thrown in … ditches and covered with earth. And as soon as those ditches were filled, more were dug. And I, Agnolo di Tura … buried my five children with my own hands … And so many died that all believed it was the end of the world.
—The Plague in Siena: An Italian Chronicle[96]
How many valiant men, how many fair ladies, breakfast with their kinfolk and the same night supped with their ancestors in the next world! The condition of the people was pitiable to behold. They sickened by the thousands daily, and died unattended and without help. Many died in the open street, others dying in their houses, made it known by the stench of their rotting bodies. Consecrated churchyards did not suffice for the burial of the vast multitude of bodies, which were heaped by the hundreds in vast trenches, like goods in a ships hold and covered with a little earth.
—Giovanni Boccaccio[97]

Thromboangitis Obliterans(Buerger Disease) Informations










The Driwan’s  Cybermuseum


(BUERGER Disease)


Leo Buerger (1879-1943)

In 1908, Mount Sinai Hospital, Dr. Leo Buerger’s disease, while studies on Buerger’s disease has managed to define the clinical entity, and histological features.

The disease is mainly young and male smokers, the lower extremity arteries is defined as a failure. Often associated tromboflebitle.
Histological appearance of a clearly tanımlanamasa; karekteritiktir segmental involvement. Occlusive lesions, recanalization mediada inward capillary growth and absence of elastic tissue is divided into aterosklerozisten.
Buerger’s disease, acute venous thrombophlebitis was noted that most attacks.


Leo Buerger was born in Vienna, his family emigrated to America.
Built in 1901 and based surgical training Colombiya graduated from the University. Lennox Hill hastenesinde Stajerliğini completed surgical section. Breslow surgery clinic in Germany in 1905 after working for a while and returned to NewYorka served as a professor of urology at Mount Sinai hastenesinde.
Buerger of the interest, as well as radiology and radium therapy on hematological tumors gelişimiylede concerned. Tilder F. Brown worked on the development in conjunction with cystoscopy and partly recognized as Brown-Buerger cystoscope later became known as Buerger cystoscope. Listen to the music, Dr. Leo is a good piano sniffer. Task used to do it again when they had married in 1929 in Los Angeles, chair of urology. California is seen as people who were offended and very negative in 1934 and again in New York Mt.Sinai Dr.Buerger in appointed.



Buerger’s disease (thromboangiitis obliterans) 75 years, although a pathology known for a long time, despite improvements in surgical or medical treatments, 2-in 4% of patients with chronic limb amputations, which are inevitable in a progressive inflammatory disease of non-atheromatous arterial (1.2) . Creates a group of small arteries in Buerger’s disease of unknown cause. Age, sex, race, hereditary factors (HLA antigen), and non-autoimmune mechanism is known as secondary etiologic factors. Smoking, the most important etiological factor is considered to be secondary. Recurrence of the disease, and the progress of agrevasyonu very tight link between smoking and there.

Amount of medium-sized vessels in the lower and upper extremity. The disease with an average around 28 years, male smokers are 95% (3). Due to the characteristics of the disease due to involvement of the distal vessel, a large group of patients, surgical revascularization is not a chance, conservative treatment techniques. The risk of peripheral gangrene in diabetic patients 70 years of age on the other hand, non-diabetic patients seen by more than 70 times. Microangiopathic dominated in this patient group, the microcirculation of functional disorders develop due to the non-glukolitik metabolism. The third clinical scenario is not applicable in the distal peripheral bypass surgery is the patient group as a result of atherosclerosis. These three clinical cases, limb amputation appears to be the last treatment option, but to be accepted by both patients and surgeons faced with extremely difficult as a result of which We remain a morbidity.

Modification of risk factors for peripheral vascular disease (smoking cessation, such as the regulation of hyperlipidemia and diabetes) can help slow the progression of the disease. Medical treatment antiagreganlar (4) (acetyl salicylic acid, klopidegrol), anticoagulants (warfarin), drugs that increase red blood cell fleksibilitesini (4), hyperlipidemia regulation (exercise, statins, fibrates), regulation of diabetes (or insulin with oral anticoagulants), α-receptor blockers, prostaglandin anaologları (5) (iloprost), Osijek hyperbaric therapy (6) options used to date. Not be performed when curative treatment is surgical sympathectomy, sympathetic blockade, debridement of infected tissue was used until the present day as the surgical approaches used with palliative intent (7). 12-in 15% of patients with ischemic foot ulcers of all kinds of medical treatment, limb amputation within 3-5 years required (8).


The disease most often begins with 20-35 years of age. Thromboangiitis obliterans, thrombophlebitis in 40% of patients seen roaming. Most of the patients seen in the lower extremity findings. The disease begins with a small artery. (Posterior tibial, anterior tibial, radial, ulnar, plantar, or palmar digital arteries). Medium and large arteries (popliteal, femoral, or brachial arteries) also affected by late season. Mayor arteries (aorta and iliac) disease involvement have been reported very rarely. Segmental lesions and episodic dağılımlıdır cruise tracks. In the acute stage, all the layers of the vessel wall is an acute inflammatory changes (panarteritis). Central thrombi and their purulent center and periphery of the foci of giant cells found. During the recovery period, (intermediate term), this characteristic is lost views. Is organized and recanalized thrombus. Recently, the lumen, which is the end product of the specified histological changes in tissue with konjektif is occluded by connective tissue.

Symptoms of the disease, pathological changes in the arterial occlusion Be cause, ie, inflammatory lesions and the destruction of the tissue after ischemia depends. Early symptoms appear as the bottom of the feet or fingers, pain and more pain is at rest. He’s mostly small-diameter arteries of the disease, intermittent claudication ASO’da (arteriosklerosis obliterans) is seen less often than seen. During periods of mild or the beginning of the disease, trophic changes, color changes, and may be changes in the form of coldness. Later periods, or standing on your toes gagren occurs. Inflammatory changes, causing ischemic pain at rest and thrombophlebitis can cause neuritis.


Doppler ultrasound method is determined with the flow and segmental pressure values ​​decreased.

Artery occlusion proximal to the smooth-looking, and usually the normal diameter. Anjiografideki most characteristic finding of occlusion of the vessel in view of increasingly finds ways to thinning and tree roots. Obstructions can also be seen around the short kolleteral network.

The diagnosis is taken into consideration the following criteria:
Coldness of the extremity ends of the asymmetric
Peripheral artery pulzasyonlarının (tibial and dorsalis pedis arteries) or the absence of relief
Tapering gradually, showing a sudden occlusion of blood vessels, and the corkscrew shaped structure showing kolleteral anjiogram
The absence of atheroma plaques
These findings are evaluated together with symptoms of the disease is decisive for diagnosis.


At the end of a long-term observations, in terms of the natural course of disease is divided into 3 groups.

Group I: In this group, the initial period of transient ischemic attack, followed by a period without incident. Patients in this group, comprises 50% of all cases.

Group II: After the initial period, show a moderate periods of recurrence of symptoms occurs. Generates 42% of the patients in this group.

Group III: This group of patients, again during the acute attack, amputation, and often have serious clinical symptoms occur. This group covers 8% of cases.


Constitute the mainstay of treatment, smoking cessation and supportive medical treatment. Foot hygiene is important to protect. Show multifocal lesions of the disease, the benefits of transactions prevents rekonsrüktif. Applicable to the method of surgical treatment of lumbar sympathectomy. In this method, the lumbar sympathetic ganglia outside the retroperitoneal ganglia removed first. The goal is to increase the blood supply by removing the vasomotor activity. Ticlopidine antiplatelet agent used in medical treatment, increases in erythrocytes fleksibiliteyi Pentoxifylline (Trental) and defibrinated Batroxobin’in agent shown to be effective as chronic arterial lesions. If no cases of wound healing and spread finger or foot amputation may be required.

