Dystonia – a heterogeneous clinical and treatment landscape

Dystonia is a little known syndrome which is estimated to affect at least 70,000 people in the UK. For Dystonia Awareness Week (5 May – 13 May 2018), we asked Dr. Ritesh Ramdhani, Editorial Board Member for Journal of Clinical Movement Disorders, to tell us more about dystonia.

Dystonia is a syndrome of involuntary contractions, which produce abnormal postures with predictable stereotyped movements in one or more body regions. The movements can vary in speed, have directionality in character and can be worsened with voluntary movements or triggered with specific actions such as writing, speaking, or walking. A sensory trick, or intended maneuver that lessens the severity of the movement can be a distinguishing feature. Dystonia also improves during sleep and is exacerbated by stress or anxiety.

Classifying dystonia – age and etiology matter

The classification of dystonia remains highly debatable. Historically it has been grouped into primary or secondary origins with early onset considered younger than 26 years. Primary dystonia is a clinical diagnosis devoid of an identifiable external cause found on brain imaging and laboratory investigation. Red flag symptoms such as presence of other neurological symptoms combined with dystonia or hemidystonia (dystonia affecting one side of the body) are suggestive of a secondary or acquired cause such as structural brain injury from anoxia, infection, trauma, stroke or exposure to drugs (e.g., dopamine blocking medications). Additionally, dystonia can manifest as part of the neurological spectrum of neurodegenerative diseases such as Parkinson’s disease or atypical parkinsonisms, Wilson’s disease, or Huntington’s disease.

Primary dystonia: from early to late

There are at least 12 genes associated with dystonia plus syndromes—combination of dystonia plus other movement disorders such as parkinsonism, tremor, and myoclonus.

Early onset primary dystonia usually starts in a leg or arm and spreads over time to the trunk and other limbs. It is inherited in an autosomal dominant nature with only some of those who have the mutation developing the disorder. Generalized dystonia can be very disabling for patients by limiting their mobility and independence.

The first dystonia gene (DYT1) was discovered in 1997 with an average age of 13 years that causes a generalized dystonia. Since then, there have been 28 genetically based dystonias discovered. While most of these inherited primary dystonia produce purely isolated dystonia, there are at least 12 genes associated with dystonia plus syndromes—combination of dystonia plus other movement disorders such as parkinsonism, tremor, and myoclonus.

Late onset dystonia (usually older than 26 years) are oftentimes focal—affecting certain muscles in specific body regions involved with learned or skilled tasks. Focal dystonia can be task specific, occurring with certain voluntary movements in the case of: writer’s cramp, musician’s hand or embouchure dystonia, typist dystonia, golfer’s yips, or laryngeal dystonia. Non-task specific dystonia is characterized as dystonia in the absence of voluntary movement triggers that occur at rest. Examples include torticollis or twisting of the neck due to excessive cervical muscle activation and blepharospasm, which are contractions of eyelid muscles causing excessive blinking or tight closure.

Cervical dystonia is the most prevalent focal dystonia, while writer’s cramp is most common among the task specific dystonias. Of note, late onset focal dystonia can also be seen in the leg and foot as a task specific dystonia. However, due to this atypical location of onset, consideration of it as an early sign of Parkinson ’s disease must be entertained.

Treatment approaches

Therapeutic treatments for dystonia remain tailored towards symptomatic alleviation. There have been few randomized controlled trials in dystonia. However, there is Class I evidence that trihexyphenidyl is especially efficacious for generalized and segmental dystonia in the pediatric population. Other oral medications that could provide benefit are levodopa, clonazepam, muscle relaxants (i.e., baclofen, tizandine), and tetrabenazine.

Key techniques that can augment medical treatment of dystonia include sensory training, use of braces or splints in certain circumstances, repetitive exercises of affecting limb(s), and adaptive movement training.

Botulinum toxin injections have emerged as an effective therapeutic agent for focal dystonia. It works by temporarily causing muscle paralysis at the local site of injection with its effect wearing off within three months warranting repeated injections. It has gained FDA approval for the treatment of blepharospasm and cervical dystonia and is considered the first line treatment for many of the focal dystonias.

Stereotactic surgery, specifically Deep Brain Stimulation(DBS), has been shown to provide robust and sustained benefits for DYT1 dystonia and primary generalized dystonia. Therapy is engendered by using electrodes implanted into specific regions of the brain that deliver electrical impulses from small pulse generators sitting in a patient’s chest. Other dystonias shown to benefit from DBS include severe cervical dystonia, tardive dystonia (related to exposure to dopamine blocking drugs) and myoclonus-dystonia—a primary dystonia syndrome that can present in adolescence.

The role of physical and occupational therapy in the treatment algorithm of dystonia should not be understated. Key techniques that can augment medical treatment of dystonia include sensory training, use of braces or splints in certain circumstances, repetitive exercises of affecting limb(s), and adaptive movement training.

Dystonia is a clinically and genetically complex condition requiring that keen attention is paid to understanding when and where it manifests, how it progresses, and what other symptoms are also present. A multidisciplinary approach is the underpinning for both the diagnostic and treatment paradigms, which serve to restore a level of functionality and quality of life to those afflicted.

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