Objective: To explore the pathways related with Holmes tremor, we evaluated the tremor suppression effect of deep brain stimulation (DBS), with the diffusion tensor imaging (DTI) of dentate-rubro-thalamic tract (DRTT) and the intraoperative local field potentials (LFPs) retrospectively in three cases.

Background: As for the pathophysiology of Holmes tremor, two pathways have been indicated from the cerebrovascular lesion studies¹: cerebello-thalamic/DRTT and nigrostriatal dopaminergic pathway. DBS has been applied for intractable Holmes tremor, and common targets are ventral intermediate nucleus (Vim) and/or caudal zona incerta (cZi). In case of the lesions of midbrain or thalamus, additional targeting of GPi can be selected^2,3. However, the DBS case series are small and the discussion from the point of two or dual pathways has not been well reported.

Method: Three cases were enrolled; case 1 is a forty-one-year-old male with the cerebellar lesion induced by SARS-Cov-2 vaccination; case 2 is a forty-three-year-old male with the midbrain and thalamic hemorrhage by cavernous hemangioma; case 3 is a sixty-three-year-old female with the thalamic hemorrhage. Targets were planned based on the MRI, and the DTI of DRTT (BrainLab neuronavigation system) was used before and after operation. LFPs were obtained intraoperatively with the bipolar recordings from the implanted electrodes. Kinetic tremor was assessed using the FTM Tremor Rating scale at the upper arm as expressed by the improvement rate (100% means full recovery).

Results: Case 1: bilateral cZi-Vim DBS with tremor suppression of 75%. The DRTT was clearly seen and the LFPs were sufficiently recorded. This shows the DTRT is related with Holmes tremor. Case 2: right cZi-Vim DBS with tremor suppression of 75%. The DRTT was hardly seen but the LFPs were sufficiently recorded. This suggests the cerebello-thalamic pathway other than DRTT is related. Case 3: two DBS targets of right Vim and GPi with tremor suppression of 0-25% in Vim DBS and 75% in GPi DBS. The DRT was sparse in Vim and never seen in GPi. The LFPs were almost no recorded in Vim but well recorded in GPi. This indicates the motor loop located the downstream of nigrostriatal pathways is related with Holmes tremor.

Conclusion: Our cases suggest DRTT or cerebello-thalamic pathway, as well as the motor loop down streaming the nigrostriatal pathways may be related in the pathophysiology of Holmes tremor.

References: [1] Choi SM. Movement Disorders Following Cerebrovascular Lesions in Cerebellar Circuits. J Mov Disord. 2016 May;9(2):80-8. doi: 10.14802/jmd.16004.
[2] Espinoza Martinez JA, et al. Deep brain stimulation of the globus pallidus internus or ventralis intermedius nucleus of thalamus for Holmes tremor. Neurosurg Rev. 2015 Oct;38(4):753-63. doi: 10.1007/s10143-015-0636-0.
[3] Kobayashi K, et a. Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes’ tremor. J Neurosurg. 2014 May;120(5):1025-32. doi: 10.3171/2014.1.JNS12392.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dual-pathways-of-holmes-tremor-suggested-from-the-experience-of-deep-brain-stimulation/