(Buerger Disease)
Leo Buerger (1879-1943)
Pada tahun 1908, Rumah Sakit Mount Sinai, penyakit Buerger Dr Leo, sedangkan penelitian pada penyakit Buerger telah berhasil mendefinisikan entitas klinis, dan fitur histologis.
Penyakit ini terutama muda dan perokok laki-laki, arteri ekstremitas bawah didefinisikan sebagai kegagalan. Sering dikaitkan tromboflebitle.
Histologis munculnya jelas tanımlanamasa; karekteritiktir keterlibatan segmental. Lesi oklusif, rekanalisasi mediada pertumbuhan kapiler ke dalam dan tidak adanya jaringan elastis dibagi menjadi aterosklerozisten.
Penyakit Buerger, tromboflebitis vena akut dicatat bahwa sebagian besar serangan.
Leo Buerger lahir di Wina, keluarganya beremigrasi ke Amerika.
Dibangun pada tahun 1901 dan pelatihan berbasis Colombiya bedah lulus dari Universitas. Lennox Hill Stajerliğini hastenesinde menyelesaikan bagian bedah. Breslow operasi klinik di Jerman pada tahun 1905 setelah bekerja untuk sementara waktu dan kembali ke NewYorka menjabat sebagai profesor urologi di Gunung Sinai hastenesinde.
Buerger dari bunga, seperti radiologi dan terapi radium pada tumor hematologi gelişimiylede bersangkutan. Tilder F. Brown bekerja pada pengembangan bersama dengan sistoskopi dan sebagian diakui sebagai Brown-Buerger cystoscope kemudian menjadi dikenal sebagai cystoscope Buerger. Mendengarkan musik, Dr Leo adalah sniffer piano yang baik. Tugas yang digunakan untuk melakukannya lagi ketika mereka telah menikah pada tahun 1929 di Los Angeles, ketua urologi. California dipandang sebagai orang-orang yang tersinggung dan sangat negatif pada tahun 1934 dan lagi di New York Mt.Sinai Dr.Buerger dalam ditunjuk.
Buerger penyakit (thromboangiitis obliterans) 75 tahun, meskipun patologi dikenal untuk waktu yang lama, meskipun peningkatan dalam perawatan bedah atau medis, 2-in 4% dari pasien dengan amputasi tungkai kronis, yang tak terelakkan dalam suatu penyakit peradangan yang progresif non-ateromatosa arteri (1,2). Menciptakan sekelompok arteri kecil pada penyakit Buerger penyebabnya tidak diketahui. Usia, jenis kelamin, ras, faktor keturunan (HLA antigen), dan non-mekanisme autoimun dikenal sebagai faktor etiologi sekunder. Merokok, faktor etiologi yang paling penting adalah dianggap sekunder. Kambuhnya penyakit, dan kemajuan agrevasyonu sangat ketat hubungan antara merokok dan ada.
Jumlah menengah pembuluh darah di ekstremitas bawah dan atas. Penyakit dengan rata-rata sekitar 28 tahun, perokok laki-laki adalah 95% (3). Karena karakteristik dari penyakit akibat keterlibatan kapal distal, sekelompok besar pasien, revaskularisasi bedah bukanlah kebetulan, teknik pengobatan konservatif. Risiko gangren perifer pada pasien diabetes berusia 70 tahun di sisi lain, pasien non-diabetes dilihat oleh lebih dari 70 kali. Mikroangiopati mendominasi pada kelompok pasien ini, gangguan mikrosirkulasi fungsional berkembang karena metabolisme non-glukolitik. Skenario klinis ketiga tidak berlaku dalam operasi bypass distal perifer adalah kelompok pasien sebagai akibat dari aterosklerosis. Ketiga kasus klinis, amputasi tungkai tampaknya menjadi pilihan pengobatan terakhir, tetapi untuk dapat diterima oleh kedua pasien dan ahli bedah dihadapkan dengan sangat sulit sebagai akibat dari yang Kami tetap morbiditas sebuah.
Modifikasi faktor risiko untuk penyakit vaskular perifer (berhenti merokok, seperti regulasi hiperlipidemia dan diabetes) dapat membantu memperlambat perkembangan penyakit. Perawatan medis antiagreganlar (4) (asetil asam salisilat, klopidegrol), antikoagulan (warfarin), obat yang meningkatkan sel darah merah fleksibilitesini (4), hiperlipidemia regulasi (olahraga, statin, fibrat), regulasi diabetes (atau insulin dengan antikoagulan oral) , α-reseptor blocker, prostaglandin anaologları (5) (iloprost), terapi hiperbarik Osijek (6) opsi yang digunakan untuk tanggal. Tidak dilakukan ketika pengobatan kuratif simpatektomi bedah, blokade simpatik, debridemen jaringan yang terinfeksi digunakan sampai hari ini sebagai pendekatan bedah yang digunakan dengan maksud paliatif (7). 12-dalam 15% dari pasien dengan ulkus kaki iskemik dari semua jenis perawatan medis, amputasi tungkai dalam waktu 3-5 tahun diperlukan (8).
Penyakit ini paling sering dimulai dengan usia 20-35 tahun. Thromboangiitis obliterans, tromboflebitis dalam 40% dari pasien terlihat berkeliaran. Sebagian besar pasien terlihat dalam temuan ekstremitas bawah. Penyakit ini dimulai dengan arteri kecil. (Posterior tibialis, tibialis anterior, radial, ulnaris, plantaris, arteri palmaris atau digital). Arteri menengah dan besar (poplitea, arteri femoralis, atau brakialis) juga dipengaruhi oleh musim terlambat. Arteri Walikota (aorta dan iliaka) keterlibatan penyakit telah dilaporkan sangat jarang. Lesi segmental dan trek dağılımlıdır episodik pesiar. Pada tahap akut, semua lapisan dinding pembuluh darah adalah suatu perubahan inflamasi akut (panarteritis). Trombi Tengah dan pusat purulen mereka dan pinggiran fokus sel raksasa ditemukan. Selama periode pemulihan, (jangka menengah), karakteristik ini hilang pandangan. Apakah trombus terorganisir dan recanalized. Baru-baru ini, lumen, yang merupakan produk akhir dari perubahan histologis yang ditentukan dalam jaringan dengan konjektif yang tersumbat oleh jaringan ikat.
Gejala dari penyakit, perubahan patologis pada oklusi arteri Jadilah penyebab, yaitu, lesi inflamasi dan kerusakan jaringan setelah iskemia tergantung. Gejala awal muncul sebagai bagian bawah kaki atau jari, rasa sakit dan nyeri lebih banyak beristirahat. Dia kebanyakan berdiameter kecil arteri dari penyakit, klaudikasio intermiten ASO’da (arteriosklerosis obliterans) terlihat kurang sering daripada terlihat. Selama periode ringan atau awal dari penyakit, perubahan trofik, perubahan warna, dan mungkin perubahan dalam bentuk dingin. Kemudian periode, atau berdiri di atas jari kaki gagren terjadi. Perubahan inflamasi, menyebabkan nyeri iskemik saat istirahat dan tromboflebitis dapat menyebabkan neuritis.
METODE Diagnosis
Metode Doppler USG ditentukan dengan aliran dan nilai tekanan segmental menurun.
Arteri proksimal halus yang tampak, dan diameter biasanya oklusi normal. Menemukan Anjiografideki paling karakteristik oklusi kapal dalam tampilan yang semakin menemukan cara untuk penipisan dan akar pohon. Penghalang juga dapat dilihat di jaringan kolleteral pendek.
Diagnosis dipertimbangkan kriteria sebagai berikut:
Dinginnya ekstremitas ujung asimetris
Peripheral pulzasyonlarının arteri (arteri dorsalis pedis dan tibialis) atau tidak adanya bantuan
Lonjong secara bertahap, menunjukkan oklusi mendadak pembuluh darah, dan struktur pembuka botol berbentuk menampilkan anjiogram kolleteral
Tidak adanya plak ateroma
Temuan ini dievaluasi bersama-sama dengan gejala penyakit ini yang menentukan untuk diagnosis.
KLINIS KURSUS dan prognosis
Pada akhir jangka panjang pengamatan, dalam hal perjalanan alami penyakit ini dibagi menjadi 3 kelompok.
Kelompok I: Dalam kelompok ini, periode awal serangan iskemik transien, diikuti dengan periode tanpa insiden. Pasien dalam kelompok ini, terdiri dari 50% dari semua kasus.
Kelompok II: Setelah periode awal, menunjukkan periode moderat kambuhnya gejala terjadi. Menghasilkan 42% dari pasien dalam kelompok ini.
Kelompok III: Kelompok ini pasien, lagi selama serangan akut, amputasi, dan sering memiliki gejala klinis yang serius terjadi. Kelompok ini mencakup 8% dari kasus.
Merupakan andalan pengobatan, berhenti merokok dan pengobatan suportif. Kebersihan kaki adalah penting untuk melindungi. Tampilkan lesi multifokal dari penyakit, manfaat dari transaksi mencegah rekonsrüktif. Berlaku untuk metode pengobatan bedah simpatektomi lumbalis. Dalam metode ini, ganglia simpatis lumbalis luar ganglia retroperitoneal dihapus terlebih dahulu. Tujuannya adalah untuk meningkatkan suplai darah dengan menghapus aktivitas vasomotor. Tiklopidin agen antiplatelet digunakan dalam pengobatan medis, peningkatan eritrosit fleksibiliteyi pentoxifylline (Trental) dan agen Batroxobin’in defibrinated terbukti efektif sebagai lesi arteri kronis. Jika tidak ada kasus penyembuhan luka dan jari kaki menyebar atau amputasi mungkin diperlukan

the end @ copyright Dr Iwan suwandy 2011

The Value Of Rusia Modern Coins










The Driwan’s  Cybermuseum


(Museum Duniamaya Dr Iwan)

Showroom :


The Value Orf Russia Modern Coin

1.2002 mintage   5.0000.0000  UNC US$ 3.00

2.2002 sp mintage 5.000.000. UNC US$3.00

3.2003 Sp mintage 5.000.000 UNC US$ 3.00

4.2004 Mintage 5.000.000 UNC US#3.00

Head  side

Ring Composituion Brass center center compositionCooper-nicvkel

Tails Side

1.2002 city arms above walled city view.

2.2002 sp Cityarm and cathedral

3.2003 ap crown doubled headed  aegle with round breast shield

4.2004sp coat of arm aboved  walled city

the end @ copyright Dr Iwan suwandy 2011

The Earliest Music Record And Phonograph Found In Indonesia




Driwan Music record Cybermuseum



The Earliest Album Record And Phonograph Found In Indonesia  

Frame One : Introduction

1. I have starting build the collections of  Gramophone plate and phonograph since study in hish school at Padang city West Sumatra in 1960.

2. Until this day in 2011 I cannot found the complete informations about the Indonesian’s  gramophone plate History, that is why I have made reasech about this topic in order to give the young generations about the development of music gramophone technology in the world since found by Mr Thomas Alfa Edison and when first arrived in Indonesia during The Dutch East colionial Era.

3. I will show my collections with information from that very rare and amizing historic collections, very lucky I had found vintage book of gramophone and also many info fram google explorations,especially from wikipedia ,for that info thanks very much.

4. This exhibtion will divide into two parts, first before World War I and second Between WWI and WWII. all during Indonesia under Dutch east Indie Colonial time.

5.The earliest Gramophone’s Plate in 19Th Century produced by Addison inc with very thick plate almost 4 times then now circa 1 cm,then became half centimer and latest 0,2 cm more thin,please look the comperative picture below:

First the mechanic gramophone look the promotion picture of His Mater Voice company below:

and later electric gramophone, still used gramophone needle look the needle promotion label below :

6.In Indonesia during Colonial time , the gramophone’s plate sold by the chinese marchant ,many at Pasar Baru Market and  Pasar Senen  Batavia (Jakarta) please look the trader mark below :

7.The Edisson first Gramophone Info from google exploration,this earliest pho0nograph still not found in Indonesia until now, I stiil hunting.


