Early-onset Multiple Sclerosis Research Articles

Pediatric traumatic brain injury and early age multiple sclerosis in Finland: A nationwide register-based cohort study.

Examine the link between pediatric traumatic brain injury (pTBI) and early-onset multiple sclerosis in Finland. Conducted nationwide register study (1998-2018) with 28,750 pTBI patients (<18) and 38,399 pediatric references with extremity fractures. Multiple sclerosis diagnoses from Finnish Social Insurance Institution. Employed Kaplan-Meier and multivariable Cox regression for probability assessment, results presented with 95% CI. Of 66 post-traumatic multiple sclerosis cases, 30 (0.10%) had pTBI, and 36 (0.09%) were in the reference group. Cumulative incidence rates (CIR) in the first 10 years were 46.5 per 100,000 (pTBI) and 33.1 per 100,000 (reference). Hazard ratio (HR) for pTBI was 1.10 (95% CI: 0.56-1.48).Stratified by gender, women's CIR was 197.9 per 100,000 (pTBI) and 167.0 per 100,000 (reference) after 15 years. For men, CIR was 44.6 per 100,000 (pTBI) and 34.7 per 100,000 (reference). In the initial 3 years, HR for female pTBI was 1.75 (95% CI: 0.05-6.32), and between years 3 and 20, it was 1.08 (95% CI: 0.51-1.67). For male patients, HR was 1.74 (95% CI: 0.69-4.39). We did not find evidence of an association between pTBI and early-onset multiple sclerosis 20 years post-initial trauma.

Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis

Association of Increased Homocysteine Levels with Impaired Folate Metabolism and Vitamin B Deficiency in Early-Onset Multiple Sclerosis

Clinical and radiologic differences between early onset, late onset, and very late onset adult multiple sclerosis

BackgroundPrevious studies suggested possible differences in clinical and radiologic characteristics between early-onset multiple sclerosis (EOMS) and late-onset MS (LOMS). However, differences between LOMS and very late onset MS (VLOMS) are largely unknown. MethodsWe performed a retrospective review of medical records of patients diagnosed with MS between 8/1/2017 and 3/1/2022 at the comprehensive MS center of the Froedtert and Medical College of Wisconsin. We included adult patients with MS diagnosis who were 60 years or older - VLOMS, 50–59 years old at diagnosis – LOMS, or were 18–30 years old at diagnosis – EOMS and had complete imaging and clinical records. Clinical presentation and location of demyelinating lesions at the onset of diagnosis were extracted and compared using the chi-square test, p<0.05. ResultsA total of 246 newly diagnosed patients were identified. Of which 54 were EOMS, 29 were LOMS, and 35 were VLOMS. The sex ratio was not different between groups. EOMS had a higher percentage of patients who self-identified as black, while LOMS had a higher percentage of patients who self-identified as white. LOMS and VLOMS showed significant differences in the presence of tremors and lesion distribution at the onset. Older onset patients were more likely to present with motor symptoms, sphincter dysfunction, fatigue, and tremor. EOMS was more likely to present with cerebellum and occipital lobe lesions, and lesions were more likely to show contrast enhancement on MRI at diagnosis. ConclusionOur findings revealed novel clinical and imaging characteristics differences between VLOMS and LOMS. The current classification of LOMS may benefit from revision to better align with chronological age classification for old age >60 instead of the current standard in the literature of >50 years.

B - 104 Late-Onset Multiple Sclerosis: a Neuropsychological Case Study.

