Joan Miravite

Sixty hertz pallidal deep brain stimulation for primary torsion dystonia

Objective: To evaluate the safety and efficacy of 60 Hz deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 15 consecutive patients with primary dystonia. Methods: We conducted a retrospective analysis of clinic charts relative to 15 consecutive patients with medically refractory primary dystonia who underwent stereotactic implantation of DBS leads within the GPi. Twelve had the DYT1 gene mutation. Frame-based MRI and intraoperative microelectrode recording were employed for targeting. All patients were treated exclusively with stimulation at 60 Hz from therapy outset. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) served as the primary measure of symptom severity at baseline and 1, 3, 6, and 12 months after treatment. Results: All patients tolerated DBS treatment well and showed a progressive median improvement of their BFMDRS motor subscores from 38% at 1 month to 89% at 1 year (p < 0.001, Wilcoxon rank sum test). The disability subscores were similarly improved. The clinical response to DBS allowed seven patients to completely discontinue their medications; six additional patients had reduced their medications by at least 50%. Surgical complications were limited to two superficial infections, which were treated successfully. Conclusions: Stimulation of the internal globus pallidus at 60 Hz is safe and effective for treating medically refractory primary dystonia.

Parkinson disease phenotype in Ashkenazi jews with and without LRRK2 G2019S mutations

The phenotype of Parkinsons disease (PD) in patients with and without leucine‐rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel‐Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinsons Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non‐Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n = 97) and non‐carriers (n = 391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P < 0.001), were more likely to be women (51.5% vs. 37.9%; P = 0.015), and more often reported first symptoms in the lower extremities (40.0% vs. 19.2%; P < 0.001). In logistic models that were adjusted for age, disease duration, sex, education, and site, carriers were more likely to have lower extremity onset (P < 0.001), postural instability and gait difficulty (PIGD) (P = 0.043), and a persistent levodopa response for >5 years (P = 0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.

Lower stimulation frequency can enhance tolerability and efficacy of pallidal deep brain stimulation for dystonia

We report the case of a patient with medically refractory primary dystonia who was treated with bilateral pallidal deep brain stimulation. Stimulation at 130 Hz or higher, by means of the more ventral contacts generated capsular side effects, which made their use impractical. Consequently, the patient was treated for 9 months at 130 to 185 Hz, by means of the more dorsal contacts, achieving modest results. By reducing the stimulation frequency to 80 Hz, we were able to activate the ventral contacts without inducing side effects. Within days, the patient experienced a dramatic improvement in function that has persisted for 1 year. A further reduction in stimulation frequency to 60 Hz resulted in a worsening of his symptoms. We conclude that chronic stimulation at frequencies of <100 Hz may be efficacious in dystonia and may enhance the tolerability of stimulation by means of contacts that are positioned posteroventrally within the internal globus pallidus, nearer the internal capsule.

Deep brain stimulation in DYT1 dystonia: a 10-year experience.

BACKGROUND Globus Pallidus Interna (GPi) deep brain stimulation (DBS) is an effective treatment for DYT1-associated dystonia, but long-term results are lacking. OBJECTIVE To evaluate the long-term effects of GPi DBS in patients with DYT1 dystonia. METHODS A retrospective chart review (cohort study) of 47 consecutive DYT1+ patients treated by a single surgical team over a 10-year period and followed for up to 96 months (mean, 46 months) was performed. Symptom severity was quantified with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor (M) and disability (D) sub-scores. RESULTS As measured with the BFMDRS (M), symptom severity was reduced to less than 20% of baseline after 2 years of DBS therapy (P = .001). The disability scores were reduced to <30% of baseline (P = .001). Symptomatic improvement was durable throughout available follow-up. Sixty-one percent of patients had discontinued all dystonia-related medications at their last follow-up. Ninety-one percent had discontinued at least 1 class of medication. Infections requiring removal and later reimplantation of hardware occurred in 4 of 47 patients (8.5%). Hardware malfunction including lead fractures occurred in 4 of 47 cases (8.5%). Lead revision to address poor clinical response was performed in 2 of 92 implanted leads (2.2%). CONCLUSION GPi DBS is an effective therapy for DYT1-associated torsion dystonia. Statistically significant efficacy is maintained for up to 7 years. Neurologic complications are rare, but long-term hardware-related complications can be significant.

