Parkinsonism

"Parkinson's syndrome" redirects here. Not to be confused with Parkinson's disease.

Medical condition

Parkinsonism

File:Sir William Richard Gowers Parkinson Disease sketch 1886.svg
Causes|

* Parkinson's disease
* Dementia with Lewy bodies
* Parkinson's disease dementia
* Other neurodegenerative disorders, including multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration
* Drugs
* Toxins
* Metabolic disease

Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), rigidity, and postural instability.[1][2] 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 conditions, drugs, toxins, metabolic diseases, and neurological conditions other than PD.[3]

## Contents

* 1 Signs and symptoms
* 2 Conditions
* 2.1 Neurological
* 2.2 Drug-induced ("pseudoparkinsonism")
* 2.3 Infectious
* 2.4 Toxins
* 2.5 Vascular
* 2.6 Other
* 3 Society and culture
* 4 References
* 5 External links

## Signs and symptoms[edit | edit source]

Parkinsonism is a clinical syndrome characterized by the four motor symptoms found in Parkinson's disease: tremor, bradykinesia (slowed movements), rigidity, and postural instability.[1][2]

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
* Apathy
* Lack of facial expressions
* Balance problems
* Frequent falls
* Very small handwriting
* Rigid, stiff muscles
* Cogwheeling (jerky feeling in arm or leg)

## Conditions[edit | edit source]

Parkinsonism occurs in many conditions.

### Neurological[edit | edit source]

Neurodegenerative conditions and Parkinson plus syndrome that can cause parkinsonism include:[4]

* Corticobasal degeneration[4]
* Dementia with Lewy bodies[4]
* The relationship (if any) with essential tremor is not clear.[5]
* Frontotemporal dementia (Pick's disease)[6]
* Gerstmann–Sträussler–Scheinker syndrome[4]
* Huntington's disease[4]
* Lytico-bodig disease (ALS complex of Guam)[4]
* Multiple system atrophy (Shy–Drager syndrome)[4]
* Neuroacanthocytosis[4]
* Neuronal ceroid lipofuscinosis[4]
* Olivopontocerebellar atrophy[4]
* Pantothenate kinase-associated neurodegeneration, also known as neurodegeneration with brain iron accumulation[4]
* Parkin mutation (hereditary juvenile dystonia)[4]
* Parkinson's disease[4]
* Parkinson's disease dementia[7]
* Progressive supranuclear palsy[4]
* Wilson's disease[4]
* X-linked dystonia parkinsonism (Lubag syndrome)[4]

### Drug-induced ("pseudoparkinsonism")[edit | edit source]

About 7% of people with parkinsonism developed symptoms as a result of side effects of medications, mainly neuroleptic antipsychotics especially the phenothiazines (such as perphenazine and chlorpromazine), thioxanthenes (such as flupenthixol 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.[8] 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.[9]

Implicated medications include:

* Antipsychotics[4]
* Lithium[4]
* Metoclopramide[10]
* MDMA addiction and frequent use[11][12]
* Tetrabenazine[4]
* Cinnarizine[8]

### Infectious[edit | edit source]

* Creutzfeldt–Jakob disease[4][13]
* Encephalitis lethargica[1]
* HIV infection[4] and AIDS[4][14]

### Toxins[edit | edit source]

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/mancozeb exposure.[15]

Chronic manganese (Mn) exposure has been shown to produce a parkinsonism-like illness characterized by movement abnormalities.[16] 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.[16] Manganese may accumulate in the basal ganglia, leading to the abnormal movements.[17] 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.[18] The Lewy bodies typical to PD are not seen in Mn-induced parkinsonism.[17]

Agent Orange may be a cause of parkinsonism, although evidence is inconclusive and further research is needed.[19]

Other toxins that have been associated with parkinsonism are:

* Annonaceae[20]
* Carbon monoxide[4]
* Carbon disulfide[4]
* Cyanide[4]
* Ethanol[4]
* Hexane[21]
* Maneb/Mancozeb[15]
* Mercury[4]
* Methanol[4]
* MPTP[4][22]
* Paraquat[23][15]
* Rotenone[23]
* Toluene[24] (inhalant abuse: "huffing")[25]

