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作者：Allison Gandey  
出處：WebMD醫學新聞

　　March 26, 2010 — 研究者們表示，對於突發性不可逆失能的擔憂不應該影響罹患多發性硬化症病患的治療決策，因為發作機率是很低的。不論病患是否接受干擾素治療都有可能發生這樣的事件。
　　
　　威斯康辛州Marshfield診所的Khemissa Bejaoui博士與Loren Rolak醫師報告，約每500次疾病再發才會發生一次嚴重發作。
　　
　　他們在文章中指出，許多疾病再發病患害怕突發性悲劇性症狀，例如「我醒來後發現自己癱瘓了」。部分醫師也有病患因急性再發而持續性失能的經驗，這些病患們因為擔憂可能發生更嚴重的失能感到害怕，而延遲、或停止治療。
　　
　　在隨後的主編評論中，麥德遜威斯康辛大學的John Fleming醫師與Michael Carrithers醫師稱讚他們的研究成果，他們稱這可以協助有起始診斷與處理執業問題的臨床醫師們，認為這在現實生活中是個嚴謹的研究。
　　
　　他們的研究報告發表在3月16日的神經學期刊上。
　　
　　主編們表示，有時候，當懷疑多發性硬化症時，診斷與治療會被形容為是醫療緊急事件。根據這個標準，應該立即採取治療來避免數月內即將發生的慘劇。這項新研究顯示，這樣的做法是不必要的。
　　
　　【不要著急】
　　Fleming與Carrithers醫師表示，當懷疑多發性硬化症時，神經學家有足夠的時間來確立正確的診斷，以及每位病患最佳的處理方式。
　　
　　在這項研究中，研究者們前瞻性地觀察了1078位多發性硬化症病患。他們量測嚴重再發事件的頻率，以造成不可逆失能的急性發作來定義，使用擴充版失能狀態指標分數超過6分以上，平均後續追蹤時間為7.4年。
　　
　　這期間總共發生了2500次以上的再發事件，每位病患平均發生2.4次，範圍自1到11次，追蹤時間介於1到15年。
　　
　　只有7位病患的疾病再發事件造成不可逆的失能。其中2個病例，嚴重再發發生在罹患腫脹性多發性硬化症的病患身上。剩下的5個病例，2個正在接受疾病調控治療，另外3位未接受治療。
　　
　　研究團隊表示，103位病患停用治療，且沒有發生嚴重再發。
　　
　　研究團隊並未確認出任何可能預測嚴重急病再發臨床、基因上或是治療相關因子。
　　
　　排除疾病發生時嚴重發作的病患，試驗作者們指出，這項研究結果顯示到嚴重發作所需時間很長，平均達6.6年。
　　
　　【新的診斷標準受到質疑】
　　上個月，研究團隊提出了多發性硬化症的新診斷標準（Neurology 2010;74:427-434）。由Medscape神經學報導，這些新的診斷標準比較寬鬆，且被設計用於改善敏感度與促使早期診斷。
　　
　　這個由Xavier Montalban醫師領導的團隊，來自西班牙巴塞隆納Vall d'Hebron大學醫院，他們表示目前的建議是很複雜的，且對神經學家或神經放射學家來說，這些建議的知識傳遞並不容易。
　　
　　這個仍有爭議的提案提倡使用單一核磁共振造影檢查，以符合診斷標準。
　　
　　然而，Fleming與Carrithers醫師卻表示，過度診斷多發性硬化症早已是最常見的診斷錯誤。這被歸咎於MRI以及匆促相關檢驗鑑別力不足的可靠度。
　　
　　【MRI以及匆促相關檢驗鑑別力不足的可靠度】
　　主編們指出，多發性硬化症的處理在疾病調控治療、以及不同選擇價值上的角色仍是不確定的。
　　
　　考柯藍綜論以及其他文獻同意目前並沒有方法學嚴謹的研究檢驗多發性硬化症長期失能的治療效果。
　　
　　主編們表示，雖然對延後疾病調控治療的擔憂可能與非再發相關失能有關，專家們在延緩治療可能相關失能的影響大小、臨床重要性、甚至是是否存在上有不同意見。
　　
　　目前並沒有研究說明延緩疾病調控治療短於一年的後果，且顯然地，沒有專家學者建議對沒有確切診斷多發性硬化症、或是臨床獨立症狀病患進行治療。
　　
　　仍有許多問題，但在同時，研究團隊希望這項新研究將會減輕對突發性失能的害怕。Bejaoui醫師與Rolak醫師強調，這樣的發作是很罕見的。
　　
　　這項研究由Marsffield診所贊助。研究者們表示已無相關資金上的往來。主編們接受國家多發性硬化症學會的研究贊助。


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.

Neurology. 2010;74:900-902.