First Symptoms Of Multiple Sclerosis Research Articles

Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis

It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository. Individuals with MS had serum collected at a median 1 year before onset (reported to the military in 2000-2011) and were matched to controls for age, sex, race and ethnicity, blood collection, and military branch. No individuals were excluded. The data were analyzed between September 1, 2022, and August 31, 2023. Antibodies (enrichment z scores) to the human virome measured using VirScan (phage-displayed immunoprecipitation and sequencing). Rate ratios (RRs) for MS for antibodies to 2263 EBV peptides (the EBV peptidome) were estimated using conditional logistic regression, adjusting for total anti-EBV nuclear antigen 1 (EBNA-1) antibodies, which have consistently been associated with a higher MS risk. The role of antibodies against other viral peptides was also explored. A total of 30 individuals with MS were matched with 30 controls. Mean (SD) age at sample collection was 27.8 (6.5) years; 46 of 60 participants (76.7%) were male. The antibody response to the EBV peptidome was stronger in individuals with MS, but without a discernible pattern. The antibody responses to 66 EBV peptides, the majority mapping to EBNA antigens, were significantly higher in preonset sera from individuals with MS (RR of highest vs lowest tertile of antibody enrichment, 33.4; 95% CI, 2.5-448.4; P for trend = .008). Higher total anti-EBNA-1 antibodies were also associated with an elevated MS risk (top vs bottom tertile: RR, 27.6; 95% CI, 2.3-327.6; P for trend = .008). After adjusting for total anti-EBNA-1 antibodies, risk estimates from most EBV peptides analyses were attenuated, with 4 remaining significantly associated with MS, the strongest within EBNA-6/EBNA-3C, while the association between total anti-EBNA-1 antibodies and MS persisted. These findings suggest that antibody response to EBNA-1 may be the strongest serologic risk factor for MS. No single EBV peptide stood out as being selectively targeted in individuals with MS but not controls. Larger investigations are needed to explore possible heterogeneity of anti-EBV humoral immunity in MS.

Pediatric multiple sclerosis - current status of epidemiology, diagnosis and treatment.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system that mostly affects younger adults. However, the first symptoms of MS can appear in children and adolescents before the age of 18, and we call this paediatric MS (PMS). It is estimated that paediatric MS accounts for 3-5% of the general population of patients with MS. Despite the fundamental si-milarities to adult MS, PMS has many distinctive features. Paediatric MS has a milder course compared to adults, but leads to sig-nificant disability at an early age. PMS is relapsing-remitting in 95-98% of cases; the primary progressive manifestation is much less common than in adults. The differential diagnosis of MS in children should include other childhood demyelinating diseases, mitochondrial and metabolic diseases, connective tissue diseases, and neuroborreliosis. Differentiating acute disseminated en-cephalomyelitis (ADEM) from the first onset of MS remains the biggest challenge. Over the past 10 years, understanding of the epidemiology, pathophysiology, diagnosis, and treatment of MS in children has significantly expanded. The diagnostic criteria leading to earlier diagnosis and initiation of disease-modifying therapy (DMT) have changed, and the number of drugs used in children has increased. However, many important issues require further research. This review discusses the current state of knowledge regarding the epidemiology, diagnosis, and treatment of multiple sclerosis in children.