### Vascular[edit | edit source]

* Binswanger's disease (subcortical leukoencephalopathy)[4]
* Vascular dementia (multi-infarct)[4]

### Other[edit | edit source]

* Chronic traumatic encephalopathy (boxer's dementia or pugilistic encephalopathy)[4]
* Damage to the brain stem (especially dopaminergic nuclei of the substantia nigra),[26]basal ganglia (especially globus pallidus)[27] and the thalamus.[28]
* Hypothyroidism[4]
* Orthostatic tremor[29]
* Paraneoplastic syndrome: neurological symptoms caused by antibodies associated with cancers[30]
* Rapid onset dystonia parkinsonism[31]
* Autosomal recessive juvenile parkinsonism[32]

## Society and culture[edit | edit source]

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.[33]

## References[edit | edit source]

1. ^ a b c Aminoff MJ, Greenberg DA, Simon RP (2005). "Chapter 7: Movement disorders". Clinical Neurology (6th ed.). Lange: McGraw-Hill Medical. pp. 241–45. ISBN 978-0-07-142360-1.
2. ^ a b Ogawa T, Fujii S, Kuya K, Kitao SI, Shinohara Y, Ishibashi M, Tanabe Y (September 2018). "Role of neuroimaging on differentiation of Parkinson's disease and its related diseases". Yonago Acta Med (Review). 61 (3): 145–55. doi:10.33160/yam.2018.09.001. PMC 6158357. PMID 30275744. "Parkinsonian syndromes are a group of movement disorders characterized by classical motor symptoms such as tremors, bradykinesia, and rigidity. They are most frequently due to primary neurodegenerative disease, resulting in the loss of dopaminergic nerve terminals along the nigrostriatal pathway, similar to idiopathic PD, MSA, PSP, CBD, and DLB."
3. ^ Christine CW, Aminoff MJ (September 2004). "Clinical differentiation of parkinsonian syndromes: prognostic and therapeutic relevance". The American Journal of Medicine. 117 (6): 412–9. doi:10.1016/j.amjmed.2004.03.032. PMID 15380498.
4. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag Jankovic J, Lang AE (2004). "Diagnosis and Assessment". In Bradley, Walter George (ed.). Neurology in Clinical Practice: Principles of diagnosis and management. Vol. 1\. Taylor & Francis. pp. 295–96. ISBN 9789997625885.
5. ^ Algarni M, Fasano A (January 2018). "The overlap between Essential tremor and Parkinson disease". Parkinsonism & Related Disorders. 46 Suppl 1: S101–S104. doi:10.1016/j.parkreldis.2017.07.006. PMID 28729090.
6. ^ Finger EC (April 2016). "Frontotemporal Dementias". Continuum (Review). 22 (2 Dementia): 464–89. doi:10.1212/CON.0000000000000300. PMC 5390934. PMID 27042904.
7. ^ McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. (July 2017). "Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium". Neurology (Review). 89 (1): 88–100. doi:10.1212/WNL.0000000000004058. PMC 5496518. PMID 28592453.
8. ^ a b Martí-Massó, José F.; Poza, Juan J. (1 May 1998). Stoessl, A. Jon; Klein, Christine; Standaert, David G. (eds.). "Cinnarizine-induced parkinsonism: ten years later". Movement Disorders. Vancouver, British Columbia, Canada: International Parkinson and Movement Disorder Society/Wiley. 13 (3): 453–456. doi:10.1002/mds.870130313. ISSN 1531-8257. PMID 9613736. S2CID 31516105.
