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==Overview==
==Overview==
'''Dystonia''' (or '''dyskinesia''') is a [[neurology|neurological]] [[movement disorder]] in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.<ref name="NINDS">Dystonia fact sheet:  National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/disorders/dystonias/detail_dystonias.htm </ref> The disorder may be [[Heredity|inherited]] or caused by other factors such as [[Birth trauma|birth-related]] or other [[physical trauma]], [[infection]] or reaction to [[Medication|drugs]].<ref name="NINDS"/>
Dystonia is a hyperkinetic movement disorder identified by involuntary sustained or intermittent contraction of a single or group of muscles that leads to repetitive movements or abnormal posture.<ref name="pmid23649720">{{cite journal |vauthors=Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK |title=Phenomenology and classification of dystonia: a consensus update |journal=Mov. Disord. |volume=28 |issue=7 |pages=863–73 |date=June 2013 |pmid=23649720 |pmc=3729880 |doi=10.1002/mds.25475 |url=}}</ref> The typical dystonic movements are usually rhythmic or patterned contractions that may be accompanied by tremor.<ref name="pmid31356289">{{cite journal |vauthors=Louis ED |title=Tremor |journal=Continuum (Minneap Minn) |volume=25 |issue=4 |pages=959–975 |date=August 2019 |pmid=31356289 |doi=10.1212/CON.0000000000000748 |url=}}</ref><ref name="pmid30237473">{{cite journal |vauthors=Balint B, Mencacci NE, Valente EM, Pisani A, Rothwell J, Jankovic J, Vidailhet M, Bhatia KP |title=Dystonia |journal=Nat Rev Dis Primers |volume=4 |issue=1 |pages=25 |date=September 2018 |pmid=30237473 |doi=10.1038/s41572-018-0023-6 |url=}}</ref>  


==Historical Perspective==
==Historical Perspective==
* The term Dystonia was first introduced by Hermann Oppenheim, a German Neurologist , in 1911 following delineating abnormal posturing (dystonia muscularum deformans) in 4 unrelated Jewish children.<ref name="pmid28920067">{{cite journal |vauthors=Newby RE, Thorpe DE, Kempster PA, Alty JE |title=A History of Dystonia: Ancient to Modern |journal=Mov Disord Clin Pract |volume=4 |issue=4 |pages=478–485 |date=2017 |pmid=28920067 |pmc=5573933 |doi=10.1002/mdc3.12493 |url=}}</ref>
*The association between hereditary factors and dystonia was made in 1959 during reporting families with similar symptoms . <ref name="pmid13661153">{{cite journal |vauthors=ZEMAN W, KAELBLING R, PASAMANICK B, JENKINS JT |title=Idiopathic dystonia musculorum deformans. I. The hereditary pattern |journal=Am. J. Hum. Genet. |volume=11 |issue=2 Part 1 |pages=188–202 |date=June 1959 |pmid=13661153 |pmc=1931983 |doi= |url=}}</ref>
* The association between genes and dystonia was made in 1989 during introducing DYT1 or TOR1A gene as a major cause of young-onset generalized dystonia .<ref name="pmid9288096">{{cite journal |vauthors=Ozelius LJ, Hewett JW, Page CE, Bressman SB, Kramer PL, Shalish C, de Leon D, Brin MF, Raymond D, Corey DP, Fahn S, Risch NJ, Buckler AJ, Gusella JF, Breakefield XO |title=The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein |journal=Nat. Genet. |volume=17 |issue=1 |pages=40–8 |date=September 1997 |pmid=9288096 |doi=10.1038/ng0997-40 |url=}}</ref><ref name="pmid2576373">{{cite journal |vauthors=Ozelius L, Kramer PL, Moskowitz CB, Kwiatkowski DJ, Brin MF, Bressman SB, Schuback DE, Falk CT, Risch N, de Leon D |title=Human gene for torsion dystonia located on chromosome 9q32-q34 |journal=Neuron |volume=2 |issue=5 |pages=1427–34 |date=May 1989 |pmid=2576373 |doi=10.1016/0896-6273(89)90188-8 |url=}}</ref>
* In 1989, Ozelius .et.al were the first to discover the association between ITD1 gene ( further known as DYT1 gene ) and the development of dystonia. <ref name="pmid2576373">{{cite journal |vauthors=Ozelius L, Kramer PL, Moskowitz CB, Kwiatkowski DJ, Brin MF, Bressman SB, Schuback DE, Falk CT, Risch N, de Leon D |title=Human gene for torsion dystonia located on chromosome 9q32-q34 |journal=Neuron |volume=2 |issue=5 |pages=1427–34 |date=May 1989 |pmid=2576373 |doi=10.1016/0896-6273(89)90188-8 |url=}}</ref>
*The variant "Focal Dystonia" was first introduced by Charles David Marsden, an English Neurologist, in 1976, following reporting different cases of adult-onset blepharospasm and/or oromandibular dystonia,, torticollis, spasmodic dysphonia, and writer’s  cramp without any hereditary background or known cause. <ref name="pmid1011031">{{cite journal |vauthors=Marsden CD |title=Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). A variant of adult-onset torsion dystonia? |journal=J. Neurol. Neurosurg. Psychiatry |volume=39 |issue=12 |pages=1204–9 |date=December 1976 |pmid=1011031 |pmc=492566 |doi=10.1136/jnnp.39.12.1204 |url=}}</ref> <br />


