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BACKGROUND: Deep learning (DL) is an artificial intelligence technology that has aroused much excitement for predictive medicine due to its ability to process raw data modalities such as images, text, and time series of signals. OBJECTIVES: Here, we intend to give the clinical reader elements to understand this technology, taking neuroinflammatory diseases as an illustrative use case of clinical translation efforts. We reviewed the scope of this rapidly evolving field to get quantitative insights about which clinical applications concentrate the efforts and which data modalities are most commonly used. METHODS: We queried the PubMed database for articles reporting DL algorithms for clinical applications in neuroinflammatory diseases and the radiology.healthairegister.com website for commercial algorithms. RESULTS: The review included 148 articles published between 2018 and 2024 and five commercial algorithms. The clinical applications could be grouped as computer-aided diagnosis, individual prognosis, functional assessment, the segmentation of radiological structures, and the optimization of data acquisition. Our review highlighted important discrepancies in efforts. The segmentation of radiological structures and computer-aided diagnosis currently concentrate most efforts with an overrepresentation of imaging. Various model architectures have addressed different applications, relatively low volume of data, and diverse data modalities. We report the high-level technical characteristics of the algorithms and synthesize narratively the clinical applications. Predictive performances and some common a priori on this topic are finally discussed. CONCLUSION: The currently reported efforts position DL as an information processing technology, enhancing existing modalities of paraclinical investigations and bringing perspectives to make innovative ones actionable for healthcare.
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BACKGROUND AND OBJECTIVES: Ten years after its authorization, data about fingolimod use in real-world setting is still scarce. Here we describe the long-term evolution of fingolimod-treated relapsing-remitting MS (RRMS) patients and determine baseline characteristics associated with risk of relapses or disability. METHODS: We analyzed baseline characteristics and clinical evolution of 1227 patients with RRMS treated with fingolimod from 2010 to 2019 in 4 French MS referral centers. We used Cox models to determine risks factors of relapses and sustained EDSS worsening. RESULTS: Median follow-up duration was 50 months, and 63% of patients remained fingolimod-treated at the end of follow-up. Mean 5-years annualized relapse rate (ARR) decreased from 0.63 (0.60-0.67) to 0.26 (0.24-0.29, P<0.001), while the mean EDSS rose from 2.5 (2.4-2.6) to 3.0 (2.8-3.1, P<0.001). Female sex, lower age, higher EDSS and use of natalizumab were associated with relapse risk. Female sex was associated with sustained EDSS increase risk. CONCLUSIONS: Based on a large real-world cohort, our results confirm the durable reduction of the ARR described in pivot studies. Switching from moderate-efficacy DMT to fingolimod decreased the relapse risk. Switching patients from high-efficacy DMT increased risk of relapse, but the overall five-years ARR remained stable.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Estudios de Cohortes , Natalizumab/efectos adversos , Recurrencia , Inmunosupresores/efectos adversosRESUMEN
BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: To analyze the humoral response after COVID-19 vaccination in patients with multiple sclerosis (MS) according to disease-modifying treatments (DMTs) and in comparison with the humoral response after SARS-CoV-2 infection. METHODS: We included 28 MS patients with serological results after COVID-19 vaccination (Pfizer-BioNTech or Moderna ARNm) and 61 MS patients with serological results after COVID-19 (COVID-19 group) among patients followed up at the MS Center of Strasbourg, France, between January and April 2021. The primary endpoint was the IgG index according to DMTs (anti-CD20 mAb, sphingosine 1-phosphate receptor [S1PR] modulator and other treatments) and COVID-19 vaccine or COVID-19 groups. RESULTS: In the vaccinated MS patients, the median IgG index was lower in patients treated with anti-CD20 mAb and in patients treated with S1PR modulator compared to patients receiving other or no DMTs (4.80 [1.58-28.6], 16.5 [16.3-48.5], 1116 [434-1747] and 1272 [658-1886], respectively, P<0.001). Similar results were found for MS patients after COVID-19. CONCLUSIONS: Patients with MS and treated with S1PR modulators or anti-CD20 mAb had a reduced humoral response after COVID-19 vaccine.
