Parkinson's disease Classification and external resources
Illustration of the Parkinson disease by Sir William Richard Gowers from A Manual of Diseases of the Nervous System in 1886
ICD-10	G20., F02.3
ICD-9	332
DiseasesDB	9651
MedlinePlus	000755
eMedicine	neuro/304  neuro/635 in young pmr/99 rehab

Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech, as well as other functions. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The 2007 version of the ICD is available online at http//wwwwho The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. A motor skill is generally agreed as a learned skill that involves voluntary movement to complete a task ^[1]

Parkinson's disease belongs to a group of conditions called movement disorders. Movement disorders include Akathisia Akinesia ( lack of movement) Athetosis ( contorted torsion It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). In Medicine ( Neurology) bradykinesia denotes "slow movement" ( Etymology: brady = slow kinesia = movement Akinesia (from the prefix a-, "without" and the Greek κίνηση kinisi, "motion" is the inability to initiate movement due to The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Motor cortex is a term that describes regions of the Cerebral cortex involved in the planning control and execution of voluntary motor functions The basal ganglia (or basal nuclei) are a group of nuclei in the Brain interconnected with the Cerebral cortex, Thalamus and Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive. In Medicine, a chronic disease is a Disease that is long-lasting or recurrent

PD is the most common cause of chronic progressive parkinsonism, a term which refers to the syndrome of tremor, rigidity, bradykinesia and postural instability. Parkinsonism (also known as Parkinson's syndrome, atypical Parkinson's, or secondary Parkinson's) is a neurological Syndrome characterized PD is also called "primary parkinsonism" or "idiopathic PD" (classically meaning having no known cause although this term is not strictly true in light of the plethora of newly discovered genetic mutations). Idiopathic is an Adjective used primarily in Medicine meaning arising spontaneously or from an obscure or unknown cause. While many forms of parkinsonism are "idiopathic", "secondary" cases may result from toxicity most notably of drugs, head trauma, or other medical disorders. The disease is named after English physician James Parkinson; who made a detailed description of the disease in his essay: "An Essay on the Shaking Palsy" (1817). James Parkinson may also refer to James Parkinson (1730-1813, the museum proprietor and land agent

Signs and symptoms

Parkinson disease affects movement (motor symptoms). Typical other symptoms include disorders of mood, behavior, thinking, and sensation (non-motor symptoms). Patients' individual symptoms may be quite dissimilar and progression of the disease is also distinctly individual.

Motor symptoms

The cardinal symptoms are (mnemonic "TRAP"):^[1]

• Tremor: normally 4-6 Hz tremor, maximal when the limb is at rest, and decreased with voluntary movement. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body The hertz (symbol Hz) is a measure of Frequency, informally defined as the number of events occurring per Second. It is typically unilateral at onset. This is the most apparent and well-known symptom, though an estimated 30% of patients have little perceptible tremor; these are classified as akinetic-rigid.
• rigidity: stiffness; increased muscle tone. Spasticity or muscular hypertonicity is a disorder of the body Motor system, and especially the central nervous system (CNS in which certain Muscles continually In combination with a resting tremor, this produces a ratchety, "cogwheel" rigidity when the limb is passively moved.
• Bradykinesia/akinesia: respectively, slowness or absence of movement. In Medicine ( Neurology) bradykinesia denotes "slow movement" ( Etymology: brady = slow kinesia = movement Akinesia (from the prefix a-, "without" and the Greek κίνηση kinisi, "motion" is the inability to initiate movement due to Rapid, repetitive movements produce a dysrhythmic and decremental loss of amplitude. Rhythm (from Greek ῥυθμός - rhythmos, "any measured flow or movement symmetry" is the variation of the length and accentuation of Amplitude is the magnitude of change in the oscillating variable with each Oscillation, within an oscillating system
• Postural instability: failure of postural reflexes, which leads to impaired balance and falls. A balance disorder is a disturbance that causes an individual to feel unsteady giddy woozy or have a sensation of movement spinning or floating A reflex action, also known as a reflex, is an involuntary and almost instant movement in response to stimulus.

Other motor symptoms include:

