Implanted System for Orthostatic Hypotension in Multiple-System Atrophy.

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.).

Deep Brain Stimulation Improves Parkinson's Disease-Associated Pain by Decreasing Spinal Nociception.

Dopamine exerts antinociceptive effects on pain in PD at cortical and spinal levels, whereas only cortical effects have been described for DBS, so far. By assessing the nociceptive flexion reflex (NFR) threshold at medication on, and DBS ON and OFF in two patients, we showed that DBS additionally decreases spinal nociception.

[Neurology: what's new in 2023]. / Neurologie: ce qui a changé en 2023.

The year 2023 is marked by the arrival on the market of lecanemab for the treatment of Alzheimer's disease. New biomarkers have demonstrated their usefulness in monitoring peripheral neuropathies and diagnosing synucleinopathies. A genetic study has highlighted the role of nervous system cells in the risk of progression of multiple sclerosis (MS). The adverse effects of anticonvulsant treatments after prenatal exposure and on lipid metabolism have been clarified. New anti-CGRP treatments have demonstrated their efficacy in migraine attacks and chronic migraines. The criteria for thrombectomy have been further broadened. And finally, rehabilitation is refining the management of cerebrovascular patients and those with secondary progressive MS.

L'année 2023 est marquée par l'arrivée sur le marché du lécanémab pour le traitement de la maladie d'Alzheimer. De nouveaux biomarqueurs ont démontré leur utilité dans le suivi des neuropathies périphériques ou dans le diagnostic des synucléinopathies. Une étude génétique a mis en évidence le rôle des cellules du système nerveux dans le risque de progression de la sclérose en plaques (SEP). Les effets indésirables des traitements anticonvulsivants lors d'exposition prénatale ou sur le métabolisme des lipides ont été précisés. De nouveaux traitements anti-CGRP ont démontré leur efficacité dans les crises migraineuses et les migraines chroniques. Les critères de thrombectomie se sont encore élargis. Et enfin, la réhabilitation affine la prise en charge des patients cérébrovasculaires et de ceux atteints d'une SEP secondaire progressive.

[Tauopathy, motricity and cognition]. / Tauopathies, motricité et cognition.

The tauopathies are one of the families of proteinopathies causing neurodegenerative diseases. They are characterized by a combination of cognitive and motor disorders. In this article, we summarize the clinical features of progressive supranuclear palsy and cortico-basal degeneration, focusing on their cognitive-behavioral impairment profiles, which in some cases allow them to be differentiated from other neurodegenerative entities. Finally, we propose tools for therapeutic management.

Les tauopathies sont une des familles de protéinopathies engendrant des maladies neurodégénératives. Elles se caractérisent par l'association de troubles cognitifs et moteurs. Dans cet article, nous résumons les caractéristiques cliniques de la paralysie supranucléaire progressive et de la dégénérescence cortico-basale, en nous attardant sur leurs profils d'atteinte cognitivo-comportementale, qui permettent, dans certains cas, de les différencier d'autres entités neurodégénératives. Enfin, nous proposons des outils de prise en charge thérapeutique.

[Neurology: what's new in 2022]. / Neurologie : ce qui a changé en 2022.

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion. The causal relationship between Epstein-Barr infection and multiple sclerosis has been proved thanks to a large cohort study. A new possibility of subcutaneous continuous levodopa administration gave promising result. Finally, numerous studies confirmed the efficacy and excellent tolerability of anti-CGRP antibodies.

L'année 2022 a été marquée par l'arrivée de nombreux traitements pour la myasthénie réfractaire. Le lien entre l'épilepsie et le risque cérébro-vasculaire a été bien étudié, démontrant que la lamotrigine semble être le meilleur traitement pour prévenir la mortalité chez les patients de 45 ans et plus. De nouvelles études ont enfin pu établir l'utilité de la thrombectomie dans les occlusions basilaires. Le lien entre le virus d'Epstein-Barr et la sclérose en plaques a pu être prouvé à la suite d'une importante étude de cohorte. Une nouvelle technique d'administration sous-cutanée de la lévodopa semble prometteuse. Enfin, de nombreuses études confirment l'efficacité et l'excellente tolérance des anticorps anti-CGRP (Calcitonine Gene Related Protein).

