Criteria For Multiple Sclerosis Research Articles

The borderland of multiple sclerosis and functional neurological disorder: A call for clinical research and vigilance.

Functional neurological disorders (FNDs) have attracted much attention from the neurological medical community over the last decades as new developments in neurosciences have reduced stigma around these by showing brain network dysfunctions. An overlap with other neurological conditions such as multiple sclerosis (MS) is well known by clinicians but there is a lack of clinical and fundamental research in this field to better define diagnosis and therapeutic decisions, as well as a lack of deep understanding of the underlying pathophysiology. We aimed to provide a critical commentary on the state of knowledge about the borderland between FNDs and MS. We based our commentary on a joint point of view between an FND specialist and an MS expert. A brief review of the previous literature and relevant new studies covering the overlap between FNDs and MS is presented, along with suggestions for future research directions. There are clear diagnostic criteria for both FNDs and MS and a strict application of these will help better diagnosis and prevent unnecessary treatment escalation in MS or absence of referral to multimodal therapy in FND. Better teaching of younger neurologists is needed as well as prospective research focusing on pathophysiology.

Diagnosis of Multiple Sclerosis.

The diagnosis of multiple sclerosis (MS) can be made based on clinical symptoms and signs alone or a combination of clinical and paraclinical features. Diagnostic criteria for MS have evolved over time, and the latest version facilitates earlier diagnosis of MS in those presenting with typical clinical syndromes. This article summarizes the current diagnostic criteria for MS, typical and atypical presentations of MS, and when diagnostic criteria should be applied with caution. The most recent version of the MS diagnostic criteria has the benefits of simplicity and greater sensitivity in comparison to previous iterations. However, misdiagnosis remains a significant issue in MS clinical care, even at MS specialty centers. It is, therefore, evident that careful clinical application of the current version of the diagnostic criteria is necessary and that tools improving the diagnostic accuracy of MS would be of substantial clinical utility. Emerging diagnostic biomarkers that may be useful in this regard, including the central vein sign, paramagnetic rim lesions, and fluid biomarkers, are discussed. Current MS diagnostic criteria facilitate the early diagnosis of MS in people presenting with typical clinical syndromes but should be used cautiously in those presenting with atypical syndromes and in special populations. Clinical judgment and existing paraclinical tools, including sequential MRIs of the neuraxis and laboratory tests, are useful in minimizing misdiagnosis and facilitating the accurate diagnosis of MS. Diagnostic biomarkers that may facilitate or refute a diagnosis of MS in these settings, and emerging imaging and fluid biomarkers may eventually become available for use in clinical settings.

Serum MOG-IgG in children meeting multiple sclerosis diagnostic criteria

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is now recognized as distinct from multiple sclerosis (MS). Objective: To evaluate the importance of considering myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin-G (IgG) serology when applying MS diagnostic criteria in children. Methods: Within a prospective cohort of children meeting MS criteria (median follow-up = 6 years, interquartile range (IQR) = 4–9), we measured MOG-IgG in serial archived serum obtained from presentation, and compared imaging and clinical features between seropositive and seronegative participants. Results: Of 65 children meeting MS criteria (median age = 14.0 years, IQR = 10.9–15.1), 12 (18%) had MOG-IgG at disease onset. Seropositive participants were younger, had brain magnetic resonance imaging (MRI) features atypical for MS, rarely had cerebrospinal fluid (CSF) oligoclonal bands (2/8, 25%), and accumulated fewer T2 lesions over time. On serial samples, 5/12 (42%) were persistently seropositive, 5/12 (42%) became seronegative, and 2/12 (17%) had fluctuating results. All 12 children experienced a disease course different from typical MS. Conclusion: While children with MOG-IgG can have clinical, CSF, and MRI features conforming to MS criteria, the presence of MOG-IgG is associated with atypical features and predicts a non-MS disease course. Given MOG-IgG seropositivity can wane over time, testing at first attack is of considerable importance for the diagnosis of MOGAD.

Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study.

The severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS. This observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration's Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS. The 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35' and 56°16') were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes <40°, more severe disease was associated with higher latitudes (β = 0.08, 95% CI 0.04-0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40° (β = -0.02, 95% CI -0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 years (β = - 0.5, 95% CI -0.6 to 0.4) and 18 years (β = - 0.6, 95% CI -0.7 to 0.4), as well as with lower lifetime UVB exposure at the time of disability assessment (β = -1.0, 95% CI -1.1 to 0.9). In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.

Towards imaging criteria that best differentiate MS from NMOSD and MOGAD: Large multi-ethnic population and different clinical scenarios

The "1/3″ brain magnetic resonance imaging (MRI) criteria including 1) a lesion adjacent to the lateral ventricle and in the inferior temporal lobe, or 2) a juxtacortical lesion, or 3) a Dawson finger-type lesion were shown to distinguish multiple sclerosis (MS) from antibody-mediated conditions. In this large multicentre study, we aimed to assess how the criteria perform 1) in different onset phenotypes, 2) distinct ethnic groups, 3) when the absence of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD)-typical fluffy infratentorial (FIT) lesions and longitudinally extensive transverse myelitis (LETM) lesions are added as features ("2/4″ and 3/5″ criteria, respectively). 577 patients with MS (n=332), aquaporin-4 antibody (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD) (n=196) and MOGAD (n=49) were recruited from 6 international centres (Buenos Aires, Sao Paolo, Maracaibo, Goyang, Oxford and Milan). Imaging scans were obtained at disease onset or relapse. Adding the absence of FIT lesions increased the specificity of the "1/3″ criteria vs. AQP4-Ab NMOSD from 84.7% to 87.2% and vs. MOGAD from 85.7% to 93.9% without compromising their sensitivity (86%). In particular, for those presenting with brain/brainstem attacks "2/4″ had significantly higher specificity than "1/3″ (85% vs. 80% against AQP4-Ab NMOSD, 88.9% vs. 72.2% against MOGAD). Positive predictive values of the "1/3″ criteria for MS were lowest for Asian patients (84.8vs. 99.1% for White) but were significantly increased by adding further criteria (94.1% for "3/5″). The "1/3″ criteria perform well in discriminating MS from NMOSD and MOGAD regardless of ethnic background and clinical scenario. Adding the absence of FIT lesions increases the specificity in those presenting with brain/brainstem symptoms.

Demyelinating events following anti-tumor necrosis factor alpha therapy: Rare but challenging to treat.

Demyelinating events are listed as adverse events with tumor necrosis factor alpha inhibitors (TNFi), but epidemiological studies have provided partly conflicting risk estimates. Furthermore, studies examining long-term outcomes of demyelinating events associated with TNFi are rare. This was a retrospective, observational study comprising validation and tracking of long-term outcomes in patients referred to a tertiary neurology referral center for suspected neurological complications associated with TNFi. Of 48 patients evaluated, only 14 showed signs of demyelinating disease on magnetic resonance imaging, where six fulfilled criteria for a clinically isolated syndrome (CIS) and eight were diagnosed with multiple sclerosis (MS). However, 13 patients had received an International Classification of Diseases code for MS at some stage. Mean follow-up from referral was 13 and 10.5years among subjects with MS and CIS, respectively. Continued disease activity was recorded among several of those fulfilling MS criteria, and two ultimately underwent autologous hematopoietic stem cell transplantation. In contrast, subjects with CIS showed no progression after cessation of TNFi. Our findings suggest that only a minority of those with suspected demyelinating disease following TNFi fulfill diagnostic criteria for MS and that MS diagnoses among those not fulfilling MS criteria may contribute to inflated epidemiological risk estimates. Nevertheless, in those fulfilling MS criteria, initiation of disease-modulating therapy, with escalation as needed, was important to suppress further disease activity.

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient’s health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients. Areas covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients. Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

Inicio temprano de alemtuzumab: cambio en el paradigma de tratamiento en esclerosis múltiple. Análisis intermedio del estudio LEMVIDA

LEMVIDA es un estudio de práctica clínica, prospectivo, de tres años de seguimiento sobre calidad de vida en pacientes con esclerosis múltiple (EM) tratados con alemtuzumab en España.

