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.^[1] Image File history File links Sir_William_Richard_Gowers_Parkinson_Disease_sketch_1886. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // G00-G99 - Diseases of the nervous system (G00-G09) Inflammatory diseases of the central nervous system (G00) Bacterial meningitis, not elsewhere classified (G01) Meningitis in bacterial diseases classified elsewhere (G02) Meningitis in other infectious and parasitic diseases classified elsewhere (G03) Meningitis due to other and unspecified causes (G04) Encephalitis, myelitis... // F00-F99 - Mental and behavioural disorders (F00-F09) Organic, including symptomatic, mental disorders (F00) Dementia in Alzheimers disease (F01) Vascular dementia (F011) Multi-infarct dementia (F02) Dementia in other diseases classified elsewhere (F020) Dementia in Picks disease (F021) Dementia in Creutzfeldt-Jakob disease (F022) Dementia in Huntingtons... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... A diagram showing the CNS: 1. ... A motor skill is a skill that requires an organism to utilize their skeletal muscles effectively in a goal directed manner. ...

Parkinson's disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). 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. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive. List of Movement disorders Akinesia (lack of movement) Athetosis (contorted torsion or twisting) Ataxia Ballismus (violent involuntary rapid and irregular movements) Hemiballismus Bradykinesia (slow movement) Chorea (rapid, involuntary movement) Sydenhams chorea Rheumatic chorea Huntingtons chorea Dystonia (sustained torsion) Dystonia muscularum Blepharospasm Writers cramp Spasmodic torticollis (twisting of... In medicine (neurology), bradykinesia denotes slow movement (etymology: brady = slow, kinesia = movement). ... Akinesia is the inability to initiate movement, due to problems with selecting and activating motor programs in the brain. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... The basal ganglia (or basal nuclei) are a group of nuclei in the brain interconnected with the cerebral cortex, thalamus and brainstem. ... For other uses, see Dopamine (disambiguation). ... It has been suggested that this article or section be merged with Dopamine#Functions in the Brain. ... 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. 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). 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). Parkinsonism (also known as Parkinsons syndrome, atypical Parkinsons, or secondary Parkinsons) is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. ... Idiopathic means arising spontaneously or from an obscure or unknown cause. ... James Parkinson (April 11, 1755 – December 21, 1824) was an English physician, geologist, paleontologist, and political activist. ...

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] A cardinal symptom is the primary or major symptom by which a diagnosis is made. ...

• Tremor: normally 4-6 Hz tremor, maximal when the limb is at rest, and decreased with voluntary movement. 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. 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. Rapid, repetitive movements produce a dysrhythmic and decremental loss of amplitude.
• Postural instability: failure of postural reflexes, which leads to impaired balance and falls.

Other motor symptoms include: For the film, see Tremors (film). ... This article is about the SI unit of frequency. ... Spasticity is a disorder of the bodys motor system,and especially the Central Nervous Systems (CNS), in which certain muscles are continuously contracted. ... In medicine (neurology), bradykinesia denotes slow movement (etymology: brady = slow, kinesia = movement). ... Akinesia is the inability to initiate movement, due to problems with selecting and activating motor programs in the brain. ... For other uses, see Rhythm (disambiguation). ... For quantum-mechanical amplitude, see probability amplitude. ... 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 or reflex is a biological control system linking stimulus to response and mediated by a reflex arc. ...

• 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). ^[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.
• 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.^[3]
  • Monotonic speech.
  • Festinating speech: excessively rapid, soft, poorly-intelligible speech.
  • Drooling: most likely caused by a weak, infrequent swallow and stooped posture.
  • 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. Can lead to aspiration, pneumonia.
• 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.

