Holmes Tremor: A delayed complication after resection of brainstem cavernomas
Introduction: Brainstem cavernomas are relatively rare vascular malformations. Surgery should be considered in selected patients, and it is possible through the well-known "safe entry zones". However, this surgery is not free from complications. Holmes tremor is a rare complication, described in only 4 case reports in the literature. It is characterized by rest, postural, and intention tremor that occurs after some time from the acute event with a low frequency muscle contraction (<5 Hz). Holmes tremor is due in most cases to the interruption of the nigrostriatal, dentatothalamic and/or rubroolivary bundles in the contralateral brainstem. Our study collects and analyzes, in relation to surgical access, a series of 21 patients collected in 11 different Neurosurgery centers in Europe and all over the world.
Methods: We selected 2 cases that we operated at the Great Metropolitan Hospital Niguarda in Milan. Then we contacted 10 other Neurosurgery centers, including 4 centers in Italy (Legnano Hospital in Milan, C. Besta Neurological Institute in Milan, University Hospital Verona in Verona, Bellaria Hospital in Bologna), 2 in Germany (University Hospital Essen in Essen, University Hospital Tübingen in Tubingen), 1 in Belgium (Saint-Luc University Clinic in Brussels), 1 in Russia (Burdenko Neurosurgical Institute in Moscow), 1 in Ukraine (University Hospital Uzhhorod in Uzhhorod) and 1 in the United States of America (Barrow Neurological Institute in Phoenix), for a total number of 21 cases. We evaluated the clinical, electromyographic and accelerometric features of the tremor, the site of the cavernoma, the surgical approach, the postoperative tractographic representation of the neuronal pathways hypothetically involved in the tremorigenesis.
Results: From the analysis of the collected cases, it emerges that this strongly invalidating tremor, can take place as a delayed complication also in patients whose postoperative clinical course has been excellent and in which surgical access has respected the safe entry zones. The circuits that support the tremor are distributed throughout the entire brainstem, and at the moment there is no intra-operative neurophysiologic monitoring that can help prevent this rare complication. Some of the patients have been effectively treated with Deep Brain Stimulation, with almost complete or complete tremor regression.
Conclusions: Brainstem cavernomas are relatively rare vascular malformations. Surgery, however complex and not without serious complications, should be considered as the treatment of choice in selected cases. It is performed through the well-known "safe entry zones" to the brainstem. Holmes tremor is one of the possible, albeit rare, complications of this type of surgery. In our study, the location of the cavernoma and the surgical access are compatible with the onset of Holmes tremor, and therefore the currently used "safe entry zones" and intraoperative neurophysiologic monitoring cannot prevent this complication. Future studies are needed to determine whether it will be possible to identify entry zones to the brainstem, able to prevent the onset of Holmes tremor as a delayed complication after brainstem cavernomas resection.