Article
Changing Lanes – the potential role of decussating and non-decussating portions of the dentatorubrothalamic bundle in delayed therapy escape after thalamic DBS for essential tremor
Spurwechsel beim Wirkverlust nach thalamischer DBS bei essentiellen Tremor – welche Rolle spielen kreuzende und nicht-kreuzende Anteile des dentato-rubrot-halamischen Bündels?
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Published: | May 25, 2022 |
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Objective: Delayed therapy escape after thalamic DBS for essential tremor (ET) is a serious condition affecting 30-40% of patients in the later postoperative course and is rarely covered in observational studies. The causes for this phenomenon are subject to debate. Attempts to alleviate symptoms include pulse width reduction to widen the therapeutic window. We assume that antidromic stimulation of cerebellothalamic fibers contributes to this phenomenon by differentially addressing decussating (DRTx) and non-decussating (DRTn) portions of the dentatorubrothalamic bundle.
Methods: 13 right-handed patients affected by delayed therapy escape (progressive intention tremor predominantly on the left, gait ataxia) after thalamic DBS for ET received stimulation optimization and pulse width reduction. They were classified as responders (n = 5) or non-responders (n = 8) according to their outcome on the scale for the assessment and rating of ataxia (meaningful improvement > 1.5 points). 3 patients without therapy escape were included as exploratory control group. Preoperative MRI and postoperative CT scans were normalized and coregistered in MNI space as well as the DRTx and DRTn derived by global tracking (seeds: superior cerebellar peduncle, red nucleus, precentral gyrus) from Human Connectome Project data. The volume of activated tissue (VAT) was calculated from stimulation parameters and the individual overlap with DRTx and DRTn determined. The ratio (DRTn/DRTx) of the right VAT (corresponding to predominantly left sided symptoms) was compared in responders and non-responders with an unpaired t-test. Exploratory analyses of the left VAT and patients without therapy escape are included as illustration.
Results: We found that VATs on the right in non-responders compared to responders address a bigger proportion of DRTn fibers at trend level (p = 0.052). Exploratory analyses denote that this pattern is not present in the left VAT but even more pronounced when comparing right VATs in non-responders and patients without therapy escape (Figure 1 [Fig. 1], Figure 2 [Fig. 2]).
Conclusion: We present preliminary evidence suggesting that delayed therapy escape after thalamic DBS may be due to an increased ratio of DRTn vs. DRTx fibers addressed by the VAT on the non-dominant side, which seems to be more vulnerable to this effect. More subjects will have to be studied to clarify the potentially mitigating role of decussating DRT in delayed therapy escape. This may help to define the target in thalamic DBS for tremor more precisely.