Comparison of Short-Term Stimulation of the Globus Pallidus Interna and Subthalamic Nucleus for Treatment of Primary Dystonia.

OBJECTIVE: To compare the efficacy and side effects of bilateral globus pallidus internus (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) in the same patient with primary dystonia. METHODS: Patients with primary dystonia from the department of functional neurosurgery in Beijing Tiantan Hospital were recruited for the study. Four electrodes were bilaterally implanted in the GPi and STN. A trial stimulation was applied to determine the preliminary therapeutic effects. Five evaluations were conducted: preoperative, postoperative (before stimulation), after sham stimulation, and after stimulation for 24 hours of GPi and STN using optimal parameters, judged by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: The BFMDRS movement score decreased after both short-term GPi stimulation (from 15.3 ± 6.9 to 7.6 ± 4.2, P < 0.05) and short-term STN stimulation (from 15.3 ± 6.9 to 8.6 ± 5.0, P < 0.05). There were significant reductions in facial (eyes and mouth) movement scores after short-term GPi and STN DBS compared with baseline (P < 0.05), but not in cervical symptoms (P > 0.05). The cervical symptoms of tonic dystonia had an improvement after long-term DBS treatment (P < 0.05). There were more adverse events with STN DBS; however, most side effects could be ameliorated by adjusting stimulation parameters. CONCLUSIONS: Both short-term GPi and STN stimulation improved the motor symptoms of dystonia, but there was no significant difference between GPi DBS and STN DBS. There were more side effects associated with STN stimulation.

Long-term clinical outcome of bilateral pallidal stimulation for intractable craniocervical dystonia (Meige syndrome). Report of 6 patients.

BACKGROUND: The aim of the present study was to report the short-term as well long-term results of bilateral pallidal stimulation in 6 consecutive patients for severe debilitating craniocervical dystonia (Meige syndrome) using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). METHODS: We evaluated 6 consecutive patients with the diagnosis of intractable long-standing craniocervical dystonia. The formal objective assessment included the motor and disability BFMDRS scores. The BFMDRS assessment was performed before and after it roughly annually up to 60months when bilateral pallidal stimulation was switched on and compared to baseline BFMDRS scores. We present short-term (3months postoperatively) follow-up as well long-term (from 6 to 60months) results. Baseline BFMDRS scores and subsequent follow-up BFMDRS scores were compared with the use of a Wilcoxon signed-rank test for matched pairs. A two-tailed probability level of 5% (p<0.05) was considered significant. RESULTS: Bilateral GPi DBS improved the BFMDRS total movement score by 65% at short-term follow-up and by 53% at long-term follow-up when compared to baseline scores. Subscores for eyes at short-term follow-up were reduced by 78%, for mouth by 58%, and for speech/swallowing by 49%. This improvements for individual subscores were maintained at long-term follow-up and were as follows for eyes by 67%, mouth by 50% and speech/swallowing by 39%. The BFMDRS disability score was reduced by 48% at short-term follow-up and by 55% at long-term follow-up when compared to baseline scores. CONCLUSION: Our results showed that bilateral GPi DBS in craniocervical dystonia is effective and safe. Phasic dystonic movements like blepharospasm or oromandibular dystonia responded very fast and favorable to pallidal stimulation reducing disabilities.

Pallidal deep brain stimulation and L-dopa do not improve qualitative aspects of skilled reaching in Parkinson's disease.

OBJECTIVE: To determine effects of dopaminergic medication and pallidal deep brain stimulation (DBS) on skilled reach in Parkinson's disease (PD). BACKGROUND: PD is a neurodegenerative disorder affecting motor control. While speed and execution of movements are improved by L-dopa, not all motor symptoms are alleviated. Little is known about the effects of DBS or medication on reaching. DESIGN METHOD: Eight PD patients with unilateral pallidal DBS reached with the contra-lateral hand for a piece of food, placing it in the mouth, and returning to starting position. Testing was performed on no treatment, medication only, DBS only, and combined treatment. Reaches were digitally recorded and analyzed on a 21 point scale adapted from Eshkol-Wachman Notation. Analysis was blinded, with patients compared to age-matched controls. RESULTS: Patients were tested 6-13 months after surgery. All showed significant improvement clinically and in UPDRS (III) scores. The following data were obtained on the reaching scale: normal controls 16.5-21.0 (mean 18.3), no treatment 3.0-12.5 (mean 7.4), medication only 7.0-14.0 (mean 10.3), DBS only 4.5-16.0 (mean 9.2), combined treatment 4.0-15.0 (mean 9.5). The difference between controls and all treatment groups was statistically significant (P<0.005). All aspects of reach were compromised. No significant differences were found among the four conditions. CONCLUSIONS: This study is consistent with accumulating evidence that some aspects of motor performance in PD patients, such as reaching, are resistant to L-dopa. Also, pallidal DBS does not improve those parameters that are resistant to L-dopa, either alone or in combination with medication.

