D. Ricard

Severe meningo-radiculo-nevritis associated with ipilimumab

SummaryPurpose Ipilimumab is a T-cell-potentiating monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) to promote antitumoural immunity. In phase III trials, ipilimumab was shown to be the first agent to improve survival in advanced melanoma patients, regardless of previous treatment. We report a case of severe neurologic disease after ipilimumab treatment. Patient and methods Neurologic symptoms including facial diplegia, tetraplegia, areflexia progressed with time a few days after the fourth monthly ipilimumab infusion. Analysis of the cerebro-spinal fluid showed elevated proteinorachy and lymphocytic meningitis. Despite high doses of steroids and symptomatic treatment, the symptoms worsened. Results Veinoglobulins were then infused and the patient began to improve and recovered almost normal activity two years later. Conclusion The adverse event profile associated with ipilimumab was primarily immune-related. This is the first case in which such a severe event has been reported.

Inertial Sensors to Assess Gait Quality in Patients with Neurological Disorders: A Systematic Review of Technical and Analytical Challenges

Gait disorders are major causes of falls in patients with neurological diseases. Understanding these disorders allows prevention and better insights into underlying diseases. InertiaLocoGraphy (ILG) –the quantification of gait by using inertial measurement units (IMUs) –shows great potential to address this public health challenge, but protocols vary widely and normative values of gait parameters are still unavailable. This systematic review critically compares ILG protocols, questions features extracted from inertial signals and proposes a semeiological analysis of clinimetric characteristics for use in neurological clinical routine. For this systematic review, PubMed, Cochrane and EMBASE were searched for articles assessing gait quality by using IMUs that were published from January 1, 2014 to August 31, 2016. ILG was used to assess gait in a wide range of neurological disorders – including Parkinson disease, mild cognitive impairment, Alzheimer disease, cerebral palsy, and cerebellar atrophy – as well as in the faller or frail older population and in people presenting rheumatological pathologies. However, results have not yet been driving changes in clinical practice. One reason could be that studies mainly aimed at comparing pathological gait to healthy gait, but there is stronger need for semiological descriptions of gait perturbation, severity or prognostic assessment. Furthermore, protocols used to assess gait using IMUs are too many. Likely, outcomes are highly heterogeneous and difficult to compare across large panels of studies. Therefore, homogenization is needed to foster the use of ILG to assess gait quality in neurological routine practice. The pros and cons of each protocol are emphasized so that a compromise can be reached. As well, analysis of seven complementary clinical criteria (springiness, sturdiness, smoothness, steadiness, stability, symmetry, synchronization) is advocated.

Syndrome d’hypersensibilité aux antiépileptiques. Cas particulier de la lamotrigine

Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

Abcès du tronc cérébral à Listeria monocytogenes

INTRODUCTIONnListeriosis commonly involves the central nervous system. Meningoencephalitis and rhomboencephalitis are the most frequent manifestations. Brain abscesses are rare.nnnCASE REPORTnWe report the case of a 63-year-old man treated with steroids for a long period; he was hospitalized for hemiparesis, confusion and fever. Clinical examination revealed meningeal signs, right hemiparesis and Parinaud syndrome. Initial CT scan was normal. The CSF contained 520 white cells/mm3 with predominance of polymorphonuclear neutrophils. An acute meningo- rhombencephalitis in an immunodepressed patient was suggested. The diagnosis of listeriosis was confirmed by blood cultures. Amoxicillin and gentamycin were started. The outcome on day 4 was severe with coma and tetraparesis. Brain MRI revealed a left peduncle abscess which descended deep into the brain reaching the internal capsule. The final clinical outcome involved residual right hemiparesis and left oculomotor nerve (III) palsy.nnnCONCLUSIONnBrain stem abscess is an uncommon form of listerial central nervous system infection. Listeria monocytogenes infection should be considered in patients with altered cell-mediated immunity that develop local neurologic deficits, a diagnosis which pursued rapidly with repeated blood cultures. Successful treatment requires early antibiotic therapy with ampicillin and gentamycin.

