Sibling disability risk at onset and during disease progression in familial multiple sclerosis

2011 ◽  
Vol 17 (9) ◽  
pp. 1060-1066 ◽  
Author(s):  
Anne Wellek ◽  
Catharina Korsukewitz ◽  
Jan P Bach ◽  
Sabine Schock ◽  
Christian Eienbröker ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Pair Correlation ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Event ◽  
Sibling Pair ◽  
Progression Rate ◽  
Continuous Variables ◽  
Sibling Pairs

Background: The objective of this study was to address the differences in onset and disease progression between familial and sporadic multiple sclerosis (MS) and the association within sibling pairs. Methods: Ninety-eight siblings and their controls were included from a database of 763 sporadic MS-patients, randomly pair-matched for age, gender, clinical course, disease duration and treatment. Sixty-eight available siblings completed a prospective six-year follow-up. Outcome parameters included baseline Expanded Disability Status Scale (EDSS), age at onset, mono- or multifocal onset, disease progression and conversion to secondary progression of initially relapsing–remitting MS. For statistical analyses Wilcoxon’s signed-rank statistics for categorical differences, t-statistics for continuous variables, McNemar’s test for relative frequencies of categories, intra-class correlations for within sibling-pair associations, or Kaplan–Meier analysis for survival analyses were used; all two-sided at the 5% level. Results: Disease onset was slightly earlier (29.01 vs. 29.44 years, p = 0.0492) and multifocal onset significantly more often ( p = 0.0052) in familial than in sporadic MS. Notably, a substantial within sibling-pair correlation for disease progression (rho = 0.40; p = 0.0062) as well as a higher risk for siblings than for controls to convert into secondary progression (0.545 vs. 0.227; p = 0.018) could be observed. Conclusions: Familial MS differs from sporadic cases with respect to age at onset, multifocal involvement as first clinical event, and conversion into secondary progression. The progression rate of one out of two affected siblings may act as a predictor for the other sib.

scholarly journals Multiple Sclerosis in Malaysia: Demographics, Clinical Features, and Neuroimaging Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
S. Viswanathan ◽  
N. Rose ◽  
A. Masita ◽  
J. S. Dhaliwal ◽  
S. D. Puvanarajah ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Demyelinating Disease ◽  
Age At Onset ◽  
Positive Family History ◽  
Disease Onset ◽  
Demyelinating Diseases ◽  
Lesion Length ◽  
Relapsing Remitting ◽  
Spectrum Disorders

Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country.Objectives. To investigate the spectrum of multiple sclerosis in Malaysia.Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia.Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald’s criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders.Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here.

Characteristics of multiple sclerosis in aboriginals living in British Columbia, Canada

2012 ◽  
Vol 18 (9) ◽  
pp. 1239-1243 ◽  
Author(s):  
Jameelah Saeedi ◽  
Peter Rieckmann ◽  
Irene Yee ◽  
Helen Tremlett ◽  
Keyword(s):  
Multiple Sclerosis ◽  
British Columbia ◽  
Clinical Characteristics ◽  
Age At Onset ◽  
Disease Onset ◽  
Patient Characteristics ◽  
Onset Date ◽  
Disease Course ◽  
Chi Squared ◽  
Student’S T

Objectives: The objectives of this study were to identify and describe the demographic and clinical characteristics of multiple sclerosis (MS) in aboriginals in British Columbia (BC), Canada and compare these findings with non-aboriginal MS patients. Methods: This retrospective chart and database review accessed patient information from the linked BC-wide MS clinical and genetics databases. Data gathered included: demographics (age, sex and ethnicity); clinical characteristics (MS onset date, disease course and disability scores (Expanded Disability Status Scale [EDSS]). Aboriginals were identified via the database linkage augmented by physician and nurse recall. Two non-aboriginal comparator groups with definite MS were selected. Group one included all definite MS patients in the BC MS database, and group two comprised MS patients matched by sex, age at onset and initial disease course. Patient characteristics were compared using the Student’s t-test, chi-squared test, and Kaplan–Meier survival analysis was used to examine disease progression (time to sustained and confirmed EDSS 6) Results: We identified 26 aboriginals with MS, of which 19/26 (73%) were female, 23/26 (89%) had relapsing-onset MS and a mean onset age of 31.1 years. There were no significant differences between the MS aboriginals and the non-matched ( n = 5708) comparator group with respect to age, sex or disease course ( p > 0.1), However, aboriginals progressed more rapidly to EDSS 6 from disease onset ( p < 0.001) when compared with the matched and unmatched comparator groups. Conclusion: We identified a small, but important cohort of aboriginals with MS; being the largest identified to date. There was evidence of more rapid MS progression in aboriginals compared with non-aboriginals.

