Parkinsonism

Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability.<ref name="Aminoff_2005">Template:Cite book</ref><ref name="Role of neuroimaging on differentia">Template:Cite journal</ref>

Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic features (cogwheel rigidity and tremors at rest) are displayed in parkinsonism.<ref name=Ganog/> These are the four motor signs that are found in Parkinson's disease (PD)Template:Sndafter which Parkinsonism is namedTemplate:Sndand in dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions.

This set of signs occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than Parkinson's disease.<ref>Template:Cite journal</ref>

Signs and symptoms

Parkinsonism is a clinical syndrome characterized by the four motor signs that are found in Parkinson's disease: tremor, bradykinesia (slowed movements), rigidity, and postural instability.<ref name="Aminoff_2005"/><ref name="Role of neuroimaging on differentia"/>

Parkinsonism gait problems can lead to falls and serious physical injuries. Other common signs and symptoms include:

• Tremors, as rest tremor (when resting, mostly in the hands) and/or postular tremor
• Short, shuffling gait
• Slow movements (bradykinesia)
• Loss of sound perception leading to soft speech, hypophonia<ref>Template:Cite journal</ref>
• Difficulty sleeping
• Dry skin
• Apathy
• Lack of facial expressions
• Balance problems
• Frequent falls
• Very small handwriting
• Rigid, stiff muscles
• Cogwheeling (jerky feeling in arm or leg)
• Upgaze impairment
• Plastic, dead feeling resistance known as "lead-pipe rigidity".<ref name="Ganog">Template:Cite book</ref>

Conditions

Parkinsonism occurs in many conditions.

Neurological

Neurodegenerative conditions and Parkinson-plus syndromes that can cause parkinsonism include:<ref name="Bradley2004">Template:Cite book</ref>

• Corticobasal degeneration<ref name="Bradley2004" />
• Dementia with Lewy bodies<ref name="Bradley2004" />
• The relationship (if any) with essential tremor is not clear.<ref>Template:Cite journal</ref>
• Frontotemporal dementia (Pick's disease)<ref name="Finger2016">Template:Cite journal</ref>
• Gerstmann–Sträussler–Scheinker syndrome<ref name="Bradley2004" />
• Huntington's disease<ref name="Bradley2004" />
• Lytico-bodig disease (ALS complex of Guam)<ref name="Bradley2004" />
• Multiple system atrophy (Shy–Drager syndrome)<ref name="Bradley2004" />
• Neuroacanthocytosis<ref name="Bradley2004" />
• Neuronal ceroid lipofuscinosis<ref name="Bradley2004" />
• Olivopontocerebellar atrophy<ref name="Bradley2004" />
• Pantothenate kinase-associated neurodegeneration, also known as neurodegeneration with brain iron accumulation<ref name="Bradley2004" />
• Parkin mutation causing hereditary juvenile dystonia<ref name="Bradley2004" />
• Parkinson's disease<ref name="Bradley2004" />
• Parkinson's disease dementia<ref name="McKeithConsensus2017">Template:Cite journal</ref>
• Progressive supranuclear palsy<ref name="Bradley2004" />
• Wilson's disease<ref name="Bradley2004" />
• X-linked dystonia parkinsonism (Lubag syndrome)<ref name="Bradley2004" />

Infectious

• Creutzfeldt–Jakob disease<ref name="Bradley2004" /><ref>Template:Cite journal</ref>
• Encephalitis lethargica<ref name="Aminoff_2005" />
• HIV infection<ref name="Bradley2004" /> and AIDS<ref name="Bradley2004" /><ref>Template:Cite journal</ref>
• Japanese encephalitis<ref name=Jong2022>Template:Cite book</ref>

Toxins

Evidence exists to show a link between exposure to pesticides and herbicides and PD; a two-fold increase in risk was seen with paraquat or maneb/mancozeb exposure.<ref name="Pezzoli2013">Template:Cite journal</ref>