 Replica of original phonograph

An ad for the phonograph

The Gramophone’s Plate procduction company whic found in Indonesia were

1) 19th century

(1) Addison Record

(2) Hias Master Voice

2)Early 20th century




(2) Odeon

(3)Earlieast Polydor records

(4)Imperial records

(5)Columbia China records


 3)Pre Wolrd war II

(1)RCA-His Master Voice Shanghai China

(2) Decca records

(3) Irama India records  with song Djali Djali

8.I hope the collectors of all over the world ,especially Indonesian Collectors plaes honor my copyright with donnot copy or tag this exhibitons without my permisssion,thanks.

Jakarta January 2011

Dr Iwan suwandy @ copyright 2011

Frame two :

The Earliest International Album Record Production Historic Collections Found In Indonesia

7.The Gramophone’s Plate procduction company whic found in Indonesia were

1) 19th century

(1) Edison Record

Edison Records

Edison Records was the one of the earliest record labels which pioneered recorded sound and was an important player in the early recording industry.
Edison Records
Parent company Thomas A. Edison, Inc.
Founded June 28, 1888
Defunct October, 1929
Revived c. 1990s
Founder Thomas Edison
Jesse H. Lippincott
Status Defunct
Distributor(s) (independent, mostly through dealers, jobbers, and mail order)
Genre Variety (classical, popular, etc.)
Country of origin United States, some major European countries
Location West Orange, New Jersey
1903 advertisement for Edison Records



Early phonographs before commercial mass produced records

Thomas A. Edison invented the phonograph, the first device for recording and playing back sound, in 1877. After inventing and patenting the phonograph, Edison and his laboratory turned their attention to the commercial development of (electric lighting), playing no further role in the development of the phonograph for a decade.

The earliest phonograph was something of a crude curiosity, although it was one that fascinated much of the public. Early machines were sold to entrepreneurs who made a living out of traveling around the country giving “phonograph concerts” and demonstrating the device for a fee at fairs. “Talking dolls” and “Talking clocks” were manufactured as expensive novelties using the early phonograph.


The start of the commercial record industry

In 1887 Edison Labs turned their attention back to improving the phonograph and the phonograph cylinder.

In 1888 the Edison company debuted the Perfected Phonograph, Edison produced wax cylinders 4 inches (10 cm) long, 2<pi> inches in diameter, playing some 2 minutes of music or entertainment, which became the industry standard. Experimental music records were made around this time. The “brown wax” cylinder made its debut in March/April 1889. “Electric Light Quadrille” by Issler’s Orchestra (external link) is an example of an 1889 brown wax cylinder (Superbatone #734–”The Real Sound of Ragtime”).

Blank records were an important part of the business early on. Most phonographs had or could be fitted with attachments for the users to make their own recordings. One important early use, in line with the original term for a phonograph as a “talking machine”, was in business for recording dictation. Attachments were added to facilitate starting, stopping, and skipping back the recording for dictation and playback by stenographers. The business phonograph eventually evolved into a separate device from the home entertainment phonograph. Edison Record’s brand of business phonograph was called The Ediphone; see Phonograph cylinder and Dictaphone. Edison also holds the achievement of being one of the first companies to record the first African-American quartet to record: The Unique Quartette.

Mass produced cylinders

Whistle and I’ll Wait for You
Performed by Ada Jones for Edison Records in 1909.


A notable technological triumph of the Edison Laboratories was devising a method to mass produce pre-recorded phonograph cylinders in molds. This was done by using very slightly tapered cylinders and molding in a material that contracted as it set. To Edison’s disappointment the commercial potential of this process was not realized for some years. Most of the regional Edison distributors were able to fill the small early market for recordings by mechanical duplication of a few dozen cylinders at a time. Molded cylinders did not become a significant force in the marketplace until the end of the 1890s, which was when molding was slow and was used only to create pantograph masters.

Mass producing cylinders at the Edison recording studio in New Jersey largely ended the local Edison retailers early practice of producing recordings in small numbers for regional markets, and helped concentrate the USA recording industry in the New York City – New Jersey area, already the headquarters of the nation’s Tin Pan Alley printed music industry.

In 1902, Edison Records introduced Edison Gold Moulded Records, cylinder records of improved hard black wax, capable of being played hundreds of times before wearing out. These new records were under the working title of “Edison Hi-Speed Extra Loud Moulded Records”, running at the speed of 160 RPM instead of the usual (ca. 1898–1902) speed of 144 RPM or (ca. 1889–1897) 120 RPM. Until ca. 1898, Edison’s speed was 125 RPM.

In 1908, Edison introduced a new line of cylinders (called “Amberols”) playing 4 rather than 2 minutes of music on the same sized record, achieved by shrinking the grooves and spacing them twice as close together. New machines were sold to play these records, as were attachments for modifying existing Edison phonographs.

In November 1912, the new Blue Amberol Records, made out of a type of plastic similar to celluloid invented by Edison labs, were introduced for public sale. The first release was number 1501, a performance of the Rossini’s overture to his opera Semiramide, performed by the American Standard Orchestra. The Blue Amberol records were much more durable than wax cylinders. The Edison lab claimed a 3000+ playback quota for the Blue Amberol. In that same year, the Edison Disc Record came out.

In 1910, artists’ names began to be added to the records; previously, Edison’s policy was to promote his cylinders (and up until 1915, discs) based on the recognition of composers and the works recorded theron in lieu of the performers themselves.

Edison Records continued selling cylinders until they went out of business in 1929. However, from January 1915 onwards the first of the that were Blue Amberols dubbed from Edison’s Diamond Disc matrices, appeared on the market. By 1919, the last decade of production, these were simply dubs of their commercial disc records intended for customers who still used cylinder phonographs purchased years before.

Edison Records was eventually run by Thomas Edison’s son, Charles Edison.

Edison Records logo from 1910s sleeve

 Materials and process used to manufacture cylinder records

Cylinders that are mentioned from 1888 are sometimes called “yellow paraffin” cylinders, but these cylinders are not paraffin, which is a soft oily wax and does not hold up under many plays. They could be a number of formulas tested by Jonas Aylsworth, Thomas Edison‘s chemist. Most of the surviving 1888 recordings would be formulated from a combination of 60% ceresin wax, 20% stearic acid, and 20% beeswax. A record of this kind has a cigar-like smell, and is physically very soft when first molded. In a year’s time, the record would harden quite considerably.[1]

In late 1888, metallic soaps were tried. At first a lead stearate was used, but in the summer months, these records started to sweat and decompose. In 1889, Aylsworth developed an aluminum wax, using acetate of alumina and stearic acid with sodium hydroxide added as a saponifying agent. It was found these records were much more durable. Problems arose, however, since there was no tempering agent and hot weather caused these records to decompose. Two problems contributed to this, stearic quality varied from different makers; Aylsworth purchased some from P&G and found it had too much olaic acid in it. The next cause of the problem is that all stearic acid without a tempering agent takes on moisture, and after many experiments it was found that Ceresine was ideal. To make the wax hard, sodium carbonate was added. Even so, a few batches of records still had some problems and became fogged. The fog problem arose from acetic acid left in the wax, this problem was solved when higher temperatures were used to make sure all the acetic acid was boiled out of the wax. As such, the records from 1889 to 1894 are a reddish brown color due to the long cooking time. By 1896, Edison started using hydrated alumina in place of acetate of alumina. The use of hydrated alumina (sheet aluminum dissolved in a mixture of sodium carbonate, sodium hydroxide, and distilled water) made better records, and the wax could be manufactured in a shorter period of time. Using the hydrated aluminum resulted in more desirable blanks, with fewer defects and shorter production time.

The Columbia Phonograph Company used Edison recording blanks until 1894. The North American Phonograph Company was dissolved in the fall of 1894, and Edison quit supplying blanks to Columbia, who had purchased 70,000 blanks from 1889 to 1894. Columbia was frantic to find a solution to make cylinder blanks in house, and the recipe for making Edison’s wax was a well kept secret. Thomas McDonald started doing experiments with wax alloys with poor results: the records fogged or decomposed in the summer, just like the early Edison blanks. The Columbia company had a deadline to either supply recordings, or have their contracts cancelled and be sued for loss of records. Columbia resorted to attempt to steal secrets from Edison company by hiring old Edison Phonograph Works employees, such as Mr. Storms. Unfortunately for Columbia, the names of the components used by Edison were not labeled with ingredients but were instead indicated by number (i.e. 1,2,3 keeping the identities of these components a secret.) Paraffin, Ceresine, and Ozokerite all look similar, making the tempering agent even more difficult to be identified by the wax mixer. Wax mixers were given instructions on how much of the numbered components to put in the mixture, and how to process it, but no idea as to what the ingredients actually were. It took over a year for Columbia to come up with the formula for cylinders. Columbia placed an ad in the Soap Makers’ Journal for a practical man to work with metallic soaps. Adolph Melzer, a soap manufacturer from Evansville, Indiana took the job. Melzer came up with a formula comparable to Edison’s with the exception of the tempering agent (using cocinic acid, derived from coconut oil.)

In 1901 The Gold Molded (originally spelled Moulded) process was perfected for commercial use by Thomas Edison and Jonas Aylsworth (Edison’s Chemist) with input from Walter Miller, the Recording Manager of Edison Records.[2]

[3] This discussion was gleaned from testimonials Walter Miller, Jonas Aylsworth, Thomas Edison, Adolphe Melzer, and Charles Wurth.

At first, no method of mass production was available for cylinder records. Copies were made by having the artist play over and over or by hooking two machines together with rubber tubing (one with a master cylinder and the other a blank) or copying the sound mechanically. By the late 1890s, an improved mechanical duplicator, the pantograph, was developed which used mechanical linkage. One mandrel had a playback stylus and the other a recording one, while weights and springs were used to adjust the tension between the styli to control recording volume and tracking.

The Edison team had experimented with Vacuum Deposited Gold masters as early as 1888, and it has been reported that some brown wax records certainly were molded,although it seems nobody has found these, in recent years, or can identify them. Frank Albert Wurth. The Edison Record, “Fisher Maiden”, was an early record that was experimented with for the process. The 1888 experiments were not very successful due to the fact the grooves of the cylinders were square, and the sound waves were saw-tooth-shaped and deep. The records came out scratched and it was very time consuming. Many failures and very few that come out. (See The Edison Papers Project, Record Experiments by Jonas Aylsworth 1888–1889)[4]


This is an example of a wax cylinder mold. Note the grooves on the inside and machined backup shell.