Outcomes of pregnancy in Egyptian women with multiple sclerosis in the new treatment era: a multi-center retrospective observational study

BackgroundPregnancy is a recent growing issue in multiple sclerosis (MS) and the update in the diagnostic criteria of MS and introduction of many disease-modifying therapies (DMTs) may cause changes in the relationship between MS, pregnancy, and breastfeeding. This study aimed to investigate the effect of pregnancy and breastfeeding on MS and vice versa. A retrospective observational study was conducted to include MS women with a history of at least one pregnancy during the last 7 years. Data were collected from the archived files in addition to a self-administrating questionnaire. The annualized relapsing rate (ARR) was calculated before, during, and after pregnancy.ResultsWe included 116 successful pregnancies from 93 MS women with mean age 32.74 ± 5.12 years. Interferon-beta was the commonly used DMT during and after pregnancy. Despite the ARR during the two years preceding the conception was 0.36 (95% CI 0.32–0.41), this rate was significantly decreased during first, second, and third trimester (0.07; 95% CI 0.04–0.15, 0.10; 95% CI 0.03–0.17, and 0.15; 95% CI 0.08–0.24, respectively; P-value < 0.001 in all). Furthermore, this ARR was significantly decreased during the first and last three months after delivery (0.27; 95% CI 0.16–0.39; P-value = 0.037, and 0.24; 95% CI 0.17–0.38; P-value = 0.023). Exclusive breastfeeding was associated with deceased risk of postpartum relapse, with HR 0.31 (95% CI 0.12–0.67; P = 0.002).ConclusionsPregnancy is protective from MS relapse, with a significant decrease of ARR from the pre-pregnancy period. Postpartum reactivation of the disease occurs from the third month after labor, rather than the early postpartum period. Exclusive breastfeeding for at least 2 months decreased the risk of postpartum relapse.

Effect of Changes in MS Diagnostic Criteria Over 25 Years on Time to Treatment and Prognosis in Patients With Clinically Isolated Syndrome

To explore whether time to diagnosis, time to treatment initiation, and age to reach disability milestones have changed in patients with clinically isolated syndrome (CIS) according to different multiple sclerosis (MS) diagnostic criteria periods. This retrospective study was based on data collected prospectively from the Barcelona-CIS cohort between 1994 and 2020. Patients were classified into 5 periods according to different MS criteria, and the times to MS diagnosis and treatment initiation were evaluated. The age at which patients with MS reached an Expanded Disability Status Scale (EDSS) score ≥3.0 was assessed by Cox regression analysis according to diagnostic criteria periods. Last, to remove the classic Will Rogers phenomenon by which the use of different MS criteria over time might result in a changes of prognosis, the 2017 McDonald criteria were applied, and age at EDSS score ≥3.0 was assessed by Cox regression. In total, 1,174 patients were included. The median time from CIS to MS diagnosis and from CIS to treatment initiation showed a 77% and 82% reduction from the Poser to the McDonald 2017 diagnostic criteria periods, respectively. Patients of a given age diagnosed in more recent diagnostic criteria periods had a lower risk of reaching an EDSS score ≥3.0 than patients of the same age diagnosed in earlier diagnostic periods (reference category Poser period): adjusted hazard ratio (aHR) 0.47 (95% confidence interval 0.24-0.90) for McDonald 2001, aHR 0.25 (0.12-0.54) for McDonald 2005, aHR 0.30 (0.12-0.75) for McDonald 2010, and aHR 0.07 (0.01-0.45) for McDonald 2017. Patients in the early-treatment group displayed an aHR of 0.53 (0.33-0.85) of reaching age at EDSS score ≥3.0 compared to those in the late-treatment group. Changes in prognosis together with early-treatment effect were maintained after the exclusion of possible bias derived from the use of different diagnostic criteria over time (Will Rogers phenomenon). A continuous decrease in the time to MS diagnosis and treatment initiation was observed across diagnostic criteria periods. Overall, patients diagnosed in more recent diagnostic criteria periods displayed a lower risk of reaching disability. The prognostic improvement is maintained after the Will Rogers phenomenon is discarded, and early treatment appears to be the most likely contributing factor.