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COVID-19 , Esclerosis Múltiple , Vacunas contra la COVID-19 , Humanos , SARS-CoV-2 , VacunaciónRESUMEN
BACKGROUND: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). OBJECTIVE: To characterize a cohort of MS patients with atypical myelitis. METHODS: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. RESULTS: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3-6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. CONCLUSION: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.
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Esclerosis Múltiple , Mielitis Transversa , Neuromielitis Óptica , Adulto , Acuaporina 4 , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/complicaciones , Mielitis Transversa/etiología , Neuromielitis Óptica/complicaciones , Adulto JovenRESUMEN
INTRODUCTION: The spinal cord is one of the two main targets of neuromyelitis optica (NMO). The aim of this study was to highlight cervical spinal cord atrophy in NMO patients as compared to controls and to assess correlations between atrophy and clinical characteristics and cervical spinal cord MRI data. METHODS: This prospective study investigated 15 patients with a diagnosis of NMOSD and 15 healthy controls. The whole cervical spinal cord was explored by MRI. The cross-sectional area (CSA) was estimate at every level of cup. This measurement was then averaged on the whole cervical spinal cord, providing a single measurement for every subject, denoted as mean CSA. RESULTS: Mean CSA was 68.5 mm2 in the population of NMO patients and 72.8 mm2 in the population of healthy subjects. NMO patients had significantly smaller cervical spinal cord area than healthy controls (T test=0.009). Cervical spinal cord atrophy was associated with clinical signs of medullary involvement (T test=0.0006). There was a tendency toward a relation between cervical spinal cord atrophy and the Expanded Disability Status Scale (EDSS) (T test=0.07). This correlation seems statistically significant (T test<0.05) at the level of the upper cervical spinal cord (C2-C3) CONCLUSION: This study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord.
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Médula Cervical , Neuromielitis Óptica , Atrofia , Humanos , Imagen por Resonancia Magnética , Neuromielitis Óptica/patología , Estudios Prospectivos , Médula Espinal/patologíaRESUMEN
INTRODUCTION: Neuromyelitis optica spectrum disorder (NMO-SD) has been recognized for the past decade. Biomarkers such as anti-Aquaporin 4 antibodies (AQP4) and anti-Myelin Oligodendrocyte Glycoprotein (MOG) have been able to classify NMO-SD into several groups. METHODS: A retrospective study was performed in the Strasbourg University Medical Center among patients with AQP4+, MOG+ and double-seronegative NMO to compare their clinical, epidemiological and paraclinical features. RESULTS: Thirty-two patients with NMO were included. The AQP4+ NMO patients had a median of age of 45 years, with associated myelitis in 62.5% of cases and other autoantibodies in 37.5% of cases. The mean number of relapses by clinical history was 3. The mean initial visual acuity during an exacerbation was 0.3 LogMAR, and the visual acuity after an exacerbation was 0.1 LogMAR. MOG+NMO patients had a median age of 23 years, with severely impaired initial visual acuity (0.6 LogMAR) but better recovery (0 LogMAR); optic disc edema was present in 80% of cases; the mean number of relapses on clinical history was 1. AQP4-/MOG- NMO's were more common in women (70%) and were bilateral in 40% of cases. CONCLUSION: The diagnostic characteristics of NMO-SD are becoming increasingly differentiated, with a positive impact on functional prognosis and long-term progression. Other biomarkers have yet to be identified to improve the diagnosis and treatment of these disorders.
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Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/epidemiología , Adulto , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/terapia , Estudios Retrospectivos , Agudeza Visual/fisiología , Adulto JovenRESUMEN
INTRODUCTION: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. OBJECTIVE: To survey the current global clinical practice of clinicians treating MOGAD. METHOD: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February-April 2019). RESULTS: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. CONCLUSION: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.
