Parkinsonism
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Parkinsonism is a clinical
syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...
characterized by tremor,
bradykinesia Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a sym ...
(slowed movements), rigidity, and
postural instability A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness, or wooziness, or having a sensation of movement, spinning, or floating. Balance ...
. These are the four motor symptoms found in
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(PD), after which it is named,
dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time an ...
(DLB), Parkinson's disease dementia (PDD), and many other conditions. This set of symptoms occurs in a wide range of conditions and may have many causes, including
neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
conditions, drugs,
toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...
s,
metabolic disease A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the ...
s, and neurological conditions other than PD.


Signs and symptoms

Parkinsonism is a clinical
syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...
characterized by the four motor symptoms found in
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
: tremor,
bradykinesia Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a sym ...
(slowed movements), rigidity, and
postural instability A balance disorder is a disturbance that causes an individual to feel unsteady, for example when standing or walking. It may be accompanied by feelings of giddiness, or wooziness, or having a sensation of movement, spinning, or floating. Balance ...
. Parkinsonism gait problems can lead to falls and serious physical injuries. Other common symptoms include: * Tremors when resting (mostly in the hands) * Short, shuffling gait * Slow movements (bradykinesia) * Loss of sound perception leading to low, soft speech * Difficulty sleeping *
Dry skin Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin. The medical term ''xeroderma'', meaning "dry skin", derives from modern Latin, ''xero-'' 'dry' + Greek ''derma'' 'skin'. In most ...
*
Apathy Apathy is a lack of feeling, emotion, interest, or concern about something. It is a state of indifference, or the suppression of emotions such as concern, excitement, motivation, or passion. An apathetic individual has an absence of intere ...
* Lack of facial expressions * Balance problems * Frequent falls * Very small handwriting * Rigid, stiff muscles * Cogwheeling (jerky feeling in arm or leg)


Conditions

Parkinsonism occurs in many conditions.


Neurological

Neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
conditions and Parkinson plus syndrome that can cause parkinsonism include: * Corticobasal degeneration *
Dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time an ...
* The relationship (if any) with
essential tremor Essential tremor (ET), also called benign tremor, familial tremor, and idiopathic tremor, is a medical condition characterized by involuntary rhythmic contractions and relaxations ( oscillations or twitching movements) of certain muscle groups in ...
is not clear. * Frontotemporal dementia ( Pick's disease) *
Gerstmann–Sträussler–Scheinker syndrome Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, usually familial, fatal neurodegenerative disease that affects patients from 20 to 60 years in age. It is exclusively heritable, and is found in only a few families all over ...
*
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...
* Lytico-bodig disease ( ALS complex of Guam) * Multiple system atrophy ( Shy–Drager syndrome) *
Neuroacanthocytosis Neuroacanthocytosis is a label applied to several genetic neurological conditions in which the blood contains misshapen, spiculated red blood cells called acanthocytes. The 'core' neuroacanthocytosis syndromes, in which acanthocytes are a typic ...
*
Neuronal ceroid lipofuscinosis Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments ( lipofuscin) in the body's tissues. These ...
* Olivopontocerebellar atrophy * Pantothenate kinase-associated neurodegeneration, also known as neurodegeneration with brain iron accumulation * Parkin mutation (hereditary juvenile dystonia) *
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
* Parkinson's disease dementia *
Progressive supranuclear palsy Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...
*
Wilson's disease Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, ...
* X-linked dystonia parkinsonism ( Lubag syndrome)


Drug-induced ("pseudoparkinsonism")

About 7% of people with parkinsonism developed symptoms as a result of side effects of medications, mainly neuroleptic
antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...
s especially the phenothiazines (such as
perphenazine Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades. Perphenazine is roughly ten times as pote ...
and
chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar di ...
),
thioxanthene Thioxanthene is a chemical compound in which the oxygen atom in xanthene is replaced with a sulfur atom. It is also related to phenothiazine. Several of its derivatives are used as typical antipsychotics in the treatment of schizophrenia and othe ...
s (such as
flupenthixol Flupentixol ( INN), also known as flupenthixol (former BAN), marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug pr ...
and
zuclopenthixol Zuclopenthixol (brand names Cisordinol, Clopixol and others), also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanth ...
) and
butyrophenone Butyrophenone is an organic compound with the formula C6H5C(O)C3H7. It is a colorless liquid. The butyrophenone structure—a ketone flanked by a phenyl ring and a butyl chain—forms the basis for many other chemicals containing various sub ...
s (such as
haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
), and rarely, antidepressants. Yet another drug that can induce parkinsonism is the antihistaminic medication cinnarizine, usually prescribed for motion sickness; this is because besides antagonizing histamine receptors this drug antagonizes the
dopamine D2 receptor Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, in ...
s. The incidence of drug-induced parkinsonism increases with age. Drug-induced parkinsonism tends to remain at its presenting level and does not worsen like Parkinson's disease. Implicated medications include: *
Antipsychotics Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...
*
Lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid ...
*
Metoclopramide Metoclopramide is a medication used for stomach and esophageal problems. It is commonly used to treat and prevent nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying, and to help with gastroesoph ...
*
MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
addiction and frequent use *
Tetrabenazine Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabena ...
* Cinnarizine