[Neurology : what's new in 2021]. / Neurologie.

In 2021, we assisted to the publication of new diagnostic criteria, classifications, and guidelines (CIDP, brain tumors, auto-immune encephalitis). Several studies helped to define the pharmacological management of focal and generalized epileptic seizures and epilepsy in pregnant women. The availability of biomarkers and the approval of immunotherapies are modifying the landscape of dementia management. Endovascular interventions without previous thrombolysis seems to be effective in anterior circulation acute ischemic stroke (AIS) and severe posterior circulation AIS. Neurologic complications of Sars-CoV-2 infection were further studied, as well as the efficacy of vaccines in immunosuppressed patients. New molecules and techniques show promising results for the treatment of migraine and cluster headache.

L'année 2021 a été marquée par la publication des nouveaux critères diagnostiques, classifications et guidelines (polyradiculonévrite inflammatoire démyélinisante chronique, tumeurs cérébrales, encéphalites autoimmunes). L'attitude thérapeutique dans les épilepsies focales ou généralisées et l'épilepsie chez la femme enceinte a été mieux définie. Les marqueurs biologiques et les immunothérapies modifient le paysage de la prise en charge des démences. Le traitement endovasculaire des AVC de la circulation antérieure semble efficace indépendamment d'une thrombolyse préalable, ainsi qu'en cas d'AVC sévère de la circulation postérieure. Les complications neurologiques du SARS-CoV-2 ont été éclaircies et l'efficacité des vaccins étudiée chez les patients immunosupprimés. Plusieurs nouvelles molécules et techniques montrent des résultats prometteurs pour les migraines et céphalées en grappe.

[Recent Advances in Neurology]. / Neurologie.

Significant developments were published in 2020 in the field of blood biomarkers in Alzheimer's disease. Several studies helped to define more accurately the management of status epilepticus and of epilepsy in women of childbearing age. The new Swiss guidelines for the pre-hospital management of acute stroke were issued, as are new targets for stroke prevention. Numerous advances concerning the management of NMO-SD (NeuroMyelitis Optica Spectrum Disorder) were published. Different neurological presentations linked to the COVID-19 pandemic were described (central and peripheral). Several studies confirmed the effectiveness of new migraine treatments (including anti-CGRP). New pharmacological therapies are available for Parkinson's disease.

L'année 2020 a vu d'importantes avancées dans le domaine des biomarqueurs sanguins pour le diagnostic biologique de la maladie d'Alzheimer. Plusieurs études permettent de mieux définir la prise en charge de l'épilepsie chez la femme en âge de procréer et de l'état de mal épileptique. Les nouvelles recommandations suisses pour la prise en charge préhospitalière de l'AVC aigu sont en cours de publication, tout comme de nouvelles cibles pour leur prévention secondaire. De nombreuses avancées concernant la prise en charge des Neuromyelitis Optica Spectrum Disorder ont été publiées. Divers tableaux neurologiques (centraux et périphériques) liés à la pandémie de Covid-19 ont été décrits. Plusieurs études ont permis de confirmer l'efficacité des nouveaux traitements de la migraine (notamment les anti-Calcitonin Gene-Related Peptide). Enfin, de nouvelles thérapies pharmacologiques sont disponibles pour la maladie de Parkinson.

Complex movement disorder in a patient with heterozygous YY1 mutation (Gabriele-de Vries syndrome).

YY1 mutations cause Gabriele-de Vries syndrome, a recently described condition involving cognitive impairment, facial dysmorphism and intrauterine growth restriction. Movement disorders were reported in 5/10 cases of the original series, but no detailed description was provided. Here we present a 21-year-old woman with a mild intellectual deficit, facial dysmorphism and a complex movement disorder including an action tremor, cerebellar ataxia, dystonia, and partial ocular apraxia as the presenting and most striking feature. Whole-exome sequencing revealed a novel heterozygous de novo mutation in YY1 [NM: 003403.4 (YY1): c.907 T > C; p.(Cys303Arg)], classified as pathogenic according to the ACMG guidelines.

