Disability progression in multiple sclerosis is slower than previously reported

Tremlett, Helen; Paty, Donald W.; Devonshire, Virginia

doi:10.1212/01.wnl.0000194259.90286.fe

Cited by 306 publications

(265 citation statements)

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“…[16][17][18][19][20][21] For the current study, 8 of the 2,485 eligible were excluded because of unclear relapse histories, leaving 2,477 patients (table). The follow-up time from MS onset totaled 51,120 person-years with 11,722 postonset relapses.…”

Section: Resultsmentioning

confidence: 99%

“…[15][16][17][18][19][20][21] Briefly, patients were selected from the populationbased British Columbia MS (BCMS) database covering all 4 MS clinics in this Canadian province. Inclusion criteria (previously depicted as a flow chart 21 ) were laboratory-supported or clinically definite MS (Poser criteria 22 ); relapsing onset with first symptoms before July 1988 (to maximize the possibility of a meaningful follow-up time [no minimum follow-up time was required; those with a rapid disease course were eligible]); Ն1 EDSS score; and registered with a BCMS clinic before July/1998 (to enable establishment of the disease course).…”

Section: Methods Patientsmentioning

confidence: 99%

“…18 Using a similar approach, a time to EDSS 6 was imputed based on 2 clinically plausible scenarios: 1) optimistic assumed EDSS 6 was reached at the first clinic visit; 2) midway assumed EDSS 6 was reached halfway between onset and the first clinic visit. Few patients had an unknown time to SPMS (n ϭ 30), 19 such that a sensitivity analysis was not warranted.…”

Section: Methods Patientsmentioning

confidence: 99%

See 2 more Smart Citations

Impact of multiple sclerosis relapses on progression diminishes with time

Tremlett¹,

Yousefi²,

Devonshire³

et al. 2009

Neurology

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206

172

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Objective:The relationship between relapses and long-term disability in multiple sclerosis (MS) remains to be fully elucidated. Current literature is conflicting and focused on early relapses. We investigated the effects of relapses at different stages on disability progression. Methods:We conducted a retrospective review of 2,477 patients with definite relapsing-onset MS followed until July 2003 in British Columbia, Canada. Time-dependent Cox proportional hazards models examined the effect of relapses at different time periods (0 -5; Ͼ5-10; Ͼ10 years postonset) on time to cane (Expanded Disability Status Scale [EDSS]) and secondary progressive MS (SPMS). Findings were derived from hazard ratios with 95% confidence intervals (CIs), adjusted for sex, onset age, and symptoms.Results: Mean follow-up was 20.6 years; 11,722 postonset relapses were recorded. An early relapse (within 5 years postonset) was associated with an increased hazard in disease progression over the short term, by 48%; 95% CI 37%-60% for EDSS 6 and 29%; 95% CI 20%-38% for SPMS. However, this substantially lessened to 10%; 95% CI 4%-16% (EDSS 6) and 2%; 95% CI Ϫ2%-7% (SPMS) after 10 years postonset. The impact of later relapses (Ͼ5-10 years postonset) also lessened over time. Effects were modulated by age, impact being greatest in younger (Ͻ25 years at onset) and least in older (Ն35 years) patients where relapses beyond 5-years postonset typically failed to reach significance. Relapses during SPMS had no measurable impact on time to EDSS 6 from SPMS. Conclusion:Relapses within the first 5 years of disease impacted on disease progression over the short term. However, the long-term impact was minimal, either for early or later relapses. Long-term disease progression was least affected by relapses in patients with an extended disease duration (Ͼ10 years) or already in the secondary progressive phase. Neurology Multiple sclerosis (MS) is a common cause of neurologic disability in young adults.1 The majority (85%) present with a relapsing-remitting (RR) course, with many later entering the secondary progressive (SP) phase. Disability accrual in MS is said to occur in 2 situations: incomplete recovery from a relapse or deterioration of functional ability outside of a relapse, synonymous with the progressive phase. 1The mechanisms involved in either relapses or irreversible disability are not fully understood. Relapses are associated with inflammation and demyelination; irreversible disability with axonal damage. However, destruction of axons and the myelin-oligodendrocyte complex occurs in early and late disease.

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Section: Resultsmentioning

confidence: 99%

Section: Methods Patientsmentioning

confidence: 99%

Section: Methods Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Impact of multiple sclerosis relapses on progression diminishes with time

Tremlett¹,

Yousefi²,

Devonshire³

et al. 2009

Neurology

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206

172

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“…2 The prognosis can be poor in the long term but progression is frequently slow; recent evidence suggests a median of 28 years before a stick is required for walking. 3 The UK annual incidence of MS is 10 in 100 000 with a prevalence of 200 in 100 000. 4 There is estimated to be over 100 000 people suffering from the condition in the UK.…”

