Dystonia

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Dystonias
Classification and external resources
Dystonia2010.JPG
A person with medication-induced dystonia.
ICD-10 G24.9
ICD-9 333
OMIM 128100 224500 314250 128101 128230 602629 602124 118800 601042 128200 159900 128235 607671 607488 612067 612406 612126 611031 611147
DiseasesDB 17912
MeSH D004421
GeneReviews

Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.[1] The movements may resemble a tremor. Dystonia is often initiated or worsened by voluntary movements, and symptoms may “overflow” into adjacent muscles.[2]

The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to pharmaceutical drugs, particularly neuroleptics.[1] Treatment must be highly customized to the needs of the individual and may include oral medications, botulinum neurotoxin injections, physical therapy and/or other supportive therapies, and/or surgical procedures such as deep brain stimulation.

History[edit]

The term "dystonia" was first used in 1911, by Hermann Oppenheim.[3]

Classification[edit]

There are multiple types of dystonia, and numerous diseases and conditions may cause dystonia.

Dystonia is classified by: 1. Clinical characteristics such as age of onset, body distribution, nature of the symptoms, and associated features such as additional movement disorders or neurological symptoms, and 2. Cause (which includes changes or damage to the nervous system and inheritance).[4] Physicians use these classifications to guide diagnosis and treatment.

Types of dystonia[edit]

Generalized dystonias[edit]

  • Normal birth history and milestones
  • Autosomal dominant
  • Childhood onset
  • Starts in lower limbs and spreads upwards
  • Also known as torsion dystonia or idiopathic torsion dystonia (old terminology "dystonia musculorum deformans")

Focal dystonias[edit]

Main article: Focal dystonia

These are the most common dystonias and tend to be classified as follows:

Name Location Description
Anismus muscles of the rectum Causes painful defecation, constipation; may be complicated by encopresis.
Cervical dystonia (spasmodic torticollis) muscles of the neck Causes the head to rotate to one side, to pull down towards the chest, or back, or a combination of these postures.
Blepharospasm muscles around the eyes The sufferer experiences rapid blinking of the eyes or even their forced closure causing functional blindness.
Oculogyric crisis muscles of eyes and head An extreme and sustained (usually) upward deviation of the eyes often with convergence causing diplopia(double vision). It is frequently associated with backward 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. Also can be caused by Chlorpromazine
Oromandibular dystonia muscles of the jaw and muscles of tongue Causes distortions of the mouth and tongue.
Spasmodic dysphonia/Laryngeal dystonia muscles of larynx Causes the voice to sound broken, become hoarse, sometimes reducing it to a whisper.
Focal hand dystonia (also known as musician's or writer's cramp). 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 sometimes "task-specific," meaning that it is generally apparent during only certain activities. Focal hand dystonia is neurological in origin, and is not due to normal fatigue. The loss of precise muscle control and continuous unintentional movement results in painful cramping and abnormal positioning that makes continued use of the affected body parts impossible.

The combination of blepharospasmodic contractions and oromandibular dystonia is called cranial dystonia or Meige's syndrome.

Segmental dystonias[edit]

Segmental dystonias affect two adjoining parts of the body:

  • Hemidystonia affects an arm and foot on one side of the body.
  • Multifocal dystonia affects many different parts of the body.
  • Generalized dystonia affects most of the body, frequently involving the legs and back.

Genetic / primary[edit]

Symbol OMIM Gene Locus Alt Name
DYT1 128100 TOR1A 9q34 Early-onset torsion dystonia
DYT2 224500 unknown unknown Autosomal recessive torsion dystonia
DYT3 314250 TAF1 Xq13 X-linked dystonia-parkinsonism
DYT4 128101 TUBB4[6] 19p13.12-13 Autosomal dominant whispering dysphonia
DYT5a 128230 GCH1 14q22.1-q22.2 Autosomal dominant dopamine-responsive dystonia
DYT5b 191290 TH[disambiguation needed] 11p15.5 Autosomal recessive dopamine-responsive dystonia
DYT6 602629 THAP1 8p11.21 Autosomal dominant dystonia with cranio-cervical predilection
DYT7 602124 unknown 18p (questionable) Autosomal dominant primary focal cervical dystonia
DYT8 118800 MR1 2q35 Paroxysmal nonkinesigenic dyskinesia
DYT9 601042 SLC2A1 1p35-p31.3 Episodic choreoathetosis/spasticity (now known to be synonymous with DYT18)
DYT10 128200 PRRT2 16p11.2-q12.1 Paroxysmal kinesigenic dyskinesia
DYT11 159900 SGCE 7q21 Myoclonic dystonia
DYT12 128235 ATP1A3 19q12-q13.2 Rapid onset dystonia parkinsonism and alternating hemiplegia of childhood
DYT13 607671 unknown, near D1S2667[7] 1p36.32-p36.13 Autosomal dominant cranio-cervical/upper limb dystonia in one Italian family
DYT14 See DYT5
DYT15 607488 unknown 18p11[8] Myoclonic dystonia not linked to SGCE mutations
DYT16 612067 PRKRA 2q31.3 Autosomal recessive young onset dystonia parkinsonism
DYT17 612406 unknown, near D20S107[9] 20p11.2-q13.12 Autosomal recessive dystonia in one family
DYT18 612126 SLC2A1 1p35-p31.3 Paroxysmal exercise-induced dyskinesia
DYT19 611031 probably PRRT2 16q13-q22.1 Episodic kinesigenic dyskinesia 2, probably synonymous with DYT10
DYT20 611147 unknown 2q31 Paroxysmal nonkinesigenic dyskinesia 2
DYT21 614588 unknown 2q14.3-q21.3 Late-onset torsion dystonia
DYT24 610110 ANO3[10] 11p14.2 Autosomal dominant cranio-cervical dystonia with prominent tremor

There is a group called myoclonus dystonia or myoclonic dystonia, where some cases are hereditary and have been associated with a missense mutation in the dopamine-D2 receptor. Some of these cases have responded remarkably to alcohol.[11][12]

Other genes that have been associated with dystonia include CIZ1, GNAL, ATP1A3 and PRRT2.[13] Another report has linked THAP1 and SLC20A2 to dystonia.[14]

Signs and symptoms[edit]

Hyperglycemia-induced involuntary movements, which, in this case, did not consist of typical hemiballismus but rather of hemichorea (dance-like movements of one side of the body; initial movements of the right arm in the video) and bilateral dystonia (slow muscle contraction in legs, chest, and right arm) in a 62-year-old Japanese woman with type 1 diabetes.

Symptoms vary according to the kind of dystonia involved. In most cases, dystonia tends to lead to abnormal posturing, in particular on movement. Many sufferers have continuous pain, cramping, and relentless muscle spasms due to involuntary muscle movements. Other motor symptoms are possible including lip smacking.[15]

Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, and dropped items), 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 diaphragm while breathing, or 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 the grinding and wearing down of teeth, or symptoms similar to TMD. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping.[citation needed]

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.[citation needed]

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-effects from treatment and medications can also present challenges in normal activities.[citation needed]

In some cases, symptoms may progress and then plateau for years, or stop progressing entirely. 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. In some cases with patients who already have dystonia, a subsequent tramatic injury or the effects of general anethesia during an unrelated surgery can cause the symptoms to progress rapidly.[citation needed]

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, carpal tunnel syndrome, TMD, Tourette's syndrome, conversion disorder or other neuromuscular movement disorders. It has been found that the prevalence of dystonia is high in individuals with Huntington's disease, where the most common clinical presentations are internal shoulder rotation, sustained fist clenching, knee flexion, and foot inversion.[16] Risk factors for increased dystonia in patients with Huntington's disease include long disease duration and use of antidopaminergic medication.[16]

Causes[edit]

Primary dystonia is suspected when the dystonia is the only sign and there is no identifiable cause or structural abnormality in the central nervous system. It 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.[citation needed]

Secondary dystonia refers to dystonia brought on by some identified cause, such as head injury[citation needed], drug side effect (e.g. tardive dystonia), or neurological disease (e.g. Wilson's disease).

Meningitis and encephalitis caused by viral, bacterial, and fungal infections of the brain have been associated with dystonia. The main mechanism is inflammation of the blood vessels, causing restriction of blood flow to the basal ganglia. Other mechanisms include direct nerve injury by the organism or a toxin, or autoimmune mechanisms.[17]

Environmental and task-related factors are suspected to trigger the development of focal dystonias because they appear disproportionately in individuals who perform high precision hand movements such as musicians, engineers, architects, and artists.[citation needed] Chlorpromazine can also cause dystonia, which can be often misjudged as a seizure.[citation needed] Neuroleptic drugs often cause dystonia, including oculogyric crisis.[citation needed]

Misfunction of the sodium-potassium pump may be a factor in some dystonias. The Na+
-K+
pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons.[18] This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the cerebellum and the brain. Indeed, an ouabain block of Na+
-K+
pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia.[19] Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations. A mutation in the Na+
-K+
pump (ATP1A3 gene) can cause rapid onset dystonia parkinsonism.[20] The parkinsonism aspect of this disease is thought to be attributable to malfunctioning Na+
-K+
pumps in the basal ganglia; the dystonia aspect is thought to be attributable to malfunctioning Na+
-K+
pumps in the cerebellum (that act to corrupt its input to the basal ganglia) - possibly in Purkinje neurons.[18]

Treatment[edit]

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.[citation needed] Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression, or denervation.[citation needed] All current treatments have negative side-effects and risks.

