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Oligoclonal Band Number As a Marker for Prognosis in Multiple Sclerosis

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Oligoclonal Band Number As a Marker for Prognosis in Multiple Sclerosis ORIGINAL CONTRIBUTION Oligoclonal Band Number as a Marker for Prognosis in Multiple Sclerosis Jagannadha R. Avasarala, MD, PhD; Anne H. Cross, MD; John L. Trotter, MD† he natural course of disease in multiple sclerosis varies. Multiple sclerosis that is clini- cally apparent but causes minimal disability over time has been labeled benign multiple sclerosis. The ability to predict the subsequent clinical course of multiple sclerosis on the basis of clinical and other supportive data at presentation would be invaluable. In Tthis article we report our findings based on a retrospective analysis of 1800 patients diagnosed as having multiple sclerosis, of which 44 patients met our inclusion criteria. There was a suggestion that a low or absent number of oligoclonal bands in the cerebrospinal fluid at the time of diagnosis predicts a better prognosis. However, quantification of oligoclonal bands in cerebrospinal fluid re- mains an insensitive prognostic indicator and must not be used to influence decisions regarding therapeutic options. Arch Neurol. 2001;58:2044-2045 The diagnosis of multiple sclerosis (MS) is thesis may predict progression to MS,5 and based on neurologic history, findings on ex- oligoclonal bands (OCBs) in CSF during amination, and exclusion of other disor- the early phase of disease are associated ders. The natural course of MS varies. It with a worse outcome.6 We report a ret- would be ideal if clinical or laboratory cri- rospective analysis of 1800 patients with teria could distinguish patients who will a diagnosis of MS as judged by clinical, progress to become disabled from those magnetic resonance imaging, and CSF who will not. Patients with benign MS com- findings at the time of presentation. prise about 10% to 15% of patients with MS and are functional in all neurologic sys- RESULTS tems 15 years after disease onset.1,2 Pa- tients with MS are typically followed up over Seven of 14 patients in the benign group time on the basis of expanded disability sta- had no OCBs, and the remainder had 2 to tus scale (EDSS) scores. Thus, cognitive 10 OCBs, with a median of 5. Seven of 30 and/or upper extremity dysfunction may patients with severe MS had no OCBs. be underestimated. In addition, the term The other 23 patients in this group had 2 benign is relative.2 It has been suggested to 17 OCBs, with a median of 7. Overall, that a progression index rather than an the mean (SD) number of bands in the EDSS cutoff may be more indicative of be- benign group was 2.86±3.59, fewer than nign disease.3 in the severe group (5.70±4.86; PϽ.06) The single most consistent labora- (Figure). There was a suggestion that tory abnormality in patients with MS ex- the absence of OCBs correlated with the clusive of magnetic resonance imaging is course of the disease (P=.10, Fisher exact increased oligoclonal immunoglobulins in test). cerebrospinal fluid (CSF).4 In patients with a single demyelinating episode, detec- tion of intrathecal immunoglobulin syn- COMMENT From the Department of Neurology, Washington University School of Medicine, It is intriguing why some patients remain St Louis, Mo. †Dr Trotter died unexpectedly on July 12, 2001. OCB negative despite meeting typical cri- (REPRINTED) ARCH NEUROL / VOL 58, DEC 2001 WWW.ARCHNEUROL.COM 2044 ©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 18 PATIENTS AND METHODS 16 14 12 From the 1800 patients, we selected those who (1) had had CSF studies done at this institution at pre- 10 sentation, (2) had preserved polyacrylamide gels at 8 the time of review, and (3) had a minimum fol- 6 low-up of 10 years. Excluded were those who had died No. of Oligoclonal Bands by the time of analysis, had indistinct OCBs, or had 4 OCBs in both serum and CSF. 2 We divided patients who met inclusion criteria 0 into benign, mild, moderate, and