Dystonia falls under the classification of movement disorders and is characterized by either sustained or intermittent contraction of a muscle or involuntary maintained contraction of agonist and antagonist muscles yielding abnormal posturing, twisting and repetitive movements, or tremulous and can be initiated or worsened by attempted movement. This leads to abnormal repetitive movements or postures which tend to have a certain pattern and may be twisting or tremulous in nature.
Dystonia is a group of movement disorders that vary in their symptoms, causes, progression, and treatments. This group of neurological conditions is generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures).
Types
Dystonia has the potential to affect any part of the body and can present at a wide range of ages.[rx]
Dystonia can be classified according to its distribution across the body:
- Focal dystonia refers to dystonia that affects only one isolated region of the body.
- Segmental dystonia refers to dystonia that affects 2 or more contiguous regions of the body.
- Multifocal dystonia refers to dystonia that affects 2 or more non-contiguous regions.
- Hemidystonia refers to dystonia which affects half of the body.
- Generalized dystonia refers to dystonia that affects the trunk along with 3 other sites.
Dystonia can have a static or progressive course of the disease. Furthermore, the variability of symptoms can be classified according to how often they occur:[rx]
- Persistent dystonia refers to dystonia that persists at the same extent throughout a day
- Action-specific dystonia refers to dystonia that only occurs when performing a certain activity
- Diurnal fluctuation refers to dystonia which fluctuates throughout the day with a circadian variation in severity
- Paroxysmal dystonia refers to sudden episodes of dystonia typically induced by a trigger
Examples of focal dystonia include blepharospasm, oromandibular dystonia, writer’s cramp, spasmodic dysphonia, and torticollis.
- focal dystonia
- blepharospasm (benign essential blepharospasm
- cervical dystonia (spasmodic torticollis
- oromandibular dystonia
- task-specific or occupational dystonia (writer cramp, musician dystonia, embouchure dystonia)
- spasmodic dysphonia
- generalized dystonia
- segmental dystonia
- DYT1-related dystonia
- DYT6-related dystonia
- DYT28-related dystonia
- dopa-responsive dystonia
- myoclonic dystonia
- X-linked dystonia-Parkinsonism
- rapid-onset dystonia-Parkinsonism
- paroxysmal dystonia choreoathetosis
- paroxysmal kinesigenic dystonia
- paroxysmal nonkinesigenic dyskinesia
- paroxysmal exertion-induced dyskinesia
- primary dystonia
- acquired dystonia
- tardive dyskinesia
- tardive dystonia
- cramp
Causes
Dystonia is a heterogeneous entity with diverse etiology and clinical presentation. One of the most useful classifications of dystonia is by etiology: primary and secondary dystonia.[rx][rx][rx]
In primary dystonia (familial or sporadic, also called idiopathic torsion dystonia), dystonia is the sole neurologic sign (with exception of the tremor) and other causes of dystonia such as acquired or neurodegenerative processes have been ruled out.
Primary dystonia is further classified into early-onset and adult-onset forms.
Primary dystonia is thought to have a greater genetic contribution, even in the absence of a family history of dystonia. The precise cause of primary dystonia is unknown. There is some genetic susceptibility in conjunction with environmental factors.
Early-onset primary dystonia typically initially affects an extremity and then spreads, in many occurrences becoming generalized. DYT 1 and DYT 6 are the two genes that are responsible for early onset of primary dystonia.
As far as adult-onset dystonia usually involves either cervical, cranial, or brachial muscles, or remains focal or segmental. Worth mentioning that cervical dystonia is the most common form and at the same time is more common than early-onset primary dystonia.
Secondary dystonias are caused by the environmental insult and are brought in by some identified causes, such as head injury, drug side effects (e.g., tardive dyskinesia) or neurological disease (e.g., Wilson disease).
An intermediary category is termed ‘dystonia plus syndromes,’ and consists of disorders in which there is no acquired etiology or neurodegeneration, but in which there are neurologic symptoms other than dystonia. This category includes dopa-responsive dystonia (DRD/DYT5), myoclonus dystonia (MD/DYT11) and rapid-onset dystonia-parkinsonism (RDP/DYT12).
