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
Background:
Pseudocystic inflammatory demyelinating lesions (PIDLs) are poorly described in MS and might represent a diagnostic challenge.
Objectives:
We described the clinical, radiological, ...pathological, and follow-up characteristics of 13 PIDL in 9 MS patients.
Methods:
We constituted a single-center retrospective case series of PIDLs in MS, defined on MRI as expansive cyst-like lesions, with a fluid-signal content, and a diameter of 1 cm or more.
Results:
PIDL often occurred at first event (56%), were often asymptomatic (69%), and encircled by a hypo-T2 diffusion-restricted rim and a thin ring-like gadolinium enhancement (100%) on magnetic resonance imaging (MRI). Associated typical MS lesions were constant. Biopsies from two PIDLs displayed classical features of active MS, except for unusual edema.
Conclusion:
PIDLs are clinically unremarkable and associated with a good outcome. Their easily recognizable MRI features could help avoid biopsy.
Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) have been reported in acute demyelinating encephalomyelitis (ADEM), optic neuritis (ON), and neuromyelitis optica spectrum disorders (NMOSD) in ...adults and pediatrics. We aimed to delineate the common features of MOG-Ab-related disorders in children and adults, and report uncommon presentations. Twenty-seven consecutive pediatric and adult patients testing positive for MOG-Ab, with a minimum follow-up of 6 months, were included. Comprehensive epidemiological, clinical, radiological, and laboratory data were retrospectively analyzed. Additionally, we compared radiological features between ADEM MOG-Ab-positive patients, and a group of ADEM MOG-Ab-negative ones, recruited during the same period. Among the whole cohort, 13 (48.1%) were pediatric, and 14 (51.9%) were female. MOG-Ab-related disorders comprised eight ADEM, eight ON, five isolated myelitis, four with NMOSD and two patients with multiple sclerosis, at last follow-up. After a median follow-up of 17.8 months, 11 (40.7%) patients presented a relapse. The most frequent clinical phenotype at onset was encephalopathy in pediatrics (53.9%) and myelitis in adults (50%) (
p
= 0.013). There were no other differences between both groups. When comparing ADEM MOG-Ab positive and negative patients, bilateral thalamic lesions were more often found in the positive group (
p
= 0.010). Unusual presentations were identified in three patients: patchy spinal cord gadolinium-enhancing lesions, an associated teratoma, and one presented with status epilepticus. MOG-Ab-related disorders shared common clinical and prognostic features, but encompass a spectrum wider than recently reported.
Background and Purpose
The aim of this study is to determine whether cerebral white matter (WM) microstructural damage, defined by decreased fractional anisotropy (FA) and increased axial (AD) and ...radial (RD) diffusivities, could be detected as accurately by measuring the T1/T2 ratio, in relapsing‐remitting multiple sclerosis (RRMS) patients compared to healthy control (HC) subjects.
Methods
Twenty‐eight RRMS patients and 24 HC subjects were included in this study. Region‐based analysis based on the ICBM‐81 diffusion tensor imaging (DTI) atlas WM labels was performed to compare T1/T2 ratio to DTI values in normal‐appearing WM (NAWM) regions of interest. Lesions segmentation was also performed and compared to the HC global WM.
Results
A significant 19.65% decrease of T1/T2 ratio values was observed in NAWM regions of RRMS patients compared to HC. A significant 6.30% decrease of FA, as well as significant 4.76% and 10.27% increases of AD and RD, respectively, were observed in RRMS compared to the HC group in various NAWM regions. Compared to the global WM HC mask, lesions have significantly decreased T1/T2 ratio and FA and increased AD and RD (p < . 001).
Conclusions
Results showed significant differences between RRMS and HC in both DTI and T1/T2 ratio measurements. T1/T2 ratio even demonstrated extensive WM abnormalities when compared to DTI, thereby highlighting the ratio's sensitivity to subtle differences in cerebral WM structural integrity using only conventional MRI sequences.
Exit strategies such as de-escalations have not been evaluated for rituximab in patients with neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that they are associated with disease ...reactivations and aimed to estimate this risk.
We describe a case series of real-world de-escalations from the French NMOSD registry (NOMADMUS). All patients met the 2015 International Panel for NMO Diagnosis (IPND) diagnostic criteria for NMOSD. A computerized screening of the registry extracted patients with rituximab de-escalations and at least 12 months of subsequent follow-up. We searched for 7 de-escalation regimens: scheduled discontinuations or switches to an oral treatment after single infusion cycles, scheduled discontinuations or switches to an oral treatment after periodic infusions, de-escalations before pregnancies, de-escalations after tolerance issues, and increased infusion intervals. Rituximab discontinuations motivated by inefficacy or for unknown purposes were excluded. The primary outcome was the absolute risk of NMOSD reactivation (one or more relapses) at 12 months. AQP4+ and AQP4- serotypes were analyzed separately.
We identified 137 rituximab de-escalations between 2006 and 2019 that corresponded to a predefined group: 13 discontinuations after a single infusion cycle, 6 switches to an oral treatment after a single infusion cycle, 9 discontinuations after periodic infusions, 5 switches to an oral treatment after periodic infusions, 4 de-escalations before pregnancies, 9 de-escalations after tolerance issues, and 91 increased infusion intervals. No group remained relapse-free over the whole de-escalation follow-up (mean: 3.2 years; range: 0.79-9.5), except pregnancies in AQP+ patients. In all groups combined and within 12 months, reactivations occurred after 11/119 de-escalations in patients with AQP4+ NMOSD (9.2%, 95% CI 4.7-15.9), from 0.69 to 10.0 months, and in 5/18 de-escalations in patients with AQP4- NMOSD (27.8%, 95% CI 9.7-53.5), from 1.1 to 9.9 months.
