Aurélie Ruet

Neuromyelitis optica in France A multicenter study of 125 patients

Background: There have been few epidemiologic studies on neuromyelitis optica (NMO) and none used the recent 2006 diagnostic criteria. Here we describe the clinical, laboratory, MRI, and disability course of NMO in a French cohort of 125 patients. Methods: We performed an observational, retrospective, multicenter study. Data were collected from September 2007 through August 2008, corresponding to the endpoint of the study. We identified 125 patients fulfilling the 2006 NMO criteria. Selection was made using hospital files and a specific clinical questionnaire for NMO. Results: Mean age at onset was 34.5 years (range 4–66) with a mean disease duration of 10 ± 7.8 years at the endpoint. The patients were mainly (87%) Caucasian, with a female:male ratio of 3:1. In 90% of cases, the association of optic neuritis, longitudinal extensive myelitis, and a Paty-negative initial brain MRI was sufficient to fulfill the supportive criteria. Eighty-eight percent of patients were treated with immunosuppressive therapies. Median delay from onset to Expanded Disability Status Scale (EDSS) score 4 was 7 years; score 6, 10 years; and score 7, 21 years. The first episode of myelitis was immediately followed by an EDSS score ≥4 in 37.3% of cases, and a severe residual visual loss was observed in 22% of patients after the first episode of optic neuritis. Multivariate analysis did not reveal any predictors of a poor evolution other than a high number of MRI brain lesions at diagnosis, which were predictive of a residual visual acuity ≤1/10. Conclusions: Our demographic data provide new data on disability in patients with neuromyelitis optica, most of whom were receiving treatment.

MRI predictors of cognitive outcome in early multiple sclerosis.

Objective: To determine MRI predictors for cognitive outcome in patients with early relapsing-remitting multiple sclerosis (MS). Methods: Forty-four patients recently diagnosed with clinically definite MS were followed up with clinical and cognitive evaluations at 1, 2, 5, and 7 years and underwent brain MRI including magnetization transfer (MT) imaging at baseline and 2 years. Cognitive evaluation was also performed in 56 matched healthy subjects at baseline. Cognitive testing included the Brief Repeatable Battery. Imaging parameters included lesion load, brain parenchymal fraction (BPF), ventricular fraction (VF), and mean MT ratio (MTR) of lesion and normal-appearing brain tissue (NABT) masks. Results: At baseline, patients presented deficits of memory, attention, and information processing speed (IPS). Over 2 years, all magnetic resonance parameters deteriorated significantly. Over 7 years, Expanded Disability Status Scale score deteriorated significantly. Fifty percent of patients deteriorated on memory cognitive domain and 22.7%of patients on IPS domain. Seven-year change of memory scores was significantly associated with baseline diffuse brain damage (NABT MTR). IPS z score change over 7 years was correlated with baseline global atrophy (BPF), baseline diffuse brain damage, and central brain atrophy (VF) change over 2 years. Conclusion: The main predictors of cognitive changes over 7 years are baseline diffuse brain damage and progressive central brain atrophy over the 2 years after MS diagnosis.

Early cognitive impairment in multiple sclerosis predicts disability outcome several years later

Cognition is frequently impaired in the early stages of multiple sclerosis (MS). The predictive value of cognitive impairment on disability is unknown. The objective of this study was to correlate cognitive impairment and the progression of disability over 7 years. Forty-five patients, recruited after MS diagnosis, were followed for 7 years by yearly Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) evaluations and were classified as cognitively impaired (CI) or unimpaired (CU) according to neuropsychological testing at baseline. At baseline, 47.8% of patients were CI, with deficits in mainly memory and information processing speed (IPS). The baseline EDSS correlated significantly with one IPS test. The EDSS, but not the MSFC, deteriorated significantly over the 7 years in the whole group and the CI group, but not the CU group. A multivariate analysis showed correlations between the EDSS change over 5 and 7 years and two baseline tests evaluating IPS and verbal memory. The deterioration of the EDSS after 7 years was significantly correlated with verbal memory testing at baseline after adjustment for age and baseline EDSS. In conclusion, in this sample of MS patients early in the disease, the baseline IPS and verbal memory impairments predict the EDSS score 5 and 7 years later.

Long-term follow-up of neuromyelitis optica with a pediatric onset

Background: Neuromyelitis optica (NMO) is a rare inflammatory disease. Average age at onset is 35 years. Few data exist on patients with pediatric-onset NMO (p-NMO), with disease onset before age 18 years. We report the clinical and paraclinical features and long-term outcome of patients with p-NMO and compare them with a large adult-onset NMO (a-NMO) cohort. Methods: We performed a retrospective, multicenter study of patients with p-NMO in pediatric and adult medical centers. We identified 125 patients with NMO (12 p-NMO; 113 a-NMO) fulfilling the 2006 criteria. Data were collected using hospital files and standardized assessment forms for NMO. Results: Patients with p-NMO were followed up during a mean 19.3 years. Median age at onset was 14.5 years (4.1–17.9) with a female:male ratio of 3:1. Three patients (25%) fulfilled Paty criteria for multiple sclerosis on first brain MRI, including one patient with acute disseminated encephalomyelitis. Median interval between onset and residual Expanded Disability Status Scale (EDSS) score 4 was 20.7 years, score 6 was 26 years, and score 7 was 28.7 years. Median interval between onset and residual visual loss ≤1/10 was 1.3 years. Compared with a-NMO, p-NMO showed a longer time to EDSS scores 4 and 6, largely explained by the severity of the first myelitis in the a-NMO group. Time to first treatment was longer in the p-NMO group (13.1 vs 3.4 years). Conclusion: Patients with p-NMO can present a diffuse inflammatory process on first brain MRI and have a longer time to disability than patients with a-NMO.