PECULIARITIES OF COMORBID PAIN SYNDROME AND COGNITIVE DYSFUNCTION IN PATIENTS WITH MULTIPLE SCLEROSIS

In this paper, we reviewed scientific sources on multiple sclerosis, analyzed the latest data on the peculiarities of cognitive dysfunction and comorbid pain syndrome in patients with multiple sclerosis. Multiple sclerosis belongs to the group of chronic progressive demyelinating diseases with a predominant lesion of the central nervous system. It affects over 2.5 million people worldwide and is considered as one of the most disabling neurological disorders. Symptoms range from physical ones including loss of vision, spasticity, bladder and bowel dysfunction, problems with walking and balance, fatigue and pain, to mental problems such as cognitive impairment, depression, and anxiety. Comorbid conditions have a significant impact on the quality of life of patients with multiple sclerosis. This evokes considerable scientific interest, since their presence can cause a delay in diagnosis, change the progression of neurological deficits, reduce physical activity and increase the severity of symptoms of the underlying disease. One of the most common comorbid conditions associated with multiple sclerosis is pain. The prevalence of pain syndrome ranges from 29% to 86%. Patients can consider pain as one of the first symptoms of multiple sclerosis. Moreover, in the treatment and diagnosis of multiple sclerosis, in most cases, the state of cognition is missed or neglected, but it always accompanies the patients in the form of cognitive disorders of varying severity. Cognitive function is understood as the most complex mechanism by which the process of rational cognition of the environment and interaction with it is carried out. Both a series of cognitive tests for multiple sclerosis and an MRI evaluation of gray matter atrophy can help to assess the state of cognition. Also, an additional diagnostic method is transcranial magnetic stimulation, with which it is possible to create a model for mapping the cerebral cortex using evoked motor potentials. Thus, the analysis of the literature has shown that the issues of the influence of comorbidity and cognitive dysfunction on the course of multiple sclerosis, the relationship of the onset of multiple sclerosis with comorbid conditions, and the correlation of neurological deficit with the cognitive ability of patients are not studied completely yet.

Pediatric Multiple Sclerosis Severity Score in a large US cohort.

To characterize disease severity and distribution of disability in pediatric-onset multiple sclerosis (POMS) and to develop an optimized modeling scale for measuring disability, we performed a multicenter retrospective analysis of disability scores in 873 persons with POMS over time and compared this to previously published data in adults with multiple sclerosis (MS). This was a retrospective analysis of prospectively collected data collected from 12 centers of the US Network of Pediatric MS Centers. Patients were stratified by the number of years from first symptoms of MS to Expanded Disability Status Scale (EDSS) assessment and an MS severity score (Pediatric Multiple Sclerosis Severity Score [Ped-MSSS]) was calculated per criteria developed by Roxburgh et al. in 2005. In total, 873 patients were evaluated. In our cohort, 52%, 19.4%, and 1.5% of all patients at any time point reached an EDSS of 2.0, 3.0, and 6.0. Comparison of our Ped-MSSS scores and previously published adult Multiple Sclerosis Severity Scores (MSSS) showed slower progression of Ped-MSSS with increasing gaps between higher EDSS score and years after diagnosis. Decile scores in our POMS cohort for EDSS of 2.0, 3.0, and 6.0 were 8.00/9.46/9.94, 7.86/9.39/9.91, and 7.32/9.01/9.86 at 2, 5, and 10 years, respectively. Notable predictors of disease progression in both EDSS and Ped-MSSS models were ever having a motor relapse and EDSS at year 1. Symbol Digit Modalities Test (SDMT) scores were inversely correlated with duration of disease activity and cerebral functional score. Persons with POMS exhibit lower EDSS scores compared to persons with adult-onset MS. Use of a Ped-MSSS model may provide an alternative to EDSS scoring in clinical assessment of disease severity and disability accrual.

Employment status of people diagnosed with multiple sclerosis in Brazil.

To describe the employment status of Brazilians with multiple sclerosis (MS). Analysis of a cross-sectional online survey including questions on demographic and occupational status at the time of diagnosis and survey completion, and time from the first symptom to diagnosis. Of those who answered the survey, 804 Brazilians with MS were included. Median age of onset and current age were 28.3 and 36.2 years; median time to diagnosis and disease duration were 2.7 and 7.9 years; 67% held a university degree and 29% finished high school; 94% had a paid occupation contributing to the family income at least once in their lives, 77% were employed at the time of diagnosis but only 59% were employed at the time of survey. Longer disease duration, longer time to diagnosis and younger age at the first symptom, were identified as factors correlated with being unemployed. The rate of unemployment doubled after the first symptoms of MS, and only 59% of highly-educated people with MS in their productive years were employed. The longer time to diagnosis may imply treatment delay, and strategies focusing on early diagnosis and adequate treatment may favor employment retention and reduce disability related costs, such as social benefits and pension fund use.

