Risk of central nervous system demyelinating attack or optic neuritis recurrence after pediatric optic neuritis in Korea.

PURPOSE: To investigate the rate of development of symptomatic central nervous system (CNS) demyelinating attacks or recurrent optic neuritis (ON) after the first episode of ON and its risk factors for Korean pediatric patients. METHODS: This multicenter retrospective cohort study included the patients under 18 years of age (n=132) diagnosed with ON without previous or simultaneous CNS demyelinating diseases. We obtained the clinical data including the results of neuro-ophthalmological examinations, magnetic resonance images (MRIs), antibody assays, and laboratory tests. We investigated the chronological course of demyelinating disease with respect to the occurrence of neurological symptoms and/or signs, and calculated the 5-year cumulative probability of CNS demyelinating disease or ON recurrence.  RESULTS: During the follow-up period (63.1±46.7 months), 18 patients had experienced other CNS demyelinating attacks, and the 5-year cumulative probability was 14.0±3.6%. Involvement of the extraorbital optic nerve or optic chiasm and asymptomatic lesions on the brain or spinal MRI at initial presentation were significant predictors for CNS demyelinating attack after the first ON. The 5-year cumulative probability of CNS demyelinating attack was 44.4 ± 24.8% in the AQP4-IgG group, 26.2±11.4% in the MOG-IgG group, and 8.7±5.9% in the double-negative group (P=0.416). Thirty-two patients had experienced a recurrence of ON, and the 5-year cumulative probability was 24.6±4.0%. In the AQP4-IgG group, the 5-year cumulative probability was 83.3±15.2%, which was significantly higher than in the other groups (P<0.001). CONCLUSIONS: A careful and multidisciplinary approach including brain/spinal imaging and antibody assay can help predict further demyelinating attacks in pediatric ON patients.

Clinical Profile and Outcome of Pediatric Demyelinating Disorders in Calabar, Nigeria: A Case Series.

BACKGROUND: Demyelinating disorders of the central nervous system (CNS) are rare disorders characterized by inflammation and the selective destruction of CNS myelin. The incidence of this disorder is increasing in developed countries. Nigerian studies on the pediatric population on the subject are very scarce. AIMS: The aim of the study was to document the epidemiology, clinical profile, and impact of late presentation on the treatment outcome of demyelinating diseases of the CNS in pediatric patients. METHODS: The retrospective review of patients aged 1-15 years admitted in a tertiary hospital from January 2018 to December 2022 with various symptoms suggestive of demyelinating CNS disorders. The diagnosis was clinically and radiologically confirmed. Information retrieved from the case notes included patients' demographics, clinical symptoms and signs, number of days with symptoms to presentation in the hospital, results of the magnetic resonance imaging (MRI), treatment, and treatment outcomes. Data were entered in Excel sheet and results were presented in tables and percentages. RESULTS: The incidence of demyelinating disorders over the period was 0.013% (10 out of 769 patients admitted over the period). Acute demyelinating encephalomyelitis (ADEM) was the most common disorder seen in the study population (60%, n = 6), followed by transverse myelitis and two (20%) had optic neuritis (ON). Most of the patients with ADEM were in the 1-5-year age group. The female-to-male ratio was 2.3:1. Paraplegia, visual impairment, and ataxia were the most common clinical presentations in the study population. One of the patients met the criteria for the diagnosis of multiple sclerosis during follow-up. Human immunodeficiency virus (HIV) was identified as the cause of demyelination in one case. Most of the patients improved with steroids. CONCLUSION: ADEM was the most common clinical phenotype seen in this study. Patients with ADEM and ON had a better prognosis than transverse myelitis. Late presentation was also identified as a poor prognostic factor. Follow-up of cases is very important to monitor disease progression to multiple sclerosis.

Impact of COVID-19 vaccination or infection on disease activity in a radiologically isolated syndrome cohort: The VaxiRIS study.

BACKGROUND: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised. OBJECTIVES: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS). METHODS: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients' history of COVID-19 infection. RESULTS: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients. CONCLUSION: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

Incidental demyelination in magnetic resonance imaging and 10-year risk of multiple sclerosis: A data lake cohort study.

