Unilateral Pallidal Deep Brain Stimulation in a Patient with Dystonia Secondary to Episodic Ataxia Type 2

Abstract

Background/Aims: This paper describes the use of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in the treatment of secondary dystonia caused by expisodic ataxia type 2 (EA2). Methods: We present the case of a patient with EA2, an autosomal dominant condition, who developed late-onset cervical and right upper limb segmental dystonia. The patient underwent left GPi DBS. Results: Within 4 months of commencing stimulation of the left GPi, the patient had resolution of his neck pain and was able to keep the head straighter for longer time intervals. There was also improvement in right arm segmental dystonia. There was an improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS 21.5) of 55% at 4 months and of 51% at 22 months. Conclusion: The treatment of secondary dystonia is difficult and the results with GPi DBS are less favourable compared with primary dystonia. This case illustrates the successful treatment of secondary dystonia caused by EA2.

It's not just the basal ganglia: Cerebellum as a target for dystonia therapeutics

“…In addition, in some cases in which dystonia is thought to be secondary to cerebellar dysfunction, DBS of the basal ganglia can alleviate dystonic postures. 72,73 Although there are multiple interpretations of this phenomenon, it is consistent with the hypothesis that in some cases the cerebellum can drive aberrant activity in the basal ganglia to induce dystonia. Because several lines of evidence already discussed indicate that burst firing of basal ganglia neurons occurs in dystonia, an obvious question is whether such firing is present in cerebellum-induced dystonia.…”

“…Because infusion of ouabain to both the cerebellum and basal ganglia was necessary to recapitulate all the features of RDP, one hypothesis is that abnormal cerebellar output in this pharmacologic model alters activity in the basal ganglia, resulting in dystonia. In addition, in some cases in which dystonia is thought to be secondary to cerebellar dysfunction, DBS of the basal ganglia can alleviate dystonic postures . Although there are multiple interpretations of this phenomenon, it is consistent with the hypothesis that in some cases the cerebellum can drive aberrant activity in the basal ganglia to induce dystonia.…”

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

“…Currently, there is lack of evidence for the efficacy of non‐invasive brain stimulation techniques, like transcranial magnetic stimulation and transcranial direct/alternating current stimulation in patients with dystonia . In contrast, surgical interventions for dystonia such as GPi‐DBS have been found effective to some extent in patients with Wilson disease, ataxia‐telangiectasia and its variant spinocerebellar ataxias, episodic ataxia type 2, Cockayne syndrome, PLA2G6‐associated neurodegeneration, and neurodegeneration with brain iron accumulation type 1 due to mutations in the PANK2 gene . Responses are often transient or partial, usually in the range of 10 to 30% of improvement, which is far less than the benefit reported in patients with primary generalized dystonia, but greater improvements of approximately 70% during the first years after surgery were also found .…”

Current Opinions and Areas of Consensus on the Role of the Cerebellum in Dystonia

“…A role for cerebellum in dystonia has also been established in the tottering mice, a model of the human disorder episodic ataxia type 2 which, in some patients, is associated with dystonia in addition to ataxia [67, 68]. As noted in the prior section, studies on tottering have repeatedly implicated the cerebellum in the episodes of ataxia and dystonia [42, 45, 69], and pharmacologically normalizing the activity of cerebellar neurons can alleviate dystonic symptoms in these animals [70, 71].…”