Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy

2014 ◽  
Vol 21 (5) ◽  
pp. 580-589 ◽  
Author(s):  
Massimiliano Calabrese ◽  
Alberto Gajofatto ◽  
Francesca Gobbin ◽  
Giulia Turri ◽  
Silvia Richelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Dysfunction ◽  
Progressive Disease ◽  
Late Onset ◽  
Disease Onset ◽  
Reference Population ◽  
Healthy Controls ◽  
Cognitively Normal ◽  
Midbrain Tegmentum ◽  
Symptoms And Signs

Objective: Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. Methods: Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. Results: Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40–58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as “The Hummingbird sign,” was observed in eight CI-MS and in three PSP patients. Discussion: Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs.

scholarly journals A logistic regression analysis of risk factors in ME/CFS pathogenesis

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Eliana M. Lacerda ◽  
Keith Geraghty ◽  
Caroline C. Kingdon ◽  
Luigi Palla ◽  
Luis Nacul
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Regression Analysis ◽  
Risk Factor ◽  
Family History ◽  
Disease Onset ◽  
Healthy Controls ◽  
Lower Income ◽  
Wide Range ◽  
History Of

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. Methods This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). Results A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). Conclusions Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.

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.

scholarly journals The epidemiology of multiple sclerosis in the entre Douro e Vouga region of northern Portugal: a multisource population-based study

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mariana Branco ◽  
Ivânia Alves ◽  
Ana Martins da Silva ◽  
Joaquim Pinheiro ◽  
Maria José Sá ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Primary Care Physicians ◽  
Western Europe ◽  
Disease Onset ◽  
Clinical Information ◽  
Reference Population ◽  
Population Based ◽  
Prevalence Studies ◽  
The North ◽  
Northern Portugal

Abstract Background The prevalence of Multiple Sclerosis (MS) has been increasing worldwide and the north–south gradient of prevalence may be disappearing in the Northern hemisphere. The few previous prevalence studies performed in Portugal have reported a lower prevalence than the average for Western Europe. The aim of this study is to estimate the prevalence of MS in the Entre Douro e Vouga region, in Northern Portugal. Methods Multiple overlapping sources were used to ascertain all cases from the reference population: records from hospitals in the region and neighbouring regions; diagnostic databases of primary care physicians; and applications for disability benefits. The prevalence date was set at 1 January 2014. The reference population was 274,859 inhabitants. Patients’ neurologists were contacted to retrieve clinical information and confirm the diagnosis based. Results A total of 177 patients were identified after eliminating duplicates from different sources. The female to male ratio was 1.9 and the mean age at disease onset was 33.5 (standard deviation: 10.3). Clinically isolated syndrome accounted for 9.0% of patients, relapsing remitting for 58.8%, secondary progressive for 20.3% and primary progressive for 11.8%. The prevalence was estimated in 64.4 patients per 100,000 (95% confidence interval: 54.9;73.9). Conclusions In this study we report a higher point prevalence of MS than had been previously described in Portugal, but still far from the higher values recently reported in other Southern European countries.

Smoking worsens the prognosis in multiple sclerosis

2008 ◽  
Vol 14 (8) ◽  
pp. 1031-1035 ◽  
Author(s):  
P Sundström ◽  
L Nyström
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Disease Duration ◽  
Cox Regression ◽  
Disease Onset ◽  
Cox Regression Analysis ◽  
Negative Effect ◽  
Never Smokers ◽  
Reported Data ◽  
Incident Cases

Objective To estimate the effect of smoking on the risk for progression in multiple sclerosis (MS). Methods Self-reported data were used on smoking habits in 122 incident cases with disability assessments made after a median of 6 years disease duration. Results Ever smokers were more likely to have progressive disease compared with never smokers ( P < 0.01). This was most pronounced in ever smokers with early smoking debut (≤15 years of age) for whom progressive disease was significantly more likely and occurred at an earlier age, compared with those with later smoking debut ( P < 0.01 for both) or never smokers ( P < 0.01 for both). Earlysmoking start also predisposed to a progressive disease from onset when compared with never smokers ( P = 0.012). A multivariate Cox regression analysis of sex, age at disease onset (above vs. under median) and smoking (ever vs. never) status showed that cases with late disease onset had three times higher risk and ever smokers had twice as high a risk for progression. Conclusion Past smoking is associated with a worsened prognosis in MS. The negative effect from smoking is most obvious in ever smokers with early smoking debut, which also affects MS phenotype significantly.

Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study

2017 ◽  
Vol 48 (3-4) ◽  
pp. 179-187 ◽  
Author(s):  
Francis Guillemin ◽  
Cédric Baumann ◽  
Jonathan Epstein ◽  
Philippe Kerschen ◽  
Teresa Garot ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Late Onset ◽  
Disease Onset ◽  
Population Based ◽  
Male Gender ◽  
Disability Progression ◽  
Relapsing Remitting ◽  
Short Time

Background: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. Methods: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling. Results: Among 3,597 patients, 245 had LOMS. Relapsing-remitting (RR) disease was less frequent with LOMS than AOMS (51.8 vs. 90.8%, p < 0.0001). PP course, LOMS and male gender predicted short time to EDSS 4 and 6. Worse outcome with LOMS (time to EDSS 4 and 6, HR 2.0 [95% CI 1.7-2.4] and 2.3 [1.9-2.9]) was independent of PP course or male gender. LOMS had greater impact on RR than PP disease (time to EDSS 4 and 6, HR 3.1 [2.3-4.0] and 4.0 [2.9-5.6]). Only LOMS predicted time from EDSS 4 to 6 (p < 0.0001). Conclusions: Late onset MS was strongly associated with poor prognosis, independent of initial disease course, in predicting the disability progression along time.