• Gait and posture disturbances:
  • Shuffling: gait is characterized by short steps, with feet barely leaving the ground, producing an audible shuffling noise. Small obstacles tend to cause the patient to trip.
  • Decreased arm-swing.
  • Turning "en bloc": rather than the usual twisting of the neck and trunk and pivoting on the toes, PD patients keep their neck and trunk rigid, requiring multiple small steps to accomplish a turn.
  • Stooped, forward-flexed posture. In severe forms, the head and upper shoulders may be bent at a right angle relative to the trunk (camptocormia). In Geometry and Trigonometry, a right angle is an angle of 90 degrees corresponding to a quarter turn (that is a quarter of a full circle ^[2]
  • Festination: a combination of stooped posture, imbalance, and short steps. It leads to a gait that gets progressively faster and faster, often ending in a fall.
  • Gait freezing: "freezing" is a manifestation of akinesia (an inability to move). Gait freezing is characterized by an inability to move the feet which may worsen in tight, cluttered spaces or when attempting to initiate gait.
  • Dystonia (in about 20% of cases): abnormal, sustained, painful twisting muscle contractions, often affecting the foot and ankle (mainly toe flexion and foot inversion) which often interferes with gait. Dystonia is a neurological Movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures
• Speech and swallowing disturbances.
  • Hypophonia: soft speech. Speech quality tends to be soft, hoarse, and monotonous. Some people with Parkinson's disease claim that their tongue is "heavy" or have cluttered speech. Cluttered speech is a common term for speech that becomes broken down cluttered or unintelligible due to a variety of reasons ^[3]
  • Monotonic speech.
  • Festinating speech: excessively rapid, soft, poorly-intelligible speech.
  • Drooling: most likely caused by a weak, infrequent swallow and stooped posture. Drooling (also known as ptyalism or sialorrhea) is when Saliva flows outside the Mouth.
  • Non-motor causes of speech/language disturbance in both expressive and receptive language: these include decreased verbal fluency and cognitive disturbance especially related to comprehension of emotional content of speech and of facial expression. ^[4]
  • Dysphagia: impaired ability to swallow. Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder Can lead to aspiration, pneumonia. In Medicine, aspiration is the entry of secretions or foreign material into the trachea and Lungs The patient may either inhale the material Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal
• Other motor symptoms:
  • Fatigue (up to 50% of cases);
  • Masked faces (a mask-like face also known as hypomimia), with infrequent blinking;^[5]
  • Difficulty rolling in bed or rising from a seated position;
  • Micrographia (small, cramped handwriting);
  • Impaired fine motor dexterity and motor coordination;
  • Impaired gross motor coordination;
  • Poverty of movement: overall loss of accessory movements, such as decreased arm swing when walking, as well as spontaneous movement;
  • Akathisia. Hypomimia, a Medical sign, is a reduced degree of facial expression Blinking, known less commonly as nictating, is the rapid closing and opening of the Eyelid. Micrographia is a medical term used to describe abnormally small cramped handwriting and/or the progression to continually smaller handwriting Gross motor coordination addresses the Gross motor skills walking running climbing jumping crawling lifting one's head sitting up etc Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of "inner" restlessness that manifests itself with an inability to sit still or remain

Non-motor symptoms

Mood disturbances

Estimated prevalence rates of depression vary widely according to the population sampled and methodology used. Reviews of depression estimate its occurrence in anywhere from 20-80% of cases. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression ^[6] Estimates from community samples tend to find lower rates than from specialist centres. Most studies use self-report questionnaires such as the Beck Depression Inventory, which may overinflate scores due to physical symptoms. The Beck Depression Inventory ( BDI, BDI-II) created by Dr Aaron T Studies using diagnostic interviews by trained psychiatrists also report lower rates of depression. More generally, there is an increased risk for any individual with depression to go on to develop Parkinson's disease at a later date. ^[7] Seventy percent of individuals with Parkinson's disease diagnosed with pre-existing depression go on to develop anxiety. Ninety percent of Parkinson's disease patients with pre-existing anxiety subsequently develop depression; apathy or abulia. Aboulia or Abulia (from the Greek "αβουλία" meaning "non-will" in Neurology, refers to a lack of will or initiative

Cognitive disturbances

• Slowed reaction time; both voluntary and involuntary motor responses are significantly slowed.
• Executive dysfunction, characterized by difficulties in: differential allocation of attention, impulse control, set shifting, prioritizing, evaluating the salience of ambient data, interpreting social cues, and subjective time awareness. This complex is present to some degree in most Parkinson's patients; it may progress to:
• Dementia: a later development in approximately 20-40% of all patients, typically starting with slowing of thought and progressing to difficulties with abstract thought, memory, and behavioral regulation. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Hallucinations, delusions and paranoia may develop. A hallucination, in the broadest sense is a Perception in the absence of a stimulus. A delusion is commonly defined as a fixed False Belief and is used in everyday language to describe a belief that is either false fanciful or derived from Deception Paranoia is a disturbed thought process characterized by excessive Anxiety or Fear, often to the point of Irrationality and Delusion.
• Short term memory loss; procedural memory is more impaired than declarative memory. Memory loss can have many causes Alzheimer's disease is an illness which can cause mild to severe memory loss Procedural memory is the long-term Memory of Skills and procedures or "how to" knowledge ( Procedural knowledge) Declarative memory is the aspect of human Memory that stores Facts It is so called because it refers to memories that can be consciously discussed or declared Prompting elicits improved recall.
• Medication effects: some of the above cognitive disturbances are improved by dopaminergic medications, while others are actually worsened. ^[8]

Sleep disturbances

• Excessive daytime somnolence
• Initial, intermediate, and terminal insomnia
• Disturbances in REM sleep: disturbingly vivid dreams, and REM Sleep Disorder, characterized by acting out of dream content — can occur years prior to diagnosis

Sensation disturbances

• Impaired visual contrast sensitivity, spatial reasoning, colour discrimination, convergence insufficiency (characterized by double vision) and oculomotor control
• Dizziness and fainting; usually attributable orthostatic hypotension, a failure of the autonomic nervous system to adjust blood pressure in response to changes in body position
• Impaired proprioception (the awareness of bodily position in three-dimensional space)
• Reduction or loss of sense of smell (microsmia or anosmia) - can occur years prior to diagnosis
• pain: neuropathic, muscle, joints, and tendons, attributable to tension, dystonia, rigidity, joint stiffness, and injuries associated with attempts at accommodation