scholarly journals Predicting Alzheimer’s disease progression trajectory and clinical subtypes using machine learning

2019 ◽  
Author(s):  
Vipul K. Satone ◽  
Rachneet Kaur ◽  
Anant Dadu ◽  
Hampton Leonard ◽  
Hirotaka Iwaki ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Disease Onset ◽  
Machine Learning Techniques ◽  
Progression Rate ◽  
Early Stages ◽  
Age Related ◽  
Learning Techniques

AbstractBackgroundAlzheimer’s disease (AD) is a common, age-related, neurodegenerative disease that impairs a person’s ability to perform day-to-day activities. Diagnosing AD is challenging, especially in the early stages. Many patients still go undiagnosed, partly due to the complex heterogeneity in disease progression. This highlights a need for early prediction of the disease course to assist its treatment and tailor therapy options to the disease progression rate. Recent developments in machine learning techniques provide the potential to not only predict disease progression and trajectory of AD but also to classify the disease into different etiological subtypes.Methods and findingsThe work shown here clusters participants in distinct and multifaceted progression subgroups of AD and discusses an approach to predict the progression rate from baseline diagnosis. We observed that the myriad of clinically reported symptoms summarized in the proposed AD progression space corresponds directly with memory and cognitive measures, which are routinely used to monitor disease onset and progression. Our analysis demonstrated accurate prediction of disease progression after four years from the first 12 months of post-diagnosis clinical data (Area Under the Curve of 0.96 (95% confidence interval (CI), 0.92-1.0), 0.81 (95% CI, 0.74-0.88) and 0.98 (95% CI, 0.96-1.0) for slow, moderate and fast progression rate patients respectively). Further, we explored the long short-term memory (LSTM) neural networks to predict the trajectory of an individual patient’s progression.ConclusionThe machine learning techniques presented in this study may assist providers in identifying different progression rates and trajectories in the early stages of the disease, hence allowing for more efficient and personalized healthcare deliveries. With additional information about the progression rate of AD at hand, providers may further individualize the treatment plans. The predictive tests discussed in this study not only allow for early AD diagnosis but also facilitate the characterization of distinct AD subtypes relating to trajectories of disease progression. These findings are a crucial step forward for early disease detection. These models can be used to design improved clinical trials for AD research.

Age at onset as a determinant of presenting phenotype and initial relapse recovery in multiple sclerosis

2011 ◽  
Vol 18 (1) ◽  
pp. 45-54 ◽  
Author(s):  
M Cossburn ◽  
G Ingram ◽  
C Hirst ◽  
Y Ben-Shlomo ◽  
TP Pickersgill ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Age At Onset ◽  
Disease Onset ◽  
Complete Recovery ◽  
Population Based ◽  
Disease Course ◽  
Index Event ◽  
Relapsing Remitting ◽  
Age Dependent

Background: Age at onset modifies prognosis in multiple sclerosis (MS) and may also exert an effect on the characteristics of disease ignition. Understanding how age influences presentation informs disease management and may allow differentiation of distinct clinical sub-groups. Objectives: To determine the nature of age-specific presentations of relapsing–remitting MS (RRMS) with respect to onset symptoms, gender ratios and index event outcomes. Methods: In a prospective, population-based sample of 1424 patients in South-East Wales we examined associations between age at onset, clinical features and outcome of the onset event, making specific comparisons between paediatric, adolescent and late-onset MS. Results: Age at onset varied significantly between sexes (Male 31.2, Female 29.3, p = 0.002), 0.7% had paediatric onset, 2.7% adolescent onset and 2.8% late-onset MS (>50 years). Optic neuritis was common in younger patients and declined after age 30. Lower limb motor, facial sensory, sexual and sphincteric symptoms rose with age independent of sex and disease course. F:M ratios were highest <16 years of age and declined with increasing age, with a male excess in those over 50. Probability of complete recovery from index event declined with age from 87.4% in the youngest group to 68% in the eldest ( p = 0.009). Conclusions: Age at disease onset in RRMS exerts a significant effect on gender ratios and presenting phenotype, and allows identification of specific clinical sub-groups. In addition, ability to recover from initial relapse declines with age, suggesting accumulation of disability in MS is an age-dependent response to relapse.