Long-term clinical, MRI, and cognitive follow-up in a large cohort of pathologically confirmed, predominantly tumefactive multiple sclerosis

Background: Limited studies have described long-term outcomes in pathology confirmed multiple sclerosis (MS). Objectives: To describe long-term clinical–radiographic–cognitive outcomes in a prospectively followed cohort of patients with pathologically confirmed CNS demyelinating disease, consistent with MS. Methods: Subjects underwent clinical assessment, standardized 3T-MRI brain, and cognitive battery. Results: Seventy-five patients were included. Biopsied lesion size was ⩾ 2 cm in 62/75. At follow-up, median duration since biopsy was 11 years. Median EDSS was 3 and lesion burden was large (median 10 cm3). At follow-up, 57/75 met MS criteria, 17/75 had clinically isolated syndrome, and 1 radiographic changes only. Disability scores were comparable to a prevalence cohort in Olmsted County (p < 0.001, n = 218). Cognitive outcomes below age-normed standards included psychomotor, attention, working memory, and executive function domains. Total lesion volume and index lesion-related severity correlated with EDSS and cognitive performance. Volumetric cortical/subcortical GM correlated less than lesion metrics to cognitive outcomes. Conclusion: Despite early aggressive course in pathologically confirmed MS, its long-term course was comparable to typical MS in our study. Cognitive impairment in this group seemed to correlate strongest to index lesion severity and total lesion volume. It remains to be established how the aggressive nature of the lesion, biopsy, and treatment affect clinical/cognitive outcomes.

Multiple sclerosis in Kenya: Demographic and clinical characteristics of a registry cohort.

BackgroundMultiple Sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. There is limited literature regarding the burden of MS in sub-Saharan Africa (SSA).ObjectiveTo describe the demographic and clinical characteristics of patients with MS (PwMS) presenting to a tertiary referral hospital in Nairobi.MethodsWe conducted a retrospective descriptive study for PwMS presenting to Aga Khan University Hospital, Nairobi from 2008–2018.Results99 cases met the diagnostic criteria for MS with a male to female ratio of 1:4. Majority (68.7%) of PwMS were indigenous Africans with a mean age of onset of 30.7 years. Mean duration from symptom onset to first neuro-imaging was 5.04 years. Only 33% of patients had sensory symptoms at onset whereas 54.5% had vitamin D deficiency/insufficiency. Majority (79.5%) had relapsing remitting MS (RRMS) and 56.6% were initiated on disease modifying therapy (DMT). Only 21.2% of patients on DMT were non-compliant. Patients with RRMS were more likely to be initiated on DMT at our hospital (p < 0.001).ConclusionClinical characteristics of these patients largely resemble those of other SSA cohorts and African American patients. There was a delay between symptom onset and neuroimaging. There were also issues with DMT compliance.

Editors' Note: Optical Coherence Tomography for Detection of Asymptomatic Optic Nerve Lesions in Clinically Isolated Syndrome

