ABSTRACT
BACKGROUND: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), a rare disorder affecting young adults, causes gradual weakness of the limbs, areflexia and impaired sensory function. New CIDP phenotypes without pathogenic antibodies but with modified cell profiles have been described. Treatments include corticotherapy, intravenous immunoglobulins, and plasmapheresis but the latter's action mechanisms remain unclear. Plasmapheresis supposedly removes toxic agents like antibodies from plasma but it is uncertain whether it has an immune-modulating effect. Also, the refining mechanisms of the two main plasmapheresis techniques-single plasma exchange and double filtration plasmapheresis (DFPP) - are different and unclear. This study aims to compare the evolution of peripheral lymphocyte profiles in patients with CIDP according to their treatment (single centrifugation plasmapheresis or DFPP) to better grasp the action mechanisms of both techniques. METHOD: In this proof-of-concept, monocentric, prospective, Single-Case Experimental Design study, 5 patients are evaluated by alternating their treatment type (single plasma exchange or DFPP) for 6 courses of treatment after randomization to their first treatment type. Each course of treatment lasts 2-4 weeks. For single plasma exchange, 60 ml/kg plasma will be removed from the patient and replaced with albumin solutes, with a centrifugation method to avoid the immunological reaction caused by the membrane used with the filtration method. For DFPP, 60 ml/kg plasma will be removed from the patient with a plasma separator membrane, then processed via a fractionator membrane to remove molecules of a greater size than albumin before returning it to the patient. This technique requires no substitution solutes, only 20 g of albumin to replace what would normally be lost during a session. The primary outcome is the difference between the two plasmapheresis techniques in the variation of the TH1/TH17 ratio over the period D0H0-D0H3 and D0H0-D7. Secondary outcomes include the variation in lymphocyte subpopulations at each session and between therapeutic plasmapheresis techniques, the clinical evolution, tolerance and cost of treatments. DISCUSSION: Understanding the action mechanisms of single plasma exchange and DFPP will help us to offer the right treatment to each patient with CIPD according to efficacy, tolerance and cost. TRIAL REGISTRATION: ClinicalTrials.gov under the no. NCT04742374 and date of registration 10 December 2020.
Subject(s)
Plasma Exchange , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Albumins , Humans , Lymphocytes , Phenotype , Plasmapheresis/methods , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy , Proof of Concept Study , Prospective Studies , Research DesignABSTRACT
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.
Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Fingolimod Hydrochloride/therapeutic use , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.
Subject(s)
Immunoglobulin kappa-Chains/metabolism , Immunoglobulin lambda-Chains/metabolism , Multiple Sclerosis/diagnosis , Oligoclonal Bands , Adult , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Female , Humans , Immunoglobulin kappa-Chains/blood , Immunoglobulin kappa-Chains/cerebrospinal fluid , Immunoglobulin lambda-Chains/blood , Immunoglobulin lambda-Chains/cerebrospinal fluid , Male , Middle Aged , Oligoclonal Bands/blood , Oligoclonal Bands/cerebrospinal fluid , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND AND PURPOSE: The prognostic value of serum neurofilament light chain (sNfL), a biomarker of neurodegeneration, compared to other prognostic factors of amyotrophic lateral sclerosis (ALS) at the time of diagnosis, remains unclear. METHODS: Sera from ALS patients were prospectively collected at the first diagnostic visit in our centre. sNfL levels were determined by single molecule array in 207 ALS patients and in 21 healthy controls. The prognostic value of sNfL was compared with that of other known clinical prognostic factors using a Cox regression model and multivariate analysis. RESULTS: Serum neurofilament light chain levels were higher in ALS patients than in controls (P < 0.0001). Seven parameters were predictive of death in ALS: older age, bulbar onset, higher ALS Functional Rating Scale revised (ALSFRS-R) score, greater weight loss, lower maximal inspiratory pressure, forced vital capacity and higher sNfL levels. A Cox regression model showed that sNfL (P < 0.0001), weight loss (P = 0.040) and site at onset (P = 0.048) were independent predictive factors of death. In a sub-cohort restricted to 139 patients with complete spirometry data, sNfL level (P < 0.005) and forced vital capacity (P = 0.022) were independent factors predictive of death. In a subgroup of 142 patients in whom ALSFRS-R score was available at several time points, sNfL levels positively correlated with ALSFRS-R rate of decline (r = 0.571, P < 10-12 ). CONCLUSIONS: Higher sNfL concentration is a strong and independent prognostic factor of death in ALS as early as the time of diagnosis.
