Parkinsonism is a clinical
syndrome 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 (PD), after which it is named,
dementia with Lewy bodies (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,
toxins,
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 characterized by the four
motor symptoms found in
Parkinson's disease:
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
Gait is the pattern of movement of the limbs of animals, including humans, during locomotion over a solid substrate. Most animals use a variety of gaits, selecting gait based on speed, terrain, the need to maneuver, and energetic efficiency. ...
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
Psychoacoustics is the branch of psychophysics involving the scientific study of sound perception and audiology—how humans perceive various sounds. More specifically, it is the branch of science studying the psychological responses associated wit ...
leading to low, soft speech
*
Difficulty sleeping
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
*
Dry skin
*
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 interes ...
* Lack of facial expressions
* Balance problems
* Frequent falls
* Very small handwriting
*
Rigid, stiff muscles
*
Cogwheeling
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 ...
(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
Corticobasal degeneration (CBD) is a rare neurodegenerative disease involving the cerebral cortex and the basal ganglia. CBD symptoms typically begin in people from 50 to 70 years of age, and the average disease duration is six years. It is chara ...
*
Dementia with Lewy bodies
* The relationship (if any) with
essential tremor is not clear.
*
Frontotemporal dementia
Frontotemporal dementia (FTD), or frontotemporal degeneration disease, or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of frontal and temporal lobes. FTDs broadly present a ...
(
Pick's disease)
*
Gerstmann–Sträussler–Scheinker syndrome
*
Huntington's disease
*
Lytico-bodig disease (
ALS
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
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 typi ...
*
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
Pantothenate kinase-associated neurodegeneration (PKAN), formerly called Hallervorden–Spatz syndrome, is a genetic degenerative disease of the brain that can lead to parkinsonism, dystonia, dementia, and ultimately death. Neurodegeneration in P ...
, also known as
neurodegeneration with brain iron accumulation
* Parkin mutation (hereditary juvenile dystonia)
*
Parkinson's disease
*
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
*
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 oth ...
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 p ...
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 dis ...
),
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 other ...
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 pre ...
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 thioxant ...
) 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 subst ...
s (such as
haloperidol), and rarely, antidepressants. Yet another drug that can induce parkinsonism is the
antihistaminic
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
medication
cinnarizine
Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is prescribed for nausea and vomiting due to motion sickness or other sources such as chemotherapy, vertigo, or Ménière's disease.
Cinnarizi ...
, usually prescribed for motion sickness; this is because besides antagonizing
histamine receptors
The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.
There are four known histamine receptors:
* H1 receptor
* H2 receptor
* H3 receptor
* H4 receptor
Comparison
There ...
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 oth ...
*
Lithium
*
Metoclopramide
*
MDMA addiction and frequent use
*
Tetrabenazine
*
Cinnarizine
Cinnarizine is an antihistamine and calcium channel blocker of the diphenylmethylpiperazine group. It is prescribed for nausea and vomiting due to motion sickness or other sources such as chemotherapy, vertigo, or Ménière's disease.
Cinnarizi ...
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
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
Toxins
Evidence exists of a link between exposure to pesticides and herbicides and PD; a two-fold increase in risk was seen with
paraquat
Paraquat (trivial name; ), or ''N'',''N''′-dimethyl-4,4′-bipyridinium dichloride (systematic name), also known as methyl viologen, is an organic compound with the chemical formula C6H7N)2l2. It is classified as a viologen, a family of redo ...
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 b ...
/
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 field ...
exposure.
Chronic
manganese (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
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra appe ...
.
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
Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside nerve cells affected by Parkinson's disease (PD), the Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), and ...
typical to PD are not seen in Mn-induced parkinsonism.
Agent Orange
Agent Orange is a chemical herbicide and defoliant, one of the "tactical use" Rainbow Herbicides. It was used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. It ...
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 Mag ...
*
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 simpl ...
*
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 non ...
*
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 a ...
*
Ethanol
*
Hexane
Hexane () is an organic compound, a straight-chain alkane with six carbon atoms and has the molecular formula C6H14.
It is a colorless liquid, odorless when pure, and with boiling points approximately . It is widely used as a cheap, relatively ...
*
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 b ...
/
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 field ...
*
Mercury
*
Methanol
*
MPTP
*
Paraquat
Paraquat (trivial name; ), or ''N'',''N''′-dimethyl-4,4′-bipyridinium dichloride (systematic name), also known as methyl viologen, is an organic compound with the chemical formula C6H7N)2l2. It is classified as a viologen, a family of redo ...
*
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 member ...
*
Toluene (
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
Binswanger's disease, also known as subcortical leukoencephalopathy and subcortical arteriosclerotic encephalopathy, is a form of small-vessel vascular dementia caused by damage to the white brain matter. White matter atrophy can be caused by man ...
(subcortical
leukoencephalopathy Leukoencephalopathy (leukodystrophy-like diseases) is a term that describes all of the brain white matter diseases, whether their molecular cause is known or unknown. It can refer specifically to any of these diseases:
*Progressive multifocal leuko ...
)
*
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 consisting ...
(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 o ...
(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 conti ...
(especially dopaminergic nuclei of the
substantia nigra
The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra appe ...
),
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
The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rod ...
) and the
thalamus.
*
Hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
*
Orthostatic tremor
*
Paraneoplastic syndrome
A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one), specifically due to the production of chemical signaling molecules (such as hormones or cytokines) by ...
: 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 (NDAA) added parkinsonism to the list of presumptive conditions associated with Agent Orange exposure, enabling affected service members to receive
Veterans Affairs
Veterans' affairs is an area of public policy concerned with relations between a government and its communities of military veterans. Some jurisdictions have a designated government agency or department, a Department of Veterans' Affairs, Minist ...
disability benefits.
References
External links
GeneReviews/NIH/NCBI/UW entry on Perry syndromeGeneReviews/NCBI/NIH/UW entry on X-Linked Dystonia-Parkinsonism
{{Antiparkinson agents
Extrapyramidal and movement disorders
Geriatrics
Parkinson's disease