Can we predict benign multiple sclerosis? Results of a 20-year long-term follow-up study

Abstract

Benign multiple sclerosis (MS) is a discussed clinical entity, with variable reported prevalence (6-64%) requiring at least 5-10 years of clinical observation. Moreover, many benign patients progress with time becoming no longer benign (NLB). The objective of this study is to compare benign MS patients (EDSS ≤3, 10 years from disease onset) who still fulfilled the definition at 20 years to those NLB. In our retrospective study based on Ottawa Hospital MS Clinic database, 175 benign patients fulfilled the inclusion criteria (clinically definite MS, EDSS ≤3 at 10 years, disease onset from 1983 to 1993, and clinical assessments performed at 10 ± 1 and 20 ± 1 years from onset). Out of the identified patients, 66.3% remained benign at 20 years; however, by changing the definition for benign to EDSS ≤2 or ≤1 at 10 years, they increased to 71.9 and 81.6%, respectively. Female sex, EDSS ≤1 at 10 years, and a pure sensory onset were associated with a benign course, while a pure motor onset with an NLB condition. According to multivariate analysis, an EDSS ≤2 at 10 years predicted a long-term benign course. Our study questions the current definition of "benign" MS, suggesting a more stringent EDSS cutoff at 10 years to predict long-term benign prognosis.

How common is truly benign MS in a UK population?

“…One commonly cited definition has been an Expanded Disability Status Scale (EDSS) score of ≤3 at 10 years from symptom onset, but around one quarter of patients meeting this definition accumulated further disability when followed up to 20 years 2–8. Recent studies have suggested that a low EDSS status after 15 years of MS may be a more reliable marker of benign status 6 9…”

Combination of cuprizone and experimental autoimmune encephalomyelitis to study inflammatory brain lesion formation and progression

“…In severe cases (i.e., Marburg's variant of MS), inflammatory demyelination can lead to severe functional deficits and sometimes dead (Nunes et al, ; Rush, MacLean, & Freedman, ). Some cases of MS are more benign, with no worsening of functional ability, even after 15 years of diagnosis, and low annualized relapse rates (Glad, Nyland, Aarseth, Riise, & Myhr, ; Sartori, Abdoli, & Freedman, ). However, in most cases, these attacks can recur with increasing frequency and proceed to secondary progressive MS, which, as with primary progressive forms, involves axonal damage and neurodegeneration (Charcot, ; Kornek et al, ; Trapp, Ransohoff, & Rudick, ) resulting in irreversible clinical disability.…”

Cardiac repolarization evolves differently during the course of benign and disabling multiple sclerosis

“…In our study, the disease course was classified as benign if the EDSS remained ≤2 at least 10 years after the first demyelinating event. This definition has recently been demonstrated to predict subsequent benign course also for another ten years, 3 thus increasing the reliability of the definition. Previously, in the absence of the changes in EDSS or brain magnetic resonance T2 lesion load, cardiac autonomic function was suggested to reflect subclinical activity in MS during 2 years follow-up.…”

“…The disease course was classified according to the EDSS score determined at a stable phase. Patients with EDSS score ≤2 after a minimum of ten years follow-up after the onset symptom were classified as benign 3 RRMS group and patients with EDSS score >2 were classified as disabling RRMS group.…”

“…1 There is a subset of patients with benign RRMS who accumulate little or no disability during the disease course. 2,3 Disability in RRMS is typically assessed by Expanded Disability Status Scale (EDSS), which relies heavily on ambulation. In the absence of changes in EDSS or brain magnetic resonance imaging lesion load over time, deterioration of cardiac autonomic function, however, may occur and reflect subclinical activity in MS. 4 Autonomic dysfunction is commonly observed in patients with RRMS, and even in patients with clinically isolated syndrome.…”