LOS ANGELES — Unilateral deep-brain stimulation (DBS) reduces essential tremor and may help some patients avoid risk for greater side effects associated with bilateral DBS, a comparison study reveals.
Investigators found that unilateral DBS was associated with more than a 50% improvement in axial essential tremor at 6 months, an effect that was maintained up to 1 year.
“I think we all know that high-frequency deep-brain stimulation of the ventral intermediate nucleus [VIN] of the thalamus is effective at suppressing contralateral arm tremor and essential tremor,” said Kyle Mitchell, MD, a clinical neurology fellow at the University of California San Francisco. “However, evidence in axial tremor is somewhat limited and controversial, especially unilateral VIN deep-brain stimulation and its effect on axial tremor.”
The study was presented here at the American Academy of Neurology (AAN) 2018 Annual Meeting.
Direct Comparison
To add to the evidence, Mitchell and colleagues conducted a substudy of 119 participants from a controlled trial of nondirectional DBS for essential tremor (Parkinsonism Relat Disord. 2017;40:18-26).
Participants included 80 people with essential tremor who underwent unilateral DBS surgery only and another 39 who had staged surgery — unilateral followed by second-side procedure (the bilateral group) — allowing a direct comparison of efficacy and side effects.
Axial tremor was defined in the study as head tremor, face tremor, and/or voice tremor. “Importantly, 81% of participants had axial tremors at baseline, a fairly high prevalence in this group of DBS candidates,” he said.
The unilateral and bilateral DBS groups featured similar demographic characteristics at baseline. The baseline axial tremor severity did not significantly differ between groups. The average age was 67 years, mean disease duration was 30 years, and right-handed tremor was the primary target for surgery in most cases. Researchers evaluated tremor using a clinical rating scale at 90, 180, and 365 days after surgery.
“The original study already showed significant improvement in contralateral arm tremor, but the data had not been analyzed for midline tremor to date,” he said.
Researchers reported a 58% improvement at 90 days after unilateral DBS in pooled midline tremor severity scores, a primary study outcome. This improvement from baseline was 65% at 180 days and 64% at 1 year.
Change in axial tremor after second surgery for bilateral stimulation showed a 63% further improvement at180 days compared with unilateral stimulation at 180 days.
Head tremor improved by 86% compared with baseline and was the only subscore that significantly improved from unilateral to bilateral stimulation.
“The staged cohort, which allowed for direct comparison of unilateral and bilateral stimulation within subjects, showed that bilateral stimulation did offer incremental benefit,” Mitchell said. “It’s traditionally thought that bilateral DBS is necessary to control these axial symptoms. However, it seems to carry an increased risk of stimulation-induced side effects.”
There were 24 stimulation surgery–related side effects reported after unilateral surgery. After the second surgery, an additional 35 adverse events occurred, 3 of which were serious and many that did not resolve with reprogramming.
“In addition, the classic adverse events of dysarthria and gait impairment were more common after that second surgery,” he added.
More than 90% of patients stayed in the study at 1 year, a strength of the research. Potential limitations include the post hoc analysis design, a lack of racial diversity that could limit generalizability, and no assessment of lead location or trajectory.
Future Directions
“There is also emerging evidence that vertically placed leads in relation to the AC-PC axis is associated with further axial tremor improvement compared to horizontally placed leads,” Mitchell said.
The researchers also used nondirectional DBS leads in the study. “Directional leads are relatively new and may allow avoidance of bilateral stimulation–related side effects. This has been studied in Parkinson’s disease but has not been studied in essential tremor yet.”
“I hope this data leads [you] to my conclusion, that for essential tremor with contralateral arm or significant axial tremor, initial unilateral DBS placement may be sufficient to manage these bothersome axial tremor symptoms and obviate a need for second-sided surgery,” Mitchell said.
Future research could look at patient feedback, including satisfaction, Mitchell said.
A meeting attendee asked Mitchell to predict the long-term efficacy of unilateral DBS. “There was no significant difference between 90 and 180 days, but I cannot comment on further long-term improvement,” he said.
“This is an abstract with direct clinical implications. This study supports that unilateral DBS alone may be sufficient for axial tremor,” Deborah Hall, MD, PhD, associate professor in the Department of Neurological Sciences at Rush Medical College in Chicago, Illinois, said during a commentary on the study.
“The findings of this study may be pertinent in answering questions for potential candidates regarding the improvement of these axial symptoms and guide primary referrals for such symptoms as head tremor that may be challenging to treat in the clinic. This study reminds us that bilateral stimulation is associated with additional adverse events compared to unilateral stimulation in this population,” she said.
“What may be a prudent approach, per Dr Mitchell, in axial tremor is to do a staged procedure, and then reassess after some timeframe whether the second side is needed when using DBS primarily for axial symptoms,” Hall added.
Abbott supported the initial study published in 2017 but not the current research. Mitchell and Hall have disclosed no relevant financial relationships.
American Academy of Neurology (AAN) 2018 Annual Meeting. Abstract S18:003. Presented April 23, 2018.
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