Infectious

*
Creutzfeldt–Jakob disease Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes ...
* Encephalitis lethargica *
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
infection and AIDS


Toxins

Evidence exists of a link between exposure to pesticides and herbicides and PD; a two-fold increase in risk was seen with paraquat or
maneb Maneb is a fungicide and a polymeric complex of manganese with the ethylene bis(dithiocarbamate) anionic ligand.Arno H. Reidies "Manganese Compounds" Ullmann's Encyclopedia of Chemical Technology 2007; Wiley-VCH, Weinheim. Applications It can ...
/
mancozeb Mancozeb is a dithiocarbamate non-systemic agricultural fungicide with multi-site, protective action on contact. It is a combination of two other dithiocarbamates: maneb and zineb. The mixture controls many fungal diseases in a wide range of f ...
exposure. Chronic
manganese Manganese is a chemical element with the symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese is a transition metal with a multifaceted array of industrial alloy use ...
(Mn) exposure has been shown to produce a parkinsonism-like illness characterized by movement abnormalities. This condition is not responsive to typical therapies used in the treatment of PD, suggesting an alternative pathway than the typical dopaminergic loss within the substantia nigra. Manganese may accumulate in the
basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an exter ...
, leading to the abnormal movements. A mutation of the SLC30A10 gene, a manganese efflux transporter necessary for decreasing intracellular Mn, has been linked with the development of this parkinsonism-like disease. The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism. Agent Orange may be a cause of parkinsonism, although evidence is inconclusive and further research is needed. Other toxins that have been associated with parkinsonism are: *
Annonaceae The Annonaceae are a family of flowering plants consisting of trees, shrubs, or rarely lianas commonly known as the custard apple family or soursop family. With 108 accepted genera and about 2400 known species, it is the largest family in the Ma ...
*
Carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...
*
Carbon disulfide Carbon disulfide (also spelled as carbon disulphide) is a neurotoxic, colorless, volatile liquid with the formula and structure . The compound is used frequently as a building block in organic chemistry as well as an industrial and chemical n ...
*
Cyanide Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of ...
*
Ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
* Hexane *
Maneb Maneb is a fungicide and a polymeric complex of manganese with the ethylene bis(dithiocarbamate) anionic ligand.Arno H. Reidies "Manganese Compounds" Ullmann's Encyclopedia of Chemical Technology 2007; Wiley-VCH, Weinheim. Applications It can ...
/
Mancozeb Mancozeb is a dithiocarbamate non-systemic agricultural fungicide with multi-site, protective action on contact. It is a combination of two other dithiocarbamates: maneb and zineb. The mixture controls many fungal diseases in a wide range of f ...
* Mercury * Methanol *
MPTP MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study d ...
* Paraquat *
Rotenone Rotenone is an odorless, colorless, crystalline isoflavone used as a broad-spectrum insecticide, piscicide, and pesticide. It occurs naturally in the seeds and stems of several plants, such as the jicama vine plant, and the roots of several mem ...
*
Toluene Toluene (), also known as toluol (), is a substituted aromatic hydrocarbon. It is a colorless, water-insoluble liquid with the smell associated with paint thinners. It is a mono-substituted benzene derivative, consisting of a methyl group (CH3) a ...
(
inhalant abuse Inhalants are a broad range of household and industrial chemicals whose volatile vapors or pressurized gases can be concentrated and breathed in via the nose or mouth to produce intoxication, in a manner not intended by the manufacturer. They ...
: "huffing")


Vascular

* Binswanger's disease (subcortical leukoencephalopathy) *
Vascular dementia Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisti ...
(multi-infarct)


Other

*
Chronic traumatic encephalopathy Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse ...
(boxer's dementia or pugilistic encephalopathy) * Damage to the
brain stem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is co ...
(especially dopaminergic nuclei of the substantia nigra),
basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an exter ...
(especially globus pallidus) and the
thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
. * Hypothyroidism *
Orthostatic tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, f ...
* Paraneoplastic syndrome: neurological symptoms caused by antibodies associated with cancers * Rapid onset dystonia parkinsonism * Autosomal recessive juvenile parkinsonism


Society and culture

In the United States, the 2021
National Defense Authorization Act The National Defense Authorization Act (NDAA) is the name for each of a series of United States federal laws specifying the annual budget and expenditures of the U.S. Department of Defense. The first NDAA was passed in 1961. The U.S. Congress o ...
(NDAA) added parkinsonism to the list of presumptive conditions associated with Agent Orange exposure, enabling affected service members to receive Veterans Affairs disability benefits. 


References


External links


GeneReviews/NIH/NCBI/UW entry on Perry syndrome

GeneReviews/NCBI/NIH/UW entry on X-Linked Dystonia-Parkinsonism
{{Antiparkinson agents Extrapyramidal and movement disorders Geriatrics Parkinson's disease