Feasibility of changing for a rechargeable constant current neurostimulator in Parkinson's disease.

BACKGROUND: Little is known about outcome and settings adaptations after replacement of constant-voltage non-rechargeable implantable pulse generator (CV-nrIPG) by constant-current rechargeable IPG (CC-rIPG). OBJECTIVE: To determine the feasibility and safety of replacing a CV-nrIPG by a CC-rIPG in Parkinson's disease (PD) and the subsequent outcome. METHODS: A prospective cohort of thirty PD patients, whose CV-nrIPG was replaced by a CC-rIPG in University Hospital of Lyon between January 2017 and December 2018 (rIPG group) and 39 PD patients, who underwent the replacement of a CV-nrIPG by the same device in 2016 (nrIPG group), were enrolled in this study. Three surgeons performed the operations. Duration of hospitalization for the replacement as well as the number of in or outpatient visits during the first 3 months after the surgery were recorded. In the rIPG group, we compared preoperative DBS settings and the theoretical amplitude estimated using Ohm's law to the amplitude used at the end of follow-up. We assessed patients' and clinicians' opinion on the patient global functioning after the replacement using Clinical Global Impression score. RESULTS: Duration of hospitalization (P=0.47) and need for additional hospitalizations (P=0.73) or consultations (P=0.71) to adapt DBS parameters did not differ between the two groups. Neurological condition (CGI score) was considered as unchanged by both patients and neurologists. Final amplitude of stimulation using CC-rIPG was not predicted by Ohm's law in most cases. CONCLUSIONS: Replacing CV-nrIPG by CC-rIPG is safe and well tolerated but require neurological expertise to set the new parameters of stimulation.

Optimizing the deep brain stimulation care pathway in patients with Parkinson's disease.

Management of Parkinson's disease (PD) using deep brain stimulation (DBS) requires complex care in specialized, multidisciplinary centers. A well-organized, efficient patient flow is crucial to ensure that eligible patients can quickly access DBS. Delays or inefficiencies in patient care may impact a center's ability to meet demand, creating a capacity bottleneck. Analysis of the current practices within a center may help identify areas for improvement. After external audit of the DBS workflow of the Lyon Neurological Hospital and comparison with other European centers, manageable steps were suggested to restructure the care pathway. Propositions of the audit comprised, for example: (1) directly admitting referred patients to hospital, without a prior neurological outpatient visit and (2) including the preoperative anesthesia consultation in the hospital stay 1 month before surgery, not separately. This reorganization (between 2013 and 2016) was performed without increases in hospital medical resources or costs. The time from patients' first referral to surgery was reduced (from 22 to 16 months; p = 0.033), as was the number of pre- and postoperative patient visits (11-5; p = 0.025) and the total cumulative length of in-hospital stay (20.5-17.5 nights; p = 0.02). Ultimately, the total number of PD consultations increased (346-498 per year), as did the number of DBS implants per year (32-45 patients). In this single center experience, restructuring the DBS care pathway allowed a higher number of PD patients to benefit from DBS therapy, with a shorter waiting time and without decreasing the quality of care.

Xeroderma pigmentosum: a rare cause of chorea.

Xeroderma pigmentosum (XP) is an uncommon inherited dermatological disorder characterized by a high degree of skin photosensitivity with development of carcinomas at an early age. Neurological manifestations may be encountered in XP but few detailed descriptions have been provided. Here we describe a sister and a brother presenting chorea, dystonia, myoclonus, ataxia and polyneuropathy related to XP.

Obsessive-compulsive disorder after unilateral caudate nucleus bleeding.

Obsessive compulsive disorders (OCD) may be encountered after basal ganglia lesions of various aetiologies. These lesions are usually bilateral. We report here the case of a 24 years old man who developed a pure compulsive behavior after a unilateral left-sided caudate nucleus hemorrhage due to a cavernoma. The pathophysiology of this compulsive disorder probably reflects a frontal cortex deafferentation mechanism. Behavioral, psychological and medical (serotoninergic) treatments are usually proposed but the efficacy of such therapy remains to be investigated in secondary OCD.

On-line motor control in patients with Parkinson's disease.