Cognitive impairment differs between primary progressive and relapsing-remitting MS

Objectives: To characterize the cognitive abilities of patients with primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) compared with healthy controls (HCs) matched for age, sex, and education level while considering the different characteristics of PPMS and RRMS and to compare the cognitive patterns of these types of multiple sclerosis. Methods: Forty-one patients with PPMS, 60 patients with RRMS, and 415 HCs were recruited in a cross-sectional study. Controls were divided into 20 groups according to age, sex, and education level. Participants were assessed with a large battery of neuropsychological (NP) tests that included a modified version of the Brief Repeatable Battery, the Stroop test, computerized tests from the Test of Attentional Performance battery, the numerical span test, and the Rey Complex Figure. Results: Patients with PPMS performed worse than their matched HCs on nearly all NP tests. Patients with RRMS performed worse than matched HCs on a computerized digit-symbol substitution task and the alertness test, reaction time for visual scanning, and Paced-Auditory Serial Addition Test-3 seconds. Patients with PPMS had worse NP scores and were more impaired in cognitive domains than patients with RRMS. After controlling for Expanded Disability Status Scale score, the results remained unchanged. Conclusion: The patients with PPMS presented with a wide range of cognitive deficits in information processing speed, attention, working memory, executive function, and verbal episodic memory, whereas the impairments in patients with RRMS were limited to information processing speed and working memory compared with their matched HCs. Cognitive deficits were more severe in patients with PPMS than in patients with RRMS.

Predictive factors for multiple sclerosis in patients with clinically isolated spinal cord syndrome

Objectives: To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome. Methods: The predictive values for conversion to MS of clinical, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) variables in 114 patients with acute partial myelitis confirmed by a spinal cord lesion on MRI were studied. Other causes of cord syndromes were excluded. Results: MS was diagnosed in 78 patients (86%) during 4.0 ± 1.9 years of follow-up. Some 67 of these patients had a second clinical episode. The diagnosis of isolated myelitis was maintained for 36 patients, 78% of whom (28 cases) were followed for at least 2 years, comparable to the MS patients. Age, bladder involvement, ≥2 cord lesions on MRI, ≥9 brain lesions, ≥3 periventricular lesions and intrathecal IgG synthesis predicted conversion to clinically definite MS. Multivariate logistic analysis identified three predictors of MS diagnosis: age ≤40 years, inflammatory CSF and ≥3 periventricular lesions on brain MRI. Conclusion: Two out of three baseline factors (age, periventricular lesions and inflammatory CSF) predicted conversion to MS with better accuracy than the revised McDonald criteria for dissemination in space.

A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis

Background: Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS). Objective: To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS. Methods: A sample of MS patients, 60 relapsing–remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT). Results: The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery. Conclusion: The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.

Early predictors of multiple sclerosis after a typical clinically isolated syndrome

Background: The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance imaging (MRI) scan. Nevertheless, not all patients at risk fulfil criteria at baseline. Other predictive factors (PFs) are: age ≤40 years, positive oligoclonal bands (OBs), and ≥3 periventricular lesions. Objective: The purpose of this study was to evaluate the 2010 McDonald criteria performance and to assess other PFs in patients without dissemination in space (DIS). Methods: Patients with clinically isolated syndrome (CIS) underwent baseline MRI and OB determination with clinical and radiological follow-up. Adjusted hazard ratios (aHRs) for clinically definite MS were estimated for DIS, dissemination in time (DIT), and DIS+DIT. Diagnostic properties at two years were calculated. In cases without DIS, combinations of ≥2 PFs were assessed. Results: A total of 652 patients were recruited; aHRs were 3.8 (2.5–5.8) for DIS, 4.2 (1.9–9.2) for DIT, and 8.6 (5.4–13.8) for DIS+DIT. Sensitivities were 69.6%, 42.3%, and 36.4%, and specificities were 67.3%, 87.9%, and 90.2%, respectively. In patients without DIS, aHRs varied between 2.7–5.5 and specificities ranged from 73.5–89.7% for PF combinations. Conclusion: The high specificity of the 2010 McDonald criteria is confirmed. In patients without DIS, PF combinations could be helpful in identifying those at risk for MS.

High-risk syndrome for neuromyelitis optica: a descriptive and comparative study

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.

Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis

Objective: We investigated whether diffusion tensor imaging (DTI) could reveal early hippocampal damage and clinically relevant correlates of memory impairment in persons with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). Methods: A total of 37 persons with CIS, 32 with MS and 36 controls prospectively included from 2011 to 2014 were tested for cognitive performances and scanned with 3T-magnetic resonance imaging (MRI) to assess volumetric and DTI changes within the hippocampus, whole brain volume and T2-lesion load. Results: While there was no hippocampal atrophy in the CIS group, hippocampal fractional anisotropy (FA) was significantly decreased compared to controls. Decrease in hippocampal FA together with increased mean diffusivity (MD) was even more prominent in MS patients. In CIS, hippocampal MD was correlated with episodic verbal memory performance (r = −0.57, p = 0.0002 and odds ratio (OR) = 0.058, 95% confidence interval (CI) = 0.0057–0.59, p = 0.016 adjusted for age, gender, depression and T2-lesion load), but not with cognitive tasks unrelated to hippocampal functions. Hippocampal MD was the only variable discriminating memory-impaired from memory-preserved persons with CIS (area under the curve (AUC) = 0.77, sensitivity = 90.0%, specificity = 70.3%, positive predictive value (PPV) = 52.9%, negative predictive value (NPV) = 95.0%). Conclusion: DTI alterations within the hippocampus might reflect early neurodegenerative processes that are correlated with episodic memory performance, discriminating persons with CIS according to their memory status.