L’alemtuzumab, anticorps monoclonal anti-CD52, est indiqué dans le traitement des scléroses en plaques (SEP) rémittentes actives. Aucun évènement indésirable vasculaire en lien avec ce traitement n’a ...été rapporté à ce jour.
Nous rapportons le cas d’une patiente de 40ans porteuse d’une SEP rémittente depuis 1999, sans antécédent personnel (à noter une taille de 1,85m) ou familial, en dehors d’une hypotension artérielle et d’une tendance à la bradycardie lors des bolus de corticoïdes. Les traitements de fond ont comporté successivement interféron β1b, mycophénolate mofétil puis natalizumab, interrompu du fait du risque de leucoencéphalopathie multifocale progressive. Malgré un relais par diméthylfumarate, la patiente a présenté une reprise d’activité inflammatoire clinique et radiologique sévère, faisant poser l’indication d’alemtuzumab. Le premier cycle (12mg/j×5jours) a été réalisé en avril 2015 avec une bonne tolérance. Trois jours après, la patiente s’est plainte d’une baisse douloureuse de l’acuité visuelle de l’œil gauche évocatrice d’une névrite optique rétrobulbaire, associée à une dysmétrie du membre supérieur droit. Le lendemain, elle a présenté brutalement une hémiplégie droite avec aphasie. L’IRM encéphalique a mis en évidence un accident vasculaire cérébral (AVC) sylvien gauche et la dissection des artères carotides et de l’artère vertébrale droite. La patiente n’a pas été thrombolisée du fait de signes constitués d’AVC à l’IRM.
La chronologie de cet AVC par rapport au cycle d’alemtuzumab fait discuter de l’imputabilité au traitement. Il n’a pas été retrouvé de traumatisme récent chez la patiente. La réanalyse des IRM antérieures n’a pas mis en évidence d’aspect pathologique des artères. La physiopathologie de cet AVC pourrait être en lien avec la réaction inflammatoire générale importante liée au relargage cytokinique.
Il s’agit du premier cas de dissection multiple des artères cervicales compliqué d’un AVC ischémique, survenant dans les suites immédiates d’un cycle d’alemtuzumab. L’imputabilité au traitement est discutée.
Objectives: In the management of multiple sclerosis (MS), defining criteria for identification of suboptimal therapy responses and switching treatment is essential to avoid worsening. Despite the ...lack of a standardised definition, criteria for first-line treatment are well documented in the literature, based on clinical measures or magnetic resonance imaging (MRI) (gadolinium enhancing Gd+ lesions or new/enlarging T2 lesions) assessed during the first 6-18 months after treatment initiation. However, it is unknown whether the same criteria can be used for second-line treatment failure.Methods: Five regional boards involving 36 French MS experts were convened to discuss published literature regarding criteria for first- and second-line treatment failure, and to identify differences in local therapeutic practices. A national board of 11 experts was subsequently conducted to identify convergences and differences between regions, and to propose second-line criteria for the definition of therapeutic failure.Results: Published information is lacking regarding second-line treatment failure criteria. In light of this, regional differences in current therapeutic practices are justifiable. Due to the risk-benefit ratio of these treatments and limited options for third-line treatments, the authors recommend a different therapeutic approach when assessing second-line treatment failure. The treatment switch for second-line treatment should be informed by confirmed disease progression, after 6 months, or combined clinical and MRI outcomes, but only after at least 1 year of treatment.Conclusions: Experts compared therapeutic attitudes and practices regarding second-line treatment failure between French regions. They identified convergences that were used to propose a national agreement on second-line treatment failure criteria, which should be evaluated in real-life prospective cohorts.