BACKGROUND AND PURPOSE: There is an absence of data from large population-based cohort studies on the incidence of radiologically isolated syndrome (RIS). The incidence of RIS and the subsequent risk for multiple sclerosis (MS) were investigated. METHODS: A population-based, retrospective cohort study was conducted using a data-lake-based analysis of digitalized radiology reports. All brain and spinal cord magnetic resonance imaging (MRI) in people aged 16-70 during the years 2005-2010 (n = 102,224) were screened using optimized search terms to detect cases with RIS. The subjects with RIS were followed up until January 2022. RESULTS: The cumulative incidence of RIS was 0.03% when all MRI modalities were included and 0.06% when only brain MRI was included according to MAGNIMS 2018 recommendation criteria. With the Okuda 2009 criteria, the respective figures were 0.03% and 0.05% (86% concordance). The overall risk for MS after RIS was similar, 32% by using the MAGNIMS and 32% by using the Okuda definition of RIS. Individuals aged <35.5 years exhibited the most significant predisposition to MS (80%), whilst those >35.5 years had less than 10% risk of MS. MS diagnosed after RIS constituted 0.8% of the incident MS cases in the population during 2005-2010. CONCLUSIONS: A population-wide context was provided for the incidence of RIS and its relationship to MS. MAGNIMS recommendations were only slightly more sensitive to detect RIS compared to the Okuda criteria. RIS has a subtle effect on the overall incidence of MS, yet the risk for MS in individuals under the age of 35.5 years is substantial.

Osmotic Demyelination Syndrome in Hospitalized Patients With Cirrhosis: Analysis of the National Inpatient Sample (NIS).

GOAL: Characterize prevalence of osmotic demyelination syndrome (ODS) in hospitalized patients with cirrhosis. BACKGROUND: ODS is a serious complication of rapid serum sodium correction. Patients with cirrhosis experience labile sodium levels related to portal hypertension and diuretic use, often with rapid correction-intentional or unintentional-during hospitalizations. STUDY: We used validated International Classification of Diseases, Ninth Revision (ICD-9) codes to identify inpatients 18 years and older with cirrhosis from the 2009-2013 National Inpatient Sample, excluding those with liver transplantation during hospitalization. The primary outcome was ODS (ICD-9 341.8). Baveno IV defined decompensated cirrhosis (stages 3 and 4); Charlson Comorbidity Index identified severe comorbid illness (score >3). Logistic regression modeled factors associated with ODS. RESULTS: Of 547,544 adult inpatients with cirrhosis, 94 (0.02%) had ODS. Inpatients with versus without ODS were younger (54 vs. 57 y, P=0.0001), and more likely to have alcohol-related cirrhosis (58% vs. 33%, P<0.0001). ODS did not associate with decompensated cirrhosis (33% vs. 37%, P=0.43), specific complications (ascites 33% vs. 33%, P=0.97; hepatic encephalopathy 24% vs. 17%, P=0.06), or severe comorbid illness (12% vs. 16%, P=0.24). In both univariable and multivariable analysis, age [adjusted odds ratio (ORadj): 0.97, 95% confidence interval (CI): 0.95-0.99], female gender (ORadj: 1.53, 95% CI: 1.01-2.30), Hispanic race (ORadj: 0.41, 95% CI: 0.19-0.89), alcohol-related cirrhosis (ORadj: 2.65, 95% CI: 1.71-4.09), and congestive heart failure (ORadj: 0.37, 95% CI: 0.15-0.95) significantly associated with ODS. CONCLUSION: In hospitalized patients with cirrhosis, ODS is extremely rare, and associated with alcohol-related cirrhosis, younger age, and female gender. ODS is not associated with liver disease severity, specific complications including ascites, or comorbid disease.

Incidence and risk factors of overcorrection in patients presenting with severe hyponatremia to the emergency department.

