The paired-pulse TMS paradigm of short intracortical inhibition is mediated by a reduction of repetitive motor neuron discharges.

Transcranial magnetic stimulation (TMS) causes repetitive spinal motoneuron discharges (repMNDs), but the effects of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) on repMNDs remain unknown. Triple stimulation technique (TST) and the extended TST-protocols that include a fourth and fifth stimulation, the Quadruple (QuadS) and Quintuple (QuintS) stimulation, respectively, offer a precise estimate of cortical and spinal motor neuron discharges, including repMNDs. The objective of our study was to explore the effects of SICI and ICF on repMNDs. We explored conventional paired-pulse TMS protocols of SICI and ICF with the TMS, TST, the QuadS, and the QuintS protocols, in a randomized study design in 20 healthy volunteers. We found significantly less repMNDs in the SICI paradigm compared with a single-pulse TMS (SP-TMS). No significant difference was observed in the ICF paradigm. There was a significant inter- and intrasubject variability in both SICI and ICF. We demonstrate a significant reduction of repMNDs in SICI, which may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no increase in repMNDs in ICF suggesting another mechanism underlying facilitation. This study provides the proof that a reduction of repMNDs mediates the inhibition seen in SICI.NEW & NOTEWORTHY Significant reduction of repetitive motor neuron discharges (repMNDs) in short-interval intracortical inhibition (SICI) may result from the suppression of later I-waves and mediate the inhibition of motor-evoked potential (MEP). There is no change in the number of repMNDs in intracortical facilitation (ICF). There was a significant variability in SICI and ICF in healthy subjects.

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 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 2019]. / Neurologie.

New studies confirm the possibility of late thrombolysis. Meta-analyses have confirmed that CGRP inhibitors are efficacious for migraines. Cladribine is a new oral treatment for relapsing-remitting multiple sclerosis. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a new clinical entity accounting for cognitive decline in old patients. The timing of levodopa introduction has no effect on the long-term course of idiopathic Parkinson's disease. Hypophosphatemia helps distinguish between seizures and syncopes in the emergency department. A second course of intravenous immunoglobulins provides no benefit for severe Guillain Barre syndrome. Outdoor therapy improves clinical scales in patients with disorder of consciousness. Ultrasound guided lumbar puncture improves the yield of the procedure.

De nouvelles études confirment la possibilité de thrombolyse tardive. Les méta-analyses confirment l'effet bénéfique des inhibiteurs du CGRP (calcitonin gene-related peptide) pour la migraine. La cladribine est un nouveau traitement oral pour la sclérose en plaque de type poussée-rémission. L'encéphalopathie à TDP-43 à prédominance limbique est une nouvelle entité en lien avec des troubles cognitifs de la personne âgée. Le délai d'introduction de la lévodopa n'a pas d'influence sur l'évolution à long terme de la maladie de Parkinson. L'hypophosphatémie aide à différencier les crises d'épilepsie des syncopes. Une deuxième cure d'immunoglobulines n'apporte pas de bénéfice dans le traitement du syndrome de Guillain-Barré. Les patients avec troubles de l'état de conscience bénéficient des thérapies à l'air libre. L'ultrason améliore le rendement de la ponction lombaire.

[Neurology]. / Neurologie.

Thrombolysis and late thrombectomy can be performed in case of compatible radiological imaging. Anti-CGRP monoclonal antibodies seem more effective for the treatment of migraine. Siponimod can reduce significantly disability progression in secondarily progressive MS. Brand-to-generic levetiracetam switching does not cause recrudescence of epileptic seizures. A new definition of Alzheimer's disease using biomarkers of cerebrospinal fluid (CSF) and imaging provides a better understanding of the underlying mechanisms. The use of levodopa-carbidopa intestinal gel and a subcutaneous apomorphine infusion allow a reduction of motor fluctuations in Parkinson's disease. Eculizumab appears as an alternative treatment in severe forms of myasthenia gravis.

La thrombolyse et la thrombectomie tardives peuvent être effectuées en cas d'imagerie favorable. Les anticorps monoclonaux anti-CGRP semblent plus efficaces pour le traitement de la migraine. Le siponimod permet de ralentir significativement la progression du handicap dans la sclérose en plaques (SEP) secondairement progressive. L'utilisation de génériques de lévétiracétam n'engendre pas de recrudescence de crises épileptiques. Une nouvelle définition de la maladie d'Alzheimer à l'aide des biomarqueurs du liquide céphalorachidien (LCR) et d'imagerie permet une meilleure compréhension des mécanismes sous-jacents. La perfusion intestinale d'un gel de lévodopa-carbidopa et la pompe d'apomorphine diminuent les fluctuations motrices dans la maladie de Parkinson. L'éculizumab apparaît comme une alternative dans les formes sévères de myasthénie.

