Health & Medical Neurological Conditions

The Treatment of Dystonic Tremor: A Systematic Review

The Treatment of Dystonic Tremor: A Systematic Review

Abstract and Introduction

Abstract


Tremor is one of the clinical manifestations of dystonia; however, there are no specific therapeutic trials evaluating the efficacy of treatments for dystonic tremor (DT), tremor associated with dystonia or primary writing tremor (PWT). We systematically reviewed the literature available up to July 2013 on the treatment of these tremors and retrieved the data of 487 patients published in 43 papers detailing the effects of given interventions on tremor severity. Treatment outcome was highly variable, depending on the specific type of intervention and tremor distribution. No specifically designed studies were available for the treatment of tremor associated with dystonia. As for the other tremors, drug efficacy was generally disappointing and a moderate effect was only found with anticholinergics, tetrabenazine, clonazepam, β-blockers and primidone; levodopa was only efficacious on tremor due to dopa-responsive dystonia. The largest amount of data was available for botulinum toxin injections, which provided a marked improvement, particularly for the management of axial tremors (head or vocal cords). In refractory DTs, deep brain stimulation of several targets was attempted. Deep brain stimulation of globus pallidus internus, thalamus or subthalamic area led to a marked improvement of dystonic axial or appendicular tremors in most cases refractory to other treatments. Few other non-invasive treatments, for example, orthotic device in PWT, have been used with anecdotal success. In conclusion, considering the lack of good-quality studies, future randomised controlled trials are needed. In absence of evidence-based guidelines, we propose an algorithm for the treatment of DT based on currently available data.

Introduction


Different forms of tremor can be associated with dystonia. Dystonic tremor (DT) is defined as a postural/kinetic tremor occurring in the body region affected by dystonia. Generally these are focal tremors with irregular amplitudes and variable frequencies (mostly below 7 Hz). In many patients with DT antagonistic gestures lead to a reduction in the tremor amplitude. Moreover, DT usually worsens when the patient voluntarily moves the affected body part against the major direction of pulling caused by dystonia (eg, a patient with right torticollis might present more DT when he turns the head towards left). Conversely, DT may diminish and even disappear when the body part is positioned where the dystonia wants to place it. Some patients exhibit focal tremors even without overt signs of dystonia. They have been included among DTs because some of them later develop dystonia. Tremor associated with dystonia (TAD) is another type of tremor, which is present in a body region not affected by dystonia, but dystonia is present elsewhere (eg, bilateral hand tremor in a patient with cervical dystonia). This is a relatively symmetric, postural and kinetic tremor usually showing higher frequencies than typical DT. Dystonia gene-associated tremor is analogous to TAD, but it is an isolated finding in a patient with a dystonic pedigree but not personally suffering from dystonia.

The prevalence of DT or TAD is not known. Head tremor in the context of cervical dystonia is the most common form of DT, found in up to 68% of these patients in one survey. In one Brazilian cross-sectional study, it was estimated that approximately 20% of patients with dystonia have postural tremor of the upper limbs (ie, TAD). This proportion does not differ between idiopathic and acquired dystonia but seems to be more common in cervical dystonia than in other forms. DT is still a debated entity and different definitions have been proposed by clinicians. Virtually, every dystonic syndrome may present with DT.

Primary writing tremor (PWT) is a condition in which tremor predominantly or only occurs during writing. Although there is some resemblance to essential tremor (ET) (where tremor is present on action, on maintenance of a posture, and may affect hand writing), its focal task-specific nature, the lack of response to propranolol and a well-documented effect of central cholinergic drugs have suggested that PWT may be more closely related to focal dystonia than ET. Other task-specific DTs have been reported. A 5 Hz jaw tremor induced only when speaking or attempting to drink from a glass has been reported as well as tremors of the lips induced by smiling or by speaking or orolingual tremor in patients with embouchure dystonia.

The pathophysiology of these tremor conditions is largely unknown but is likely related to the basal ganglia abnormality postulated for dystonia itself. Consequently, in spite of their profound impact on patients' functioning and quality of life, there is a paucity of information about the treatment of the DT syndromes. The present systematic review is aimed at collecting the available evidence guiding clinicians in the treatment of DT, TAD and PWT.

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