Autonomic disturbances

• Oily skin and seborrheic dermatitis^[9]
• Urinary incontinence, typically in later disease progression
• Nocturia (getting up in the night to pass urine) — up to 60% of cases
• Constipation and gastric dysmotility that is severe enough to endanger comfort and even health
• Altered sexual function: characterized by profound impairment of sexual arousal, behavior, orgasm, and drive is found in mid and late Parkinson disease. Somnolence (or " drowsiness " is a state of near- Sleep, a strong desire for sleep or sleeping for unusually long periods (c Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity The oculomotor nerve is the third of twelve paired Cranial nerves. Many different terms are often used to describe what is collectively known as dizziness. Orthostatic hypotension (also known as postural hypotension, and colloquially as head rush or a dizzy spell) is a form of Hypotension in which &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control Proprioception (ˌproʊpriːəˈsɛpʃən PRO -pree-o-SEP-shun from Latin proprius, meaning "one's own" and perception is the Sense Olfaction (also known as olfactics or smell) refers to the Sense of smell. Anosmia is the lack of Olfaction, or an absence of the ability to smell Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Seborrhoeic Eczema (also Seborrheic dermatitis AmE, seborrhea) is a skin disorder affecting the scalp face and trunk causing scaly flaky Urinary incontinence ( UI) is any involuntary leakage of Urine. Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that In Human anatomy, the stomach is a J-shaped hollow muscular organ of the Gastrointestinal tract involved in the second phase of Digestion, following Current data addresses male sexual function almost exclusively.
• Weight loss, which is significant over a period of ten years. Weight loss, in the context of Medicine or Health or Physical fitness, is a reduction of the total Body weight, due to a mean loss of fluid

Diagnosis

18F PET scan shows decreased dopamine activity in the basal ganglia, a pattern which aids in diagnosing Parkinson's disease. The basal ganglia (or basal nuclei) are a group of nuclei in the Brain interconnected with the Cerebral cortex, Thalamus and

There are currently no blood or laboratory tests that have been proven to help in diagnosing PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. The Unified Parkinson's Disease Rating Scale is the primary clinical tool used to assist in diagnosis and determine severity of PD. The Unified Parkinson's Disease Rating Scale ( U nified' P' arkinson's D isease R ating S cale is a Rating scale used to follow Indeed, only 75% of clinical diagnoses of PD are confirmed at autopsy. ^[10] Early signs and symptoms of PD may sometimes be dismissed as the effects of normal aging. The physician may need to observe the person for some time until it is apparent that the symptoms are consistently present. Usually doctors look for shuffling of feet and lack of swing in the arms. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases. However, CT and MRI brain scans of people with PD usually appear normal.

Clinical practice guidelines introduced in the UK in 2006 state that the diagnosis and follow-up of Parkinson's disease should be done by a specialist in the disease, usually a neurologist with an interest in movement disorders. A medical guideline (also called a clinical guideline, clinical protocol or clinical practice guideline) is a document with the aim of guiding decisions The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located ^[11]

Classification

"Parkinson's disease" is the synonym of "primary parkinsonism", i. e. isolated parkinsonism due to a neurodegenerative process without any secondary systemic cause. In some cases, it would be inaccurate to say that the cause is "unknown", because a small proportion is caused by genetic mutations. It is possible for a patient to be initially diagnosed with Parkinson's disease but then to develop additional features, requiring revision of the diagnosis. ^[11]

There are other disorders that are called Parkinson-plus diseases. Parkinson-plus syndromes are a group of diseases featuring the classical features of Parkinson's disease (tremor rigidity akinesia/bradykinesia postural instability with additional These include: multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Multiple system atrophy (MSA is a Degenerative Neurological disorder. Progressive supranuclear palsy ( PSP) (or the Steele-Richardson-Olszewski syndrome, after the Canadian physicians who described it in 1963 is a rare degenerative disorder Corticobasal degeneration (CBD is a sporadic progressive Neurodegenerative disease associated with Atrophy of the Cerebral cortex and the Basal ganglia Some include dementia with Lewy bodies (DLB) — while idiopathic Parkinson's disease patients also have Lewy bodies in their brain tissue, the distribution is denser and more widespread in DLB. Dementia with Lewy bodies (DLB is a type of Dementia characterized by abnormal levels of Lewy bodies, a nervous system protein Lewy bodies are abnormal aggregates of Protein that develop inside Nerve cells They are identified under the Microscope when Histology is performed Even so, the relationship between Parkinson disease, Parkinson disease with dementia (PDD), and dementia with Lewy bodies (DLB) might be most accurately conceptualized as a spectrum, with a discrete area of overlap between each of the three disorders. The natural history and role of Lewy bodies is little understood.

These Parkinson-plus diseases may progress more quickly than typical idiopathic Parkinson disease. If cognitive dysfunction occurs before or very early in the course of the movement disorder then DLBD may be suspected. Early postural instability with minimal tremor especially in the context of ophthalmoparesis should suggest PSP. Early autonomic dysfunction including erectile dysfunction and syncope may suggest MSA. The presence of extreme asymmetry with patchy cortical cognitive defects such dysphasia and apraxias especially with "alien limb" phenomena should suggest CBD.

The usual anti-Parkinson's medications are typically either less effective or not effective at all in controlling symptoms; patients may be exquisitely sensitive to neuroleptic medications like haloperidol. Haloperidol is a Typical antipsychotic. It is in the Butyrophenone class of Antipsychotic medications and has pharmacological effects similar Additionally, the cholinesterase inhibiting medications have shown preliminary efficacy in treating the cognitive, psychiatric, and behavioral aspects of the disease, so correct differential diagnosis is important. An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine

Essential tremor may be mistaken for Parkinson's disease but lacks all other features besides tremor, and has particular characteristics distinguishing it from Parkinson's, such as improvement with beta blockers and alcoholic beverages. Essential tremor ( ET) is a progressive Neurological disease whose most recognizable feature is a tremor of the Arms that is apparent during voluntary movements Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias ^[1]

Wilson's disease (hereditary copper accumulation) may present with parkinsonistic features; young patients presenting with parkinsonism or any other movement disorder are frequently screened for this rare condition, because it may respond to medical treatment. Wilson's disease or hepatolenticular degeneration is an Autosomal recessive Genetic disorder in which Copper accumulates in tissues Typical tests are liver function, slit lamp examination for Kayser-Fleisher rings, and serum ceruloplasmin levels. Liver function tests (LFTs or LFs which include liver enzymes, are groups of Clinical biochemistry laboratory blood assays designed to give information about the Ceruloplasmin (or caeruloplasmin) is officially known as ferroxidase or iron(IIoxygen oxidoreductase.