A neuropsychological case study of Late-Onset Multiple Sclerosis (LOMS). Cognitive impairment often accompanies Multiple Sclerosis (MS). Depending on disease phase/type, 40-65% of MS patients develop various degrees of cognitive impairment. LOMS is a rare branch of Multiple Sclerosis with an onset of 50years or older. Like MS it has demyelinating qualities, however it typically has a neurodegenerative course rather than inflammatory properties. Additionally, unlike traditional MS, LOMS presents with greater motor and cognitive dysfunction. The patient, a 61-year-old, Caucasian, right-handed male, 18years of education initially presented with acute onset of vague cognitive changes along with significant motor dysfunction. A cerebral MRI revealed white matter disease in the cerebral hemispheres with the largest lesion adjacent to the right frontal horn. Lesions involved bifrontal/parietal lobes, specific lesion posteriorly in the left centrum and right caudate head. Patient was administered the Meyers Neuropsychological Battery (MNB). Findings were consistent with level one central processing deficits with attention/concentration and processing speed. Deficits were noted with primary and psychomotor abilities. Patient's premorbid estimate was T-58. Overall Test Battery Mean (T-52) and Domain Test Battery Mean (T-51) were generally within the expected range. Remaining neuropsychological abilities were relatively intact (e.g., memory, abstraction, language, spatial). Consistent with the literature, higher-order cognitive abilities were relatively intact. LOMS mirrored early-onset MS in this case. However, a significant risk factor for LOMS is the possibility of co-occurring neurodegenerative disease. This underscores the need for comprehensive neuropsychological assessment that includes motor testing for MS.

Association between interleukin-12B gene polymorphisms and multiple sclerosis in turkish population

Elevated levels of IL-12p40 have been observed in the cerebrospinal fluid and serum of MS patients, and it has been suggested that genetic variants in the IL-12B gene may contribute to MS susceptibility and/or pathogenesis. In this study, we investigated the association between MS and IL-12B gene rs17860508 and rs3212227 polymorphisms in the Turkish population. We identified two polymorphic regions in the IL-12B gene using bioinformatics tools and genotyped 351 MS patients and 221 healthy controls for these variants. Our results showed a significant association between the IL-12B rs17860508 polymorphism and MS, but no significant relationship between rs17860508 genotype distribution and allele frequency and MS age onset or subtypes. Genotype distribution and allele frequency of IL-12B rs3212227 polymorphism did not show any significant association with MS directly. However, AC genotype of IL-12B rs3212227 polymorphism in early-onset multiple sclerosis (EOMS) was a risk factor according to age of onset. Additionally, we observed a higher risk for the relapsing-remitting multiple sclerosis (RRMS) subtype in females. This is the first study to investigate the association between IL-12B polymorphisms and MS in the Turkish population.

Childhood-onset epilepsy in patients with dyskinetic cerebral palsy caused by basal ganglia and thalamic lesions

ObjectiveTo elucidate the incidence and outcomes of childhood-onset epilepsy and associated factors in term-born patients with basal ganglia and thalamic lesion (BGTL)-induced dyskinetic cerebral palsy (DCP) caused by perinatal hypoxic-ischemic encephalopathy (HIE). MethodsWe studied 104 term-born patients with BGTL-induced DCP (63 males and 41 females, aged 2–22 years) to investigate the incidence of epilepsy and the factors related to its development. We used multivariate analysis to assess perinatal factors, gross motor function, and the extent of brain lesions. We also investigated the seizure onset, clinical course, and electroencephalography (EEG) characteristics. ResultsThe cumulative epilepsy incidence was 36%. Multiple logistic regression analysis revealed that deep white matter lesions were the only independent risk factor for epilepsy. The confirmed seizure types included epileptic spasms (ES, n = 13), myoclonic seizures (MS, n = 6), and focal-onset seizures (FS, n = 24). Only patients with deep white matter lesions exhibited ES or MS. The symptoms of FS resembled those of self-limited epilepsy with centrotemporal spikes; however, only half of the patients reached remission by the time of investigation, and four patients had more than one seizure per month despite appropriate drug therapy. Focal spikes in the peri-rolandic area were detected not only in patients with FS but also in half of the patients without epilepsy. ConclusionsOne-third of term-born patients with BGTL-induced DCP caused by perinatal HIE develop epilepsy, and deep white matter lesions increase the likelihood of epilepsy. Preparation for early-onset ES, MS, and subsequent FS is beneficial.