Medications associated with dystonia:
- Antipsychotics
- Metoclopramide
- Antiepileptics
- Dopamine agonists
- MAO inhibitors
- Amphetamines, cocaine
- Caffeine
- Antihistamines
- Beta-adrenergic agents
- Lithium
- Oral contraceptives
- Cimetidine
The principal cause of dystonia has been thought to be dysfunction of the basal ganglia, which emerged from the concept of the basal ganglia as the brain region responsible for integrating motor control. Also, secondary dystonia is often due to lesions of the basal ganglia, specifically the putamen or globus pallidus.
However, the absence of neurodegeneration in primary dystonia, as well as observations that lesions of brain regions other than the basal ganglia can cause secondary dystonia, has guided to the idea that dystonia is a neuro-functional disorder, i.e. a disorder characterized by abnormal connectivity that may occur in a structurally normal-appearing brain.
Dystonia is considered to be a motor system disorder rather than a disease of a particular motor structure. Studies have provided evidence of dysfunction in almost every region of the central nervous system involved in motor control and sensorimotor integration, including cortex, brainstem, cerebellum, and spinal cord.
Dystonia is worsened by stress, fatigue, anxiety, or lack of sleep.
Diagnosis
It is important to distinguish between idiopathic and symptomatic dystonia (due to another disease process).
Idiopathic dystonia may be inherited, often has an insidious onset, and may come into sight initially during the execution of a specific, repetitive, well-learned action. In contrast, symptomatic (secondary) dystonia occurs after a stroke, tumor, infection, hypoxia-ischemia, encephalitis, neurodegenerative disease (e.g., hepato-lenticular degeneration or Wilson’s disease), and toxins.
Neurophysiological studies demonstrate a variety of changes consistent with abnormalities in inhibitory control, sensorimotor integration, and brain plasticity. The EMG in the dystonia shows co-contraction of agonist and antagonist muscles with prolonged bursts and overflow to the muscles.
The clinical examination in dystonia may exhibit involuntary writhing/twisting movements precipitated by specific voluntary movements, such as walking or writing. Focal task-specific limb dystonia can begin as painful hand cramping or involuntary wrist/finger spasms when writing, while torticollis presents as an uncontrollable head-turning when driving or watching television.
- Oro-mandibular dystonia can manifest as night-time bruxism (jaw spasms producing forceful jaw closure) and may follow dental procedures, oro-mandibular-facial trauma, or temporomandibular joint dysfunction.
- Spasmodic dysphonia can commence as a strained voice. Despite the name dystonia, the tone of affected extremities at rest is often normal at the onset. Deep tendon reflexes may also be normal.
- A tremor in a patient with dystonia (dystonic tremor) is sometimes distinguished from other tremor types by the presence of a null point (e.g., a neutral position at which tremor attenuates).
- In cervical dystonia, head tremor sometimes decreases with the head held in a specific position, and displacement from that position, such as turning the head to one side, may worsen it.
- Dystonic tremor may be nonuniform in amplitude and frequency, can be linked with myoclonus (jerk-like movements), and disappears in sleep. Dystonia may cause hypertrophy and pain in affected muscles such as the sternocleidomastoid in spasmodic torticollis.
In its early stages, it may be viewed as an annoying mannerism or hysteria, and only later due to unremitted postural abnormality, lack of the typical psychological characteristics of hysteria, and becoming an apparent feature of the illness, the correct diagnosis is made.
Dystonic movements tend to be exacerbated by fatigue, stress, and emotional states; they tend to be suppressed with relaxation, hypnosis, and sleep.
A characteristic and almost unique feature of dystonic movements is that they can abate by tactile or proprioceptive sensory tricks (geste antagoniste). For example, patients with cervical dystonia (torticollis) often place a hand on the chin or side of the face to diminish nuchal contractions, and oro-lingual dystonia is often relieved by touching the lips or placing an object in the mouth. Lying down may reduce truncal dystonia; walking backward or running may reduce leg dystonia.
Some dystonic movements last several seconds/minutes but others can last for weeks/months. This can lead to permanent bone deformity, contractures and impairment in function.