Subject(s)
Amyotrophic Lateral Sclerosis/blood , Amyotrophic Lateral Sclerosis/diagnosis , Neurofilament Proteins/blood , Aged , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Survival Analysis , Vital Capacity , Weight LossSubject(s)
Cerebral Hemorrhage, Traumatic/etiology , Craniocerebral Trauma/complications , Glymphatic System/pathology , Adult , Cerebral Hemorrhage, Traumatic/diagnosis , Craniocerebral Trauma/diagnosis , Dilatation, Pathologic/complications , Dilatation, Pathologic/diagnosis , Frontal Lobe/diagnostic imaging , Frontal Lobe/injuries , Frontal Lobe/pathology , Glymphatic System/injuries , Humans , Magnetic Resonance Imaging , Male , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/injuries , Prefrontal Cortex/pathology , Soccer/injuriesSubject(s)
Multiple Sclerosis/immunology , Vaccination , Attitude to Health , Causality , Contraindications , France/epidemiology , Humans , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis/pathology , Practice Guidelines as Topic , Risk Factors , Vaccination/adverse effects , Vaccination/methods , Vaccination/statistics & numerical dataABSTRACT
BACKGROUND: Neuroimaging studies suggest that social distress and suicidal vulnerability share common cerebral bases. Moreover, increased peripheral inflammatory activity is involved in both social distress and suicidal behavior. OBJECTIVE: To evaluate, in suicidal and non-suicidal individuals, the association between the activation of specific cerebral regions (anterior cingulate, insula and orbitofrontal cortex) during experimental social exclusion and the baseline blood levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) and of the anti-inflammatory cytokine interleukin-2 (IL-2). METHODS: In total, 101 euthymic women were recruited: 42 suicide attempters (SA), 40 affective controls (AC), and 19 healthy controls (HC). During functional MRI (fMRI), they performed the Cyberball game, a validated social exclusion task. Blood levels of IL-1ß, IL-6, TNF-α and IL-2 were measured prior to fMRI. The activation of insula, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) during the explicit social exclusion (ESE) vs social inclusion (INC) conditions of the Cyberball game was analyzed in function of the baseline cytokine levels. RESULTS: IL-1ß was negatively associated with right OFC activation (p = 0.01) in ESE vs. INC, whereas IL-2 was positively associated with activation of the right ACC (p = 0.02), insula (p = 0.002) and OFC (p = 0.004) in ESE vs. INC. These associations remained significant after controlling for group, indicating that they were independent of the suicidal status. CONCLUSION: Baseline IL-1ß and IL-2 blood levels are differentially associated with cerebral activation involved in the perception of social exclusion, independently of suicidal behavior. Our results may help to better understand the role of basal inflammation in social distress and its link with mood disorder pathophysiology.
Subject(s)
Cytokines/analysis , Suicide, Attempted/psychology , Suicide/psychology , Adult , Cerebral Cortex/physiopathology , Cytokines/blood , Depressive Disorder, Major/psychology , Female , Gyrus Cinguli/physiopathology , Humans , Inflammation/blood , Interleukin-1beta/analysis , Interleukin-1beta/blood , Interleukin-2/analysis , Interleukin-2/blood , Interleukin-6/analysis , Interleukin-6/blood , Magnetic Resonance Imaging/methods , Middle Aged , Prefrontal Cortex/physiopathology , Psychological Distance , Social Behavior , Suicidal Ideation , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/bloodSubject(s)
Demyelinating Diseases/pathology , Demyelinating Diseases/therapy , Multiple Sclerosis/prevention & control , Prodromal Symptoms , Demyelinating Diseases/diagnosis , Diagnosis, Differential , Disease Progression , Humans , Magnetic Resonance Imaging , Multiple Sclerosis/pathology , Risk Assessment , SyndromeABSTRACT
Multiple sclerosis (MS) is a complex heterogeneous disease. Diagnostic criteria are based on symptoms, biomarkers, MRI data and exclusion of differential diagnoses. Over the past few years, the usefulness of biomarkers has progressively decreased with the development of new MRI criteria, yet dozens of new biomarkers, especially in cerebrospinal fluid, for MS diagnosis and prognosis have been described. Large-scale studies validating some of these new biomarkers have also provided confirmation of a restricted set of biomarkers (presented here in this review) as having potential value for different stages of the disease, including as early as clinically isolated syndrome and radiologically isolated syndrome. However, differentiating progressive forms of MS from relapsing-remitting MS remains a genuine challenge, and could help to predict future conversion to secondary-progressive MS. In addition, new approaches combining multiple biomarkers might allow us to unravel the complexity of the disease and determine disease stages more precisely. Moreover, recent technological developments allowing analysis of biomarkers in plasma have also provided less invasive analysis of MS, and should serve to predict MS evolution and therapeutic responses during follow-up.
