Search

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

ObjectiveTo characterize the full spectrum, relative frequency, and prognosis of the neurologic manifestations in Zika virus (ZIKV) postnatal infection.MethodsWe conducted an observational study in consecutive ZIKV-infected patients presenting with neurologic manifestations during the French West Indies 2016 outbreak.ResultsEighty-seven patients, including 6 children, were enrolled. Ninety-five percent of all cases required hospitalization. Guillain-Barré syndrome was the most frequent manifestation (46.0%) followed by encephalitis or encephalomyelitis (20.7%), isolated single or multiple cranial nerve palsies (9.2%), other peripheral manifestations (6.9%), and stroke (1.1%). Fourteen patients (16.1%), including one child, developed a mixed disorder involving both the central and peripheral nervous system. Mechanical ventilation was required in 21 cases, all of whom had ZIKV RNA in at least one biological fluid. Two adult patients died due to neuroZika. Clinical follow-up (median 14 months; interquartile range, 13–17 months) was available for 76 patients. Residual disability (modified Rankin Scale score ≥2) was identified in 19 (25.0%) patients; in 6 cases (7.9%), disability was severe (modified Rankin Scale score ≥4). Among patients with ZIKV RNA detected in one biological fluid, the risk of residual disability or death was higher (odds ratio 9.19; confidence interval 1.12–75.22; p = 0.039).ConclusionsNeuroZika spectrum represents a heterogeneous group of clinical neurologic manifestations. During an outbreak, clinicians should consider neuroZika in patients presenting with cranial nerve palsies and a mixed neurologic disorder. Long-term sequelae are frequent in NeuroZika. ZIKV reverse-transcription PCR status at admission can inform prognosis and should therefore be taken into consideration in the management of hospitalized patients.

Background HTLV1-associated myelitis (HAM) is a slowly progressive myelopathy in which spinal cord MRI demonstrates no lesion or atrophy. Objective We examined the overlap between NMOSD features and HTLV1 infection. Methods We included all HTLV1-infected patients recruited in French West Indies (FWI) or referred from different centers, and suffering from at least one NMOSD feature. Literature connecting HTLV1-infection and NMOSD was reviewed. Results We included six NMOSD-like HAM with acute onset, seronegative against AQP4 and MOG-Abs. All displayed extensive longitudinal myelitis, and the optic nerve was involved in three. We gathered 39 cases of NMOSD-like HAM patients from the literature. Atypical signs of HAM were relapses (15.4%), sensory level (50%), upper limb symptoms (35.9%), optic neuritis (10.2%). Typical lesions involved lateral funiculi and featured a double rope sign (56.3%). Conclusion We propose that acute onset of NMOSD-like HAM could be more frequent than expected and should be evoked in high-risk patients. Extensive but often transient cord lesions could be the hallmark of an excessive inflammation of the funiculi targeted by HTLV1 infection. Although usually minor, a few HAM cases demonstrate specific MRI lesions, and the most severe cases may mimic NMOSD attacks.

Background and Purpose Carotid web (CaW) is an intimal variant of fibromuscular dysplasia responsible for ipsilateral cerebral ischemic events (CIE). Symptomatic CaW likely has a high risk of recurrent CIE, but no salient prospective data are available. We aimed to assess recurrence rate and its predictors after a first-ever CIE.Methods Consecutive Afro-Caribbean patients who had cryptogenic first-ever CIEs (ischemic stroke [IS] or transient ischemic attack [TIA]) associated with ipsilateral CaW were included in this multicenter observational cohort study. The follow-up (January 2008 to March 2019) focused on CIE recurrences. Kaplan-Meier method assessed rates of recurrences and Cox proportional hazards regression analyzed risk factors.Results Ninety-two patients (79 first-ever ISs and 13 TIAs; mean age±standard deviation, 49.8±9.9 years; 52 [56.5%] women) were included. During a mean follow-up of 50.5±29.6 months, 19 (20.7%) patients experienced recurrent ipsilateral CIEs (16 ISs and three TIAs). Of 23 patients receiving surgery/stenting treatment, no recurrence occurred after the intervention (median follow-up, 39.8 months [interquartile range, 27.6 to 72.4]). Under medical treatment alone, the annual recurrent CIE rate was 6.9%, and the cumulative rate was 4.4% at 30-day, 10.8% at 1-year, 19.8% at 2-year, 23.2% at 3-year, and 27.3% at 5-year. Presence of silent cerebral infarctions was the only independent risk factor of CIE recurrences (hazard ratio, 6.99; 95% confidence interval, 2.4 to 20.4; P=0.004).Conclusions Under medical treatment alone, symptomatic CaW was associated with a high rate of recurrence that reached 27.3% at 5-year. Surgery/stenting seems to be efficient, and randomized control trials are required to confirm the benefit of these interventions.

International audience

In a matched case-control study where 24 cases developed Guillain-Barré syndrome (GBS) during the 2014 chikungunya outbreak in the French West Indies and 72 controls were blood donors during the same period, chikungunya infection was a risk factor for GBS (odds ratio, 8.3; 95% confidence interval, 2.3–29.7; P = .001).

