French guidelines for the diagnosis and management of Tourette syndrome.

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

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.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Initial treatment of Parkinson's disease in 2016: The 2000 consensus conference revisited.

In 2000, a French consensus conference proposed guidelines for the treatment of Parkinson's disease (PD). Since then, new drugs have been concocted, new studies have been published and clinicians have become aware of some drug-induced adverse effects that were little known in the past. This has led us to reconsider the recommendations published 16 years ago. Thus, the aim of the present review is to present the recent data related to the different medications and non-pharmacological approaches available for PD, with a special focus on early-stage PD. Levodopa (LD), dopamine agonists (DAs), catechol-O-methyltransferase inhibitors (COMT-Is), anticholinergics, monoamine oxidase inhibitors (MAOB-Is) and amantadine have been considered, and their efficacy and safety for both motor as well as non-motor aspects are reported here. This has led to our proposal for a revised therapeutic strategy for the initiation of treatment in newly diagnosed PD patients, based on the available literature and the relative benefits/side effects balance.

A rare case of SPG11 mutation with multiple sclerosis.

We describe a patient with SPG11 hereditary spastic paraplegia (HSP), who developed walking disorder in childhood. He presented three episodes of subacute gait disorders worsening between the age of 20 and 22 years. Brain and spinal MRI revealed multiple T2 hypersignal lesions, consistent with inflammatory lesions. Surprisingly, CSF analysis showed neither oligoclonal bands nor increased IgG index. He was dramatically improved by intravenous methylprednisolone. A relapsing-remitting multiple sclerosis (MS) was suspected. This is the first description of SPG11 HSP associated with MS.

[Imaging non motor signs in Parkinson's disease]. / Imagerie des signes non moteurs dans la maladie de Parkinson.

Parkinson's disease is mainly considered as a motor disorder defined by a motor triad. However, various non-motor manifestations may be encountered in Parkinson's disease, including hyposmia, pain, fatigue, sleep disorders, cognitive and behavioral disorders. The pathophysiology of these signs is complex, not univocal and remains poorly understood. Functional imaging techniques either by positron emission tomography, single photon emission tomography or functional magnetic resonance imaging provide an invaluable opportunity to better understand the pathophysiology of these signs. In this paper, we present a review of the recent advances provided by functional imaging in this area.

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.

Molecular analyses of the LRRK2 gene in European and North African autosomal dominant Parkinson's disease.

BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.

[Postural tremor as first symptom of Huntington disease]. / Un tremblement d'attitude révélant une maladie de Huntington.

INTRODUCTION: Initial manifestations of Huntington's disease (HD) are varied and chorea is not always the first motor symptom. CASE REPORT: We report the case of a 44-year-old woman, with a family history of HD, who presented isolated head and upper limbs tremor for 4 years. Genetic testing confirmed the diagnosis of HD and no cause of secondary postural tremor was found. Propanolol was introduced with success. CONCLUSION: This kind of presentation is unusual and has mostly been reported in the juvenile form of HD.

[Behavioral disorders in Parkinson's disease: from pathophysiology to the mastery of dopaminergic treatment]. / Maladie de Parkinson: de la physiopathologie des troubles psychiques à la maîtrise du traitement dopaminergique.

INTRODUCTION: Behavioral changes in Parkinson's disease are complex and their pathophysiology is not yet fully understood. The dopaminergic system seems to play a major role and most of the behavioral disorders in Parkinson's disease can be classified into either hypodopaminergic if related to the disease itself or hyperdopaminergic if related to dopaminergic treatment. STATE OF THE ART: Subthalamic stimulation, which enables withdrawal of dopaminergic medication at an advanced stage in the disease, provides a model for the study of certain nonmotor, dopamine-sensitive symptoms. Such a study has shown that apathy, which is the most frequent behavioral problem in Parkinson's disease, is part of a much broader hypodopaminergic behavioral syndrome which also includes anxiety and depression. Nonmotor fluctuations--essential fluctuations in the patient's psychological state--are an expression of mesolimbic denervation, as shown in positron emission tomography. Drug-induced sensitization of the denervated mesolimbic system accounts for hyperdopaminergic behavioral problems that encompass impulse control disorders that can be alternatively classified as behavioral addictions. The association of impulse control disorders and addiction to the dopaminergic medication has been called dopamine dysregulation syndrome. While L-dopa is the most effective treatment for motor symptoms, dopamine agonists are more effective in improving the nonmotor levodopa-sensitive symptoms. On the other hand, L-dopa induces more motor complications and dopamine agonist more behavioral side effects. There is increasing data and awareness that patients' quality of life appears to be dictated by hypo- and hyperdopaminergic psychological symptoms stemming from mesolimbic denervation and dopaminergic treatment rather than by motor symptoms and motor complications related to nigrostriatal denervation and dopaminergic treatment. PERSPECTIVES: Better management requires knowledge of the clinical syndromes of hyper- and hypodopaminergic behaviors and nonmotor fluctuations, a better understanding of their underlying mechanisms and the development of new evaluation tools for these nonmotor symptoms. CONCLUSIONS: The neurologist who strives to gain mastery of dopaminergic treatment needs to fine tune the dosage of levodopa and dopamine agonists on an individual basis, depending on the presence of motor and nonmotor signs respectively.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD.

Management of apathy, depression and anxiety in Parkinson's disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.