In the article “Optical Coherence Tomography for Detection of Asymptomatic Optic Nerve Lesions in Clinically Isolated Syndrome,” Dr. Outteryck et al. evaluated the ability of intereye retinal thickness difference (IETD) measured by optical coherence tomography (OCT) to detect asymptomatic optic nerve involvement in 130 patients who had presented with clinically isolated syndrome (CIS) within 4.5 months of enrollment. They found that detection of asymptomatic optic nerve lesions in CIS required lower ganglion cell–inner plexiform layer (GC-IPL) IETD thresholds than previously reported and concluded that GC-IPL IETD represents an alternative biomarker to MRI for the detection of such lesions. Although lowering the IETD thresholds may improve the sensitivity of detecting an optic nerve lesion, it comes at the expense of lowering the specificity and this will potentially increase the risk of a false diagnosis of an optic nerve lesion. In response, Dr. Shubhakaran suggests that such a biomarker could help in early intervention to improve the prognosis of patients with multiple sclerosis (MS) and also highlights the utility of OCT in diagnosing macular lesions that may differentiate MS from other disorders. Dr. Shubhakaran notes that OCT is more readily available in certain practice regions than MRI, oligoclonal band testing, and evoked potentials. Responding to these comments, Dr. Outteryck agrees with the utility of OCT in the evaluation of demyelinating diseases, and with the disparate accessibility to OCT and MRI in different parts of the world, but cautions that optic nerve involvement is still not part of the diagnostic criteria for MS for dissemination in space. Noting that optic nerve involvement in patients with CIS is associated with the presence of asymptomatic gadolinium enhancing lesions, Dr. Outteryck argues that optic nerve involvement should be accommodated in future iterations of the MS diagnostic criteria. This exchange illuminates the potential role that OCT can play in the evaluation of the optic nerves in patients with suspected demyelinating disease, even in the absence of ocular symptoms, and also highlights the enduring debate about how optic nerve involvement could be incorporated in the diagnostic criteria for MS. In the article “Optical Coherence Tomography for Detection of Asymptomatic Optic Nerve Lesions in Clinically Isolated Syndrome,” Dr. Outteryck et al. evaluated the ability of intereye retinal thickness difference (IETD) measured by optical coherence tomography (OCT) to detect asymptomatic optic nerve involvement in 130 patients who had presented with clinically isolated syndrome (CIS) within 4.5 months of enrollment. They found that detection of asymptomatic optic nerve lesions in CIS required lower ganglion cell–inner plexiform layer (GC-IPL) IETD thresholds than previously reported and concluded that GC-IPL IETD represents an alternative biomarker to MRI for the detection of such lesions. Although lowering the IETD thresholds may improve the sensitivity of detecting an optic nerve lesion, it comes at the expense of lowering the specificity and this will potentially increase the risk of a false diagnosis of an optic nerve lesion. In response, Dr. Shubhakaran suggests that such a biomarker could help in early intervention to improve the prognosis of patients with multiple sclerosis (MS) and also highlights the utility of OCT in diagnosing macular lesions that may differentiate MS from other disorders. Dr. Shubhakaran notes that OCT is more readily available in certain practice regions than MRI, oligoclonal band testing, and evoked potentials. Responding to these comments, Dr. Outteryck agrees with the utility of OCT in the evaluation of demyelinating diseases, and with the disparate accessibility to OCT and MRI in different parts of the world, but cautions that optic nerve involvement is still not part of the diagnostic criteria for MS for dissemination in space. Noting that optic nerve involvement in patients with CIS is associated with the presence of asymptomatic gadolinium enhancing lesions, Dr. Outteryck argues that optic nerve involvement should be accommodated in future iterations of the MS diagnostic criteria. This exchange illuminates the potential role that OCT can play in the evaluation of the optic nerves in patients with suspected demyelinating disease, even in the absence of ocular symptoms, and also highlights the enduring debate about how optic nerve involvement could be incorporated in the diagnostic criteria for MS.

Magnetic resonance imaging in the diagnosis of non-tumorous multifocal brain lesions mimicking multiple sclerosis

The diagnosis of multiple sclerosis (MS) is quite challenging due to its variable clinical manifestations and lack of a definitive test. Magnetic resonance imaging (MRI) is one of the tools to confirm the diagnosis and also helps in differential diagnosis with other disorders and in exclusion of MS-mimicking diseases. In this article, based on the analysis of clinical cases, we discuss the differential diagnosis of MS with the following non-tumorous multifocal brain lesions: vascular abnormalities caused by hypoxia and ischemia, cerebral autosomal dominant angiopathy with subcortical infarctions and leukoencephalopathy, Susac syndrome, primary angiitis of the central nervous system, and neurosarcoidosis. We present both MRI criteria for MS and disorders that have similar MRI signs, and additional clinical and laboratory data that is essential for correct diagnosis.

Demyelination with autoimmune features: a distinct clinical entity? Results from a longitudinal cohort.