Magnetic resonance spectroscopy has emerged as a sensitive modality to detect early and diffuse alterations in multiple sclerosis. Recently, the hypothesis of neurodegenerative pathogenesis has ...highlightened the interest for measurement of metabolites concentrations, to gain specificity, in a large brain volume encompassing different tissue alterations. Therefore, we proposed in this paper the implementation of an absolute quantification method based on localized spectroscopy at short (30 ms) and long (135 ms) echo time of a volume including normal appearing white matter, cortical gray matter, and lesions. First, methodological developments were implemented including external calibration, and corrections of phased-array coil sensitivity and cerebrospinal fluid volume contribution. Second, these improvements were validated and optimized using an original methodology based on simulations of brain images with lesions. Finally, metabolic alterations were assessed in 65 patients including 26 relapsing-remitting, 17 primary-progressive (PP), 22 secondary-progressive (SP) patients, and in 23 normal subjects. Results showed increases of choline, creatine, and myo-inositol concentrations in PP and SP patients compared to controls, whereas the concentration of N-acetyl compounds remained constant. The major finding of this study was the identification of Cho concentration and Cho/tNA ratio as putative markers of progressive onset, suggesting interesting perspectives in detection and followup of neurodegenerative processes.
Acute transverse myelitis had many names and definitions, based primarily on clinical criteria. The role of MRI in the exploration of myelitis has increased recently after the individualization of ...neuromyelitis optica (NMO) in 2004. This approach has enabled clarification of the diagnostic and prognostic value of acute longitudinally extensive transverse myelitis (LETM), defined by an extensive T2 lesion affecting three vertebral segments in the sagittal plane. The limitations of this definition, the multiplicity of terms used to characterize it as well as the large number of etiologies associated with it led our group of experts to clarify its etiology and nosology. We conducted a national survey on this subject in order to propose a new definition of LETM. Additional first- and second-intention examinations were determined according to the clinical context. Infectious/para-infectious, inflammatory or paraneoplastic causes can thus be identified. To determine within a short time the cause of LETM is essential, since most of its causes are severe and require urgent treatment.
•Eight weekly doses of macrocyclic GBCA do not accumulate in the brain.•Gadobutrol do not accumulate in the dentate nucleus or the Globus pallidus.•Macrocyclic gadolinium-based contrast agents (GBCA) ...use is safer than linear GBCA.
Gadolinium-based contrast agents (GBCAs) administration have drastically improved the accuracy of Multiple Sclerosis (MS) diagnosis by highlighting any damage to the brain blood barrier, thereby differentiating between active and non-active lesions. Following multiple administrations of GBCAs, several MS studies have reported a signal intensity (SI) increase on unenhanced T1-weighted images in certain brain regions such as the dentate nucleus (DN) and the globus pallidus (GP). Our aim was therefore to determine the accumulation of macrocyclic GBCAs on enhanced T1-weighted images SI in the DN and the GP of MS patients injected eight times.
Five MS patients underwent eight weekly consecutive MRI scans. Enhanced 3D T1-weighted images with Gadobutrol as a macrocyclic GBCA, were acquired. A ROI-based approach was applied for the evaluation of SI in the DN to middle cerebellar peduncle (DN-MCP) and GP to semi-oval white matter (GP-SOWM) ratios. An analysis of variance on repeated measures was used for the statistical analysis of each ratio.
No DN-MCP and GP-SOWM SI ratio differences were observed over the eight-weeks period using the macrocyclic GBCA.
Iterative and weekly injections of macrocyclic GBCAs are not associated with T1 signal increase in the DN and GP of MS patients. These results would suggest a no gadolinium accumulation in the brain using macrocyclic GBCA even after several close injections and promote the use of a macrocylcic GBCA rather than linear agents for MS patients.
In vivo metabolite quantification by short echo time MR spectroscopy is a challenge for which various methods have been proposed. In this study, the reproducibility of quantification outcomes is ...questioned at three distinct levels: (i) between-software (LCModel and cQUEST), (ii) withinsoftware (with different parameter sets), and (iii) across software executions (when the fitting algorithm uses random seeds, like cQUEST). After running multiple quantification tasks on a dedicated platform (VIP), metrics from Bland-Altman analysis were used to assess the variability of outcomes in signals acquired on a lysolecithin rat model, from a study on demyelination. Results show substantial variations at the three levels, allowing for more potent analyses than from a single parameter set / single software point of view.