The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study

The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathogenesis and treatment practice in relapse-onset MS (ROMS). Utilising a unique, prospectively collected clinical data from a longitudinal cohort of 279 first demyelinating event cases followed for up to 15 years post-onset, we examined indirect associations between relapses and treatment and the risk of disability worsening, and vice-versa. Indirect association parameters were estimated using joint models for longitudinal and survival data. Early relapses within 2.5 years of MS onset predicted early disability worsening outcomes (HR = 3.45, C.I 2.29–3.61) per relapse, but did not contribute to long-term disability worsening thereinafter (HR = 0.21, C.I 0.15–0.28). Conversely, disability worsening outcomes significantly contributed to relapse risk each year (HR = 2.96, C.I 2.91–3.02), and persisted over time (HR = 3.34, C.I 2.90–3.86), regardless of DMT treatments. The duration of DMTs significantly reduced the hazards of relapses (1st-line DMTs: HR = 0.68, C.I 0.58–0.79; 3rd-line DMTs: HR = 0.37, C.I 0.32–0.44) and disability worsening events (1st-line DMTs: HR = 0.74, C.I 0.69–0.79; 3rd-line DMTs: HR = 0.90, C.I 0.85–0.95), respectively. Results from time-dynamic survival probabilities further revealed individuals having higher risk of future relapses and disability worsening outcomes, respectively. The study provided evidence that in ROMS, relapses accrued within 2.5 years of MS onset are strong indicators of disability worsening outcomes, but late relapses accrued 2.5 years post onset are not overt risk factors for further disability worsening. In contrast, disability worsening outcomes are strong positive predictors of current and subsequent relapse risk. Long-term DMT use and older age strongly influence the individual outcomes and their associations.

Characterization of a late-onset multiple sclerosis Portuguese cohort.

Late-onset multiple sclerosis (LOMS) is defined as the onset of symptoms above 50 years, corresponding to an increasingly recognized subset of MS. This study aimed at comparing demographic and clinical data of patients with LOMS to those of early-onset MS (EOMS) from a Portuguese cohort. Retrospective chart review of an MS cohort from a Portuguese tertiary center. From 746 patients with MS (61.7% female), we identified 39 cases with presentation after 50 years of age (22 males and 17 females), corresponding to 5.3%. The mean age at onset was 55.4 (±5.0) for LOMS and 29.5 (±8.9) for EOMS. There was no significant difference in disease duration. The most common type was relapsing-remitting MS, accounting for 51.5% and 83.9% of LOMS and EOMS patients, respectively. Primary-progressive MS (PPMS) was significantly more represented in the LOMS group (41.0%) (p<0.01). The median EDSS was significantly higher in the LOMS group (4.75, 0.0-7.5) when compared to the EOMS group (2.0, 0.0-9,0). The most frequent presenting feature was myelitis in both LOMS (48.7%) and EOMS patients (47.4%), resulting in significantly higher EDSS (p=0.003). LOMS is associated with higher EDSS when considering the same disease duration, translating into increased disability.

Early onset multiple sclerosis and the effect of disease onset age on neurological disability in multiple sclerosis