Observational Study of 180° Turning Strategies Using Inertial Measurement Units and Fall Risk in Poststroke Hemiparetic Patients

Objective We analyzed spontaneous 180° turning strategies in poststroke hemiparetic patients by using inertial measurement units (IMUs) and the association of turning strategies with risk of falls. Methods We included right paretic (RP) and left paretic (LP) post-stroke patients, and healthy controls (HCs) from a physical and rehabilitation department in France between July 2015 and October 2015. All subjects were right-handed and right-footed for mobilization tasks. Participants were instructed to turn 180° in a self-selected direction after a 10-m walk while wearing three IMUs on their trunk and both feet. We defined three turning patterns based on the number of external steps (pattern Iu2009=u20091; IIu2009=u20092–4 steps; and IIIu2009≥u20095) and four turning strategies based on the side chosen to turn (healthy or paretic) and the stance limb used during the first step of the turn (healthy or paretic). Falls in the 6u2009months after measurement were investigated. Results We included 17 RP [mean (SD) age 57.5 (9.5) years (range 43–73)], 20 LP patients [mean age 60.7 (8.8) years (range 43–63)], and 15 HCs [mean age 56.7 (16.1) years (range 36–83)]. The LP and RP groups behaved similarly in turning patterns, but 90% of LP patients turned spontaneously to the paretic side versus 59% of RP patients. This difference increased with turning strategies: 85% of LP versus 29% of RP patients used strategy 4 (paretic turn side with paretic limb). Patients using strategy 4 had the highest rate of falls. Conclusion We propose to consider spontaneous turning strategies as new indicators to evaluate the risk of fall after stroke. IMU could be routinely used to identify this risk and guide balance rehabilitation programs.

SMART syndrome: Classic transient symptoms leading to an unusual unfavorable outcome

BACKGROUNDnStroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare complication of cerebral radiation therapy that usually presents>10 years after treatment as reversible paroxysmal episodes of neurological dysfunction associated with headaches.nnnCASESnWe report here on two cases of SMART syndrome in long-term survivors of high-grade glioma for whom neuropathological data were available. The course of the disease was unfavorable. Although the clinico-radiological picture of SMART syndrome clearly differs from classic cerebral radionecrosis, the gross neuropathological lesions observed in our two patients appeared to be similar to those described in focal radionecrosis.nnnCONCLUSIONnSMART syndrome may progress from a benign reversible form to a severe and eventually irreversible form. This severe course may also be confused with tumor progression, and lead to permanent disability and inadequate antitumor treatment. Clinicians should be aware of this latter atypical presentation.

Paramyotonie congénitale d'Eulenburg

Resume Introduction La paramyotonie congenitale d’Eulenburg est une canalopathie de transmission autosomique dominante, liee a des mutations sur le gene codant pour la sous-unite α du canal sodium musculaire. Observation Un homme âge de 38 ans presentait depuis l’enfance des contractures musculaires qui survenaient electivement a l’effort lors d’une exposition au froid. Leur topographie etait cheiro-facio-orale. Elles etaient parfois suivies d’acces de faiblesse musculaire. Plusieurs membres de sa famille presentaient une symptomatologie similaire. L’examen clinique mit en evidence une myotonie mecanique a la percussion musculaire. L’electromyogramme revela des salves myotoniques diffuses. L’analyse de l’ADN a mis en evidence une mutation faux-sens Arg1448Cys a l’etat heterozygote dans l’exon 24 du gene codant pour la sous-unite α du canal sodium musculaire (SCN4A) sur le chromosome 17. Conclusion Cette affection est rarement evolutive. Le traitement repose essentiellement sur des mesures preventives. A visee symptomatique, differentes molecules peuvent etre proposees : des stabilisateurs de membrane comme les antiarythmiques (mexiletine, tocainide), ou l’inhibiteur de l’anhydrase carbonique (acetazolamide). Des precautions sont a prendre en cas d’anesthesie generale compte tenu du risque de crises paralytiques et de myotonie, notamment du diaphragme.