There is a risk of NMOSD reactivation whatever the rituximab de-escalation regimen.
Registered on ClinicalTrials.gov: NCT02850705.
This study provides Class IV evidence that de-escalation of rituximab increases the probability of disease reactivation.
Background and purpose
Diagnostic criteria for adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) due to colony‐stimulating factor 1 receptor (CSF1R) mutation have ...recently been proposed. Our objective was to assess their accuracy in an independent multicenter cohort.
Methods
We evaluated the sensitivity and specificity of the diagnostic criteria for ALSP (including the “probable” and “possible” definitions) in a national cohort of 22 patients with CSF1R mutation, and 59 patients with an alternative diagnosis of adult onset inherited leukoencephalopathy.
Results
Overall, the sensitivity of the diagnostic criteria for ALSP was 82%, including nine of 22 patients diagnosed as probable and nine of 22 diagnosed as possible. Twenty of the 59 CSF1R mutation‐negative leukoencephalopathies fulfilled the diagnostic criteria, leading to a specificity of 66%.
Conclusions
Diagnostic criteria for ALSP have an overall limited sensitivity along with a modest specificity. We suggest that in patients suspected of genetic leukoencephalopathy, a comprehensive magnetic resonance imaging pattern‐based approach is warranted, together with white matter gene panel or whole exome sequencing.
Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is due to heterozygous CSF1R mutations. It is increasingly recognized as a major cause of inherited leukoencephalopathies in adulthood. Our study assessed the sensitivity and specificity of diagnostic criteria for ALSP and suggests that they may be misleading. Instead, we propose that every patient with an unexplained rapidly evolving leukoencephalopathy should be tested for a CSF1R mutation, as a potential therapy (allogenic hematopoietic stem cell transplantation) exists.
Objective
The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG‐Ab–associated ...disease (MOGAD).
Methods
This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time‐to‐event data and Kaplan–Meier curves for time to antibody negativity were performed for the objectives.
Results
Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow‐up reached only by 10 of 97 10.3% vs 66/247 26.7%, p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval CI = 1.12–1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9–86.5) of nonrelapsing children became MOG‐Ab negative compared to 14.1% (95% CI = 4.7–38.3) of relapsing children (log‐rank p < 0.001), with no differences observed in adults (log‐rank p = 0.280).
Interpretation
MOGAD patients differ in the clinical presentation at onset, showing an age‐related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG‐Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30–41
OBJECTIVETo address the frequency of myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) in an unselected large cohort of adults with MS.
METHODSThis is a cross-sectional study in 2 MS expert ...centers (Lyon and Strasbourg University Hospitals, France) between December 1, 2017, and June 31, 2018. Patients aged ≥18 years with a definite diagnosis of MS according to 2010 McDonald criteria were tested for MOG-Ab by using a cell-based assay (CBA) in Lyon and subsequently included. Positive samples were tested by investigators blinded to the first result with a second assay in a different laboratory (Barcelona, Spain) by using the same plasmid and secondary Ab.
RESULTSSerum samples from 685 consecutive patients with MS were analyzed for MOG-Ab. Median disease duration at sampling was 11.5 (interquartile range, 5.8–17.7) years, and 72% were women. Two (0.3%) patients resulted to be MOG-Ab-positive. The 2 patients were women aged 42 and 38 at disease onset and were diagnosed with secondary and primary progressive forms of MS, respectively. This positive result was confirmed by the CBA in Barcelona.
CONCLUSIONOur findings indicate that MOG-Ab are exceptional in MS phenotype, suggesting that the MOG-Ab testing should not be performed in typical MS presentation.
Background:
Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised.
...Objectives:
We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS).
Methods:
This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients’ history of COVID-19 infection.
Results:
No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients.
Conclusion:
Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.
•Generating synthetic brain networks is not trivial due to multiple interconnections between different nodes.•Generative Adversarial Autoencoder neural network is employed for the generation of ...synthetic structural brain network with Multiple Sclerosis.•Structural comparison between real and synthetic brain network is performed for assessing the quality of generated samples.•Classification performance comparison shows significant improvement over traditional upsampling methods.
Background and objective:Machine learning frameworks have demonstrated their potentials in dealing with complex data structures, achieving remarkable results in many areas, including brain imaging. However, a large collection of data is needed to train these models. This is particularly challenging in the biomedical domain since, due to acquisition accessibility, costs and pathology related variability, available datasets are limited and usually imbalanced. To overcome this challenge, generative models can be used to generate new data.
Methods: In this study, a framework based on generative adversarial network is proposed to create synthetic structural brain networks in Multiple Sclerosis (MS). The dataset consists of 29 relapsing-remitting and 19 secondary-progressive MS patients. T1 and diffusion tensor imaging (DTI) acquisitions were used to obtain the structural brain network for each subject. Evaluation of the quality of newly generated brain networks is performed by (i) analysing their structural properties and (ii) studying their impact on classification performance.
Results: We demonstrate that advanced generative models could be directly applied to the structural brain networks. We quantitatively and qualitatively show that newly generated data do not present significant differences compared to the real ones. In addition, augmenting the existing dataset with generated samples leads to an improvement of the classification performance (F1score 81%) with respect to the baseline approach (F1score 66%).
Conclusions: Our approach defines a new tool for biomedical application when connectome-based data augmentation is needed, providing a valid alternative to usual image-based data augmentation techniques.
PDF
