Development of an Objective Structured Clinical Examination (OSCE) to evaluate the diagnosis announcement of chronic neurological disease by residents in neurology.

BACKGROUND: There is little consensus on how to make a diagnosis announcement of severe chronic disease in neurology. Other medical specialties, such as oncology, have developed assessment methods similar to the Objective Structured Clinical Examination (OSCE) to address this issue. Here we report the implementation of an OSCE focused on the diagnosis announcement of chronic disease in neurology by residents. OBJECTIVE: We aimed to evaluate the acceptability, feasibility and validity in routine practice of an OSCE combined with a theoretical course focused on diagnosis announcement in neurology. METHOD: Eighteen neurology residents were prospectively included between 2019 and 2022. First, they answered a questionnaire on their previous level of training in diagnosis announcement. Second, in a practical session with a simulated patient, they made a 15-min diagnosis announcement and then had 5mins of immediate feedback with an expert observer, present in the room. The OSCE consisted of 4 different stations, with standardized scenarios dedicated to the announcement of multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Third, in a theory session, expert observers covered the essential theoretical points. All residents and expert observers completed an evaluation of the "practical session" and the "theory session". RESULTS: Residents estimated their previous level of diagnosis announcement training at 3.1/5. The most feared announcements were AD and ALS. The "practical session" was rated at a mean of 4.1/5 by the residents and 4.8/5 by the expert observers, and the "theory session" at a mean of 4.7/5 by the residents and 5/5 by the expert observers. After the OSCEs, 11 residents felt more confident about making an announcement. CONCLUSION: This study has shown a benefit of using an OSCE to learn how to make a diagnosis announcement of severe chronic disease in neurology. OSCEs could be used in many departments in routine practice and seem adapted to residents.

Paradigm shifts in multiple sclerosis management: Implications for daily clinical practice.

Multiple sclerosis (MS) is the most common chronic inflammatory neurological disease. The emergence of disease-modifying therapies (DMTs) has greatly improved disease activity control and progression of disability in MS patients. DMTs differ in their mode of action, route of administration, efficacy, and safety profiles, offering multiple options for clinicians. Personalized medicine aims at tailoring the therapeutic strategy to patients' characteristics and disease activity but also patients' needs and preferences. New therapeutic options have already changed treatment paradigms for patients with active relapsing MS (RMS). The traditional approach consists in initiating treatment with moderate-efficacy DMTs and subsequently, escalating to higher-efficacy DMTs when there is evidence of clinical and/or radiological breakthrough activity. Recent real-world studies suggest that initiation of high-efficacy DMTs from disease onset can improve long-term outcomes for RMS patients. In this article, we review different treatment strategies and discuss challenges associated with personalized therapy.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

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.

Secondary progressive multiple sclerosis: A national consensus paper on diagnostic criteria.

BACKGROUND: In clinical practice, the diagnosis of secondary progressive multiple sclerosis (SPMS) is often delayed, retrospective and non-reproducible, as there are no consensus criteria that define the advent of SPMS. Early identification of SPMS is essential to improve patient care. METHODS: Eight regional board meetings in France involving 56 multiple sclerosis (MS) experts (neurologists) were convened to discuss diagnostic criteria for SPMS. Subsequently, a national board meeting of 13 neurologists (with an expert representing each geographical region) was held to review points of convergence or divergence between regions and to develop a national consensus document. RESULTS: Based on the discussions from the regional boards, the MS experts at the national board retained the worsening of the EDSS score, with compatible clinical features, as the only consensus criterion for the diagnosis of SPMS in clinical practice. The patient should have experienced during at least the previous 6 months and in the absence of any relapse, a worsening in the EDSS score of +1.0 point (if the previous EDSS was≤5.0) or of +0.5 point (if the previous EDSS was≥5.5), with a pyramidal or cerebellar functional system score≥2 and without setting a minimum EDSS score; or, in case of a stable EDSS score≥4.0, a worsening of a functional score. This worsening should be confirmed within 3 to 6 months. According to the MS experts, the patient's age, duration of illness and a minimal threshold EDSS score are only risk factors for transition to SPMS. Patient reports during consultation and cognitive impairment are important warning signs, which should trigger an objective assessment with specific tests or closer monitoring. Clinical relapse and/or MRI activities are non-discriminatory for making the diagnosis of SPMS. CONCLUSIONS: The experts defined precise diagnostic criteria adapted to clinical practice for earlier identification of SPMS, paving the way for better management of this stage of the disease.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders.