New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study

BackgroundRadiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria.MethodsPatients referred to our center for deterioration in cognitive complaint at least 6xa0months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded.ResultsForty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53xa0Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30xa0Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL).ConclusionsRIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Étude observationnelle du demi-tour à l’aide de capteurs inertiels chez les sujets victimes d’AVC et relation avec le risque de chute

Introduction Le demi-tour est evalue en routine a l’aide du nombre de pas exterieurs et de sa duree. Ces deux parametres ne rendent pas compte de toute la cinematique du demi-tour ce que pourraient permettre en routine les capteurs inertiels (IMUs). Nous avonsxa0: –xa0compare les strategies de demi-tour spontanees des sujets hemiparetiques droits (HD) et gauches (HG) post-AVC avec des IMUsxa0; –xa0etudie la correlation des strategies avec la survenue de chute. Materiel et methodes Tous les sujets etaient droitiersxa0; 17xa0HD (43xa0a 73xa0ans, moyenne 57,5) et 20xa0HG (43xa0a 63xa0ans, moyenne 59,6) ont ete inclus. Ils devaient realiser un demi-tour dans la direction de leur choix apres 10xa0m de marche en portant 1xa0IMUs a la ceinture et 1xa0sur chaque pied. Nous avons defini 3xa0patterns de demi-tour bases sur le nombre de pas exterieurs (pattern Ixa0=xa01xa0; IIxa0=xa02–4xa0pasxa0; IIIxa0≥xa05) et 4xa0strategies de demi-tour basees sur le cote spontanement choisi pour tourner (sain ou paretique) et le premier pied d’appui du demi-tour (sain ou paretique). Le nombre de chute dans les 6xa0mois suivant la mesure a ete evalue par questionnaire telephonique. Resultats Les HG et les HD ont des resultats similaires en termes de patterns de demi-tour, cependant 90xa0% des HG tournent spontanement du cote hemiparetique contre seulement 59xa0% des HD ( p xa0=xa00,01, Chi 2 ). Cette difference augmente lorsque l’on regarde les strategies de demi-tourxa0: 85xa0% des HG versus 29xa0% des HD ( p xa0=xa00,04, Chi 2 ) etaient en strategie 4 (demi-tour du cote paretique avec premier appui sur le pied paretique). Les patients utilisant la strategie 4xa0avaient un risque de chute plus eleve. Discussion – conclusion Les strategies de demi-tour evaluees en routine avec des IMUs pourraient constituer un indicateur supplementaire de chute.

À la recherche de marqueurs objectifs de la fatigue dans la sclérose en plaques

Introduction La fatigue est omnipresente dans la SEP, souvent en l’absence de handicap important. Objectifs Reveler des marqueurs objectifs quantitatifs de la fatigue permettant d’aider le clinicien et d’approfondir la comprehension physiopathologique de la fatigue dans la SEP. Methodes Vingt-six patients, a distance d’une poussee, ont evalue leur fatigue par l’echelle EMIF-SEP puis ont ete soumis (1) a la mesure de variables refletant la fatigue chez le sujet sain surentraine, telles que la variabilite de la frequence cardiaque (VFC) au changement de posture, la force musculaire des membres superieurs et des dosages de marqueurs salivaires ou sanguins, et (2) a la mesure de variables plus specifiques de la SEP telles que les taux sanguins de cytokines et la baisse de performance au test cognitif PASAT. Resultats Un tiers des patients s’est evalue fatigue (score EMIF total ≥ 79/104). La frequence cardiaque matinale et la VFC etaient correlees aux scores EMIF. Le profil des autres marqueurs du surentrainement ne permettait pas de caracteriser la fatigue des patients. Les taux sanguins de TNFα et ADH etaient correles a la fatigue physique des patients. Enfin la fatigabilite revelee par le test PASAT n’etait correlee qu’a la fatigue sociale de l’EMIF et ne rendait pas compte de la plainte dans sa globalite. Discussion L’etude confirme l’intervention d’un dysfonctionnement neuro-vegetatif dans la fatigue observee dans la SEP qui differe de celui lie au surentrainement. De plus, l’individualisation de marqueurs inflammatoires objectifs tel que le TNFα sanguin suggere que le controle de la regulation immune peut influencer le symptome fatigue. Enfin, la notion de fatigabilite demasquee par le PASAT ne reflete pas la fatigue ressentie par les patients. Conclusion Il existe un pattern biologique specifique a la fatigue dans la SEP. La plainte de fatigue ne correspond pas a la mesure objective de la fatigabilite. La reponse immune pourrait etre en lien avec la fatigue ressentie.