BACKGROUND: Hyponatremia is one of the most common electrolyte abnormalities. Overcorrection of severe hyponatremia can result in serious neurological complications such as osmotic demyelination syndrome, but the incidence and risk factors of overcorrection and osmotic demyelination have not been thoroughly investigated. METHODS: This is a single-center retrospective cohort study of 50 patients admitted through the emergency department with initial serum sodium (serum Na) < 125 mEq/L between January 2015 and December 2017. Incidence and risk factors of overcorrection and osmotic demyelination were examined. Overcorrection was defined as an increase in serum sodium concentration > 10 mEq/L at 24 h and/or > 18 mEq/L at 48 h, respectively. RESULTS: Six patients (12%) and one patient (2%) had overcorrection at 24 h and 48 h, respectively. A total of 5 (10%) patients had a brain MRI completed after overcorrection, and no patient showed radiologic evidence of osmotic demyelination. Symptomatic hyponatremia at presentation and 3% saline use were associated with the risk of overcorrection in univariable analysis (p < 0.001; p = 0.006, respectively). CONCLUSIONS: Among patients admitted with severe hyponatremia, overcorrection occurred in 14%. Symptomatic hyponatremia at presentation and 3% saline use were associated with the risk of overcorrection.

Factors Related to the Progression of Clinically Isolated Syndrome to Multiple Sclerosis: A Retrospective Study in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski's reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski's reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.

A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes.

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74.

Prevalence of radiologically isolated syndrome in a pediatric population-based cohort: A longitudinal description of a rare diagnosis.

BACKGROUND: Radiologically isolated syndrome (RIS) is typified by multiple sclerosis (MS)-like lesions on imaging, without clinical MS symptoms. The prevalence of pediatric RIS is largely unknown. OBJECTIVE: The objective of the study is to provide an estimated RIS prevalence in a population-based cohort of children. METHODS: We used data from the Generation R study to identify the childhood RIS prevalence. RESULTS: In 5238 participants, only one RIS case was identified (prevalence: 0.02%; 95% confidence interval (CI): 0.00-0.11). During a 62-month follow-up, imaging examinations showed accrual of new focal demyelinating lesions; however, no clinical MS symptoms occurred. CONCLUSIONS: This study shows that the occurrence of RIS in children from the general population is rare.

Long-term trajectory of acquired demyelinating syndrome and multiple sclerosis in children.

AIM: We assessed the frequency, characteristics, and future trajectory of monophasic acquired demyelinating syndromes (ADS) associated with conversion to paediatric multiple sclerosis. METHOD: This was a retrospective observational study of Sardinian children (<18y of age) with onset of ADS between 2001 and 2018. RESULTS: We identified 44 children with ADS (21 males, 23 females; median age at onset 16y, range 4mo-18y), 21 of whom were already presenting with criteria for paediatric multiple sclerosis. The mean crude prevalence of ADS in Sardinian children was 59.2 per 100 000, while incidence was 3.1 per 100 000 per year (1.3 in children aged ≤10y and 11.9 in those aged 10-17y). After a mean (SD) follow-up of 8 years 5 months (5y 4mo), the most common (n=32) trajectory was conversion to paediatric multiple sclerosis. At onset, the total prevalence and mean annual incidence of paediatric multiple sclerosis were 35.6 per 100 000 and 2.3 per 100 000 respectively (0.5 in individuals aged ≤10y, 10.0 in the older group). INTERPRETATION: Sardinia is a very high risk area for ADS in children. Nearly half of this population can already be diagnosed with paediatric multiple sclerosis at onset. Overall, 72% of those with ADS will have paediatric multiple sclerosis after a mean of 8 years. What this paper adds Sardinia is a very high risk area for paediatric acquired demyelinating syndromes (ADS). A high proportion of those with paediatric multiple sclerosis are diagnosed at onset of ADS. After an average 8 years from onset of paediatric ADS, three-quarters of patients are diagnosed with paediatric multiple sclerosis.

Risk of neuroinflammatory events in arthritis patients treated with tumour necrosis factor alpha inhibitors: a collaborative population-based cohort study from Denmark and Sweden.

OBJECTIVES: To investigate whether tumour necrosis factor alpha inhibitors (TNFis) are associated with an increased risk of neuroinflammatory diseases among patients with arthritic diseases. METHODS: Cohorts of patients with rheumatoid arthritis (RA, n=25 796), psoriatic arthritis (PsA, n=8586) and ankylosing spondylitis (AS, n=9527) who initiated a TNFi treatment year 2000-2017 were identified from nationwide clinical rheumatology registers in Sweden and Denmark. Information on demyelinating disease and inflammatory neuropathy diagnoses was retrieved from prospective linkage to National Patients Register. A Cox proportional hazard model was used to estimate HRs and 95% CI comparing TNFi exposed and non-exposed, by disease and country. RESULTS: Among 111 455 patients with RA, we identified 270 (Sweden) and 51 (Denmark) events (all types of neuroinflammatory diseases combined), corresponding to crude incidence rates (per 1000 person-years) of 0.37 (Sweden) and 0.39 (Denmark) in TNFi-treated patients vs 0.39 (Sweden) and 0.28 (Denmark) in unexposed patients, and an age-sex-calendar-period-adjusted HR (95% CI) of 0.97 (0.72 to 1.33) (Sweden) and 1.45 (0.74 to 2.81) (Denmark) in TNFi exposed compared with non-exposed patients. For a total of 64 065 AS/PsA patients, the corresponding numbers were: 196 and 32 events, crude incidence rates of 0.59 and 0.87 in TNFi-treated patients vs 0.40 and 0.19 in unexposed patients, and HRs of 1.50 (1.07 to 2.11) and 3.41 (1.30 to 8.96), for Sweden and Denmark, respectively. For multiple sclerosis, the patterns of HRs were similar. CONCLUSIONS: Use of TNFi in AS/PsA, but not in RA, was associated with increased risk of incident neuroinflammatory disease, though the absolute risk was below one in 1000 patients/year.

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing.

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A-related leukodystrophy, Peroxisomal biogenesis disorders, POLR3-related Leukodystrophy, Vanishing White Matter, and Pelizaeus-Merzbacher Disease. Despite the relative frequency of these conditions, carrier-screening laboratories regularly test only 20 of the 55 leukodystrophy-related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.

Trigeminal neuralgia in multiple sclerosis: Prevalence and association with demyelination.

OBJECTIVES: The association of trigeminal neuralgia (TN) with multiple sclerosis (MS) is still widely unaddressed in larger, systematical clinical series. In this study, a cohort of Finnish MS patients was assessed regarding the incidence and prevalence of TN, as well as the presence of demyelinating lesions near the trigeminal ganglion, thus searching for a causative role of MS plaques in TN onset. MATERIALS & METHODS: All consecutive patients treated and followed up for MS (ICD-code G35) in Helsinki University Hospital during 2004-2017 were identified from the Finnish MS register. A hospital administrative database search was used to identify all patients treated and followed up for TN during the same period. Among the MS patients, head MRI scans available from the diagnostic phase of TN or thereafter were analysed. RESULTS: We identified a total of 2575 patients with MS and 2008 patients with TN. Both diagnoses could be verified for 55 patients, giving a prevalence of 2.1% for TN in MS. The incidence of TN in MS patients was 149/100 000 person-years (95% CI 108-190). In the general outpatient population of our neurological department, the incidence of TN was 9.9/100 000 person-years (95% CI 9.5-10.3). A demyelinating lesion in the proximity of the trigeminal ganglia was seen for 63% of the 41 patients with relevant MRI data available. CONCLUSIONS: Incidence of TN among MS patients was 15-fold higher than in the general neurological outpatient population, thus in favour of a strong association between MS and TN.

Risk factors for academic difficulties in children with myelin oligodendrocyte glycoprotein antibody-associated acute demyelinating syndromes.

AIM: To describe cognitive abilities through the evaluation of academic difficulties in children with acute demyelinating syndromes (ADS) and myelin oligodendrocyte glycoprotein (MOG) antibodies. METHOD: This was an observational, retrospective study of a French paediatric cohort that included children aged 18 years and younger. Clinical, biological, and imaging data were collected and academic outcome was measured. RESULTS: Seventy-six children were included in the study with a mean (SD) follow-up of 4 years 7 months (6y 4mo). Median age at disease onset was 9 years 1 months (interquartile range=4y 7mo-13y 11mo; 36 females, 40 males). Thirty-six children relapsed and 20 had academic difficulties at the last follow-up. Academic difficulties, as well as deep grey matter and putaminal lesions (p=0.047 and p=0.006 respectively), were significantly more prevalent in children aged 10 years and younger (p=0.02). Using univariate binary regression analysis, we found that age at disease onset of 10 years and younger (odds ratio [OR] 3.72 [95% confidence interval {CI} 1.19-11.64]; p=0.024), acute disseminated encephalomyelitis at disease onset (OR 52.5 [95% CI 5.97-461.4]; p<0.001), and deep grey matter lesions (OR 17.33 [95% CI 3.87-77.72]; p<0.001) were associated with academic difficulties. INTERPRETATION: MOG antibody-associated ADS have distinct clinical and radiological patterns that are age-dependent. Indirect cognitive evaluation through academic difficulties was prevalent in younger children and is associated with specific clinical and magnetic resonance imaging factors that need to be considered earlier on when assessing this patient population.