CNS demyelinating syndromes occurring in the context of SLE may represent a manifestation of neuropsychiatric lupus, or an overlap of SLE and multiple sclerosis (MS). We evaluated prospectively patients presenting with demyelinating syndrome for clinical and serological evidence of SLE and characterized the evolution of their clinical syndrome to a defined disease. Patients with CNS demyelinating syndromes not fulfilling the criteria for MS were evaluated in a rheumatology unit for features of SLE and followed longitudinally (enrolment period 2016-20). Clinical, laboratory and neuroimaging data were recorded at every visit, following multidisciplinary evaluation. At end of follow-up, patients were assessed for their final neurological and rheumatological diagnosis, and classified accordingly. A total of 79 patients were included in the study [91.1% female, mean (s.d.) age at first demyelinating episode 38.4 (10.3) years, median (interquartile range) observation period 39 (57) months]. At last follow-up, 38 patients (48.1%) had evolved into MS. Of the remaining patients, 7 (17.1%) had SLE, while 34 (82.9%) had features of systemic autoimmunity without fulfilling classification criteria for SLE. The most common rheumatological features of these patients were inflammatory arthritis (73.5%), acute cutaneous lupus (47.1%) and positive ANA (72.1%). Importantly, these patients were less likely to have elevated IgG index (odds ratio 0.11, 95% CI 0.04, 0.32) and positive oligoclonal bands (odds ratio 0.21, 95% CI 0.08, 0.55). A significant number of patients with demyelination do not fulfill criteria for either MS or SLE at follow-up. These patients exhibit lupus-like autoimmune features and may represent a distinct entity, 'demyelination with autoimmune features'.

Assessment of Body Composition in Patients with Multiple Sclerosis: Institutional-Based Cross-Sectional Study

Background: Multiple sclerosis (MS) is the most common progressive neurologic disease all over the world. MS is an immune-mediated disease and there is contradictory data regarding cardiovascular morbidity and mortality risk factors in MS patients. Objective: To assess the body composition in MS patients, and to explore the associations of anthropometric indices and metabolic risk factors with the phenotypic features of MS. Patients and Methods: a cross-sectional study included 150 patients fulfilling the diagnostic criteria for MS according to the revised McDonald’s criteria 2010, and 145 age and sex-matched healthy controls. Fat mass index (FMI) and free fat mass index (FFMI) were assessed by dual-energy X-Ray absorptiometry (DEXA). Results: This study was conducted on MS patients with phenotypes; RRMS (82%) and SPMS (18%). our results revealed that the distribution of body composition among MS patients was 30 %, overweight was 48% and lean was 22%. Also, MS patients had significantly higher values of systolic and diastolic blood pressure as well as dyslipidemia, obesity indices, and hs-CRP compared to the control group, P-value < 0.001. Interestingly, there were significantly higher values of the expanded disability status scale (EDSS), dyslipidemia, obesity indices, and hypertension in the obese group compared to other groups. Conclusions: MS patients had higher values of dyslipidemia and obesity indices than control groups. Among MS, the prevalence of overweight patients was higher than lean and obese MS patients.

Multiple sclerosis with intractable vomiting and atypical area postrema lesion

Area postrema syndrome is considered as one of the most typical presentations of neuromyelitis optica spectrum disorders (NMOSDs) (Wingerchuketal., 2015). The involvement of area postrema is rarely seen in multiple sclerosis (MS). We are here report a case of a young woman with multiple sclerosis, presented with intractable vomiting, and her MRI brain showed acute T2 hyperintense signal over the area postrema. A 36-year-old Asian woman who is known to have schizophrenia and multiple sclerosis since 2012. She was noted to have spastic gait, and the MRI brain in 2012 showed multiple perpendicular periventricular T2 lesions suggestive of multiple sclerosis (MS). However, she defaulted her neurologist follow-up and was not on any treatment for MS. She was admitted in 2016 with intractable vomiting, and her MRI brain showed T2 hyperintense signal over area postrema with focal contrast enhancement. Her MRI cervical spine was normal. The visual evoked potential study showed bilateral prolonged P100 latencies. Oligoclonal bands were detected in her CSF analysis. Both the serum aquaporin-4 IgG (AQP4 IgGs) antibody and myelin oligodendrocyte glycoprotein (MOG-IgGs) were negative. Her intractable vomiting resolved after a short course of intravenous methylprednisolone. She was treated as MS with interferon-beta 1a. She has been in remission since 2016, and her functional status also improved from the expanded disability status scale (EDSS) of 2.0 (in 2016) to 1.0 (in 2020). We proposed that although area postrema lesion is typically seen in NMOSDs, it may also be seen in MS. Current MRI criteria for MS and NMOSDs are not sufficiently specific, and the diagnostic criteria should only be used in the appropriate clinical context.

