APOE genotypes and disease severity in multiple sclerosis

2002 ◽  
Vol 8 (2) ◽  
pp. 98-103 ◽  
Author(s):  
T Masterman ◽  
Z Zhang ◽  
D Hellgren ◽  
H Salter ◽  
M Anvret ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Onset ◽  
Membrane Repair ◽  
Genome Wide ◽  
Disability Status ◽  
Unfavorable Clinical Outcome ◽  
Edss Score ◽  
E4 Allele ◽  
Apoe Genotypes ◽  
Chromosome 19Q13

Apolipoprotein E (apoE) is involved in the transport of lipids necessary for membrane repair and is encoded by a gene on chromosome 19q13, a region positive for linkage in two multiple sclerosis (MS) genome-wide screens. The APOE e4 allele confers susceptibility to both familial and sporadic Alzheimer’s disease (AD). Carriage of e4 is associated with defective dendritic remodeling in AD, and with unfavorable clinical outcome in head trauma and cerebrovascular disease. According to the results of previous studies, APOE e4 does not increase the risk of developing MS, but it may influence disease progression and ultimate disability. From a total cohort of over 900 MS patients, we compared APOE e2-4 genotypes in, roughly, the cohort’s least disabled and most disabled septiles. ‘Benign MS’ (n=124) was defined as an Expanded Disability Status Scale (EDSS) score of 3.0 or less, despite at least 10 years of disease duration, and ‘severe MS’ (n=140) as the attainment of an EDSS score of 6.0 within 8 years of disease onset. We found no significant differences in genotype or phenotype frequencies between the benign-MS and severe-MS septiles; however, the risk conferred by e4 rose progressively upon comparison of carriage rates in more narrowly defined anti-podal quantiles.

Apoliprotein E and multiple sclerosis: impact of the epsilon-4 allele on susceptibility, clinical type and progression rate

2000 ◽  
Vol 6 (4) ◽  
pp. 226-230 ◽  
Author(s):  
Peter Hùgh ◽  
Anette Oturai ◽  
Karen Schreiber ◽  
Morten Blinkenberg ◽  
Ole Steen Jùrgensen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Onset ◽  
Apoe Genotype ◽  
Progression Rate ◽  
Cross Sectional ◽  
Homogeneous Population ◽  
Allele Distribution ◽  
Increased Risk ◽  
E4 Allele ◽  
Apoe Genotypes

The purpose of this study was to investigate the relation between APOE genotype and Multiple Sclerosis (MS) in a genetically homogeneous population. We examined 240 patients consulting the MS-clinic during a period of 3 years (1996-1999). The mean age of the patients was 41.7 years (range 19-80 Y, SD 10.0 Y). As a measure of the progression rate (PR) the last registered Expanded Disability Status Scale (EDSS) score was divided by the time span (years) from disease onset until the latest assessment. The APOE genotype was determined from saliva and/or blood samples using PCR-techniques. The prevalence of different APOE genotypes was compared with the allele-distribution in a population of 361 persons from a Danish cross-sectional population study. The frequency of APOE-e4/e4 homozygotes was significantly higher in the MS-group as compared to controls (P<0.05, odds ratio: 2.3), whereas the frequency distribution of other genotypes did not differ significantly. The rate of progression was significantly faster in the APOE-e4/e4 homozygotes compared to other genotypes in the MS group (P<0.05). This study suggests that the APOE-e4/e4 homozygotes have an increased risk of developing MS. MS patients with the APOE-e4/e4 allele may also have an increased rate of disease progression.

scholarly journals A Pilot Study of 24-h Motor Activity Patterns in Multiple Sclerosis: Pre-Planned Follow-Up at 2 Years

2021 ◽  
Vol 3 (3) ◽  
pp. 366-376
Author(s):  
Lorenzo Tonetti ◽  
Federico Camilli ◽  
Sara Giovagnoli ◽  
Vincenzo Natale ◽  
Alessandra Lugaresi
Keyword(s):  
Multiple Sclerosis ◽  
Motor Activity ◽  
Activity Pattern ◽  
Activity Patterns ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Edss Score ◽  
Activity Prognosis

Early multiple sclerosis (MS) predictive markers of disease activity/prognosis have been proposed but are not universally accepted. Aim of this pilot prospective study is to verify whether a peculiar hyperactivity, observed at baseline (T0) in early relapsing-remitting (RR) MS patients, could represent a further prognostic marker. Here we report results collected at T0 and at a 24-month follow-up (T1). Eighteen RRMS patients (11 females, median Expanded Disability Status Scale-EDSS score 1.25, range EDSS score 0–2) were monitored at T0 (mean age 32.33 ± 7.51) and T1 (median EDSS score 1.5, range EDSS score 0–2.5). Patients were grouped into two groups: responders (R, 14 patients) and non-responders (NR, 4 patients) to treatment at T1. Each patient wore an actigraph for one week to record the 24-h motor activity pattern. At T0, NR presented significantly lower motor activity than R between around 9:00 and 13:00. At T1, NR were characterized by significantly lower motor activity than R between around 12:00 and 17:00. Overall, these data suggest that through the 24-h motor activity pattern, we can fairly segregate at T0 patients who will show a therapeutic failure, possibly related to a more active disease, at T1. These patients are characterized by a reduced morning level of motor activation. Further studies on larger populations are needed to confirm these preliminary findings.