Imaging
Evaluation and work-up are based on the type of dystonia where clinical presentation remains the cornerstone of evaluation.[rx][rx][rx]
In primary dystonia, clinical evaluation and genetic testing (DYT1 and DYT6) can guide to the correct diagnosis. The gene at the DYT1 locus has been determined to serve as a cause of the dystonia described by Oppenheim. In a vast majority of patients with DYT1 dystonia, symptoms begin in childhood or adolescence, and the mean age of onset is 13 years. Oppenheim dystonia affects most ethnic groups but is considerably wider in the Ashkenazi Jewish population.
Dystonia plus syndrome encompasses nondegenerative disorders in which parkinsonism dopa-responsive dystonia (DRD) and rapid-onset dystonia-parkinsonism (RDP) or Myoclonus-Dystonia (M-D) co-occur with dystonia. Dopa-responsive dystonia predominantly starts between ages six and 16 but can arise at any age. When it begins in infants has the appearance of cerebral palsy. When it occurs in adults, it often manifests as pure parkinsonism, responding to levodopa with a benign course. Dopa-responsive dystonia affects girls more often than boys, has a worldwide distribution, and is not known to have a higher specific prevalence in any particular ethnic group. Mutations in the gene for GTP cyclohydrolase 1(GCH1) located at 14q22.1 are accountable for the greater number of dopa-responsive dystonia. Dopa-responsive dystonia can be suspected if a young patient with dystonia responds greatly to a low dose of anticholinergics. On the other hand, the most effective agent is levodopa.
Clues suggestive of secondary dystonia emerge from the definition of the disorder that develops as a result of environmental factors that affect the brain, especially the basal ganglia. Spinal cord injury and peripheral injury can serve as a cause of dystonia as well. So the history of possible head trauma, encephalitis, toxin and drug exposure, perinatal anoxia, also the presence of neurologic abnormality independently from dystonia, for example, Parkinsonism, dementia, seizures, ocular symptoms, ataxia, pain, numbness, tingling, or weakness. সহজ বাংলা: স্নায়ুর ক্ষতি/সমস্যা।" data-rx-term="neuropathy" data-rx-definition="Neuropathy means nerve damage or irritation causing pain, numbness, tingling, or weakness. সহজ বাংলা: স্নায়ুর ক্ষতি/সমস্যা।">neuropathy, spasticity with abnormal brain imaging will guide to the diagnosis of secondary dystonia.
Because many of the neurodegenerations are a result of genetic abnormalities, the term Heredodegenerative dystonia is applied to this category. Dystonia in Neurodegeneration is a prominent feature. MRI of the brain, ceruloplasmin level, slit-lamp exam, lysosomal screen, peripheral blood smear, nerve conduction studies, creatine kinase (CK) level, vitamin E are a few worth mentioning investigations.
Imaging studies may identify central lesions, hemorrhage or hypoxic damage.
Treatment
The medications that are most potent in the treatment of dystonia include anticholinergics (trihexyphenidyl), GABA agonists (baclofen and benzodiazepines), and dopaminergic agents. The mechanism of action of these drugs is due to modifications in dopaminergic and cholinergic neurotransmission and reduced GABA-mediated inhibition in the dystonic central nervous system (CNS).
- Trihexyphenidyl is the first-line medication for the management of childhood-onset primary generalized or segmental dystonia. The toxin blocks the vesicular release of acetylcholine into the neuromuscular junction, generating temporary local chemo-denervation and muscle weakness, lessening the excessive activity of the affected dystonic muscles.
- Botulinum toxin is the first-line treatment for cervical dystonia and blepharospasm and is also habitually used to treat laryngeal dystonia (spasmodic dysphonia), and focal limb dystonia. Apart from its direct peripheral effect of weakening affected muscles, botulinum toxin injections may also reduce afferent feedback from affected muscles, possibly normalizing the abnormal plastic changes in the CNS.
- Diphenhydramine is used for its anticholinergic effect and central nervous system (CNS) penetration. Intravenous administration is preferred to intramuscular administration due to its faster onset. Typical dosing for diphenhydramine is 50 mg intravenous (IV) in adults and 1 mg/kg up to 50mg IV in pediatric patients. Once the acute dystonic reaction is treated and symptoms improve, diphenhydramine should be administered via the oral route every 6 hours for 1 to 2 days to prevent recurrence of symptoms.