Subject(s)
Biomarkers/analysis , Diagnostic Techniques, Neurological , Multiple Sclerosis/diagnosis , Biomarkers/blood , Biomarkers/metabolism , Diagnosis, Differential , Humans , Magnetic Resonance Imaging , Multiple Sclerosis/blood , Multiple Sclerosis/metabolism , PrognosisABSTRACT
BACKGROUND: Density heterogeneity and fluid-blood levels (FBLs) are frequently seen on acute CT scans of deep brain hemorrhage. Our aim was to analyze the density heterogeneity and FBLs seen on acute/subacute CT in patients aged>55 with lobar haemorrhage (LH), and to study the relationship of these brain abnormalities with other parameters, including cerebral amyloid angiopathy (CAA)-related abnormalities. METHODS: This was an observational study and retrospective analysis of early CT scans (<7 days) in patients aged>55 years with acute lobar hemorrhage who, between 2012 and 2015, were entered into our stroke database. A total of 37 LH episodes (without trauma, abnormal coagulation/platelet counts, vascular malformation, tumor or vasculitis) in 35 patients were analyzed. Other studied parameters were gender, age, history of hypertension, blood pressure on admission, prior antiplatelet treatment, aPTT, PTT, platelet count, hematocrit, timing of first CT, LH volume, involved lobe, cortical superficial siderosis, microbleeds, chronic LH and CAA (classic and modified Boston) criteria. CAA-related abnormalities seen on MRI were also scored. RESULTS: Overall, in 26 LH episodes (70%), CT was performed within 24h. Density heterogeneity and FBLs were seen in 19 (51%) and 9 (24%) LH episodes, respectively. Also, according to classic and modified Boston criteria, 18 (51%) and 24 (69%) patients, respectively, fulfilled criteria for probable/definite CAA. As for the presence of FBLs, a statistically significant association was found with both the presence of probable/definite CAA according to modified Boston criteria (P=0.033) and the presence of superficial siderosis (P=0.019). CONCLUSION: Density heterogeneity and, to a lesser degree, FBLs are frequently seen in patients aged>55 with LH. FBLs may also be associated with CAA-related hemorrhage.
Subject(s)
Blood Volume , Brain/pathology , Hematoma/pathology , Hydrodynamics , Intracranial Hemorrhages/pathology , Aged , Aged, 80 and over , Brain/physiopathology , Female , Fluid Shifts , Frontal Lobe/blood supply , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Frontal Lobe/physiopathology , Hematoma/blood , Hematoma/diagnostic imaging , Hematoma/physiopathology , Humans , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/diagnostic imaging , Intracranial Hemorrhages/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Occipital Lobe/blood supply , Occipital Lobe/diagnostic imaging , Occipital Lobe/pathology , Occipital Lobe/physiopathology , Retrospective Studies , Stroke , Temporal Lobe/blood supply , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology , Temporal Lobe/physiopathology , Tomography, X-Ray ComputedSubject(s)
Brain Ischemia/complications , Cerebral Infarction/complications , Medulla Oblongata/pathology , Nystagmus, Pathologic/etiology , Aged , Brain Ischemia/diagnostic imaging , Brain Ischemia/pathology , Cerebral Infarction/diagnostic imaging , Computed Tomography Angiography , Humans , Magnetic Resonance Imaging , Male , Medulla Oblongata/diagnostic imaging , Nystagmus, Pathologic/diagnostic imaging , Nystagmus, Pathologic/pathologyABSTRACT
BACKGROUND: Despite sensitivity of MRI to diagnose multiple sclerosis (MS), prognostic biomarkers are still needed for optimized treatment. OBJECTIVE: The objective of this paper is to identify cerebrospinal fluid (CSF) diagnostic biomarkers of MS using quantitative proteomics and to analyze their expression at different disease stages. METHODS: We conducted differential analysis of the CSF proteome from control and relapsing-remitting MS (RRMS) patients followed by verification by ELISA of candidate biomarkers in CSF and serum in control, clinically isolated syndrome (CIS), RRMS and progressive MS (PMS) patients. RESULTS: Twenty-two of the 527 quantified proteins exhibited different abundances in control and RRMS CSF. These include chitinase 3-like protein 1 (CHI3L1) and 2 (CHI3L2), which showed a strong expression in brain of MS patients, especially in astrocytes and microglial cells from white matter plaques. CSF and serum CHI3L1 levels increased with the disease stage and CIS patients with high CSF (>189 ng/ml) and serum (>33 ng/ml) CHI3L1 converted more rapidly to RRMS (log rank test, p < 0.05 and p < 0.001, respectively). In contrast, CSF CHI3L2 levels were lower in PMS than in RRMS patients. Accordingly, CSF CHI3L1/CHI3L2 ratio accurately discriminated PMS from RRMS. CONCLUSIONS: CSF CHI3L1 and CHI3L2 and serum CHI3L1 might help to define MS disease stage and have a prognostic value in CIS.
