• Marco Cenzato, Davide Colistra, Giorgia Iacopino, Christian Raftopoulos, Ulrich Sure, Marcos Tatagiba, Robert F Spetzler, Alexander N Konovalov, Andriy Smolanka, Volodymir Smolanka, Roberto Stefini, Carlo Bortolotti, Paolo Ferroli, Giampietro Pinna, Angelo Franzini, Philipp Dammann, Georgios Naros, Davide Boeris, Paolo Mantovani, Domenico Lizio, Mariangela Piano, and Enrica Fava.
• 1Neurosurgery, Great Metropolitan Hospital Niguarda, Milan.
• J. Neurosurg. 2021 Sep 1; 135 (3): 693703693-703.

ObjectiveIn this paper, the authors aimed to illustrate how Holmes tremor (HT) can occur as a delayed complication after brainstem cavernoma resection despite strict adherence to the safe entry zones (SEZs).MethodsAfter operating on 2 patients with brainstem cavernoma at the Great Metropolitan Hospital Niguarda in Milan and noticing a similar pathological pattern postoperatively, the authors asked 10 different neurosurgery centers around the world to identify similar cases, and a total of 20 were gathered from among 1274 cases of brainstem cavernomas. They evaluated the tremor, cavernoma location, surgical approach, and SEZ for every case. For the 2 cases at their center, they also performed electromyographic and accelerometric recordings of the tremor and evaluated the post-operative tractographic representation of the neuronal pathways involved in the tremorigenesis. After gathering data on all 1274 brainstem cavernomas, they performed a statistical analysis to determine if the location of the cavernoma is a potential predicting factor for the onset of HT.ResultsFrom the analysis of all 20 cases with HT, it emerged that this highly debilitating tremor can occur as a delayed complication in patients whose postoperative clinical course has been excellent and in whom surgical access has strictly adhered to the SEZs. Three of the patients were subsequently effectively treated with deep brain stimulation (DBS), which resulted in complete or almost complete tremor regression. From the statistical analysis of all 1274 brainstem cavernomas, it was determined that a cavernoma location in the midbrain was significantly associated with the onset of HT (p < 0.0005).ConclusionsDespite strict adherence to SEZs, the use of intraoperative neurophysiological monitoring, and the immediate success of a resective surgery, HT, a severe neurological disorder, can occur as a delayed complication after resection of brainstem cavernomas. A cavernoma location in the midbrain is a significant predictive factor for the onset of HT. Further anatomical and neurophysiological studies will be necessary to find clues to prevent this complication.

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