Introduction L’année 2020 a été marquée par l’épidémie de COVID-19 qui a durement impacté les systèmes de soin. La filière accident vasculaire cérébral (AVC) a pu être désorganisée par ces changements. Objectifs Comparer le nombre d’AVC pris en charge au CHU de la Martinique (CHUM) pendant le confinement et hors période confinement et les différents délais de prise en charge durant ces deux périodes. Patients et méthodes Étude rétrospective observationnelle monocentrique descriptive au CHUM durant le 1er confinement (55 jours) et sur une période de durée équivalente hors confinement (17/12/2019–09/02/2020) à partir des registres de passage aux urgences, des hospitalisations en neurologie et des différentes imageries. Résultats Le nombre d’AVC pendant le confinement (n = 85) et hors confinement (n = 98) est comparable. Pendant le confinement, 45,9 % (n = 39) des AVC ont été pris en charge en 4 h 30, le délai médian « onset-arrivée aux urgences » était doublé pendant le confinement (22 h 29 contre 11 h 00 hors confinement–p = 0,042). Discussion Le confinement n’a pas eu de retentissement sur le nombre global d’AVC au CHUM mais a diminué le nombre de patients en alerte thrombolyse et majoré les délais de prise en charge. La peur de l’hôpital pourrait avoir impacté la filière AVC extra-hospitalière. La réorganisation des services d’urgences avec sectorisation des patients suspects de Covid-19 semble avoir impacté la filière AVC intra-hospitalière. Conclusion Devant l’évolution de la pandémie COVID-19, des campagnes d’information sur l’AVC devraient être menées afin de limiter les effets collatéraux du confinement. Une meilleure structuration des filières intra-hospitalières est également à anticiper.

Introduction La maladie de Behcet (MDB) est liee en partie a des facteurs genetiques. Des symptomes neurologiques sont frequemment retrouves. Nous rapportons le premier cas de neuroBehcet chez des jumeaux monozygotes. Observation Au CHU de la Martinique, entre fevrier 2018 et fevrier 2019, un patient de 20 ans a ete pris en charge pour 3 acces de symptomes neurologiques (diplopie avec atteinte du III, ataxie cerebelleuse, cephalees, confusion, amnesie anterograde et hyperthermie). L’IRM cerebrale retrouvait des lesions inflammatoires du diencephale, des lobes temporaux et du mesencephale. La ponction lombaire (PL) montrait 2900 elements lymphocytaires et 2,70 g/L de proteinorachie. Le fond d’œil retrouvait un œdeme papillaire bilateral. Il souffrait d’aphtose bipolaire depuis ses 11 ans. L’etude du HLA a retrouve l’allele B8-72. Nous avons pose le diagnostic de MDB et obtenu une recuperation complete sous bolus de corticoides puis entretien par cyclophosphamide. En juillet 2020, son jumeau monozygote etait hospitalise pour hemiparesie gauche d’apparition progressive sur 1 mois. L’IRM cerebrale retrouvait une volumineuse lesion inflammatoire touchant le lobe temporal interne, le diencephale et plongeant dans le mesencephale avec rehaussement au gadolinium. La PL retrouvait 18 elements et 0,54 g/L de proteinorachie. Le fond d’œil montrait une vascularite veineuse. Il souffrait d’aphtose buccale depuis 3 mois. Nous avons donc pose le diagnostic de NeuroBehcet familial. Discussion L’agregation familiale de MDB est connue et souvent rapportee au HLAB51. Dans notre cas comme dans la cohorte Antillaise de MDB aucun patient ne presentait cet allele suggerant l’implication d’autres facteurs genetiques pour les patients en dehors de la « Route de la Soie ». Plusieurs cas de jumeaux monozygotes ont ete rapportes mais jamais dans une forme neurologique. Conclusion La survenue rapprochee dans le temps de lesions IRM typiques chez nos jumeaux suggere que l’âge de survenue de la MDB et la topographie des lesions pourraient etre genetiquement determines.

Background Few data on stroke outcomes and no data on stroke recurrence are available in Black mono-racial population with high socio-economic status. Aims We investigated outcomes and stroke recurrence at one year in the Black Afro-Caribbean population of Martinique and examined potential predictors of poor prognosis and recurrence. Methods Patients from ERMANCIA II (Etude Réalisée en MArtinique et Centrée sur l’Incidence des Accidents vasculaires cérébraux), a Black population-based and prospective observational study, were followed up at 28-days, three months and one year post stroke. Stroke characteristics, survival, disability (modified Rankin Scale > 2), and stroke recurrence were assessed. A survival-based approach was used for time-to-event analysis, and multivariable regression analysis assessed the predictors of death, disability and stroke recurrence. Results Of 544 first-ever stroke patients, cumulative risks of death increased from 17.6% (95% confidence interval, 14.5–20.4) at 28 days to 22.8% (18.6–25.0) at three months and to 31.3% (27.4–34.6) at one year. Disability rates in survivors decreased from 43.7% (39.5–47.2) at 28 days to 35% (30.9–38.4) at three months and to 28.8% (24.9–32.1) at one year. Cumulative risks of recurrent stroke were estimated to 2.1% (0.9–2.9) at 28 days, 4.5% (2.7–6.1) at three months and 9.3% (6.1–11.6) at one year. Age (odds ratio (OR), 1.08 (1.05–1.10)), admission NIHSS (OR, 1.22 (1.17–1.29)), metabolic syndrome (OR, 2.07 (1.22–3.52)) and recurrence (OR, 5.06 (1.87–13.7)) were independent predictors of death or disability at one year. Conclusion Stroke Outcomes in Black Afro-Caribbean population with a high socio-economic status appear globally similar to outcomes reported in Caucasian population. After a first-ever stroke, the implementation of early programs of recurrence prevention seems crucial to reduce the risk of poor prognosis at one year.

