[Use of central anticholinergics in 2022]. / Utilisation des anticholinergiques centraux en 2022.

Cholinergic antagonists have been used for 60 years in the treatment of movement disorders. Their effect arises from a modulating activity within basal ganglia motor circuitry. Due to diffuse distribution among many organs, anticholinergic medications have numerous adverse effects. Nowadays, the indication of these molecules in the treatment of Parkinson disease is reduced, due to more effective and better tolerated alternatives. Iatrogenic parkinsonism is hardly alleviated by anticholinergics. These medications allow to prevent acute dystonic reactions induced by highly-dosed first generation antipsychotic agents. Once acute dystonia has appeared, parenteral treatment is to be preferred, but oral cholinergic antagonists may be used after the acute phase to prevent relapse. Botulinum toxin is preferred to anticholinergics for focal dystonia. In generalized dystonia, anticholinergic moderately alleviate symptoms.

Les anticholinergiques sont utilisés depuis plus de 60 ans pour traiter les mouvements anormaux. Leur effet thérapeutique provient d'une modulation, via des récepteurs muscariniques, des boucles motrices des noyaux gris centraux. Ce type de traitement a aussi de nombreux effets indésirables en lien avec la large distribution de récepteurs muscariniques dans plusieurs organes. Actuellement, la place de ces molécules est marginale dans le traitement de la maladie de Parkinson en raison d'alternatives plus efficaces et mieux tolérées. Leur efficacité est limitée en cas de parkinsonisme iatrogène. Ils contribuent à la prévention de la dystonie aiguë liée à l'utilisation de neuroleptiques de première génération à fortes doses. Lorsque la dystonie aiguë est présente, une solution parentérale est à privilégier, avec un relais possible par les anticholinergiques par voie orale. En cas de dystonie focale, les injections de toxine botulique sont plus efficaces. En cas de dystonie généralisée, les anticholinergiques ont une efficacité modérée.

[Multiple sclerosis : a neurological dysimmune inflammatory disease]. / La sclérose en plaques : une maladie neurologique dysimmunitaire inflammatoire.

Multiple sclerosis is a central nervous system autoimmune disease of the white and grey matters. Its pathophysiology is much better well known. It results from the interaction between genetic and environmental susceptibility factors. The role of EBV virus has recently been highlighted. Imaging techniques and neuropathology knowledge allow to distinguish several distinct processes responsible for focal and more diffuse inflammation. Therapeutic advances in recent years have been considerable. Different molecules and treatment sequences can be proposed to the patient with a demonstrated positive impact on the risk of disability secondary progression. Precise follow-up is a key. It requires optimal and early use of various treatments. The therapeutic choice must be guided by obtaining stabilization of the disease, both clinically and in terms of imaging, without exposing the patient to an excessive risk of side effects. Continuous and sequential treatments are available.

: La sclérose en plaques est une maladie auto-immune du système nerveux central qui concerne la substance blanche mais aussi la substance grise. Sa physiopathologie est beaucoup mieux connue. Elle résulte de l'interaction entre des facteurs génétiques de susceptibilité et environnementaux. Le rôle du virus EBV a été récemment souligné. Les techniques d'imagerie et les connaissances de neuropathologie ont permis de distinguer plusieurs processus distincts responsables d'une inflammation focale, mais également plus diffuse. Les progrès thérapeutiques des dernières années sont considérables. Différentes molécules et séquences de traitements peuvent être proposées au patient avec un impact positif démontré sur le risque de progression secondaire du handicap. La précision du suivi est un élément clé de la prise en charge. Elle requiert une utilisation optimale, et surtout précoce, des différents traitements. Le choix thérapeutique doit être guidé par l'obtention d'une stabilisation de la maladie, tant sur le plan clinique qu'en imagerie, sans exposer le patient à un risque excessif d'effets secondaires négatifs. Des traitements continus et séquentiels sont disponibles.

The Complex Interplay Between Trait Fatigue and Cognition in Multiple Sclerosis.