Pathology

Dopaminergic pathways of the human brain in normal condition (left) and Parkinson's disease (right). Red Arrows indicate suppression of the target, blue arrows indicate stimulation of target structure.

The symptoms of Parkinson's disease result from the loss of pigmented dopamine-secreting (dopaminergic) cells in the pars compacta region of the substantia nigra (literally "black substance"). Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates The pars compacta is a portion of the Substantia nigra. Anatomy The pars compacta contains Neurons which in humans are coloured black by the The substantia nigra ( Latin for "black substance" Sömmering) or locus niger is a heterogeneous portion of the midbrain, separating These neurons project to the striatum and their loss leads to alterations in the activity of the neural circuits within the basal ganglia that regulate movement, in essence an inhibition of the direct pathway and excitation of the indirect pathway. The striatum is a subcortical (ie inside rather than on the outside part of the Telencephalon. The Striatum modulates movement by two pathways a direct pathway and an indirect pathway. Indirect pathway of movement describes the one of the pathways modulated by the Striatum, the other being a Direct pathway of movement.

The direct pathway facilitates movement and the indirect pathway inhibits movement, thus the loss of these cells leads to a hypokinetic movement disorder. The lack of dopamine results in increased inhibition of the ventral anterior nucleus of the thalamus, which sends excitatory projections to the motor cortex, thus leading to hypokinesia. Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates Motor cortex is a term that describes regions of the Cerebral cortex involved in the planning control and execution of voluntary motor functions Hypokinesia refers to slow or diminished movement of body musculature.

There are four major dopamine pathways in the brain; the nigrostriatal pathway, referred to above, mediates movement and is the most conspicuously affected in early Parkinson's disease. The other pathways are the mesocortical, the mesolimbic, and the tuberoinfundibular. Disruption of dopamine along the non-striatal pathways likely explains much of the neuropsychiatric pathology associated with Parkinson's disease.

The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. Alpha-synuclein is a Synuclein Protein of unknown function primarily found in Neural tissue, where it is seen mainly in Presynaptic terminals The alpha-synuclein-ubiquitin complex cannot be directed to the proteosome. Alpha-synuclein is a Synuclein Protein of unknown function primarily found in Neural tissue, where it is seen mainly in Presynaptic terminals This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Lewy bodies are abnormal aggregates of Protein that develop inside Nerve cells They are identified under the Microscope when Histology is performed Latest research on pathogenesis of disease has shown that the death of dopaminergic neurons by alpha-synuclein is due to a defect in the machinery that transports proteins between two major cellular organelles — the endoplasmic reticulum (ER) and the Golgi apparatus. Certain proteins like Rab1 may reverse this defect caused by alpha-synuclein in animal models. ^[12]

Excessive accumulations of iron, which are toxic to nerve cells, are also typically observed in conjunction with the protein inclusions. Iron and other transition metals such as copper bind to neuromelanin in the affected neurons of the substantia nigra. In Chemistry, the term transition metal (sometimes also called a transition element) has two possible meanings It commonly refers to any element in Melanin is a class of compounds found in the Plant, Animal and Protista kingdoms, where it serves predominantly as a Pigment. The substantia nigra ( Latin for "black substance" Sömmering) or locus niger is a heterogeneous portion of the midbrain, separating Neuromelanin may be acting as a protective agent. Melanin is a class of compounds found in the Plant, Animal and Protista kingdoms, where it serves predominantly as a Pigment. The most likely mechanism is generation of reactive oxygen species. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and ^[13] Iron also induces aggregation of synuclein by oxidative mechanisms. ^[14] Similarly, dopamine and the byproducts of dopamine production enhance alpha-synuclein aggregation. The precise mechanism whereby such aggregates of alpha-synuclein damage the cells is not known. The aggregates may be merely a normal reaction by the cells as part of their effort to correct a different, as-yet unknown, insult. Based on this mechanistic hypothesis, a transgenic mouse model of Parkinson's has been generated by introduction of human wild-type alpha-synuclein into the mouse genome under control of the platelet-derived-growth factor-β promoter. This article is about organisms which have been genetically modified In Molecular biology, Platelet-derived growth factor ( PDGF) is one of the numerous Growth factors or Proteins that regulate cell growth ^[15]

Causes

Most people with Parkinson's disease are described as having idiopathic Parkinson's disease (having no specific cause). Idiopathic is an Adjective used primarily in Medicine meaning arising spontaneously or from an obscure or unknown cause. There are far less common causes of Parkinson's disease including genetic, toxins, head trauma, cerebral anoxia, and drug-induced Parkinson's disease. Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate

Genetic

In recent years, a number of specific genetic mutations causing Parkinson's disease have been discovered, including in certain populations (Contursi, Italy). Contursi Terme is a village and Comune in the Province of Salerno in the Campania region of south-western Italy. These account for a small minority of cases of Parkinson's disease. Someone who has Parkinson's disease is more likely to have relatives that also have Parkinson's disease. However, this does not mean that the disorder has been passed on genetically.