Chronic manganese (Mn) exposure has been shown to produce a parkinsonism-like illness characterized by movement abnormalities.<ref name="Guilarte2015">Template:Cite journal</ref> 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.<ref name="Guilarte2015" /> Manganese may accumulate in the basal ganglia, leading to the abnormal movements that characterize parkinsonism.<ref name="Kwakye2015">Template:Cite journal</ref> 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.<ref name="Peres2016">Template:Cite journal</ref> The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism.<ref name="Kwakye2015" />

Agent Orange may be a cause of parkinsonism, although evidence is inconclusive and further research is needed.<ref name=McKnight2020>Template:Cite journal</ref>

Other toxins that have been associated with parkinsonism are:

• Annonaceae<ref>Template:Cite journal</ref>
• Carbon monoxide<ref name="Bradley2004" />
• Carbon disulfide<ref name="Bradley2004" />
• Cyanide<ref name="Bradley2004" />
• Ethanol<ref name="Bradley2004" />
• Hexane<ref name="Kim2010">Template:Cite journal</ref>
• Mercury<ref name="Bradley2004" />
• Methanol<ref name="Bradley2004" />
• MPTP<ref name="Bradley2004" /><ref name="Watanabe_2005">Template:Cite journal</ref>
• Rotenone<ref name="Nandipati">Template:Cite journal</ref>
• Toluene<ref>Weiss J. Chapter 151. Toluene and Xylene. In: Olson KR, ed. Poisoning & Drug Overdose. 6th ed. New York: McGraw-Hill; 2012. http://www.accessmedicine.com/content.aspx?aID=55982958. Accessed April 21, 2013.</ref> (inhalant abuse: "huffing")<ref>Template:Cite journal</ref>

Vascular

• Binswanger's disease (subcortical leukoencephalopathy)<ref name="Bradley2004" />
• Vascular dementia (multi-infarct)<ref name="Bradley2004" />
• Dural arteriovenous fistula / dAVF (reversible parkinsonism through fistula treatment)<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Dural arteriovenous malformation / dAVM (reversible through dAVM treatment) <ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Other

• Chronic traumatic encephalopathy (boxer's dementia or pugilistic encephalopathy)<ref name="Bradley2004" />
• Damage to the brain stem (especially dopaminergic nuclei of the substantia nigra),<ref>Template:Cite journal</ref> basal ganglia (especially globus pallidus)<ref>Template:Cite journal</ref> and the thalamus.<ref>Template:Cite journal</ref>
• Hypothyroidism<ref name="Bradley2004" />
• Orthostatic tremor<ref>Template:Cite journal</ref>
• Paraneoplastic syndrome: neurological symptoms caused by antibodies associated with cancers<ref>Template:Cite journal</ref>
• Rapid onset dystonia parkinsonism<ref>Template:Cite journal</ref>
• Autosomal recessive juvenile parkinsonism<ref>Template:Cite journal</ref>

Differential diagnosis

Secondary parkinsonism, including vascular parkinsonism and drug-induced parkinsonism.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Drug-induced parkinsonism

About 7% of people with parkinsonism developed symptoms as a result of side effects of medication, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupentixol and zuclopenthixol) and butyrophenones (such as haloperidol), 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 receptors.<ref name="Marti-Masso" /> 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.<ref>Template:Cite web</ref>

Implicated medications include:

• Antipsychotics<ref name="Bradley2004" />
• Lithium<ref name="Bradley2004" />
• Metoclopramide<ref>Template:Cite journal</ref>
• MDMA (addiction and frequent use)<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Tetrabenazine<ref name="Bradley2004" />
• Cinnarizine<ref name="Marti-Masso">Template:Cite journal</ref>

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 disability benefits.<ref name= VAParkinsonism>Template:Cite web</ref> 

External links

• GeneReviews/NIH/NCBI/UW entry on Perry syndrome
• GeneReviews/NCBI/NIH/UW entry on X-Linked Dystonia-Parkinsonism