La mesure de la perte du volume cérébral est un marqueur IRM de la neurodégénérescence dans la sclérose en plaques. Les techniques actuelles permettent de quantifier soit directement la perte de ...volume cérébral entre deux examens, soit de la mesurer indirectement à partir du volume cérébral de chaque examen. La fiabilité de ces techniques reste difficile à évaluer en l’absence de gold standard. Ce travail a consisté premièrement, en une étude de reproductibilité réalisée chez 9 patients à partir d’acquisitions semestrielles (3 IRM), sur deux machines différentes et post-traitées par sept algorithmes : BBSI, FreeSurfer, Intégration Jacobienne, KNBSI, un algorithme Segmentation / Classification, SIENA et SIENAX. Deuxièmement, un suivi longitudinal et prospectif a été effectué chez 90 patients SEP. L’étude des variabilités inter-techniques et inter-sites a montré que les techniques de mesures indirectes (Segmentation/Classification, FreeSurfer) et SIENAX fournissaient des pourcentages d’atrophie hétérogènes. A l’inverse, les techniques de mesures directes telles que BBSI, KNBSI, Intégration Jacobienne et à un moindre degré SIENA obtenaient des résultats reproductibles. Toutefois BBSI, KNBSI et l’Intégration Jacobienne obtenaient des pourcentages faibles, suggérant une possible sous-estimation de l’atrophie. L’évaluation de la perte du volume cérébral par Intégration Jacobienne a montré sur 2½ ans de suivi, une atrophie de 1,21% pour les 90 patients et de 1,55%, 1,51%, 0,84%, 1,21% respectivement pour les patients CIS, RR, SP et PP. A l’avenir l’évaluation de la perte de volume cérébral impose des défis d’ordre technique afin d’améliorer la fiabilité des algorithmes actuels.
Brain volume loss is currently a MRI marker of neurodegeneration in MS. The available algorithms for its quantification perfom either direct measurements, or indirect measurements. Their reliability remains difficult to assess especially since there is no gold standard technique. This work consisted first, in a reproducibility study performed on nine patients’ biannual MRI acquisitions (3 time points). These acquisitions were performed on two different MRI systems. Post-processing was applied using seven algorithms: BBSI, FreeSurfer, Jacobian Integration, KNBSI, an algorithm based on segmentation/classification, SIENA and SIENAX. Second, a longitudinal and prospective study was performed in 90 MS patients. The study of inter-technique and inter-site variabilities showed that direct measurement techniques and SIENAX provided heterogeneous values of atrophy. In contrast, indirect measurement algorithms such as BBSI, KNBSI, Jacobian Integration and to a lesser extent SIENA obtained reproducible results. However BBSI, KNBSI and Jacobian Integration algorithms showed lower percentages, suggesting a possible underestimation of atrophy. The evaluation of brain volume loss by Jacobian Integration has shown an atrophy rate of 1.21% over 2 ½ years of the 90 patients’ follow up, and of 1.55%, 1.51%, 0.84%, 1.21% for CIS, RR, SP and PP patients respectively. Jacobian Integration showed its importance in individual monitoring. In the future, assessing brain volume loss requires overcoming of some technical challenges to improve the reliability of the currently available algorithms.
Objective
The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).
Methods
A ...multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome CIS or relapsing‐remitting MS) and were also compared to two other population‐ and clinic‐based PPMS cohorts.
Results
Of the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow‐up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (
p
> 0.05). Median time to PPMS was 3.5 years (range, 1.6–5.4). RIS evolved to PPMS more commonly in men (
p
= 0.005) and at an older age (
p
< 0.001) when compared to CIS/MS, independent of follow‐up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow‐up period (
P
= 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS.
Interpretation
Subjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age‐dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum. Ann Neurol 2016;79:288–294
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