Genetic forms that have been identified include (external links in this section are to Online Mendelian Inheritance in Man):

Toxins

One theory holds that the disease may result in many or even most cases from the combination of a genetically determined vulnerability to environmental toxins along with exposure to those toxins. A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low ^[23] This hypothesis is consistent with the fact that Parkinson's disease is not distributed homogeneously throughout the population; its incidence varies geographically. However, it is not consistent with the fact that the first appearance of the syndrome predates the first synthesis of the compounds often attributed to causing Parkinson's disease. The toxins most strongly suspected at present are certain pesticides and transition-series metals such as manganese or iron, especially those that generate reactive oxygen species,^[13][24] and/or bind to neuromelanin, as originally suggested by G. A pesticide is a substance or mixture of substances used to kill a pest. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and Melanin is a class of compounds found in the Plant, Animal and Protista kingdoms, where it serves predominantly as a Pigment. C. Cotzias. ^[25][26] In the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation, individuals who were exposed to pesticides had a 70% higher incidence of PD than individuals who were not exposed. ^[27]

MPTP (pro-toxin N-methyl-4-phenyl-1,2,3,6-tetrahyropyidine) is used as a model for Parkinson's, as it can rapidly induce parkinsonian symptoms in human beings and other animals of any age. MPTP (1- Methyl -4- Phenyl -1236-tetrahydro Pyridine) is a Neurotoxin that causes permanent symptoms of Parkinson's disease by MPTP was notorious for a string of Parkinson's disease cases in California in 1982 when it contaminated the illicit production of the synthetic opiate MPPP. MPPP ( 1-methyl-4-phenyl-4-propionoxypiperidine, Desmethylprodine) is an Opioid Analgesic drug Its toxicity likely comes from generation of reactive oxygen species through tyrosine hydroxylation. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and ^[28]

Other toxin-based models employ PCBs,^[29] paraquat^[30] (a herbicide) in combination with maneb (a fungicide),^[31] rotenone^[32] (an insecticide), and specific organochlorine pesticides including dieldrin^[33] and lindane. Paraquat is the trade name for NN'-Dimethyl-44'-bipyridinium dichloride, a Viologen. Rotenone is an odorless chemical that is used as a broad-spectrum Insecticide, Piscicide, and Pesticide. ^[34] Rotenone is an inhibitor of complex 1 of the electron transport chain. It easily crosses membranes due to its extremely hydrophobic properties. Rotenone, therefore, does not rely on the dopamine transporter to enter into the cytoplasm. Numerous studies have found an increase in PD in persons who consume rural well water; researchers theorize that water consumption is a proxy measure of pesticide exposure. In agreement with this hypothesis are studies which have found a dose-dependent increase in PD in persons exposed to agricultural chemicals.

Head trauma

Past episodes of head trauma are reported more frequently by sufferers than by others in the population. ^[35][36][37] A methodologically strong recent study^[35] found that those who have experienced a head injury are four times more likely to develop Parkinson’s disease than those who have never suffered a head injury. The risk of developing Parkinson’s increases eightfold for patients who have had head trauma requiring hospitalization, and it increases 11-fold for patients who have experienced severe head injury. The authors comment that since head trauma is a rare event, the contribution to PD incidence is slight. They express further concern that their results may be biased by recall, i. e. , the PD patients because they reflect upon the causes of their illness, may remember head trauma better than the non-ill control subjects. These limitations were overcome recently by Tanner and colleagues,^[38] who found a similar risk of 3. 8, with increasing risk associated with more severe injury and hospitalization.

Treatment

Parkinson's disease is a chronic disorder that requires broad-based management including patient and family education, support group services, general wellness maintenance, physiotherapy, exercise, and nutrition. ^[11] At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms.

Levodopa

Stalevo for treatment of Parkinson's disease

The most widely used form of treatment is L-dopa in various forms. L-dopa is transformed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive.

Carbidopa and benserazide are dopa decarboxylase inhibitors. Carbidopa (MK-486 tradename Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral Metabolism of Levodopa Benserazide (also called Serazide or Ro 4-4602 is a DOPA decarboxylase inhibitor which is unable to cross the Blood-brain barrier. They help to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons and are generally given as combination preparations of carbidopa/levodopa (co-careldopa) (e. The combination of Carbidopa and Levodopa is used to treat Parkinson's disease and Dopa-Responsive Dystonia (DRD g. Sinemet, Parcopa) and benserazide/levodopa (co-beneldopa) (e. Benserazide (also called Serazide or Ro 4-4602 is a DOPA decarboxylase inhibitor which is unable to cross the Blood-brain barrier. g. Madopar). There are also controlled release versions of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed. There is also Stalevo (Carbidopa, Levodopa and Entacapone).

Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. Tolcapone is a Drug that inhibits the Enzyme Catechol-O-methyl transferase (COMT Catechol- O -methyl transferase ( COMT;) is one of several Enzymes that degrade Catecholamines such as Dopamine, Epinephrine However, due to its possible side effects such as liver failure, it's limited in its availability.

A similar drug, entacapone, has similar efficacy and has not been shown to cause significant alterations of liver function. Entacapone ( INN) (ˌɛntəkəˈpoʊn/ /ɛnˈtækəpoʊn A recent follow-up study by Cilia and colleagues^[39] looked at the clinical effects of long-term administration of entacapone, on motor performance and pharmacological compensation, in advanced PD patients with motor fluctuations: 47 patients with advanced PD and motor fluctuations were followed for six years from the first prescription of entacapone and showed a stabilization of motor conditions, reflecting entacapone can maintain adequate inhibition of COMT over time. ^[39]

Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa, and has been under some investigation. Mucuna pruriens ( Syn Dolichos pruriens) is a tropical legume known by a multitude of Common names (see below ^[40]