From Baló’s concentric sclerosis to multiple sclerosis: a series of 6 patients

Baló's concentric sclerosis (BCS) is a rare CNS disorder characterized by alternating bands of demyelination on MRI. One of the main issues is its relationship with multiple sclerosis (MS). To describe 6 BCS patients. To review the risk of developing MS in BCS patients. We retrospectively recorded clinical and radiological findings of 6 BCS patients and performed a review of the literature. Six patients (5 women) with a mean age of 25 years old were included. Main symptoms were hemiparesis/hemihypoesthesia. On MRI, two patients had a single BCS lesion and four had additional MS-like lesions. Alternating bands were usually more visible on DWI. A patient had reduced central perfusion and SWI hypointensity suggestive of a central vein. Oligoclonal bands were identified in 5/6 patients. After 7 years of follow-up, all patients achieved MS criteria with mild disability (mean EDSS 1.75; 0-4). Our literature review included 65 BCS patients from 30 studies: although CSF oligoclonal bands and the presence of additional MS lesions were associated with subsequent relapses, this was not significant. Our series allows a detailed MRI description in BCS and gives a new insight into BCS evolution and its strong relationship with MS.

Efficacy of Subcutaneous Interferon Β-1a in Patients with a First Clinical Demyelinating Event in REFLEX is Maintained After Application of the 2017 McDonald Criteria

In REFLEX, subcutaneous interferon β-1a (scIFNβ-1a) reduced conversion to McDonald (2005 criteria) and clinically definite (CD) multiple sclerosis (MS) versus placebo in patients with a first clinical demyelinating event. Retrospective analysis demonstrated overall results were unchanged after application of McDonald-2010 MS criteria. Revised McDonald-2017 MS criteria included presence of cerebrospinal fluid specific oligoclonal bands, symptomatic lesions, and cortical lesions. Effect of scIFNβ-1a on time to McDonald-2005 MS and CDMS, and annualised relapse rate (ARR) during REFLEX was assessed, stratified by retrospective diagnosis of patients at baseline that did/did not meet McDonald-2017 MS criteria.

Does MRZ Reaction Have a Real Significance in the Diagnosis of Multiple Sclerosis?

Despite the diagnostic criteria for multiple sclerosis have been well established, there still remain a significant group of patients presenting with various clinical symptoms suspicious of demyelinating disease but not fulfilling these diagnostic criteria. MRZ reaction evaluates intrathecal synthesis of specific IgG antibodies against neurotrophic viruses of morbilli (M), rubella (R) and zoster (Z). MRZ reaction (positive was evaluated 2/3 or 3/3 for clinically isolated syndrome (CIS) or multiple sclerosis (MS) and negative 0/3 or 1/3), brain magnetic resonance imaging (MRI) (positive vs. negative regarding fulfilling diagnostic criteria for MS) and oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) were examined in 57 subjects with CIS and 55 with MS. At the time of lumbar puncture the diagnosis was not yet known. In the subgroup of CIS the sensitivity of brain MRI was 63.16%, of OCB 87.72% and MRZ 35.09%, and the specificity of brain MRI was 83.44%, of OCB 65.23 and of MRZ 91.72%. In the subgroup of MS the sensitivity of brain MRI was 81.82%, of OCB 87.27% and MRZ 38.18%, and the specificity of brain MRI was 86.51%, of OCB 64.80 and of MRZ 92.11%. In the subgroup analysis we found 4 out of 55 subjects with final diagnosis of MS (7.27%) and 7 out of 57 in the final CIS group (12.28%) with positive MRZ reaction (2/3 or 3/3) and brain MRI not fulfilling the diagnostic criteria for MS. Of course in vast majority (but not all) of cases the diagnosis of CIS or MS is easily made by fulfilling revised McDonald criteria – with contribution of brain and spinal cord MRI. Despite low sensitivity of MRZ reaction found in our cohort this diagnostic tool can be of special significance in the cases with clinical symptoms consistent with demyelinating disease of the CNS, but with initial brain MRI not fulfilling the diagnostic criteria. In these cases very high specificity of MRZ reaction can shift the diagnosis to either CIS or MS and thus contribute to earlier diagnosis and treatment.