Look up Gait in Wiktionary, the free dictionary. ... This article is about angles in geometry. ... Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. ... Cluttered speech is a common term for speech that becomes broken down, cluttered, or unintelligible due to a variety of reasons. ... Drooling (also known as ptyalism) is when saliva flows outside the mouth. ... Dysphagia () is a medical term defined as difficulty swallowing. ... In medicine, aspiration is the entry of secretions or foreign material into the trachea and lungs. ... This article is about human pneumonia. ... The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ... Hypomimia, a Medical sign, is a reduced degree of facial expression. ... This article refers to the sight organ. ... Micrographia is a medical term used to describe abnormally small, cramped handwriting and/or the progression to continually smaller handwriting. ... Explain the dystonias connected with motor coordination. ...

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.^[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. 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. On the Threshold of Eternity. ... The Beck Depression Inventory (BDI, BDI-II), created by Dr. Aaron T. Beck, is a twenty-one question multiple choice self-report inventory that is one of the widely used instruments for measuring the severity of depression. ... This article does not cite any references or sources. ... Aboulia or Abulia, 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. Hallucinations, delusions and paranoia may develop.
• Short term memory loss; procedural memory is more impaired than declarative memory. Prompting elicits improved recall.
• Medication effects: some of the above cognitive disturbances are improved by dopaminergic medications, while others are actually worsened.^[8]

The executive system is a theorised cognitive system in psychology that controls and manages other cognitive processes. ... For other uses, see Dementia (disambiguation). ... A hallucination is a false sensory perception in the absence of an external stimulus, as distinct from an illusion, which is a misperception of an external stimulus. ... A delusion is commonly defined as a false belief, and is used in everyday language to describe a belief that is either false, fanciful or derived from deception. ... For other senses of this word, see paranoia (disambiguation). ... Memory loss can be caused by many things. ... Procedural memory, also known as implicit memory, is the long-term memory of skills and procedures, or how to knowledge. ... It has been suggested that Explicit_memory be merged into this article or section. ...

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

Somnolence (or drowsiness) is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods. ... This article is about the sleeping disorder. ... Rapid eye movement (REM) sleep is the normal stage of sleep characterized by rapid movements of the eyes. ... Rapid eye movement (REM) sleep is the normal stage of sleep characterized by rapid movements of the eyes. ...

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

It has been suggested that this article or section be merged with contrast threshold function. ... Color is an important part of the visual arts. ... Double vision may refer to: Diplopia, the perception of two images from a single object. ... 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, orthostatic intolerance and, colloquially, as head rush or a dizzy spell) is a sudden fall in blood pressure, typically greater than 20/10 mm Hg, that occurs when a person assumes a standing position, usually after a prolonged period of rest. ... This article or section is in need of attention from an expert on the subject. ... // Proprioception (PRO-pree-o-SEP-shun (IPA pronunciation: ); from Latin proprius, meaning ones own and perception) is the sense of the relative position of neighbouring parts of the body. ... Olfaction (also known as olfactics) refers to the sense of smell. ... Anosmia is the lack of olfaction, or a loss of the ability to smell. ... Look up Pain in Wiktionary, the free dictionary. ...

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. Current data addresses male sexual function almost exclusively.
• Weight loss, which is significant over a period of ten years.

Seborrhoeic dermatitis is a skin disorder affecting the scalp, face and trunk causing scaly, flaky, itchy, red skin. ... The tone or style of this article or section may not be appropriate for Wikipedia. ... Constipation or irregularity, is a condition of the digestive system where a person (or animal) experiences hard feces that are difficult to egest; it may be extremely painful, and in severe cases (fecal impaction) lead to symptoms of bowel obstruction. ... In anatomy, the stomach (in ancient Greek στομάχι) is an organ in the alimentary canal used to digest food. ... 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, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue. ...

Diagnosis

18F PET scan shows decreased dopamine activity in the basal ganglia, a pattern which aids in diagnosing Parkinson's disease.

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. 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. Image File history File links PET_scan_Parkinson's_Disease. ... Image File history File links PET_scan_Parkinson's_Disease. ... The basal ganglia (or basal nuclei) are a group of nuclei in the brain interconnected with the cerebral cortex, thalamus and brainstem. ... The Unified Parkinsons Disease Rating Scale (UPDRS) is a rating scale used to follow the longitudinal course of Parkinsons Disease. ...