Effects of Age and Disease Duration on Excess Mortality in Patients With Multiple Sclerosis From a French Nationwide Cohort

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012224
Author(s):  
Fabien ROLLOT ◽  
Mathieu Fauvernier ◽  
Zoe Uhry ◽  
Sandra Vukusic ◽  
Nadine Bossard ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Excess Mortality ◽  
Disease Duration ◽  
Age At Onset ◽  
Disease Onset ◽  
Death Rates ◽  
Excess Death ◽  
Clinical Onset ◽  
Lost To Follow Up ◽  
The Impact

ObjectiveTo determine the effects of current age and disease duration on excess mortality in multiple sclerosis, we described the dynamics of excess deaths rates over these two time scales and studied the impact of age at multiple sclerosis clinical onset on these dynamics, separately in each initial phenotype.MethodsWe used data from 18 French multiple sclerosis expert centers participating in the Observatoire Français de la Sclérose en Plaques. Patients with multiple sclerosis living in metropolitan France and having a clinical onset between 1960 and 2014 were included. Vital status was updated on January 1st, 2016. For each multiple sclerosis phenotype separately (relapsing onset (R-MS) or primary progressive (PPMS)), we used an innovative statistical method to model the logarithm of excess death rates by a multidimensional penalized spline of age and disease duration.ResultsAmong 37524 patients (71% women, mean age at multiple sclerosis onset ± standard deviation 33.0 ± 10.6 years), 2883 (7.7%) deaths were observed and 7.8% of patients were lost-to-follow-up. For R-MS patients, there was no excess mortality during the first 10 years after disease onset; afterwards, whatever age at onset, excess death rates increased with current age. From current age 70, the excess death rates values converged and became identical whatever the age at disease onset, which means that disease duration had no more impact. Excess death rates were higher in men with an excess hazard ratio of 1.46 (95% confidence interval 1.25-1.70). In contrast, in PPMS patients, excess death rates rapidly increased from disease onset, and were associated with age at onset, but not with sex.ConclusionsIn R-MS, current age has a stronger impact on multiple sclerosis mortality than disease duration while their respective effects are not so clear in PPMS.

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.

Causes of delayed diagnosis of multiple sclerosis in egypt

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
A A Tohamy ◽  
M S Swelam ◽  
D M Abdelgawad ◽  
H A Aref
Keyword(s):  
Multiple Sclerosis ◽  
Age At Onset ◽  
Disease Onset ◽  
Diagnostic Delay ◽  
Delayed Diagnosis ◽  
P Value ◽  
Common Source ◽  
University Hospitals ◽  
Phone Calls ◽  
Diagnostic Delays

Abstract © 2018 Institute of Psychiatry, Ain Shams University Copyright r 2018 Institute of Psychiatry, Ain Shams University. Unauthorized reproduction of this article is prohibited. Background MS is an inflammatory and neurodegenerative disease. Early inflammatory activity might have a profound impact on the risk of developing early disability, and might be a risk factor for early transition into the progressive phase of the illness. However, there are a number of barriers implementing early MS diagnosis and treatment as the patients may delay consulting a physician about their neurological symptoms or may be reluctant to start DMT. Objective The aim of this study is to highlight the causes of delayed diagnosis of multiple sclerosis in Egypt to shorten the time of diagnosis and improve the prognosis for patients with MS. Patients and Methods Retrospective descriptive study .500 Patients coming to multiple sclerosis unit at Ain Shams University hospitals with delayed diagnosis of MS for more than 2 years had been screened. A questionnaire could be applied on 320 patients out of 500. Contacting (direct and via phone calls) the patients for evaluating the causes of delayed diagnosis of MS was done. Results In this study we found number of significant factors adversely affected a timely diagnosis including the age at onset finding that those younger at onset of MS (vs. older) experienced diagnostic delays (P-value = 0.005) and denial of symptoms which was a leading cause for delayed time to first doctor consultation and delayed diagnosis of MS (P-value =0.009). Also there was a correlation between types of MS and delayed diagnosis as we found that PPMS versus RRMS had delayed diagnosis for more than 2 years. Meanwhile, sensory symptoms at onset of the disease were associated with longer diagnostic delay. Although the first specialties the patients visit were ophthalmology and orthopedic services, that the most common Source of referral to a neurologist was suggestion by family and media. Conclusion multiple causes significantly affect time to diagnosis of MS including age at onset of the disease, denial of symptoms sensorial symptoms at the disease onset and referral delay from other specialties.