The contribution of secondhand tobacco smoke exposure to pediatric multiple sclerosis risk.

BACKGROUND: Pediatric acquired demyelinating syndromes (ADSs) are monophasic (mono-ADS) in 70% of cases and represent the first attack of multiple sclerosis (MS) in 30%. Secondhand tobacco smoke (SHS) exposure has been implicated as a risk factor for adult-onset MS. Little is known about whether SHS presents an additive risk beyond genetic factors and other environmental exposures associated with pediatric MS. METHODS: This study examined SHS exposure in 216 children with mono-ADS and 81 children with MS. Interactions between SHS, HLA-DRB1*15 alleles, serum 25-hydroxyvitamin D concentrations, and serological evidence of remote Epstein-Barr virus (EBV) exposure were evaluated. RESULTS: SHS exposure was more common in children with MS (37% exposed) compared to mono-ADS (29.5% exposed). Compared to mono-ADS, SHS exposure was not an independent risk factor for MS. When both SHS exposure and HLA-DRB1*15 were present, the odds for MS increased (odds ratio (OR) = 3.7; 95% confidence interval (CI): 1.17-11.9) compared to mono-ADS. Interactions between SHS and vitamin D or EBV did not associate with MS. CONCLUSION: Exposure to SHS is a risk factor for central nervous system (CNS) demyelination. Results suggest that SHS exposure and HLA-DRB1*15 interact to increase risk for MS in children diagnosed with mono-ADS.

A healthy dietary pattern associates with a lower risk of a first clinical diagnosis of central nervous system demyelination.

BACKGROUND: The evidence associating diet and risk of multiple sclerosis is inconclusive. OBJECTIVE: We investigated associations between dietary patterns and risk of a first clinical diagnosis of central nervous system demyelination, a common precursor to multiple sclerosis. METHODS: We used data from the 2003-2006 Ausimmune Study, a case-control study examining environmental risk factors for a first clinical diagnosis of central nervous system demyelination, with participants matched on age, sex and study region. Using data from a food frequency questionnaire, dietary patterns were identified using principal component analysis. Conditional logistic regression models (n = 698, 252 cases, 446 controls) were adjusted for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, race, education, body mass index and dietary misreporting. RESULTS: We identified two major dietary patterns - healthy (high in poultry, fish, eggs, vegetables, legumes) and Western (high in meat, full-fat dairy; low in wholegrains, nuts, fresh fruit, low-fat dairy), explaining 9.3% and 7.5% of variability in diet, respectively. A one-standard deviation increase in the healthy pattern score was associated with a 25% reduced risk of a first clinical diagnosis of central nervous system demyelination (adjusted odds ratio 0.75; 95% confidence interval 0.60, 0.94; p = 0.011). There was no statistically significant association between the Western dietary pattern and risk of a first clinical diagnosis of central nervous system demyelination. CONCLUSION: Following healthy eating guidelines may be beneficial for those at high risk of multiple sclerosis.

The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis.

BACKGROUND: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have been associated with lower brain volumes. It is currently unknown if this association already exists in early MS and how it develops over time. METHODS: We identified 82 patients with clinically isolated syndrome (CIS) ( n = 61) or with early relapsing-remitting MS ( n = 21) and assessed their VRF including arterial hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2-lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up magnetic resonance imaging (MRI) and assessed the percentage of brain volume change (PBVC) using SIENA. RESULTS: Patient mean age was 32.4 (±8.7) years and 54 (65%) were women. Median follow-up period was 42 (29-54) months. In total, 26 patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a lower NBV (1530.9 cm3 vs 1591.2 cm3, p = 0.001), a lower cGMV (628.5 cm3 vs 668.6 cm3, p = 0.002) and WMV (752.2 cm3 vs 783.9 cm3, p = 0.009) than VRF-negative patients. Similar results were obtained at follow-up. PBVC was comparable between patients with and without VRF. CONCLUSION: VRF are associated with lower brain volume already in early MS but do not lead to increased brain volume loss during 3.5 years of follow-up.