International audience; Background: Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016.Methods: We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS.Results: Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease.Conclusions: ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases.

International audience; The Guillain–Barré syndrome (GBS) has been reported as a possible complication of acute chikungunya infection. The chikungunya epidemics, which occurred in Martinique and Guadeloupe in 2014, affected 308,000 people in these two islands. GBS occurred during or immediately after acute chikungunya infection in 13 patients (10 men, three women; mean age: 61 years). Median time from acute chikungunya to GBS onset was 9 days. Twelve patients were treated with intravenous polyvalent immunoglobulins, nine of whom improved within 7 days. Five of 13 patients required mechanical ventilation. Two patients with severe GBS died. At 6 months of follow-up, 7/13 achieved a good functional recovery with no or minor residual symptoms. A 2-fold increase in incidence was observed during the year of chikungunya outbreak. This study supports prior reports suggesting that GBS may be a complication of chikungunya.

Background and Purpose— Seldom studies are available on trends in stroke incidence in blacks. We aimed to evaluate whether stroke risk prevention policies modified first-ever stroke incidence and outcomes in the black Afro-Caribbean population of Martinique. Methods— Etude Réalisée en Martinique et Centrée sur l’Incidence des Accidents Vasculaires Cérébraux (ERMANCIA) I and II are 2 sequential prospective population-based epidemiological studies. There have assessed temporal trends in first-ever stroke incidence, risk factors, pathological types, and early outcomes in the black Afro-Caribbean population of Martinique comparing two 12-month periods (1998–1999 and 2011–2012). Crude and age-standardized incidence and 30-day outcomes for stroke in the 2 study periods were compared using Poisson regression. Results— We identified 580 and 544 first-ever strokes in the 2 studies. World age-standardized incidence rates decreased by 30.6% in overall (111 [95% confidence interval, 102–120] versus 77 [95% confidence interval, 70–84]). Rate decline was greater in women than in men (34% versus 26%) particularly in women aged 65 to 74 years (−69%) and 75 to 84 years (−43%). Frequencies of hypertension and diabetes mellitus were unchanged, whereas dyslipidemia, smoking, and atrial fibrillation significantly increased. Only ischemic stroke types showed significant rate reduction in overall and in women, incidence rate ratio (95% confidence intervals) of 0.69 (0.50–0.97) and 0.61 (0.42–0.88), respectively. The overall 30-day case-fatality ratio remained stable (19.3%/17.6%), whereas a better 30-day outcome was found (modified Rankin Score, ≤2 in 47%/37.6%; P =0.03). Conclusions— Over 13 years, there has been a significant decrease (30.6%) in the age-specific first-ever stroke incidence in our Afro-Carribean population. Although prevention policies seem effective, we need to focus on new risk factors limitation and on male population adherence to prevention program.

We report two cases of encephalopathy (one with seizures, one with electroencephalogram changes) in patients with Zika virus infection. The cases occurred on Martinique in February 2016, during the Zika virus outbreak. Awareness of the various neurological complications of Zika virus infection is needed for patients living in areas affected by Zika virus infections or for travellers to these areas.

We report two cases of Guillain–Barré syndrome who had concomitant Zika virus viruria. This viruria persisted for longer than 15 days after symptom onset. The cases occurred on Martinique in January 2016, at the beginning of the Zika virus outbreak. Awareness of this possible neurological complication of ZikV infection is needed.

HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of the central nervous system induced by human T-lymphotropic virus type 1. As a potential therapeutic approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response. We conducted a single-center, 2-year, open-label trial, with 19 HAM/TSP volunteers treated with oral VPA. Proviral load, CD38/HLA-DR expression, and CD8+ lysis efficiency were not significantly affected by VPA. Mean scores of HAM/TSP disability did not differ between baseline and final visit. Walking Time Test increased significantly (> 20%) in 3 patients and was in keeping with minor VPA side effects (drowsiness and tremor). Walking Time Test improved rapidly after VPA discontinuation. We conclude that long-term treatment with VPA is safe in HAM/TSP.