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.^[11] Clinical practice guidelines are collections of practical information for use by doctors and other medical professionals. ... Neurology is a branch of medicine dealing with disorders of the nervous system. ...

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. These include: multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). 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. 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. Parkinson-plus syndromes are a group of diseases featuring the classical features of Parkinsons disease (tremor; rigidity; akinesia/bradykinesia; postural instability) with additional features that distinguish them from simple idiopathic Parkinsons disease. ... 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 involving the gradual deterioration and death of selected areas of the brain. ... Corticobasal degeneration (CBD) is a progressive neurodegenerative disease associated with atrophy of the cerebral cortex and the basal ganglia. ... Dementia with Lewy bodies is the second most frequent cause of hospitalization for dementia, after Alzheimers disease. ... Lewy bodies are abnormal aggregates of protein that develop inside nerve cells. ...

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. 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. Haloperidol (sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol, Halosten, Keselan, Linton, Peluces, Serenace, Serenase, Sigaperidol) is a conventional, or typical, butyrophenone antipsychotic drug. ... A cholinesterase inhibitor or anticholinesterase is a chemical that inhibits a cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter 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.^[1] This article or section does not cite its references or sources. ... Beta blockers or beta-adrenergic blocking agents are a class of drugs used to treat a variety of cardiovascular conditions and some other diseases. ... Alcoholic beverages An alcoholic beverage is a drink containing ethanol, commonly known as alcohol, although in chemistry the definition of an alcohol includes many other compounds. ...

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. Typical tests are liver function, slit lamp examination for Kayser-Fleisher rings, and serum ceruloplasmin levels. Wilsons disease or hepatolenticular degeneration is an autosomal recessive hereditary disease, with an incidence of about 1 in 30,000 in most parts of the world and a male preponderance. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ... Ceruloplasmin Ceruloplasmin (or caeruloplasmin), officially known as ferroxidase or iron(II):oxygen oxidoreductase, is a copper transport protein found in the blood. ...

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"). 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. Image File history File links Download high-resolution version (1050x834, 129 KB) JPG version of Image:DA-loops in PD.gif. ... Image File history File links Download high-resolution version (1050x834, 129 KB) JPG version of Image:DA-loops in PD.gif. ... For other uses, see Dopamine (disambiguation). ... The substantia nigra (Latin for black substance) is a portion of the midbrain thought to be involved in certain aspects of movement and attention. ... The substantia nigra, (Latin for black substance, Soemering) or locus niger is a heterogeneous portion of the midbrain, separating the pes (foot) from the tegmentum (covering), and a major element of the basal ganglia system. ... Coronal slices of human brain showing the basal ganglia, the striatum and pallidum globus pallidus: external segment (GPe), subthalamic nucleus (STN), globus pallidus: internal segment (GPi), and substantia nigra (SN). ...

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. For other uses, see Dopamine (disambiguation). ... To meet Wikipedias quality standards, this article or section may require cleanup. ... 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. These pathways are associated with, respectively: volition and emotional responsiveness; desire, initiative, and reward; and sensory processes and maternal behavior. 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. The alpha-synuclein-ubiquitin complex cannot be directed to the proteosome. This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies. 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] Alpha-synuclein is a normal protein found in the brain. ... Alpha-synuclein is a normal protein found in the brain. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... Lewy bodies are abnormal aggregates of protein that develop inside nerve cells. ...

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. Neuromelanin may be acting as a protective agent. The most likely mechanism is generation of reactive oxygen species.^[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.^[15] This article is in need of attention. ... Melanin is a polymer of either or both of two monomer molecules: indolequinone, and dihydroxyindole carboxylic acid. ... The substantia nigra, (Latin for black substance, Soemering) or locus niger is a heterogeneous portion of the midbrain, separating the pes (foot) from the tegmentum (covering), and a major element of the basal ganglia system. ... Melanin is a polymer of either or both of two monomer molecules: indolequinone, and dihydroxyindole carboxylic acid. ... Reactive oxygen species (ROS) include oxygen ions, free radicals and peroxides both inorganic and organic. ... GMO redirects here. ... This article or section is in need of attention from an expert on the subject. ...