Dopamine agonists

The dopamine agonists bromocriptine, pergolide, pramipexole, ropinirole , cabergoline, apomorphine, and lisuride are moderately effective. Bromocriptine (brand names include Parlodel an Ergoline derivative is a Dopamine agonist that is used in the treatment of Pituitary Tumors Pergolide is an Ergoline -based Dopamine receptor Agonist used for the treatment of Parkinson's disease. Pramipexole ( INN, trade names Mirapex and Sifrol) is a Medication indicated for treating Parkinson's disease and Restless legs Ropinirole (marketed under the brand names Requip and Ropark, in Extended release form as Requip XL) is a non- Ergoline Dopamine Cabergoline (brand names Dostinex and Cabaser an ergot derivative is a potent Dopamine receptor Agonist on D2 receptors Lisuride (brand name in Germany Dopergin) is an anti- Parkinson's Drug of the iso-ergoline class chemically related to the Dopaminergic These have their own side effects including those listed above in addition to somnolence, hallucinations and/or insomnia. Several forms of dopamine agonism have been linked with a markedly increased risk of problem gambling. Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.

Dopamine agonists can be useful for patients experiencing on-off fluctuations and dyskinesias as a result of high doses of L-dopa. Apomorphine can be administered via subcutaneous injection using a small pump which is carried by the patient. A low dose is automatically administered throughout the day, reducing the fluctuations of motor symptoms by providing a steady dose of dopaminergic stimulation. After an initial "apomorphine challenge" in hospital to test its effectiveness and brief patient and primary caregiver (often a spouse or partner), the latter of whom takes over maintenance of the pump. A primary caregiver is the person who takes care of an Infant or Child most of the time The injection site must be changed daily and rotated around the body to avoid the formation of nodules. In Medicine, a nodule refers to a relatively hard roughly spherical abnormal structure Apomorphine is also available in a more acute dose as an autoinjector pen for emergency doses such as after a fall or first thing in the morning. An autoinjector (or auto-injector) is a Medical device designed to deliver a single Dose of a particular (typically life-saving drug. Nausea and vomiting are common, any may require domperidone (an antiemetic). Domperidone (trade name Motilium or Motillium) is an Antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally

MAO-B inhibitors

Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. Selegiline (l-deprenyl Eldepryl Zelapar or Anipryl Veterinary) is a drug used for the treatment of early-stage Parkinson's disease, Depression Rasagiline (trade name Azilect) is an irreversible inhibitor of Monoamine oxidase used as a monotherapy in early Parkinson's disease or as an Metabolites of selegiline include L-amphetamine and L-methamphetamine (not to be confused with the more notorious and potent dextrorotary isomers). This might result in side effects such as insomnia. Use of L-dopa in conjunction with selegiline has increased mortality rates that have not been effectively explained. Another side effect of the combination can be stomatitis. One report raised concern about increased mortality when MAO-B inhibitors were combined with L-dopa;^[41] however subsequent studies have not confirmed this finding. ^[42] Unlike other non selective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression.

Speech therapies

The most widely practiced treatment for the speech disorders associated with Parkinson's disease is Lee Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness. ^[43]

A study found that an electronic device providing frequency-shifted auditory feedback (FAF) improved the clarity of Parkinson's patients' speech. ^[44]

Physical exercise

Regular physical exercise and/or therapy, including yoga, tai chi, and dance, can be beneficial to the patient for maintaining and improving mobility, flexibility, balance, and range of motion. Physicians and physical therapists often recommend basic exercises, such as bringing the toes up with every step, carrying a bag with weight to decrease the bend on one side, and practicing chewing hard and moving the food around the mouth. ^[45]

Surgery and deep brain stimulation

Illustration showing an electrode placed deep seated in the brain

Treating Parkinson's disease with surgery was once a common practice, but after the discovery of levodopa, surgery was restricted to only a few cases. Studies in the past few decades have led to great improvements in surgical techniques, and surgery is again being used in people with advanced PD for whom drug therapy is no longer sufficient.

Deep brain stimulation is presently the most used surgical means of treatment, but other surgical therapies that have shown promise include surgical lesion of the subthalamic nucleus^[46] and of the internal segment of the globus pallidus, a procedure known as pallidotomy. In Neurotechnology, deep brain stimulation ( DBS) is a surgical treatment involving the implantation of a medical device called a Brain pacemaker The subthalamic nucleus is a small lens-shaped nucleus in the Brain where it is a part of the Basal ganglia system The globus pallidus ( Latin for "pale globe" is a sub- cortical structure of the Brain. Pallidotomy is a procedure where a tiny Electrical probe is placed in the globus pallidus (one of the basal ganglia of the Brain) which is then heated to 80 ^[47]

Methods undergoing evaluation

Gene therapy

Currently under investigation is gene therapy. This involves using a non-infectious virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. Glutamate decarboxylase (GAD is an Enzyme that catalyzes the decarboxylation of Glutamate to GABA and CO2 See Chemical synapse for an introduction to concepts and terminology used in this article Gamma-aminobutyric acid (GABA is the chief inhibitory Neurotransmitter in the Mammalian Central nervous system. ^[48] GABA acts as a direct inhibitor on the overactive cells in the STN.

GDNF infusion involves the infusion of GDNF (glial-derived neurotrophic factor) into the basal ganglia using surgically implanted catheters. Glial cell derived neurotrophic factor, also known as GDNF, is a small protein that potently promotes the survival of many types of Neurons Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still in development.

Implantation of stem cells genetically engineered to produce dopamine or stem cells that transform into dopamine-producing cells has already started being used. These could not constitute cures because they do not address the considerable loss of activity of the dopaminergic neurons. Initial results have been unsatisfactory, with patients still retaining their drugs and symptoms.