Objectives Human T-cell lymphotropic virus type 1 (HTLV-1) infection leads to the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in less than 5% of cases. The mechanism of disease progression in HAM/TSP remains unknown. A significant role of certain human leukocyte antigen (HLA) genotypes in determining the risk of HAM/TSP has been reported in Japan, where the HLA-A*02 gene has been found to be associated with a lower HTLV-1 provirus load and with protection from HAM/TSP, whereas HLA-DRB1*0101 has been found to be associated with an increased susceptibility to HAM/TSP. The aim of the present case–control study was to investigate the HLA class I and class II allele distribution in HTLV-seropositive French Afro-Caribbean individuals, originating from the French West Indies. Methods Associations with HLA class I (A and B) and class II (DRB1 and DQB1) alleles were tested in 123 HAM/TSP patients and 85 asymptomatic HTLV-1 carriers. HLA typing was undertaken on genomic DNA extracted from peripheral blood leukocytes. Results In our cohort, no significant effect on either the risk of developing HAM/TSP or HTLV-1 provirus load was found for HLA class I or class II, including HLA-A*02 ( p =0.43). Conclusions Our findings are in contrast to those in the Japanese population, however the literature on HLA associations in HTLV-1 infections across different populations over the past decade have reported conflicting results and this suggests strong ethnic disparities.

Resume Introduction La maladie de Horton est la plus frequente des vascularites. Elle est responsable d’infarctus cerebraux chez environ 4 % des patients, le plus souvent par stenose serree ou occlusion du vaisseau au niveau des lesions d’arterite. Le traitement de ces patients est mal codifie et leur evolution est souvent pejorative. Observation Une femme, âgee de 78 ans, presentait depuis six mois une alteration de l’etat general avec cephalees. Le bilan mit en evidence un syndrome inflammatoire biologique et la biopsie de l’artere temporale confirma le diagnostic de maladie de Horton. Moins de trois semaines apres l’instauration de la corticotherapie et malgre un traitement par antiagregant plaquettaire, la patiente presenta brutalement des troubles cognitifs et une paraparesie. L’imagerie cerebrale revela des infarctus cerebraux dans les territoires jonctionnels sur stenoses serrees bicarotidiennes internes. En raison d’une majoration systematique de la paraparesie a l’orthostatisme, sans diminution significative de la pression arterielle, associee a l’apparition de nouvelles lesions ischemiques cerebrales sur l’IRM, la patiente fut traitee avec succes par angioplastie et pose de stent . Conclusion Apres un infarctus cerebral secondaire a une maladie de Horton, le traitement endovasculaire de la stenose arteritique devrait etre envisage en cas d’instabilite hemodynamique ou de recidive ischemique cerebrale ; en effet chez ces patients le traitement medical actuel semble insuffisant.

Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.

HTLV-1 (human T-lymphotropic virus type 1) and BLV (bovine leukemia virus) are two related retroviruses infecting CD4+ and B lymphocytes in humans and ruminants, respectively. During infection, the host-pathogen interplay is characterized by very dynamic kinetics resulting in equilibrium between the virus, which attempts to proliferate, and the immune response, which seeks to exert tight control of the virus. A major determinant of disease induction by both viruses is the accumulation of provirus in peripheral blood. In the absence of viral proteins, virus infected cells escape recognition and destruction by the host immune response. We propose a novel therapeutic strategy based on transient activation of viral expression using epigenetic modulators; this exposes infected cells to the immune response and results in significant reductions in proviral loads. In the absence of satisfactory therapies, this viral gene-activation strategy might delay progression, or even be curative, for HTLV-1 induced myelopathy / tropical spastic paraparesis (HAM/TSP).

Resume Introduction Le spectre des affections neurologiques liees aux auto-anticorps anti-acide glutamique decarboxylase (anti-GAD) comprenait principalement le syndrome de l’homme raide. Il englobe desormais des affections cerebelleuses dont moins de 30 cas ont ete rapportes. Ces formes peuvent presenter une evolution severe et n’ont pas fait l’objet d’essai therapeutique. Objectifs Nous rapportons quatre cas originaux d’ataxie cerebelleuse a auto-anticorps anti-GAD, traites dans le cadre d’un essai therapeutique ouvert par bolus mensuels de methylprednisolone. Methodes Les bolus ont ete administres pendant six mois suivis par six mois de placebo. Les parametres cliniques (echelle International Cooperative Cerebellar Ataxia Rating Scale [ICARS]) et biologiques (taux d’anticorps anti-GAD) etaient recueillis mensuellement. Resultats La reponse clinique a ete inconstante et discrete. Les taux d’anticorps ont diminue transitoirement chez deux patients. Une importante fluctuation mensuelle des taux d’anticorps anti-GAD a ete observee. Conclusion La corticotherapie a forte dose est associee a une reponse clinique et biologique faible et inconstante au cours de l’ataxie cerebelleuse a anticorps anti-GAD.

Epigenetic modifications of chromatin may play a role in maintaining viral latency and thus persistence of the human T-lymphotropic virus type 1 (HTLV-1), which is responsible for HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A major determinant of disease progression is increased peripheral blood proviral load (PVL), possibly via the accumulation of infected cells in the central nervous system (CNS) creating a damaging inflammatory response. Current therapeutic approaches that focus on reducing either cell proliferation, viral replication, or tissue invasion are still unsatisfactory. Contrasting with these inhibitory strategies, we evaluated the efficacy of a novel approach aimed, paradoxically, at activating viral gene expression to expose virus-positive cells to the host immune response. We used valproate (VPA), a histone deacetylase inhibitor that has been used for decades as a chronic, safe treatment for epileptic disorders. Based on in vitro and in vivo data, we provide evidence that transient activation of the latent viral reservoir causes its collapse, a process that may alleviate the condition of HAM/TSP. This represents the first such approach to treating HAM/TSP, using gene activation therapy to tilt the host-pathogen balance in favor of an existing antiviral response. This trial is registered at http://clinicaltrials.gov/as no. NCT00519181.

