In multiple sclerosis, gadolinium enhancement is used to classify lesions as active. Regarding th... more In multiple sclerosis, gadolinium enhancement is used to classify lesions as active. Regarding the need for a standardized and accurate method for detection of multiple sclerosis activity, we compared 2D-spin-echo with 3D-gradient-echo T1WI for the detection of gadolinium-enhancing MS lesions. Fifty-eight patients with MS were prospectively imaged at 3T by using both 2D-spin-echo and 3D-gradient recalled-echo T1WI in random order after the injection of gadolinium. Blinded and independent evaluation was performed by a junior and a senior reader to count gadolinium-enhancing lesions and to characterize their location, size, pattern of enhancement, and the relative contrast between enhancing lesions and the adjacent white matter. Finally, the SNR and relative contrast of gadolinium-enhancing lesions were computed for both sequences by using simulations. Significantly more gadolinium-enhancing lesions were reported on 3D-gradient recalled-echo than on 2D-spin-echo (n = 59 versus n = 30 ...
ABSTRACT Auteur correspondant. Hôpital Pellegrin, Service de Neurologie, place Amélie-Raba-Léon, ... more ABSTRACT Auteur correspondant. Hôpital Pellegrin, Service de Neurologie, place Amélie-Raba-Léon, 33076 Bordeaux, France.
The aim of this work is to study the relationship between information processing speed (IPS) impa... more The aim of this work is to study the relationship between information processing speed (IPS) impairment and motor testing that reflects cerebellar function in persons with multiple sclerosis (PwMS). 60 persons with relapsing-remitting multiple sclerosis with a mean disease duration of 4.2 ± 4 years were studied cross-sectionally. Motor cerebellar functioning was studied using the Nine-Hole Peg Test (NHPT) and the Kurtzke Functional Status Scales, and several cognitive domains were evaluated (IPS, working memory, episodic memory, attention, executive function). Correlations between the global NHPT score and neuropsychological test scores or impairment in each cognitive domain were studied using univariate and multivariate analyses. The NHPT and a test of IPS significantly differentiated PwMS with and without cerebellar impairment. The NHPT total score was correlated with measures of IPS. Multivariate analyses showed a correlation between the NHPT and measures of IPS, but not between the NHPT and other neuropsychological tests that did not have a speed component. In this sample of PwMS, motor cerebellar impairment assessed by the NHPT was correlated with IPS impairment.
The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated i... more The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge. To collect data from patients with MS switching from natalizumab to fingolimod. The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod. Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod. Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05). In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.
The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance i... more 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. 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). 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. 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. 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.
To determine MRI predictors for cognitive outcome in patients with early relapsing-remitting mult... more To determine MRI predictors for cognitive outcome in patients with early relapsing-remitting multiple sclerosis (MS). 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. 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. 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.
To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord ... more To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome. 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. 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. 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.
Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelit... more 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. To describe HRS patients and compare them with NMO patients. 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. 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. 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.
In multiple sclerosis, gadolinium enhancement is used to classify lesions as active. Regarding th... more In multiple sclerosis, gadolinium enhancement is used to classify lesions as active. Regarding the need for a standardized and accurate method for detection of multiple sclerosis activity, we compared 2D-spin-echo with 3D-gradient-echo T1WI for the detection of gadolinium-enhancing MS lesions. Fifty-eight patients with MS were prospectively imaged at 3T by using both 2D-spin-echo and 3D-gradient recalled-echo T1WI in random order after the injection of gadolinium. Blinded and independent evaluation was performed by a junior and a senior reader to count gadolinium-enhancing lesions and to characterize their location, size, pattern of enhancement, and the relative contrast between enhancing lesions and the adjacent white matter. Finally, the SNR and relative contrast of gadolinium-enhancing lesions were computed for both sequences by using simulations. Significantly more gadolinium-enhancing lesions were reported on 3D-gradient recalled-echo than on 2D-spin-echo (n = 59 versus n = 30 ...
ABSTRACT Auteur correspondant. Hôpital Pellegrin, Service de Neurologie, place Amélie-Raba-Léon, ... more ABSTRACT Auteur correspondant. Hôpital Pellegrin, Service de Neurologie, place Amélie-Raba-Léon, 33076 Bordeaux, France.
The aim of this work is to study the relationship between information processing speed (IPS) impa... more The aim of this work is to study the relationship between information processing speed (IPS) impairment and motor testing that reflects cerebellar function in persons with multiple sclerosis (PwMS). 60 persons with relapsing-remitting multiple sclerosis with a mean disease duration of 4.2 ± 4 years were studied cross-sectionally. Motor cerebellar functioning was studied using the Nine-Hole Peg Test (NHPT) and the Kurtzke Functional Status Scales, and several cognitive domains were evaluated (IPS, working memory, episodic memory, attention, executive function). Correlations between the global NHPT score and neuropsychological test scores or impairment in each cognitive domain were studied using univariate and multivariate analyses. The NHPT and a test of IPS significantly differentiated PwMS with and without cerebellar impairment. The NHPT total score was correlated with measures of IPS. Multivariate analyses showed a correlation between the NHPT and measures of IPS, but not between the NHPT and other neuropsychological tests that did not have a speed component. In this sample of PwMS, motor cerebellar impairment assessed by the NHPT was correlated with IPS impairment.
The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated i... more The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge. To collect data from patients with MS switching from natalizumab to fingolimod. The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod. Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod. Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05). In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.
The 2010 McDonald criteria allow diagnosing multiple sclerosis (MS) with one magnetic resonance i... more 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. 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). 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. 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. 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.
To determine MRI predictors for cognitive outcome in patients with early relapsing-remitting mult... more To determine MRI predictors for cognitive outcome in patients with early relapsing-remitting multiple sclerosis (MS). 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. 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. 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.
To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord ... more To identify predictors of conversion to definite multiple sclerosis (MS) in patients with a cord clinically isolated syndrome. 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. 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. 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.
Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelit... more 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. To describe HRS patients and compare them with NMO patients. 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. 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. 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.
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