mentioning

confidence: 99%

Management of neuropsychiatric symptoms in multiple sclerosis

Sommerlad¹,

Price²,

Trip³

2014

Prog Neurol Psychiatry

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M ultiple sclerosis (MS) is the commonest cause of neurological disability in young and middleaged adults. 1 The characteristic pathological features are demyelinating plaques, astrocytic gliosis and immune-mediated inflammation anywhere within the CNS, with the periventricular region, brainstem, juxta cortical region, optic nerves and spinal cord being particularly common targets. The neurological manifestations are diverse, although they usually reflect the function of the affected anatomical site, and the course of the illness is variable and initially difficult to predict with accuracy.In 80-90 per cent of cases, MS is relapsing-remitting in nature with two-thirds of these cases developing a secondary progressive form of the condition a variable number of years after onset and a third having a relapsing-remitting course that does not result in long-term serious disability. The remaining 10-20 per cent of patients have a primary progressive course with gradually worsening symptoms. 2 The prognosis can be poor in the long term but progression is frequently slow; recent evidence suggests a median of 28 years before a stick is required for walking. 3 The UK annual incidence of MS is 10 in 100 000 with a prevalence of 200 in 100 000. 4 There is estimated to be over 100 000 people suffering from the condition in the UK. The median age of onset is 31 years and it is approximately twice as common in women. 5 It has a multifactorial aetiology with genetic and environmental factors shown to be important. There is 31 per cent monozygotic concordance compared to 5 per cent in dizygotic twins 6 while the environmental influence is demonstrated by marked variations in prevalence in genetically homogenous populations. 7 Prevalence increases with increasing distance from the equator and those who emigrate in childhood have prevalence rates consistent with their adopted country. 8 MS commonly presents with weakness, tingling or numbness in the limbs; diplopia, visual loss or impaired visual acuity; vertigo; dysarthria and ataxia; fatigue; and bladder and bowel disturbance. 5 The array of presenting symptoms in MS can lead to diagnostic uncertainty and neuropsychiatric conditions such as somatisation disorder are sometimes suspected. A study demonstrated that 16 per cent of patients with MS had been referred to a psychiatrist between the onset of neurological symptoms and diagnosis of MS. In spite of neurological symptoms being present in the majority of cases, these remained largely overlooked and diagnoses of conversion disorder and hysterical personality disorder were applied, 9 although the increased use of MRI scans since this finding was reported has improved diagnostic accuracy. While neurological features are the most recognised manifestations of MS, psychopathology, including affective, psychotic and cognitive disorders, is also common. The identification of these symptoms is often more difficult and diagnosis can be delayed. Psychiatric symptoms can occur at onset or later in the MS disease process and initial psych...

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“…In either case, patients have entered the secondary progressive (SP) MS phase [6][7] . The pace at which disability accumulates in the RRMS phase is variable, and some patients never convert to SPMS during their disease course [55][56][57] . The use of disease modulating drugs (DMD) prevents relapses and postpones the accumulation of disability in the RRMS phase [58] .…”

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confidence: 99%

Mapping the effects of vitamin D in multiple sclerosis

Rolf¹

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Columbus (1451Columbus ( -1506 on one of his four voyages Er zijn verrassend veel parallellen te trekken tussen onderzoek doen en een van mijn favoriete vrijetijdsbestedingen, namelijk koken. Alles begint met een inspiratie, nieuwsgierigheid en een idee. Dan volgt de planning en de uitvoering en na (lang…) wachten kun je het resultaat proeven. Het blijft altijd spannend of het gelukt is en of het wel lekker is. Als het lekker is, dan smaakt het vaak ook naar meer! Zo niet, dan moet je het recept aanpassen, of crucialer, iets heel anders verzinnen...De weg naar een goed gelukt gerecht is, althans voor mij, minstens zo belangrijk: watertandend recepten zoeken en menu's samenstellen, op zoek gaan naar de juiste producten, lekker creatief combineren en (al of niet met succes) uitproberen. Dat kon ook in de voor mij nieuwe keuken van de wetenschap, en wel in een restaurant met een excellente ambiance. Verder is de diversiteit aan smaken, waar ik bij eten zo van houd, zeker ook terug te vinden in de verschillende hoofdstukken.Of kookkunsten gewaardeerd worden is vervolgens een kwestie van smaak, maar ook van kennis. De fijnproevers zullen zich op de details storten en boeren die het niet kennen zullen het niet eten, maar voor iedereen die aan tafel schuift: hopelijk is datgene wat in dit boekje geserveerd wordt smakelijk en levert het gespreksstof op voor het natafelen! Abbreviations and glossary & G L O S S A R Y AB BR EVI ATI ONS 23General IntroductionHistorical explorers discovered new land around the world, and with every journey more details have been added to global maps. For multiple sclerosis research, explorers of the 20 th century put vitamin D on the map, and from 2008 onwards, our research team in Maastricht has tried to add more details to this area. Today, vitamin D in multiple sclerosis is still an active area of research. Many reviews concentrate on the role of vitamin D in multiple sclerosis, illustrated by clinical and immunological studies. Also in this thesis two reviews elaborate on this topic. Therefore, the introduction to this thesis is restricted to the essential players, i.e. multiple sclerosis, its immune pathogenesis, and vitamin D, followed by the outline of the thesis.Multiple sclerosis (MS) is the most common disabling neurological disease among young people. Initial symptoms generally occur in the age of 20-40 years and MS affects women 2-3 times more often compared to men [1][2] . Currently, almost 1 in 1000 people suffers from MS in the Netherlands [3] . MS is characterized by inflammation and neurodegeneration of the central nervous system (CNS; brain and spinal cord). Though, it is still a matter of debate whether it is neurodegenerative or inflammatory from onset [1,4] . Most accepted, however, is the thought that inflammatory processes lead to damage of the fatty myelin sheaths covering the neuronal axons, which normally support fast transduction of signals, and this process is called demyelination. The inflammation can be accompanied by axonal injury and over time this result...

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Disability progression in multiple sclerosis is slower than previously reported

Abstract: Disability progression in multiple sclerosis (MS) accrued more slowly than found in earlier longitudinal studies. The authors also challenged two fundamental concepts in MS, demonstrating that neither male sex nor older onset age was associated with worse disease outcome.

Cited by 306 publications

References 23 publications

Impact of multiple sclerosis relapses on progression diminishes with time

Impact of multiple sclerosis relapses on progression diminishes with time

Management of neuropsychiatric symptoms in multiple sclerosis

Mapping the effects of vitamin D in multiple sclerosis

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