Multiple Sclerosis Multidisciplinary Care: A National Survey and Lessons for the Global Community.

BACKGROUND: Access to, standardization and reimbursement of multidisciplinary care for people with MS (PwMS) is lacking in many countries. Therefore, this study aims to describe the current multidisciplinary care for people with MS (PwMS) in Belgium and identify benefits, needs and future perspectives METHODS: A survey for PwMS questioned various aspects of MS and viewpoints on care. For MS nurses (MSN) and neurologists, employment, education, job-content, care organization and perspectives were inquired. Descriptive and univariate statistics were performed RESULTS: The PwMS survey comprised 916 respondents with a mean age of 46±12.7 years and 75,4 % of the respondents being female. The majority of the participants had relapsing remitting MS (60.8 %) and the mean patient determined disease steps (PDDS) was 2.0 (IQR=3). 65.3 % and 60.4 % of the PwMS reported having access to a multidisciplinary team (MDT) or MSN. Access to an MSN was associated with more frequent disease modifying treatment (p=.015), spasticity (p=.042) and gait treatment (p=.035), but also more physiotherapy (p=.004), driver's license adjustment (p<.001) and a higher employment rate (p=.004). MDT access was associated with more frequent symptomatic bladder treatment (p=.047), higher physiotherapy rate (p<.001), higher work- (p=.002), insurance- (p<.001) and home support measures (p=.019). PwMS without an available MDT more often indicated that MS care needs improvement (p<.001). MSN's (n = 22) were mainly funded through various budgets, including hospital and neurology practice budgets. Finally, 69 % and 75 % neurologists (n = 62) working without an MSN or MDT stated a need of such support and 61 % agreed that MDT's should be organized at hospital-network level CONCLUSION: MDT and MSN availability may enhance medical and socio-economic support for PwMS. Guidelines, alignment and reimbursement are needed.

Cognitive trajectories in relapsing-remitting multiple sclerosis: Evidence of multiple evolutionary trends.

BACKGROUND: Cognitive impairment (CI) frequently occurs in multiple sclerosis (MS) and is assumed to increase over time. However, recent studies have suggested that the evolution of cognitive status in patients with MS may be more heterogeneous than expected. Predicting CI remains also challenging, and longitudinal studies exploring the baseline determinants of cognitive performances are limited. No studies have explored the predictive value of patient-reported outcome measures (PROMs) regarding future CI. OBJECTIVE: To explore the evolutionary patterns of cognitive status in a cohort of RRMS patients initiating a new disease modifying treatment (DMT), and to determine whether PROMs may have a predictive value for future CI. METHODS: The present prospective study is a 12-month follow-up of a cohort of 59 RRMS patients who underwent yearly a comprehensive, multiparametric assessment combining clinical (with EDSS assessment), neuropsychological (BVMT-R, SDMT, CVLT-II), MRI-derived metrics and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A longitudinal logistic regression analysis was performed to find baseline correlates of CI at 12 months (T1). RESULTS: A total of 33 patients (56%) were defined as cognitively impaired at baseline, and 20 (38%) were defined as impaired at follow-up after 12 months. The mean raw scores and Z-scores of all the cognitive tests were significantly improved at T1 (p < 0.05). There was a statistically significant improvement in most PROM scores at T1 (p < 0.05) in comparison with baseline scores. Among the variables assessed, lower education and physical disability level at baseline correlated with impaired SDMT (OR: 1.68, p = 0.01; OR: 3.10, p = 0.02, respectively) and impaired BVMT-R (OR: 4.08, p=<0.001; OR: 4.82, p = 0.001, respectively) at T1. Neither baseline PROMs nor MRI volumetric parameters were predictive of cognitive performances at T1. CONCLUSIONS: These findings provide additional evidence that evolution of CI in MS may be a dynamic phenomenon and will not usually follow an inevitable, declining trajectory, and do not support the utility of PROMs in predicting CI in RRMS. The present study is still ongoing to determine whether our findings are confirmed at 2 and 3 years of follow-up.

Patient-reported outcome measurements in a selective cohort of relapsing-remitting multiple sclerosis patients: relationships with physical disability, cognitive impairment, and MRI-derived metrics.

BACKGROUND: The added value of patient-reported outcome measures (PROMs) in addition to standard clinical outcome tools in the assessment of relapsing-remitting multiple sclerosis (RRMS) patients' status is increasingly recognized. PROMs facilitate the detection of hidden aspects of MS and help to integrate the patient's subjective experience of health-related quality of life (HRQoL) status and treatment satisfaction in a holistic way. However, the relationship between PROMs and clinical and cognitive status has been scarcely investigated up to now. OBJECTIVE: To investigate the association of PROMs with physical and cognitive disability in a cohort of RRMS patients at initiation of a new disease-modifying treatment. METHODS: In this cross-sectional bicenter study, 59 consecutive RRMS patients underwent neurological examination with EDSS assessment, comprehensive cognitive tests (BVMT-R, SDMT, CVLT-II) and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix® software (Icometrix®, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A cross-sectional logistic regression analysis was performed to find baseline correlates of cognitive impairment. RESULTS: Of the 59 RRMS patients (mean age 39 ± 9.8 years, 79.7% female, median EDSS 2.0), 33 (56%) had cognitive impairment. While almost all dimensions of health, explored by PROMs, were impacted in the overall sample, no significant difference was observed in patients with and without cognitive impairment. All PROMs were significantly associated with EDSS (R = 0.37-0.55; p < 0.05), except for the psychological component of MSIS-29, BDI and DEX-Q scores. No significant correlation was found between PROMs and cognitive performances. The cross-sectional logistic regression analysis included age, gender (female), education, EDSS, hippocampus and FLAIR lesion volumes as significant predictors of cognitive impairment. CONCLUSIONS: The data highlight that PROMs provide valuable information on the well-being of PwMS closely paralleling the extent of MS-related disability, as measured by the EDSS. Additional research should determine the relevance of PROMs as longitudinal outcome measures.

