Dyskinesia

What is dyskinesia?

Abnormal involuntary movements (AIMs) are known as 'dyskinesias'. There are several varieties of dyskinesia which have different clinical appearances, underlying causes and treatments, for example, tremor, chorea, dystonia and myoclonus.

Tics and stereotypies may also be considered to be related but some experts call these 'unvoluntary' because there is an element of control.¹

Cerebrovascular disease is a common cause of secondary movement disorders. Post-stroke movement disorders include Parkinsonism and a wide range of hyperkinetic movement disorders, including chorea, ballism, athetosis, dystonia, tremor, myoclonus, stereotypies, and akathisia.

Athetosis²

Athetosis causes sinuous, slow, involuntary writhing movements usually affecting the hands and feet but the arms, legs, neck and tongue may also be affected. Athetosis occurs where there has been damage to the corpus striatum (caudate and putamen) in the basal ganglia; causes include asphyxia, neonatal jaundice, Huntington's chorea, cerebrovascular disease and trauma. Management can be difficult but treatment options include medications (muscle relaxants and anticholinergics), botulinum toxin injections and use of physiotherapy, speech and language therapy and occupational therapy.

Corea³

Chorea causes continuous jerky movements in which each movement is sudden and the resulting posture is held for a few seconds. This usually affects the head, face or limbs. The focus may move from one part of the body to another at random.

Causes of chorea include the following:

Inherited

• Huntington's chorea - autosomal dominant inheritance, usually presents in middle age with chorea and dementia. Insidious onset with motor, cognitive and psychiatric abnormalities. There is no treatment.

• Benign hereditary chorea.

• Wilson's disease.

• Spinocerebellar ataxia.

• X-linked parkinsonism.

Acquired

• Drug-related: levodopa, oral contraceptives, neuroleptics, antihistamines, cocaine, amphetamine, tricyclics.

• Vasculitis and auto-immune: lupus eritematoso sistémico (SLE), antiphospholipid antibody syndrome, poliarteritis nodosa, Enfermedad de Behçet, esclerosis múltiple, CNS angiitis, and Churg-Strauss syndrome.

• Infectious: meningitis, encephalitis, enfermedad de Lyme, HIV-AIDS, new variant enfermedad de Creutzfeldt-Jakob, syphilis, subacute sclerosing panencephalitis, Lyme disease, toxoplasmosis, Sydenham's chorea (associated with acute rheumatic fever and therefore extremely rare now in the Western world), and subacute bacterial endocarditis.

• Vascular: accidente cerebrovascular (ischaemic or haemorrhagic), polycythaemia, y Moyamoya disease.

• Hormonal: pregnancy (chorea gravidarum) and oral contraceptives.

• Endocrine and metabolic: hypernatraemia and hyponatraemia, hyperglycaemia and hipoglucemia, hypomagnesaemia, hypocalcaemia, hipertiroidismo, hypoparathyroidism with hypocalcaemia and hepatic or renal failure.

• Malignancy and paraneoplastic disease: primary brain tumours, metastatic disease, and anti-Hu and anti-CRMP5 antibody formation.

• Toxins: carbon monoxide, cyanide, alcohol, methanol, solvents, thallium, mercury, and manganese.

Chorea may occur with athetosis and is then called choreoathetosis.

Dystonias⁴

A dystonia is a sustained muscle contraction, frequently causing repetitive twisting movements or abnormal postures.⁵⁶ It is a dynamic condition that often changes in severity, depending on the posture assumed and on voluntary activity of the area of the body involved. The diagnosis is clinical and there are no specific tests available; neurology referral should be made. Dystonia may lead to permanent contractions, by causing tendons to shorten.

Dystonias may be primary or secondary.⁷⁶

In primary dystonia, dystonia is the only symptom. It can be early- or adult-onset, and is inherited in a mainly autosomal dominant pattern. Two genes have been identified: DYT1 and DYT6. It is most common in the Ashkenazi Jewish population and mean age of onset is 13 years.⁶Secondary dystonia is caused by an environmental insult, such as a head injury, drug side effects (e.g., tardive dyskinesia) or neurological disease (e.g., Wilson disease). There is an intermediate group known as "dystonia plus" where symptoms and signs are broader than simply dystonia but where there is no obvious cause. ⁶

Drugs associated with secondary dystonia include amphetamines, antiepileptics, antihistamines, antipsychotics, beta-adrenergic agents, caffeine, cimetidine, cocaine, dopamine agonists, lithium, MAO inhibitors, metoclopramide, and oral contraceptives.