Causes

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

Genetic

In recent years, a number of specific genetic mutations causing Parkinson's disease have been discovered, including in certain populations (Contursi, 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. Contursi Terme is a small village in Italy that became famous in 1997 because it hosts a large family that had a high rate of Parkinson disease syndromes that could be traced back over 6 generations (60 cases over 6 generations). ...

Genetic forms that have been identified include (external links in this section are to Online Mendelian Inheritance in Man): The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ...

Short and long arms Chromosome. ... A representation of the 3D structure of myoglobin showing coloured alpha helices. ... Alpha-synuclein is a normal protein found in the brain. ... It has been suggested that this article or section be merged into Dominance relationship. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Homozygote cells are diploid or polyploid and have the same alleles at a locus (position) on homologous chromosomes. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Parkin is an E3 ligase in the ubiquitin-proteasome system. ... Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) (EC 3. ... Penetrance is a term used in genetics that describes the extent to which the properties controlled by a gene, its phenotype, will be expressed. ...

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.^[23] This hypothesis is consistent with the fact that Parkinson's disease is not distributed homogeneously throughout the population; its incidence varies geographically. It appears that incidence varies by time as well, for although the later stages of untreated PD are distinct and readily recognizable, the disease was not remarked upon until the beginning of the Industrial Revolution and not long thereafter became a common observation in clinical practice. 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.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] For other uses, see Toxin (disambiguation). ... A pesticide is a substance or mixture of substances used for preventing, controlling, or lessening the damage caused by a pest. ... Reactive oxygen species (ROS) include oxygen ions, free radicals and peroxides both inorganic and organic. ... Melanin is a polymer of either or both of two monomer molecules: indolequinone, and dihydroxyindole carboxylic acid. ...

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 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. Its toxicity likely comes from generation of reactive oxygen species through tyrosine hydroxylation.^[28] This article is about the chemical. ... MPPP (1-methyl 4-phenyl 4-propionoxypiperidine) is an opioid analgesic drug. ... Reactive oxygen species (ROS) include oxygen ions, free radicals and peroxides both inorganic and organic. ...

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.^[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. Paraquat is the trade name for N,N-Dimethyl-4,4-bipyridinium dichloride, a viologen. ... Rotenone is a colorless-to-red, odorless solid. ...

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. Physical therapy can help restore lost functionality in many people. ...

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. Image File history File linksMetadata Download high-resolution version (2000x1468, 916 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Parkinsons disease Metadata This file contains additional information, probably added from the digital camera or scanner used... Image File history File linksMetadata Download high-resolution version (2000x1468, 916 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Parkinsons disease Metadata This file contains additional information, probably added from the digital camera or scanner used... // Therapeutic use L-DOPA is used to replace dopamine lost in Parkinsons disease because dopamine itself cannot cross the blood-brain barrierwhere its precursor can. ...

Carbidopa and benserazide are dopa decarboxylase inhibitors. 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.g. Sinemet, Parcopa) and benserazide/levodopa (co-beneldopa) (e.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). Carbidopa (MK-486) is a drug given to people with Parkinsons disease in order to inhibit peripheral metabolism of levodopa. ... Benserazide is an inhibitor of DOPA decarboxylase that does not enter the central nervous system. ... The combination of carbidopa and levodopa is used to treat Parkinsons disease and Dopa-Responsive Dystonia (DRD). ... Benserazide is an inhibitor of DOPA decarboxylase that does not enter the central nervous system. ...

Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. However, due to its possible side effects such as liver failure, it's limited in its availability. Tolcapone, an inhibitor of catechol-O-methyltransferase (COMT), is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. ... Catechol-O-methyl transferase (COMT) (EC 2. ...