scholarly journals Reduced peripheral blood regulatory B cell levels are not associated with the Expanded Disability Status Scale score in multiple sclerosis

2018 ◽  
Vol 46 (9) ◽  
pp. 3970-3978 ◽  
Author(s):  
Shujun Guo ◽  
Qingqing Chen ◽  
Xiaoli Liang ◽  
Mimi Mu ◽  
Jing He ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Serum Levels ◽  
Memory B Cells ◽  
Healthy Controls ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Edss Score

Objective To investigate levels of regulatory B (Breg) cells, plasma cells, and memory B cells in the peripheral blood, and interleukin (IL)-10 in the serum of multiple sclerosis (MS) patients, and to determine the correlation between Breg cell levels and the Expanded Disability Status Scale (EDSS) score. Methods Levels of Breg cells, plasma cells, and memory B cells in the peripheral blood of 12 MS patients were measured using flow cytometry. IL-10 serum levels were measured by enzyme-linked immunosorbent assay. The correlation between Breg cell levels and MS EDSS score was measured using Pearson’s correlation coefficient. Results Compared with healthy controls, MS patients had decreased levels of CD19+CD24hiCD38hi Breg cells in their peripheral blood and reduced serum levels of IL-10; however, the ratios of CD19+CD27hiCD38hi plasma cells and CD19+CD27+CD24hi memory B cells to total B cells did not differ significantly between healthy controls and MS patients. CD19+CD24hiCD38hi Breg cell levels in the peripheral blood of MS patients were not significantly correlated with MS EDSS score. Conclusion Peripheral blood CD19+CD24hiCD38hi Breg cell levels and serum IL-10 levels were reduced in MS patients compared with controls, but Breg cell levels were not correlated with MS EDSS score.

scholarly journals Brain Function Assessment of Patients with Multiple Sclerosis in the Expanded Disability Status Scale

2020 ◽  
Vol 22 (1) ◽  
pp. 31-35
Author(s):  
Ricardo N. Alonso ◽  
Maria B. Eizaguirre ◽  
Berenice Silva ◽  
Maria C. Pita ◽  
Cecilia Yastremiz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Function ◽  
Cognitive Assessment ◽  
Functional System ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Before And After ◽  
Survey Results ◽  
Edss Score ◽  
The Brain

Abstract Background: There is no consensus regarding assessment of the brain function functional system (FS) of the Expanded Disability Status Scale (EDSS) in patients with multiple sclerosis (MS). We sought to describe brain function FS assessment criteria used by Argentinian neurologists and, based on the results, propose redefined brain function FS criteria. Methods: A structured survey was conducted of 113 Argentinian neurologists. Considering the survey results, we decided to redefine the brain function FS scoring using the Brief International Cognitive Assessment for MS (BICAMS) battery. For 120 adult patients with MS we calculated the EDSS score without brain function FS (basal EDSS) and compared it with the EDSS score after adding the modified brain function FS (modified EDSS). Results: Of the 93 neurologists analyzed, 14% reported that they did not assess brain function FS, 35% reported that they assessed it through a nonstructured interview, and the remainder used other tools. Significant differences were found in EDSS scores before and after the inclusion of BICAMS (P &lt; .001). Redefining the brain function FS, 15% of patients modified their basal EDSS score, as did 20% of those with a score of 4.0 or less. Conclusions: The survey results show the importance of unifying the brain function FS scoring criteria in calculating the EDSS score. While allowing more consistent brain function FS scoring, including the modified brain function FS led to a change in EDSS score in many patients, particularly in the lower range of EDSS scores. Considering the relevance of the EDSS for monitoring patients with MS and for decision making, it is imperative to further validate the modified brain function FS scoring.

Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review

2001 ◽  
Vol 7 (5) ◽  
pp. 345-347 ◽  
Author(s):  
Geeta Ramsaransing ◽  
Natasha Maurits ◽  
Cornelis Zwanikken ◽  
Jacques De Keyser
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Disease Onset ◽  
Clinical Factors ◽  
Presentation Duration ◽  
Disease Modifying Therapies ◽  
Disability Status ◽  
Adequate Quality ◽  
First Remission ◽  
Benign Course

Background: There is growing consensus that neurologists should consider disease-modifying therapies early in multiple sclerosis (MS). However, there is a subgroup with a natural benign course, in which treatment could be postponed. We sought to determine the frequency of benign MS and early clinical factors that may predict a benign course. Methods: We performed a systematic review of the existing literature on benign MS, which was defined as minimal or no disability equivalent to a score on the Expanded Disability Status Scale (EDSS) 43.0 at least 10 years after disease onset. Results: Only a small number of studies of adequate quality was available. In total there were nine published studies representing 2204 patients. The estimated frequency of benign MS was 26.7%. Onset with optic neuritis, onset before the age of 40 years, absence of pyramidal signs at presentation, duration of first remission more than 1 year, and only one exacerbation in the first 5 years after onset of MS, were associated with a benign course. Conclusions: From the existing literature a set of unrelated clinical characteristics emerged that was associated with a benign course of MS. However, there is a need for prospective studies to define more precisely clinical and paraclinical predictors of benign MS.

No association of apolipoprotein E ε4 genotype with faster progression or less recovery of relapses in a Spanish cohort of multiple sclerosis

2006 ◽  
Vol 12 (1) ◽  
pp. 13-18 ◽  
Author(s):  
M J Sedano ◽  
P Calmarza ◽  
L Perez ◽  
J M Trejo
Keyword(s):  
Multiple Sclerosis ◽  
Apolipoprotein E ◽  
Age Of Onset ◽  
Clinical Recovery ◽  
The North ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Apoe Genotypes ◽  
Relationship Of ◽  
North Of Spain

Background Recent data have suggested a faster deterioration of multiple sclerosis (MS) patients who harbour the o4 allele of the apolipoprotein E (APOE) gene. We investigate the relationship of APOE genotypes with disease severity and clinical recovery of relapses in a MS population of the north of Spain. Methods One hundred and thirty-three patients with clinically defined MS were studied. Disease course (relapsing versus progressive), age of onset, duration of the disease and disability measured by the Expanded Disability Status Scale (EDSS) were recorded. Worsening was measured by the Progression Index (PI) and by EDSS 4 and 6 latencies. In 79 patients with relapsing-remitting (RR) MS the degree of clinical recovery of relapses (total versus partial) was assessed. Results The frequency of the APOE o4 allele in our patients was similar to that found in other southern European populations. APOE o4 patients did not have a faster progression as assessed by PI and EDSS 4 and 6 latencies. Among 79 patients with RRMS there were no significant differences in the degree of recovery of relapses. Conclusions In this MS population, APOE o4 polymorphism is not associated with a more severe clinical course and does not appear to influence recovery of exacerbations.

Predicting risk of secondary progression in multiple sclerosis: A nomogram

2018 ◽  
Vol 25 (8) ◽  
pp. 1102-1112 ◽  
Author(s):  
Ali Manouchehrinia ◽  
Feng Zhu ◽  
Daniela Piani-Meier ◽  
Markus Lange ◽  
Diego G Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Onset ◽  
Predictive Ability ◽  
Progressive Multiple Sclerosis ◽  
Patient Counselling ◽  
Derivation Cohort ◽  
Efficacious Treatment ◽  
Disability Status ◽  
Using Data ◽  
Worse Prognosis

Objectives: We aimed at designing a nomogram, a prediction tool, to predict the individual’s risk of conversion to secondary progressive multiple sclerosis (SPMS) at the time of multiple sclerosis (MS) onset. Methods: One derivation and three validation cohorts were established. The derivation cohort included 8825 relapsing-onset MS patients in Sweden. A nomogram was built based on a survival model with the best statistical fit and prediction accuracy. The nomogram was validated using data from 3967 patients in the British Columbia cohort, 176 patients in the ACROSS and 2355 patients in FREEDOMS/FREEDOMS II extension studies. Results: Sex, calendar year of birth, first-recorded Expanded Disability Status Scale (EDSS) score, age at the first EDSS and age at disease onset showed significant predictive ability to estimate the risk of SPMS conversion at 10, 15 and 20 years. The nomogram reached 84% (95% confidence intervals (CIs): 83–85) internal and 77% (95% CI: 76–78), 77% (95% CI: 70–85) and 87% (95% CI: 84–89) external accuracy. Conclusions: The SPMS nomogram represents a much-needed complementary tool designed to assist in decision-making and patient counselling in the early phase of MS. The SPMS nomogram may improve outcomes by prompting timely and more efficacious treatment for those with a worse prognosis.

