Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions occur involuntarily, resulting 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.
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. It is also classified by cause, which includes changes or damage to the nervous system and inheritance. Types include generalized dystonia, focal dystonia, psychogenic dystonia, acute dystonic reaction, and vegetative-vascular dystonia.
Following the 2013 consensus update, dystonia is now primarily classified as "isolated" when it is the sole neurological sign or "combined" when it appears alongside other features like Parkinson’s. While service-based estimates are lower, rigorous population research suggests a prevalence as high as 732 per 100,000 individuals for adult-onset focal dystonia, indicating that a significant portion of the affected population remains undiagnosed. Notably, psychiatric comorbidities like anxiety and depression are recognized as the most important determinants of a patient's quality of life, often impacting daily function more significantly than the physical severity of the involuntary motor movements.
Focal dystonias
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 or fecal incontinence. 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.
Genetic/primary
Symbol OMIM Gene Locus Alt Name DYT1
TOR1A 9q34 Early-onset torsion dystonia DYT2
HPCA 1p35-p34.2 Autosomal recessive primary isolated dystonia DYT3
TAF1 Xq13 X-linked dystonia parkinsonism DYT4
TUBB4 19p13.12-13 Autosomal dominant whispering dysphonia DYT5a
GCH1 14q22.1-q22.2 Autosomal dominant dopamine-responsive dystonia DYT5b
TH 11p15.5 Autosomal recessive dopamine-responsive dystonia DYT6
THAP1 8p11.21 Autosomal dominant dystonia with cranio-cervical predilection DYT7
unknown 18p (questionable) Autosomal dominant primary focal cervical dystonia DYT8
MR1 2q35 Paroxysmal nonkinesigenic dyskinesia DYT9
SLC2A1 1p35-p31.3 Episodic choreoathetosis/spasticity (now known to be synonymous with DYT18) DYT10
PRRT2 16p11.2-q12.1 Paroxysmal kinesigenic dyskinesia DYT11
SGCE 7q21 Myoclonic dystonia DYT12
ATP1A3 19q12-q13.2 Rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood DYT13
unknown, near D1S2667 1p36.32-p36.13 Autosomal dominant cranio-cervical/upper limb dystonia in one Italian family DYT14 See DYT5 DYT15
unknown 18p11 Myoclonic dystonia not linked to SGCE mutations DYT16
PRKRA 2q31.3 Autosomal recessive young onset dystonia parkinsonism DYT17
unknown, near D20S107 20p11.2-q13.12 Autosomal recessive dystonia in one family DYT18
SLC2A1 1p35-p31.3 Paroxysmal exercise-induced dyskinesia DYT19
probably PRRT2 16q13-q22.1 Episodic kinesigenic dyskinesia 2, probably synonymous with DYT10 DYT20
unknown 2q31 Paroxysmal nonkinesigenic dyskinesia 2 DYT21
unknown 2q14.3-q21.3 Late-onset torsion dystonia DYT24
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.
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.
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.
Malfunction of the sodium-potassium pump may be a factor in some dystonias. The - 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 - 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 - pump (ATP1A3 gene) can cause rapid onset dystonia parkinsonism. The parkinsonism aspect of this disease may be attributable to malfunctioning - pumps in the basal ganglia; the dystonia aspect may be attributable to malfunctioning - pumps in the cerebellum (that act to corrupt its input to the basal ganglia) possibly in Purkinje neurons.
Cerebellar involvement in dystonia has been described as follows:
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 improve the current standards of dystonia treatment or to provide curative treatment.
Treatment Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression, or selective denervation surgery. Almost all treatments have negative side-effects and risks. A geste antagoniste is a physical gesture or position (such as touching one's chin) that temporarily interrupts dystonia, it is also known as a sensory trick. Patients may be aware of the presence of a geste antagoniste that provides some relief. Therapy for dystonia can involve prosthetics that passively simulate the stimulation.
Physical intervention While research in the area of effectiveness of physical therapy intervention for dystonia remains weak, there is reason to believe that rehabilitation can benefit dystonia patients. Physical therapy can be utilized to manage changes in balance, mobility and overall function that occur as a result of the disorder. A variety of treatment strategies can be employed to address the unique needs of each individual. Potential treatment interventions include splinting, therapeutic exercise, manual stretching, soft tissue and joint mobilization, postural training and bracing, neuromuscular electrical stimulation, constraint-induced movement therapy, activity and environmental modification, and gait training.