==Classification==
==Classification==
Dystonia may be classified into several subtypes based on age of onset, topographic distribution, temporal aspects, associated clinical features and etiology .<ref name="pmid23649720">{{cite journal |vauthors=Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK |title=Phenomenology and classification of dystonia: a consensus update |journal=Mov. Disord. |volume=28 |issue=7 |pages=863–73 |date=June 2013 |pmid=23649720 |pmc=3729880 |doi=10.1002/mds.25475 |url=}}</ref><ref name="pmid25485288">{{cite journal |vauthors=Jinnah HA, Albanese A |title=The New Classification System for the Dystonias: Why Was it Needed and How was it Developed? |journal=Mov Disord Clin Pract |volume=1 |issue=4 |pages=280–284 |date=December 2014 |pmid=25485288 |pmc=4254809 |doi=10.1002/mdc3.12100 |url=}}</ref><ref name="pmid29503327">{{cite journal |vauthors=Batla A |title=Dystonia: A review |journal=Neurol India |volume=66 |issue=Supplement |pages=S48–S58 |date=2018 |pmid=29503327 |doi=10.4103/0028-3886.226439 |url=}}</ref>


==Pathophsyiology==
* Dystonia may be classified into five subtypes based on the age of onset; infancy (up to two years), childhood (3-12 years), adolescence (13-20 years), early adulthood (21-40 years) and late adulthood (>40 years)
* Dystonia  may be classified into five subtypes based on the topographic distribution : focal, segmental, multifocal, generalized or hemidystonia


==Causes==
-  Focal : if only one body part of the body is involved. The examples include writing dystonia, cervical dystonia, blepharospasm, Oromandibular dystonia and laryngeal or lingual dystonia
The cause(s) of dystonia are not yet known or understood, however, they are categorized as follows on a theoretical basis:


''Primary dystonia'' is suspected to be caused by a pathology of the [[central nervous system]], likely originating in those parts of the [[brain]] concerned with motor function, such as the [[basal ganglia]], and the GABA ([[Gamma-aminobutyric acid]]) producing Purkinje neurons. The precise cause of primary dystonia is unknown. In many cases it may involve some genetic predisposition towards the disorder combined with environmental conditions.
-  Segmental : if two or more contiguous parts are involved. The examples include bi-brachial and cranial dystonia.


''Secondary dystonia'' refers to dystonia brought on by some identified cause, usually involving brain damage, or by some unidentified cause such as chemical imbalance. Some cases of (particularly focal) dystonia are brought on after trauma, are induced by certain drugs (tardive dystonia), or may be the result of diseases of the nervous system such as [[Wilson's disease]].
-  Multifocal : if two or more noncontiguous parts are involved. The examples include dystonia of the right arm and the left leg


There appear to be higher incidents of dystonia and related movement disorders in some geographic areas (like East Texas) indicating the possibility of a contributing factor from the environment.
-  Hemidystonia : if half of the body is involved.  


===Drug Causes===
- Dystonia is classified as generalized if trunk and two or more other parts are involved.


* [[Clozapine]], [[Diphenhydramine]], [[Entacapone]], [[Fluphenazine]], [[Haloperidol]], [[Loxapine]], [[Nabilone]], [[Pergolide]], [[Perphenazine]], [[Rasagiline]], [[Rotigotine]], [[Thiothixene]], [[Thioridazine hydrochloride]], [[trientine]]
* Dystonia may be classified into eight subtypes based on the temporal aspects of the disease : manner of onset (acute versus insidious), symptoms variability (diurnal, intermittent, or action induced), and overall progression (static versus progressive). 
*Dystonia may be classified into five subtypes based on associated clinical features:   


==Symptoms==
* Dystonia is classified into four subtypes based on the etiology: Known Pathology of the nervous system, inherited, acquired or idiopathic
Symptoms vary according to the kind of dystonia involved. In most cases, dystonia tends to lead to abnormal posturing, particularly on movement. Many sufferers have continuous pain, cramping and relentless muscle spasms due to involuntary muscle movements.


Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, dropped items and a noticeable increase in dropped or chipped dishes), cramping pain with sustained use and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to [[restless leg syndrome]]. Affected persons may notice trembling in the [[Thoracic diaphragm|diaphragm]] while breathing, the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down and the constant movement to avoid pain may result in [[TMJ]]-like symptoms and the grinding and wearing down of teeth. The voice may crack frequently or become harsh triggering frequent throat clearing and swallowing can become difficult and accompanied by painful cramping.
- Nervous system pathology : if there are any structural lesion or confirmed degeneration 


Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide a definitive diagnosis by showing pulsating nerve signals being transmitted to the muscles even when they are at rest. The brain appears to signal portions of fibers within the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate, tremble and contort. When called upon to perform an intentional activity, the muscles fatigue very quickly and some portions of the muscle groups do not respond (causing weakness) while other portions over-respond or become rigid (causing micro-tears under load). The symptoms worsen significantly with use, especially in the case of focal dystonia, and a "mirror effect" is often observed in other body parts: use of the right hand may cause pain and cramping in that hand as well as in the other hand and legs that were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures can worsen symptoms.
-  Inherited: if there is autosomal dominant, autosomal recessive , X-linked recessive or mitochondrial pattern of inheritance


Direct symptoms may be accompanied by secondary effects of the continuous muscle and brain activity including disturbed sleep patterns, exhaustion, mood swings, mental stress, difficulty concentrating, blurred vision, digestive problems and short temper. People with dystonia may also become depressed and find great difficulty adapting their activities and livelihood to a progressing disability. Side affects from treatment and medications can also present challenges in normal activities.
- Acquired : if there is any history of brain injury, infection, toxic or drug consumption, vascular event, neoplasm or psychogenic cause


In some cases, symptoms may progress and then plateau for years or stop progressing entirely and the progression may be delayed by treatment or adaptive lifestyle changes while forced continued use may make symptoms progress more rapidly. In others, the symptoms may progress to total disability making some of the more risky forms of treatment worth considering.
- Idiopathic
 
==Pathophysiology==
An accurate diagnosis may be difficult because of the way the disorder manifests itself. Sufferers may be diagnosed as having similar and perhaps related disorders including Parkinson's Disease, Essential Tremor (ET), Carpel Tunnel Syndrome, TMJ, Tourette's Syndrome or other neuromuscular movement disorders.
Th exact pathogenesis of dystonia is not fully understood. However, the main mechanism has been attributed to the impaired central inhibitory circuits. It is thought that dystonia is the result of changes in synaptic pathways, reduced brain inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and decreased inhibition at the level of spinal, brain stem and especially cortex of the brain. <ref name="pmid9679773">{{cite journal |vauthors=Berardelli A, Rothwell JC, Hallett M, Thompson PD, Manfredi M, Marsden CD |title=The pathophysiology of primary dystonia |journal=Brain |volume=121 ( Pt 7) |issue= |pages=1195–212 |date=July 1998 |pmid=9679773 |doi=10.1093/brain/121.7.1195 |url=}}</ref><ref name="pmid10910346">{{cite journal |vauthors=Hallett M |title=Transcranial magnetic stimulation and the human brain |journal=Nature |volume=406 |issue=6792 |pages=147–50 |date=July 2000 |pmid=10910346 |doi=10.1038/35018000 |url=}}</ref><ref name="pmid9004351">{{cite journal |vauthors=Mink JW |title=The basal ganglia: focused selection and inhibition of competing motor programs |journal=Prog. Neurobiol. |volume=50 |issue=4 |pages=381–425 |date=November 1996 |pmid=9004351 |doi=10.1016/s0301-0082(96)00042-1 |url=}}</ref><ref name="pmid20817092">{{cite journal |vauthors=Hallett M |title=Neurophysiology of dystonia: The role of inhibition |journal=Neurobiol. Dis. |volume=42 |issue=2 |pages=177–84 |date=May 2011 |pmid=20817092 |pmc=3016461 |doi=10.1016/j.nbd.2010.08.025 |url=}}</ref><ref name="pmid11782988">{{cite journal |vauthors=Levy LM, Hallett M |title=Impaired brain GABA in focal dystonia |journal=Ann. Neurol. |volume=51 |issue=1 |pages=93–101 |date=January 2002 |pmid=11782988 |doi= |url=}}</ref> It is also thought that dystonia may be associated with microscopic changes in brain stem nuclei, loss of Purkinje cells and axonal swelling in the cerebellum, changes in basal ganglia-cerebello-thalamo-cortical pathway and cerebellar and basal ganglia structures.<ref name="pmid21220015">{{cite journal |vauthors=Standaert DG |title=Update on the pathology of dystonia |journal=Neurobiol. Dis. |volume=42 |issue=2 |pages=148–51 |date=May 2011 |pmid=21220015 |pmc=3073692 |doi=10.1016/j.nbd.2011.01.012 |url=}}</ref><ref name="pmid23195594">{{cite journal |vauthors=Prudente CN, Pardo CA, Xiao J, Hanfelt J, Hess EJ, Ledoux MS, Jinnah HA |title=Neuropathology of cervical dystonia |journal=Exp. Neurol. |volume=241 |issue= |pages=95–104 |date=March 2013 |pmid=23195594 |pmc=3570661 |doi=10.1016/j.expneurol.2012.11.019 |url=}}</ref><ref name="pmid26385708">{{cite journal |vauthors=Batla A, Sánchez MC, Erro R, Ganos C, Stamelou M, Balint B, Brugger F, Antelmi E, Bhatia KP |title=The role of cerebellum in patients with late onset cervical/segmental dystonia?--evidence from the clinic |journal=Parkinsonism Relat. Disord. |volume=21 |issue=11 |pages=1317–22 |date=November 2015 |pmid=26385708 |doi=10.1016/j.parkreldis.2015.09.013 |url=}}</ref><ref name="pmid7922471">{{cite journal |vauthors=Bhatia KP, Marsden CD |title=The behavioural and motor consequences of focal lesions of the basal ganglia in man |journal=Brain |volume=117 ( Pt 4) |issue= |pages=859–76 |date=August 1994 |pmid=7922471 |doi=10.1093/brain/117.4.859 |url=}}</ref><ref name="pmid29123945">{{cite journal |vauthors=Jinnah HA, Neychev V, Hess EJ |title=The Anatomical Basis for Dystonia: The Motor Network Model |journal=Tremor Other Hyperkinet Mov (N Y) |volume=7 |issue= |pages=506 |date=2017 |pmid=29123945 |pmc=5673689 |doi=10.7916/D8V69X3S |url=}}</ref><ref name="pmid30237473">{{cite journal |vauthors=Balint B, Mencacci NE, Valente EM, Pisani A, Rothwell J, Jankovic J, Vidailhet M, Bhatia KP |title=Dystonia |journal=Nat Rev Dis Primers |volume=4 |issue=1 |pages=25 |date=September 2018 |pmid=30237473 |doi=10.1038/s41572-018-0023-6 |url=}}</ref>
 