ObjectivesThe incidence of early onset multiple sclerosis (EOMS) is increasing. We therefore aimed to compare the demographic, clinical, and magnetic resonance imaging features of early onset and adult onset multiple sclerosis patients. Furthermore, the effects of age of onset were evaluated for patients who reached an expanded disability status scale (EDSS) scores of six. Patients and methodsThis was a retrospective study of MS patient medical charts between 1977 and 2021, which were registered in the MS database. Only patients with relapsing remitting MS longer than 1 year were included in the study. The patients included in the study were divided into the EOMS and adult onset MS (AOMS) groups. General demographic datas, clinical datas such as the characteristics of the first clinical period, the time between the first two attacks, the attack rate in the first 2 and 3 years, the treatment status, the EDSS at the first evaluation, the EDSS score at 6 month intervals, the time to reach an EDSS score of six, and magnetic resonance imaging features such brain and spinal T2 lesions were recorded. ResultsTotal of 3477 including 353 (10.2 %) EOMS and 3124 (89.8 %) AOMS patients were analyzed. There was no statistically significant difference in symptom patterns between the EOMS and AOMS groups ( p = 0.649). Supratentorial clinical features at first attack were more common in AOMS patients, while optic neuropathy at first attack was more common in EOMS patients. Using univariable analysis, clinical supratentorial features at first attack, clinical optic neuropathy at first attack, clinical spinal cord at fist attack, spinal cord lesions, first EDSS score, relapse in the first 3 years, and onset patterns in terms of age were found to be statistically significant risk factors. In multivariable-adjusted analysis, clinical supratentorial features at first attack, clinical spinal cord lesions at first attack, first EDSS scores relapses in the first 3 years, and onset patterns in terms of age were found to be independent risk factors for EDSS in reaching a score of six. Early treatment start was associated with reduced hazard rate of reaching an EDSS score of 6. ConclusionOnset pattern in terms of age was an independent prognostic factor for neurological disabilities in MS patients.

Quality of Life Changes in Early-Onset Multiple Sclerosis: A 4-Year Follow-Up Study.

This study investigates longitudinal changes in health-related quality of life (HRQoL) in early-onset multiple sclerosis (MS) patients and explores the impact of disease activity (relapses) on such changes. People with MS (PwMS) onset between 12 and 25 years of age were followed longitudinally. At baseline and at year 4, patients were asked to fill the Paediatric Quality of life inventory (PedsQL). Demographic and clinical features were collected at both time points. Longitudinal within-group comparison of HRQoL total score and sub-scores was performed via paired samples t-test. The effect of relapses on the HRQoL changes over time was explored via linear mixed-effects analysis. No longitudinal changes were observed in the overall PedsQL score, nor in the physical, school and psychological functioning. An increase in the social functioning subscale (p < 0.001) and a decrease in the emotional subscale (p = 0.006) were observed. The change in social functioning, but not the one in the emotional subscale, was affected by the occurrence of relapses (p = 0.044). In conclusion, stimulating the patients to accept their emotional responses to health-related limitations, while preserving their social and relational resources seems key to the preservation of an adequate QoL over time in juvenile-onset MS.

Diagnostic Cerebrospinal Fluid Biomarker in Early and Late Onset Multiple Sclerosis.

Background: The intrathecal humoral response is the characteristic diagnostic finding in the cerebrospinal fluid (CSF) analysis of patients with multiple sclerosis (MS). Although the average age of MS patients increases, little is known about the sensitivity of diagnostic markers in elderly MS patients. Methods: In this retrospective two-center study, intrathecal free light chains kappa fraction (FLCk IF) and oligoclonal bands (OCB) were studied in a large cohort of patients with early and late onset relapsing (RMS) and progressive (PMS) MS. Furthermore, the humoral immune profile in CSF was analyzed, including the polyspecific intrathecal immune response measured as the MRZ reaction. Results: While the frequency of CSF-specific OCB did not differ between early and late onset RMS and PMS, the sensitivity of positive FLCk IF and absolute FLCk IF values were lower in PMS. The positivity of the MRZ reaction was equally frequent in early and late onset RMS and PMS. PMS patients had higher local IgA concentrations than RMS patients (p = 0.0123). Conclusions: OCB are slightly superior to FLCk IF in progressive MS in terms of sensitivity for detecting intrathecal immunoglobulin synthesis. The MRZ reaction, as the most specific parameter for MS, is also applicable in patients with late onset and progressive MS.

