Risk of Sudden Irreversible Disability Low in Multiple Sclerosis
By Allison Gandey
Medscape Medical News
March 26, 2010 — The fear of sudden irreversible disability should not influence therapeutic decisions for patients with multiple sclerosis, say researchers, because such attacks are very rare. And when they occur, they happen whether or not patients are treated with interferons.
Khemissa Bejaoui, PhD, and Loren Rolak, MD, from the Marshfield Clinic in Wisconsin, report that severe attacks occur in just 1 of every 500 relapses.
"Many patients with relapsing disease fear a sudden catastrophic symptom, such as, 'I might wake up paralyzed,'" they point out in their paper. "Some physicians also have anecdotal experience of patients with persistent disability from an acute relapse and may fear delaying or stopping treatment out of concern that a severe deficit could occur."
Severe attacks occur in just 1 of every 500 relapses.
In an accompanying editorial, John Fleming, MD, and Michael Carrithers, MD, from the University of Wisconsin at Madison, complimented the work, saying it should help clinicians with practical problems relating to initial diagnosis and management. They call this a careful study in a real-world setting.
The work appears in the March 16 issue of Neurology.
"Sometimes the issues of diagnosis and therapy when multiple sclerosis is suspected are portrayed as virtual medical emergencies," the editorialists note. "By this standard, treatment should be instituted immediately to prevent an imminent catastrophe within months." This new study suggests this approach is not necessary.
No Rush
"When multiple sclerosis is suspected, the neurologist has sufficient time to establish an accurate diagnosis and the optimal management for the individual patient," Dr. Fleming and Dr. Carrithers suggest.
In the study, investigators prospectively observed 1078 multiple sclerosis patients. They measured the frequency of severe relapse, which they defined as an acute attack producing an irreversible deficit — an Expanded Disability Status Scale score of 6 or higher. The average follow-up was 7.4 years.
There were more than 2500 relapses. The mean per patient was 2.4, with a range of 1 to 11 attacks during 1 to 15 years.
Only 7 patients had a relapse resulting in irreversible disability. In 2 cases, the severe relapse occurred at onset in patients with tumefactive multiple sclerosis. In the remaining 5 cases, 2 were receiving disease-modifying treatment and 3 were not.
Investigators show that 103 patients discontinued therapy without having a severe relapse.
The researchers did not identify any clinical, genetic, or treatment-related factors that might predict severe relapse.
Excluding patients with a severe attack at onset, the study authors point out that this study demonstrates that the time from onset to severe attack was long — with a mean of 6.6 years.
New Diagnostic Criteria Debated
Last month, investigators proposed new diagnostic criteria for multiple sclerosis (Neurology. 2010;74:427-434). As reported by Medscape Neurology, the new standards are less stringent than other proposals and are designed to improve sensitivity and promote early diagnosis.
The group, led by Xavier Montalban, MD, from the Hospital Universitari Vall d'Hebron in Barcelona, Spain, suggests that current recommendations are complex and that "a good working knowledge of them is not always evident even among neurologists and neuroradiologists."
The controversial proposal advocates using a single magnetic resonance imaging examination to fulfill diagnostic criteria.
However, Dr. Fleming and Dr. Carrithers argue that overdiagnosis in suspected multiple sclerosis is already the most common diagnostic error. "It has been ascribed to uncritical reliance on MRI and hasty workup."
Uncritical Reliance on MRI and Hasty Workup
The editorialists point out the management of multiple sclerosis is controversial in terms of both the role of disease-modifying treatment and the merits of various options.
Cochrane reviewers and others agree that there is no methodologically rigorous study of the effects of treatment on disability in multiple sclerosis long term.
"Although there is concern that delayed disease-modifying treatment may be associated with non-relapse related disability, experts disagree on the magnitude, clinical significance, or even reality of possible delay related disability," the editorialists note.
"No study has addressed the consequences of disease-modifying treatment delays of less than a year, and, obviously, no authority recommends treatment for patients in which an accurate diagnosis of multiple sclerosis or active clinically isolated syndrome is not established."
Many questions remain, but in the meantime, investigators hope this new study will allay fears of sudden irreversible disability. Dr. Bejaoui and Dr. Rolak emphasize, "Such attacks are very rare."
This study was funded by the Marshfield Clinic. The researchers have disclosed no relevant financial relationships. The editorialists receive research support from the National Multiple Sclerosis Society.