==Causes==
==Classification==
Common known causes of dystonia include:<ref name="pmid29503327">{{cite journal |vauthors=Batla A |title=Dystonia: A review |journal=Neurol India |volume=66 |issue=Supplement |pages=S48–S58 |date=2018 |pmid=29503327 |doi=10.4103/0028-3886.226439 |url=}}</ref><ref name="pmid11160968">{{cite journal |vauthors=Furukawa Y, Graf WD, Wong H, Shimadzu M, Kish SJ |title=Dopa-responsive dystonia simulating spastic paraplegia due to tyrosine hydroxylase (TH) gene mutations |journal=Neurology |volume=56 |issue=2 |pages=260–3 |date=January 2001 |pmid=11160968 |doi=10.1212/wnl.56.2.260 |url=}}</ref><ref name="pmid21935284">{{cite journal |vauthors=Lee JH, Ki CS, Kim DS, Cho JW, Park KP, Kim S |title=Dopa-responsive dystonia with a novel initiation codon mutation in the GCH1 gene misdiagnosed as cerebral palsy |journal=J. Korean Med. Sci. |volume=26 |issue=9 |pages=1244–6 |date=September 2011 |pmid=21935284 |pmc=3172666 |doi=10.3346/jkms.2011.26.9.1244 |url=}}</ref><ref name="pmid7922471">{{cite journal |vauthors=Bhatia KP, Marsden CD |title=The behavioural and motor consequences of focal lesions of the basal ganglia in man |journal=Brain |volume=117 ( Pt 4) |issue= |pages=859–76 |date=August 1994 |pmid=7922471 |doi=10.1093/brain/117.4.859 |url=}}</ref><ref name="pmid15098338">{{cite journal |vauthors=Sławek J, Friedman A, Bogucki A, Budrewicz S, Banach M |title=[Dopa-responsive dystonia (Segawa variant): clinical analysis of 7 cases with delayed diagnosis] |language=Polish |journal=Neurol. Neurochir. Pol. |volume=37 Suppl 5 |issue= |pages=117–26 |date=2003 |pmid=15098338 |doi= |url=}}</ref>
===Types of Dystonia===
* Generalized
* Segmental
* Intermediate
 
===The Focal Dystonias===
These are the most common dystonias and tend to be classified as follows:
 
* Cervical dystonia ([[spasmodic torticollis]]). This affects the muscles of the neck, causing the head to rotate to one side, to pull down towards the chest, or back, or a combination of these postures.
 
