Multiple sclerosis relapses: a multivariable analysis of residual disability determinants

Vercellino, Marco; Romagnolo, Alberto; Mattioda, Alessandra; Masera, Silvia; Piacentino, Chiara; Merola, Aristide; Chiò, Adriano; Mutani, Roberto; Cavalla, Paola

doi:10.1111/j.1600-0404.2008.01076.x

Cited by 53 publications

(47 citation statements)

References 15 publications

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“…Studies of these groups have shown quantifiable residual neurologic dysfunction in 40-50% of subjects experiencing relapses. [2][3][4] The degree of residual dysfunction from relapses may well be underestimated in these studies as they measured residual with changes in Expanded Disability Status Scale (EDSS), likely not the most sensitive measure of persistent deficit. These results nicely complement the earlier natural history studies that correlate early relapse frequency and residual with rapidity of reaching disability status scale (DSS) 6.…”

mentioning

confidence: 99%

Relapses do not matter in relation to long-term disability: No (they do)

Lublin

2011

Mult Scler

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MULTIPLE SCLEROSIS MSJ JOURNALIt seems rather perverse to have to defend the most defining element of multiple sclerosis (MS), the relapse. And yet here we are…The relapse is best defined as patient-reported symptoms or objectively observed signs typical of an acute inflammatory demyelinating event in the central nervous system (CNS), current or historical, with duration of at least 24 hours, in the absence of fever or infection. 1 The clinical, radiologic (as a measure of in vivo pathology) and pathologic evidence for a role of relapses in the long-term evolution of MS is considerable. The onset of a relapse is relatively easy to discern (although determining the end is more problematic). The neurologic deficits are obvious and the residual dysfunction is observable and measurable. Despite this, the role of relapses in production of long-term disability has been questioned in several natural history cohorts.Relapses produce immediate and obvious neurologic dysfunction, frequently with MRI correlation. The early course of MS is most often dominated by exacerbations and remissions. The role of relapses in the accrual of disability has been most directly addressed in studies that have utilized well-characterized cohorts, frequently followed over a period of years. Studies of these groups have shown quantifiable residual neurologic dysfunction in 40-50% of subjects experiencing relapses. [2][3][4] The degree of residual dysfunction from relapses may well be underestimated in these studies as they measured residual with changes in Expanded Disability Status Scale (EDSS), likely not the most sensitive measure of persistent deficit. These results nicely complement the earlier natural history studies that correlate early relapse frequency and residual with rapidity of reaching disability status scale (DSS) 6. 5,6 The differences in the types of populations that have been utilized to study this problem highlight some of the methodological issues at play. Natural history cohorts and clinical trial studies differ markedly in their study populations, length of follow up, standardization of assessments (e.g. use of DSS or EDSS), frequency of assessments, rigor of data collection, consistency of examiners, data collection methods and other factors. 7 Is the DSS or EDSS too insensitive to change in any functional system other than ambulation after one reaches a level of 4? If an exacerbation affected upper extremity or brain stem function, might the EDSS in the 4-7 range remain unchanged? These factors alone may explain the discrepancies. This issue can best be resolved through analysis of prospectively studied, wellcontrolled populations for longer duration than the usual MS clinical trial.All pivotal clinical trials in relapsing-remitting MS have demonstrated the development of irreversible disability over time in a proportion of subjects. This is most likely produced by stepwise worsening from relapses, as development of secondary progressive MS has been uncommon in these studies of early MS patients.Several more recent na...

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confidence: 99%

Relapses do not matter in relation to long-term disability: No (they do)

Lublin

2011

Mult Scler

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“…57 Residual disability is seen in one third to half of all relapses [59][60][61][62] and is more likely if the relapse is severe, multifocal, initially slow to recover, and in people 30 years or older. 60 62 One study indicates that a lack of recovery from a relapse predicts incomplete remission of future relapses.…”

Section: Recovery From Individual Relapsementioning

confidence: 99%

Relapse in multiple sclerosis

Galea

Ward-Abel

Heesen

2015

BMJ

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“…Disease progression was defined as an increase of at least 1.5 points on the Expanded Disability Status Scale (EDSS) score [16]. Disabling relapse was defined as a relapse with a residual disability, which was defined as incomplete recovery at 1 month from a relapse [17,18]. As the panel did not conduct any novel experimental research, no ethics approval was necessary.…”

Section: Methodsmentioning

confidence: 99%

Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring

Alroughani¹,

Aref²,

Bohlega³

et al. 2014

Multiple Sclerosis and Related Disorders

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Background: Natalizumab, a highly specific α4-integrin antagonist, , has recently been registered across the Middle East and North Africa region. It improves clinical and magnetic resonance imaging (MRI) outcomes and reduces the rate of relapse and disability progression in relapsing-remitting multiple sclerosis (MS). Natalizumab is recommended for patients who fail first-line disease-modifying therapy or who have very active disease. Progressive multifocal leukoencephalopathy is a rare, serious adverse event associated with natalizumab. We aim to develop regional recommendations for the selection and monitoring of MS patients to be treated with natalizumab in order to guide local neurological societies. Methods: After a review of available literature, a group of neurologists with expertise in the management of MS met to discuss the evidence and develop regional recommendations to guide appropriate use of natalizumab in the region. Results: Disease breakthrough is defined as either clinical (relapse or disability progression) or radiological activity (new T2 lesion or gadolinium-enhancing lesions on MRI), or a combination of both. Natalizumab is recommended as an escalation therapy in patients with breakthrough disease based on its established efficacy in Phase III studies. Several factors including prior immunosuppressant therapy, anti-John Cunningham virus (JCV) antibody status and patient choice will affect the selection of natalizumab. In highly active MS, natalizumab is considered as a first-line therapy for naive patients with disabling relapses in association with MRI activity. The anti-JCV antibody test is used to assess anti-JCV antibody status and identify the risk of PML. While seronegative patients should continue treatment with natalizumab, anti-JCV antibody testing every 6 months and annual MRI scans are recommended as part of patient monitoring. In seropositive patients, the expected benefits of natalizumab treatment have to be weighed against the risks of PML. Clinical vigilance and follow-up MRI scans remain the cornerstone of monitoring. After 2 years of natalizumab therapy, monitoring should include more frequent MRI scans (every 3-4 months) for seropositive patients, and the risk-benefit ratio should be reassessed and discussed with patients. Conclusions: Recommendations have been developed to guide neurologists in the Middle East and North Africa on patient selection for natalizumab treatment and monitoring.

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Multiple sclerosis relapses: a multivariable analysis of residual disability determinants

Abstract: Incomplete recovery at 1 month is a predictor of long-term persistence of RD. Higher relapse severity is associated with higher risk of RD. Risk of severe relapses is lower in patients treated with immunomodulating drugs.

Cited by 53 publications

References 15 publications

Relapses do not matter in relation to long-term disability: No (they do)

Relapses do not matter in relation to long-term disability: No (they do)

Relapse in multiple sclerosis

Natalizumab treatment for multiple sclerosis: Middle East and North Africa regional recommendations for patient selection and monitoring

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