Teriflunomide real-world evidence: Global differences in the phase 4 Teri-PRO study

BackgroundThe demographics and management of patients with multiple sclerosis (MS) differ across geographical regions, but it is unclear whether/how these differences affect treatment outcomes. The aim of this post-hoc analysis was to assess teriflunomide use and patient-reported outcomes in the United States (US) and the rest of the world (ROW) in the phase 4 Teri-PRO study (NCT01895335). MethodsIn the phase 4, real-world, Teri-PRO study, patients with relapsing forms of MS received teriflunomide for 48 weeks according to local labeling. The primary endpoint was treatment satisfaction measured using the Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM 1.4). Secondary endpoints included scores on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Performance Scale (MSPS), and Patient-Determined Disease Steps (PDDS), and occurrence of adverse events. Primary and secondary endpoints were assessed at baseline and Week 48. An exploratory subgroup analysis assessed PROs in the black patient population. ResultsThe US and ROW groups included 545 and 455 patients, respectively. The mean age of patients in the ROW group was lower, they had a shorter mean time since first symptoms of MS, and had lower mean EDSS scores at baseline, compared with the US group (all p < 0.0001). Black patients made up 9% of US patients vs 0.2% of ROW patients. TSQM global satisfaction scores and effectiveness, side effects, and convenience subscale scores were significantly improved from baseline to Week 48 (all p < 0.0001). Disability measures were stable from baseline to Week 48 for both groups, despite different baseline level scores between the two groups. The overall proportion of patients who experienced an AE was similar across both groups. Fewer patients in the US group vs the ROW group reported hair thinning (16.1% vs 31.2%). Black patients showed comparable baseline demographics and disease characteristics and similar change over time in PROs compared with the overall US group. ConclusionPatient differences observed at baseline between the US and ROW groups suggest variation in teriflunomide prescribing practices in the real-world Teri-PRO study. Improvement in treatment satisfaction and stability of disability measures were comparable between patients in the US and ROW. This suggests that teriflunomide was effective despite differences in baseline demographics and possible cultural and management differences between these geographical regions.

Characterization of the first symptoms of multiple sclerosis in a Brazilian center: cross-sectional study.

Multiple sclerosis (MS) is a chronic, immune-mediated and degenerative central nervous system (CNS) disease with well-established diagnostic criteria. Treatment can modify the course of the disease. The objective of this study was to describe the initial symptoms of multiple sclerosis in a Brazilian medical center. Descriptive study, conducted in a Brazilian reference center for multiple sclerosis treatment. Data on 299 patients with confirmed diagnoses of MS were included in the study. Their medical files were evaluated and the data were analyzed. The most common symptom involved the cranial nerves (50.83%) and unifocal manifestation was presented by the majority of this population (73.91%). The mean time between the first symptom and the diagnosis was 2.84 years. Unifocal symptoms correlated with longer time taken to establish the diagnosis, with an average of 3.20 years, while for multifocal symptoms the average time taken for the diagnosis was 1.85 years. Unifocal onset was related to greater diagnostic difficulty. MS is a heterogeneous disease and its initial clinical manifestation is very variable.

The importance of HLA DRB1 gene allele to clinical features and disability in patients with multiple sclerosis in Lithuania.

BackgroundThe association of HLA DRB1 alleles with susceptibility to multiple sclerosis (MS) has been consistently reported although its effect on the clinical features and disability is still unclear probably due to diversity in ethnicity and geographic location of the studied populations. The aim of the present study was to investigate the influence of HLA DRB1 alleles on the clinical features and disability of the patients with MS in Lithuania.MethodsThis was a prospective study of 120 patients with MS. HLA DRB1 alleles were genotyped using the polymerase chain reaction.ResultsThe first symptoms of MS in patients with HLA DRB1*15 allele manifested at younger age than in those without this allele (28.32 +/− 5.49 yrs vs. 30.94 +/− 8.43 yrs, respectively, p = 0.043). HLA DRB1*08 allele was more prevalent among relapsing-remitting (RR) MS patients than among patients with progressive course of MS (25.0% vs. 8.3%, respectively, chi^2 = 6.000, p = 0.05). MS patients with this allele had lower relapse rate than those without this allele (1.00 +/− 0.97 and 1.44 +/− 0.85, respectively, p = 0.043). Degree of disability during the last visit was lower among the patients with HLA DRB1*08 allele (EDSS score 3.15 +/− 1.95 vs. 4.49 +/− 1.96, p = 0.006), and higher among those with HLA DRB1*15 allele (EDSS score 4.60 +/− 2.10 vs.4.05 +/− 1.94, p = 0.047) compared to patients without these alleles but there were no significant associations between these alleles and the duration of the disease to disability. HLA DRB1*08 allele (OR = 0.18, 95% CI 0,039-0,8, p = 0.029) was demonstradet to be independent factor to take a longer time to reach an EDSS of 6, while HLA DRB1*01 allele (OR = 5.92, 95% CI 1,30-26,8, p = 0.021) was related in a shorter time to reach and EDSS of 6. Patients with HLA DRB1*08 allele had lower IgG index compared to patients without this allele (0.58 +/− 0.17 and 0.73 +/− 0.31, respectively, p = 0.04), and HLA DRB1*15 allele was more often found among MS patients with oligoclonal bands (OCBs) in cerebrospinal fluid than among those without OCBs (OR 2.3, CI 95% 1.017-5.301; p = 0.043).ConclusionsHLA DRB1*15 allele was related with an earlier manifestation of the first MS symptoms, progressive course of the disease and higher degree of disability. HLA DRB1*08 allele was more prevalent among the RR MS patients and was associated with the lower rate of relapse, degree of disability and IgG index.