* [[Blepharospasm]]. This affects the muscles around the eyes. The sufferer experiences rapid blinking of the eyes or even their forced closure causing effective blindness.
 
* [[Oculogyric crisis]]. An extreme and sustained (usually) upward deviation of the eyes often with convergence causing [[diplopia]]. It is frequently associated with backwards and lateral flexion of the neck and either widely opened mouth or jaw clenching. Frequently a result of [[antiemetics]] such as the [[neuroleptics]] (e.g. [[prochlorperazine]]) or [[metoclopramide]].
 
* Oromandibular dystonia. This affects the muscles of the jaw and tongue, causes distortions of the mouth and tongue.
 
* [[Spasmodic dysphonia]]/Laryngeal dystonia. This affects the muscles of the larynx, causing the voice to sound broken or reducing it to a whisper.
 
* Focal hand dystonia (also known as writer's/musician's cramp). This affects a single muscle or small group of muscles in the hand. It interferes with activities such as writing or playing a musical instrument by causing involuntary muscular contractions. The condition is "task specific," meaning that it is generally only apparent during certain activities.
 
The combination of blepharospasmodic contractions and oromandibular dystonia is called cranial dystonia or [[Meige's syndrome]].
 
=== Segmental Dystonias===
Segmental Dystonias affect two adjoining parts of the body


* Hemidystonia. This affects an arm and a leg on one side of the body.
* Genetic mutations in TOR1A, THAP1, GCH1 and KMT2B
*Brain injury or infections including perinatal hopoxic injury, encephalitis, brain abscess or neoplasms, stroke and neurotoxic agents that affect basal ganglia (especially putamen), cerebellum, thalamus regions
*Diseases contributing to degenerative changes in central nervous system including Wilson's disease, GM1 and GM2 gangliosidosis, homocyctinuria, Lesch Nyhan syndrome and ataxia-telangiectasia
*Drugs including dopamin receptor blocking agents, amine depletors, serotonin-reuptake inhibitors, monoamine-oxidase inhibitors, calcium antagonists, benzodiazepines, general anesthetic agents, carbamazepine, phenytoin, triptans, ranitidine, cocaine or ecstasy


* Multifocal Dystonia. This affects many different parts of the body
<br />


* Generalized Dystonia. This affects most of the body, frequently involving the legs and back
<br />


==Differential diagnosis==
==Differential diagnosis==

Latest revision as of 14:49, 19 August 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: : Shadi Ghourchian, M.D.

Dystonia
ICD-10 G24.9
ICD-9 333
DiseasesDB 17912
MeSH D004421

Overview

Dystonia is a hyperkinetic movement disorder identified by involuntary sustained or intermittent contraction of a single or group of muscles that leads to repetitive movements or abnormal posture.[1] The typical dystonic movements are usually rhythmic or patterned contractions that may be accompanied by tremor.[2][3]

Historical Perspective

  • The term Dystonia was first introduced by Hermann Oppenheim, a German Neurologist , in 1911 following delineating abnormal posturing (dystonia muscularum deformans) in 4 unrelated Jewish children.[4]
  • The association between hereditary factors and dystonia was made in 1959 during reporting families with similar symptoms . [5]
  • The association between genes and dystonia was made in 1989 during introducing DYT1 or TOR1A gene as a major cause of young-onset generalized dystonia .[6][7]
  • In 1989, Ozelius .et.al were the first to discover the association between ITD1 gene ( further known as DYT1 gene ) and the development of dystonia. [7]
  • The variant "Focal Dystonia" was first introduced by Charles David Marsden, an English Neurologist, in 1976, following reporting different cases of adult-onset blepharospasm and/or oromandibular dystonia,, torticollis, spasmodic dysphonia, and writer’s cramp without any hereditary background or known cause. [8]

Classification

Dystonia may be classified into several subtypes based on age of onset, topographic distribution, temporal aspects, associated clinical features and etiology .[1][9][10]

  • Dystonia may be classified into five subtypes based on the age of onset; infancy (up to two years), childhood (3-12 years), adolescence (13-20 years), early adulthood (21-40 years) and late adulthood (>40 years)
  • Dystonia may be classified into five subtypes based on the topographic distribution : focal, segmental, multifocal, generalized or hemidystonia

- Focal : if only one body part of the body is involved. The examples include writing dystonia, cervical dystonia, blepharospasm, Oromandibular dystonia and laryngeal or lingual dystonia

- Segmental : if two or more contiguous parts are involved. The examples include bi-brachial and cranial dystonia.

- Multifocal : if two or more noncontiguous parts are involved. The examples include dystonia of the right arm and the left leg

- Hemidystonia : if half of the body is involved.

- Dystonia is classified as generalized if trunk and two or more other parts are involved.

