Emmanuel Cuny

Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study

BACKGROUND Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause of disability in children and in adults, and responds poorly to medical treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. Our aim was to test the effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP. METHODS We did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI. The primary endpoint was change in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as assessed with the Burke-Fahn-Marsden dystonia rating scale. The accuracy of surgical targeting to the GPi was assessed masked to the results of neurostimulation. Analysis was by intention to treat. FINDINGS The mean Burke-Fahn-Marsden dystonia rating scale movement score improved from 44.2 (SD 21.1) before surgery to 34.7 (21.9) at 1 year post-operatively (p=0.009; mean improvement 24.4 [21.1]%, 95% CI 11.6-37.1). Functional disability, pain, and mental health-related quality of life were significantly improved. There was no worsening of cognition or mood. Adverse events were related to stimulation (arrest of the stimulator in one patient, and an adjustment to the current intensity in four patients). The optimum therapeutic target was the posterolateroventral region of the GPi. Little improvement was seen when the neurostimulation diffused to adjacent structures (mainly to the globus pallidus externus [GPe]). INTERPRETATION Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome. FUNDING National PHRC; Cerebral Palsy Foundation: Fondation Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

Parkinson's disease patients with bilateral subthalamic deep brain stimulation gain weight

Weight, body mass index (BMI) and energy expenditure/energy intake (EE/EI) was studied in 19 Parkinsons disease (PD) patients after subthalamic deep brain stimulation (STN‐DBS) versus 14 nonoperated ones. Operated patients had a significant weight gain (WG, + 9.7 ± 7 kg) and BMI increase (+ 4.7 kg/m2). The fat mass was higher after STN‐DBS. Resting EE (REE; offdrug/ON stimulation) was significantly decreased in STN‐DBS patients, while their daily energy expenditure (DEI) was not significantly different. A significant correlation was found among WG, BMI increase, and pre‐operative levodopa‐equivalent daily dose, their reduction after STN‐DBS, and the differential REE related to stimulation and the REE in the offdrug/OFF stimulation condition. In conclusion, STN‐DBS in PD induces a significant WG associated with a reduction in REE without DEI adjustment.

Distinct striatal targets in treating obsessive-compulsive disorder and major depression.

The ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). However, the respective roles of these structures in the pathophysiology of OCD and MD remain to be clarified. To address this issue, DBS of the ventral striatum was tested in 2 patients with severely distressing and intractable forms of OCD and MD. Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. These findings suggest that the caudate nucleus and nucleus accumbens participate differently in the pathogenesis of both of these psychiatric conditions.

Minimal tissue damage after stimulation of the motor thalamus in a case of chorea-acanthocytosis

Autopsy findings are reported from a patient with chorea-acanthocytosis treated for 2 years by deep brain stimulation (DBS) of the motor thalamus. Postoperative testing showed a progressive improvement in axial truncal spasms. Although relatively high currents were used for 2 years in this patient, postmortem analysis showed minimal tissue damage in the vicinity of the electrode tip. It is concluded that DBS has little impact on the surrounding tissues.

Neuronal Correlates of Obsessions in the Caudate Nucleus

BACKGROUND Metabolic overactivity of corticosubcortical loops including the caudate nucleus (CN) has been reported in obsessive-compulsive disorder (OCD) using functional imaging techniques. However, direct proof of a modification of neuronal activity within the CN of OCD patients is still lacking. We tested the hypothesis that obsessions or compulsions might be associated with particular features of neuronal activity in the CN of OCD patients. METHODS Single unit recordings were performed peroperatively in the CN of three patients with severe forms of obsessive-compulsive disorder (OCD) who were candidates for deep brain stimulation of the CN. Severity of obsessions was assessed preoperatively with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and peroperatively with a subjective obsession score based on a visual analog scale (VAS). RESULTS Frequency of CN discharge and variability of interspike intervals were found to be abnormally high in two patients with a high VAS score during surgery but not in one with a low VAS score. Lateralization and depth of recording influenced neuronal activity variably among patients. CONCLUSIONS Because the three patients had high Y-BOCS scores before surgery, these findings suggest that caudate hyperactivity in OCD is concomitant with the occurrence of the obsession process.

Deep brain pallidal stimulation for movement disorders in neuroacanthocytosis

Neuroacanthocytosis (NA) encompasses a heterogeneous set of neurodegenerative disorders associated with abnormal red blood cell morphology.1 The movement disorders of NA are often severe and incapacitating and may resist conventional drug therapy (i.e., neuroleptics and tetrabenazine). Encouraged by our previous experience in treating severe truncal spasms in a patient with chorea-acanthocytosis by chronic bilateral high-frequency stimulation of the posterior ventral oral nucleus of the thalamus2 and by the recent literature on the treatment of chorea by bilateral internal globus pallidus stimulation,3,4 we proposed this technique in two cases of NA with severe and intractable movement disorders. The first patient was a 32-year-old man with an 8-year history of choreatic-dystonic syndrome, dysarthria with recurrent distressing tasteless belching, and dramatic tongue biting. Walking was disturbed by intermittent moderate foot and back-arching dystonia. Cognitive impairment was obvious on clinical examination but impossible to test for linguistic reasons. The patient had 10% of acanthocytes among the circulating red blood cells, and an intronic mutation in the CHaC gene was consistent with the diagnosis of choreoacanthocytosis. Risperidone …