International audience; Objective To compare the natural history of familial transthyretin amyloid polyneuropathies (FAP) due to the Val30Met, Ser77Tyr, and Ile107Val mutations in France with the classical Portuguese Val30Met FAP. Methods We compared 84 French patients with a control group of 110 Portuguese patients carrying the Val30Met mutation also living in France, all referred to and followed at the French National FAP Reference Center from 1988 to 2010. Clinical examination, functional and walking disability scores, nerve conduction studies, and muscle biopsies are reported. We also conducted a comprehensive literature review to further determine the range of phenotypic expression. Results By comparison with Portuguese Val30Met FAP, French Ile107Val, Ser77Tyr, and LateVal30Met FAP showed more rapid and severe disease progression; onset of gait disorders was 3 times more rapid (p 50 years; LateMet30) FAP (p = 0.0005). Other distinctive features relative to the Portuguese patients included atypical clinical presentations, demyelination on nerve conduction studies (p = 0.0005), and difficult identification of amyloid deposits in nerve and muscle biopsies. Interpretation Ile107Val and LateMet30 mutations are associated with the most debilitating and severe FAP ever described, with rapid onset of tetraparesis and shorter median survival. It could be explained by frequent large‐fiber involvement and associated demyelination and more severe axonal loss. These findings have major implications for genetic counseling and patient management as new therapeutic options are being assessed in clinical trials (TTR gene silencing). Ann Neurol 2015;78:901–916

Background Human T-Lymphotropic virus 1 (HTLV-1) has been discovered in 1980 and linked to tropical spastic paraparesis (HAM/TSP) in 1985 in Martinique. There is no data on HAM/TSP incidence trends. We report, in the present work, the temporal trends incidence of HAM/TSP in Martinique based on patients diagnosed in our unique Neurology Department in HAM/TSP diagnosis and management over 25 years. Methods: A registry has been set up since 1986 and HAM/TSP characteristics were collected carefully. All patients, living in Martinique, with a definite HAM/TSP onset between 1986 and 2010 were included in the present hospital-based study. The 25-year study time was stratified in five-year and ten-year periods. Crude incidence rates with 95% confidence interval (95%CI) were calculated using Poisson distribution for each period. The denominator was based on data provided by French National Institute for Statistical and Economic Studies (http://www.insee.fr) Results: Overall, 153 patients were identified (mean age at onset, 53+/13.1 years; female: male ratio, 4:1). HAM/TSP incidence rates per 100,000 per 5 years (95%CI) in 1986-1990, 1991-1995, 1996-2000, 2001-2005 and 2006-2010 periods were 10 (6.8-7.3), 12.6 (9-16.1), 11.5 (8.1-14.9), 4.4 (2.56.4) and 2 (1.4-3.5). Between the two decades (1991-2000 and 2001-2010), ten-year HAM/TSP incidence rate decreased by 75% [19.1 (14.8-23.6) versus 4.9 (2.7-7.1)]. Age at onset did not differ between the different periods. Conclusion: There has been a significant decrease (75%) in HAM/TSP incidence in Martinique in the last decade. Prevention policies might have been effective in reducing HTLV-1 seroprevalence in our population. However, environmental factors such as parasite burden decrease could also account for HAM/TSP incidence dramatic fall.

Resume Introduction Les lesions de neuromyelite optique interessent la moelle et les nerfs optiques en epargnant l’encephale. Les aspects neuroradiologiques classiques, integres aux criteres diagnostiques, sont l’integrite encephalique initiale et l’extension longitudinale des lesions medullaires. L’evolution temporelle des lesions et leur frequence au cours des poussees sont peu connues. Objectifs Nous rapportons les donnees neuroradiologiques medullaires et cerebrales d’une serie de sujets NMO. Methodes La cohorte etait composee de 32 sujets afro-antillais atteints de NMO. Les donnees IRM medullaires et encephaliques etaient systematiquement revues. Resultats Les lesions medullaires etaient etendues dans 44,7 p. 100, de moins de trois segments dans 26,3 p. 100 et absentes dans 21,1 p. 100 des cas. Un suivi longitudinal des poussees suggerait la disparition progressive des lesions aigues. Le developpement d’une atrophie etait inversement correle au traitement de fond. La charge lesionnelle encephalique, initialement nulle, etait correlee a la duree de suivi. Les criteres diagnostiques encephalique et medullaire etaient valides par 82,8 p. 100 et 48,1 p. 100 des sujets en condition de non-recursivite. Conclusion Les poussees medullaires de NMO ont des aspects radiologiques polymorphes. La condition de la sensibilite du critere medullaire exige plusieurs evenements. Une lesion medullaire typique surviendra toujours au cours de l’evolution, mais dans moins de la moitie des pousses, l’exiger risquerait de retarder le diagnostic.

