Globus pallidus internus deep brain stimulation as rescue therapy for refractory dyskinesias following effective subthalamic nucleus stimulation.

BACKGROUND: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) or globus pallidus internus (GPi) can effectively treat the motor symptoms of Parkinson's disease, but dual implantation is rare. We report the first cases of additional GPi stimulation as rescue therapy for disabling dyskinesias following successful STN stimulation. METHODS: Two patients, initially treated with bilateral STN DBS, underwent subsequent bilateral GPi DBS after the development of refractory dyskinesias within 1 and 6 years of STN surgery. Patients were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgeries for STN and GPi DBS. RESULTS: GPi DBS effectively suppressed dyskinesias in these patients and improved their quality of life, as demonstrated by their videos and UPDRS scores. CONCLUSIONS: Additional bilateral GPi DBS may be considered in the rare instance of patients who develop refractory dyskinesias early or late after bilateral STN DBS.

Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome.

BACKGROUND: We have previously reported the results of Deep Brain Stimulation (DBS) of the antero-medial globus pallidus interna (GPi) for severe Tourette Syndrome (TS) in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean age 29.1 years, range 17-51 years) with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS). Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8-46 months) following surgery. RESULTS: Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6%) patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1), transient anxiety (2), dizziness (1), poor balance (1) and worsening of stuttering (1). CONCLUSIONS: This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.

Dopamine dysregulation syndrome, impulse control disorders and punding after deep brain stimulation surgery for Parkinson's disease.

Data regarding the effect of deep brain stimulation (DBS) surgery on the dopamine dysregulation syndrome (DDS), impulse control disorders (ICDs) and punding in Parkinson's disease (PD) are limited. We present a case series of 21 operated PD patients who had exhibited DDS, ICDs or punding at some stage during the disease. DDS remained unimproved or worsened post-operatively in 12/17 patients with pre-operative DDS (71%) (nine bilateral subthalamic nucleus [STN], one right-sided STN, two bilateral globus pallidus internus [GPi] DBS). DDS improved or resolved after bilateral STN DBS in 5/17 patients with pre-operative DDS. DDS apparently developed for the first time after bilateral STN DBS in two patients, although only after a latency of eight years in one case. One patient without reported pre-operative DDS or ICDs developed pathological gambling post-STN DBS. One patient had pathological gambling which resolved pre-operatively, and did not recur post-DBS. Thus, DDS, ICDs and punding may persist, worsen or develop for the first time after DBS surgery, although a minority of patients improved dramatically. Predictive factors may include physician vigilance, motor outcome and patient compliance.

Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease.

Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = -0.65, P < 0.001 and r = -0.33, P < 0.001 for activities over 13-30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.