Physiologic assessment of autonomic dysfunction in pallidopontonigral degeneration with N279K mutation in the tau gene on chromosome 17.

Autonomic function was investigated in five affected and five at-risk members of a single kinship of pallidopontonigral degeneration (PPND), which is a progressive syndrome of parkinsonism and frontotemporal dementia resulting from a mutation in the N279K tau gene on chromosome 17. Affected subjects reported symptoms including hyperhidrosis, sialorrhea, urinary frequency or incontinence, thermal intolerance, male sexual dysfunction, lacrimation, and dryness of the eyes or mouth. None had orthostatic hypotension. Autonomic testing revealed mild-to-moderate abnormalities in all five affected subjects and minor abnormalities in the three oldest, asymptomatic, at-risk subjects. Findings in affected subjects consisted of preganglionic sudomotor dysfunction in all five, impaired cardiovagal function in three, and reduced or absent pupillary near responses in four. Tests of adrenergic function were normal in all subjects. The degree of autonomic dysfunction correlated significantly with disease duration and with indices of disease severity. In conclusion, there is evidence in PPND of a disturbance in the central autonomic network.

Site of deep brain stimulation and jaw velocity in Parkinson disease.

OBJECT: While deep brain stimulation (DBS) has proven to be an effective treatment for many symptoms of Parkinson disease (PD), a deterioration of axial symptoms frequently occurs, particularly for speech and swallowing. These unfavorable effects of DBS may depend on the site of stimulation. The authors made quantitative measures of jaw velocity to compare the relative effectiveness of DBS in the globus pallidus internus (GPi) or the subthalamic nucleus (STN). This was a randomized, double-blind, and longitudinal study, with matched healthy controls. METHODS: The peak velocities of self-scaled and externally scaled jaw movements were studied in 27 patients with PD before and after 6 months of bilateral DBS in the GPi or the STN. A mixed-effects model was used to identify differences in jaw velocity before DBS surgery (baseline) while off and on levodopa therapy, and after 6 months of DBS (postoperative) during 4 treatment conditions (off- and on-levodopa states with and without DBS). RESULTS: Self-scaled jaw velocity was impaired by the DBS procedure in the STN; velocity was significantly decreased across all postoperative conditions compared with either the off- or on-levodopa baseline conditions. In contrast, the postoperative velocity in the GPi group was generally faster than the baseline off-levodopa state. Turning the DBS off and on had no effect on jaw velocity in either group. Unlike baseline, levodopa therapy postoperatively no longer increased jaw velocity in either group, and this lack of effect was not related to postoperative changes in dose. The externally scaled jaw velocity was little affected by PD, but DBS still slightly affected performance, with the STN group significantly slower than the GPi group for most conditions. CONCLUSIONS: The authors' results suggest that either the electrode implant in STN or the subsequent period of continuous STN stimulation negatively affected voluntary jaw velocity, including the loss of the preoperative levodopa-induced improvement. While the GPi group showed some improvement in voluntary jaw velocity postoperatively, their performance during the combination of DBS and levodopa was not different from their best medical management presurgery. The results have implications for DBS target selection, particularly for those patients with oromotor dysfunctions.

First case of X-linked dystonia-parkinsonism ("Lubag") to demonstrate a response to bilateral pallidal stimulation.

"Lubag" or X-linked dystonia-parkinsonism (XDP) is a genetic syndrome afflicting Filipino men. Intracranial surgical procedures for Lubag have been unsuccessful. We report a 45-year-old Filipino male with genetically confirmed XDP who underwent bilateral pallidal deep brain stimulation (DBS) surgery. The patient started to exhibit improvement on initial programming, most notably of his severe jaw-opening dystonia. At 1-year follow-up, his Burke-Fahn-Marsden dystonia score and motor Unified Parkinson's Disease Rating Scale score were improved by 71% and 62%, respectively, with the stimulators on compared to stimulators off state. Bilateral pallidal DBS may be a viable option for Lubag patients with medically refractory symptoms.