A similar drug, entacapone, has similar efficacy and has not been shown to cause significant alterations of liver function. 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] Cant give you an article unless I copy my pharmacists notes, but the common name for ENTACAPONE is COMTAN, at least that is the name NOVARTIS uses. ...

Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa, and has been under some investigation.^[40] Binomial name Mucuna pruriens (L.) DC. Mucuna pruriens (syn. ...

Dopamine agonists

The dopamine-agonists bromocriptine, pergolide, pramipexole, ropinirole , cabergoline, apomorphine, and lisuride, are moderately effective. 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. Bromocriptine is an ergoline derivative dopamine agonist that is used in the treatment of pituitary tumors and Parkinsons disease. ... Pergolide is an ergoline-based dopamine receptor agonist used for the treatment of Parkinsons disease. ... Pramipexole (INN, trade names Mirapex® and Sifrol®) is a medication indicated for treating Parkinsons disease and restless legs syndrome (RLS). ... Requip (ropinirole) is so far the only medication in the United States with an FDA approved indication for the treatment of Restless Legs Syndrome. ... // Introduction and Phrmacology Cabergoline (brand names Dostinex® and Cabaser®), an ergot-derivative, is a potent dopamine receptor agonist on D2-Receptors. ... Apomorphine is a type of dopaminergic agonist, a morphine derivative. ... Lisuride (brand name in Germany Dopergin) is an anti-Parkinsons drug of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinsons drugs. ...

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. The injection site must be changed daily and rotated around the body to avoid the formation of nodules. 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. Nausea and vomiting are common, any may require domperidone (an antiemetic). In medicine, a nodule refers to a small aggregation of cells. ... This article or section does not adequately cite its references or sources. ... Domperidone (trade name Motilium or Motillium) is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally or intravenously, generally to suppress nausea and vomiting. ...

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. 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. Selegiline (l-deprenyl, Eldepryl® or Anipryl® [veterinary]) is a drug used for the treatment of early-stage Parkinsons disease and senile dementia. ... Rasagiline (trade name Azilect®) is a irreversible inhibitor of monoamine oxidase used as a monotherapy in early Parkinsons disease or as an adjunct therapy in more advanced cases. ... Monoamine oxidase inhibitors (MAOIs) are a class of 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. Image File history File links Download high-resolution version (787x1174, 751 KB) incertion of electrode during parkinson surgery Source: taken by user File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Neurosurgery Deep brain stimulation ... Image File history File links Download high-resolution version (787x1174, 751 KB) incertion of electrode during parkinson surgery Source: taken by user File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Neurosurgery Deep brain stimulation ...

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.^[47] In neurotechnology, deep brain stimulation (DBS) is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain. ... Coronal slices of human brain showing the basal ganglia, globus pallidus: external segment (GPe), subthalamic nucleus (STN), globus pallidus: internal segment (GPi), and substantia nigra (SN). ... The globus pallidus (Latin for pale body) is a sub-cortical structure in the brain. ... Palliodotomy is a procedure where a tiny electrical probe is placed in the brain, which destroys a small number of brain cells that misfunction and cause rigidity. ...

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.^[48] GABA acts as a direct inhibitor on the overactive cells in the STN. Glutamate decarboxylase is involved in a catabolic reaction in which NADPH is turned into its ground state form: peptidoglycanase. ... Chemical structure of D-aspartic acid, a common amino acid neurotransmitter. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model...

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

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.^[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. Serving to protect neurons from injury or degeneration. ...

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.^[53] Research in African green monkeys suggests that the use of stem cells might in future provide a similar benefit without inducing dystonias.^[54] Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. ... Species Chlorocebus sabaceus Chlorocebus aethiops Chlorocebus djamdjamensis Chlorocebus tantalus Chlorocebus pygerythrus Chlorocebus cynosuros The vervet monkeys or green monkeys are primates from the family of Old World monkeys. ... Mouse embryonic stem cells with fluorescent marker. ...

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. 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] For the artist, see Qigong (artist). ...

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.^[61] Botulin toxin or botox is the toxic compound produced by the bacterium Clostridium botulinum. ...

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 di