Narrow therapeutic window is a major cause of thrombolysis exclusion in acute ischemic stroke. Whether prehospital medicalization increases t-PA treatment rate is investigated in the present study.Intrahospital processing times and t-PA treatment were analyzed in stroke patients calling within 6h and admitted in our stoke unit. Patients transferred by our mobile medical team (SAMU) and by Fire Department (FD) paramedics were compared.193 (61.6%) SAMU patients and 120 (38.4%) FD patients were included within 30 months. Clinical characteristics and onset-to-call intervals were similar in the two groups. Mean door-to-imaging delay was deeply reduced in the SAMU group (52 vs. 159 min, p0.0001) and was25 min in 50% of SAMU patients and 14% of FD patients (p0.0001). SAMU management was the only independent factor of early imaging (p=0.0006). t-PA administration rate was higher in SAMU group than in FD group (42% vs. 28%, p=0.04). Proportion of patients with delayed therapeutic window was higher in FD group than in SAMU group (38% vs. 26%, p0.0001).Prehospital transfer medicalization promotes emergency room bypass, direct radiology room admission and high thrombolysis rate in acute ischemic stroke.

In order to define clinical patterns of light-chain amyloid (AL) polyneuropathy, we reviewed the data of 24 patients. At diagnosis, the mean duration of the symptoms was 21 months (range,...

Although human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy, or tropical spastic paraparesis (HAM/TSP), is usually considered as a progressive myelopathy, a subacute variant has been described. It is unusual for optic neuritis (ON) to be associated with an HTLV-1 infection. Neuromyelitis optica (NMO) is characterised by severe attacks of acute transverse myelitis and ON of unknown aetiology. We report a 61-year-old Afro-Caribbean male patient with subacute HAM/TSP associated with bilateral ON that occurred 5 years previously. To our knowledge this is the first report of recurrent NMO syndrome associated with HTLV-1 infection.

Resume Observation Un homme de 65 ans, aux antecedents de gastrectomie a l’âge de 25 ans et suivi pour un syndrome myelodysplasique, developpa progressivement une ataxie proprioceptive. Une carence en vitamine B12 fut retrouvee et traitee. Mais, devant l’aggravation neurologique, un deficit en cuivre fut evoque, puis confirme avec hypocupremie et hypo-ceruloplasminemie. La supplementation en cuivre permit de stopper la progression neurologique et de normaliser le bilan hematologique. Conclusion Cette observation illustre les complications neurologiques d’un deficit en cuivre, ici masque par un deficit associe en vitamine B12.

Introduction Le SESA syndrome est une encephalopathie subaigue convulsivante survenant chez les alcooliques chroniques. Sa premiere description par Niedermeyer remonte a 25 ans. En 2014, des criteres diagnostiques ont ete proposes. Objectifs Nous rapportons les cas de patients martiniquais ayant presente un SESA syndrome afin de mieux preciser les caracteristiques cliniques, paracliniques et evolutives de ce syndrome epileptique. Patients et methodes Nous decrivons retrospectivement a partir des dossiers medicaux les cas de six patients hospitalises au centre hospitalo-universitaire de Fort-de-France entre 2009 et 2013 pour un tableau compatible avec un SESA syndrome. Les patients ont tous ete examines par un neurologue. Une exploration electroencephalographique ainsi que par scanner et/ou par imagerie par resonance magnetique encephaliques a ete effectuee chez les patients. Resultats Les patients presenterent des crises generalisees tonicocloniques, souvent associees a des crises partielles motrices. En intercritique une confusion, une hemiplegie et/ou une aphasie furent constatees. Les electroencephalogrammes retrouverent des foyers epileptiques. Le scanner revela un œdeme hemispherique unilateral et l’imagerie par resonance magnetique encephalique des images d’etat de mal epileptique partiel. Quatre patients eurent plusieurs episodes de SESA. Quatre patients garderent des sequelles neurologiques. Discussion La physiopathologie du SESA syndrome reste discutee. Des lesions vasculaires cerebrales chroniques associees a un facteur declenchant chez l’alcoolique chronique favoriseraient cette encephalopathie convulsivante focale. Une atrophie cerebrale frequente peut devenir asymetrique au decours du SESA. Une atteinte bi-hemispherique recidivante rapportee chez un de nos patients represente une forme particulierement agressive de cette affection. Conclusion Le SESA syndrome represente une complication de l’alcoolisme chronique a part entiere. Ces nouveaux cas illustrent son caractere souvent recidivant pouvant aboutir a des deficits neurologiques permanents.