Subject(s)
Adipokines/blood , Adipokines/cerebrospinal fluid , Chitinases/cerebrospinal fluid , Lectins/blood , Lectins/cerebrospinal fluid , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnosis , Adult , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Brain/metabolism , Chitinase-3-Like Protein 1 , Chitinases/blood , Disease Progression , Female , Humans , Male , Middle Aged , ProteomicsABSTRACT
BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
Subject(s)
Multiple Sclerosis/pathology , Adult , Cohort Studies , Disease Progression , Endonucleases , Female , Follow-Up Studies , Humans , Immunoglobulin G/analysis , Magnetic Resonance Imaging , Male , Multiple Sclerosis/cerebrospinal fluid , Nuclear Proteins/analysis , Oligoclonal Bands/genetics , Predictive Value of Tests , Prognosis , Risk Assessment , Survival Analysis , Vitamin D/bloodABSTRACT
BACKGROUND AND PURPOSE: Vitamin D deficiency is a recognized risk factor for multiple sclerosis (MS) and is associated with increased disease activity. It has also been proposed that the lower the vitamin D levels are, the higher is the handicap. METHODS: To refine the links between vitamin D insufficiency and disability in MS patients, a retrospective cohort analysis was performed including 181 patients prospectively followed without previous vitamin D supplementation, and age, gender, age at MS onset, MS type, MS activity, Expanded Disability Status Scale (EDSS) were analysed in correlation with plasma vitamin D levels. RESULTS: Vitamin D levels were significantly higher in relapsing-remitting MS than in progressive forms of MS in multivariate analyses adjusted for age, ethnicity, gender, disease duration and season (P = 0.0487). Overall, there was a negative correlation between vitamin D level and EDSS score (P = 0.0001, r = -0.33). In relapsing-remitting MS, vitamin D levels were only correlated with disability scores for EDSS < 4 (P = 0.0012). Patients with >20 ng/ml of vitamin D were 2.78 times more likely to have an EDSS < 4 (P = 0.0011, 95% confidence interval 1.49-5.00). CONCLUSION: Data support previous work suggesting that vitamin D deficiency is associated with higher risk of disability in MS. Vitamin D levels also correlated with the degree of disability in fully ambulatory patients with relapsing-remitting MS. These additional results support the pertinence of randomized controlled trials analysing the interest of an early vitamin D supplementation in MS patients to influence evolution of disability.
Subject(s)
Multiple Sclerosis, Chronic Progressive/blood , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Severity of Illness Index , Vitamin D/blood , Adult , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Product Surveillance, Postmarketing , Adult , Cohort Studies , Female , Humans , Male , Natalizumab , Prospective StudiesABSTRACT
INTRODUCTION: Cerebellar ataxia and stiff person-syndrome are the main neurological syndromes associated with antibodies to glutamic acid decarboxylase (GAD). CASE REPORT: A 59-year-old patient, with history of polymyalgia rheumatica and active smoking, was admitted for subacute cerebellar ataxia and memory dysfunction explained by limbic encephalitis on brain MRI. He also presented with orthostatic hypotension and erectile dysfunction revealing autonomic dysfunction. CSF was inflammatory and antibodies to GAD were positive. Onconeuronal antibodies including GABA(B) receptor antibodies were negative. Patient's condition quickly improved after intravenous immunoglobulins. A few months later, a small cell lung carcinoma was diagnosed and precociously treated. CONCLUSION: This case report underlines the importance of appropriate studies to confirm a primitive neoplasia, when confronted with limbic encephalitis and cerebellar ataxia, even if anti-GAD antibodies rarely define paraneoplastic syndromes.
Subject(s)
Autoantibodies/adverse effects , Autonomic Nervous System Diseases/complications , Cerebellar Ataxia/etiology , Glutamate Decarboxylase/immunology , Limbic Encephalitis/etiology , Paraneoplastic Syndromes, Nervous System/etiology , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/immunology , Autoantibodies/analysis , Autonomic Nervous System Diseases/diagnosis , Cerebellar Ataxia/diagnosis , Humans , Limbic Encephalitis/diagnosis , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Male , Middle Aged , Paraneoplastic Syndromes, Nervous System/diagnosis , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/diagnosis , Small Cell Lung Carcinoma/etiology , Small Cell Lung Carcinoma/pathology , Smoking/adverse effectsSubject(s)
Melanoma/diagnosis , Meningeal Neoplasms/diagnosis , Brain Neoplasms/diagnosis , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Disease Progression , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Melanoma/diagnostic imaging , Melanoma/pathology , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/pathology , Middle Aged , Radionuclide ImagingABSTRACT
BACKGROUND: Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies. OBJECTIVE: To describe HRS patients and compare them with NMO patients. METHODS: We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database. RESULTS: Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup. CONCLUSION: The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.