Neuroprotective treatments

Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny. The term neuroprotection refers to mechanisms within the Nervous system which protect Neurons from Apoptosis or Degeneration, for example following ^[49] These agents could protect neurons from cell death induced by disease presence resulting in a slower progression of disease. Agents currently under investigation as neuroprotective agents include apoptotic drugs (CEP 1347 and CTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors. ^[50] Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitors selegiline^[51] and rasagiline, dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10.

Neural transplantation

The first prospective randomised double-blind sham-placebo controlled trial of dopamine-producing cell transplants failed to show an improvement in quality of life although some significant clinical improvements were seen in patients below the age of 60. ^[52] A significant problem was the excess release of dopamine by the transplanted tissue, leading to dystonias. Dystonia is a neurological Movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures ^[53] Research in African green monkeys suggests that the use of stem cells might in future provide a similar benefit without inducing dystonias. Stem cells are cells found in most if not all multi-cellular Organisms. ^[54]

Nutrients

Nutrients have been used in clinical studies and are widely used by people with Parkinson's disease in order to partially treat PD or slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of symptoms. ^[55] Ferrous iron, the essential cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of symptoms in 110 out of 110 patients. ^{[56] [57]}

More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis. ^[58] Vitamin C and vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in Parkinson's disease. This is because the enzymes superoxide dismutase and catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly produced in damaged cells. However, in the randomized controlled trial, DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen. ^[51]

Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to coenzyme Q10.

Qigong

There have been two studies looking at qigong in Parkinson's disease. Qigong (or ch'i kung) refers to a wide variety of traditional cultivation practices that involve methods of accumulating circulating and working with Qi or energy In a trial in Bonn, an open-label randomised pilot study in 56 patients found an improvement in motor and non-motor symptoms amongst patients who had undergone one hour of structured qigong exercise per week in two 8-week blocks. The authors speculate that visualizing the flow of "energy" might act as an internal cue and so help improve movement. ^[59]

The second study, however, found qigong to be ineffective in treating Parkinson's disease. In that study, researchers used a randomized cross-over trial to compare aerobic training with qigong in advanced Parkinson's disease. Two groups of PD patients were assessed, had 20 sessions of either aerobic exercise or qigong, were assessed again, then after a 2-month gap were switched over for another 20 sessions, and finally assessed again. The authors found an improvement in motor ability and cardiorespiratory function following aerobic exercise, but found no benefit following qigong. The authors also point out that aerobic exercise had no benefit for patients' quality of life. ^[60]

Botox

Recently, Botox injections are being investigated as a non-FDA approved possible experimental treatment. Botulinum toxin is a Neurotoxin Protein produced by the Bacterium Clostridium botulinum. ^[61]

Prognosis

PD is not considered to be a fatal disease by itself, but it progresses with time. The average life expectancy of a PD patient is generally lower than for people who do not have the disease. ^[62] In the late stages of the disease, PD may cause complications such as choking, pneumonia, and falls that can lead to death.

The progression of symptoms in PD may take 20 years or more. In some people, however, the disease progresses more quickly. There is no way to predict what course the disease will take for an individual person. With appropriate treatment, most people with PD can live productive lives for many years after diagnosis.

In at least some studies, it has been observed that mortality was significantly increased, and longevity decreased among nursing home patients as compared to community dwelling patients. ^[63]

One commonly used system for describing how the symptoms of PD progress is called the Hoehn and Yahr scale. The Hoehn and Yahr scale is a commonly used system for describing how the symptoms of Parkinson's disease progress Another commonly used scale is the Unified Parkinson's Disease Rating Scale (UPDRS). The Unified Parkinson's Disease Rating Scale ( U nified' P' arkinson's D isease R ating S cale is a Rating scale used to follow This much more complicated scale has multiple ratings that measure motor function, and also mental functioning, behavior, mood, and activities of daily living; and motor function. Both the Hoehn and Yahr scale and the UPDRS are used to measure how individuals are faring and how much treatments are helping them. It should be noted that neither scale is specific to Parkinson's disease; that patients with other illnesses can score in the Parkinson's range.

History

Symptoms of Parkinson's disease have been known and treated since ancient times. ^[64] However, it was not formally recognized and its symptoms were not documented until 1817 in An Essay on the Shaking Palsy^[65] by the British physician James Parkinson. Year 1817 ( MDCCCXVII) was a Common year starting on Wednesday (link will display the full calendar of the Gregorian calendar (or a Common James Parkinson may also refer to James Parkinson (1730-1813, the museum proprietor and land agent Parkinson's disease was then known as paralysis agitans, the term "Parkinson's disease" being coined later by Jean-Martin Charcot. Jean-Martin Charcot ( 29 November 1825 – 16 August 1893) was a French Neurologist and professor of Anatomical pathology The underlying biochemical changes in the brain were identified in the 1950s due largely to the work of Swedish scientist Arvid Carlsson, who later went on to win a Nobel Prize. Biochemistry is the study of the chemical processes in living Organisms It deals with the Structure and function of cellular components such as The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain The 1950s Decade refers to the years of 1950 to 1959 inclusive Arvid Carlsson (born January 25, 1923) is a Swedish Scientist who is best known for his work with the Neurotransmitter Dopamine The Nobel Prize (Nobelpriset (Nobelprisen is a Swedish prize established in the 1895 will of Swedish chemist Alfred Nobel; it was first awarded in Peace, Literature L-dopa entered clinical practice in 1967,^[66] and the first large study reporting improvements in patients with Parkinson's disease resulting from treatment with L-dopa was published in 1968. ^[67]

Notable sufferers

Further information: People with Parkinson's disease

One famous sufferer of young-onset Parkinson's is Michael J. Fox, whose book, Lucky Man (2000), focused on his experiences with the disease and his career and family travails in the midst of it. Michael J Fox (born Michael Andrew Fox; June 9 1961 is a Canadian / American 2000 ( MM) was a Leap year that started on Saturday of the Common Era, in accordance with the Gregorian calendar. Fox established The Michael J. Fox Foundation for Parkinson's Research to develop a cure for Parkinson's disease within this decade.