scholarly journals Cortical grey matter sodium accumulation is associated with disability and secondary progressive disease course in relapse-onset multiple sclerosis

2019 ◽  
Vol 90 (7) ◽  
pp. 755-760 ◽  
Author(s):  
Wallace J Brownlee ◽  
Bhavana Solanky ◽  
Ferran Prados ◽  
Marios Yiannakas ◽  
Patricia Da Mota ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Disease Onset ◽  
Healthy Controls ◽  
Disease Course ◽  
Cross Sectional ◽  
Sodium Accumulation ◽  
Secondary Progressive ◽  
Cortical Grey Matter

ObjectiveSodium (23Na)-MRI is an emerging imaging technique to investigate in vivo changes in tissue viability, reflecting neuroaxonal integrity and metabolism. Using an optimised 23Na-MRI protocol with smaller voxel sizes and improved tissue contrast, we wanted to investigate whether brain total sodium concentration (TSC) is a biomarker for long-term disease outcomes in a cohort of patients with relapse-onset multiple sclerosis (MS), followed from disease onset.MethodsWe performed a cross-sectional study in 96 patients followed up ~ 15 years after a clinically isolated syndrome (CIS) and 34 healthy controls. Disease course was classified as CIS, relapsing-remitting MS or secondary progressive MS (SPMS). We acquired 1H-MRI and 23Na-MRI and calculated the TSC in cortical grey matter (CGM), deep grey matter, normal-appearing white matter (WM) and WM lesions. Multivariable linear regression was used to identify independent associations of tissue-specific TSC with physical disability and cognition, with adjustment for tissue volumes.ResultsTSC in all tissues was higher in patients with MS compared with healthy controls and patients who remained CIS, with differences driven by patients with SPMS. Higher CGM TSC was independently associated with Expanded Disability Status Scale (R2=0.26), timed 25-foot walk test (R2=0.23), 9-hole peg test (R2=0.23), Paced Auditory Serial Addition Test (R2=0.29), Symbol Digit Modalities Test (R2=0.31) and executive function (R2=0.36) test scores, independent of grey matter atrophy.ConclusionsSodium accumulation in CGM reflects underlying neuroaxonal metabolic abnormalities relevant to disease course heterogeneity and disability in relapse-onset MS. TSC and should be considered as an outcome measure in future neuroprotection trials.

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

2020 ◽  
Vol 9 (5) ◽  
pp. 1326 ◽  
Author(s):  
Omid Mirmosayyeb ◽  
Serge Brand ◽  
Mahdi Barzegar ◽  
Alireza Afshari-Safavi ◽  
Nasim Nehzat ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Visual Impairments ◽  
Disease Onset ◽  
Adult Onset ◽  
Disability Progression ◽  
Secondary Progressive ◽  
Spinal Lesions ◽  
Relapsing Remitting ◽  
Sensory Disturbances

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.

No association of CCR5D32 gene mutation with multiple sclerosis in Croatian and Slovenian patients

2006 ◽  
Vol 12 (3) ◽  
pp. 360-362 ◽  
Author(s):  
Smiljana Ristić ◽  
Luca Lovrečić ◽  
Nada Starčević-Čizmarević ◽  
Bojana Brajenović-Milić ◽  
Saša Šega Jazbec ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Onset ◽  
Disease Process ◽  
Polymerase Chain Reaction Method ◽  
Carrier Status ◽  
Healthy Controls ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
And Control

Several studies investigating the role of the CCR5D32 mutation in multiple sclerosis (MS) have reported varied, often contradictory results. Therefore in the present study we have analysed whether the CCR5D32 mutation is associated with the risk of/or disease process in Croatian and Slovene MS patients. Three hundred and twenty-five MS patients and 356 healthy controls were genotyped by the polymerase chain reaction method. Our results showed no significant differences in the distribution of CCR5D32 mutations between MS and control subjects, indicating that this mutation does not influence susceptibility to MS. Furthermore, we did not observe that CCR5D32 carrier-status could modulate age of disease onset or progression of the disease. It is therefore our conclusion that the present study indicates that the CCR5D32 mutation is neither protective of, nor a risk factor, for MS development.

Effect of gender on late-onset multiple sclerosis

2012 ◽  
Vol 18 (10) ◽  
pp. 1472-1479 ◽  
Author(s):  
Riley M Bove ◽  
Brian Healy ◽  
Ann Augustine ◽  
Alexander Musallam ◽  
Taha Gholipour ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Late Onset ◽  
Disease Onset ◽  
Rank Test ◽  
Disease Course ◽  
Course Characteristics ◽  
Log Rank Test ◽  
Disability Status ◽  
Interval Censored ◽  
Males And Females

Objectives: We aimed to examine the incidence and disease course of late-onset multiple sclerosis (LOMS) compared with adult-onset MS (AOMS) in our clinic cohort, stratified based on gender and race, since both have been reported as important modifiers of disease outcomes in MS. Methods: Patients with LOMS and AOMS were compared in terms of demographic characteristics and disease course characteristics. Combined effects were investigated with a logistic regression model. Time from disease onset to sustained Expanded Disability Status Scale (EDSS) score of 6 was investigated using an extension of log-rank test appropriate for interval-censored data. Results: Some 7.96% of 4273 patients studied had an onset of MS after the age of 50 years (LOMS), and 1.33% experienced an onset after age 60. Progressive onset was more common in LOMS relative to AOMS. The proportion of women with progressive-onset disease was similar in AOMS and LOMS. Time to EDSS 6 was delayed in AOMS females compared with males; however, it was similar between males and females in the LOMS group. Conclusions: Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation.

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