M. Fiorella Contarino

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial

BACKGROUND Patients with advanced Parkinsons disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinsons disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinsons disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinsons disease. FUNDING Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Directional steering: A novel approach to deep brain stimulation.

Objective: The aim of this study was to investigate whether directional steering through a novel 32-contact electrode is safe and can modulate the thresholds for beneficial and side effects of stimulation. Methods: The study is a single-center, performance and safety study. Double-blind intraoperative evaluations of the thresholds for therapeutic benefit and for side effects were performed in 8 patients with Parkinson disease while stimulating in randomized order in spherical mode and in 4 different steering modes with the 32-contact electrode, and in monopolar mode with a commercial electrode. In addition, simultaneous recordings of local field potentials through all 32 contacts were performed. Results: There were no adverse events related to the experimental device. For 13 of 15 side effects (87%), the threshold could be increased by ≥1 mA while steering in at least one direction in comparison to conventional spherical stimulation, thereby increasing the therapeutic window by up to 1.5 mA. Recording local field potentials through all 32 electrode contacts yielded spatiotemporal information on pathologic neuronal activity. Conclusions: Controlled steering of current through the brain may improve the effectiveness of deep brain stimulation (DBS), allow for novel applications, and provide a tool to better explore pathophysiologic activity in the brain. Classification of evidence: This study provides Class IV evidence that for patients with Parkinson disease, steering DBS current is well tolerated, increases the threshold for side effects, and may improve the therapeutic window of subthalamic nucleus DBS as compared with current standard spherical stimulation.

Management of status dystonicus: Our experience and review of the literature

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase‐associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.

Phenotypic characterization of DYT13 primary torsion dystonia

We describe the phenotype of DYT13 primary torsion dystonia (PTD) in a family first examined in 1994. A complete neurological evaluation was performed on all available family members: 8 individuals were definitely affected by dystonia. The family was re‐evaluated in March 2000: at that time, 3 more individuals had developed symptoms of dystonia. Inheritance of PTD was autosomal dominant, with affected individuals spanning three consecutive generations and male‐to‐male transmission. Age at onset ranged from 5 to 43 years. Onset occurred either in the craniocervical region or in upper limbs. Progression was mild, and the disease course was benign in most affected individuals; generalization occurred only in 2 cases. We did not find anticipation of age at onset or of disease severity through generations. Most subjects presented with jerky, myoclonic‐like dystonic movements of the neck or shoulders. DYT13‐PTD is an autosomal dominant disease, with incomplete penetrance (58%). Clinical presentation and age at onset were more variable than in DYT1‐PTD, and the neck was involved in most of those affected. Moreover, the individuals with generalised dystonia were not severely disabled and were able to lead independent lives. To date, this is the only family with DYT13‐PTD.

Structural changes in cerebellar outflow tracts after thalamotomy in essential tremor

BACKGROUND This study set out to determine whether structural changes are present outside the thalamus after thalamotomy in patients with essential tremor (ET), specifically in the cerebellorubrothalamic tracts. We hypothesized that diffusion tensor imaging (DTI) would detect these changes. METHODS We collected DTI scans and analyzed differences in Fractional Anisotropy (FA) and Mean Diffusivity (MD) between the left and right superior and middle cerebellar peduncle in ET patients that have undergone unilateral, left, thalamotomy and ET patients that did not undergo thalamotomy (control group). We used classical ROI-based statistics to determine whether changes are present. RESULTS We found decreased FA and increased MD values in the right superior cerebellar peduncle leading to the left, lesioned thalamus, only in the thalamotomy group. CONCLUSIONS Our study suggests long-term structural changes in the cerebellorubrothalamic tract after thalamotomy. This contributes to further understanding of the biological mechanism following surgical lesions in the basal ganglia.