title: Worsening essential tremor following deep brain stimulation: disease progression versus tolerance.
abstract: A major concern regarding ventralis intermedius nucleus deep brain stimulation for essential tremor has been the loss of surgical efficacy over time in a minority of patients. Some experts have ascribed the worsening tremor to tolerance, while other evidence has suggested that disease progression may play a role. Suboptimal lead placement has also been reported to be a factor in worsening tremor following deep-brain stimulation; however, most authors consider this phenomenon to manifest within a few months of the actual surgery. We aimed to dissect the tolerance versus disease progression issue by analysing preoperative versus long-term post-surgical Fahn-Tolosa-Marin Tremor Rating Scale scores both on and off stimulation among 28 patients who underwent ventralis intermedius nucleus deep brain stimulation and 21 age-matched controls. Of the 28 patients in the treatment arm of the cohort, seven (25%) demonstrated evidence of tremor progression, and had a 34% increase in the tremor score off stimulation at the 36 month follow-up compared with a 32% increase among controls (P = 0.67). In one of the seven patients there was evidence of suboptimal lead placement given the lateral position of the lead, and the motor side effects during threshold testing. This patient demonstrated a loss of stimulation benefit between 24 and 36 months, which may have been more indicative of tolerance. The other six subjects (86%) maintained stimulation benefit throughout the follow-up period, despite worsening tremor off stimulation (at a comparable rate to that of controls), making disease progression the most likely explanation. The data suggest that deep brain stimulation tolerance may be over-reported in the literature, and that a tolerance versus disease progression work-up should include: examining the trend in off stimulation scores, accounting for image based lead locations, and during programming sessions checking for thresholds which may elicit clinical benefits and side effects.
authors.affiliation: Department of Neurology, Centre for Movement Disorders and Neurorestoration, University of Florida College of Medicine, 100 S Newell Drive, Gainesville, FL 32610, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Favilla
authors.forename: David
authors.initials: D
authors.lastname: Ullman
authors.forename: Aparna
authors.initials: A
authors.lastname: Wagle Shukla
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Foote
authors.forename: Charles E
authors.initials: CE
authors.lastname: Jacobson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D018450:Disease Progression; D004567:Electrodes, Implanted; D020329:Essential Tremor / Q000628:therapy*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D020646:Intralaminar Thalamic Nuclei / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome