Unravelling delayed therapy escape after thalamic deep brain stimulation for essential tremor? – Additional clinical and neuroimaging evidence

BACKGROUND: Delayed therapy escape after thalamic deep brain stimulation (DBS) for essential tremor is a serious yet frequent condition. It is often difficult to detect this process at onset due to its gradual evolution. OBJECTIVE: Here we aim to identify clinical and neuroimaging hallmarks of delayed therapy escape. METHODS: We retrospectively studied operationalized and quantitative analyses of tremor and gait, as well as [(18)F]fluorodeoxyglucose (FDG) PET of 12 patients affected by therapy escape. All examinations were carried out with activated DBS (ON) and 72 h after deactivation (OFF(72h)); gait and tremor were also analyzed directly after deactivation (OFF(0h)). Changes of normalized glucose metabolism between stimulation conditions were assessed using within-subject analysis of variance and statistical parametric mapping. Additionally, a comparison to the [(18)F]FDG PET of an age-matched control group was performed. Exploratory correlation analyses were conducted with operationalized and parametric clinical data. RESULTS: Of the immediately accessible parametric tremor data (i.e. ON or OFF(0h)) only the rebound (i.e. OFF(0h)) frequency of postural tremor showed possible correlations with signs of ataxia at ON. Regional glucose metabolism was significantly increased bilaterally in the thalamus and dentate nucleus in ON compared to OFF(72h). No differences in regional glucose metabolism were found in patients in ON and OFF(72h) compared with the healthy controls. CONCLUSIONS: Rebound frequency of postural tremor seems to be a good diagnostic marker for delayed therapy escape. Regional glucose metabolism suggests that this phenomenon may be associated with increased metabolic activity in the thalamus and dentate nucleus possibly due to antidromic stimulation effects. We see reasons to interpret the delayed therapy escape phenomenon as being related to long term and chronic DBS.