Physical intervention[edit]

While research in the area of effectiveness of physical therapy intervention for dystonia remains weak,[21] there is reason to believe that rehabilitation will benefit patients with dystonia.[22] Physical therapy can be utilized to manage changes in balance, mobility and overall function that occur as a result of the disorder.[23] A variety of treatment strategies can be employed to address the unique needs of each individual. Potential treatment interventions include splinting,[24] therapeutic exercise, manual stretching, soft tissue and joint mobilization, postural training and bracing,[22] neuromuscular electrical stimulation, constraint-induced movement therapy, activity and environmental modification, and gait training.[23]

A patient with dystonia may have significant challenges in activities of daily living (ADL), an area especially suited for treatment by occupational therapy (OT). An occupational therapist (OT) may perform needed upper extremity splinting, provide movement inhibitory techniques, train fine motor coordination, provide an assistive device, or teach alternative methods of activity performance to achieve a patient's goals for bathing, dressing, toileting, and other valued activities.

Recent research has investigated further into the role of physiotherapy in the treatment of dystonia. A recent study showed that reducing psychological stress, in conjunction with exercise, is beneficial for reducing truncal dystonia in patients with Parkinson’s Disease.[25] Another study emphasized progressive relaxation, isometric muscle endurance, dynamic strength, coordination, balance, and body perception, seeing significant improvements to patients’ quality of life after 4 weeks.[26]

Some focal dystonias have been proven treatable through movement retraining in the Taubman approach, particularly in the case of musicians. However other focal dystonias may not respond and may even be made worse by this treatment.

Due to the rare and variable nature of dystonia, research investigating the effectiveness of these treatments is limited. There is no gold standard for physiotherapy rehabilitation.[25] To date, focal cervical dystonia has received the most research attention;[23] however, study designs are poorly controlled and limited to small sample sizes.[21]

Medication[edit]

Different medications are tried in an effort to find a combination that is effective for a specific person. Not all people will respond well to the same medications. Medications that have had positive results in some include: diphenhydramine, benzatropine, anti-Parkinsons agents (such as trihexyphenidyl and bromocriptine), and muscle relaxants (such as diazepam).

Anticholinergics

Medications such as anticholinergics (benztropine), which act as inhibitors of the neurotransmitter acetylcholine, may provide some relief. In the case of an acute dystonic reaction, diphenhydramine is sometimes used (though this drug is well known as an antihistamine, in this context it is being used primarily for its anticholinergic role).[citation needed]. See also Procyclidine.

Baclofen

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 cord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin.[27]

Botulin toxin injection

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. Botox injections have the advantage of ready availability (the same form is used for cosmetic surgery) and the effects 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 a Type B toxin approved for treatment of dystonia; often, those that develop resistance to Type A may be able to use Type B.[28]

Muscle relaxants

Clonazepam, an anti-seizure medicine, is also sometimes prescribed. However, for most, their effects are limited and side-effects like mental confusion, sedation, mood swings, and short-term memory loss occur.[citation needed]

Parkinsonian drugs

Dopamine agonists: One type of dystonia, dopamine-responsive dystonia, can be completely treated with regular doses of L-DOPA in a form such as Sinemet (carbidopa/levodopa). Although this does not remove the condition, it does alleviate the symptoms most of the time. (In contrast, dopamine antagonists can sometimes cause dystonia.)[citation needed]

Surgery[edit]

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 reversible and should be considered only in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proven successful in a number of cases of severe generalised dystonia.[29] DBS as treatment for medication-refractory dystonia, on the other hand, may increase the risk of suicide in patients. However, reference data of patients without DBS therapy are lacking.[30]

See also[edit]

References[edit]

  1. ^ a b Dystonia fact sheet: National Institute of Neurological Disorders and Stroke
  2. ^ http://www.ncbi.nlm.nih.gov/pubmed/24978640 "Dystonia: an update on phenomenology, classification, pathogenesis and treatment" 2014
  3. ^ Tarsy, Daniel; Simon, David K. (24 Aug 2006). "Dystonia". New England Journal of Medicine 355 (8): 818–829. doi:10.1056/NEJMra055549. PMID 16928997. 
  4. ^ http://www.ncbi.nlm.nih.gov/pubmed/24978640 "Dystonia: an update on phenomenology, classification, pathogenesis and treatment"
  5. ^ http://www.emsvillage.com/articles/article.cfm?id=1137
  6. ^ Hersheson, Joshua; Mencacci, Niccolo E.; Davis, Mary; MacDonald, Nicola; Trabzuni, Daniah; Ryten, Mina; Pittman, Alan; Paudel, Reema; Kara, Eleanna; Fawcett, Katherine; Plagnol, Vincent; Bhatia, Kailash P.; Medlar, Alan J.; Stanescu, Horia C.; Hardy, John; Kleta, Robert; Wood, Nicholas W.; Houlden, Henry (2013). "Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia". Annals of Neurology 73 (4): 546–553. doi:10.1002/ana.23832. PMC 3698699. PMID 23424103. 
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  26. ^ Zetterberg, Lena; Halvorsen, Kjartan; Färnstrand, Catarina; Aquilonius, Sten-Magnus; Lindmark, Birgitta (2008). "Physiotherapy in cervical dystonia: Six experimental single-case studies". Physiotherapy Theory and Practice 24 (4): 275–90. doi:10.1080/09593980701884816. PMID 18574753. 
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External links[edit]