Objective: We aim to differentiate networks associated with deep brain stimulation (DBS) induced ataxia in essential tremor (ET) patients and test if connectivity to these networks is predictive for these side-effects in an independent cohort.

Background: DBS of the (sub)thalamic area has been shown to be an effective treatment in medication-refractory ET. However, studies have reported a DBS-induced ataxia which can onset directly after DBS-therapy or years after. We hypothesize different stimulation induced network alterations.

Method: In this study FDG-PET scans were taken in side effect and non-side effect condition of 14 patients with ET and bilateral thalamic DBS. Seven showed delayed-onset gait ataxia and were programmed to settings without gait-symptoms (2 men; age 74±6; disease duration 25±13). The other seven patients showed no gait difficulties and were programmed to acute supratherapeutic ataxia (3 men; age 64±9; disease duration 20±13).
A separate cohort of 50 patients (27men; age 66±10; disease duration 33±19) was clinically examined based on preoperative- and follow up videos using the Fahn-Tolosa-Martin scale (FTM) and the scale for the assessment and rating of ataxia (SARA). Structural normative connectivity was estimated seeding from individual stimulation site. A prediction model was built using 40 randomly selected patients to train the algorithm it was k-fold crossvalidated and then tested against the remaining 10 patients.

Results: Increased metabolic uptake was observed in the cerebellar nodule in delayed-onset gait ataxia and in the SCM, M1, putamen, red nucleus and the posterior parietal cortex in supratherapeutic ataxia.
In the independent cohort tremor improved by 11±10 points on the FTM-scale and the SARA-score worsened by 2±2 points. Structural connectivity to each network correlated significantly to a worsening of ataxia but not to overall tremor control. The network-model cross validation returned a R2 = 0.39 and a RMSE = 2.05 on the SARA while the validation on the test cohort returned R2 = 0.64, RMSE = 1.48.

Conclusion: Our results could indicate that side effects of delayed onset ataxia and acute supra-therapeutic ataxia are based on different brain network modulations. Connectivity to these networks is linked to a worsening of gait ataxia while having no relations with tremor control. Based on these results a prediction model for ataxia in thalamic DBS could be build.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/network-detection-and-connectivity-analysis-to-predict-dbs-induced-ataxia-in-essential-tremor/