Pallidal stimulation for Holmes tremor: clinical outcomes and single-unit recordings in 4 cases

Abstract

OBJECT Holmes tremor (HT) is characterized by irregular, low-frequency (< 4.5 Hz) tremor occurring at rest, with posture, and with certain actions, often affecting proximal muscles. Previous reports have tended to highlight the use of thalamic deep brain stimulation (DBS) in cases of medication-refractory HT. In this study, the authors report the clinical outcome and analysis of single-unit recordings in patients with medication-refractory HT treated with globus pallidus internus (GPi) DBS. METHODS The authors retrospectively reviewed the medical charts of 4 patients treated with pallidal DBS for medication-refractory HT at the University of California, San Francisco, and San Francisco Veterans Affairs Medical Center. Clinical outcomes were measured at baseline and after surgery using an abbreviated motor-severity Fahn-Tolosa-Marin (FTM) tremor rating scale. Intraoperative microelectrode recordings were performed with patients in the awake state. The neurophysiological characteristics identified in HT were then also compared with characteristics previously described in Parkinson's disease (PD) studied at the authors' institution. RESULTS The mean percentage improvement in tremor motor severity was 78.87% (range 59.9%–94.4%) as measured using the FTM tremor rating scale, with an average length of follow-up of 33.75 months (range 18–52 months). Twenty-eight GPi neurons were recorded intraoperatively in the resting state and 13 of these were also recorded during contralateral voluntary arm movement. The mean firing rate at rest in HT was 56.2 ± 28.5 Hz, and 63.5 ± 19.4 Hz with action, much lower than the GPi recordings in PD. GPi unit oscillations of 2–8 Hz were prominent in both patients with HT and those with PD, but in HT, unlike PD, these oscillations were not suppressed by voluntary movement. CONCLUSIONS The efficacy of GPi DBS exceeded that reported in prior studies of ventrolateral thalamus DBS and suggest GPi may be a better target for treating HT. These clinical and neurophysiological findings help illuminate evolving models of HT and highlight the importance of cerebellar–basal ganglia interactions.

Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

“…Lastly, our cohort assumed a single category of tremor syndromes, namely essential tremor. this could be of concern since other tremor syndromes equally benefit from DBS surgery (Kumar et al, 2003;Herzog et al, 2004;Foote et al, 2006;Mandat et al, 2010;Kilbane et al, 2015;Cury et al, 2017). For example, Parkinsonian tremor is successfully treated with subthalamic nucleus (Diamond et al, 2007) and VIM (Kumar et al, 2003) DBS .…”

Deep brain stimulation for movement disorders

“…For the same reason, Holmes tremor is one of the most difficult conditions to treat and Vim DBS is often ineffective. A good outcome has been recently reported in four patients treated with GPi DBS [100] or in four other cases treated with double implantation of Vop/Vim and the STA [101]. It is difficult to draw conclusions on the ideal target for Holmes tremor, especially due to the heterogeneity of this condition.…”

Clinical Outcome and Characterization of Local Field Potentials in Holmes Tremor Treated with Pallidal Deep Brain Stimulation

“…Several reports have highlighted the efficacy of thalamic ventralis intermedius nucleus (VIM) deep brain stimulation (DBS) in HT. 5 – 8 However, there is no consensus regarding the best stereotactic target for HT treatment. We identified 17 patients in the literature with HT treated with contralateral VIM DBS, 11 patients treated with globus pallidus interna (GPi) DBS, four patients treated with dual-lead stimulation in the VIM and posterior subthalamic area (PSA), and three patients treated with dual leads located at the border of VIM/ventralis oralis posterior nucleus (Vop) and ventralis oralis anterior nucleus (Voa)/Vop, three patients treated with VIM DBS with the deepest contact located in the PSA, and individual cases of stimulation of the Voa and zona incerta (Zi), VIM and subthalamic nucleus (STN), lenticular fasciculus, and caudal Zi 5 – 11 ( Table 1 ).…”

“…An overall improvement of 64% and 78% in tremor scales was observed, and in a few exceptional cases there was complete tremor resolution. 8 …”

“… Bilateral VIM Moderate partial benefit (CGI scale 3). No TRS available N/A Follett et al 9 Post-traumatic HT (symptoms for 15 years) Bilateral VIM Reduction of tremor from a score of 3 to a score of 1 in the right arm and from 3.5 to 0 in the left arm (TETRAS scale) 12 months Espinoza-Martinez et al 5 1 patient with ICH due to cavernous malformations, 1 patient with cerebral infarction, 1 patient with MS 1 patient with bilateral VIM (MS case) and 2 patients with unilateral VIM 83.3% mean improvement in TRS Mean length of follow-up 7.3 years Studies reporting other DBS targets for HT Bandt et al 2008 19 Left midbrain cerebral infarction (symptoms for 7 months) Left lenticular fasciculus Almost complete resolution of postural and intention tremors; scored 1/4 on the WHIGET 16 months Plaha et al 2008 20 No obvious MRI abnormality (symptoms for 6 years) Caudal Zi 70.2% improvement in total TRS N/A Kilbane et al 8 1. Multicystic brainstem tegmentum lesions2.…”