The DKI-IVIM model that incorporates DKI (diffusional kurtosis imaging) into the IVIM (Intravoxel Incoherent Motion) concept was investigated to assess its utility for both enhanced diffusion ...characterization and perfusion measurements in ischemic stroke at 3 T.
Fifteen stroke patients (71 ± 11 years old) were enrolled and DKI-IVIM analysis was performed using 9 b-values from 0 to 1500 s/mm2 chosen with the Cramer-Rao-Lower-Bound optimization approach. Pseudo-diffusion coefficient D*, perfusion fraction f, blood flow-related parameter fD*, the diffusion coefficient D and an additional parameter, the kurtosis, K were determined in the ischemic lesion and controlateral normal tissue based on a region of interest approach. The apparent diffusion coefficient (ADC) and arterial spin labelling (ASL) cerebral blood flow (CBF) parameters were also assessed and parametric maps were obtained for all parameters.
Significant differences were observed for all diffusion parameters with a significant decrease for D (p < 0.0001), ADC (p < 0.0001), and a significant increase for K (p < 0.0001) in the ischemic lesions of all patients. f decreased significantly in these regions (p = 0.0002). The fD* increase was not significant (p = 0.56). The same significant differences were found with a motion correction except for fD* (p = 0.47). CBF significantly decreased in the lesions. ADC was significantly positively correlated with D (p < 0.0001) and negatively with K (p = 0.0002); K was also negatively significantly correlated with D (p = 0.01).
DKI-IVIM model enables for simultaneous cerebral perfusion and enhanced diffusion characterization in an acceptable clinically acquisition time for the ischemic stroke diagnosis with the additional kurtosis factor estimation, that may better reflect the microstructure heterogeneity.
•DKI-IVIM imaging at 3T enables simultaneous measurement of K, D, f and fD*in acute/subacute stroke.•ADC was significantly positively correlated with D and significantly negatively correlated with K in the ischemic lesions.•Combined f/fD*/D/K potentially enhance ischemic lesions analysis in a shorter acquisition time than DWI and ASL do separately.
Abstract
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).
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 < 0.0001) and the rate of modified Norris test decline was up to 40 times faster in Ile107Val patients (p < 0.0001). Median survival was much shorter in Ile107Val and in Val30Met mutation with late onset (>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
Dans les pathologies du spectre de la neuromyélite optique (NMOSD), la prévention de nouvelles poussées inflammatoires est fondamentale. Les nouvelles molécules efficaces dans la maladie sont souvent ...coûteuses, voire indisponibles dans certaines régions.
Évaluer l’efficacité et la sécurité d’alternatives thérapeutiques plus accessibles est une nécessité. Notre objectif était d’évaluer l’efficacité et la tolérance de la mitoxantrone (MiTX) dans la NMOSD.
Étude multicentrique comportant 86 NMOSD traités par MiTX au cours d’un suivi prospectif. Le critère de jugement principal était la survenue d’une rechute avant 96 semaines après introduction de MiTX. Les critères de jugement secondaires portaient sur le délai de rechute, l’évolution du taux de poussée (ARR) et de l’Expanded Disability Status Scale (EDSS) à 96 semaines, sur la recherche de facteurs de risque, et la survenue d’effets indésirables.
À 96 semaines, 71 % des patients étaient indemnes de rechute. L’ARR moyen était passé de 0,85 à 0,32 (61 %), l’EDSS moyen de 4,9 à 4,2 (−0,71). Un délai d’introduction de la MiTX supérieur à 24 mois après la première poussée (HR 2,76), un statut anti-AQP4+(HR 12,3), et un ARR prétraitement 3 1 (HR 2,38) étaient des facteurs de risque de rechute. Trois effets indésirables graves (3,5 %) sont survenus (Fig. 1 et Fig. 2).
Cette étude est la plus vaste cohorte multicentrique prospective de patients NMOSD traités par MiTX, incluant des patients NMOSD double-séronégatifs et des patient MOG+. L’efficacité et la tolérance de la MiTX semblent comparables à celles des autres molécules actuellement utilisées dans la NMOSD pour un coût 10 à 100 fois moindre et une accessibilité nettement meilleure à l’échelle mondiale.
La MiTX est un traitement efficace et sûr dans la NMOSD, peu coûteuse et très accessible, qui pourrait être une alternative thérapeutique dans des zones géographiques d’accès aux soins limité.
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.
La maladie de Behçet (MDB) est liée en partie à des facteurs génétiques. Des symptômes neurologiques sont fréquemment retrouvés. Nous rapportons le premier cas de neuroBehçet chez des jumeaux ...monozygotes.