9. ^ "Information Sheet: Drug-induced Parkinsonism" (PDF). Parkinson’s Disease and Society. Archived from the original (PDF) on 2013-06-26. Retrieved 2013-04-15.
10. ^ Shuaib UA, Rajput AH, Robinson CA, Rajput A (March 2016). "Neuroleptic-induced Parkinsonism: Clinicopathological study". Movement Disorders. 31 (3): 360–5. doi:10.1002/mds.26467. PMC 5064745. PMID 26660063.
11. ^ Louis ED, Ottman R (November 2013). "Is there a one-way street from essential tremor to Parkinson's disease? Possible biological ramifications". European Journal of Neurology (Review). 20 (11): 1440–4. doi:10.1111/ene.12256. PMC 3801177. PMID 24033795.
12. ^ Fabrizi, Monaco, Dalla Libera (2004). "Parkinsonian syndrome following MDMA (Ecstasy) addiction". Movement Disorders. 19: S73–S74.`{{cite journal}}`: CS1 maint: multiple names: authors list (link)
13. ^ Maltête D, Guyant-Maréchal L, Mihout B, Hannequin D (March 2006). "Movement disorders and Creutzfeldt-Jakob disease: a review". Parkinsonism & Related Disorders. 12 (2): 65–71. doi:10.1016/j.parkreldis.2005.10.004. PMID 16364674.
14. ^ Tse W, Cersosimo MG, Gracies JM, Morgello S, Olanow CW, Koller W (August 2004). "Movement disorders and AIDS: a review". Parkinsonism & Related Disorders. 10 (6): 323–34. doi:10.1016/j.parkreldis.2004.03.001. PMID 15261874.
15. ^ a b c Pezzoli G, Cereda E (May 2013). "Exposure to pesticides or solvents and risk of Parkinson disease". Neurology (Meta-analysis). 80 (22): 2035–41. doi:10.1212/WNL.0b013e318294b3c8. PMID 23713084. S2CID 13628268.
16. ^ a b Guilarte TR, Gonzales KK (August 2015). "Manganese-Induced Parkinsonism Is Not Idiopathic Parkinson's Disease: Environmental and Genetic Evidence". Toxicological Sciences (Review). 146 (2): 204–12. doi:10.1093/toxsci/kfv099. PMC 4607750. PMID 26220508.
17. ^ a b Kwakye GF, Paoliello MM, Mukhopadhyay S, Bowman AB, Aschner M (July 2015). "Manganese-Induced Parkinsonism and Parkinson's Disease: Shared and Distinguishable Features". International Journal of Environmental Research and Public Health (Review). 12 (7): 7519–40. doi:10.3390/ijerph120707519. PMC 4515672. PMID 26154659.
18. ^ Peres TV, Schettinger MR, Chen P, Carvalho F, Avila DS, Bowman AB, Aschner M (November 2016). "Manganese-induced neurotoxicity: a review of its behavioral consequences and neuroprotective strategies". BMC Pharmacology & Toxicology (Review). 17 (1): 57. doi:10.1186/s40360-016-0099-0. PMC 5097420. PMID 27814772.
19. ^ McKnight S, Hack N (November 2020). "Toxin-Induced Parkinsonism". Neurol Clin (Review). 38 (4): 853–865. doi:10.1016/j.ncl.2020.08.003. PMID 33040865. S2CID 222299758.
20. ^ Carod-Artal FJ (2003). "[Neurological syndromes linked with the intake of plants and fungi containing a toxic component (I). Neurotoxic syndromes caused by the ingestion of plants, seeds and fruits]". Revista de Neurología (Review) (in Spanish). 36 (9): 860–71. PMID 12717675.