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.

MRI characteristics of MOG-Ab associated disease in adults: An update.

Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.

MSCopilot, a new multiple sclerosis self-assessment digital solution: results of a comparative study versus standard tests.

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.

Recommendations for the use of Rituximab in neuromyelitis optica spectrum disorders

There is growing evidence of a preventive effect of Rituximab (RTX) in neuromyelitis optica spectrum disorders (NMO-SD). This monoclonal antibody against CD20 is becoming the most widely used preventive therapy in NMO-SD, as a first-line therapy or as a rescue therapy. Nevertheless, considerable heterogeneity still exists concerning the pre-treatment work-up, the vaccinations required before and under treatment, the number and dosage of infusions, prevention of the risk of infusion-related reactions, prevention of infections under treatment, and frequency of therapeutic cycles. Thanks to a collaborative work among NMO-SD experts belonging to the NOMADMUS project, we provide here recommendations for all these topics concerning RTX use in NMO-SD.

Efficacy of rituximab in refractory neuromyelitis optica.

BACKGROUND: Despite a growing use of rituximab (RTX) in neuromyelitis optica (NMO), data are lacking in patients with refractory NMO (RNMO), defined as cases with at least one relapse during immunosuppressive therapy. OBJECTIVE: The purpose of this study was to assess RTX as a maintenance therapy in RNMO. METHODS: Out of a total of 305 NMO cases from a population-based cohort, 21 RNMO patients received RTX during a mean follow-up period of 31 months. RESULTS: After RTX, 11 patients (52.3%) were relapse free, meaning that 47.7% were refractory to RTX. The mean annualized relapse rate decreased from 1.3 to 0.4 (p<0.001) and median EDSS from 5 to 3 (p=0.02). Body mass index (BMI) was predictive of EDSS worsening. CONCLUSIONS: RTX is an effective and well-tolerated treatment in RNMO. BMI could be a predictive factor for efficacy.

Diffusion tensor imaging of normal-appearing white matter in neuromyelitis optica.

OBJECTIVES: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis and myelitis. Brain was classically, unlike in multiple sclerosis (MS), spared. Nevertheless recent studies showed that brain lesions can be seen with MRI. We studied the diffusion characteristics of normal-appearing white matter (NAWM) and abnormal white matter in NMO patients compared with NAWM in healthy subjects. PATIENTS AND METHODS: Diffusion tensor imaging (DTI) scans of the brain and spinal cord were obtained from 25 patients with NMO and 20 age- and gender-matched healthy subjects. Region of interest (ROI) analysis of the apparent diffusivity coefficient (ADC) and fractional anisotropy (FA) was performed in brain NAWM (optic radiations, corpus callosum [CC] and anterior and posterior limbs of the internal capsule [IC]) and in spinal cord NAWM and in lesions. RESULTS: ADC was increased and FA decreased in NMO patients in the posterior limb of the IC in the optic radiations and in spinal cord NAWM. FA was lower in spinal cord lesions. In contrast, there was no difference between the two groups in the anterior limb of the IC nor in the CC. CONCLUSION: These results suggest that DTI abnormalities are very severe in NMO spinal cord lesions. In our study, DTI abnormalities in NAWM were restricted to optic radiations and cortico-spinal tracts, suggesting secondary Wallerian degeneration. In contrast, NAWM outside these tracts (CC and anterior IC) remained normal suggesting that, unlike what is observed in MS, there is no infra-lesional abnormality in NMO.

[A case of bilateral horizontal gaze ophthalmoplegia: The 1+1 syndrome]. / Un cas d'ophtalmoplégie horizontale bilatérale : le syndrome 1+1.