A 55-year-old man with alcoholism required sigmoid resection for complicated diverticulitis. A few weeks after starting parenteral nutrition, he developed multidirectional gaze nystagmus, gait ataxia, and confusion, leading to the diagnosis of Wernicke encephalopathy. Thiamine treatment was started and his …

Background and Purpose— Intravenous tissue-type plasminogen activator (IV tPA) frequently fails to recanalize proximal middle cerebral artery (MCA-M1) obstructions, preventing favorable outcomes. Only neurointerventional procedures prevail in these cases, but well-equipped centers remain scarce. A new therapeutic strategy consisting of a second IV thrombolysis with low-dose tenecteplase was applied. Methods— Consecutive patients with an MCA-M1 occlusion that did not reopen at the end of IV tPA perfusion received IV tenecteplase (0.1 mg/kg). Partial or complete thrombolysis in myocardial infarction recanalization (Thrombolysis In Myocardial Infarction grade 2/3) and intracerebral hemorrhage were assessed by magnetic resonance imaging ≈24 hours later. Clinical outcomes at 3 months were evaluated with the modified Rankin score. Results— Among 40 patients with MCA-M1 occlusions who received IV tPA, 13 were treated according to the protocol of sequential combined IV thrombolytics. Baseline National Institutes of Health Stroke Scale score was 15. At a mean of 16.8 hours after IV thrombolysis, the recanalization rate was 100% (2 with Thrombolysis In Myocardial Infarction grade 2, 11 with Thrombolysis In Myocardial Infarction grade 3). Intracerebral hemorrhage occurred in 4 of 13 (31%) patients, with no symptomatic hemorrhage. Good clinical outcomes (modified Rankin score=0/1) were achieved in 9 of 13 (69%) patients. Functional outcomes were very similar to those of 13 patients with early IV-tPA recanalization. Among 4 patients treated as protocol violations, 1 presented with a lack of recanalization and a parenchymal hematoma type 2. Conclusions— For patients with MCA-M1 occlusions treated with IV tPA but without early recanalization, a second bolus of IV tenecteplase (0.1 mg/kg) may be a relatively safe, effective, and easy option in carefully selected cases, but additional studies are needed to confirm these findings.

We report a 55-year-old woman with intracranial hypertension due to unilateral extrinsic compression of the left transverse sinus by a meningioma. Because of the high risk of the conventional neurosurgical intervention, she underwent an endovascular procedure consisting of a transstenotic stent placement in the left transverse sinus. One month after stenting, her ophthalmological examination revealed complete regression of the bilateral papilledema, with persistent improvement at 1 year. Cerebral venous-stenting could be a safe alternative for patients suffering from intracranial hypertension caused by extrinsic sinus compression.

Gait disturbances and sensory deficit in the hands are the most common clinical features in cervical spondylotic myelopathy (CSM). The disease course is often insidious and slow. The treatment for the underlying cervical-canal stenosis is surgical decompression or stabilisation. Functional scales have been used in CSM to assess neurological impairment, including the Nurick scale1 and the modified Japanese Orthopedic Association (mJOA) scale.2 Whereas functional scales are helpful in quantifying patient disability, they lack the objectivity of a neurological examination. A timed walking test as a quantitative functional test focusing on gait impairment has recently been developed.3 The present study has assessed hand disability in CSM patients with the quantitative Nine-Hole-Peg Test (9-HPT). This easy-to-use test was developed in 1985,4 and is now extensively applied to measure hand dexterity in multiple sclerosis (MS).5 Nine-HPT could constitute a quantifying complementary test to the Walking Time test in CSM to explore the two main symptoms—gait and hand disability. Forty patients with CSM, corroborated by MRI, were recruited between January 2003 and March 2006. Patients with other known neurological disease were excluded from this study. A posterior decompressive procedure was undergone in all patients. Twenty healthy subjects were assessed with the 9-HPT to give the normal range values in our …

A high proviral load of human T cell lymphotropic virus type 1 (HTLV-1) in peripheral blood mononuclear cells (PBMCs) has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of the present study was to investigate the role of HTLV-1 proviral load in PBMCs (expressed as the number of copies per 10(6) PBMCs) in HAM/TSP disease course. One hundred consecutive HAM/TSP patients were recruited and assigned on the basis of the disability score and disease duration to either a rapid (n=38) or a slow (n=62) progression group. Thirty-four asymptomatic HTLV-1 carriers were also included. HTLV-1 proviral load was quantified in all HAM/TSP patients and asymptomatic subjects. The mean HTLV-1 proviral load was 6-fold lower in asymptomatic carriers than in HAM/TSP patients (18,224+/-24,811 vs. 107,905+/-96,651, p

Auteur(s) : Lydia DESCHAMPS1 lydia.deschamps@chu-fortdefrance.fr, Aissatou SIGNATE2, Christine DELAUNAY3, Ivana MORALES4, Andre WARTER1, Didier SMADJA2, Christian DERANCOURT4 1 Department of Pathology, 2 Department of Neurology, 3 Department of Internal Medicine, 4 Department of Dermatology, Zobda-Quitman Hospital, B.P 632, 97261 Fort-de-France cedex, Martinique, French West Indies A 71-year-old Afro-Caribbean man presented with a four-month history of nocturnal sweats, fever, weight loss, [...]