- Benztropine is another anticholinergic medication with significant CNS penetration. Use, however, may be limited due to availability in the emergent setting. IV and intramuscular (IM) routes are of a similar time to onset of effect. Typical dosing of benztropine is a single dose of 1 to 2 mg IV followed by 1 to 2 mg by mouth twice a day for up to 7 days to prevent a recurrence. Benztropine use in pediatric patients for acute dystonia is considered off-label.
- Second-line therapy with IV benzodiazepines may be considered for patients that fail to respond completely to anticholinergic therapy. IV or IM lorazepam at 0.05 to 0.10 mg/kg or IV diazepam at 0.1 mg/kg may be considered.
- A muscle relaxant known as baclofen, which may help periodically to reduce muscle spasms, may be prescribed and delivered by means of an implantable pump that releases the drug directly into the area around the spinal cord. Baclofen can stimulate the body’s ability to process the neurotransmitter GABA.
Other medications target chemicals in your brain (neurotransmitters) that affect muscle movement. The options include:
- Carbidopa-levodopa (Duopa, Rytary, others). This medication can increase levels of the neurotransmitter dopamine. This drug may also be used as a trial to help diagnose certain types of dystonia. There is no standard treatment for rapid-onset dystonia-parkinsonism (RDP), although levodopa/carbidopa medications and dopamine agonists (drugs that stimulate dopamine receptors in the absence of dopamine) may provide mild improvement for some affected individuals.
- Tetrabenazine (Xenazine) and deutetrabenazine (Austedo). These two medications block dopamine. Side effects can include sedation, nervousness, depression, or insomnia.
- Diazepam (Valium, Diastat, others), clonazepam (Klonopin) and baclofen (Lioresal, Gablofen, others). These medications reduce neurotransmission and might help some forms of dystonia. They may cause side effects, such as drowsiness.
Patients who experience respiratory symptoms or required supportive oxygen should be observed for 12 to 24 hours following resolution of symptoms to monitor for recurrence.
The drug-induced tardive dyskinesia requires specialized treatment.
Historically, dystonia patients were treated surgically with pallidotomy or thalamotomy. These lesional surgeries provided significant benefit to dystonia symptoms in some cases, but also frequently caused permanent, debilitating side effects, particularly dysarthria. Lesional surgeries have now been succeeded by deep brain stimulation (DBS), which resembles a lesional effect but is reversible and adjustable. In the past two decades, DBS has come to the leading edge as an important treatment option for patients with severe medically refractory primary dystonia. The currently established target in DBS for dystonia is the globus pallidus (GPI). DBS is thought to produce its clinical effect by inducing functional changes within the abnormal motor networks in dystonia and ultimately normalizing pathologically overactive motor activation responses. In opposition to the rapid effect of DBS that occurs in Parkinson’s disease or essential tremor, the effect of DBS is typically delayed in dystonia, often taking weeks to months, confirming the concept of dystonia as a disorder of sensorimotor connectivity that compels time to restyle and adapt to changes along the entire motor circuit after DBS.
There is a distinct variability in response to DBS among dystonia patients, with some patients showing dramatic improvement whereas others benefit only modestly or not at all, and no single factor, including DYT1 gene status, has been found to be undeniably predictive of response. The question of which patient with primary dystonia will have the best response to DBS remains open and requires further investigation.
Therapy
Your health care provider might suggest:
- Physical therapy or occupational therapy or both to help ease symptoms and improve function. Physical therapy may help individuals with focal or segmental dystonic movements. Speech therapists can offer communication aids and provide techniques to relax the jaw.
- Speech therapy if dystonia affects your voice
- Stretching or massage to ease muscle pain
Surgery
If your symptoms are severe, surgery might help. There are a few types of surgery to treat dystonia:
- Deep brain stimulation. Electrodes are surgically implanted into a specific part of your brain and connected to a generator implanted in your chest. The generator sends electrical pulses to your brain that might help control your muscle contractions. The settings on the generator can be adjusted to treat your specific condition.
- Selective denervation surgery. This procedure involves cutting the nerves that control muscle spasms. It might be an option when other treatments for cervical dystonia haven’t worked.
References
