Deep Brain Stimulation of the Thalamic Ventral Lateral Anterior Nucleus for DYT6 Dystonia

Abstract

Background: A missense mutation of the THAP1 gene results in DYT6 primary dystonia. While deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in treating primary dystonia, recent reports indicate that GPi DBS is only mildly effective for DYT6 dystonia. Objective: To describe a patient with DYT6 dystonia who underwent thalamic ventral lateral anterior (VLa) nucleus DBS. Patient: A 35-year-old Japanese man had been experiencing upper limb dystonia and spasmodic dysphonia since the age of 15. His dystonic symptoms progressed to generalized dystonia. He was diagnosed as having DYT6 dystonia with mutations in the THAP1 gene. Because his dystonic symptoms were refractory to pharmacotherapy and pallidal DBS, he underwent thalamic VLa DBS. Results: Continuous bilateral VLa stimulation with optimal parameter settings ameliorated the patient's dystonic symptoms. At the 2-year follow-up, his Burke-Fahn-Marsden Dystonia Rating Scale total score decreased from 71 to 11, an improvement of more than 80%. Conclusions: The thalamic VLa nucleus could serve as an alternative target in DBS therapy for DYT6 dystonia.

Unilateral thalamic and pallidal deep brain stimulation for idiopathic hemidystonia: results of individual and combined stimulations. Case report

“…This sustained effect also explains the persistent good motor response when the battery charge is low, and the speech disturbance was attributed to the progressiveness of dystonia. Dysarthria happened when a different configuration in the GPi was tested, as observed by Mure et al 17 in a patient with DYT6 primary dystonia, although Gruber et al 6 only noticed this adverse event in Vim DBS.…”

“…It modulates pallidal bursts to the thalamocortical relay, 7,15 but it is compromised by the abnormal plasticity in dystonia. 6,7 Despite the reference of Vop connection to the cerebellum, 5,17,21 studies with its direct reading, 11,15 including an analysis of pallidal stimulation effects on Vop, showed that "Vop is a major target of GPi efferents" 6,11,15,16 and attributed to Vim the cerebellar connection. 11,15,16 In another study analyzing the pallidal-thalamic circuit, after GPi and Vim DBS for hemidystonia, a 5-to 18-Hz activity was observed, but some of the readings recorded at the Vim could have originated from the adjacent pallidal-receiving thalamus (the Vop).…”

“…22,24 Not all studies were designed initially for combined stimulation; in some studies a secondary surgery was performed to implant electrodes at different targets after failure of the first. 9,17,24 A 2006 meta-analysis 9 showed that the GPi stimulation had significantly better outcomes compared with the posterior portion of the ventrolateral nucleus of the thalamus, which includes Vim and part of the ventral oral (Vo) complex, 9,16 but the majority of the patients reviewed had primary dystonia. 9 The thalamic anatomy has many descriptions that could lead to targeting changes, and the fact that it has unclear and overlapped nuclear borders interferes with the clinical analysis.…”

“…Final programming was in the GPi: 450 μsec, 130 Hz, 1.0 V; and in the ventral oral complex: 60 μsec, 130 Hz, 3.0 V. Other studies did not find benefits with thalamic stimulation. 17,22,24 In a retrospective evaluation of 19 patients, Vercueil et al 24 found that those treated with GPi DBS had a better outcome, and 3 patients in the thalamic group had rescue GPi DBS, with subsequent improvement. One hemidystonic patient lost thalamic stimulation benefits; this individual had a greater response with pallidal stimulation.…”

“…However, other targets such as the thalamus and the subthalamic nucleus (STN) show good results in tremor, myoclonus, and task-specific dystonia, and for rescue therapy. [4][5][6][8][9][10][12][13][14][16][17][18]20 A precise target has not been established for each type of dystonia, 14,16 and it is known that the etiology interferes with the surgical outcome. Hemidystonia is not well treated by a single target because of its complex rearrangement of the motor network, 4 and hypokinetic symptoms don't respond well to pallidal modulation.…”