gms | German Medical Science

Objective: Up to 20 % of patients with DBS of the VIM/dentato-rubro-thalamic bundle (DRT) for essential tremor develop a stimulation-induced cerebellar syndrome, which is difficult to treat and has effects on the quality of life. While the exact cause is elusive, different theories have been discussed. Among them is the (supratherapeutic) co-stimulation of further cerebellar output pathways in addition to the DRT (Groppa et al., Brain 2014) and antidromic stimulation of the cerebellum (Reich et al., Brain 2016). A thorough diagnostic work up was performed in affected patients and multi-modal data were retrospectively analyzed to identify common symptom patterns and potential causes.

Methods: In eight patients who complained about recurrent tremor and cerebellar symptoms after VIM/DRT-DBS a cerebral [¹⁸F]FDG PET, tremor (accelerometer & EMG) and gait (video-based markerless motion capture system) analyses were performed with activated DBS (DBS_ON) and 72 hours after deactivation (DBS_{OFF_72h}); gait and tremor were also analyzed directly after deactivation (DBS_OFF). Exploratory PET analyses (categorical comparisons and correlations) were done with SPM.

Results: Across all patients, we found a significantly increased metabolism of the thalamus and dentate nucleus and a decreased metabolism of the cerebellar hemispheres with DBS_ON (p <.01). Thalamic metabolism correlated positively with the metabolism of the dentate nucleus (both conditions pooled, (p <.01). The coefficient of variation (CoV) of step length (a marker of gait ataxia) withDBS_ON correlated negatively with the change in metabolism of the right cerebellar hemisphere (DBS_ON-DBS_{OFF_72h}; p <.01). The drop of frequency of postural tremor of the right hand upon deactivation of DBS (DBS_OFF-DBS_ON) correlated with gait ataxia (CoV_{step length}) with DBS_ON (p <.05). The frequency of postural tremor on the right showed a differential course across patients.

Conclusion: We observed differential changes of neuronal activity in the dentate nucleus and cerebellar hemispheres according to stimulation state (DBS_ON-DBS_{OFF_72h}). Increased neuronal activity of the thalamus withDBS_ON correlated positively with the increase of neuronal activity of the dentate nucleus, supporting the theory of antidromic stimulation, while reduced activity of the cerebellar hemispheres correlated with gait ataxia. The course of tremor frequency before and after deactivation of DBS may help to identify patients developing a stimulation-induced cerebellar syndrome