Managing Risks with Biologics.

PURPOSE OF REVIEW: With a rapidly evolving complement of advanced targeted therapies in inflammatory bowel disease, additional safety and side effect concerns emerge. It is the purpose of this review to consider various risks with biologic therapies in inflammatory bowel disease and discuss mitigating strategies. RECENT FINDINGS: Two recently approved monoclonal antibodies (vedolizumab and ustekinumab) and a Janus kinase inhibitor small molecule (tofacitnib) have introduced a number of novel safety and risk considerations. We review the clinical trial and real-world safety data to date on these agents as well as review new data and considerations with anti-tumor necrosis factor agents. New vaccines for varicella zoster virus, hepatitis B virus, and high-dose influenza have been studied, and we discuss the clinical importance of these findings. Lastly, we make management recommendations in the event of particular side effects or complications. Understanding the risks of new agents in inflammatory bowel disease, potential mitigating strategies, and management considerations is important to achieving and maintaining clinical outcomes in IBD patients.

Inflammatory demyelinating diseases of the central nervous system in Niger.

BACKGROUND: In sub-Saharan Africa (SSA), few studies have been reported on inflammatory demyelinating diseases of the central nervous system (CNS). Neuromyelitis optica spectrum disorders (NMOSD) seems to be the most frequent inflammatory demyelinating disease of CNS in sub-Saharan Africans or people of sub-Saharan African descent. METHODS: We report the observations of seven patients from Niger diagnosed with inflammatory demyelinating diseases of CNS over a period of 21 years (1996-2017). RESULTS: They were four women and three men aged 19 to 66 years (mean age: 37 years), with no known past medical history. Four patients were diagnosed with NMOSD (2 men and 2 women) and the three other patients with multiple sclerosis (MS, 2 women and 1 man). The three patients diagnosed with MS had the relapsing-remitting form. The cerebrospinal fluid study revealed the presence of oligoclonal bands in the three patients. Of the patients diagnosed with NMOSD, two patients negative anti-aquaporin 4 antibodies (anti-MOG antibodies not done), one of whom had bilateral optic neuritis (ON) with longitudinally extensive transverse myelitis (LETM) and the other unilateral ON with LETM. Two patients with MS were treated with interferon beta-1a and the third patient with azathioprine. The Expanded Disability Status Scale ranged from 1 to 2 in these three patients at the time of initiation of background treatment. Azathioprine was the treatment prescribed in the four patients with NMOSD. We did not find any case of acute disseminated encephalomyelitis. CONCLUSION: Our case series suggests the rarity of inflammatory demyelinating diseases of CNS in Niger, and NMOSD seems to be more frequent than MS.

Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis.

Approved in 2006, human papillomavirus (HPV) vaccines were initially targeted for girls aged 9-14 years. Although the safety of these vaccines has been monitored through post-licensure surveillance programmes, cases of neurological events have been reported worldwide. The present study aimed to assess the risk of developing demyelination after HPV immunization by meta-analysing risk estimates from pharmacoepidemiologic studies. A systematic review was conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from inception to 10 May 2017, without language restriction. Only observational studies including a control group were retained. Study selection was performed by two independent reviewers with disagreements solved through discussion. This meta-analysis was performed using a generic inverse variance random-effect model. Outcomes of interest included a broad category of central demyelination, multiple sclerosis (MS), optic neuritis (ON), and Guillain-Barré syndrome (GBS), each being considered independently. Heterogeneity was investigated; sensitivity and subgroup analyses were performed when necessary. In parallel, post-licensure safety studies were considered for a qualitative review. This study followed the PRISMA statement and the MOOSE reporting guideline. Of the 2,863 references identified, 11 articles were selected for meta-analysis. No significant association emerged between HPV vaccination and central demyelination, the pooled odds ratio being 0.96 [95% CI 0.77-1.20], with a moderate but non-significant heterogeneity (I2 = 29%). Similar results were found for MS and ON. Sensitivity analyses did not alter our conclusions. Findings from qualitative review of 14 safety studies concluded in an absence of a relevant signal. Owing to limited data on GBS, no meta-analysis was performed for this outcome. This study strongly supports the absence of association between HPV vaccines and central demyelination.