dystonia dystonia dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. the movements may resemble a tremor. dystonia is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles. dystoniaa person with medication-induced dystoniaspecialtyneurologycomplicationsphysical disabilities (contractures, torticollis), pain and fatiguecauseshereditary (dyt1); birth injury; head trauma; medication; infection; toxinsdiagnostic methodgenetic testing, electromyography, blood tests, mri or ct scantreatmentmedication, physical therapy, botulinum toxin injection, deep brain stimulationmedicationanticholinergics, dopamine agonists 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, or stress. treatment must be highly customized to the needs of the individual and may include oral medications, chemodenervation botulinum neurotoxin injections, physical therapy, or other supportive therapies, and surgical procedures such as deep brain stimulation. classification there are multiple types of dystonia, and many diseases and conditions may cause dystonia. dystonia is classified by: 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 cause (which includes changes or damage to the nervous system and inheritance). physicians use these classifications to guide diagnosis and treatment. types generalized focal segmental psychogenic acute dystonic reaction vegetative-vascular generalized dystonias for example, dystonia musculorum deformans (oppenheim, flatau-sterling syndrome): 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 main article: focal dystonia these most common dystonias are typically 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 patient 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. 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 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 symbol omim gene locus alt name dyt1 128100 tor1a 9q34 early-onset torsion dystonia dyt2 224500 hpca 1p35-p34.2 autosomal recessive primary isolated dystonia dyt3 314250 taf1 xq13 x-linked dystonia parkinsonism dyt4 128101 tubb4 19p13.12-13 autosomal dominant whispering dysphonia dyt5a 128230 gch1 14q22.1-q22.2 autosomal dominant dopamine-responsive dystonia dyt5b 191290 th 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 1p36.32-p36.13 autosomal dominant cranio-cervical/upper limb dystonia in one italian family dyt14 see dyt5 dyt15 607488 unknown 18p11 myoclonic dystonia not linked to sgce mutations dyt16 612067 prkra 2q31.3 autosomal recessive young onset dystonia parkinsonism dyt17 612406 unknown, near d20s107 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 11p14.2 autosomal dominant cranio-cervical dystonia with prominent tremor there is a group called 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 well to alcohol. other genes that have been associated with dystonia include ciz1, gnal, atp1a3, and prrt2. another report has linked thap1 and slc20a2 to dystonia. signs and symptoms symptoms vary according to the kind of dystonia involved. in most cases, dystonia tends to lead to abnormal posturing, in particular on movement. many individuals with the condition have continuous pain, cramping, and relentless muscle spasms due to involuntary muscle movements. other motor symptoms are possible including lip smacking. 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 temporomandibular joint disorder. the voice may crack frequently or become harsh, triggering frequent throat clearing. swallowing can become difficult and accompanied by painful cramping. 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. 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. 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 traumatic injury or the effects of general anesthesia during an unrelated surgery can cause the symptoms to progress rapidly. an accurate diagnosis may be difficult because of the way the disorder manifests itself. affected individuals may be diagnosed as having similar and perhaps related disorders including parkinson's disease, essential tremor, carpal tunnel syndrome, temporomandibular joint disorder, 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. risk factors for increased dystonia in patients with huntington's disease include long disease duration and use of antidopaminergic medication. causes 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. researchers suspect it is 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. secondary dystonia refers to dystonia brought on by some identified cause, such as head injury, drug side effect (e.g. tardive dystonia), or neurological disease (e.g. wilson's disease, stroke). 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. 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. chlorpromazine can also cause dystonia, which can be often misjudged as a seizure. neuroleptic drugs often cause dystonia, including oculogyric crisis. malfunction 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. 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. 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. the parkinsonism aspect of this disease may be attributable to malfunctioning na+-k+ pumps in the basal ganglia; the dystonia aspect may be attributable to malfunctioning na+-k+ pumps in the cerebellum (that act to corrupt its input to the basal ganglia) possibly in purkinje neurons. cerebellum issues causing dystonia is described by filip et al. 2013: "although dystonia has traditionally been regarded as a basal ganglia dysfunction, recent provocative evidence has emerged of cerebellar involvement in the pathophysiology of this enigmatic disease. it has been suggested that the cerebellum plays an important role in dystonia etiology, from neuroanatomical research of complex networks showing that the cerebellum is connected to a wide range of other central nervous system structures involved in movement control to animal models indicating that signs of dystonia are due to cerebellum dysfunction and completely disappear after cerebellectomy, and finally to clinical observations in secondary dystonia patients with various types of cerebellar lesions. it is proposed that dystonia is a large-scale dysfunction, involving not only cortico-basal ganglia-thalamo-cortical pathways, but the cortico-ponto-cerebello-thalamo-cortical loop as well. even in the absence of traditional "cerebellar signs" in most dystonia patients, there are more subtle indications of cerebellar dysfunction. it is clear that as long as the cerebellum's role in dystonia genesis remains unexamined, it will be difficult to significantly