  • Dystonia may be classified into eight subtypes based on the temporal aspects of the disease : manner of onset (acute versus insidious), symptoms variability (diurnal, intermittent, or action induced), and overall progression (static versus progressive).
  • Dystonia may be classified into five subtypes based on associated clinical features:
  • Dystonia is classified into four subtypes based on the etiology: Known Pathology of the nervous system, inherited, acquired or idiopathic

- Nervous system pathology : if there are any structural lesion or confirmed degeneration

- Inherited: if there is autosomal dominant, autosomal recessive , X-linked recessive or mitochondrial pattern of inheritance

- Acquired : if there is any history of brain injury, infection, toxic or drug consumption, vascular event, neoplasm or psychogenic cause

- Idiopathic

Pathophysiology

Th exact pathogenesis of dystonia is not fully understood. However, the main mechanism has been attributed to the impaired central inhibitory circuits. It is thought that dystonia is the result of changes in synaptic pathways, reduced brain inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and decreased inhibition at the level of spinal, brain stem and especially cortex of the brain. [11][12][13][14][15] It is also thought that dystonia may be associated with microscopic changes in brain stem nuclei, loss of Purkinje cells and axonal swelling in the cerebellum, changes in basal ganglia-cerebello-thalamo-cortical pathway and cerebellar and basal ganglia structures.[16][17][18][19][20][3]

Causes

Common known causes of dystonia include:[10][21][22][19][23]

  • Genetic mutations in TOR1A, THAP1, GCH1 and KMT2B
  • Brain injury or infections including perinatal hopoxic injury, encephalitis, brain abscess or neoplasms, stroke and neurotoxic agents that affect basal ganglia (especially putamen), cerebellum, thalamus regions
  • Diseases contributing to degenerative changes in central nervous system including Wilson's disease, GM1 and GM2 gangliosidosis, homocyctinuria, Lesch Nyhan syndrome and ataxia-telangiectasia
  • Drugs including dopamin receptor blocking agents, amine depletors, serotonin-reuptake inhibitors, monoamine-oxidase inhibitors, calcium antagonists, benzodiazepines, general anesthetic agents, carbamazepine, phenytoin, triptans, ranitidine, cocaine or ecstasy



Differential diagnosis

Dystonia must be differentiated from other diseases that cause neurological manifestations in infants.

Diseases Type of motor abnormality Clinical findings Laboratory findings and diagnostic tests Radiographic findings
Spasticity Hypotonia Ataxia Dystonia
Leigh syndrome - - + +
Niemann-Pick disease type C - - + +
  • Abnormal liver function tests
  • Fibroblast cell culture with filipin staining
Infantile Refsum disease - + + - Elevated plasma VLCFA levels --
Adrenoleukodystrophy + - - -
  • Elevated plasma VLCFA levels
  • Molecular genetic testing for mutations in the ABCD1 gene
 --
Zellweger syndrome - + - - --
Pyruvate dehydrogenase deficiency + + + -
  • Elevated lactate and pyruvate levels in blood and CSF
  • Abnormal PDH enzymatic activity in cultured fibroblasts
 --
Arginase deficiency + - - - --
Holocarboxylase synthetase deficiency - + - - Elevated levels of:
  • Beta-hydroxyisovalerate
  • Beta-methylcrotonylglycine
  • Beta-hydroxypropionate
  • Methylcitrate
  • Tiglylglycine
 --
Glutaric aciduria type 1 - - - + Elevated levels of:
Ataxia telangiectasia - - + - --
Pontocerebellar hypoplasias - + - - Genetic testing for PCH gene mutations
Metachromatic leukodystrophy - + + -
  • Deficient arylsulfatase A enzyme activity in leukocytes or cultured skin fibroblasts
 --
Pelizaeus-Merzbacher + - + -
Angelman syndrome - - + -
  • Methylation studies and chromosome microarray to detect chromosome 15 anomalies and UBE3A mutations
 --
Rett syndrome + - - +
  • Occurs almost exclusively in females
  • Normal development during first six months followed by regression and loss of milestones
  • Loss of speech capability
  • Stereotypic hand movements
  • Seizures
  • Autistic features
  • Clinical diagnosis
  • Genetic testing for MECP2 mutations
 --
Lesch-Nyhan syndrome + - - + --
Miller-Dieker lissencephaly + + - -
  • Cytogenetic testing for 17p13.3 microdeletion
 --
Dopa-responsive dystonia + - - +
  • Onset in early childhood
  • Symptoms worsen with fatigue and exercise
  • Positive response to a trial of levodopa
 --


Treatment

Treatment has been limited to minimizing the symptoms of the disorder as there is yet no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief as does reducing stress, getting plenty of rest, moderate exercise and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression or denervation. All current treatments have negative side affects and risks.