The Gold Molded process involved taking a wax master and putting it in a vacuum chamber. The master record was put on a spinning mandrel, the pump sucked all the air out of a glass bell jar, and 2 pieces of gold leaf were hooked to an induction coil. The current was turned on, a magnet was spun around the outside to turn the mandrel, and the gold vaporized a very thin coating on the master. This master was put on a motor in a plating tank and copper was used to back the gold up. The master record was melted, then taken out of the mold to reveal a negative of the grooves in the metal. The master cylinder had to have wider feed as the grooves shrink in length through each process. The master mold is used to create “mothers” and these are then further processed to make working molds.

The Gold molded record used an aluminum-based wax, like the post-1896 Edison brown wax. However, carnauba wax was added, as well as pine tar and lampblack resulting in a black, shiny, durable record. The molds with mandrels placed in the center were heated and dipped in a tank of the molten wax. These were removed and trimmed while still hot, and put on a table from where the molds were put in lukewarm water. The water caused the records to shrink in diameter so that they could be removed. The records were then trimmed, dried and cleaned, then later put on warm mandrels for 2 hours where they shrank evenly. Jonas Aylsworth developed this formula.

In 1908, Edison introduced Amberol Records which had a playing time of just over 4 minutes. The process of making the finished record was the same as the Gold Molded records, however a harder wax compound was used. In 1912, celluloid was used in place of wax, and the name was changed to Blue Amberol, as the dye was a blue color. The master was recorded and then the process of making the mold was the same as the Gold Molded process. What is different is that a steam jacketed mold with an air bladder in the center was used. Celluloid tubing was put in the mold and the end gate was closed. The rubber bladder expanded the celluloid to the side of the heated mold, and printed the negative record in positive on the celluloid. The bladder was then deflated, and cold air was used to shrink the tubing so the celluloid print could be removed. The printed tubing was put in a plaster filler. When the plaster was hard the cylinders were then baked in an oven, then the ribs made on the inside of the plaster with knives. The records were cleaned and then packaged.[5][citation needed]

Ediphone Wax Formula and Procedure for making Ediphone Cylinders

Noted C.H. 11/21/1946

1. 1,200 lbs of double pressed stearic acid (130 degree F. Titer) and 4 lbs of nigrosine base B dye are placed in a 200 gallon cast iron cauldron. The cauldron is directly heated by an oil burner of the household type. (Our Present ones are Eisler, the manufacture of which has been discontinued.) Heat is applied until the stearic acid has been melted and the temperature has reach 360 degrees F. 2. 2,000 grams of metallic aluminum are placed in a 75 gallon steam-jacketed open kettle. To this are added 7,000 grams of NaOH and 10 gallons of water. When the reaction has subsided, 92 lbs of anhydrous sodium carbonate are added and finally 50 gallons of water. Note: The aluminum scrap is usually obtained from the Storage Battery Division in the form of punched strips. It is important that the size and thickness of this material be such as to insure a fairly rapid rate of solution. All of this reaction takes place under a hood. An alternative method consists of dissolving 8,900 grams of sodium aluminate in about 10 gallons of water and adding 5,000 grams of NaOH pellets. When complete solution has taken place, 92 lbs of anhydrous sodium carbonate are added and the necessary amount of water to bring the bulk up to 60 gallons.

In both cases solution is affected by means of pressure steam in the jacketed portion of the kettle. When the solution is substantially clear it is slowly added, a pail at a time (3 gallons) by means of a 2 quart dipper, to the heated stearic acid as prepared in 1. The oil burner is kept on during this operation in order to keep the temperature of the mixture fairly constant at 360 degrees F. Care must be exercised in adding this “Saponifying” solution so that excess foaming is prevented. After all the solution has been added the resulting “formula wax” is heated to 400 degrees F. and maintained at this temperature for four hours, at which time a sample is removed, a congealing point determined, (see under “tests”), and any addition made of stearic acid or sodium carbonate solution for correction, and the mixture held without additional heat for 10 hours. It is then heated again to bring the temperature up to 400 degrees F and allowed to cool gradually, usually overnight. When the temperature has again been reduced to 350 degrees F the was is pumped by means of a Kinney pump into 10 gallon pails from which the wax is poured into shallow pans containing approximately 50 lbs of the wax per pan. After the material has cooled to room temperature it is removed from the pans and stacked.

3. Into a 200 gallon cast iron cauldron heated by and oil burner of the household type, (or as required at present by war conditions, heated by bituminous coal) are placed 500 to 900 labs of “formula wax”. Note: The amount of “formula wax” to make up a batch various according to the amount of scrap wax which is to be added to the cauldron. Scrap wax represents commercial wax of which “formula wax” is a part. To the amount of “formula wax placed in the cauldron are added 19½% Paraffin (133 degrees-135 degrees F., usual source Standard Oil of New Jersey) and 2% stearine pitch (M. P. 40 Degrees Centigrade). This mixture, consisting of “formula wax”, paraffin and stearine pitch, represents commercial wax. Finally, commercial scrap wax of the composition given above in added until the total weight of the mixture is approximately 1,600 lbs. This mixture is usually heated beginning at 12 midnight and carried through until the temperature is 410-415 degrees F. at 8 a.m. Note; This may be regarded as standard procedure, although at the present time (Dec., 1943) this has been modified so that only Sunday nights is this done. On other days of the week except Saturday the kettles are started at 6 A.M. This method was adopted due to man shortages which necessitated starting the molding operation later in the day.) At this time a congealing point is taken and the necessary adjustments made (see under “tests”) after which the mixture is transferred to a closed agitating tank by means of a Kinney pump, the latter forced the hot material through a 2″ pipe.

4. To the mixture in the agitation tank there is added 3/10 percent Johns-Manville # 503 Filter Aid. The temperature is maintained at 375 degrees F. by means of a ring gas burner, at the bottom of the tank. At this temperature the wax is supplied by a Worthington pump at 30 lbs to a one square foot Shriver press whose head and follower are steam jacketed and which has 7 sections. The effluent from this press passes through a second Shriver press which has 2 sections of one square foot each. The mixture from the outlet here finally passes though a 1″ pipe which has a 100 × 150 mesh Monel ,metal screen held in its cross sections by means of a union, into one of four 75 gallon aluminum kettles. . These kettles are protected by conical hoods to prevent dust particles being carried into the body of the wax. After allowing the wax to remain at 330 degrees F. for three hours it is ready to be poured into the blank moulds. The temperature is maintained by gas burners beneath the kettles and controlled automatically by Partlow Corp. thermostatic controls.

5. By means of a pot with 2 spouts the moulds are filled with molten wax. The pot has a capacity of about five pounds (slightly less than 2 quarts and is specially designed of aluminum and made by Theodore Walter, Newark N.J… The molding table revolves at the rate of 6 blanks per minute, approximately, and the size of the pouring pot spout is only sufficient to permit the hot wax to flow into the molds at a rate slightly faster than the speed of the molds which rotate past a given point around the table.

The blanks are extracted at a temperature of 200-205 degrees F. and place on boards which hold 30 blanks. These boards when filled move by gravity down a conveyor. The length of time on the conveyor is about two hours after which time they are sufficiently cool and hard to be put into production boxes holding 63 blanks. The boxes are placed in racks for the following day’s production. Into each production box there is placed a semi-finished cylinder, which has been edged and reamed and which conforms to a standard internal diameter at 70 degrees F of 1.826 ” at the thin end. The purpose of this is to permit the edging operation to take place on the un-finished blank at any temperature by adjusting the machine to conform to the standard. Thus, in each production box, there is a total of 63 unfinished cylinders. One day’s production is held at least 34 hours before further processing.

6. The blanks are first reamed. The reamer consists of a twisted tapered and eight fluted tool. The blanks are forced on the reamer by hand to a stop. The position of the stop is adjusted so that sufficient material will be removed from both ends of the blanks when the blank is edged in the next operation. The reamer revolves at approximately 300 RPM

7. The edging operation consists in placing a reamed blank on a tapered mandrel and by means of two special cutters working in unison the ends of the blank are formed to conform in couture to a standard template. A second gauge is used to insure proper length (6⅛”). IN each case the edged blank must rest on a tapered mandrel gauge in exactly the same position as the standard blank which is in the production box. The usual procedure is to make the necessary adjustments of the knives of the first blank which is edged so that is conforms to the standard, and then continue the operation on the rest of the blanks in the production box at the identical position of the first blank. Note; since there are 63 blanks for each standard blank it will be observed that every 63rd cylinder is checked mandrel gauge. The accuracy of the method and the facility with which it is done depend on the care and skill of the operator. This is probably, is the most critical of all the operations. The edging machine revolves at 2,200 RPM

8. Following the edging operation is the stamping. This consists in applying a hot printing die to the thick end of the cylinder as it is placed accurately in a vertical position under the die. The heating of the die is done by means of a resistance wire coiled within a hollow torus near the under edge of the circular die. The coiled wire is connected to a source of current and the latter is adjusted by means of a rheostat. The heated died has raised lettering and makes and impression on the end surface of the wax cylinder. The depressed positive lettering on the cylinder is filled with a thick paste of zinc carbonate, the excess of which is brushed or wiped off after drying.

9. The cylinders are next shaved on a ganged shaving machine consisting of a rough shaving knife free from “blinds” and “lines”, accurate concentricity and a minimum of taper. These factors depend on the tension of the driving belt, tension upon the rotating mandrel between centers and the position and sharpness of the knives. Speed of the mandrel 2,200 RPM

10. The finished cylinders are placed in boxes which contain 16 pegs and run down a conveyor. At a point on this conveyor the cylinders are held and brushed on the inside to remove wax shavings and dust.