Treatments available for dystonia include anticholinergics (trihexyphenidyl), GABA agonists (baclofen and benzodiazepines), and dopaminergic agents , botulinum toxin and deep brain stimulation. Oral medications are generally used for generalised and segmental dystonia. Botulinum toxin is the mainstay of treatment for focal dystonia.⁶

The prognosis with primary dystonia tends to be worse as it is more likely to progress from focal to generalised dystonia. However, long-term treatment can significantly improve the outcomes.

Blefaroespasmo y writer's cramp are both focal dystonias. Blepharospasm involves recurrent spasms of eye closure. Writer's cramp is the inability to write or use any manual instrument, due to abnormal posture of the hand and arm.⁸ Botulinum toxin injection is the first-line treatment for most types of focal dystonia.⁹ Hemidystonia involves half of the body and is usually secondary to a structural lesion in the contralateral basal ganglia.

Functional dystonia resembles other forms of dystonia but has a different pathophysiology as a subtype of functional neurological disorders (FND). It can present from childhood to late adulthood and is the second most common form of functional movement disorder.¹⁰

Hemiballism ¹¹

Hemiballism or hemiballismus is a movement disorder, characterised by sudden wild flinging/throwing movements of one arm or leg. It is a subcategory of chorea, and is sometimes known as hemichorea. It is caused by damage to the pathways of the basal ganglia and dopamine overactivity, as a result of a evento cerebrovascular (a basilar artery CVA is the commonest cause in those over 65 although other CVAs are also implicated¹²and CVAs cause fewer than 50% of cases), intracranial haemorrhage, neoplasm, head trauma, nonketotic hyperglycaemic hyperosmolar syndrome, tuberculosis, toxoplasmosis, esclerosis múltiple, paraneoplastic syndromes, vasculitis, excess alcohol, or infections.¹³

The episodes can vary in intensity from mild to severe. They usually subside over a period of 3-6 months but can be treated with first and second-generation antidopaminergic drugs to target D2 receptors (e.g. risperidone, haloperidol, perphenazine, pimozide, chlorpromazine), benzodiazepines (clonazepam), anti-epileptics (topiramate), and tetrabenazine. If very severe, neurosurgery might be advised - stereotactic posteroventral pallidotomy is the procedure of choice currently although intrathecal baclofen has also been shown to be successful in post-traumatic hemiballismus.

Myoclonus¹⁴

Myoclonus is an involuntary and uncontrollable muscle contraction disorder consisting of sudden, brief, and lightning-like movements of a specific muscle, group of muscles, or even the entire body. It can be benign and temporary or persistent and debilitating.

It can be primary or secondary.

Primary causes include:

• Physiological myoclonus - occurs in everybody to a greater or lesser extent. Examples include a startle reflex, hiccups or a hypnogogic jerk on entering sleep.

• Essential myoclonus - myoclonus is the only symptom and it does not usually progress. It may be idiopathic or may have a genetic explanation (usually inherited in an autosomal dominant pattern).

• Epileptic myoclonus - myoclonus is part of, or all of, the seizure activity.

Secondary causes include:

• Drug-induced - bismuth, lithium, antibiotics (including penicillins, cephalosporins, and fluoroquinolones), narcotics (including tramadol, morphine, and fentanyl), anaesthetics (including lidocaine, midazolam, and propofol), anticonvulsants (including gabapentin, pregabalin, lamotrigine, valproic acid, and carbamazepine), antidepressants (including SSRIs and TCAs), anti-Parkinsonians (including L-dopa, bromocriptine, amantadine, selegiline), calcium channel blockers, amiodarone and chemotherapeutic agents (including cyclophosphamide, ifosfamide, and chlorambucil) have all been implicated, though many more drugs can precipitate myoclonus; in addition, renal or hepatic failure can raise the active levels of myoclonus-inducing drugs. Polypharmacy increases the likelihood of drugs acting synergistically to cause myoclonus.

• Metabolic derangements - renal failure, post-dialysis syndrome, hepatic failure, disorders of glucose metabolism (hypo- or hyper-), deficiency of biotin (including in multiple carboxylase deficiency) or vitamin E, hyperthyroidism, hyponatremia, metabolic alkalosis, and hypoxia have all been implicated in secondary myoclonus.

• Neurodegenerative diseases - myoclonus is common in many neurodegenerative diseases, including spinocerebellar degeneration, enfermedad de Wilson, progressive supranuclear palsy, Enfermedad de Huntington, enfermedad de Parkinson, multiple system atrophy, as well as many others.

• Demencia.

• Encephalitis (both autoimmune and infective).

• Paraneoplastic syndrome.

• Infections - myoclonus is common in subacute sclerosing panencephalitis (sarampión), HIV, coronavirus, syphilis, and Whipples disease.

• Post-hypoxic.