Methotrexate-Induced Stroke-Like Encephalopathy: Beware the Stroke Mimic.

We report a case of methotrexate (MTX)-induced stroke-like encephalopathy in an 18-year-old woman, with acute lymphoblastic leukemia, who developed a sudden neurological deficit mimicking a cerebrovascular event. Bain MRI showed hyperintensities on diffusion-weighted-imaging (DWI) with matching apparent diffusion coefficient hypointensities, which also represent the commonest MRI findings in acute cerebral infarction. DWI changes spared the cerebral cortex and did not respect vascular territories, supporting a non-vascular mechanism. MRI plays a crucial role in the diagnostic work-up and is essential to avoid unnecessary intervention such as thrombolytic therapy. Teaching Point: Methotrexate-induced stroke like neurotoxicity should be considered in patients treated with methotrexate and presenting with a stroke-like clinical picture and radiological findings consistent with acute cerebral infarction.

Validation of the French version of the Multiple Sclerosis Intimacy And Sexuality Questionnaire-19: A preliminary study.

INTRODUCTION: Patients with multiple sclerosis (MS) suffer from various symptoms, including sexual dysfunction. The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a scale that explores the impact of MS on sexual activity and satisfaction. AIM: This observational cohort study aimed to provide a validated, cross-cultural, French version of the MSISQ-19 in patients with MS. METHODS: The original version of MSISQ-19 was translated into French according to standardized guidelines. Patients were asked to complete all questionnaires during the inclusion visit and the MSISQ-19 a second time two weeks later. Content validity was assessed by face validity. Internal consistency was evaluated using Cronbach's alpha. Construct validity was checked by the exploratory factor analysis. Concurrent validity was assessed by performing Spearman's correlation coefficient with the Female Sexual Function Index (FSFI), the Male Sexual Health Questionnaire (MSHQ), and the Multiple Sclerosis International Quality of Life questionnaire (MusiQoL). Spearman's correlation coefficient was also used to evaluate the relationship with the Expanded Disability Status Scale (EDSS), age, and disease duration. Test-retest reliability was assessed by intraclass correlation coefficient (ICC). Responsiveness was assessed by the standard error of measurement (SEM) and the minimum detectable change (MDC). MAIN OUTCOME MEASURES: MSISQ-19 is the main outcome measure. RESULTS: We enrolled 71 patients with MS (49 female, 22 male). The mean age was 42.6 ± 9.7 years with a median disease duration of 8 [3-16] years. Sixty-four (90%) patients had relapsing-remitting MS, 4 (6%) primary progressive MS, and 3 (4%) secondary progressive MS. French MSISQ-19 showed a Cronbach's alpha coefficient of 0.89. MSISQ-19 scores correlated significantly and moderately between each other and correlated significantly and moderately with scores on the FSFI, MSHQ, MusiQoL and EDSS. Reproducibility was excellent with intraclass correlation coefficients > 0.80. Exploratory factor analysis was performed using principal component analysis. A three-factor solution was adopted giving eigenvalues higher than 1, supporting the primary, secondary, and tertiary dimensions. SEM was 4.55 and MDC was 12.6 (13.3%). CONCLUSION: This study provides a preliminary validation of the French version of the MSISQ-19 which could be a reliable, and reproducible instrument to assess sexual dysfunction in patients with MS. These results need to be confirmed in a larger cohort which will be more representative of the general MS population.

Longitudinally extensive transverse myelitis following acute COVID-19 infection.

Corona Virus Disease 2019 (COVID-19) is a new illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the increasing number of confirmed cases and the accumulating clinical data, a broad spectrum of neurological complications has been reported in the literature, including encephalopathy, stroke, Guillain-Barré syndrome, meningo-encephalitis, acute necrotizing hemorrhagic encephalopathy, and inflammatory central nervous system syndromes. Here, we describe the case of a 38-year-old woman presenting with longitudinally extensive transverse myelitis, revealed by bilateral lower limb weakness, decreased sensation below the Th4 level and urinary retention, and occuring 15 days after she had been diagnosed with COVID-19.

Simultaneous bilateral optic neuropathy and myelitis revealing paraneoplastic neurological syndrome associated with multiple onconeuronal antibodies.