Physicians may prescribe a series of different medications on a trial-and-error basis in an effort to find a combination that is effective for a specific patient. Not all patients will respond well to the same medications. Drugs that have had positive results in some patients include anti-Parkinsons agents (Trihexyphenidyl), muscle relaxers (Valium), keppra, and beta-blockers including "off-label" uses for some blood pressure medications.

Drugs, such as anticholinergics which act as an inhibitor of the neurotransmitter acetylcholine, may provide some relief. Clonazepam, an anti-seizure medicine, is also sometimes prescribed. However, for most sufferers their effects are limited and side affects like mental confusion, sedation, mood swings and short term memory loss occur.

Botulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 3-6 months, depending on the kind of dystonia. Bo-Tox injections have the advantage of ready avalibility (the same form is used for cosmetic surgery) and the affects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking of the toxin into adjacent muscle groups causing weakness or paralysis in them. The injections have to be repeated as the effects wear off and around 15% of recipients will develop immunity to the toxin. There is a Type A and Type B toxin approved for treatment of dystonia; often those that develop resistance to Type A may be able to use Type B.[24]

Surgery, such as the denervation of selected muscles, may also provide some relief, however, the destruction of nerves in the limbs or brain is not reversable and should only be considered in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proved successful in a number of cases of severe generalised dystonia.[25]

One type of dystonia, dopa-responsive dystonia can be completely treated with regular doses of L-dopa in a form such as Sinemet (carbidopa/levodopa). Although this doesn't remove the condition, it does alleviate the symptoms most of the time.

A baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal chord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin.[26]

Physical therapy can sometimes help with focal dystonia. A structured set of exercises are tailored to help the affected area.