11. Cylinders are inspected, packed and placed in the stock room for a minimum of thirty days before shipping.

12. The reinforcing liners are made as follows: Crinoline cloth of specifications given under “Tests”, are cut into a trapezoid (Paper Products Dept.) base length 6¼, altitude 5⅝” top length 5¾”. A pack of these are placed in a vise edgewise and thinned glue, one part Le Pages Glue, one part water, brushed onto one slant edge. A liner is then wrapped a tapered mandrel of such size as to fit no too snuggly on the molding core. The liner is held on the mandrel by means of two jaws actuated by a foot lever and the lapped edges of the liner glued by means of a gas iron held for an instant along the line of the lap.

(2a) Homokord records


Rare Homokord 2 Labels Glockenspiel & Xylophone Solos


Rare Homokord 2 Labels Glockenspiel & Xylophone Solos Homokord Record
10″ and 78 speed
First Side:
Grand Galopp de Gouvert
(R. Poltmann)
Xylophone Solo
mit Orchesterbegleitung
Matrix #: A5120 and 11174
Second Side:
von Komzak
Albert Muller
Xylophon-u. Glockenspeilvirtuos
mit Orchesterbegleitung
Matrix #: 22614A and 11175
Notes: 2 labels! N o visual cracks, chips or repairs to the record. Couple small scratches on each side.
The word “about” in our descriptions is used with all measurements to indicate readily relatable sizes. If you need precise measurements, pleas

(2b)His Master Voice records

His Master’s Voice

His Master’s Voice
His Master's Voice.jpg
Parent company EMI (British Commonwealth except Canada)
RCA (western hemisphere)
JVC (Japan)
Founded 1908
Status defunct (fate: trade mark sold to HMV Group)
Genre Various
Country of origin United Kingdom

His Master’s Voice is a famous trademark in the music business, and for many years was the name of a large record label. The name was coined in 1899 as the title of a painting of the dog Nipper listening to a wind-up gramophone. In the photograph on which the painting was based, the dog was listening to a cylinder phonograph.

the end @copyright dr Iwan suwandy 2011

The Rare Dragon Handle Yuan Qingbay Ewer Found In Indonesia










The Driwan’s  Cybermuseum


(Museum Duniamaya Dr Iwan)

Showroom :






A rare Qingbai Ewer and Cover. Yuan Dynasty. Photo Sotheby’s

well potted, the pear-shaped body rising to a tall flared neck, supported on a splayed foot with a prominent flange, the body set with a slender curved spout issuing from the mouth of a dragon, connected to the body by an elaborate S-shaped bridge, set opposite with a curved handle formed by the scaly body of a fish-dragon with the opened mouth swallowing the top of the handle, its mane forming a small loop for attaching the cover, its tail fanning out into a large trefoil motif applied in relief, the body decorated on either side with a phoenix in flight with upturned scrolling tail and a cloud motif, cut from thin sheets of clay and applied with incised details, above a band of upright lappets containing ruyi heads, the neck collared by a key-fret band of pearl strings and slip-painted upright petal lappets containing scroll motifs, all beneath an icy blue-green transparent glaze, fitted with a stepped domed cover and a small eyelet for attachment to the ewer, surmounted by a seated lion delicately modelled with a thick beard, long mane, and bushy tail bent to one side, its left foreleg resting on a ball with thin freely modelled ribbons and a bell tied around its neck, overall 34 cm., 13 3/8 in. Estimate 1,200,000—1,500,000 HKD. Lot Sold  4,220,000 HKD

PROVENANCE: Messrs John Sparks, London.
Collection of Mr and Mrs Otto Doering, Snr.
Christie’s New York, 9th November 1978, lot 125.
J.J. Lally & Co., New York.

EXHIBITED: The Art Institute of Chicago (on loan).
Chinese Porcelain and Silver in the Song Dynasty, J. J. Lally & Co., New York, 2002, cat. no. 30 (illustrated).

LITERATURE AND REFERENCES: John Ayers, ‘Some Characteristic Wares of the Yüan Dynasty’, Transactions of the Oriental Ceramic Society, vol. 29, 1954-5, pl. 38, fig. 17.
Margaret Medley, Yüan Porcelain and Stoneware, London, 1974, pl. 10.
Anthony du Boulay, Christie’s Pictorial History of Chinese Ceramics, London, 1984, p. 110, fig. 1.
Regina Krahl, Chinese Ceramics from the Meiyintang Collection, London, 1994-2010, vol. 4, no. 1614.

NOTE: This ewer reflects the quest for richer ornamentation in the second half of the Yuan dynasty, which eventually was satisfied by the introduction of underglaze painting in colour. It shows the remarkably wide repertoire of decoration techniques experimented with at the time, such as moulding, incising, slip painting, dotted surface structuring, application of clay sheets, freely modelled motifs and pearl strings.

A very similar ewer without cover in the Tokyo National Museum is published in Yutaka Mino, Chūgoku no tōji. Hakuji/Chinese Ceramics. White Porcelain, Tokyo, 1998, col. pl. 79, perhaps the piece illustrated also in Mikami Tsugio, ed., Sekai tōji zenshū/Ceramic Art of the World, vol. 13, Tokyo, 1981, col. pl. 42. A simpler version of this design, perhaps made somewhat earlier than the present ewer, was among the porcelains recovered from the shipwreck off Shinan, Korea, which can be dated to AD 1323; that ewer has a similar phoenix design in relief, but is lacking any applied motifs and has a plain spout, handle and cover; see Relics Salvaged from the Seabed off Sinan. Materials I, Seoul, 1985, pl. 67. A similar smaller ewer without cover, from the collection of a Vietnamese Princess, was sold at Christie’s New York, 22nd April 1999, lot 256.

A pair of meiping vases with similar, but perhaps also somewhat simpler lion covers, excavated from a tomb of AD 1324 in Wannian county, Jiangxi province, is published in Wenwu 1977, no. 4, pl. 9, fig. 5. A fragment of a similar ewer, excavated from a Yuan city site in Inner Mongolia, is published in Chen Yongzhi, ed., Nei Menggu Jininglu gu cheng yizhi chutu ciqi/Porcelain Unearthed from Jininglu Ancient City Site in Inner Mongolia, Beijing, 2004, p. 20, fig. 13; and a similar fragment of a dragon handle, excavated from the Yuan remains at Luomaqiao, Jingdezhen, Jiangxi province, in Ceramic Finds from Jingdezhen Kilns (10th – 17th Century), Fung Ping Shan Museum, University of Hong Kong, Hong Kong, 1992, cat. no. 116.

the end @ copyright Dr Iwan suwandy

How To Understand And Cure Rest Leg syndrome











The Driwan’s  Cybermuseum


(Museum Duniamaya Dr Iwan)

Showroom :




This year is the fourth year I have experienced RLS syndrome,
Once I learned and try to improve the sport so that legs can increase blood circulation and prevent berdirit too long or sitting with legs hanging prevented, many suggestions from friends that I was walking on hot gravel stones, but no progress.
Currently numbness and edema at the end of the soles of the feet and toes are always still there, especially feelings of edema accompanied saa56t rest on the palm and the tip of your toes, with respect to the above I started doing the research literature on pathophysiolog8is, how this disorder develops, clinical gelaja and pengoba56tan that exist today, for that I hope the support of all patients who experience it to be willing to give komentra and info,.
I Hope This discussion forum will yield information that can be processed into a final conclusion that can be used by anyone who experience this disorder S6yndrome RLS.
Abnormalities that I experienced RLS syndrome are symmetrical, so the possibility of disorder in the neural spine or brain stem, what menyebabkannnya, from some literaturs ditemyukan mineral magnesium deficiency da copper poisoning, xehingga beginning of this info I will move to consult to the experts.
I hope you are all blessed to be able Segers These abnormalities resolved.
Jakarta October 2011
Dr Iwan Suwandy



A simple and natural explanation for why restless leg syndrome with its related symptoms occurs.


The Restless leg syndrome phenomenon has more than one name. It is often referred to as restless legs syndrome, RLS, irritable legs, restless legs, fidgety legs, creepy legs, periodic limb movement disorders, PLMD, and few others. Many names have been given to restless leg syndrome but, “incredibly annoying!” is most likely the name that everyone who suffers from restless leg syndrome will know it best by. Contrary to what some might say, the cause of restless leg syndrome is quite simple and understandable if you think about it from a simpler point of view.

The difference in understanding an ailment lies if differentiating what an ailment does, which in the case of restless legs is produce annoyance in the legs, from what an ailment actually is. In other words; if you chase the symptom, you will never get at its cause.

The biggest problem in today’s health world is misinformation, information presented in such a way that no normal person can confirm, information that is so vague as to be so open ended as to offer no possibility of a solution expect for an implied solution or, totally incomprehensible information because it is completely unnatural or, even illogical.

Always remember that in reality, “there is nothing new under the Sun!” Many experts have confirmed that on Earth we live in a closed system. Any viruses that existed millions of years ago still exist today and, for the most part, we coexist peacefully with them. Anything new has to be man made or, man manipulated. There is no other possibility.

Without being too poetic, when a clear headed person looks into nature, it is not hard to draw parallel relationships between what is going on in nature and what is happening within the body. If everything we see comes from nature, then nature must also be somehow within everything we see otherwise it could not exist in nature in the first place. This not only applies to creatures but also to processes.

Therefore, from the natural point of view, Restless Leg Syndrome is not a new ailment at all. It is just a different form of a very common problem produced by the same process but, in milder form. Restless Leg syndrome according to the legendary medieval Swiss physician, Paracelsus falls into the category of disease he named “podagra” which literally means “bitter waters.” When you connect this to internal bodily fluids, the analogy makes perfect sense. The correctness of this classification will be better explained in the related articles in the pages within the section on restless leg syndrome (see links above and below) where it is shown that Restless leg syndrome, far from being a neurological problem, is actually a very mild yet incredibly annoying form of arthritis; at least as far as Paracelsus was concerned.

What manifests as Restless leg syndrome is less severe than arthritis and replaces what would otherwise be actual pain with a hard to describe irritating, creeping, crawling, tingling in the legs generally often depriving the sufferer of peace and sleep. For the sufferer of Restless leg syndrome, it can occur at any time while being still; whether it is during sitting, lying down or reclining. It’s form may have changed but, the problem itself is not that complicated. The incredible level of annoyance and discomfort produced by restless legs defies belief. It is like “Chinese water torture” for the legs!