[Deep brain stimulation]. / Tiefe Hirnstimulation.

Deep brain stimulation Abstract. Deep brain stimulation, a neurosurgical therapy, consists of implanting electrodes in certain brain regions via which electrical impulses are applied by means of a neurostimulator (brain pacemaker). The therapeutic efficacy has been scientifically proven in various neurological and psychiatric indications. Deep Brain Stimulation offers a treatment option for severe disease progression and inadequate response to medication. Fluctuations and dyskinesias in Parkinson's disease, dystonia, refractory tremor and epilepsy, and certain pain syndromes are approved indications for deep brain stimulation in Switzerland.

[Current developments in Parkinson's disease]. / Actualité de la maladie de Parkinson.

Our understanding of Parkinson's disease has considerably evolved in the last few years. While the cardinal motor features bradykinesia, rigidity, and tremor define the disease and respond to dopamine replacement therapy, there is a wider-spread neurodegeneration causing non motor symptoms and their impact on the quality of life of patients is being increasingly recognized. The follow-up requires a good collaboration between primary care physicians and neurologists. The purpose of this article is to offer a practical treatment guide of uncomplicated Parkinson's disease for general practitioners and internal medicine specialists. The management of late complications of Parkinson's disease will be addressed in another article.

Notre compréhension de la maladie de Parkinson a été bouleversée ces dernières années. Alors que les manifestations motrices cardinales (bradykinésie, rigidité, tremblement) définissent toujours la maladie et sont traitées efficacement avec la substitution dopaminergique, nous reconnaissons de plus en plus l'importance des symptômes non moteurs, qui résultent d'une neurodégénérescence plus étendue et qui grèvent substantiellement la qualité de vie des patients. Ces connaissances renouvellent la collaboration entre le médecin traitant et le neurologue. Nous proposons ici un vade-mecum de la maladie de Parkinson non compliquée, à l'attention du médecin généraliste et interniste. Le traitement des complications est le sujet d'un autre article.

[Neurology]. / Neurologie.

Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. A form of gene therapy, patisiran, has shown positive results in transthyretin familial amyloidosis. In the treatment of headaches, particularly migraines, non-pharmacological approaches have shown some interesting results. The criteria for Lewy body dementia have been revised. Generic use of lamotrigine does not result in recrudescence of epileptic seizures or adverse effects.

L'ocrélizumab (Ocrevus), un anticorps monoclonal anti-CD20, a été homologué dans le traitement de la sclérose en plaques. L'éculizumab (Soliris) a été approuvé dans plusieurs pays pour les formes réfractaires de myasthénie grave généralisée séropositive. Une forme de thérapie génique, le patisiran a montré des résultats positifs dans l'amyloïdose à transthyrétine. Dans le traitement des céphalées, en particulier des migraines, les approches non pharmacologiques ont montré quelques avancées. Les critères de la démence à corps de Lewy ont été révisés. L'utilisation de génériques de la lamotrigine n'engendre pas de recrudescence de crises épileptiques ni d'effets indésirables.

[Neurology]. / Neurologie.

Aducanumab reduces the burden of amyloid plaques in Alzheimer's disease, with significant improvement of clinical scores. Endovascular thrombectomy is recommended in patients with acute stroke with proximal occlusion of the anterior circulation. CGRP antagonists and botulinum toxin are effective in migraine. ZIKA virus infection has been linked to the Guillain-Barré syndrome. Edaravone has been approved for amyotrophic lateral sclerosis. Two monoclonal antibodies (ocrelizumab and daclizumab) and siponimod show positive results in multiple sclerosis. Thalamotomy of ventral intermediate nucleus (by gamma-knife or by magnetic resonance-guided focused ultrasound) is effective in drug-resistant essential tremor. The dose-dependent risk of foetal malformations associated with valproate and topiramate is confirmed.

L'aducanumab réduit la présence de plaques amyloïdes dans la maladie d'Alzheimer, avec amélioration significative des scores cliniques. Dans l'AVC aigu, la thrombectomie endovasculaire est recommandée en présence d'une occlusion proximale de la circulation antérieure. La toxine botulinique est efficace dans la migraine chronique. L'infection à virus Zika est associée au syndrome de Guillain-Barré. L'édaravone a été approuvé pour la sclérose latérale amyotrophique. Deux anticorps monoclonaux (ocrélizumab et daclizumab) et le siponimod montrent des résultats positifs dans la sclérose en plaques. La thalamotomie du noyau ventral intermédiaire par gamma-knife et par ultrasons focalisés guidés par résonance magnétique est efficace dans le tremblement pharmaco-résistant. Le risque dose-dépendant de malformations fœtales liées au valproate et au topiramate est confirmé.

[Neurology]. / Neurologie.