Lessons Learned from Open‐label Deep Brain Stimulation for Tourette Syndrome: Eight Cases over 7 Years

Background Deep brain stimulation (DBS) remains an experimental but promising treatment for patients with severe refractory Gilles de la Tourette syndrome (TS). Controversial issues include the selection of patients (age and clinical presentation), the choice of brain targets to obtain optimal patient-specific outcomes, and the risk of surgery- and stimulation-related serious adverse events. Methods This report describes our open-label experience with eight patients with severe refractory malignant TS treated with DBS. The electrodes were placed in the midline thalamic nuclei or globus pallidus, pars internus, or both. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video Protocol and the Yale Global Tic Severity Scale (YGTSS). Results Although three patients had marked postoperative improvement in their tics (>50% improvement on the YGTSS), the majority did not reach this level of clinical improvement. Two patients had to have their DBS leads removed (one because of postoperative infection and another because of lack of benefit). Discussion Our clinical experience supports the urgent need for more data and refinements in interventions and outcome measurements for severe, malignant, and medication-refractory TS. Because TS is not an etiologically homogenous clinical entity, the inclusion criteria for DBS patients and the choice of brain targets will require more refinement.

Neuropsychiatric characteristics of GBA-associated Parkinson disease

Mutations in GBA1 are a well-established risk factor for Parkinson disease (PD). GBA-associated PD (GBA-PD) may have a higher burden of nonmotor symptoms than idiopathic PD (IPD). We sought to characterize the relationship between GBA-PD and neuropsychiatric symptoms. Subjects were screened for common GBA1 mutations. GBA-PD (n=31) and non-carrier (IPD; n=55) scores were compared on the Unified Parkinson Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Beck Depression Inventory (BDI), and the State-Trait Anxiety Index (STAI). In univariate comparisons, GBA-PD had a greater prevalence of depression (33.3%) versus IPD (13.2%) (p<0.05). In regression models controlling for age, sex, disease duration, motor disability, and MoCA score, GBA-PD had an increased odds of depression (OR 3.66, 95% CI 1.13-11.8) (p=0.03). Post-hoc analysis stratified by sex showed that, among men, GBA-PD had a higher burden of trait anxiety and depression than IPD; this finding was sustained in multivariate models. Among women, GBA-PD did not confer greater psychiatric morbidity than IPD. These results suggest that GBA1 mutations confer greater risk of neuropsychiatric morbidity in PD, and that sex may affect this association.

Psychiatric and Cognitive Effects of Deep Brain Stimulation for Parkinson’s Disease

Deep brain stimulation (DBS) is effective for Parkinson’s disease (PD), dystonia, and essential tremor (ET). While motor benefits are well documented, cognitive and psychiatric side effects from the subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS for PD are increasingly recognized. Underlying disease, medications, microlesions, and post-surgical stimulation likely all contribute to non-motor symptoms (NMS).

A Case of Myoclonus–Dystonia Responding to Low-frequency Pallidal Stimulation

Background High-frequency pallidal stimulation has been shown to improve various types of dystonia, including myoclonus-dystonia. Case Report We report a case of epsilon sarcoglycan mutation-negative myoclonus–dystonia with response to low-frequency bilateral pallidal stimulation. Discussion Low-frequency pallidal stimulation provides an effective means of treating various dystonias, regardless of genetic status, as in our case, as it provides increased programming options with fewer adverse effects.

Parkinsonism and dystonia in Lubag disease respond well to high pulse width/low-frequency globus pallidus interna DBS

Lubag disease ( DYT3 ), an X-linked neurodegenerative condition featuring dystonia and parkinsonism, is caused by mutations in the TAF1 gene.1 DYT3 has been reported to respond to globus pallidus interna (GPi) deep brain stimulation (DBS) using frequencies above 100 Hz (table). We describe the first case of DYT3 responding to high pulse width and low-frequency stimulation.