In order to comprehend what gives rise to restless leg syndrome, a simple and very straight forward logic using analogies from nature are needed to explain what is going on in the body when it happens. This way of thinking uses very simple concepts. You will need to read them through – perhaps more than once, because the logic behind them is deceptively simple, while not being simple minded.

Many have already found that these completely natural explanations from “outside of the box” do indeed offer a logical explanation of what restless legs syndrome is. If you are looking for a virus or bacteria as the culprit, you will not find one because these are not the cause of restless legs. That abnormal environments and organisms may be present in the body to produce restless legs is not disputed but, where they arise from is! In the past, this would have been called “the arcanum;” the hidden reason or, cause.

The explanations of Restless leg Syndrome or, Restless Legs being presented in this group of pages should leave the sufferer with an understanding of Restless leg syndrome and hope for relief. Like any problem. When you understand it, it can be controlled or even removed.

Sebuah penjelasan sederhana dan alami bagi mengapa sindrom kaki gelisah dengan gejala terkait terjadi.

Fenomena sindrom kaki gelisah memiliki lebih dari satu nama. Hal ini sering disebut sebagai sindrom kaki gelisah, RLS, kaki mudah tersinggung, kaki gelisah, kaki gelisah, kaki menyeramkan, gangguan tungkai periodik gerakan, PLMD, dan beberapa orang lainnya. Banyak nama telah diberikan untuk sindrom kaki gelisah tapi, “sangat menyebalkan!” kemungkinan besar nama yang setiap orang yang menderita dari sindrom kaki gelisah akan tahu terbaik. Bertentangan dengan apa yang beberapa mungkin mengatakan, penyebab sindrom kaki gelisah cukup sederhana dan mudah dipahami jika Anda berpikir tentang hal ini dari sudut pandang sederhana.

Perbedaan dalam memahami suatu penyakit kebohongan jika membedakan suatu penyakit apa yang tidak, yang dalam kasus kaki gelisah adalah menghasilkan gangguan di kaki, dari apa suatu penyakit sebenarnya. Dengan kata lain, jika Anda mengejar gejala, Anda tidak akan pernah mendapatkan penyebabnya.

Masalah terbesar dalam dunia kesehatan saat ini adalah informasi yang keliru, informasi yang disajikan sedemikian rupa bahwa tidak ada orang normal dapat mengkonfirmasi, informasi yang sangat samar-samar menjadi begitu terbuka berakhir untuk tidak menawarkan kemungkinan solusi harapkan untuk solusi tersirat atau, benar-benar dimengerti informasi karena benar-benar tidak wajar atau, bahkan tidak logis.
Selalu ingat bahwa dalam kenyataannya, “tidak ada yang baru di bawah matahari!” Banyak ahli telah menegaskan bahwa di Bumi kita hidup dalam sistem tertutup. Setiap virus yang ada jutaan tahun lalu masih ada hari ini dan, untuk sebagian besar, kita hidup berdampingan secara damai dengan mereka. Sesuatu yang baru harus dibuat atau manusia, manusia dimanipulasi. Tidak ada kemungkinan lain.

Tanpa terlalu puitis, ketika seseorang menuju ke alam yang jelas terlihat, tidak sulit untuk menarik hubungan paralel antara apa yang terjadi di alam dan apa yang terjadi dalam tubuh. Jika semuanya kita lihat berasal dari alam, maka alam juga harus entah bagaimana dalam semua yang kita lihat jika tidak maka tidak bisa ada di alam di tempat pertama. Ini tidak hanya berlaku untuk makhluk tetapi juga untuk proses.

Oleh karena itu, dari sudut pandang alam, Sindrom Kaki Resah bukan penyakit baru sama sekali. Ini hanya bentuk yang berbeda dari masalah yang sangat umum yang dihasilkan oleh proses yang sama tetapi, dalam bentuk yang lebih ringan. Kaki sindrom gelisah menurut Swis dokter legendaris abad pertengahan, Paracelsus jatuh ke dalam kategori penyakit yang bernama “podagra” yang secara harfiah berarti “air pahit.” Ketika Anda menghubungkan ini ke cairan tubuh internal yang, analogi masuk akal. Kebenaran klasifikasi ini akan lebih baik dijelaskan dalam artikel yang terkait di halaman dalam bagian tentang sindrom kaki gelisah (lihat link di atas dan di bawah) di mana itu menunjukkan bahwa sindrom kaki gelisah, jauh dari masalah neurologis, sebenarnya sangat ringan namun sangat mengganggu bentuk arthritis, setidaknya sejauh sebagai Paracelsus prihatin.
Apa yang bermanifestasi sebagai sindrom kaki gelisah kurang parah dari arthritis dan menggantikan apa yang sebaliknya akan menjadi sakit aktual dengan keras untuk menggambarkan menjengkelkan, merayap, merangkak, kesemutan di kaki umumnya sering mencabut penderita perdamaian dan tidur. Untuk penderita sindrom kaki gelisah, dapat terjadi kapan saja ketika sedang masih, apakah itu adalah selama duduk, berbaring atau berbaring. Bentuknya mungkin telah berubah tetapi, masalah itu sendiri tidaklah rumit. Tingkat luar biasa jengkel dan ketidaknyamanan yang dihasilkan oleh kaki gelisah menentang keyakinan. Hal ini seperti “penyiksaan air Cina” untuk kaki!

 Dalam rangka untuk memahami apa yang menimbulkan sindrom kaki gelisah, sebuah logika sederhana dan sangat lurus ke depan menggunakan analogi dari alam yang diperlukan untuk menjelaskan apa yang terjadi di dalam tubuh ketika itu terjadi. Cara berpikir menggunakan konsep-konsep yang sangat sederhana. Anda akan perlu membaca mereka melalui – mungkin lebih dari sekali, karena logika di belakang mereka tampak sederhana, sementara tidak berpikiran sederhana.

Banyak telah menemukan bahwa penjelasan ini benar-benar alami dari “luar kotak” memang menawarkan penjelasan logis dari apa yang gelisah kaki sindrom ini. Jika Anda mencari virus atau bakteri sebagai pelakunya, Anda tidak akan menemukan satu karena ini bukan penyebab kaki gelisah. Bahwa lingkungan abnormal dan organisme dapat hadir dalam tubuh untuk memproduksi kaki gelisah tidak diperdebatkan, tetapi, di mana mereka muncul dari ini! Di masa lalu, ini akan disebut “Arcanum;” alasan tersembunyi atau, menyebabkan.

Penjelasan Sindrom kaki gelisah atau, Restless Legs yang disajikan dalam kelompok ini halaman harus meninggalkan penderita dengan pemahaman tentang sindrom kaki gelisah dan harapan untuk bantuan. Seperti masalah apapun. Ketika Anda memahaminya, itu dapat dikendalikan atau bahkan dihapus.




Restless Leg Syndrome Symptoms – 3 Symptoms To Watch For


The restless leg syndrome symptoms can ruin a good night’s sleep and make lengthy sitting a really painful and irritating problem. So now what? Well consider that no matter what your symptoms are you’ll be able to find some relief.  Let’s look at the most common restless leg syndrome symptoms to learn about if your suffering with it. If you have got the symptoms you probably have it, but don’t panic about it, there’s cures available! Try some Exercises to get even better results.

This is primary a condition that is neurologic based. The condition is defined by some strange feelings inside the legs and the need to move them. In just about all cases, the person that suffers from this condition will go through just about all the symptoms when they lay down to try to go to sleep. It may be helpful to try some Home Remedies For Restless Leg Syndrome.


Although moving the legs can bring some relief, the impulse linked with the movements can interrupt the person’s ability to rest or sleep well. All right…

Here are the 3 main restless leg syndrome symptoms to watch for…

>>>> Anxiety… Anxiousness is another basic symptom that’s experienced by those suffering from this condition. For those people that are bothered by the relentless urge to keep moving their legs to get some relief from the strange feelings, anxiousness could be experienced if the leg movements are not made. If the leg movements are giving relief to the sensations, the individual might go through anxiousness since they’re not able to sleep or concentrate on other tasks.

>>>> The ongoing need to move the legs…When a restless leg syndrome sufferer goes through the odd sensations that they have in their legs, they will have a very strong desire to move their legs. They could merely move their legs from one spot to another position to get some relief. Then, there are those people that have to shake their legs back and forth or up and down to have some relief.

>>>> Strange feelings… The 1st symptom usually experienced are strange sensations inside the legs. The sensations might be felt in one leg or both legs at the same time. A lot of persons may feel as though there legs are tingling. There are other people that may experience a burning sensation on their legs.

A lot of people likewise suffer from sensations that are likened to pins and needles similar to the feeling when your foot falls asleep. Then, there are numerous people who suffer from feelings that there are many insects  crawling on their skin. For some others, this is the most grueling aspect of this condition. Some people have found relief from various Homeopathy Remedies.

A lot of persons discover that they have to in reality get up and take a short walk or run around. This ongoing urge to continually move can cause a disruption in their day to day living or their sleep cycle. If you believe that you’re suffering with restless leg syndrome symptoms , it’s crucial to get some medical help for a confirmed diagnosis because there are treatments that may Eliminate Restless Leg Syndrome and help you in coping with the symptoms.


Gejala-gejala sindrom kaki gelisah dapat merusak tidur malam yang baik dan membuat panjang duduk masalah yang benar-benar menyakitkan dan menjengkelkan. Jadi sekarang apa? Yah menganggap bahwa tidak peduli apa gejala Anda Anda akan dapat menemukan beberapa bantuan. Mari kita melihat gejala yang paling umum sindrom kaki gelisah untuk belajar tentang jika penderitaan Anda dengan itu. Jika Anda memiliki gejala-gejala Anda mungkin memiliki, tapi jangan panik tentang hal itu, ada obat tersedia! Cobalah beberapa Latihan untuk mendapatkan hasil yang lebih baik.
Ini adalah primer suatu kondisi yang berbasis neurologis. Kondisi ini ditentukan oleh beberapa perasaan aneh di dalam kaki dan kebutuhan untuk memindahkan mereka. Dalam hampir semua kasus, orang yang menderita dari kondisi ini akan melalui hampir semua gejala-gejala ketika mereka berbaring untuk mencoba tidur. Ini mungkin membantu untuk mencoba beberapa Home remedies Untuk Sindrom Kaki Resah.