Slowly expanding lesions relate to persisting black-holes and clinical outcomes in relapse-onset multiple sclerosis

BackgroundSlowly expanding lesions (SELs) are MRI markers of chronic active lesions in multiple sclerosis (MS). T1-hypointense black holes, and reductions in magnetization transfer ratio (MTR) are pathologically correlated with myelin and axonal loss. While all associated with progressive MS, the relationship between these lesion’s metrics and clinical outcomes in relapse-onset MS has not been widely investigated. ObjectivesTo explore the relationship of SELs with T1-hypointense black holes, and longitudinal T1 intensity contrast ratio and MTR, their correlation to brain volume, and their contribution to MS disability in relapse-onset patients. Methods135 patients with relapsing-remitting MS (RRMS) were studied with clinical assessments and brain MRI (T2/FLAIR and T1-weighted scans at 1.5/3 T) at baseline and two subsequent follow-ups; a subset of 83 patients also had MTR acquisitions. Early-onset patients were defined when the baseline disease duration was ≤ 5 years (n = 85). SELs were identified using deformation field maps from the manually segmented baseline T2 lesions and differentiated from the non-SELs. Persisting black holes (PBHs) were defined as a subset of T2 lesions with a signal below a patient-specific grey matter T1 intensity in a semi-quantitative manner. SELs, PBH counts, and brain volume were computed, and their associations were assessed through Spearman and Pearson correlation. Clusters of patients according to low (up to 2), intermediate (3 to 10), or high (more than 10) SEL counts were determined with a Gaussian generalised mixture model. Mixed-effects and logistic regression models assessed volumes, T1 and MTR within SELs, and their correlation with Expanded Disability Status Scale (EDSS) and confirmed disability progression (CDP). ResultsMean age at study onset was 35.5 years (73% female), disease duration 5.5 years and mean time to last follow-up 6.5 years (range 1 to 12.5); median baseline EDSS 1.5 (range 0 to 5.5) and a mean EDSS change of 0.31 units at final follow-up. Among 4007 T2 lesions, 27% were classified as SELs and 10% as PBHs. Most patients (n = 65) belonged to the cluster with an intermediate SEL count (3 to 10 SELs). The percentage of PBHs was higher in SELs than non-SELs (up to 61% vs 44%, p < 0.001) and within-patient SEL volumes positively correlated with PBH volumes (r = 0.53, p < 0.001). SELs showed a decrease in T1 intensity over time (beta = -0.004, 95%CI −0.005 to −0.003, p < 0.001), accompanied by lower cross-sectional baseline and follow-up MTR. In mixed-effects models, EDSS worsening was predicted by the SEL log-volumes increase over time (beta = 0.11, 95%CI 0.03 to 0.20, p = 0.01), which was confirmed in the sub-cohort of patients with early onset MS (beta = 0.14, 95%CI 0.04 to 0.25, p = 0.008). In logistic regressions, a higher risk for CDP was associated with SEL volumes (OR = 5.15, 95%CI 1.60 to 16.60, p = 0.006). ConclusionsSELs are associated with accumulation of more destructive pathology as indicated by an association with PBH volume, longitudinal reduction in T1 intensity and MTR. Higher SEL volumes are associated with clinical progression, while lower ones are associated with stability in relapse-onset MS.

A retrospective study on the clinico-demographic profile of multiple sclerosis patients in various tertiary care hospitals in Mangalore city of South India

Objectives. To study the risk factors, clinical presentations, course of the disease, investigations and management practices in MS. Materials and methods. Records of 23 patients diagnosed with MS using the McDonald diagnostic criteria were analysed. Outcomes. The mean age at diagnosis was 34.6±17.1 years. 17 (73.9%) patients were females. Early and late onset MS were present among 2 (8.7%) and 4 (17.4%) patients respectively. The most common symptom at diagnosis was paraesthesia [9 (39.1%)]. Motor symptoms and sensory symptoms at the time of diagnosis were present among 9(39.1%) patients each. 20 (87%) patients had motor system involvement, 9 (39.1%) had sensory system involvement, 12 (52.2%) had cranial nerve involvement, 4 (17.4%) had sphincter dysfunction and 2 (8.7%) had cerebellar involvement. Relapsing and remitting MS (RRMS) were present among 18 (78.3%) patients. Oligoclonal bands were present among 17 (73.9%) patients. Vitamin D levels in the blood were found deficient among 4 (80%) out of 5 patients with available reports of the same. Juxtacortical region was the most common [9 (39.1%)] site of involvement. Steroids were used for management among majority [12 (52.2%)] of the patients. Non-pharmacological methods for management constituted only physiotherapy which was advised among 13 (56.5%) patients. Improvement in treatment outcome were seen among 19 (82.6%) patients. Conclusions. Almost three fourth of the patients were females. RRMS was the most common course of the disease. Juxtacortical region was the most common site involved. Steroids were most commonly used for management. More non-pharmacological methods need to be introduced for MS management.