severe categories on the basis of their level of disability, as assessed Benign Severe by their EDSS scores. Of the 1800 patients, 44 who met the inclusion criteria had “benign” (EDSS Comparison of number of oligoclonal bands in benign vs severe multiple Ͻ3.5; n=14) or “severe” (EDSS Ͼ7.5; n=30) dis- sclerosis. Median lines are shown within bars that represent the 25th to 75th ease. All 44 patients included in our study had had percentile. Error bars indicate 90th percentiles; solid dots, outliers. more than 1 clinical attack. Mean follow-up for benign and severe groups was 15.8 and 16.2 years, respectively. ton University School of Medicine, Campus Box 8111, 660 The OCB assays were performed at the time of S Euclid Ave, St Louis, MO 63017 (e-mail: avasaralaj diagnosis by means of gel electrophoresis and iso- @neuro.wustl.edu). electric focusing with silver staining, and were stan- dardized for all patients. One of us (J.L.T.) deter- mined OCB number in the 44 patients in blinded REFERENCES fashion. 1. Kurtzke JF, Beebe GW, Nagler B, Kurland LT, Auth TL. Studies on the natural history of multiple sclerosis, 8: early prognostic features of the later course of the illness. J Chronic Dis. 1977;30:819-830. teria for diagnosis of MS.7 One explanation could be that 2. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology. 1996;46:907-911. demyelination in MS may occur independent of anti- 3. Hawkins SA, McDonnell GV. Benign multiple sclerosis? clinical course, long term body, or CSF electrophoresis methods may be insensi- follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychia- tive to detect local synthesis of antibody in all clinically try. 1999;67:148-152. definite cases of MS.8 Although our study suggests that 4. Paty DW, Noseworthy JH, Ebers GC. Diagnosis of multiple sclerosis. In: Paty a low number or absence of OCBs in CSF at diagnosis DW, Ebers GC, eds. Multiple Sclerosis. Philadelphia, Pa: FA Davis Co; 1988:48- 134. predicts a better prognosis, no differences in the clinical 5. Paolino E, Fainardi E, Ruppi P, et al. A prospective study on the predictive value course and EDSS scores were noted in OCB-negative pa- of CSF oligoclonal bands and MRI in acute isolated neurological syndromes for tients in a study from Japan.9 Immunoglobulins may con- subsequent progression to multiple sclerosis. J Neurol Neurosurg Psychiatry. tribute to the pathogenesis of MS,10 and oligoclonal IgM 1996;60:572-575. 6. Amato MP, Ponziani G. A prospective study of the prognosis of multiple sclero- bands may predict progression to MS better than mag- sis. Neurol Sci. 2000;21(suppl):S831-S838. 11 netic resonance imaging or IgG testing does. Neverthe- 7. Farrell MA, Kaufmann JCE, Gilbert JJ, Noseworthy JH, Armstrong HA, Ebers GC. less, quantification of CSF OCBs remains an insensitive Oligoclonal bands in multiple sclerosis: clinical-pathologic correlation. Neurol- prognostic indicator and should not be used to influ- ogy. 1985;35:212-218. ence decisions regarding therapy. 8. Zeman AZ, Kidd D, McLean BN, et al. A study of oligoclonal band negative mul- tiple sclerosis. J Neurol Neurosurg Psychiatry. 1996;60:27-30. 9. Fukazawa T, Yanagawa T, Kikuchi S, et al. CTLA-4 gene polymorphism may modu- Accepted for publication August 27, 2001. late disease in Japanese multiple sclerosis patients. J Neurol Sci. 1999;171:49- Dr Avasarala is a fellow of the National Multiple 55. Sclerosis Society, New York, NY, and received grant 10. Cross AH, Trotter JL, Lyons JA. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol. 2001;112:1-14. FG1386-A-1. 11. Sharief MK, Thompson EJ. The predictive value of intrathecal immunoglobulin Corresponding author and reprints: Jagannadha R. synthesis and magnetic resonance imaging in acute syndromes for subsequent Avasarala, MD, PhD, Department of Neurology, Washing- development of multiple sclerosis. Ann Neurol. 1991;29:147-151. (REPRINTED) ARCH NEUROL / VOL 58, DEC 2001 WWW.ARCHNEUROL.COM 2045 ©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021.
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