Paraneoplastic neurological syndromes (PNS) are immune-mediated complications of cancer associated with a broad spectrum of clinical manifestations. Optic neuropathy (ON) and myelitis are frequent manifestations of multiple sclerosis and neuromyelitis optic spectrum disorders but are considered as non-classical in PNS. Here, we report a case of PNS revealed by simultaneous bilateral ON and myelitis related to a cluster of three neural autoantibodies, in the setting of small cell lung cancer.

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients.

BACKGROUND: Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations. METHODS: Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated. RESULTS: Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients. CONCLUSIONS: In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Chromothripsis in an Early Recurrent Chordoid Meningioma.

BACKGROUND: Chromothripsis is characterized by a multitude of chromosomal rearrangements during a unique cataclysmic event in a cell life. Disintegration of one or several chromosomes is followed by a chaotic rearrangement of generated fragments. It might play a role in oncogenesis and tumor progression. It is observed in 2%-3% of cancers and is rarely reported in benign tumors. We report a case of massive chromothripsis in a fast growing chordoid meningioma. CASE DESCRIPTION: A 55-year-old woman was admitted for a meningeal mass developing in the right parietal parasagittal area. She underwent subtotal resection of the tumor. Histologic analysis revealed a chordoid meningioma (World Health Organization grade II). Six months later, magnetic resonance imaging showed a large bilateral tumor recurrence. After a second surgery, the patient received radiotherapy. Thereafter, the clinical course was uneventful. Comparative genomic hybridization showed only a monosomy X in the primary tumor. In the recurrent meningioma, this anomaly was associated with a massive chromothripsis including more than 370 chromosomal abnormalities affecting chromosomes 1-22. CONCLUSIONS: Chromothripsis is rarely described in benign tumors and especially in meningiomas. In the presented case, the high number of chromosomal rearrangements and the onset of this phenomenon at a later stage of tumor progression are very unusual. The role of surgical stress on the emergence of chromothripsis and its relation with tumor aggressiveness are discussed.

Optical coherence tomography: a window to the optic nerve in clinically isolated syndrome.

In this study, we aimed to evaluate the association of asymptomatic optic nerve demyelinating lesion in patients presenting a clinically isolated syndrome with the asymptomatic retinal neuro-axonal loss previously reported at clinically isolated syndrome. We prospectively recruited 66 patients presenting a clinically isolated syndrome and 66 healthy control subjects matched according to age and gender. All patients underwent brain magnetic resonance imaging including 3D-double inversion recovery (DIR) sequence, optical coherence tomography examination and visual function evaluation, at 2.5-4.5 months after CIS. Evaluation criteria were presence and length of optic nerve DIR hypersignal, retinal layers (including ganglion cell inner plexiform layer and inner nuclear layer) thickness/volume, and low contrast monocular vision acuity (number of letters correctly identified). All clinically isolated syndrome eyes with past history of optic neuritis (CIS-ON) presented an optic nerve DIR hypersignal. We observed asymptomatic optic nerve DIR hypersignal in 22.2% of clinically isolated syndrome eyes without optic neuritis (CIS-NON). In comparison with healthy control, GCIPL volume (in mm3) was significantly lower in CIS-ON eyes [ß (95% confidence interval, CI) = -0.121 (-0.168 to -0.074); P < 0.0001], and to a lesser extent in CIS-NON [ß (95% CI) = -0.023 (-0.039 to -0.008); P = 0.004]. In comparison to healthy controls, eyes with asymptomatic optic nerve DIR hypersignal presented significantly lower macular ganglion cell inner plexiform layer volume [ß (95% CI) = -0.043 (-0.068 to -0.019); P = 0.001], and eyes without did not [ß (95% CI) = -0.016 (-0.034 to 0.003); P = 0.083]. Among CIS-NON, macular ganglion cell inner plexiform layer volume decrease was associated with asymptomatic optic nerve DIR hypersignal independently of optic radiations T2 lesions and primary visual cortex volumes (P = 0.012). Symptomatic optic nerve DIR hypersignal were significantly longer (13.8 ± 6.7 mm) than asymptomatic optic nerve hypersignal (10.0 ± 5.5 mm; P = 0.047). Length of optic nerve DIR hypersignal was significantly associated with thinner inner retinal layers (P ≤ 0.001), thicker inner nuclear layer (P = 0.017) and lower low contrast monocular vision acuity (P < 0.05). Compared to healthy control, low contrast monocular vision acuity was significantly lower in CIS-ON eyes (P < 0.0001) and CIS-NON eyes with (P = 0.03) or without asymptomatic optic nerve DIR hypersignal (P = 0.0005). Asymptomatic demyelinating optic nerve DIR hypersignal at the earliest clinical stage of multiple sclerosis is frequent and associated with asymptomatic retinal neuro-axonal loss reported at clinically isolated syndrome stage. Length of optic nerve DIR hypersignal is a biomarker of retinal neuro-axonal loss and visual disability at clinically isolated syndrome stage. Visual disability of clinically isolated syndrome eyes without clinical and subclinical optic nerve involvement might be due to missed optic nerve lesions on MRI. At the earliest clinical stage of multiple sclerosis, our results support considering optical coherence tomography as a window to the optic nerve rather than to the brain.