Age at onset in multiple sclerosis as a possible predictor for cognitive impairment in children and adolescents

Pediatric-onset multiple sclerosis (MS) can lead to cognitive impairment (CI). In general, in early-onset MS, there are disturbances in cognitive processes, such as information processing speed, attention, and controlling functions. Also, unlike adults with MS, children show a failure in various spheres of speech activity. The age of onset in MS, its duration and recurrence rate can affect not only the accumulation of a stable neurological deficit, but also the state of the cognitive sphere.Objective: to study of the features of CI in children and adolescents with MS; to assess the relationship of CI to clinical characteristics, such as age at onset in the disease and its duration.Patients and methods. The study involved 45 pediatric and adolescent patients with an established diagnosis of MS, who underwent a general neuropsychological examination of the cognitive sphere (Luria’s tests) with transfer to a point system; in addition, psychometric techniques were used to assess attention, controlling functions, memory, verbal fluency, and various types of thinking. Clinical characteristics, such as age at onset in MS and its duration at the time of the examination, were also taken into account.Results and discussion. The leading factors that combine certain symptom complexes of CI in children and adolescents with MS were established. These factors include attention, controlling functions, auditory-verbal and visuospatial memories, various spheres of speech activity. Early-onset MS (at age of 5–8 years) was ascertained to have a greater impact on the formation of speech and controlling functions than adolescence- onset (at age of 13–16-years).Conclusion. The risk of cognitive deficit and subsequent disability was found to be highest in early-onset MS.

Clinical Characteristics and Disability Progression of Early- and Late-Onset Multiple Sclerosis Compared to Adult-Onset Multiple Sclerosis.

Background: Compared to the adult onset of multiple sclerosis (AOMS), both early-onset (EOMS) and late-onset (LOMS) are much less frequent, but are often under- or misdiagnosed. The aims of the present study were: 1. To compare demographic and clinical features of individuals with EOMS, AOMS and LOMS, and 2. To identify predictors for disability progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS). Method: Data were taken from the Isfahan Hakim MS database. Cases were classified as EOMS (MS onset 18 years), LOMS (MS onset >50 years) and AOMS (MS >18 and 50 years). Patients’ demographic and clinical (initial symptoms; course of disease; disease patterns from MRI; disease progress) information were gathered and assessed. Kaplan–Meier and Cox proportional hazard regressions were conducted to determine differences between the three groups in the time lapse in conversion from relapsing remitting MS to secondary progressive MS. Results: A total of 2627 MS cases were assessed; of these 127 were EOMS, 84 LOMS and 2416 AOMS. The mean age of those with EOMS was 14.5 years; key symptoms were visual impairments, brain stem dysfunction, sensory disturbances and motor dysfunctions. On average, 24.6 years after disease onset, 14.2% with relapsing remitting MS (RRMS) were diagnosed with secondary progressive MS (SPMS). The key predictor variable was a higher Expanded Disability Status Scale (EDSS) score at disease onset. Compared to individuals with AOMS and LOMS, those with EOMS more often had one or two relapses in the first two years, and more often gadolinium-enhancing brain lesions. For individuals with AOMS, mean age was 29.4 years; key symptoms were sensory disturbances, motor dysfunctions and visual impairments. On average, 20.5 years after disease onset, 15.6% with RRMS progressed to SPMS. The key predictors at disease onset were: a higher EDSS score, younger age, a shorter inter-attack interval and spinal lesions. Compared to individuals with EOMS and LOMS, individuals with AOMS more often had either no or three and more relapses in the first two years. For individuals with LOMS, mean age was 53.8 years; key symptoms were motor dysfunctions, sensory disturbances and visual impairments. On average, 14 years after disease onset, 25.3% with RRMS switched to an SPMS. The key predictors at disease onset were: occurrence of spinal lesions and spinal gadolinium-enhancement. Compared to individuals with EOMS and AOMS, individuals with LOMS more often had no relapses in the first two years, and higher EDSS scores at disease onset and at follow-up. Conclusion: Among a large sample of MS sufferers, cases with early onset and late onset are observable. Individuals with early, adult and late onset MS each display distinct features which should be taken in consideration in their treatment.