Primate models of dystonia

Several models of dystonia have emerged from clinical studies providing a comprehensive explanation for the pathophysiology of this movement disorder. However, several points remain unclear notably concerning the specific role of brainstem, basal ganglia nuclei and premotor cortex. We review data collected in sub-human primate to see whether they might provide new insights into the pathophysiology of dystonia. As in human patients, lesions of the putamen induce dystonia, as well as pharmacological manipulations of the dopaminergic system. In addition, primate studies revealed that lesions in brain stem areas involved in the control of muscular tone and GABAergic manipulations in various basal ganglia nuclei or thalamus also lead to dystonia. Moreover, there is a dramatic disruption in the processing of proprioceptive information with abnormal large receptive fields in the basal ganglia, thalamus, primary somesthetic cortex and premotor cortex of dystonic monkeys. These data highlight the idea that dystonia is associated with aberrant sensory representations interfering with motor control. Considering that the supplementary motor area (SMAp) is the target of basal ganglia projections within the motor loop, we propose a model of dystonia in which abnormal excitability, associated with alteration in sensory receptive fields within the SMAp, leads to an abnormal synchronization between primary motor cortex columns. Such a phenomenon might account for the co-contractions of antagonist muscles favored by action and the abnormal postures observed in dystonia.

Use of intraoperative monitoring of somatosensory evoked potentials to prevent ischaemic stroke after surgical exclusion of middle cerebral artery aneurysms.

SummaryObjective. The aim of this study was to assess the value of monitoring somatosensory evoked potentials (SEP) in the prevention of ischaemic stroke occurring during surgical exclusion of middle cerebral artery aneurysms.Methods. SEP monitoring was performed during the surgical exclusion of 131 aneurysms in 122 patients. All SEP variations over 30% were notified to the surgeon and those over 50% were considered as highly significant. If this happened, and in concert with the conduct of the operation, a return to the basal level was systematically sought.Results. Post-operative ischemic stroke was observed after 15 (11.4%) operations, leading to a permanent neurological deficit in 12 (9.2%). During nine (6.9%) operations there was a highly significant SEP change that persisted, or was only partially reversed, after corrective procedure. Nine of these patients had a post-operative is chaemic stroke. In 25 (19%), operations there was a highly significant SEP change followed by complete recovery. Of these 25 patients, 2 suffered a post-operative ischemic stroke. Following 49 operations (37.4%) with less significant SEP modifications, 4 patients suffered a post-operative stroke (8%). A stroke did not occur in the 48 (36.6%) operations during which there was not a variation in SEP. The strokes were related to temporary clipping in 9 patients to definitive clipping in 3 to sylvian fissure opening in 1 to brain retraction in and to dissection of the aneurysm in 1 (1 case).Conclusion. Changes in the SEP correlated well with the occurrence of post-operative stroke. This early detection of ischemia directs attention to the need for measures such as withdrawal of temporary clipping or identification of another factor (e.g. release of brain retraction or repositioning of an occlusive clip) so that the risk of post-operative is reduced.

Short and long term outcome of bilateral pallidal stimulation in chorea-acanthocytosis

Background Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS. Methods Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months). Results Motor severity, assessed by the Unified Huntington’s Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery. Conclusion This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.

Long-term efficacy and tolerability of bilateral pallidal stimulation to treat tardive dyskinesia.

Objective: To confirm the efficacy and safety of deep brain stimulation (DBS) of the internal part of the globus pallidus in improving severe tardive dyskinesia (TD). Methods: Nineteen patients with severe pharmacoresistant TD were included. All were assessed at baseline and at 3, 6 (main outcome measure), and 12 months, and in the long term (6–11 years) for 14 patients, after bilateral pallidal DBS, using motor scales (Extrapyramidal Symptoms Rating Scale [ESRS], Abnormal Involuntary Movement Scale [AIMS]), cognitive scales, and a psychiatric assessment. At 6 months, a double-blind ESRS evaluation was performed in the stimulation “on” and stimulation “off” conditions. Results: At 6 months, all patients had a decrease of more than 40% on the ESRS. The efficacy of the procedure was confirmed by a double-blind evaluation. This improvement was maintained at 12 months (ESRS: decrease of 58% [21%–81%]; AIMS: decrease of 50% [7%–77%]) and in the long term (ESRS: decrease of 60% [22%–90%]; AIMS: decrease of 63% [14%–94%], n = 14). All the subscores of the ESRS (parkinsonism, dystonia, and chorea) and of the AIMS (facial, oral, extremities, and trunk movements) improved. Despite psychiatric comorbidities at baseline, cognitive and psychiatric tolerability of the procedure was excellent. No cognitive decline was observed and mood was improved in most of the patients. Conclusions: Pallidal DBS procedure should be considered as a therapeutic option in disabling TD refractory to medical treatment. Classification of evidence: This study provides Class II evidence that in patients with severe pharmacoresistant TD with implanted pallidal leads, the stimulation “on” condition significantly improved ESRS scores compared to the stimulation “off” condition.