Cognitive impairments are frequent in patients with Multiple Sclerosis (MS). Yet, the influence of MS-related symptoms on cognitive status is not clear. Studies investigating the impact of trait fatigue along with anxio-depressive symptoms on cognition are seldom, and even less considered fatigue as multidimensional. Moreover, these studies provided conflicting results. Twenty-nine MS patients and 28 healthy controls, matched on age, gender and education underwent a full comprehensive neuropsychological assessment. Anxio-depressive and fatigue symptoms were assessed using the HAD scale and the MFIS, respectively. Six composite scores were derived from the neuropsychological assessment, reflecting the cognitive domains of working memory, verbal and visual learning, executive functions, attention and processing speed. Stepwise regression analyses were conducted in each group to investigate if trait cognitive and physical fatigue, depression and anxiety are relevant predictors of performance in each cognitive domain. In order to control for disease progression, patient's EDSS score was also entered as predictor variable. In the MS group, trait physical fatigue was the only significant predictor of working memory score. Cognitive fatigue was a predictor for executive functioning performance and for processing speed (as well as EDSS score for processing speed). In the healthy controls group, only an association between executive functioning and depression was observed. Fatigue predicted cognition in MS patients only, beyond anxio-depressive symptoms and disease progression. Considering fatigue as a multidimensional symptom is paramount to better understand its association with cognition, as physical and cognitive fatigue are predictors of different cognitive processes.

Incidental Verbal Semantic Processing Recruits the Fronto-temporal Semantic Control Network.

The frontoparietal semantic network, encompassing the inferior frontal gyrus and the posterior middle temporal cortex, is considered to be involved in semantic control processes. The explicit versus implicit nature of these control processes remains however poorly understood. The present study examined this question by assessing regional brain responses to the semantic attributes of an unattended stream of auditory words while participants' top-down attentional control processes were absorbed by a demanding visual search task. Response selectivity to semantic aspects of verbal stimuli was assessed via a functional magnetic resonance imaging response adaptation paradigm. We observed that implicit semantic processing of an unattended verbal stream recruited not only unimodal and amodal cortices in posterior supporting semantic knowledge areas, but also inferior frontal and posterior middle temporal areas considered to be part of the semantic control network. These results indicate that frontotemporal semantic networks support incidental semantic (control) processes.

[Paraneoplastic neurological syndromes]. / Les syndromes neurologiques paranéoplasiques.

Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.

Les syndromes neurologiques paranéoplasiques sont des complications neurologiques non métastatiques de cancers systémiques résultant, le plus souvent, d'une réaction immunitaire croisée dirigée contre des antigènes neuronaux membranaires ou intracellulaires. Certains de ces syndromes paranéoplasiques sont classiques comme les ataxies cérébelleuses, les neuronopathies sensitives ou ganglionopathies, l'encéphalite limbique, les encéphalomyélites ou le syndrome de Lambert-Eaton. Devant de tels tableaux cliniques, une étiologie paranéoplasique doit, surtout chez les patients présentant des facteurs de risque, être systématiquement recherchée. Bien que cette règle souffre de nombreuses exceptions, il y a souvent concordance entre un syndrome clinique spécifique, un type d'anticorps et une tumeur associée. Le diagnostic d'un syndrome neurologique paranéoplasique est essentiel puisqu'il révèle souvent le cancer sous-jacent. Le traitement comporte deux axes principaux : celui du cancer responsable et le contrôle de la réponse immunitaire.

[Carcinoid heart disease]. / Grande clinique intégrée. La maladie cardiaque carcinoïde.

Carcinoid syndrome is the term applied to a constellation of symptoms mediated by a variety of humoral factors produced by the well-differentiated neuroendocrine tumours (NET) localised usually in the gastrointestinal tract and the lungs. This syndrome includes a characteristic triad of diarrhea, flushing and cardiac disease. This cardiopathy occurs in 20 % of the cases and prevails on the right side of the heart. It evolves to a potentially severe heart failure. Therefore, early diagnosis and appropriate cardiac care are crucial to improve the prognosis of these patients. We report a case of a carcinoid syndrome with a trivalvular insufficiency and cardiac decompensation which required surgical replacement of the tricuspid and aortic valves.

Le syndrome carcinoïde est l'éponyme qui englobe une constellation de symptômes médiés par divers facteurs humoraux élaborés par des tumeurs neuroendocrines (NET) bien différenciées, situées le plus souvent au niveau du tube digestif et des poumons. Dans sa forme classique, il comprend une triade caractéristique associant diarrhée, flush cutané et cardiopathie. Cette cardiopathie est présente dans 20 % des cas et prédomine sur le versant droit du coeur. Cette affection peut évoluer vers une insuffisance cardiaque potentiellement sévère. C'est pourquoi un diagnostic et une prise en charge précoce semblent essentiels pour améliorer le pronostic de ces patients. Nous rapportons un cas de syndrome carcinoïde avec une insuffisance trivalvulaire et une décompensation cardiaque ayant nécessité une intervention chirurgicale de remplacement des valves tricuspide et aortique.