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Autoanticuerpos , Inmunoglobulinas Intravenosas , Adulto , Niño , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Glicoproteína Mielina-Oligodendrócito , Plasmaféresis , Encuestas y CuestionariosRESUMEN
BACKGROUND AND PURPOSE: Three different sets of criteria have been proposed for the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The objective was to compare the specificity, sensitivity and diagnostic accuracy of the three different sets of NMOSD criteria in patients presenting with inflammatory disorders of the central nervous system suggestive of NMOSD. METHODS: For 236 suspected NMOSD patients referred for serum aquaporin-4 immunoglobulin G antibody (AQP4-IgG) testing between 2012 and 2014, the three sets of NMOSD criteria [1999, 2006 NMO criteria and 2015 International Panel for NMO Diagnosis (IPND) criteria] were applied and compared to the final diagnosis. RESULTS: Seventy-six patients fulfilled at least one set of criteria and 28 patients fulfilled all NMOSD sets of criteria. The final diagnosis was NMOSD in 66 cases, multiple sclerosis according to the MacDonald 2010 criteria in 85 cases and another diagnosis in 85 cases. The 2006 NMO criteria have the highest specificity (99%) and the 2015 IPND NMOSD criteria the highest sensitivity (97%). For the 1999, 2006 and 2015 IPND NMOSD criteria, the accuracy was respectively 82%, 87% and 97%. CONCLUSIONS: Our study highlights the limitations of the first set of criteria that include the optico-spinal form of multiple sclerosis. The accuracy of NMOSD diagnostic criteria improved from 1999 to 2015. It confirms the increased performance of the last set of criteria which covers a larger spectrum of clinical presentation. This study raises some concerns for classifying patients with seronegative transverse myelitis or optic neuritis, and myelin oligodendrocyte glycoprotein (MOG) antibody- associated disease.
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Esclerosis Múltiple , Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Humanos , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/diagnósticoAsunto(s)
Betacoronavirus , Enfermedades del Sistema Nervioso Central/complicaciones , Infecciones por Coronavirus/complicaciones , Pandemias , Neumonía Viral/complicaciones , COVID-19 , Enfermedades del Sistema Nervioso Central/virología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Humanos , Neurólogos , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , SARS-CoV-2RESUMEN
During the 20 past years, the management of multiple sclerosis (MS) has largely changed especially concerning therapeutical approach. Before 1996, treatments were restricted to corticosteroids for relapses, several symptomatic treatments and unselective immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate) with a low evidence of any efficacy. In the present review, we analyze the principal real-life cohorts of MS during several periods (before therapeutical modern area, first-generation treatment area and most recent period). Despite many methodological problems, we observe globally a delay of around 3-5 years between untreated cohorts and first-generation treatments for going to EDSS 6 which is probably the most robust score. This delay is clearly increase to at least 15 years with the most recent cohort treated first and second-line treatments confirming that early and more intensive treatment are necessary to have a long-term efficacy on disability progression and especially on severe disability represent by EDSS 6. Larger cohorts with longer follow-up is necessary to confirm these tendencies and OFSEP observatory or MS base will probably provide us the possibility to conclude in a couple of years.
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Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Inmunosupresores/clasificación , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/patología , Esclerosis Múltiple Crónica Progresiva/epidemiología , Esclerosis Múltiple Crónica Progresiva/prevención & control , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/prevención & control , Preparaciones Farmacéuticas/clasificación , RecurrenciaRESUMEN
BACKGROUND AND PURPOSE: Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). METHODS: This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. RESULTS: In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P < 0.001). The test-retest study demonstrated the good reproducibility of MSCopilot. CONCLUSION: This study confirms the reliability of MSCopilot and its usability in clinical practice for the monitoring of MS-related disability.