References

  1. ↑ 1.0 1.1 Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK (June 2013). "Phenomenology and classification of dystonia: a consensus update". Mov. Disord. 28 (7): 863–73. doi:10.1002/mds.25475. PMC 3729880. PMID 23649720.
  2. ↑ Louis ED (August 2019). "Tremor". Continuum (Minneap Minn). 25 (4): 959–975. doi:10.1212/CON.0000000000000748. PMID 31356289.
  3. ↑ 3.0 3.1 Balint B, Mencacci NE, Valente EM, Pisani A, Rothwell J, Jankovic J, Vidailhet M, Bhatia KP (September 2018). "Dystonia". Nat Rev Dis Primers. 4 (1): 25. doi:10.1038/s41572-018-0023-6. PMID 30237473.
  4. ↑ Newby RE, Thorpe DE, Kempster PA, Alty JE (2017). "A History of Dystonia: Ancient to Modern". Mov Disord Clin Pract. 4 (4): 478–485. doi:10.1002/mdc3.12493. PMC 5573933. PMID 28920067.
  5. ↑ ZEMAN W, KAELBLING R, PASAMANICK B, JENKINS JT (June 1959). "Idiopathic dystonia musculorum deformans. I. The hereditary pattern". Am. J. Hum. Genet. 11 (2 Part 1): 188–202. PMC 1931983. PMID 13661153.
  6. ↑ Ozelius LJ, Hewett JW, Page CE, Bressman SB, Kramer PL, Shalish C, de Leon D, Brin MF, Raymond D, Corey DP, Fahn S, Risch NJ, Buckler AJ, Gusella JF, Breakefield XO (September 1997). "The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein". Nat. Genet. 17 (1): 40–8. doi:10.1038/ng0997-40. PMID 9288096.
  7. ↑ 7.0 7.1 Ozelius L, Kramer PL, Moskowitz CB, Kwiatkowski DJ, Brin MF, Bressman SB, Schuback DE, Falk CT, Risch N, de Leon D (May 1989). "Human gene for torsion dystonia located on chromosome 9q32-q34". Neuron. 2 (5): 1427–34. doi:10.1016/0896-6273(89)90188-8. PMID 2576373.
  8. ↑ Marsden CD (December 1976). "Blepharospasm-oromandibular dystonia syndrome (Brueghel's syndrome). A variant of adult-onset torsion dystonia?". J. Neurol. Neurosurg. Psychiatry. 39 (12): 1204–9. doi:10.1136/jnnp.39.12.1204. PMC 492566. PMID 1011031.
  9. ↑ Jinnah HA, Albanese A (December 2014). "The New Classification System for the Dystonias: Why Was it Needed and How was it Developed?". Mov Disord Clin Pract. 1 (4): 280–284. doi:10.1002/mdc3.12100. PMC 4254809. PMID 25485288.
  10. ↑ 10.0 10.1 Batla A (2018). "Dystonia: A review". Neurol India. 66 (Supplement): S48–S58. doi:10.4103/0028-3886.226439. PMID 29503327.
  11. ↑ Berardelli A, Rothwell JC, Hallett M, Thompson PD, Manfredi M, Marsden CD (July 1998). "The pathophysiology of primary dystonia". Brain. 121 ( Pt 7): 1195–212. doi:10.1093/brain/121.7.1195. PMID 9679773.
  12. ↑ Hallett M (July 2000). "Transcranial magnetic stimulation and the human brain". Nature. 406 (6792): 147–50. doi:10.1038/35018000. PMID 10910346.
  13. ↑ Mink JW (November 1996). "The basal ganglia: focused selection and inhibition of competing motor programs". Prog. Neurobiol. 50 (4): 381–425. doi:10.1016/s0301-0082(96)00042-1. PMID 9004351.
  14. ↑ Hallett M (May 2011). "Neurophysiology of dystonia: The role of inhibition". Neurobiol. Dis. 42 (2): 177–84. doi:10.1016/j.nbd.2010.08.025. PMC 3016461. PMID 20817092.
  15. ↑ Levy LM, Hallett M (January 2002). "Impaired brain GABA in focal dystonia". Ann. Neurol. 51 (1): 93–101. PMID 11782988.
  16. ↑ Standaert DG (May 2011). "Update on the pathology of dystonia". Neurobiol. Dis. 42 (2): 148–51. doi:10.1016/j.nbd.2011.01.012. PMC 3073692. PMID 21220015.
  17. ↑ Prudente CN, Pardo CA, Xiao J, Hanfelt J, Hess EJ, Ledoux MS, Jinnah HA (March 2013). "Neuropathology of cervical dystonia". Exp. Neurol. 241: 95–104. doi:10.1016/j.expneurol.2012.11.019. PMC 3570661. PMID 23195594.
  18. ↑ Batla A, Sánchez MC, Erro R, Ganos C, Stamelou M, Balint B, Brugger F, Antelmi E, Bhatia KP (November 2015). "The role of cerebellum in patients with late onset cervical/segmental dystonia?--evidence from the clinic". Parkinsonism Relat. Disord. 21 (11): 1317–22. doi:10.1016/j.parkreldis.2015.09.013. PMID 26385708.
  19. ↑ 19.0 19.1 Bhatia KP, Marsden CD (August 1994). "The behavioural and motor consequences of focal lesions of the basal ganglia in man". Brain. 117 ( Pt 4): 859–76. doi:10.1093/brain/117.4.859. PMID 7922471.
  20. ↑ Jinnah HA, Neychev V, Hess EJ (2017). "The Anatomical Basis for Dystonia: The Motor Network Model". Tremor Other Hyperkinet Mov (N Y). 7: 506. doi:10.7916/D8V69X3S. PMC 5673689. PMID 29123945.
  21. ↑ Furukawa Y, Graf WD, Wong H, Shimadzu M, Kish SJ (January 2001). "Dopa-responsive dystonia simulating spastic paraplegia due to tyrosine hydroxylase (TH) gene mutations". Neurology. 56 (2): 260–3. doi:10.1212/wnl.56.2.260. PMID 11160968.
  22. ↑ Lee JH, Ki CS, Kim DS, Cho JW, Park KP, Kim S (September 2011). "Dopa-responsive dystonia with a novel initiation codon mutation in the GCH1 gene misdiagnosed as cerebral palsy". J. Korean Med. Sci. 26 (9): 1244–6. doi:10.3346/jkms.2011.26.9.1244. PMC 3172666. PMID 21935284.
  23. ↑ Sławek J, Friedman A, Bogucki A, Budrewicz S, Banach M (2003). "[Dopa-responsive dystonia (Segawa variant): clinical analysis of 7 cases with delayed diagnosis]". Neurol. Neurochir. Pol. (in Polish). 37 Suppl 5: 117–26. PMID 15098338.
  24. ↑ Brin MF, Lew MF, Adler CH, Comella CL, Factor SA, Jankovic J, O'Brien C, Murray JJ, Wallace JD, Willmer-Hulme A, Koller M (1999). "Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia". Neurology. 53 (7): 1431–8. PMID 10534247.
  25. ↑ Bittar RG, Yianni J, Wang S, Liu X, Nandi D, Joint C, Scott R, Bain PG, Gregory R, Stein J, Aziz TZ (2005). "Deep brain stimulation for generalised dystonia and spasmodic torticollis". J Clin Neurosci. 12 (1): 12–6. PMID 15639404.
  26. ↑ Jankovic, Dr. Joseph (2007). Parkinson's Disease & Movement Disorders (fifth edition ed.). Philadelphia, Penn.: Lippincott Williams & Wilkins. pp. pp. 349-350. ISBN 0-7817-7881-6. Unknown parameter |coauthors= ignored (help)

See also


Template:Diseases of the nervous system

ca:Distonia de:Dystonie nl:Dystonie fi:Dystonia


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