21. ^ Kim EA, Kang SK (December 2010). "Occupational neurological disorders in Korea". Journal of Korean Medical Science (Review). 25 (Suppl): S26-35. doi:10.3346/jkms.2010.25.S.S26. PMC 3023358. PMID 21258587.
22. ^ Watanabe Y, Himeda T, Araki T (January 2005). "Mechanisms of MPTP toxicity and their implications for therapy of Parkinson's disease" (PDF). Medical Science Monitor. 11 (1): RA17-23. PMID 15614202.
23. ^ a b Nandipati S, Litvan I (September 2016). "Environmental Exposures and Parkinson's Disease". International Journal of Environmental Research and Public Health (Review). 13 (9): 881. doi:10.3390/ijerph13090881. PMC 5036714. PMID 27598189.
24. ^ 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.
25. ^ Uitti RJ, Snow BJ, Shinotoh H, Vingerhoets FJ, Hayward M, Hashimoto S, Richmond J, Markey SP, Markey CJ, Calne DB (May 1994). "Parkinsonism induced by solvent abuse". Annals of Neurology. 35 (5): 616–9. doi:10.1002/ana.410350516. PMID 8179306. S2CID 23657208.
26. ^ Jubault T, Brambati SM, Degroot C, Kullmann B, Strafella AP, Lafontaine AL, Chouinard S, Monchi O (December 2009). Gendelman HE (ed.). "Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI". PLOS ONE. 4 (12): e8247. Bibcode:2009PLoSO...4.8247J. doi:10.1371/journal.pone.0008247. PMC 2784293. PMID 20011063.
27. ^ Kuoppamäki M, Rothwell JC, Brown RG, Quinn N, Bhatia KP, Jahanshahi M (April 2005). "Parkinsonism following bilateral lesions of the globus pallidus: performance on a variety of motor tasks shows similarities with Parkinson's disease". Journal of Neurology, Neurosurgery, and Psychiatry. 76 (4): 482–90. doi:10.1136/jnnp.2003.020800. PMC 1739601. PMID 15774432.
28. ^ Halliday, Glenda M. (2009-12-15). "Thalamic changes in Parkinson's disease". Parkinsonism & Related Disorders. 15: S152–S155. doi:10.1016/S1353-8020(09)70804-1. PMID 20082979.
29. ^ Apartis E, Tison F, Arné P, Jedynak CP, Vidailhet M (November 2001). "Fast orthostatic tremor in Parkinson's disease mimicking primary orthostatic tremor". Movement Disorders. 16 (6): 1133–6. doi:10.1002/mds.1218. PMID 11748748. S2CID 36301428.
30. ^ Panzer J, Dalmau J (August 2011). "Movement disorders in paraneoplastic and autoimmune disease". Current Opinion in Neurology. 24 (4): 346–53. doi:10.1097/WCO.0b013e328347b307. PMC 3705177. PMID 21577108.
31. ^ Liu Y, Lu Y, Zhang X, Xie S, Wang T, Wu T, Wang C (November 2016). "A case of rapid-onset dystonia-parkinsonism accompanied by pyramidal tract impairment". BMC Neurology. 16 (1): 218. doi:10.1186/s12883-016-0743-8. PMC 5105251. PMID 27835968.
32. ^ Saito M, Maruyama M, Ikeuchi K, Kondo H, Ishikawa A, Yuasa T, Tsuji S (September 2000). "Autosomal recessive juvenile parkinsonism". Brain & Development. 22 Suppl 1: S115-7. doi:10.1016/s0387-7604(00)00137-6. PMID 10984671. S2CID 22733500.
33. ^ "VA adds three new Agent Orange presumptions". U. S. Department of Veteran Affairs. September 10, 2021. Retrieved March 2, 2022.

