Cognitive Outcomes for Essential Tremor Patients Selected for Thalamic Deep Brain Stimulation Surgery Through Interdisciplinary Evaluations.

Objective: Deep brain stimulation (DBS) targeted to the ventral intermediate (VIM) nucleus of the thalamus is effective for motor symptoms in essential tremor (ET), but there is limited data on cognitive outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients (pre-DBS and 1+ year after DBS). Methods: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive outcomes. Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function. Results: We identified 50 ET DBS patients; 29 (58%) males; the mean age of tremor onset was 35.84 (±21.50) years with a median age of 38 years. The mean age at DBS was 68.18 (±10.07) years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment (pre vs. post) and age of tremor onset (<38 vs. >38 years); F (1,30) = 4.47; p = 0.043 for working memory. The post hoc testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment (pre vs. post) and complications vs. no complications subgroups; F (1,45) = 4.34; p = 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant. Conclusion: In this large cohort of ET patients with (>30% improvements), DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS.

Longitudinal follow-up with VIM thalamic deep brain stimulation for dystonic or essential tremor.

OBJECTIVE: To assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET). METHODS: We retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2-3 years, 4-5 years, and ≥6 years after surgery. RESULTS: Twenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4-5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2-3 years follow-up. CONCLUSION: Overall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.

Gait characterization for patients with orthostatic tremor.

INTRODUCTION: Orthostatic tremor (OT) patients frequently report gait unsteadiness with the advancement of disease; however, there is little understanding of its physiology. We sought to examine in OT, the spatial and temporal characteristics of gait, and the relationship with tremor physiology. METHODS: Gait parameters for OT (n = 16) were recorded with an instrumented Zeno walkway system. All participants complained of gait unsteadiness, especially during slow walking. In a subset of OT, recordings were synchronized with a wireless EMG system for tremor assessment and feet pressure recording. Gait assessments were performed at self-selected habitual, fast, and slow speeds. RESULTS: Compared to data available for an age- and sex-matched healthy controls, OT patients had a significantly reduced step length, increased step width, and increased gait variability (p < 0.0001). Tremor discharges related to OT were consistently recorded across three different speeds of walking. These discharges persisted through all phases of the gait cycle, including the swing phase when the limb was not weight-bearing. The highest tremor amplitude was recorded in the single support phase, followed by double support, and least during the swing phase. CONCLUSION: OT patients have distinct gait abnormalities similar to cerebellar disorders. Tremor discharges from the non-weight bearing leg in the swing phase suggests that muscle contractions, even when occurring without resistance, contribute to OT generation.

Importance of the initial response to GPi deep brain stimulation in dystonia: A nine year quality of life study.

BACKGROUND: Long-term efficacy of deep brain stimulation (DBS) on health-related quality-of-life (HRQoL) for isolated dystonia is not well established. This study aims to determine the long-term impact of DBS on HRQoL outcomes and identify clinical predictors. METHODS: We retrospectively investigated 16 inherited or idiopathic isolated dystonia patients treated with bilateral globus pallidus internus DBS who were followed beyond 9 years at our center. The cohort consisted of 9 males, 7 females; 10 generalized, 6 segmental; mean (range) age at implantation, 37.0 (8-67) years; mean follow-up duration after implantation, 10.9 (9-13) years. We employed the Unified Dystonia Rating Scale for motor and Short Form Health Survey for HRQoL assessments to monitor the change longitudinally. We analyzed the changes in motor and HRQoL at 1-2 years (short-term) and ≥9 years (long-term) follow-up as compared to baseline with a Wilcoxon signed-rank test. We assessed the factors that predicted motor and HRQoL improvement with univariate regression analyses. RESULTS: Motor (41.6%; p = 0.004) and HRQoL (total score, p = 0.039) improvements remained significant at long-term follow-up and, in the regression analysis, change in HRQoL outcomes correlated significantly with change in motor outcomes (R2 = 0.384, p = 0.010). Additionally, short-term motor and HRQoL improvements predicted the long-term motor (R2 = 0.384, p = 0.010) and HRQoL (total score, R2 = 0.594, p < 0.001) outcomes, respectively. CONCLUSION: Motor and HRQoL improvements with DBS in isolated dystonia remain sustained for nearly a decade and may largely be predictable by the short-term response to DBS.