Meskipun bergerak kaki dapat membawa beberapa bantuan, dorongan terkait dengan gerakan dapat mengganggu kemampuan seseorang untuk beristirahat atau tidur nyenyak. Baiklah …
Berikut adalah 3 utama gejala sindrom kaki gelisah untuk menonton …
>>> Anxiety…” Ff=”>>>> Anxiety…” Gf=”>>>> Kecemasan … ” closure_uid_5q9o9q=”109″>>>>> Kecemasan … Kecemasan adalah gejala lain dasar yang dialami oleh mereka yang menderita dari kondisi ini. Bagi orang-orang yang terganggu oleh dorongan tanpa henti untuk terus bergerak kaki mereka untuk mendapatkan beberapa bantuan dari perasaan yang aneh, kecemasan bisa dialami jika gerakan kaki tidak dibuat. Jika gerakan kaki yang memberikan bantuan kepada sensasi, individu mungkin akan pergi melalui kecemasan karena mereka tidak bisa tidur atau berkonsentrasi pada tugas-tugas lainnya.
>>> The ongoing need to move the legs…When a restless leg syndrome sufferer goes through the odd sensations that they have in their legs, they will have a very strong desire to move their legs.” Ff=”>>>> The ongoing need to move the legs…When a restless leg syndrome sufferer goes through the odd sensations that they have in their legs, they will have a very strong desire to move their legs.” Gf=”>>>> Kebutuhan yang sedang berlangsung untuk menggerakkan kaki … Ketika seorang penderita sindrom kaki gelisah berjalan melalui sensasi aneh yang mereka miliki di kaki mereka, mereka akan memiliki keinginan yang sangat kuat untuk menggerakkan kaki mereka. ” closure_uid_5q9o9q=”113″>>>>> Kebutuhan yang sedang berlangsung untuk menggerakkan kaki … Ketika seorang penderita sindrom kaki gelisah berjalan melalui sensasi aneh yang mereka miliki di kaki mereka, mereka akan memiliki keinginan yang sangat kuat untuk menggerakkan kaki mereka. Mereka hanya bisa menggerakkan kaki mereka dari satu tempat ke posisi lain untuk mendapatkan beberapa bantuan. Lalu, ada orang-orang yang telah mengguncang kaki mereka bolak-balik atau naik dan turun untuk memiliki beberapa bantuan.
 >>> Strange feelings…” Ff=”>>>> Strange feelings…” Gf=”>>>> Perasaan aneh … ” closure_uid_5q9o9q=”116″>>>>> Perasaan aneh … Gejala yang biasanya dialami 1 adalah sensasi yang aneh di dalam kaki. Mungkin sensasi dirasakan di satu kaki atau kedua kaki pada waktu yang sama. Banyak orang mungkin merasa seolah-olah ada kaki kesemutan. Ada orang lain yang mungkin mengalami sensasi terbakar pada kaki mereka.
Banyak orang juga menderita sensasi yang disamakan dengan pin dan jarum mirip dengan perasaan ketika kaki Anda jatuh tertidur. Lalu, ada banyak orang yang menderita dari perasaan bahwa ada banyak serangga merayap di kulit mereka. Bagi beberapa orang lain, ini adalah aspek yang paling melelahkan dari kondisi ini. Beberapa orang telah menemukan bantuan dari berbagai Homeopati remedies.
Banyak orang menemukan bahwa mereka harus dalam realitas bangun dan berjalan-jalan pendek atau berlari-lari. Dorongan yang berkelanjutan untuk terus bergerak dapat menyebabkan gangguan di hari mereka untuk hidup hari atau siklus tidur mereka. Jika Anda yakin bahwa Anda menderita dengan gejala sindrom kaki gelisah, itu penting untuk mendapatkan bantuan medis untuk diagnosis dikonfirmasi karena ada pengobatan yang dapat Hilangkan Sindrom Kaki Resah dan membantu Anda dalam menghadapi gejala-gejala.

Restless Leg Syndrome Symptoms


How do you know you have restless leg syndrome?

  • Do you have an unbearable urge to move your legs?
  • Do you feel uncomfortable sensations in your legs?
  • Do your symptoms begin to get worse towards the evening or when you are in bed?
  • Do your symptoms begin to feel better when you move your legs?
  • Do you have trouble sleeping because of the pain or discomfort in your legs?


What is Restless Leg Syndrome?

     Restless leg syndrome involves unpleasant leg sensations when it is time to go to bed.  Some patients describe it as a tingling in the legs.  Others say it feels more like a prickling sensation, or a feeling like pins and needles in the legs.  This tingling is very difficult to ignore, and many patients complain that it is frustrating, irritating, and leads to lack of sleep.  Other patients experience sudden jerking of the legs during sleeping time or even while driving the car.  This jerking of the legs can occur every twenty to thirty seconds.  Many patients state that when they are experiencing restless leg syndrome, they must get up and move around immediately, or the sensations in their legs will get worse.  Restless leg syndrome typically begins slowly, and the legs will become more affected as time goes on.  Restless leg syndrome causes the legs to become painful.  It usually will ease when the legs are in motion.  Restless leg syndrome becomes more noticeable at times of rest.  During the early evening and later at night, the pain in restless legs tends to increase.  The result is typically insomnia.  Lack of sleep has many effects on your life.  It will impact your relationships, your work, and your overall health.


What are the causes of restless leg syndrome?

     The cause of restless leg syndrome is unknown, although there are some associated factors with restless leg syndrome.  Some of these factors include drugs and medications, including alcohol, caffeine, H-2 Histamine blockers, and some antidepressants.  Health factors include being pregnant, obese, or having an iron deficiency or anemia.  Nerve disease, polyneuropathy, exposure to toxins, diabetes, and kidney failure are also associated with restless leg syndrome.  In addition, choosing to smoke may increase your chances for developing restless leg syndrome.  In some instances, restless legs have run in families.  It also seems to develop in people as they become older.

Ada sekarang mungkin akan meringankannya bagi sebagian orang dengan RLS.
Para peneliti telah menemukan bahwa obat yang digunakan untuk mengobati kejang dan kecemasan sekarang dapat membantu orang yang menderita sindrom kaki gelisah (RLS).

Restless kaki sindrom (RLS) “. Adalah suatu kondisi neurologis yang ditandai oleh dorongan tak tertahankan untuk menggerakkan kaki” Menurut Yayasan RLS, kriteria tertentu yang harus dipenuhi untuk dapat didiagnosis dengan kondisi ini:

    * Anda memiliki keinginan kuat untuk menggerakkan kaki Anda yang Anda mungkin tidak mampu melawan. Kebutuhan untuk bergerak sering disertai dengan sensasi tidak nyaman. Beberapa kata yang digunakan untuk menggambarkan sensasi ini meliputi: merayap, gatal, menarik, menyeramkan-crawly, menarik, atau menggerogoti.
    * Anda gejala RLS memulai atau menjadi lebih buruk ketika Anda sedang beristirahat. Semakin lama Anda sedang beristirahat, semakin besar kesempatan gejala akan terjadi dan lebih parah mereka mungkin.
    * Anda RLS gejala menjadi lebih baik ketika Anda memindahkan kaki Anda. Lega bisa lengkap atau hanya parsial tetapi umumnya dimulai segera setelah memulai suatu kegiatan. Bantuan berlanjut selama aktivitas motorik terus.
    * Anda gejala RLS lebih buruk di malam hari terutama ketika anda berbaring. Kegiatan yang mengganggu Anda di malam hari tidak mengganggu Anda selama hari.

Sebuah studi dilakukan dua belas minggu yang melibatkan 58 orang dengan RLS. Para pregabalin obat diberikan kepada 30 orang, sedangkan sisanya menerima plasebo. Orang-orang berpartisipasi dalam studi tidur dilakukan pada awal dan akhir penelitian.

Para peneliti menemukan bahwa sekitar dua-pertiga dari orang yang memakai pregabalin tidak punya gejala RLS, sementara pada obat. Bagi orang-orang yang masih melaporkan gejala, gejala-gejala ditingkatkan dengan 66 persen. Gejala-gejala orang-orang dalam kelompok plasebo telah memburuk sebesar 29 persen.

Peserta juga melaporkan tidur lebih baik.

“Karena gejala RLS bertambah buruk pada malam hari, sulit bagi orang-orang dengan RLS untuk mendapatkan tidur yang cukup,” kata penulis studi Diego Garcia-Borreguero, MD, Direktur Sleep Research Institute di Madrid, Spanyol. “Namun, temuan pregabalin acara kami membantu orang mendapatkan tidur yang lebih dalam. Obat ditahan dengan baik dan merupakan alternatif yang menjanjikan untuk pengobatan saat ini karena efek unggul pada kualitas tidur. “

Penelitian ini didukung oleh Pfizer Inc dan akan dipresentasikan pada American Academy of Neurology Pertemuan Tahunan ke-61 itu.
Sumber: ScienceDaily



Understanding the Symptoms of Restless Leg Syndrome

Restless leg syndrome is a very real problem that causes a sudden desire to move your legs. It is important to have an understanding of restless leg syndrome in order to obtain targeted treatment. Understanding the symptoms of restless leg syndrome can help your doctor obtain a proper diagnosis, and is based on history and description of the symptoms. 

The urge to move the legs is irresistible and is associated with uncomfortable feelings. The symptoms of restless leg syndrome are worse when sleeping, and can interfere with rest. 