Dyskinesia-inducing lead contacts optimize outcome of subthalamic stimulation in Parkinson's disease.

BACKGROUND: Acute dyskinesias elicited by STN-DBS, here referred to as stimulation-induced dyskinesias, predict optimal clinical outcome in PD. However, it remains elusive whether stimulation-induced dyskinesias can guide DBS programming. OBJECTIVES: Here, we characterized stimulation-induced dyskinesias clinically and anatomically. We then tested whether dyskinesia-inducing contacts could be effectively programmed using independent current source technology. METHODS: We characterized stimulation-induced dyskinesias with directional and ring stimulation retrospectively in 20 patients. We then localized dyskinesia-inducing contacts by imaging coregistration and eventually programmed those contacts. RESULTS: We elicited dyskinesias in half of our patients. Dyskinesia-inducing contacts were mainly directional and were all located ventrally within the dorsolateral motor STN. When these dyskinesia-inducing contacts were programmed using independent current source technology, dyskinesia disappeared and robust antibradykinetic effects were obtained. CONCLUSION: We confirm that stimulation-induced dyskinesias are helpful clinical observations, which may guide programming of directional STN-DBS in PD. © 2019 International Parkinson and Movement Disorder Society.

Alcohol improves cerebellar learning deficit in myoclonus-dystonia: A clinical and electrophysiological investigation.

OBJECTIVE: To characterize neurophysiological subcortical abnormalities in myoclonus-dystonia and their modulation by alcohol administration. METHODS: Cerebellar associative learning and basal ganglia-brainstem interaction were investigated in 17 myoclonus-dystonia patients with epsilon-sarcoglycan (SGCE) gene mutation and 21 age- and sex-matched healthy controls by means of classical eyeblink conditioning and blink reflex recovery cycle before and after alcohol intake resulting in a breath alcohol concentration of 0.08% (0.8g/l). The alcohol responsiveness of clinical symptoms was evaluated by 3 blinded raters with a standardized video protocol and clinical rating scales including the Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale. RESULTS: Patients showed a significantly reduced number of conditioned eyeblink responses before alcohol administration compared to controls. Whereas the conditioning response rate decreased under alcohol intake in controls, it increased in patients (analysis of variance: alcohol state × group, p = 0.004). Blink reflex recovery cycle before and after alcohol intake did not differ between groups. Myoclonus improved significantly after alcohol intake (p = 0.016). The severity of action myoclonus at baseline correlated negatively with the conditioning response in classical eyeblink conditioning in patients. INTERPRETATION: The combination of findings of reduced baseline acquisition of conditioned eyeblink responses and normal blink reflex recovery cycle in patients who improved significantly with alcohol intake suggests a crucial role of cerebellar networks in the generation of symptoms in these patients. Ann Neurol 2017;82:543-553.

Systematic review of movement disorders and oculomotor abnormalities in Whipple's disease.

Whipple's disease, affecting the CNS, can cause a wide variety of symptoms. Movement disorders are very prevalent, and some are pathognomonic of the disease. This systematic review analyzed all published cases of movement disorders because of CNS Whipple's disease, providing detailed information on clinical and associated features. We have also attempted to address sources of confusion in the literature, particularly related to differing uses of the terminology of movement disorder. This comprehensive overview of Whipple's disease-induced movement disorders aims to aid neurologists in recognizing this very rare disorder and successfully reaching a laboratory-confirmed diagnosis in order to initiate appropriate therapy. © 2018 International Parkinson and Movement Disorder Society.

[Movement disorders emergencies]. / Mouvements anormaux aux urgences.

Unlike most basal ganglia disorders, which usually progress slowly and relentlessly, a number of movement disorders may develop as acute or subacute conditions. Their occurrence commonly prompts patients to rush into the emergency room. A proper diagnosis is not always straightforward and requires a detailed analysis of the movement disorder phenomenology and a thorough medication screening, as many of these acute situations may be iatrogenic and drug-related. An accurate identification of the problem may enable an effective management and an appropriate therapy. This article is an overview of three distinct movement disorder emergencies, namely acute dystonia, acute chorea, and acute complications that can be observed in Parkinson's disease. Each topic is illustrated with a case report.