Atteintes hypothalamiques dans la sclérose en plaques

Hypothalamic involvement is a rare condition in patients with multiple sclerosis (MS). We report two patients with a long history of MS who presented with severe acute hypothermia with associated thrombocytopenia and elevated transaminase levels. Several cases of hypothermia or hyperthermia in patients with MS have been reported in the literature. They could be linked with hypothalamic lesions, in particular in the pre-optic area. However, other anatomical locations seem to be involved in thermoregulation and can be affected by MS. Besides, some cases of syndrome of inappropriate antidiuretic hormone secretion have been reported in patients with MS. Finally, some sleep disorders, particularly hypersomnia or narcolepsy, could be related to hypothalamic lesions, through the fall in hypocretin-1 in the cerebrospinal fluid. Hypocretin-1 is a neuropeptide that is secreted by some hypothalamic cells. It plays a role in the sleep-awake rhythm. We report one patient with narcolepsy and cataplexy before the first symptoms of MS appeared. Hypothalamic signs are rare in MS. However, several series of autopsies have shown a high frequency of demyelinating lesions in the hypothalamic area. Among these lesions, the proportion of active lesions seems elevated. Yet only few of them have a clinical or biological translation such as thermoregulation dysfunction, sleep disorders or natremia abnormalities. Thus, it seems unlikely that inflammatory hypothalamic lesions alone, even when bilateral, could be the explanation of these signs. A sufficient number of inflammatory demyelinating lesions, which we can observe in patients with a long history of MS and an already severe disability, is probably necessary to develop such a rare symptomatology. Hypothalamic signs might be a factor of poor prognosis for the disease course and progression of the disability.

Recent Use of Oral Contraceptives and the Risk of Multiple Sclerosis

Exogenous estrogens affect the onset and clinical course of experimental allergic encephalomyelitis. Oral contraceptives, a frequent source of exogenous estrogens in humans, could have a role in the development of multiple sclerosis (MS). To examine whether recent oral contraceptive use and pregnancy history are associated with the risk of MS. A case-control study nested in the General Practice Research Database. This database contains prospective health information (drug prescriptions and clinical diagnoses) on more than 3 million Britons who are enrolled with selected general practitioners. One hundred six female incident cases of MS, younger than 50 years, with at least 3 years of continuous recording in the General Practice Research Database before the date of first symptoms (index date), identified between January 1, 1993, and December 31, 2000, and 1001 controls matched on age, practice, and date of joining the practice. Main Outcome Measure Incidence of first symptoms of MS, confirmed through medical records. The incidence of MS was 40% lower (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) in oral contraceptive users compared with nonusers during the previous 3 years. The risk of MS increased in the 6 months after pregnancy (odds ratio, 2.9, 95% confidence interval, 1.2-6.6), but it was not otherwise related to parity. The hormonal changes that occur during oral contraceptive use and pregnancy may be associated with a short-term reduction in the risk of MS, and the postpartum period may be associated with a short-term increase in the risk of MS.

