16 Deep Brain Stimulation for Rare Movement Disorders
Abstract
Since it was FDA approved for Essential Tremor (ET), deep brain stimulation (DBS) has been used to treat many other conditions. This chapter reviews off-label and exempted DBS treatment for the hyperkinetic movement disorders of myoclonus, chorea and Tourette’s syndrome.
16.1 Introduction
Hyperkinetic movement disorders comprise a heterogeneous group of challenging disorders, either because of lack of medical efficacy or from medication side effects. As such, DBS has been explored as an alternative therapy. This chapter will cover DBS for myoclonus, chorea, and Tourette’s syndrome (TS).
16.2 Myoclonus
Myoclonus is defined as a brief, jerking muscle movement. It can be caused by metabolic, post anoxic or degenerative injury. Its medical treatment includes anticholinergics, anti-epileptics and benzodiazepines.
Most of the treatment by DBS in myoclonus has been for myoclonus dystonia, which is a rare, autosomal dominant condition, also known as DYT 11. It is caused by mutations in the epsilon sarcoglycan gene (chromosome 7q). Symptoms of action myoclonus often present in childhood or adolescence; dystonia, either cervical or in the limbs, and psychiatric symptoms, such as obsessive-compulsive disorder (OCD), complete the common phenotype. The myoclonic symptoms be sensitive to alcohol, which along with ET may lead to alcoholism. Pharmacologic agents used include benzodiazepines, anticholinergic, serotonergic and dopaminergic agents. Use of these medications is often limited by their partial benefit and side effects at higher doses.
Given these limitations, DBS has been explored to manage both the myoclonus and dystonia seen in this disorder. Early case studies focused on the ventro-intermedius nucleus of the thalamus (Vim) and Globus pallidus interna (GPi) as stimulation targets based on experience with ET and dystonia treatment, respectively. The literature suggests that GPi may be a preferred target in the treatment of both myoclonus and dystonia. 1
In the largest case series, published by Gruber et al., ten patients with myoclonus-dystonia were implanted. 2 Eight patients had both GPi and VIM stimulators, one had bilateral Vim electrodes, and one had both GPi and Vim electrodes inserted, but only GPi electrodes connected. Myoclonus symptoms improved when measured on the Unified Myoclonus Rating Scale (UMRS) score. Dystonia did also when assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and by measures of quality of life. The UMRS score and BFMDRS disability score improved in all patients, regardless of targets, by 61–66% and 45–48%, respectively on initial evaluation and at 128 months.
Similar findings were supported in a review of 40 cases. 3 Myoclonic symptom improvement was significantly greater than that measured with dystonia. UMRS improved by at least 50% in 94% of cases and BFMDRS improved by at least 50% in 72% of cases. 3
Youth and a shorter symptom duration before intervention are favorable signs. 3 Single case reports for the treatment of myoclonus of other causes also suggest a favorable outcome with DBS intervention. 4 , 5 There are fewer reports on the effects of DBS on secondary myoclonus, as may arise from anoxia. In summary, Vim DBS may provide greater improvement in myoclonus, but GPi may be slightly superior overall. It leads to less dysarthria and more effective treatment of dystonia.
16.2.1 Chorea
The term chorea describes the unpredictable, dance-like movements that flow from one body part to another. Neurodegenerative, rheumatogical, and developmental disorders may lead to chorea, as can hyperglycemia, pregnancy, and encephalopathy. Huntington’s Disease (HD) is one of the most commonly investigated for possible DBS therapy.
HD is an autosomal dominant neurodegenerative disorder, that derives from an expanded trinucleotide repeat CAG on chromosome 4, encoding for the protein huntingtin. While the abnormal protein is expressed throughout the body, medium spiny neurons in the striatum are affected early and significantly. These changes disrupt the balance between the indirect and direct pathways of movement processing in the basal ganglia causing motor, psychiatric, and cognitive manifestations. The motor signs are diverse, most often of course, including chorea, but also include parkinsonian tremors, dystonia and ataxia. Chorea can involve any voluntary muscle, and as such, can affect, speech, swallowing, balance, and fine motor movements.
Given the benefit of DBS in treatment of levodopa-induced choreic dyskinesias in Parkinson’s disease (PD), the GPi has been explored as a target. Moro et al. published the first case report of DBS in a patient with refractory chorea from Huntington’s disease. Low frequency stimulation of the dorsal GPi improved the chorea and dystonia without causing further bradykinesia. Higher frequency stimulation correlated with an increase in bradykinesia.
Similar findings were reported in a large, open-label prospective pilot study of seven consecutive patients treated with bilateral GPi DBS for three years. 6 All of the patients had genetically confirmed HD with chorea refractory to tetrabenazine and a combination of a neuroleptic and at least one other drug. They had a United Huntington Disease Rating Scale (UHDRS) independence score of less than or equal to 70, a total functional capacity score of less than or equal to 8, and the absence of severe cognitive or psychiatric impairment.
There was an improvement of 10.91% in the UHDRS total motor score after one year. This worsened over time. The chorea subscore of the UHDRS improved by a mean of 58.34% and the improvement was sustained throughout the study period. In particular, chorea involving the orolingual area and upper limbs improved significantly. In these patients, it was possible to reduce or discontinue drug therapy. Bradykinesia, however, worsened during the study period.
HD presents challenges that arise from the complex origin of the observed movements and multiply affected circuits. Both limbic and cognitive pathways are involved. There is brain atrophy and progressive atrophy in time may alter the implanted lead position relative to the internal capsule. In an autopsy study reported by Vedam-Mai et al. no adverse effects were seen from this migration. 7 The worsening bradykinesia and rigidity leads to postural instability. It may represent stimulation effect or disease progression. The cognitive decline and related apathy is likely to impair assessment of some outcome measures. It may also pose an ethical concern in patient selection for treatment.
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