Multiphasic acute disseminated encephalomyelitis and differential with early onset multiple sclerosis.

Multiple sclerosis is considered the most frequent demyelinating disorder of the Central Nervous System (CNS) among young adults, yet is very rare before 10 years old. Acute disseminated encephalomyelitis is a monophasic, polysymptomatic disorder that involves the CNS white matter with demyelinating lesions, which usually occurs after systemic viral infections. These two demyelinating diseases can present initially as an acute focal neurological syndrome and they can be difficult to distinguish. We describe a case of a nine-year-old girl that presented initially with dysphonia, gait ataxia, eyelid myokymia and brainstem disturbances. This was her second episode; the first episode was at the age of four years old. She recovered without neurological sequelae. The brain magnetic resonance imaging (MRI) demonstrated multiple demyelinating lesions in the white matter, cortical regions of the frontal lobe, periventricular distribution, internal capsule, corpus callosum and cerebellum. The purpose of the presentation of this case was to highlight the similarities between these two entities, since the clinical picture and neuroimaging are difficult to distinguish, mainly in relation to the first episode.

Epidemiology of MS in Tehran Province, Iran: A Population- Based Study

There is a significant increase of Multiple Sclerosis (MS) in Asia, special in Iran. Familial recurrence studies in MS are useful to identify the correlated effects in etiology of the disease. This is a cross-sectional study based on Iranian MS Society data from 1999 to 2018 with the aim of estimating incidence, prevalence and assessing associations among most important variables related to familial MS (gender, age at disease onset, types of MS and familial history). Multiple regressions were used to indicate the predictors of MS via SPSS. Among 21580 MS subjects, the crude incidence and prevalence rate was 6.93 and 151.3 per 100000 populations in 2018 respectively. Completely 16187 (75%) were female and female to male ratio was 3:1.Mean age at disease onset was 28.82 years old, 9.7% of the population had early onset MS (<=18 years old). Female gender was a strong significant predictor for onset age (p<0.001). 749 (14.4%) of male patients and 2066 (13.1%) of female patients had a history of familial MS which was significantly different between them, p value=0.017, (OR=1.11; 95% CI=1.02, 1.22). Crude odds ratio for familial recurrence of MS in first degree of relatives was significantly different among genders (OR=1.30; 95% CI=1.12, 1.5). The age standardized prevalence rate of MS was estimated 54.1 (95%CI: 53.6-54.6) among males and 174.5 (95%CI: 173.6-175.4) per 100,000 among females. Totally, 75.7% were relapsing remitting MS, 16.4% were primary progressive MS and 7.9% were secondary progressive MS. MS incidence and prevalence in Tehran has increased with a decreased female to male ratio. Despite the higher prevalence of MS amongst females, the familial recurrence was higher among males except in first degree of relatives.