In 2015, cerebral stimulation becomes increasingly established in the treatment of pharmacoresistant epilepsy. Efficacy of endovascular treatment has been demonstrated for acute ischemic stroke. Deep brain stimulation at low frequency improves dysphagia and freezing of gait in Parkinson patients. Bimagrumab seems to increase muscular volume and force in patients with inclusion body myositis. In cluster-type headache, a transcutaneous vagal nerve stimulator is efficient in stopping acute attacks and also reducing their frequency. Initial steps have been undertaken towards modulating memory by stimulation of the proximal fornix. Teriflunomide is the first oral immunomodulatory drug for which efficacy has been shown in preventing conversion from clinical isolated syndrome to multiple sclerosis.

[Non-invasive brain stimulation for Parkinson's disease]. / Stimulation cérébrale non invasive: évolution d'un nouveau concept pour la thérapie de la maladie de Parkinson.

Parkinson's disease (PD) is a major socio-economic burden increasing with the aging population. In advanced PD, the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation (NIBS) as an alternative therapeutic tool. NIBS could offer an alternative approach for patients at risk who are excluded from surgery and/or to treat refractory symptoms. The treatment of the freezing of gait, a major cause of disability and falls in PD patients, could be enhanced by transcranial direct current stimulation (tDCS). A therapeutic study is currently performed at the Department of Neurology at the CHUV.

[News in neurology 2014]. / Neurologie.

In 2014, breastfeeding during maternal antiepileptic therapy seems to be safe for the children and can be recommended. Intravenous thrombolysis by Alteplase improves the outcome after a stroke if administered within 4.5 hours and it is also recommended in elderly population over 80 years. ProSavin genic therapy for Parkinson disease is under investigation. The Transcranial Magnetic Stimulation (TMS) has an analgesic effect in neuropathic pain as well as an antidepressant effect. Antagonists of calcitonin gene-related peptide can have a beneficial role in migraine prevention. Diagnostic biomarker panels for Alzheimer disease are under investigation. Oral teriflunomide and dimethyl fumarate (BG-12) for relapsing multiple sclerosis treatment are now available in Switzerland.

[Follow-up of nerve and muscle disorders: the collaboration between general practitioner and specialist]. / Suivi des malades neuromusculaires: collaboration entre praticien et spécialiste.

The follow-up of neuromuscular diseases varies widely as the etiologies and requires specialized care. Yet, the inter-disciplinary and collaborative approach with the General Practitioner (GP) is indispensable, and we may review the international recommandations according to the Evidence-based Medicine (EBM) of frequent symptoms like cramps and neuropathic pain. Besides, we discuss some principles of our daily pratice, which--we hope--would facilitate the communication with the GPs.

[News in neurology 2013]. / Neurologie.

In 2013, perampanel is approved as an add-on treatment for generalised and focal seizures in pharmaco-resistant epilepsy. New anticoagulants are superior to antivitamin K in stroke secondary prevention in case of atrial fibrillation. DBS remains a valid therapeutic option for advanced Parkinson's disease. Intranasal ketamine seems to reduce the intensity of severe migraine aura. High concentrations of topic capsaicin improve post-herpetic neuralgia. In Alzheimer's disease, statins might deteriorate cognitive functions. Oral immuno-modifing treatments for relapsing remitting multiple sclerosis have shown to slow cerebral atrophy progression at two years.

Slowing gait during turning: how volition of modifying walking speed affects the gait pattern in healthy adults.

Background: Turning during walking and volitionally modulating walking speed introduces complexity to gait and has been minimally explored. Research question: How do the spatiotemporal parameters vary between young adults walking at a normal speed and a slower speed while making 90°, 180°, and 360° turns? Methods: In a laboratory setting, the spatiotemporal parameters of 10 young adults were documented as they made turns at 90°, 180°, and 360°. A generalized linear model was utilized to determine the effect of both walking speed and turning amplitude. Results: Young adults volitionally reducing their walking speed while turning at different turning amplitudes significantly decreased their cadence and spatial parameters while increasing their temporal parameters. In conditions of slower movement, the variability of certain spatial parameters decreased, while the variability of some temporal parameters increased. Significance: This research broadens the understanding of turning biomechanics in relation to volitionally reducing walking speed. Cadence might be a pace gait constant synchronizing the rhythmic integration of several inputs to coordinate an ordered gait pattern output. Volition might up-regulate or down-regulate this pace gait constant (i.e., cadence) which creates the feeling of modulating walking speed.

Clinical neurophysiology in the treatment of movement disorders: IFCN handbook chapter.