Contrairement à la plupart des affections des ganglions de la base, qui évoluent généralement sur un mode lentement progressif, certains mouvements anormaux peuvent se développer sur un mode aigu ou subaigu, amenant les patients à consulter en urgence. Le diagnostic est souvent délicat. Il repose sur une analyse détaillée de la phénoménologie et une anamnèse médicamenteuse fouillée, dans la mesure où ces situations sont volontiers iatrogènes. Une identification correcte du problème permet souvent une thérapeutique efficace. Le présent article propose une mise au point de trois problématiques de ce type, à savoir la dystonie aiguë, la chorée aiguë et les complications aiguës que l'on peut observer dans la maladie de Parkinson. Chaque sujet est illustré par un cas clinique.

[Advanced Parkinson's disease : indication for complex treatments]. / Maladie de Parkinson au stade avancé : indication aux traitements complexes.

Advanced Parkinson's disease (PD) is characterized by severe motor and non-motor complications that negatively impact on patients' autonomy and health-related quality of life. In early disease, the therapeutic strategy consists of gradual increase in dopaminergic treatment and levodopa dose fragmentation. In more advanced stages, this approach becomes insufficient and three therapeutic options can be considered: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, and continuous levodopa/carbidopa intestinal gel infusion.

La maladie de Parkinson (MP) avancée est caractérisée par la présence de complications motrices et non motrices qui ont un impact significatif sur l'autonomie et la qualité de vie des patients. La stratégie thérapeutique consiste à fractionner le traitement dopaminergique, à recourir aux formes à libération prolongée, et aux inhibiteurs des enzymes de dégradation de la dopamine. Lorsque ces mesures sont insuffisantes, trois options thérapeutiques plus invasives peuvent être envisagées : la stimulation cérébrale profonde, la perfusion sous-cutanée continue d'apomorphine et l'administration intrajéjunale de gel de lévodopa/carbidopa. L'objectif de cet article est de décrire les indications, bénéfices et effets secondaires potentiels de ces traitements dits « complexes ¼.

[Deep brain stimulation: new targets and new indications]. / Stimulation cérébrale profonde: nouvelles cibles et nouvelles indications.

It is thanks to great advances in the field of neuroscience, which allowed identifying dysfunctions in neural networks as the cause of many psychiatric and neurological diseases, that the number of indications for deep brain stimulation (DBS) has quickly expanded. Although the precise mechanism of action of DBS is unknown, this method probably works by influencing the neural pathways through stimulation of deep targeted brain nuclei which behave as "hubs" in these complex networks. Currently, there is growing interest on DBS' potential benefit, especially in the psychiatric field. This review intends to tackle the current and future psychiatric and neurological indications of DBS.

Drug- and Toxin-Induced Opsoclonus - a Systematized Review, including a Case Report on Amantadine-Induced Opsoclonus in Multiple System Atrophy.

Background: Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus. Methods: Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies. Results: The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus. Conclusion: Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.

Exercise and gait/movement analyses in treatment and diagnosis of Parkinson's Disease.

Cardinal motor symptoms in Parkinson's disease (PD) include bradykinesia, rest tremor and/or rigidity. This symptomatology can additionally encompass abnormal gait, balance and postural patterns at advanced stages of the disease. Besides pharmacological and surgical therapies, physical exercise represents an important strategy for the management of these advanced impairments. Traditionally, diagnosis and classification of such abnormalities have relied on partially subjective evaluations performed by neurologists during short and temporally scattered hospital appointments. Emerging sports medical methods, including wearable sensor-based movement assessment and computational-statistical analysis, are paving the way for more objective and systematic diagnoses in everyday life conditions. These approaches hold promise to facilitate customizing clinical trials to specific PD groups, as well as personalizing neuromodulation therapies and exercise prescriptions for each individual, remotely and regularly, according to disease progression or specific motor symptoms. We aim to summarize exercise benefits for PD with a specific emphasis on gait and balance deficits, and to provide an overview of recent advances in movement analysis approaches, notably from the sports science community, with value for diagnosis and prognosis. Although such techniques are becoming increasingly available, their standardization and optimization for clinical purposes is critically missing, especially in their translation to complex neurodegenerative disorders such as PD. We highlight the importance of integrating state-of-the-art gait and movement analysis approaches, in combination with other motor, electrophysiological or neural biomarkers, to improve the understanding of the diversity of PD phenotypes, their response to therapies and the dynamics of their disease progression.