Association of age at onset and first symptoms with disease progression in patients with metachromatic leukodystrophy

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011047 ◽  
Author(s):  
Christiane Kehrer ◽  
Saskia Elgün ◽  
Christa Raabe ◽  
Judith Böhringer ◽  
Stefanie Beck-Wödl ◽  
...  
Keyword(s):  
Disease Progression ◽  
Metachromatic Leukodystrophy ◽  
Age At Onset ◽  
Disease Onset ◽  
Tube Feeding ◽  
Motor Symptoms ◽  
Cognitive Symptoms ◽  
Adult Onset ◽  
Clinical Genetic ◽  
Language Functions

Objective:To compare disease progression between different onset forms of Metachromatic Leukodystrophy (MLD) and to investigate the influence of the type of first symptoms on the natural course and dynamic of disease progression.Methods:Clinical, genetic and biochemical parameters were analyzed within a nationwide study of patients with late-infantile (LI, onset ≤ 2.5 years), early-juvenile (EJ, onset 2.6 - < 6 years), late-juvenile (LJ, onset 6 – < 16 years), and adult (onset ≥ 16 years) forms of MLD. First symptoms were categorized as motor symptoms only, cognitive symptoms only, or both.. Standardized clinical endpoints included loss of motor and language functions, as well as dysphagia/tube feeding.Results:97 Patients with MLD were enrolled. Patients with LI (n=35) and EJ (n=18) MLD exhibited similarly rapid disease progression, all starting with motor symptoms (with or without additional cognitive symptoms). In LJ (n=38) and adult-onset (n=6) patients, the course of the disease was as rapid as in the early-onset forms, when motor symptoms were present at disease onset, while patients with only cognitive symptoms at disease onset exhibited significantly milder disease progression, independent of their age at onset. A certain genotype-phenotype correlation was observed.Conclusions:In addition to age at onset, the type of first symptoms predicts the rate of disease progression in MLD. These findings are important for counselling and therapy.Classification of Evidence:This study provides Class II evidence that in patients with MLD, age at onset and the type of first symptoms predict the rate of disease progression.

scholarly journals Side of Limb-Onset Predicts Laterality of Gray Matter Loss in Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Qiuli Zhang ◽  
Cuiping Mao ◽  
Jiaoting Jin ◽  
Chen Niu ◽  
Lijun Bai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Disease Progression ◽  
Gray Matter ◽  
Brain Atrophy ◽  
Disease Onset ◽  
Progression Rate ◽  
Imaging Evaluation ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Limb Onset

Conflicting findings have been reported regarding the lateralized brain abnormality in patients with amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the probable lateralization of gray matter (GM) atrophy in ALS patients. We focused on the relationship between the asymmetry in decreased GM volume and the side of disease onset in patients with limb-onset. Structural imaging evaluation of normalized atrophy (SIENAX) and voxel-based morphometry (VBM) were used to assess differences in global and local brain regions in patients with heterogeneous body onset and subgroups with different side of limb-onset. We found global brain atrophy and GM losses in the frontal and parietal areas in each patient group as well as left predominant GM losses in the total cohort. The intriguing findings in subgroup analyses demonstrated that the motor cortex in the contralateral hemisphere of the initially involved limb was most affected. We also found that regional brain atrophy was related to disease progression rate. Our observations suggested that side of limb-onset can predict laterality of GM loss in ALS patients and disease progression correlates with the extent of cortical abnormality.

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