Bilateral thalamic deep brain stimulation: midline tremor control.

OBJECTIVES: To determine the efficacy of bilateral deep brain stimulation (DBS) for management of midline tremor (head, voice, tongue, trunk) in patients with essential tremor. DESIGN: Prospective assessment of tremor at baseline (presurgical), and postoperatively at 1, 3, and 12 months, and annually thereafter. METHODS: A clinical series of 22 individuals undergoing staged, bilateral DBS for treatment of essential tremor. The tremor rating scale was the primary outcome measure. RESULTS: Midline tremor showed significant improvement with stimulation "on" at nearly every postoperative interval when compared with stimulation "off" and with baseline tremor. Bilateral stimulation was associated with a significant incremental improvement in midline tremor control compared with unilateral stimulation: average "stimulation on" percentage change in midline tremor from the unilateral to bilateral period was 81%. Head and voice tremor showed the most consistent improvement. Among those requiring a change in stimulation parameters because of side effects, dysarthria, disequilibrium, motor disturbances, and paraesthesiae were the most common. Dysarthria was more common with bilateral (n = 6; 27%) than with unilateral (n = 0) stimulation. Stimulation parameters remained largely unchanged after the first three months. Nine of 44 leads placed (20%) required subsequent repositioning or replacement. CONCLUSIONS: Unilateral thalamic stimulation significantly improves midline tremor, and subsequent bilateral thalamic stimulation offers an additional incremental improvement in midline tremor control.

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis.

OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET). METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living. RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study. CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.

Thalamic deep brain stimulation for tremor-predominant Parkinson's disease.

OBJECTIVES: Determine the long-term efficacy of thalamic deep brain stimulation (DBS) for treatment of tremor among individuals with tremor-predominant Parkinson's disease (PD).Design. Longitudinal, unblinded assessment of tremor and activities of daily living (ADL) at baseline (pre-surgical), and post-operative intervals of 1, 3, and 12 months, and annually thereafter up to 3 years. METHODS: A clinical series of 19 individuals undergoing placement of a DBS system for treatment of PD-related tremor. A battery of subjective and objective measures of tremor was completed at planned pre- and post-operative intervals. RESULTS: Stimulation was associated with significant improvement on subjective and objective measures of ADL performance, midline tremor, and contralateral upper and lower extremity tremor, including parkinsonian resting and action tremors, over the follow-up period. Ipsilateral tremor showed little or no effect of stimulation after the first 3 months. Antiparkinsonian medication use and stimulation parameters showed little or no change over the course of follow-up. About half (53%) of all individuals reported at least one side effect, generally mild, during the follow-up period, with paresthesias and dysarthria being the most common. A total of two leads required replacement due to (1) infection, and (2) adverse side effects (i.e. burning and tingling with stimulation). CONCLUSION: DBS is associated with stable tremor control in PD. Side-effects are typically easily managed with stimulation adjustments, although in some cases lead replacement may be required.

Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate genes.

Parkinson's disease (PD) is a common neurodegenerative disorder with clinical features of bradykinesia, rigidity, resting tremor and postural instability resulting from the deficiency of dopamine in the nigrostriatal system. Previously we mapped a susceptibility gene for an autosomal dominant form of PD to a 10.6 cM region of chromosome 2p (PARK3; OMIM 602404). A common haplotype shared by two North American kindreds (Families B and C) genealogically traced to Southern Denmark and Northern Germany suggested a founder effect. Here we report progress in the refinement of the PARK3 locus and sequence analysis of candidate genes within the region. Members of families B and C were genotyped using polymorphic markers, reducing the minimum common haplotype to eight markers spanning a physical distance of 2.5 Mb. Analysis of 14 genes within the region did not reveal any potentially pathogenic mutations segregating with the disease, implying that none of these genes are likely candidates for PARK3.