Recent models based, in part on a study of Huntington's disease, suggest that the basal ganglia are involved in on-line movement guidance. Two experiments were conducted to investigate this idea. First, we studied advanced Parkinson's disease patients performing a reaching task known to depend on on-line guidance. The task was to 'look and point' in the dark at visual targets displayed in the peripheral visual field. In some trials, the target location was slightly modified during saccadic gaze displacement (when vision is suppressed). In both patient and control groups, the target jump induced a gradual modification of the movement which diverged smoothly from its original path to reach the new target location. No deficit was found in the patients, except for an increased latency to respond to the target jump (Parkinson's disease: 243 ms; controls: 166 ms). A computational simulation indicated that this response slowing was likely to be a by-product of bradykinesia. The unexpected inconsistency between this result and previous reports was investigated in a second experiment. We hypothesized that the relevant factor was the characteristics of the corrections to be performed. To test this prediction, we investigated a task requiring corrections of the same type as investigated in Huntington's disease, namely large, consciously detected errors induced by large target jumps at hand movement onset. In contrast with the smooth adjustments observed in the first experiment, the subjects responded to the target jump by generating a discrete corrective sub-movement. While this iterative response was relatively rapid in the control subjects (220 ms), Parkinson's disease patients exhibited either dramatically late (>730 ms) or totally absent on-line corrections. When on-line corrections were absent, the initial motor response was completed before a second corrective response was initiated (the latency of the corrective response was the same as the latency of the initial response). Considered together, these results suggest that basal ganglia dependent circuits are not critical for feedback loops involving a smooth modulation of the ongoing command. These circuits may rather contribute to the generation of discrete corrective sub-movements. This deficit is in line with the general impairment of sequential and simultaneous actions in patients with basal ganglia disorders.

Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism.

The DJ-1 gene was identified as responsible for early onset autosomal recessive parkinsonism in two families (PARK7). In this study, after excluding mutations in the parkin gene, the authors screened a large series of early onset autosomal recessive parkinsonism families and consanguineous isolated patients of diverse geographic origins for DJ-1 mutations. No mutations were found. This indicates that PARK7 is not a common locus for early onset autosomal recessive parkinsonism, and that one or more new loci remains to be identified.

The timing of antiparkinsonian treatment reduction after subthalamic nucleus stimulation.

The objective of this work was to precisely analyse the reduction of the antiparkinsonian treatment in 18 consecutive patients with Parkinson's disease (PD) operated on for bilateral subthalamic nucleus (STN) stimulation, first after 1 month of follow-up, then at 1 year postoperatively. Trihexyphenidyle, selegiline, entacapone, apomorphine and lisuride could be withdrawn shortly after starting STN electrical stimulation. The levodopa mean daily dose was reduced by 57% at 1 month after surgery and remained stable at 1 year. The mean ropinirole and bromocriptine daily dose decrements after surgery corresponded to 54 and 63%, respectively, at 1 month and to 77 and 40% at 1 year. At 12 months postoperatively, one third of the patients no longer received any antiparkinsonian drugs and the others were on monotherapy of either levodopa or dopamine agonists or received a combined treatment of a dopaminergic agonist and levodopa. In conclusion, STN stimulation allows a major reduction and simplification of antiparkinsonian treatment which can usually be achieved during the early postoperative period.

[Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (Melas) associated with a Fahr disease and cerebellar calcifications]. / Encéphalomyopathie mitochondriale de type Melas associée à un syndrome de Fahr avec calcifications cérébelleuses.

INTRODUCTION: Melas syndrome is a mitochondrial disease which corresponds to the association of mitochondrial encephalopathy, lactic acidosis and stroke-like espisodes. CASE REPORT: The authors report the case of a 39 year-old woman presenting with hearing loss, seizures, visual field deficit, three stroke-like episodes and calcifications of the basal ganglia and cerebellar dentate nuclei. Melas syndrome was suspected and confirmed by muscle biopsy, showing ragged red fibers and the presence of an A3243G mutation of mitochondrial DNA. CONCLUSION: This clinical, pathological and radiological observation shows that intracerebral calcifications may involve the dentate nuclei of the cerebellum in the Melas syndrome.

Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients.

The aim of the present study was to assess the efficacy and safety of chronic subthalamic nucleus deep-brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). 18 consecutive severely affected PD patients were included (mean age, SD: 56.9+/-6 years; mean disease duration: 13.5+/-4.4 years). All the patients were evaluated clinically before and 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS). Additionally, a 12 months follow-up was available in 14 patients. The target coordinates were determined by ventriculography under stereotactic conditions, followed by electrophysiology and intraoperative stimulation. After surgery, continuous monopolar stimulation was applied bilaterally in 17 patients at 2.9+/-0.4 V through 1 (n = 31) or 2 contacts (n = 3). One patient had bilateral bipolar stimulation. The mean frequency of stimulation was 140+/-16 Hz and pulse width 68+/-13 micros. Off medication, the UPDRS part III score (max = 108) was reduced by 55 % during on stimulation (score before surgery: 44.9+/-13.4 vs at 6 months: 20.2+/-10; p < 0.001). In the on medication state, no difference was noted between the preoperative and the postoperative off stimulation conditions (scores were respectively: 17.9+/-9.2 and 23+/-12.6). The severity of motor fluctuations and dyskinesias assessed by UPDRS IV was reduced by 76 % at 6 months (scores were respectively: 10.3+/-3 and 2.5+/-3; p < 0.001). Off medication, the UPDRS II or ADL score was reduced by 52.8 % during on stimulation (26.9+/-6.5 preop versus 12.7+/-7 at 6 months). The daily dose of antiparkinsonian treatment was diminished by 65.5 % (levodopa equivalent dose -- mg/D -- was 1045 +/- 435 before surgery and 360 +/- 377 at 6 months; p < 0.01). These results remained stable at 12 months for the 14 patients studied. Side effects comprised lower limb phlebitis (n = 2), pulmonary embolism (n = 1), depression (n = 6), dysarthria and freezing (n = 1), sialorrhea and drooling (n = 1), postural imbalance (n = 1), transient paresthesias and dyskinesias. This study confirms the great value of subthalamic nucleus stimulation in the treatment of intractable PD. Some adverse events such as depression may be taken into account in the inclusion criteria and also in the post-operative outcome.

Pre- and postnatal enzyme analysis for infantile, late infantile and adult neuronal ceroid lipofuscinosis (CLN1 and CLN2).

The recent development of simple, fluorogenic enzyme assays for infantile and late infantile neuronal ceroid lipofuscinosis (INCL and LINCL; CLN1 and CLN2) has greatly facilitated the diagnostic process for these diseases. In leucocytes and fibroblasts from INCL (n = 38) patients we found profound deficiencies of palmitoyl-protein thioesterase I (PPT1), the residual activity was < 5% of mean control activity. In fibroblasts from LINCL patients we found a similar deficiency of tripeptidyl-peptidase I activity (TPP-I), with < 2% activity in 16 patients. The residual TPP-I activity in leucocytes from LINCL patients seemed substantially higher. We also showed the feasibility of reliable prenatal enzyme analysis. In five first-trimester and two second-trimester prenatal analyses for INCL, four affected foetuses were detected (PPT activity 3-6%). Two first trimester pregnancies at risk for LINCL were analysed and a clear TPP-I deficiency was detected in both cases (TPP-I activity 3-4%). The first patient with adult neuronal ceroid lipofuscinosis (ANCL) due to a deficiency of PPT is presented; her present age is 53 years and the onset of the disease was at 38 years with psychiatric symptoms.

[Cortical thrombophlebitis and developmental venous anomalies]. / Thrombophlébite corticale et anomalie veineuse du développement.

Abnormal intracranial venous drainage called cerebral venous angioma is usually asymptomatic. Hemorrhages and seizures may however occur. The malformation may rarely be revealed by thrombosis. We report the case of a 25-year-old right-handed woman who developed cortical thrombophlebitis subsequent to developmental venous anomalies. After a course of anticoagulant therapy, outcome was good, demonstrating that anticoagulant therapy may be indicated in spite of the high risk of hemorrhage.