Another foundation that supports Parkinson's research was established by Davis Phinney, a notable figure in the cycling world. Davis Phinney (born July 10, 1959 in Boulder, Colorado) is a former professional Road bicycle racer from the United States Phinney has competed in the Olympics, Pan-Am Games and has competed as a pro-cyclist for nearly twenty years. The Davis Phinney Foundation strives to improve the lives of those living with Parkinson's disease.

Other famous sufferers include Pope John Paul II, playwright Eugene O'Neill, artist Salvador Dalí, evangelist Billy Graham, former US Attorney General Janet Reno, and boxer Muhammad Ali. Pope Eugene Gladstone O'Neill (October 16 1888–November 27 1953 was a Nobel -prize winning American playwright Salvador Domingo Felipe Jacinto Dalí i Domènech 1st Marquis of Púbol (May 11 1904 &ndash January 23 1989 was a Spanish Catalan Surrealist William Franklin Graham Jr KBE (born November 7 1918 better known as Billy Graham, is an evangelist and an Evangelical Christian Janet Reno (born July 21, 1938) was the Attorney General of the United States ( 1993 &ndash 2001) Biography Early life Cassius Clay Jr was born on January 17 1942 Political figures suffering from it have included Adolf Hitler, Francisco Franco, Deng Xiaoping and Mao Zedong, and former Prime Minister of Canada Pierre Trudeau. Hi and welcome to Wikipedia! Please understand that this article is frequently vandalized and vandalism is reverted immediately Francisco Paulino Hermenegildo Teódulo Franco y Bahamonde (born December 4, 1892 in Ferrol, died November 20, 1975 in Madrid Deng Xiaoping ( 22 August 1904 19 February 1997) was a prominent Chinese Revolutionary, Politician, Pragmatist and Reformer Mao Zedong ( 26 December 1893 – 9 September 1976) was a Chinese Military and political leader who led Numerous actors have also been afflicted with Parkinson's such as: Terry-Thomas, Deborah Kerr, Kenneth More, Vincent Price, Jim Backus and Michael Redgrave. Thomas Terry Hoar-Stevens ( 14 July 1911 &ndash 8 January 1990) was a distinctive English comic Actor, known Deborah Jane Kerr-Trimmer, CBE (30 September 1921 &ndash 16 October 2007 was a Scottish stage television and film actress Kenneth Gilbert More CBE ( 20 September 1914 – 12 July 1982) was an English Actor. Vincent Leonard Price Jr ( May 27 1911 &ndash October 25 1993) was an American Film Actor, remembered James Gilmore Backus ( February 25, 1913  &ndash July 3, 1989) was a radio Television, Film actor, Character Sir Michael Scudamore Redgrave CBE ( 20 March, 1908 — 21 March, 1985) was an English actor author director and Helen Beardsley (of Yours, Mine and Ours fame) also suffered from this disease toward the end of her life. Helen Eileen Beardsley ( née Brandmeir formerly North April 5, 1930 &ndash April 26, 2000) was the mother of the famous Blended Yours Mine and Ours is a 1968 Film, directed by Melville Shavelson and starring Lucille Ball, Henry Fonda and Van Director George Roy Hill (The Sting, Butch Cassidy and the Sundance Kid) also suffered from Parkinson's disease. George Roy Hill ( December 20, 1921 – December 27, 2002) was an Academy Award winning American Film director. The Sting is a 1973 Caper film set in September 1936 and revolving around a complicated plot by two professional grifters ( Paul Butch Cassidy and the Sundance Kid is a American Western film that tells the story of bank robbers Butch Cassidy (played by Paul Newman) and

The film Awakenings (starring Robin Williams and Robert De Niro and based on genuine cases reported by Oliver Sacks) deals sensitively and largely accurately with a similar disease, postencephalitic parkinsonism. Awakenings is a 1990 Drama film based on Oliver Sacks ' memoir of the same name. Robin McLaurim Williams (born July 21 1951 or 1952 is an American television stage and film actor and Comedian who has won an Academy Award for his performance Robert Mario De Niro Jr (born August 17 1943 is a two-time Academy Award -winning American Film Actor, director and producer Oliver Wolf Sacks, CBE (born July 9, 1933, London is a British Neurologist residing in the United States who has written popular books about Postencephalitic parkinsonism is a disease that is believed to have been caused by a viral illness stimulating degeneration of the nerve cells in the Substantia nigra, leading

Michael Gibson (TV presenter) host of MTV Select was diagnosed with Parkinson's at the age of 18. Michael Gibson (born October 29 1980 in Blackburn, England) is a TV presenter and documentary director MTV Select was a Television program which aired weekday afternoons on MTV across Europe launched in 1997 (a similar series MTV Dial aired between 1996-1997 on Michael lived in denial about his condition for six years. He then pitched a documentary proposal to Channel 4 who commissioned him to make a documentary following Michael's journey with Parkinson's. Channel 4 is a public-service Television and Radio broadcaster in the United Kingdom centred around a television channel of the same name which began All shook up: Parkinson's at 25 aired on Channel 4 in 2006.

References

External links

• Parkinson's Disease at the Open Directory Project
• Parkinson's Disease: Hope Through Research (National Institute of Neurological Disorders and Stroke)
• World Parkinson Disease Association