The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability

Abstract

The relationship of relapses to long-term disability in multiple sclerosis is uncertain. Relapse reduction is a common therapeutic target but clinical trials have shown dissociation between relapse suppression and disability accumulation. We investigated relationships between relapses and disability progression for outcomes of requiring assistance to walk, being bedridden and dying from multiple sclerosis [Disability Status Scale 6, 8, 10] by analysing 28 000 patient-years of evolution in 806-bout onset patients from the London Ontario natural history cohort. Having previously shown no effect of relapse frequency among progressive multiple sclerosis subtypes, here we examined these measures in the pre-progressive or relapsing–remitting phase. Survival was compared among groups stratified by (i) early relapses—number of attacks during the first 2 years of multiple sclerosis; (ii) length of first inter-attack interval; (iii) interval between onset and Disability Status Scale 3 (moderate disability); (iv) number of attacks from the third year of disease up to onset of progression; and (v) during the entire relapsing–remitting phase. Early clinical features can predict hard disability outcomes. Frequent relapses in the first 2 years and shorter first inter-attack intervals predicted shorter times to reach hard disability endpoints. Attack frequencies, in the first 2 years, of 1 versus ≥3, gave differences of 7.6, 12.8 and 20.3 years in times from disease onset to Disability Status Scale 6, 8 and 10, respectively. Time to Disability Status Scale 3 highly and independently predicted time to Disability Status Scale 6, 8 and 10. In contrast, neither total number of relapsing–remitting phase attacks nor of relapses experienced during the relapsing–remitting phase after the second year up to onset of progression showed a deleterious effect on times from disease onset, from progression onset and from Disability Status Scale 3 to these hard endpoints. The failure of a regulatory mechanism tied to neurodegeneration is suggested. Relapse frequency beyond Year 2 does not appear to predict the key outcome of secondary progression or times to Disability Status Scale 6, 8 or 10, highlighting two distinct disease phases related to late outcome. These appear to be separated by a watershed within the relapsing–remitting phase, just a few years after clinical onset. Higher early relapse frequencies and shorter first inter-attack intervals herald more rapid deterioration via interaction with the neurodegeneration characterizing secondary progression. They increase the probability of its occurrence, its latency and influence—to a lesser degree—its slope. The prevention or delay of the progressive phase of the disease is implicated as a key therapeutic target in relapsing–remitting patients.

Problematic clinical features of powered wheelchair users with severely disabling multiple sclerosis

“…Disability features (n) Spasticity (10) Pressure sores/leg ulcers (9) Urinary incontinence (3) Low back pain (9) Choking/swallowing issues (2) Dependent oedema/cellulitis (5) Constipation (2) Shoulder pain (4) Faecal incontinence (2) (kypho)scoliosis (4) MS fatigue (2) Neck pain (4) Trigeminal neuralgia (2) Thromboembolic disorders (2) Visual impairment (2) Weight gain (1) Contractures (1) Urinary tract infection (1) Intractable pain -cause unclear (1) EPIOC prescription as spasticity can be managed through positioning in the wheelchair. Our results suggest that six users with poorly controlled spasticity were provided with both TIS and SS.…”

“…This is due to weakness, spasticity, balance problems and/or fatigue alone or in any combination [2]. A recent report indicates that, for those with relapse-remitting MS, the median time from diagnosis to requiring a wheelchair for mobility is 28 years [3], as measured by the Disability Status Scale (DSS) for MS [4] where a score of eight is defined as ''essentially restricted to bed or chair or perambulated in wheelchair, but may be out of bed itself much of the day; retains many self-care functions; generally has effective use of arms''. This group of people with MS (PwMS) are the most likely to benefit from the provision of powered mobility and it has been estimated from a Canadian survey, that approximately 8% of people with MS (PwMS) will use powered wheelchairs [5].…”

The Path to Self-Management: A Qualitative Study Involving Older People with Multiple Sclerosis

“…2 About 15 years after diagnosis, the course usually becomes chronically progressive; most people will become dependent on mobility aids after about 20 years. 2,3 In MS clinics, one of the most important questions patients ask is, ''What should I expect in the future, and how will the disease progress?'' Although initial severity of disease predicts how quickly someone will develop walking impairment, 4 once this level of limitation is reached, disease variables are no longer predictive of disease progression; 2,5 that is, early predictors of disease progression, such as severity, do not predict how a person with MS will function in the long term.…”

Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives

“…Longterm natural history studies [11] provide precious information about negative prognostic factor presenting early at onset or during follow-up and infer that late disability can be predicted on the basis these factor, though helping in identify patients at risk of a more aggressive disease course [12] (Table 1). An epidemiological study assessed on a database of 5891 patients with MS, the proportion of patients that could be defined as affected by "aggressive MS" according to an Expanded Disability Status Scale (EDSS) of 6 (reached in 5 years or before the age of 40) or development of secondary progressive MS (SPMS).…”