[Multiple sclerosis : therapy update]. / Actualités thérapeutiques dans la sclérose en plaques.

Multiple sclerosis is still a severe disease potentially associated with a short- or long-term disability in young adults. Since a few years therapeutic progresses are considerable. New drugs and new therapy rationale considerably improved our knowledge and patient's care. Early treatment is a key within dedicated specialized and multidisciplinary units. Clinical and neuroradiological no evidence of disease activity (NEDA) is a goal, which is more often reached. Patient's evolution and follow-up is completely changed in recent years with more efficacy.

La sclérose en plaques (SEP) reste une maladie grave du système nerveux central (SNC), potentiellement responsable d'un handicap, physique ou non, à moyen et long termes, chez des adultes jeunes. Les progrès thérapeutiques au cours des dernières années ont été considérables grâce à l'avènement de nouvelles molécules, mais aussi, et peut-être surtout, de schémas thérapeutiques nettement plus performants. Les progrès des connaissances en immunologie ont eu un impact majeur dans ce domaine. La prise en charge précoce des patients au sein d'unités intégrées et multidisciplinaires est une étape essentielle qui permet de guider l'utilisation rationnelle des médicaments. L'obtention d'une stabilité clinique et neuroradiologique est un défi qui est, de plus en plus souvent, relevé avec un bénéfice majeur pour les patients.

[Progressive ataxia and falls in a 62 year old woman]. / La vignette diagnostique de l'étudiant. Ataxie subaiguë et chutes chez une patiente de 62 ans.

We discuss the diagnostic workup of a 62 year old woman without any significant past medical history. We take this opportunity to point out three aspects : 1. The necessary contextualization of the whole process allowing to avoid unrealistic differentials; 2. The requirement to prioritize the diagnostic tests as a function of their expected contribution to the diagnosis, their invasive characteristic and their availability, including their cost and 3. The evolving character of the diagnostic process that, if needed, has to be reconsidered to integrate the information obtained from the first diagnostic tests and the evolution of the patient.

Nous discutons la démarche sémiologique et diagnostique d'un cas d'ataxie chez une patiente de 62 ans, indemne de tout antécédent médical significatif. A l'occasion de cette vignette diagnostique, nous insistons sur trois aspects : 1. La nécessité de contextualiser la démarche pour éviter d'évoquer des diagnostics différentiels irréalistes; 2. La nécessité de choisir les examens complémentaires pertinents en les hiérarchisant en fonction de la probabilité de contribuer au diagnostic, de leur invasivité et de leur disponibilité, y compris de leur coût et 3. Le caractère évolutif de la démarche diagnostique qu'il faut pouvoir remettre en question au fil des informations que fournissent l'évolution du patient et les résultats des investigations.

[Neurological consequences of alcoholism]. / Conséquences neurologiques centrales et périphériques de l'alcoolisme.

Chronic alcohol consumption results in multiple peripheral and central nervous system dysfunctions. Some are due to the direct action of alcohol or its derivatives, others are induced by the vitamin deficiencies associated with alcoholism, others are eventually related to the failure of other vital organs, such as the liver. In this short review, we describe alcohol-induced neuropathy, Gayet-Wernicke syndrome, Korsakoff syndrome, alcoholic dementia, Marchiafava-Bignami syndrome, hepatic encephalopathy, alcoholic epilepsy and manifestations of alcohol withdrawal.

La consommation éthylique chronique provoque de multiples dysfonctions des tissus nerveux périphérique et central. Certaines sont dues à l'action directe de l'alcool ou de ses dérivés, d'autres sont induites par les carences vitaminiques qui accompagnent l'éthylisme, d'autres enfin sont liées à la défaillance d'autres organes vitaux, tels que le foie. Nous décrivons, dans cette courte revue, la neuropathie éthylique, le syndrome de Gayet-Wernicke, le syndrome de Korsakoff, la démence alcoolique, le syndrome de Marchiafava-Bignami, l'encéphalopathie hépatique, l'épilepsie alcoolique et les manifestations du sevrage éthylique.

[Clinical management of acute stroke]. / L'accident vasculaire cérébral : Prise en charge urgente en pratique.

Stroke management dramatically changed during the last decades. Evidence shows that an early admission in a stroke unit offers the best chance of recovery to the stroke patient. The most spectacular aspect of the stroke unit activity consists of the hyperacute diagnostic and therapeutic stroke procedures, including prompt neuroimaging, intravenous thrombolysis and mechanical thrombectomy.

