Case Report: GPi DBS for Non-parkinsonian Midline Tremor: A Normative Connectomic Comparison to a Failed Thalamic DBS

Introduction: The clinical efficacy of deep brain stimulation (DBS) for midline tremor has been heterogenous. Here, we present an atypical case with facial and palatal tremor treated with DBS. We aimed to show the difference between the fibers affected by stimulation of the two targets [globus pallidus interna (GPi) and ventral intermediate (Vim) thalamic nucleus] using a normative connectome analysis.Case Report: A 76-year-old woman with a 4-year history of severe facial and palatal tremor due to craniofacial dystonia. Following a failed bilateral Vim DBS, explantation of preexisting leads and implantation of bilateral GPi leads resulted in the resolution of tremor symptoms following a failed bilateral Vim DBS. We performed a normative connectome analysis using the volume of tissue activated (VTA) as a region of interest. The results revealed that the fiber tracts associated with VTA of GPi DBS had connections with the facial area of the motor cortex while the Vim DBS did not.Conclusion: This case study suggests the possibility that GPi DBS may be considered for midline tremor, and that the normative connectome analysis may possibly offer clues as to the structures underpinning a positive response. We may refine targets for some of the more difficult to control symptoms such as the midline tremor in this case.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies—a prerequisite for the surveillance of patients at risk.Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered.Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures.Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549.