INTRODUCTION: Oculomotor deficiencies in multiple sclerosis (MS) are frequently characterized by internuclear ophthalmpoplegia or isolated abduction or adduction palsies. Complete unilateral conjugate gaze paralysis and the "one and a half" syndrome are rare. Complete bilateral horizontal gaze paralysis has been exceptionally reported. OBSERVATION: Here, we describe an unusual oculomotor paralysis as a suspected first event of MS. A 24-year-old woman with an uneventful medical history presented for sudden onset of binocular diplopia. On examination, abduction and adduction saccades were impossible, whereas vertical eye saccades and convergence were normal. Oculocephalic reflex failed to improve horizontal eye movement. No nystagmus and no other sign of brainstem dysfunction were observed. Visual acuity was 4/10 in the right eye and 6/10 in the left eye. A sign of Marcus Gunn was noted in the right eye. Blood samples and cerebrospinal fluid were normal, no oligoclonal bands were detected. Visual evoked potentials were significantly impaired in both eyes and argued for bilateral optic neuritis. Brain MRI scans showed white matter T2-hypersignal abnormalities, which fulfill Barkhof criteria for MS. A small symmetric lesion was noted in the posterior part of the medial pontine tegmentum. As a first episode of MS was suspected, treatment with methylprednisolone 1000 mg/d for 3 days was started, and was followed by complete recovery of eye movements and visual acuity after 3 weeks. DISCUSSION: To our knowledge, only two cases of complete horizontal bilateral ophthalmoplegia have been reported in the literature. Both were associated with peripheral facial nerve palsy as a first event in MS. In our case report, we describe for the first time a complete bilateral horizontal ophthalmoplegia with no other brainstem dysfunction. By analogy with the "one and a half" syndrome, such complete horizontal gaze paralysis could be named a "one and one" syndrome and seems to be specifically related to a first event of MS.

[Inaugural audiovisual impairment disclosing specific neurological disorders]. / Atteinte audiovisuelle inaugurale de pathologies neurologiques spécifiques.

The association of visual and auditory impairments, simultaneously or consecutively, is a rare condition at the onset of neurological diseases. To determine whether audiovisual impairment can be associated with a specific group of neurological disorders at onset, we performed a prospective study of 307 patients over 6 months in a specialized neurological unit in inflammatory diseases. Six patients (2%) experienced inaugural audiovisual impairments. The mean age of patients at onset was 39.5 ± 14.7 years, with a male:female ratio of 1:2. Both deficiencies were reported in three cases, including loss of visual acuity with tinnitus (two cases) or hearing loss (one case). Initial visual dysfunction, characterised by loss of visual acuity, was noted in one patient. Initial auditory impairment, characterised by dizziness and hearing loss, was noted in two patients. The mean interval between the occurrence of visual and auditory impairments was 3.8 ± 4.3 months. A neurological diagnosis was made in four cases (67%) at a mean time of 4.6 ± 4.6 months after disease onset. Visual impairments were optic neuritis for multiple sclerosis, serous retinal detachment for Vogt-Koyanagi-Harada's disease, a central retinal artery occlusion for Susac's syndrome and a retinal vasculitis for Cogan's syndrome. The systematic investigation of inaugural audiovisual impairment in young patients could help shorten the time to a specific neurological diagnosis.

Neuromyelitis optica and pregnancy.

OBJECTIVE: The purpose of our study was to assess the influence of pregnancy on the course of neuromyelitis optica (NMO) and the impact of epidural analgesia and breastfeeding on its activity in the postpartum period. METHODS: We performed a retrospective study of patients with NMO diagnosed according to Wingerchuk criteria. We noted the number of relapses during the year before pregnancy (BP), during pregnancy (first trimester, second trimester, third trimester), and the year after (Y + 1: first trimester, second trimester [PP2], and third and fourth trimesters postpartum). Epidural analgesia and breastfeeding were recorded. Disability was evaluated with the Kurtzke Expanded Disability Status Scale (EDSS). The annualized relapse rate (ARR) was calculated. RESULTS: We identified 124 patients (85 female) in the French NOMADMUS cohort on November 1, 2010. A total of 20 women (including 25 pregnancies) were informative with complete files. Comparisons between the ARR of each period and BP (1.0 ± 0.09) only showed an increased tendency for PP2 (0.8 ± 0.06, p = 0.07). Epidural analgesia and breastfeeding had no influence on the course of NMO. The EDSS score increased from 1.5 ± 1.7 BP to 2.6 ± 1.9 Y + 1 (p = 0.027). CONCLUSION: This study shows that pregnancy influences the activity of NMO, a finding that justifies close medical monitoring. We found no evidence to suggest that either epidural analgesia or breastfeeding has an aggravating effect on NMO.