Au CHU de la Martinique, entre février 2018 et février 2019, un patient de 20 ans a été pris en charge pour 3 accès de symptômes neurologiques (diplopie avec atteinte du III, ataxie cérébelleuse, céphalées, confusion, amnésie antérograde et hyperthermie). L’IRM cérébrale retrouvait des lésions inflammatoires du diencéphale, des lobes temporaux et du mésencéphale. La ponction lombaire (PL) montrait 2900 éléments lymphocytaires et 2,70g/L de protéinorachie. Le fond d’œil retrouvait un œdème papillaire bilatéral. Il souffrait d’aphtose bipolaire depuis ses 11 ans. L’étude du HLA a retrouvé l’allèle B8-72. Nous avons posé le diagnostic de MDB et obtenu une récupération complète sous bolus de corticoïdes puis entretien par cyclophosphamide. En juillet 2020, son jumeau monozygote était hospitalisé pour hémiparésie gauche d’apparition progressive sur 1 mois. L’IRM cérébrale retrouvait une volumineuse lésion inflammatoire touchant le lobe temporal interne, le diencéphale et plongeant dans le mésencéphale avec rehaussement au gadolinium. La PL retrouvait 18 éléments et 0,54g/L de protéinorachie. Le fond d’œil montrait une vascularite veineuse. Il souffrait d’aphtose buccale depuis 3 mois. Nous avons donc posé le diagnostic de NeuroBehçet familial.
L’agrégation familiale de MDB est connue et souvent rapportée au HLAB51. Dans notre cas comme dans la cohorte Antillaise de MDB aucun patient ne présentait cet allèle suggérant l’implication d’autres facteurs génétiques pour les patients en dehors de la « Route de la Soie ». Plusieurs cas de jumeaux monozygotes ont été rapportés mais jamais dans une forme neurologique.
La survenue rapprochée dans le temps de lésions IRM typiques chez nos jumeaux suggère que l’âge de survenue de la MDB et la topographie des lésions pourraient être génétiquement déterminés.
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.
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.
Étude rétrospective observationnelle monocentrique descriptive au CHUM durant le 1er confinement (55jours) 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.
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<4h 30 contre 61,2 % (n=60) hors confinement (p=0,042). Le délai médian « arrivée urgences-imagerie » était allongé pendant le confinement (1h 56) versus hors confinement (1h 05) (p=0.042). Pour les AVC>4h 30, le délai médian « onset-arrivée aux urgences » était doublé pendant le confinement (22h 29 contre 11h 00 hors confinement–p=0,042).
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.
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.
The link between transthyretin cardiac amyloidosis (CATTR), and cerebral ischemic events (CIE) has only been hinted at till now, impeding progress in patient management. We seek to evaluate the ...frequency and characteristics of CIE in Afro-Caribbean patients followed for CATTR at our institution.
In this single-center retrospective observational study, Afro-Caribbean patients followed for CATTR between July 2005 and October 2019 were included. Occurrence of CIE was investigated, and their cardioembolic origin determined. Analysis of patient characteristics was conducted according to CIE and CATTR profiles.
Overall, 120 CATTR patients were included: 17 wild-type ATTR (14.2%), 73 ATTR-V122I (60.8%), and 22 ATTR-I107V (18.3%). Thirty-six patients (30.0%) presented with CIE, including three transient ischemic attacks and 33 permanent ischemic strokes (75.8% with a cardioembolic pattern). CIE was concomitant with CATTR diagnosis in 16 (16/36: 44.4%) patients, while 14 patients (14/36: 38.9 %) experienced CIE over a median CATTR follow-up of 2.0 years (min-max range: 0.8-4.4 years). CATTR-CIE patients presented with atrial fibrillation (66.7%), left atrial enlargement (77.8%), a CHA
DS
-VASc ≥ 3 (97.2%) and a high anticoagulant intake (75.0%). Multivariate analysis retained only a high CHA
DS
-VASc score as an independent predictor of CIE risk (Hazard Ratio 95% CI: 12.03 1.62-89.24).
Concomitant CIE, and CATTR diagnosis, potentially carries a worse prognosis. A CHA
DS
-VASc score ≥3 seems to be a strong and independent predictive factor of CIE in CATTR patients. Further studies are needed to assess the efficacy and timeliness of anticoagulation in CATTR patients, independently of atrial fibrillation.
(1) Background: Limited data are available on lumbar spine stenosis management in sub-Saharan African populations and Afro-descendant patients are underrepresented in European and US clinical trials. ...We aimed to compare the clinical response between decompressive surgery and conservative treatments in a population of self-reported Afro-Caribbean patients with lumbar spine stenosis over a 2-year follow-up period. (2) Methods: Prospective cohort of 137 self-reported Afro Caribbeans with lumbar spine stenosis based on clinical and radiological criteria. Patients were assigned to decompression surgery or to conservative treatments according to their outcome after a first course of steroid epidural injection and their preferences. The primary outcome was evolution of the Oswestry disability index at 3 months (3 M), 12 M, 18 M and 24 M follow-up. (3) Results: Decrease of ODI was significantly more important in the “decompression surgery” arm compared to “conservative treatment” arm at 3 M, 12 M and 18 M: −17.36 vs. 1.03 p < 10−4; −16.38 vs. −1.53 p = 0.0059 and −19.00 vs. −4.52 p = 0.021, respectively. No difference was reported at 24 M. (4) Conclusions: In this first comparative study between surgery and conservative treatments in an exclusively afro-descendant lumbar spine stenosis cohort, we report long term superiority of decompression surgery versus conservative treatments over an 18-month period.
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.
PDF