Contexte : la sclerose en plaques (SEP) est la pathologie inflammatoire recurrente du systeme nerveux central (SNC) la plus frequente a travers le monde. Elle est d'apparition recente aux Antilles francaises mais son incidence est en constante augmentation. La frontiere entre SEP et neuromyelite optique (NMO), longtemps consideree comme un variant rare et grave de la SEP, reste un sujet debattu. Objectifs : description de la cohorte antillaise francaise de maladies inflammatoires recurrentes du SNC, d'un point de vue demographique, clinique, radiologique, biologique et pronostique. Methodes : nous avons inclus l'ensemble des patients recenses dans le registre des pathologies inflammatoires recurrentes du SNC tenu aux Antilles francaises, et remplissant les criteres de Poser pour la SEP cliniquement definie. Resultats : 312 patients ont ete inclus : 55.9% presentaient un phenotype de SEP classique, 20.8% repondaient aux criteres du spectre NMO. Le ratio phenotype clinique dissemine/optico-spinal (OS) pur a augmente de 0.84 avant 1965 a 1.19 pour la generation nee apres 1965. 26.6% des patients presentaient un phenotype OS pur, mais 11.4% etaient seronegatifs pour l'IgG-NMO, n'avaient pas de lesion medullaire extensive (LME) et presentaient une evolution relativement benigne. 28.9% des patients presentaient une LME, mais 9.6% etaient egalement seronegatifs, avaient un phenotype clinique dissemine et un pronostic severe. Conclusion : on retrouve dans la population antillaise deux types de phenotypes chevauchants entre la SEP et la NMO, deja decrits dans la population japonaise : phenotype OS LME(-) et phenotype extra-OS LME (+).

Few data are available on the relationship between fluid-attenuated inversion recovery vascular hyperintensities and proximal middle cerebral artery occlusion prognosis.To assess a fluid-attenuated inversion recovery vascular hyperintensities score (FVHS) and explore its relationship with recanalization status and clinical outcomes after intravenous thrombolysis.Retrospective study.Stroke unit in a university hospital.Consecutive patients with proximal middle cerebral artery occlusion, thrombolysed within 6 hours, were selected from our prospective database. The FVHS (range,0-10; divided into low, medium, and high thirds) was quantified on the magnetic resonance image obtained at admission. Recanalization rates, infarction size (Alberta Stroke Program Early CT Score applied to diffusion weighted imaging [ASPECTS-DWI]), and 3-month functional outcomes (modified Rankin Scale score) were determined. Poor outcomes and large infarctions were defined as a modified Rankin Scale score higher than 2and an ASPECTS-DWI score of 5 or lower, respectively.Interaction among FVHS,recanalization status, and outcomes.Thirty-four patients had a low FVHS (4), 32 had a medium FVHS (5 or 6), and 39 had a high FVHS (≥7). The rate of poor functional outcome (modified Rankin Scale score2) was higher for the group with low FVHSs than those with medium FVHSs and high FVHSs(82.3% vs 43.7% and 43.5%, respectively; P.001). Therate of 24-hour large infarctions(ASPECTS-DWI score 5)was higher for those with low FVHSs than those with medium and high FVHSs (88.2% vs 56.2% and 51.3%, respectively;P=.002). The recanalization rate was not associated with FVHS. Multivariate analysis retained low FVHS as an independent early predictor of poor clinical outcome (odds ratio=9.91; 95% CI, 2.01-48.93; P=.004)and large infarction (odds ratio=6.99; 95% CI, 1.78-27.46; P=.005).Low FVHS remained associated with poor outcomes regardless of recanalization status. Early recanalization in patients with a low FVHS decreased the poor functional outcome rate from 100% to 64.7% (P=.02).The FVHS is an early independent prognostic marker for patients with proximal middle cerebral artery occlusion. Synergy between FVHS and recanalization status appears to be a critical determinant of final outcomes, supporting intensive reperfusion treatment for patients with a low FVHS.

Background The progression of neurological disability in human T-lymphotropic virus 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) remains undefined. Objectives To determine the time course of disability scores and to identify predictors of outcome among patients with HAM/TSP. Design Clinical 14-year follow-up study. Setting University hospital. Patients One hundred twenty-three patients with HAM/TSP. Main Outcome Measures We determined time from onset to the following 4 Kurtzke Disability Status Scale (DSS) end points: scores of 6 (unilateral aid required), 6.5 (bilateral aid required), 8 (wheelchair confinement), and 10 (death related to the disease). Times to reach selected DSS scores were estimated using the Kaplan-Meier method. Univariate and multivariate analyses identified variables related to the rate of progression to DSS 8. The HTLV-1 proviral loads were also assessed. Results The disability of the cohort progressed throughout the follow-up period. The median times from onset to DSS 6, 6.5, and 8 were 6, 13, and 21 years, respectively. The median time from DSS 6 to DSS 8 was 8 years; DSS 10 was reached by one fourth of the patients within 20 years. Age at onset of 50 years or older and high HTLV-1 proviral load were associated with a shorter time to DSS 8 ( P = .01 and P = .02, respectively). A shorter time to DSS 6 significantly adversely affected the time to progression from DSS 6 to DSS 8. Conclusions Human T-lymphotropic virus 1–associated myelopathy/tropical spastic paraparesis is a rapidly disabling disease. Monitoring for HTLV-1 proviral load is recommended in future therapeutic trials.