Associations between cognitive impairment at onset and disability accrual in young people with multiple sclerosis

Differently from the adult multiple sclerosis (MS) population, the predictive value of cognitive impairment in early-onset MS is still unknown. We aim to evaluate whether cognitive performances at disease onset predict disease progression in young people with MS. This is a retrospective study on early onset (<25 years) MS patients, who had a baseline cognitive evaluation at disease onset. Demographic and longitudinal clinical data were collected up to 7 years follow up. Cognitive abilities were assessed at baseline through the Brief Repeatable Battery. Associations between cognitive abilities and clinical outcomes (occurrence of a relapse, and 1-point EDSS progression) were evaluated with stepwise logistic and Cox regression models. We included 51 patients (26 females), with a mean age at MS onset of 17.2 ± 3.9 years, and an EDSS of 2.5 (1.0–6.0). Over the follow-up, twenty-five patients had at least one relapse, and 7 patients had 1-point EDSS progression. Relapse occurrence was associated with lower 10/36 SPART scores (HR = 0.92; p = 0.002) and higher WLG scores (HR = 1.05; p = 0.01). EDSS progression was associated with lower SDMT score (OR: 0.70; p = 0.04). Worse visual memory and attention/information processing were associated with relapses and with increased motor disability after up to 7-years follow-up. Therefor, specific cognitive subdomains might better predict clinical outcomes than the overall cognitive impairment in early-onset MS.

Familial risk of early- and late-onset multiple sclerosis: a Swedish nationwide study

BackgroundPersons who develop multiple sclerosis (MS) at a young age may bear a higher genetic risk load than persons who develop MS later in life; however, the contribution of familial influence to the risk of MS, in relation to onset age, has not been established.ObjectiveTo investigate the familial risk of MS at two extremes of the spectrum of MS onset age: early onset (first MS symptom < 18 years of age) and late onset (first MS symptom ≥ 50 years).MethodsNationwide registries in Sweden were used to identify cases of MS and controls, and their familial relations. We estimated the odds ratio (OR) of an MS diagnosis for individuals with a relative diagnosed with early-onset or late-onset MS compared with those whose relatives did not have MS, using a nested case–control design.Results629 early-onset and 1148 late-onset MS patients were identified and matched to 10 controls from the general population by age and sex. The OR of MS for individuals with a first-degree relative diagnosed with early-onset MS was 10.86 (95% CI 6.87–17.17); and for late-onset MS was 8.08 (95% CI 6.12–10.67).ConclusionsOur findings demonstrate no substantial differences in familial risk in persons with early- and late-onset MS.

Anti-Myelin Oligodendrocyte Glycoprotein and Human Leukocyte Antigens as Markers in Pediatric and Adolescent Multiple Sclerosis: on Diagnosis, Clinical Phenotypes, and Therapeutic Responses.

Early-onset (pediatric and adolescent) multiple sclerosis (MS) is a well-established demyelinating disease that accounts for approximately 3-5% of all MS cases. Thus, identifying potential biomarkers that can reflect the pathogenic mechanisms, disease course and prognosis, and therapeutic response in such patients is of paramount importance. Myelin oligodendrocyte glycoprotein (MOG) has been regarded as a putative autoantigen and autoantibody target in patients with demyelinating diseases for almost three decades. However, recent studies have suggested that antibodies against MOG represent a distinct clinical entity of dominantly humoral profile, with a range of clinical phenotypes closely related to the age of onset, specific patterns of disease course, and responses to treatment. Furthermore, the major histocompatibility complex (MHC)—which has been regarded as the “gold standard” for attributing genetic burden in adult MS since the early 1970s—has also emerged as the primary genetic locus in early-onset MS, particularly with regard to the human leukocyte antigen (HLA) alleles DRB1⁎1501 and DRB1⁎0401. Recent studies have investigated the potential interactions among HLA, MOG, and environmental factors, demonstrating that early-onset MS is characterized by genetic, immunogenetic, immunological, and familial trait correlations. In this paper, we review recent evidence regarding HLA-genotyping and MOG antibodies—the two most important candidate biomarkers for early-onset MS—as well as their potential application in the diagnosis and treatment of MS.