La prise en charge de l'accident vasculaire cérébral s'est considérablement modifiée durant la dernière décennie et continue d'évoluer, au bénéfice direct des patients victimes de cette urgence très fréquente. L'accent est mis sur la prise en charge la plus précoce possible par un centre hospitalier équipé d'une unité neurovasculaire. Celle-ci rassemble une équipe multidisciplinaire de professionnels habitués à prendre en charge cette pathologie : neurologues, neuroradiologues, neurochirurgiens, neuropsychologues, logopèdes, médecins physiques, infirmières. La manifestation la plus visible de cette unité consiste en la prise en charge diagnostique et thérapeutique à l'admission du patient. Celle-ci permet de distinguer rapidement les accidents ischémiques des hémorragies ou des thrombophlébites intracrâniennes puis, dans le cas ischémique, de procéder à la désocclusion de l'artère coupable, soit par thrombolyse intraveineuse, soit par thrombectomie mécanique, ou les deux.

Brain Metabolic Dysfunction in Capgras Delusion During Alzheimer's Disease: A Positron Emission Tomography Study.

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer's disease (AD) and Capgras syndrome was compared with those of 24-healthy elderly participants and 26 patients with AD without delusional syndrome. Comparing the healthy group with the AD group, the patient with AD had significant hypometabolism in frontal and posterior midline structures. In the light of current neural models of face perception, our patients with Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex.

[Stroke and aging]. / Accident vasculaire cérébral du sujet âgé.

Stroke risk increases with aging and one third of ischemic strokes occurs in very elderly (> or = 80 years). These are responsible of two thirds of the overall stroke-related morbi-mortality. Stroke in very elderly differs from younger individuals by sex ratio (more women), risk factors (more atrial fibrillation and hypertension) and usually a worse functional outcome. Very elderly are likely to benefit from stroke unit care and early revascularisation treatments although they have historically been excluded from this urgent management. These issues are likely to worsen in the future with the increasing impact of stroke on our aging societies.

[Narcolepsy-cataplexy today]. / La narcolepsie-cataplexie aujourd'hui.

Diagnostic criteria and pathophysiology of narcolepsy-cataplexy have evolved considerably over the last 10 years. The main cause, already mentioned in a previous paper, in the Revue Médicale de Liège (65), in 2002, is based, in human beings, on a destruction of specific cells located in the lateral and posterior part of the hypothalamus (the perifornical nuclei, containing some 70,000 neurons), producing peptides which stimulate the central nervous system; they are called hypocretins or orexins. The role of autoimmunity in their disappearance becomes more evident. The treatment is simplified, but remains symptomatic. It is mainly based on Sodium Oxybate or Gamma-Hydroxybutyrate, syrup, prescribed for the night. The authors report on their own experience in this regard and on future therapeutics more targeted towards the cause of the disease.

Hypnotic modulation of resting state fMRI default mode and extrinsic network connectivity.

Resting state fMRI (functional magnetic resonance imaging) acquisitions are characterized by low-frequency spontaneous activity in a default mode network (encompassing medial brain areas and linked to self-related processes) and an anticorrelated "extrinsic" system (encompassing lateral frontoparietal areas and modulated via external sensory stimulation). In order to better determine the functional contribution of these networks to conscious awareness, we here sought to transiently modulate their relationship by means of hypnosis. We used independent component analysis (ICA) on resting state fMRI acquisitions during normal wakefulness, under hypnotic state, and during a control condition of autobiographical mental imagery. As compared to mental imagery, hypnosis-induced modulation of resting state fMRI networks resulted in a reduced "extrinsic" lateral frontoparietal cortical connectivity, possibly reflecting a decreased sensory awareness. The default mode network showed an increased connectivity in bilateral angular and middle frontal gyri, whereas its posterior midline and parahippocampal structures decreased their connectivity during hypnosis, supposedly related to an altered "self" awareness and posthypnotic amnesia. In our view, fMRI resting state studies of physiological (e.g., sleep or hypnosis), pharmacological (e.g., sedation or anesthesia), and pathological modulation (e.g., coma or related states) of "intrinsic" default mode and anticorrelated "extrinsic" sensory networks, and their interaction with other cerebral networks, will further improve our understanding of the neural correlates of subjective awareness.

Multimodal neuroimaging in patients with disorders of consciousness showing "functional hemispherectomy".