## External links[edit | edit source]

Classification|

* ICD-10: G21, G22
* ICD-9-CM: 332
* MeSH: D020734
* DiseasesDB: 24212

|

External resources|

* MedlinePlus: 000759

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

* v
* t
* e

Diseases of the nervous system, primarily CNS

Inflammation|

| Brain|

* Encephalitis
* Viral encephalitis
* Herpesviral encephalitis
* Limbic encephalitis
* Encephalitis lethargica
* Cavernous sinus thrombosis
* Brain abscess
* Amoebic

|

Brain and spinal cord|

* Encephalomyelitis
* Acute disseminated
* Meningitis
* Meningoencephalitis

Brain/
encephalopathy|

| Degenerative|

| Extrapyramidal and
movement disorders|

* Basal ganglia disease
* Parkinsonism
* PD
* Postencephalitic
* NMS
* NBIA
* PKAN
* Tauopathy
* PSP
* Striatonigral degeneration
* Hemiballismus
* HD
* OA

* Dyskinesia
* Dystonia
* Status dystonicus
* Spasmodic torticollis
* Meige's
* Blepharospasm
* Athetosis
* Chorea
* Choreoathetosis
* Myoclonus
* Myoclonic epilepsy
* Akathisia

* Tremor
* Essential tremor
* Intention tremor
* Restless legs
* Stiff-person

|

Dementia|

* Tauopathy
* Alzheimer's
* Early-onset
* Primary progressive aphasia
* Frontotemporal dementia/Frontotemporal lobar degeneration
* Pick's
* Lewy bodies dementia
* Posterior cortical atrophy

* Vascular dementia

Mitochondrial disease|

* Leigh syndrome

Demyelinating|

* Autoimmune
* Inflammatory
* Multiple sclerosis
* For more detailed coverage, see Template:Demyelinating diseases of CNS

Episodic/
paroxysmal|

| Seizures and epilepsy|

* Focal
* Generalised
* Status epilepticus
* For more detailed coverage, see Template:Epilepsy

|

Headache|

* Migraine
* Cluster
* Tension
* For more detailed coverage, see Template:Headache

Cerebrovascular|

* TIA
* Stroke
* For more detailed coverage, see Template:Cerebrovascular diseases

Other|

* Sleep disorders
* For more detailed coverage, see Template:Sleep

CSF|

* Intracranial hypertension
* Hydrocephalus
* Normal pressure hydrocephalus
* Choroid plexus papilloma
* Idiopathic intracranial hypertension
* Cerebral edema
* Intracranial hypotension

Other|

* Brain herniation
* Reye syndrome
* Hepatic encephalopathy
* Toxic encephalopathy
* Hashimoto's encephalopathy
* Static Encephalopathy

Both/either|

| Degenerative|

| SA|

* Friedreich's ataxia
* Ataxia–telangiectasia

|

MND|

* UMN only:
* Primary lateral sclerosis
* Pseudobulbar palsy
* Hereditary spastic paraplegia

* LMN only:
* Distal hereditary motor neuronopathies
* Spinal muscular atrophies
* SMA
* SMAX1
* SMAX2
* DSMA1
* Congenital DSMA
* Spinal muscular atrophy with lower extremity predominance (SMALED)
* SMALED1
* SMALED2A
* SMALED2B
* SMA-PCH
* SMA-PME
* Progressive muscular atrophy
* Progressive bulbar palsy
* Fazio–Londe
* Infantile progressive bulbar palsy

* both:
* Amyotrophic lateral sclerosis

* v
* t
* e

Antiparkinson agents (N04)

Dopaminergics|

| DA precursors|

* Levodopa#
* Melevodopa

|

DA receptor agonists|

* Ergoline: Bromocriptine
* Cabergoline
* Dihydroergocryptine
* Lisuride
* Pergolide

* Non-ergoline: Apomorphine
* Piribedil
* Pramipexole
* Ropinirole
* Rotigotine
* Talipexole

MAO-B inhibitors|

* Rasagiline
* Safinamide
* Selegiline

COMT inhibitors|

* Entacapone
* Opicapone
* Tolcapone

AAAD inhibitors|

* Benserazide
* Carbidopa#

Anticholinergics|

* Benzatropine
* Biperiden#
* Bornaprine
* Chlorphenoxamine
* Cycrimine
* Dexetimide
* Diphenhydramine
* Etanautine
* Etybenzatropine
* Mazaticol
* Metixene
* Orphenadrine
* Phenglutarimide
* Piroheptine
* Procyclidine
* Profenamine
* Tigloidine
* Trihexyphenidyl
* Tropatepine

Others|

* Amantadine
* Budipine
* Istradefylline
* Methylxanthines (e.g., caffeine)
* Rimantadine

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

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*[t]: Discuss this template
*[e]: Edit this template