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Cognición/fisiología , Autoevaluación Diagnóstica , Evaluación de la Discapacidad , Destreza Motora/fisiología , Esclerosis Múltiple/diagnóstico , Visión Ocular/fisiología , Caminata/fisiología , Adulto , Anciano , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Estándares de Referencia , Reproducibilidad de los Resultados , Evaluación de Síntomas , Adulto JovenAsunto(s)
Esclerosis Múltiple/inmunología , Vacunación , Actitud Frente a la Salud , Causalidad , Contraindicaciones , Francia/epidemiología , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/patología , Guías de Práctica Clínica como Asunto , Factores de Riesgo , Vacunación/efectos adversos , Vacunación/métodos , Vacunación/estadística & datos numéricosRESUMEN
Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory disease of the central nervous system characterized, in particular, by disabling episodes of optic neuritis and longitudinal extensive transverse myelitis. Its main pathogenic characteristic is the presence of anti-aquaporin-4 antibodies (AQP4-Abs) in the serum of affected patients. However, a proportion of patients with the typical NMOSD phenotype are, in fact, negative (seronegative) for AQP4-Abs and, within this category of patients, a proportion of them instead express antibodies to myelin oligodendrocyte glycoprotein (MOG-Abs). The presence of MOG-Abs in the sera of seronegative NMOSD patients is more frequently associated with monophasic disease and moderate symptom severity, and also appears to predict a better outcome. The present report is a review of the clinical and immunological features of MOG-Ab-positive NMOSD.
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Autoanticuerpos/sangre , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/inmunología , Acuaporina 4/inmunología , Humanos , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/patologíaRESUMEN
Over the past few years, new-generation cell-based assays have demonstrated a robust association of autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis and brainstem encephalitis, as well as with acute disseminated encephalomyelitis (ADEM)-like presentations. Most experts now consider MOG-IgG-associated encephalomyelitis (MOG-EM) a disease entity in its own right, immunopathogenetically distinct from both classic multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD). Owing to a substantial overlap in clinicoradiological presentation, MOG-EM was often unwittingly misdiagnosed as MS in the past. Accordingly, increasing numbers of patients with suspected or established MS are currently being tested for MOG-IgG. However, screening of large unselected cohorts for rare biomarkers can significantly reduce the positive predictive value of a test. To lessen the hazard of overdiagnosing MOG-EM, which may lead to inappropriate treatment, more selective criteria for MOG-IgG testing are urgently needed. In this paper, we propose indications for MOG-IgG testing based on expert consensus. In addition, we give a list of conditions atypical for MOG-EM ("red flags") that should prompt physicians to challenge a positive MOG-IgG test result. Finally, we provide recommendations regarding assay methodology, specimen sampling and data interpretation, and propose for the first time diagnostic criteria for MOG-EM.
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Autoanticuerpos , Encefalomielitis , Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Autoanticuerpos/sangre , Encefalomielitis/sangre , Encefalomielitis/diagnóstico , Testimonio de Experto , Humanos , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/sangre , Neuromielitis Óptica/diagnósticoRESUMEN
BACKGROUND: Despite a recent interest in Real World Data, such studies are scarce in multiple sclerosis (MS) disease. The objective was to describe the patients, disease progression and use of DMDs in France and compare clinical effectiveness of first-line injectable DMDs. METHODS: We conducted a retrospective multicenter study in France, using data collected by 11 expert centers with the EDMUS software. RESULTS: Overall, 15,039 French MS patients were followed for a mean of 11.5 years. Mean age at start of disease was 32 years and 74% were women. After the disease onset, median time to reach EDSS 3 was 11 years and 51.8% of patients were relapse-free 2 years after the disease's onset. The mean delay between onset of disease and initiation of treatment was 5.7⯱â¯6.9 years. Over time, it decreased from 8.8⯱â¯7.8 to 0.7⯱â¯0.7 years for initiation of treatment before 2000â¯vs. after 2010, respectively. Two years after the initiation of treatment, the persistence rate of injectable disease modifying drugs (DMDs) was 60.7%. The effectiveness of these drugs were quite similar. CONCLUSION: This study brings new insight on the natural history of MS and the use and effectiveness of injectable DMDs in this condition.