Beside behavioral assessment of patients with disorders of consciousness, neuroimaging modalities may offer objective paraclinical markers important for diagnosis and prognosis. They provide information on the structural location and extent of brain lesions (e.g., morphometric MRI and diffusion tensor imaging (DTI-MRI) assessing structural connectivity) but also their functional impact (e.g., metabolic FDG-PET, hemodynamic fMRI, and EEG measurements obtained in "resting state" conditions). We here illustrate the role of multimodal imaging in severe brain injury, presenting a patient in unresponsive wakefulness syndrome (UWS; i.e., vegetative state, VS) and in a "fluctuating" minimally conscious state (MCS). In both cases, resting state FDG-PET, fMRI, and EEG showed a functionally preserved right hemisphere, while DTI showed underlying differences in structural connectivity highlighting the complementarities of these neuroimaging methods in the study of disorders of consciousness.

Functional neuroanatomy associated with the expression of distinct movement kinematics in motor sequence learning.

A broad range of motor skills, such as speech and writing, evolves with the ability to articulate elementary motor movements into novel sequences that come to be performed smoothly through practice. Neuroimaging studies in humans have demonstrated the involvement of the cerebello-cortical and striato-cortical motor loops in the course of motor sequence learning. Nonetheless, the nature of the improvement and brain mechanisms underlying different parameters of movement kinematics are not yet fully ascertained. We aimed at dissociating the cerebral substrates related to the increase in performance on two kinematic indices: velocity, that is the speed with which each single movement in the sequence is produced, and transitions, that is the duration of the gap between these individual movements. In this event-related fMRI experiment, participants practiced an eight-element sequence of finger presses on a keypad which allowed to record those kinematic movement parameters. Velocity was associated with activations in the ipsilateral spinocerebellum (lobules 4-5, 8 and medial lobule 6) and in the contralateral primary motor cortex. Transitions were associated with increased activity in the neocerebellum (lobules 6 bilaterally and lobule 4-5 ipsilaterally), as well as with activations within the right and left putamen and a broader bilateral network of motor cortical areas. These findings indicate that, rather than being the product of a single mechanism, the general improvement in motor performance associated with early motor sequence learning arises from at least two distinct kinematic processes, whose behavioral expressions are supported by partially overlapping and segregated brain networks.

Spectral quality of light modulates emotional brain responses in humans.

Light therapy can be an effective treatment for mood disorders, suggesting that light is able to affect mood state in the long term. As a first step to understand this effect, we hypothesized that light might also acutely influence emotion and tested whether short exposures to light modulate emotional brain responses. During functional magnetic resonance imaging, 17 healthy volunteers listened to emotional and neutral vocal stimuli while being exposed to alternating 40-s periods of blue or green ambient light. Blue (relative to green) light increased responses to emotional stimuli in the voice area of the temporal cortex and in the hippocampus. During emotional processing, the functional connectivity between the voice area, the amygdala, and the hypothalamus was selectively enhanced in the context of blue illumination, which shows that responses to emotional stimulation in the hypothalamus and amygdala are influenced by both the decoding of vocal information in the voice area and the spectral quality of ambient light. These results demonstrate the acute influence of light and its spectral quality on emotional brain processing and identify a unique network merging affective and ambient light information.

Bispectral index correlates with regional cerebral blood flow during sleep in distinct cortical and subcortical structures in humans.

The relationship between the Bispectral Index (BIS), an EEG-based monitor of anesthesia, and brain activity is still unclear. This study aimed at investigating the relationship between changes in BIS values during natural sleep and regional cerebral blood flow (rCBF) variations, as measured by Positron Emission Tomography (PET). Data were obtained from six young, healthy, right-handed, male volunteers (20-30 years old) using the H2(15)O infusion method. PET scans were performed both during waking and various stages of sleep. BIS values were monitored continuously and recorded during each PET scan. Positive correlations were detected between BIS and rCBF values in dorsolateral prefontal, parietal, anterior and posterior cingulate, precuneal, mesiofrontal, mesiotemporal and insular cortices. These areas belong to a frontoparietal network known to be related to awareness of self conscious sensory perception, attention and memory. BIS values also positively correlated with activity in brainstem and thalami, both structures known to be involved in arousal and wakefulness. These results show that BIS changes associated with physiological sleep depth co-vary with the activity of specific cortical and subcortical areas. The latter are known to modulate arousal, which in turn allows sustained thalamo-cortical enhancement of activity in a specific frontoparietal network known to be related to the content of consciousness. Thus, although mainly derived from frontal EEG, BIS could represent a wider index of cerebral activity.