Epilepsy in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 89 (24) ◽  
pp. 2462-2468 ◽  
Author(s):  
Joachim Burman ◽  
Johan Zelano
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Features ◽  
Cumulative Incidence ◽  
Progressive Disease ◽  
Disease Duration ◽  
Population Based ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Edss Score

Objective:To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.Methods:All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.Results:The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).Conclusions:Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

scholarly journals Some Aspects of Balance Disorder in Patients with Multiple Sclerosis

2008 ◽  
Vol 8 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Adnan Burina ◽  
Osman Sinanović ◽  
Dževdet Smajlović ◽  
Mirjana Vidović ◽  
Fuad Brkić
Keyword(s):  
Multiple Sclerosis ◽  
Auditory Evoked Potentials ◽  
Pathological Finding ◽  
Initial Symptom ◽  
Disability Status ◽  
Balance Disorder ◽  
Edss Score ◽  
Interpeak Latency ◽  
Mri Changes ◽  
The Brain

The aim of this study was to analyze: frequency of balance disorder (vertigo and disequilibrium), frequency of abnormalities in auditory evoked potentials (AEP) and magnetic resonance imaging (MRI) changes of the brain in multiple sclerosis (MS) patients with balance disorder, relation of patients disability status to balance disorder and relation of the changes in MRI of the brainstem to AEP abnormalities. It was analyzed 60 patients with relapsing-remitting form of MS. Two groups of patients were made consecutively under Expanded Disability Status Scale score (EDSS): A (EDSS <4,5) and B (EDSS >5,0). The study was retrospective-prospective. After the neurological exam AEP and MRI of the brain have been done. Balance disorder has been verified as initial symptom in 29 (48,4%) and out of them disequilibrium experienced 24 (83,4%) patients. During the relapses balance disorder experienced 48 (80%) patients and in 37 (77,1%) it was disequilibrium. Among them 33 (68,7%) were with lower EDSS (<4,5) and 15 (31,3%) with higher EDSS score (>5). There is no correlation between disability status and vertigo which means that vertigo is not more frequent in more disabled patients and vice-versa. The AEP were pathological in 57 (95%) patients. Of all 29 patients with vertigo AEP were pathological in 28 (96,5%) while in 31 patients without vertigo pathological AEP were in 29 (93,5%) but it is not statistical significant. The most frequent characteristic of AEP changes were prolonged inter-peak latency III-V waves (48 patients or 80%). The plaque in brainstem visualized by MRI was found in 41 (71,8%) of patients (38 or 92,6% of them had pathological AEP and in three patients AEP were normal). In group of patients with pathological AEP, 38 (66,6%) of them had plaque in brainstem. In other three patients with normal AEP it was visualized plaque in brainstem. In the group of 29 patients with balance disorder, 20 (68,9%) had plaque in brainstem as well as 21 (67,7%) out of 31 patients without balance disorder had plaque in the brainstem. This difference is not statistical significant. It is concluded that the vertigo (including disequilibrium) is relatively often (48,4%) initial symptom of MS. Vertigo is not more frequent in patients with higher EDSS score and vice-versa. Pathological AEP are frequent neurophysiologic finding in both (95%) patients with (96,5%) and without (93,5%) vertigo. The most often pathological characteristic of AEP are prolonged interpeak latency of III-V waves (78,5%), as well as abnormalities of V and than IV wave. MS plaques in brainstem visualized by MRI technique are frequent in both groups of patients with and without pathological finding of the AEP.

Pregnancy in women with MS: Impact on long-term disability accrual in a nationwide Danish Cohort

2021 ◽  
pp. 135245852110577
Author(s):  
Johanna Balslev Andersen ◽  
Malthe Faurschou Wandall-Holm ◽  
Per Kragh Andersen ◽  
Finn Sellebjerg ◽  
Melinda Magyari
Keyword(s):  
Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Time Dependent ◽  
Disease Course ◽  
Expanded Disability Status Scale ◽  
Cox Models ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Edss Score

Background: Pregnancy is considered to influence the disease course in women with multiple sclerosis (MS). Objective: The aim of this study was to investigate the effect of pregnancy on long-term disability accrual in women with MS. Methods: The Danish Multiple Sclerosis Registry (DMSR) was used to identify women diagnosed with clinically isolated syndrome or relapsing-remitting MS. Cox models with pregnancy as a time-dependent exposure and propensity score (PS) models were used to evaluate time to reach confirmed Expanded Disability Status Scale (EDSS) score of 4 and 6. Results: A total of 425 women became parous and 840 remained nulliparous. When including pregnancy as a time-dependent exposure, a non-significant association with time to reach EDSS 4 (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.61–1.20) and EDSS 6 (HR 0.70, 95% CI 0.40–1.20) was found. Correspondingly, the PS model showed no association with pregnancy on time to reach EDSS 4 (HR 0.85, 95% CI 0.56–1.28). Conclusion: This study concludes that pregnancy does not affect long-term disability accumulation.

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