Sleep deprivation from restless leg syndrome can interfere with productivity at work and at home. Some individuals experience frequent jerking movements that occur intermittently and disrupt sleep. Sensations in the legs are described as “crawling”, “itching”, “pulling” and “creeping


Diagnosis of restless leg syndrome is based on the following:



Sudden desire to move your legs accompanied by unusual or uncomfortable sensations
Increased urge when trying to rest
Symptoms are better when the legs move
Symptoms are worse at night

Restless leg syndrome affects all genders, ethnicity, and age groups. It is considered a hereditary disease . According to the Mayo Clinic, restless leg syndrome affects five to eleven percent of individuals in North America and Europe. In July, 2009, findings that restless leg syndrome is linked to a gene mutation were published.

According to Carles Vilariño-Güell, Ph.D., a neuroscientist at Mayo Clinic, Jacksonville, the gene mutation associated with restless leg syndrome…” is in a portion of the protein that is identical in species as distinct to human as frogs and fish, which tells us that this portion is very important for the proper function of the protein and that the mutation has a very high chance of causing disease.”

Restless leg syndrome is also linked to increased estrogen levels during pregnancy, making women more susceptible. The study was published February 2009 in the Journal, Sleep, and was conducted by German researchers.

Dr. Thomas Pollmächer, principal investigator for the study said, “We, for the first time, have quite direct evidence that RLS in pregnancy … “is obviously directly related to hormonal changes (estrogens),” according to information from Reuters Health.

Restless leg syndrome is also common among patients with chronic kidney disease (CKD). The symptoms are also worse for those who take antihistamines to sleep. Multiple sclerosis is linked to increased risk for restless leg syndrome.

Restless leg syndrome not only decreases sleep quality, but was also found to be linked to increased risk of heart disease and stroke, in a large study conducted by Harvard researchers and published in the January 1, 2008, issue of Neurology, the medical journal of the American Academy of Neurology.


Treatment options for restless leg syndrome


The goal of treatment for restless leg syndrome is to relieve the symptoms. Addressing the underlying cause can help, especially if there is a problem with the nerves or blood flow in the legs that is most common in diabetics. 

Low levels of iron, folate , and magnesium can contribute to symptoms of restless legs. Your doctor can measure with a simple blood test and may suggest supplements if levels are low. Avoidance of caffeine , alcohol and tobacco can help treat restless leg syndrome. If you smoke, consume alcohol and enjoy caffeine, decreasing consumption can help. Moderate, versus vigorous exercise helps some individuals decrease the severity of symptoms. For some, massage, heat, and a warm bath helps decrease, but not eliminate restless leg syndrome symptoms. 




Ropinirole is an approved drug from the FDA that is also used to treat Parkinson’s disease , and can be prescribed to treat restless leg syndrome. Sedatives can help with sleep and relax the muscles as a treatment option. Pain medication can help with uncomfortable feelings associated with restless leg syndrome.


Symptoms of restless leg syndrome should not be ignored. Understanding restless leg syndrome symptoms, causes and treatment options are important to prevent risk of stroke, and improve sleep quality. There is no known cure for restless leg syndrome. Speak with your doctor if you think you have been experiencing symptoms

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Sindrom kaki gelisah adalah masalah yang sangat nyata yang menyebabkan keinginan mendadak untuk memindahkan kaki Anda. Hal ini penting untuk memiliki pemahaman tentang sindrom kaki gelisah untuk mendapatkan pengobatan yang ditargetkan. Memahami gejala sindrom kaki gelisah dapat membantu dokter mendapatkan diagnosa yang tepat, dan didasarkan pada sejarah dan deskripsi dari gejala.

Dorongan untuk menggerakkan kaki yang tak tertahankan dan berhubungan dengan perasaan tidak nyaman. Gejala-gejala sindrom kaki gelisah lebih buruk ketika tidur, dan dapat mengganggu istirahat.

Kurang tidur dari sindrom kaki gelisah dapat mengganggu produktivitas di tempat kerja dan di rumah. Beberapa individu mengalami gerakan yang menghentak sering yang terjadi sebentar-sebentar dan mengganggu tidur. Sensasi di kaki digambarkan sebagai “merangkak”, “gatal”, “menarik” dan “merayap”.

Diagnosis sindrom kaki gelisah didasarkan pada hal berikut:

Tiba-tiba keinginan untuk menggerakkan kaki Anda disertai oleh sensasi yang tidak biasa atau tidak nyaman
Peningkatan dorongan ketika mencoba untuk beristirahat
Gejala lebih baik bila kaki bergerak
Gejala memburuk pada malam hari

Sindrom kaki gelisah mempengaruhi semua jenis kelamin, etnis, dan kelompok umur. Hal ini dianggap sebagai penyakit keturunan. Menurut Mayo Clinic, sindrom kaki gelisah mempengaruhi 5-11 persen individu di Amerika Utara dan Eropa. Pada bulan Juli, 2009, temuan bahwa sindrom kaki gelisah terkait dengan mutasi gen diterbitkan.
Menurut Carles Vilariño-Güell, Ph.D., seorang ahli syaraf di Mayo Clinic, Jacksonville, mutasi gen yang terkait dengan sindrom kaki gelisah … “adalah bagian dari protein yang identik pada spesies yang berbeda untuk manusia sebagai katak dan ikan , yang mengatakan kepada kita bahwa bagian ini sangat penting untuk fungsi yang tepat dari protein dan bahwa mutasi memiliki kesempatan yang sangat tinggi menyebabkan penyakit. “
Sindrom kaki gelisah juga terkait dengan meningkatnya kadar estrogen selama kehamilan, membuat wanita lebih rentan. Studi ini dipublikasikan Februari 2009 di Journal, Tidur, dan dilakukan oleh para peneliti Jerman.
Dr Thomas Pollmächer, peneliti utama penelitian mengatakan, “Kami, untuk pertama kalinya, memiliki bukti cukup langsung bahwa RLS pada kehamilan …” jelas langsung berhubungan dengan perubahan hormonal (estrogen), “menurut informasi dari Reuters Health .
Sindrom kaki gelisah juga umum di antara pasien dengan penyakit ginjal kronis (CKD). Gejala tersebut juga lebih buruk bagi mereka yang mengambil antihistamin untuk tidur. Multiple sclerosis adalah terkait dengan peningkatan risiko untuk sindrom kaki gelisah.
Sindrom kaki gelisah tidak hanya mengurangi kualitas tidur, tetapi juga ditemukan dihubungkan dengan peningkatan risiko penyakit jantung dan stroke, dalam sebuah penelitian besar yang dilakukan oleh para peneliti Harvard dan diterbitkan dalam edisi 1 Januari 2008, Neurologi, jurnal medis dari American Academy of Neurology.

Pengobatan pilihan untuk sindrom kaki gelisah

 Tujuan pengobatan untuk sindrom kaki gelisah adalah untuk meringankan gejala. Mengatasi penyebab yang mendasari dapat membantu, terutama jika ada masalah dengan saraf atau aliran darah di kaki yang paling umum pada penderita diabetes.

Rendahnya tingkat zat besi, folat, dan magnesium dapat berkontribusi untuk gejala kaki gelisah. Dokter dapat mengukur dengan tes darah yang sederhana dan mungkin menyarankan suplemen jika tingkat rendah. Menghindari kafein, alkohol dan tembakau dapat membantu mengobati sindrom kaki gelisah. Jika Anda merokok, mengkonsumsi alkohol dan menikmati kafein, konsumsi menurun dapat membantu. Latihan moderat, dibandingkan yang kuat membantu beberapa individu mengurangi keparahan gejala. Untuk beberapa, pijat, panas, dan mandi air hangat membantu mengurangi, namun tidak menghilangkan gejala sindrom kaki gelisah.


Ropinirole adalah obat yang disetujui dari FDA yang juga digunakan untuk mengobati penyakit Parkinson, dan dapat diresepkan untuk mengobati sindrom kaki gelisah. Sedatif dapat membantu dengan tidur dan rileks otot-otot sebagai pilihan pengobatan. Obat nyeri dapat membantu dengan perasaan tidak nyaman yang berhubungan dengan sindrom kaki gelisah.

Gejala sindrom kaki gelisah tidak boleh diabaikan. Memahami gejala sindrom kaki gelisah, penyebab dan pilihan pengobatan yang penting untuk mencegah risiko stroke, dan meningkatkan kualitas tidur. Tidak ada obat dikenal untuk sindrom kaki gelisah. Bicaralah dengan dokter Anda jika Anda berpikir Anda telah mengalami gejala


































Indonesian Version




Tahun ini merupakan tahun ke-empat saya mengalami RLS Syndrome,

Setelah saya pelajari dan berusaha meningkatkan olah raga agar sirkulasi darah dikaki dapat meningkat dan mencegah berdirit terlalu lama atau duduk dengan  kaki tergantung di cegah, banyak usul dari teman-teman agar saya berjalan di atas kerikil batu panas , tetapi tidak ada kemajuannya.

Saat ini rasa kebal dan edema pada ujung telapak kaki dan jari kaki selalu masih ada terutama saa56t istirahat diserta perasaan edema pada telapak dan jari kaki bagian ujung, sehubungan dengan hal tersebut diatas saya mulai melakukan penelitian kepustakaan tentang pathophysiolog8is, bagaimana kelainan ini berkembang, gelaja klinis dan pengoba56tan yang ada saat ini, untuk itu saya harap bantuan dari seluruh pasien yang mengalaminya untuk bersedia memberikan komentra dan info,.

Saya Harap forum diskusi ini akan menghasilkan informasi yang dapat diolah menjadi suatu conclusion akhir yang dapat dimanfaatkan oleh siapa saja yang mengalami kelainan RLS S6yndrome ini.

Kelainan RLS syndrome yang saya alami bersifat simetris, sehingga kemungkinan kelainannya berada di saraf tulangbelakang atau Batang otak, apa yang menyebabkannnya ,dari beberapa literaturs ditemyukan adanya defisiensi mineral magnesium da keracunan tembaga, xehingga mulai dari info ini saya akan bergerak untuk berkonsultasi kepada para ahlinya.

Saya harap anda semua mendoakan agar kelainan Ini akan dapat segers diatasi.

Jakarta October 2011

Dr Iwan Suwandy