Multitarget, dual-electrode deep brain stimulation of the thalamus and subthalamic area for treatment of Holmes' tremor

Abstract

Holmes' tremor (HT) is generally considered to be a symptomatic tremor associated with lesions of the cerebellum, midbrain, or thalamus. Deep brain stimulation (DBS) therapy for essential tremor and parkinsonian tremor has proved quite successful. In contrast, surgical treatment outcomes for HT have often been disappointing. The use of 2 ipsilateral DBS electrodes implanted in parallel within the thalamus for severe essential tremor has been reported. Since dual-lead stimulation within a single target can cover a wider area than single-lead stimulation, it produces greater effects. On the other hand, DBS of the subthalamic area (SA) was recently reported to be effective for refractory tremor. The authors implanted 2 DBS electrodes (one at the nucleus ventralis oralis/nucleus ventralis intermedius and the other at the SA) in 4 patients with HT. For more than 2 years after implantation, each patient's tremor was evaluated using a tremor rating scale under the following 4 conditions of stimulation: "on" for both thalamus and SA DBS; "off" for both thalamus and SA DBS; "on" for thalamus and "off" for SA DBS; and "on" for SA and "off" for thalamus DBS. The tremor in all patients was improved for more than 2 years (mean 25.8 ± 3.5 months). Stimulation with 2 electrodes exerted greater effect on the tremor than did 1-electrode stimulation. Interestingly, in all patients progressive effects were observed, and in one patient treated with DBS for 1 year, tremor did not appear even while stimulation was temporarily switched off, suggesting irreversible improvement effects. The presence of both resting and intentional/action tremor implies combined destruction of the pallidothalamic and cerebellothalamic pathways in HT. A larger stimulation area may thus be required for HT patients. Multitarget, dual-lead stimulation permits coverage of the wide area needed to suppress the tremor without adverse effects of stimulation. Some reorganization of the neural network may be involved in the development of HT because the tremor appears several months after the primary insult. The mechanism underlying the absence of tremor while stimulation was temporarily off remains unclear, but the DBS may have normalized the abnormal neural network. The authors successfully treated patients with severe HT by using dual-electrode DBS over a long period. Such DBS may offer an effective and safe treatment modality for intractable HT.