In this review, different aspects of the use of clinical neurophysiology techniques for the treatment of movement disorders are addressed. First of all, these techniques can be used to guide neuromodulation techniques or to perform therapeutic neuromodulation as such. Neuromodulation includes invasive techniques based on the surgical implantation of electrodes and a pulse generator, such as deep brain stimulation (DBS) or spinal cord stimulation (SCS) on the one hand, and non-invasive techniques aimed at modulating or even lesioning neural structures by transcranial application. Movement disorders are one of the main areas of indication for the various neuromodulation techniques. This review focuses on the following techniques: DBS, repetitive transcranial magnetic stimulation (rTMS), low-intensity transcranial electrical stimulation, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), and focused ultrasound (FUS), including high-intensity magnetic resonance-guided FUS (MRgFUS), and pulsed mode low-intensity transcranial FUS stimulation (TUS). The main clinical conditions in which neuromodulation has proven its efficacy are Parkinson's disease, dystonia, and essential tremor, mainly using DBS or MRgFUS. There is also some evidence for Tourette syndrome (DBS), Huntington's disease (DBS), cerebellar ataxia (tDCS), and axial signs (SCS) and depression (rTMS) in PD. The development of non-invasive transcranial neuromodulation techniques is limited by the short-term clinical impact of these techniques, especially rTMS, in the context of very chronic diseases. However, at-home use (tDCS) or current advances in the design of closed-loop stimulation (tACS) may open new perspectives for the application of these techniques in patients, favored by their easier use and lower rate of adverse effects compared to invasive or lesioning methods. Finally, this review summarizes the evidence for keeping the use of electromyography to optimize the identification of muscles to be treated with botulinum toxin injection, which is indicated and widely performed for the treatment of various movement disorders.

Effects of physiotherapy and home-based training in parkinsonian syndromes: protocol for a randomised controlled trial (MobilityAPP).

INTRODUCTION: Gait and mobility impairment are pivotal signs of parkinsonism, and they are particularly severe in atypical parkinsonian disorders including multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A pilot study demonstrated a significant improvement of gait in patients with MSA of parkinsonian type (MSA-P) after physiotherapy and matching home-based exercise, as reflected by sensor-based gait parameters. In this study, we aim to investigate whether a gait-focused physiotherapy (GPT) and matching home-based exercise lead to a greater improvement of gait performance compared with a standard physiotherapy/home-based exercise programme (standard physiotherapy, SPT). METHODS AND ANALYSIS: This protocol was deployed to evaluate the effects of a GPT versus an active control undergoing SPT and matching home-based exercise with regard to laboratory gait parameters, physical activity measures and clinical scales in patients with Parkinson's disease (PD), MSA-P and PSP. The primary outcomes of the trial are sensor-based laboratory gait parameters, while the secondary outcome measures comprise real-world derived parameters, clinical rating scales and patient questionnaires. We aim to enrol 48 patients per disease group into this double-blind, randomised-controlled trial. The study starts with a 1 week wearable sensor-based monitoring of physical activity. After randomisation, patients undergo a 2 week daily inpatient physiotherapy, followed by 5 week matching unsupervised home-based training. A 1 week physical activity monitoring is repeated during the last week of intervention. ETHICS AND DISSEMINATION: This study, registered as 'Mobility in Atypical Parkinsonism: a Trial of Physiotherapy (Mobility_APP)' at clinicaltrials.gov (NCT04608604), received ethics approval by local committees of the involved centres. The patient's recruitment takes place at the Movement Disorders Units of Innsbruck (Austria), Erlangen (Germany), Lausanne (Switzerland), Luxembourg (Luxembourg) and Bolzano (Italy). The data resulting from this project will be submitted to peer-reviewed journals, presented at international congresses and made publicly available at the end of the trial. TRIAL REGISTRATION NUMBER: NCT04608604.

Spatiotemporal parameters during turning gait maneuvers of different amplitudes in young and elderly healthy adults: A descriptive and comparative study.

BACKGROUND: Turning during walking adds complexity to gait and has been little investigated until now. Research question What are the differences in spatiotemporal parameters between young and elderly healthy adults performing quarter-turns (90°), half-turns (180°) and full-turns (360°)? METHODS: The spatiotemporal parameters of 10 young and 10 elderly adults were recorded in a laboratory while turning at 90°, 180° and 360°. Two-way mixed ANOVA were performed to determine the effect of age and turning amplitude. RESULTS: Elderly were slower and needed more steps and time to perform turns of larger amplitude than young adults. Cadence did not differ across age or across turning amplitude. Generally, in the elderly, the spatial parameters were smaller and the temporal parameters enhancing stability (i.e., double-support phase and stance/cycle ratio) were larger, especially for turns of larger amplitudes. In elderly adults, the variability of some spatial parameters was decreased, whereas the variability of some temporal parameters was increased. Stride width of the external leg showed the most substantial difference between groups. Most parameters differed between turning at 90° and turning at larger amplitudes (180°, 360°). Significance This study extends the characterization of turning biomechanics with respect to ageing. It also suggested paying particular attention to the turning amplitude. Finally, the age-related differences may pave the way for new selective rehabilitation protocols in the elderly.

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee.

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.