Treatment of Dystonia

Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. It may involve just one body part (as with cervical dystonia), be present with one specific action (as with writer’s cramp or musician’s dystonia), or involve multiple areas of the body and be constant. Examination should focus on demonstrating the movement or posture in question to better characterize it. It may be useful to ask the patient to perform specific tasks such as writing or playing an instrument if they report this triggers the dystonic movement.

A.

Dopa-responsive dystonia (DRD) is a genetic form of dystonia that improves significantly with levodopa therapy. Unlike patients with Parkinson disease, patients with DRD do not develop dyskinesias or motor fluctuations, and the beneficial effect of levodopa can last throughout their lifetime. Typical patients with DRD are young patients with a gait disorder from lower limb dystonia that improves with sleep and that worsens as the day goes by. This phenomenon is known as diurnal fluctuation. The most common cause of DRD is GTP cyclohydrolase 1 deficiency, but deficiencies in tyrosine hydroxylase, sepiapterin reductase, and other enzymes that are involved in the biosynthesis of dopamine can cause a similar phenotype.
B.

The distribution of dystonia symptoms guides selection of initial therapy. Patients with multifocal or generalized dystonia should be offered deep brain stimulation (DBS) surgery early in the course of their disease to prevent the development of disabling contractures that can limit the benefit this therapy can provide. Patients with focal or segmental dystonia, however, may respond to oral medications or botulinum toxin injections, and should try these strategies before pursuing a surgical option.
C.

Injected botulinum toxins provide highly specific inhibition of presynaptic neurotransmitter (acetylcholine) release. This results in chemical denervation of the muscle injected, the effect lasting on average about 3 months. With repeated use, botulinum toxin can rarely lead to the formation of neutralizing antibodies that limit efficacy; when this happens, switching to a different type of botulinum toxin can help to recover clinical benefit. Botulinum toxin injections can provide significant symptom relief and spare patients from the systemic side effects of oral medications; however, they can cause problematic muscle weakness.
D.

Oral medications useful for treating dystonia include the anticholinergic trihexyphenidyl, the benzodiazepine clonazepam, and in some cases muscle relaxants such as baclofen, cyclobenzaprine, and tizanidine. Trihexyphenidyl tends to be poorly tolerated by the elderly and those with cognitive impairment, and should be avoided in these populations. It also causes dry eyes, dry mouth, constipation, urinary retention, glaucoma, forgetfulness, and confusion. Benzodiazepines, however, cause dose-related sedation and have a potential for abuse. Muscle relaxants are frequently limited by the side effect of somnolence.
E.

DBS can help patients with any form of dystonia, but is most successful in the treatment of certain genetic forms of dystonia (e.g., DYT1 due to torsinA mutations and DYT11 typically due to SGCE mutations) and focal dystonias such as cervical or task-specific dystonia. Whereas genetic testing can be helpful to predict the success of the procedure in certain populations, it is not a preoperative requirement if patients are otherwise good surgical candidates and have failed (or are not likely to respond) to other treatment modalities. Potential complications of DBS include dysarthria, gait changes, Parkinsonism, hardware-related infections, and perioperative bleeding. The most common surgical target in these patients is the globus pallidus pars interna, but there is literature to suggest the subthalamic nucleus is an acceptable alternative.