Myoclonus is difficult to treat. Antiepileptic drugs tend to be the first-line management though they can worsen symptoms for some patients. Sodium valproate, levetiracetam, clonazepam and parampanel have all been shown to have some benefit. Deep-brain stimulation may have benefits; transcranial magnetic stimulation has been suggested as a possible future treatment.

Spasmodic torticollis

Torticollis is a twisting of the head and neck caused by a shortened sternocleidomastoid muscle, tipping the head toward the shortened muscle, while rotating the chin in the opposite direction. Spasmodic torticollis is also known as wry neck or cervical dystonia. Exercises usually resolve the symptoms but, in persistent cases, botulinum toxin injections, neuromuscular electrical stimulation, extracorporeal shockwave therapy, vibration therapy, electromyographic biofeedback therapy and acupuncture have all been shown to have some benefit.¹⁵ Not all of these treatments are available on the NHS. See also the separate Neck pain (cervicalgia) and torticollis article.

Tardive dyskinesia¹⁶

Tardive dyskinesia is a movement disorder, characterised by orofacial mouthing with lip-smacking and tongue protrusion, body rocking and distal chorea. In younger patients it may also cause axial and cranial dystonia. It is caused by prolonged exposure to dopamine receptor–blocking agents, most commonly antipsychotics and, less frequently, antiemetics with central dopaminergic antagonism. The prevalence of tardive dyskinesia is around 20-25% of those on anti-psychotics. Longitudinal studies in older populations have demonstrated cumulative rates of approximately 25% after 1 year, 34% after 2 years, and 53% after 3 years of antipsychotic treatment. Older adults have significantly higher prevalence, particularly those on older anti-psychotics.

Preventing tardive dyskinesia is the best option, and clinicians should follow best practice for prescribing antipsychotic medication, including limiting the prescription for specific indications, using the minimum effective dose, and minimising the duration of therapy. Treatment breaks when appropriate may also help.

The first-line management of tardive dyskinesia is the withdrawal of antipsychotic medication if clinically feasible. However, for many patients with serious mental illness, the discontinuation of antipsychotics is not possible due to disease relapse. For these patients, switching from a first-generation to a second-generation antipsychotic, such as clozapine or quetiapine, may be effective in reducing tardive dyskinesia symptoms.

VMAT2 inhibitors (vesicular monoamine transporter 2) are integral membrane proteins that regulate monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release. There are 3 VMAT2 inhibitors: tetrabenazine, valbenazine, and deutetrabenazine. Tetrabenazine is available for use in the UK for moderate-severe tardive dyskinesia; the main adverse effects are depression and parkinsonism. Valbenazine is not available in the UK. Deutrabenazine is currently being assessed by NICE for its suitability for UK use for tardive dyskinesia.¹⁷

Tremor¹⁸

Vea también el separado Tremor article.

This is a rhythmic movement of part of the body. Essential tremor and Parkinsonian tremor are the most common forms of tremor. There are three types of pathological tremor:

• Static - occurs in a relaxed limb when fully supported at rest. Causes include Parkinson's disease, Parkinsonism, other extrapyramidal diseases, multiple sclerosis.

• Postural - occurs if a limb is static (can also remain during movement). Types include physiological tremor, exaggerated physiological tremor - for example, in thyrotoxicosis, anxiety states, alcohol abuse, drugs (for example, sympathomimetics, antidepressants, valproate, lithium), heavy metal poisoning ('hatter's shakes' from mercury). Neurological disease - for example, severe cerebellar lesions, Wilson's disease, neurosyphilis, peripheral neuropathies, benign essential (familial) tremor, task-specific tremors (for example, primary writing tremor).

• Kinetic or action tremor - occurs during voluntary active movement of an upper body part. Intention tremor is one that occurs when a tremor worsens as a goal-directed hand movement nears its intended target. Brainstem or cerebellar disease including multiple sclerosis, spinocerebellar degenerations, vascular disease, tumours.

Tremors and dystonias that are not secondary to Parkinson's disease may be effectively treated with deep brain electrical stimulation.¹⁹ Beta-blockers or primidone are also used.

The majority of people with Parkinson's disease will experience levodopa-induced dyskinesia (LID) during the course of their treatment, some after just a few years of medication.²¹ Risk factors include: female sex, cumulative L-Dopa exposure, the severity of motor and functional impairment, anxiety and non-tremor dominant PD. There are three main forms of LIDs:

• 'Peak-dose' dyskinesias are choreic movements related to high levodopa plasma concentrations.

• Diphasic on/off dyskinesias, which coincide with rising and decreasing plasma concentrations of levodopa and may include both chorea and dystonia.

• 'Off' dystonia, which is an often painful dystonic posture, appears early in the morning or at night and occurs when plasma levels of levodopa are very low.

Amantadine remains the only firmly established pharmacological option.