Avoiding Misdiagnosis in Global Rostral Midbrain Syndrome (GRMS): Clinical Insights and Neurorehabilitation Approaches.

This study reports two cases of Global Rostral Midbrain Syndrome (GRMS) and corpus callosum infarction in the context of shunt overdrainage caused by obstructive hydrocephalus due to aqueductal stenosis. We detail how thorough clinical evaluation and appropriate investigation helped avoid a coma misdiagnosis and describe the excellent response to pharmacological treatment and successful neurorehabilitation in both cases. We analyze the cognitive profile of patients with GRMS, a rare condition that mimics disorders such as coma and progressive supranuclear palsy at various stages. In conscious cases, GRMS typically presents with parkinsonian syndrome, Parinaud syndrome, and cognitive issues. The awareness of this rare complication of shunt overdrainage facilitates more accurate diagnosis and better management.

YY1 mutations disrupt corticogenesis through a cell-type specific rewiring of cell-autonomous and non-cell-autonomous transcriptional programs.

Germline mutations of YY1 cause Gabriele-de Vries syndrome (GADEVS), a neurodevelopmental disorder featuring intellectual disability and a wide range of systemic manifestations. To dissect the cellular and molecular mechanisms underlying GADEVS, we combined large-scale imaging, single-cell multiomics and gene regulatory network reconstruction in 2D and 3D patient-derived physiopathologically relevant cell lineages. YY1 haploinsufficiency causes a pervasive alteration of cell type specific transcriptional networks, disrupting corticogenesis at the level of neural progenitors and terminally differentiated neurons, including cytoarchitectural defects reminiscent of GADEVS clinical features. Transcriptional alterations in neurons propagated to neighboring astrocytes through a major non-cell autonomous pro-inflammatory effect that grounds the rationale for modulatory interventions. Together, neurodevelopmental trajectories, synaptic formation and neuronal-astrocyte cross talk emerged as salient domains of YY1 dosage-dependent vulnerability. Mechanistically, cell-type resolved reconstruction of gene regulatory networks uncovered the regulatory interplay between YY1, NEUROG2 and ETV5 and its aberrant rewiring in GADEVS. Our findings underscore the reach of advanced in vitro models in capturing developmental antecedents of clinical features and exposing their underlying mechanisms to guide the search for targeted interventions.

"De mandibulae dysarthria"--thinking outside the box.

BACKGROUND: Urgent decisions in the Emergency Department allow for only a short history and physical examination. OBJECTIVES: To highlight the risks associated with a strict application of protocols, especially in the emergency setting. CASE REPORT: An unusual case of acute dysarthria is presented. CONCLUSION: Even in the emergency setting, thorough history-taking and physical examination remain fundamental, and it is necessary to "think outside the box."

Therapies for obsessive-compulsive disorder: Current state of the art and perspectives for approaching treatment-resistant patients.

Even though obsessive compulsive disorder (OCD) is one of the ten most disabling diseases according to the WHO, only 30-40% of patients suffering from OCD seek specialized treatment. The currently available psychotherapeutic and pharmacological approaches, when properly applied, prove ineffective in about 10% of cases. The use of neuromodulation techniques, especially Deep Brain Stimulation, is highly promising for these clinical pictures and knowledge in this domain is constantly evolving. The aim of this paper is to provide a summary of the current knowledge about OCD treatment, while also discussing the more recent proposals for defining resistance.