Early-onset Multiple Sclerosis Patients Research Articles

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 and cognitive functions in early onset multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the CNS occurring in young adults and even in children in 5% of cases. Lower quality of life (QoL) and cognitive impairment (CI) (40-54%) have been reported in early-onset MS (EO-MS) patients. To assess QoL and cognitive function in EO-MS and their relationship, also considering demographic and clinical variables. Paediatric Quality of life inventory Version 4.0 for patients aged 13-18 and 19-25 years, Beck Depression Inventory II (BDI II) and the Rao Brief Repeatable Battery were performed in EO-MS patients (onset age ≤25years). EDSS and MSSS were performed at same time. After testing for normal distribution, group comparisons were performed through the two-tailed Student's t test, one-way analysis of variance (ANOVA) and linear or logistic regression when appropriate. The Bonferroni correction for multiple testing was used when appropriate. 59 patients were included (mean age: 20±3.6; Female sex 52.54%). 34 patients had a paediatric onset (<18 years) while 20 patients had a juvenile onset (18<age<25 years) of disease. 5 patients were excluded for missing data. HR-QoL was higher in paediatric than juvenile MS patients (p=0.02), and it was inversely related to EDSS (p=0.0005) and Multiple Sclerosis Severity score (MSSS) (p=0.0001). Sixtyone % of patients showed a CI at BRB. No association was found between CI and any socio-demographic and clinical data. HR-QoL total score was not related to CI status nor to any domain-specific cognitive function score, even considering BDI as possible bias. CI was related to social, physical functioning score and EDSS (p=0.01) at a logistic regression backward stepwise estimation. HR-QoL resulted to be better in paediatric than juvenile MS onset patients and was inversely related to rapidity of disability accumulation, while cognitive impairment was influenced by physical disability and poor social involvement (school, education …). Social participation, affective relations and psychological flexibility could have a protective function on CI.

HLA-DRB1* Allele Frequencies in Pediatric, Adolescent and Adult-Onset Multiple Sclerosis Patients, in a Hellenic Sample. Evidence for New and Established Associations

Studies in many populations consistently have showed that the human leukocyte antigens (HLA) and especially the DRB1*15 allele has by far the strongest genetic association with multiple sclerosis (MS). The aim of this study was to investigate the role of HLA-DRB1* alleles in MS risk/resistance and onset. A sample of 165 Hellenic MS patients (18 with pediatric-, 24 with adolescent- and 123 with adult-onset MS) and 107 healthy volunteers were examined with molecular techniques. Comparisons were made according to the Benjamini-Yekutieli method for p value correction. Both adult-onset MS patients and early-onset MS patients (age at onset below 20 years-old) had a significantly higher frequency of the DRB1*15 allele and a significantly lower frequency of the DRB1*11 allele compared to controls. For the early-onset vs. healthy group comparison, subgroup analyses revealed that both the pediatric- and the adolescent-onset MS groups contributed to the aforementioned DRB1*15 significant difference, while the DRB1*11 difference was ascribed solely to the adolescent-MS onset vs. healthy group comparison. Within MS patients comparisons revealed that early-onset MS patients had a tendency for higher DRB1*03 allele and a lower DRB1*16 allele frequency frequencies compared to adult-onset MS patients, although both non-significant. Notably, pediatric-onset MS patients showed complete absence of the DRB1*16 allele, along with a non-significant tendency for higher DRB1*15 allele frequency relative to the adult-onset group. Finally, the adolescent-onset MS group was presented with a lower DRB1*11 allele frequencies compared both to the pediatric- and the adult-onset MS group. Our findings confirm previous studies on the role of HLA-DRB1* in MS. New findings that need to be confirmed by further studies are the pathogenetic role of DRB1*03 for early-onset MS and the putative protective role of the DRB1*16 allele in the pediatric-onset MS.

Epileptic seizures in early-onset multiple sclerosis.

Early-onset multiple sclerosis (EOMS) is defined as the first presentation of symptoms in childhood (before the age of 16 years). EOMS occurs in about 0.4% to 10.5% of multiple sclerosis (MS) patients. In this retrospective population-based study we aimed to describe the clinical/paraclinical details and frequency of epileptic seizures in Iranian EOMS patients registered with the Isfahan Multiple Sclerosis Society (IMSS) from April 2003 to July 2010. EOMS cases were extracted from the Isfahan total MS cohort and included 3522 patients. A total of 117 EOMS patients (19 males and 98 females) with a mean age at onset of 14.2 ± 2.0 years (range: 7-16 years) were extracted from our database (3.3% of the total cohort). Of cases, ten (one male and nine females) had experienced at least two epileptic seizures, providing a crude prevalence of 8.5%. The frequency of epilepsy in EOMS patients (8.5%, 10/117) was significantly greater (P < 0.001) than that of non-EOMS cohort (2.0%, 71/3405). Epileptic seizures occurred before MS onset in two patients, after MS onset in seven, and at MS onset in one as the presenting symptom of the disease. Our findings mostly indicate an excessive prevalence of epileptic seizures in Iranian EOMS patients (8.5%), which is higher than any other report concerning seizures or epileptic seizures in a large MS series.

Clinical characteristics and long term prognosis in early onset multiple sclerosis

The clinical features, disease course and long term prognosis of early onset multiple sclerosis (EOMS) are variable. A preponderance of female sex, a high incidence of visual and brainstem symptoms at onset and a relapsing-remitting disease course with slower progression rate all have been considered relatively frequent in this subgroup of MS patients. Unfortunately, follow-up in previous studies has usually been limited to less than 10 years, precluding general statements on the long term evolution and prognosis in EOMS. In this retrospective study of EOMS with a substantially longer follow-up of 20.8 years, clinical characteristics, disease course and long term prognosis are described in 49 EOMS patients. In a representative subgroup of 28 patients disability was scored using Kurtzke's Functional System (FS) and Expanded Disability Status Scale (EDSS). The mean period of follow- up for these patients was 28.7 years. The present study confirms that several specific clinical characteristics can be identified in EOMS patients, such as a mainly relapsing-remitting disease onset and frequent presentation with brainstem- cerebellar dysfunction (28.6 %), pyramidal symptoms (18.4 %) and optic neuritis (14.3%). However, after a long period of follow-up the overall disease course and prognosis do not seem to differ from that in adult onset MS. By consequence a young age at onset in MS cannot be considered a favourable prognostic factor.