Incidence of Seizures in Patients With Multiple Sclerosis: A Population-Based Study

Objective To determine whether multiple sclerosis (MS) is associated with occurrence of seizure activity. Patients and Methods The medical records of all incidence patients with MS in Olmsted County, Minnesota, from 1935 to 1991 were reviewed. The incidence of seizures was calculated by using 3 methods: including only seizures that occurred after definite diagnosis of MS, including all seizures occurring after onset of the first symptoms of MS, and including any seizures regardless of the time of onset relative to MS. These incidences were age-adjusted to the 1970 US population and then compared with the age- adjusted incidence rate of seizures in the general population of Olmsted County. Results The age-adjusted incidence of seizures among MS patients was not significantly higher than the age-adjusted incidence of seizures in the general population of Olmsted County. The age-adjusted incidence of first unprovoked seizures in Rochester, Minn, was 61 per 100,000 person-years. In patients with the definite diagnosis of MS, the age-adjusted incidence was calculated at 61 per 100,000 person-years (95% confidence interval [CI], 7-114). In the group with seizures after onset of symptoms, the age-adjusted incidence rate was 80 per 100,000 person-years (95% CI, 24-135). In the group with seizures at any time in their life, the ageadjusted incidence rate was 82 per 100,000 person-years (95% CI, 41-158). Conclusion The present study does not suggest that occurrence of seizures is more common in MS patients than in the general population. To determine whether multiple sclerosis (MS) is associated with occurrence of seizure activity. The medical records of all incidence patients with MS in Olmsted County, Minnesota, from 1935 to 1991 were reviewed. The incidence of seizures was calculated by using 3 methods: including only seizures that occurred after definite diagnosis of MS, including all seizures occurring after onset of the first symptoms of MS, and including any seizures regardless of the time of onset relative to MS. These incidences were age-adjusted to the 1970 US population and then compared with the age- adjusted incidence rate of seizures in the general population of Olmsted County. The age-adjusted incidence of seizures among MS patients was not significantly higher than the age-adjusted incidence of seizures in the general population of Olmsted County. The age-adjusted incidence of first unprovoked seizures in Rochester, Minn, was 61 per 100,000 person-years. In patients with the definite diagnosis of MS, the age-adjusted incidence was calculated at 61 per 100,000 person-years (95% confidence interval [CI], 7-114). In the group with seizures after onset of symptoms, the age-adjusted incidence rate was 80 per 100,000 person-years (95% CI, 24-135). In the group with seizures at any time in their life, the ageadjusted incidence rate was 82 per 100,000 person-years (95% CI, 41-158). The present study does not suggest that occurrence of seizures is more common in MS patients than in the general population.

Incidence of Seizures in Patients With Multiple Sclerosis: A Population-Based Study

To determine whether multiple sclerosis (MS) is associated with occurrence of seizure activity. The medical records of all incidence patients with MS in Olmsted County, Minnesota, from 1935 to 1991 were reviewed. The incidence of seizures was calculated by using 3 methods: including only seizures that occurred after definite diagnosis of MS, including all seizures occurring after onset of the first symptoms of MS, and including any seizures regardless of the time of onset relative to MS. These incidences were age-adjusted to the 1970 US population and then compared with the age-adjusted incidence rate of seizures in the general population of Olmsted County. The age-adjusted incidence of seizures among MS patients was not significantly higher than the age-adjusted incidence of seizures in the general population of Olmsted County. The age-adjusted incidence of first unprovoked seizures in Rochester, Minn, was 61 per 100,000 person-years. In patients with the definite diagnosis of MS, the age-adjusted Incidence was calculated at 61 per 100,000 person-years (95% confidence interval [CI], 7-114). In the group with seizures after onset of symptoms, the age-adjusted incidence rate was 80 per 100,000 person-years (95% CI, 24-135). In the group with seizures at any time in their life, the age-adjusted incidence rate was 82 per 100,000 person-years (95% CI, 41-158). The present study does not suggest that occurrence of seizures is more common in MS patients than in the general population.

Paroxysmal symptoms as the first manifestations of multiple sclerosis.

Paroxysmal symptoms are described in 14 patients with undoubted or suspected multiple sclerosis (MS). In seven of the patients the paroxysms were the first symptom of the disease, although only one has developed definite MS so far. The clinical features have been compared with 153 patients previously reported in the literature which has been reviewed, with special reference to 36 in whom paroxysmal symptoms were the initial manifestations of MS. Attention has been focused on paroxysmal symptoms of brain stem and spinal cord origin of the following types: paroxysmal dysarthria and ataxia, diplopia, tonic seizures, paroxysmal akinesia, paroxysmal sensory disturbances and pains. Examples of each type have been reported as the first symptoms of MS with remissions ranging from less than one to 21 years before other manifestations of MS have developed.