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Objective To evaluate antibodies to myelin oligodendrocyte glycoprotein (MOG) in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and control individuals. Design Prospective case-control series. Setting Academic referral center. Patients Twenty-six controls with noninflammatory neurologic disease and 35 patients with MS donated serum and CSF for recombinant MOG (rMOG) antibody determination. Main Outcome Measures Serum and CSF rMOG antibody and albumin levels were used to calculate an rMOG index. Clinical disability, CSF markers, and magnetic resonance metrics were correlated with the rMOG index. Results The rMOG index was elevated in MS patients compared with controls ( P = .01). Patients with progressive MS exhibited elevated rMOG indexes compared with patients with relapsing-remitting MS ( P = .04). The rMOG index was inferior to the IgG index in differentiating MS patients from controls. However, 7 of 16 patients with MS who had normal immunoglobulin G indexes had an elevated rMOG index. The rMOG index did not correlate with clinical disability, other CSF markers, or radiographic outcome measures. Conclusions The rMOG index, a marker of intrathecal MOG antibody production, may provide complementary information to routine CSF testing in the diagnosis of MS. Furthermore, intrathecal anti-MOG antibody production may be more pronounced in progressive than in relapsing forms of MS.

Background B cells are implicated in the pathogenesis of multiple sclerosis. A beneficial effect of B-cell depletion using rituximab has been shown, but the complete mechanism of action for this drug is unclear. Objective To determine the relationship between T and B cells and changes in cerebrospinal fluid (CSF) chemokine levels with rituximab, a monoclonal antibody that targets CD20. Design Phase 2 trial of rituximab as an add-on therapy. Setting The John L. Trotter Multiple Sclerosis Center, Washington University. Participants and Intervention Thirty subjects who had relapsing-remitting multiple sclerosis with clinical and magnetic resonance imaging activity despite treatment with an immunomodulatory drug received 4 weekly doses of rituximab (375 mg/m 2 ). Main Outcome Measures Lumbar puncture was performed before and after rituximab infusions in 26 subjects. Levels of B and T lymphocytes in the CSF were enumerated by flow cytometry, and chemoattractant levels were measured by enzyme-linked immunosorbent assay. Results After rituximab administration, CSF B-cell levels were decreased or undetectable in all subjects, and CSF T-cell levels were reduced in 21 subjects (81%). The mean reduction in CSF cellularity was 95% for B cells and 50% for T cells. After rituximab infusion, CSF CXCL13 and CCL19 levels decreased ( P = .002 and P = .03, respectively). The proportional decline in CSF T-cell levels correlated with the proportional decrease in CXCL13 levels ( r = 0.45; P = .03), suggesting a possible relationship. The CSF IgG index, IgG concentration, and oligoclonal band number were unchanged following treatment. Conclusions In subjects with multiple sclerosis, B cells are critical for T-cell trafficking into the central nervous system and may alter the process by influencing chemokine production within the central nervous system.

Background Fatigue is experienced by most patients with multiple sclerosis (MS) and often is profoundly debilitating. No large-scale studies to our knowledge have examined circadian rhythm abnormalities in MS patients or the relationship of fatigue to circadian rhythms. Objective To determine if patients with MS and fatigue have sleep disturbances or circadian rhythm abnormalities associated with fatigue. Design Case-control study. Setting Washington University School of Medicine, St Louis, Mo. Patients Fifteen patients with MS and fatigue were compared with 15 patients with MS without fatigue and 15 age- and sex-matched, healthy controls. Main Outcome Measures Sleep disturbances and circadian rhythm abnormalities were quantitated by actigraphy, fatigue by the Fatigue Descriptive Scale, and excessive sleepiness by the Epworth Sleepiness scale (ESS). Results Of the 15 fatigued patients with MS, 2 had delayed sleep phase, 10 had disrupted sleep, and 3 had normal sleep. One of the 15 nonfatigued MS patients had irregular sleep cycles, 2 others had disrupted sleep, and 12 had normal sleep. All 15 of the healthy controls had normal sleep. Nine patients with MS and fatigue scored 10 or higher on the ESS, suggesting excessive daytime sleepiness. Only 2 patients with MS without fatigue scored higher than 10 on the ESS. None of the healthy controls were fatigued, and 14 were not excessively sleepy. A relationship was found between fatigue and abnormal sleep cycles or disrupted sleep (Fisher exact test, P = .003). There was also a relationship between subjective excessive daytime sleepiness and fatigue in MS patients ( P = .02). Conclusion There is a significant correlation between fatigue in MS patients and disrupted sleep or abnormal sleep cycles.

The natural course of disease in multiple sclerosis varies. Multiple sclerosis that is clinically 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 this 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 remains an insensitive prognostic indicator and must not be used to influence decisions regarding therapeutic options.

Acute aphasia is rare in multiple sclerosis. We describe 3 patients with multiple sclerosis who had acute exacerbations presenting as aphasias. One patient had a mixed transcortical aphasia, 1 had a transcortical motor aphasia, and 1 had a Broca aphasia. Magnetic resonance imaging scans of the brain with contrast enhancement revealed new white matter lesions in the left hemisphere in all 3 patients. Two of the 3 patients had a good response to treatment with methylprednisolone sodium succinate. Arch Neurol. 2000;57:1207-1209

To evaluate directional diffusivities within the optic nerve in a first event of acute optic neuritis to determine whether decreased axial diffusivity (AD) would predict 6-month visual outcome and optic nerve integrity measures.Cohort study.Academic multiple sclerosis center. Patients Referred sample of 25 individuals who presented within 31 days after acute visual symptoms consistent with optic neuritis. Visits were scheduled at baseline, 2 weeks, and 1, 3, 6, and 12 months.Visual acuity, contrast sensitivity, visual evoked potentials (VEPs), and thickness of the retinal nerve fiber layer (RNFL).An incomplete 6-month visual recovery was associated with a lower baseline AD (1.50 μm(2)/ms [95% confidence interval {CI}, 1.36-1.64 μm(2)/ms for incomplete recovery vs 1.75 μm(2)/ms [95% CI, 1.67-1.83 μm(2)/ms] for complete recovery). Odds of complete recovery decreased by 53% (95% CI, 27%-70%) for every 0.1-unit decrease in baseline AD. A lower baseline AD correlated with worse 6-month visual outcomes in visual acuity (r = 0.40, P = .03), contrast sensitivity (r = 0.41, P = .02), VEP amplitude (r = 0.55, P .01), VEP latency (r = -0.38, P = .04), and RNFL thickness (r = 0.53, P = .02). Radial diffusivity increased between months 1 and 3 to become higher in those with incomplete recovery at 12 months than in those with complete recovery (1.45 μm(2)/ms [95% CI, 1.31-1.59 μm(2)/ms] vs 1.19 μm(2)/ms [95% CI, 1.10-1.28 μm(2)/ms]).Decreased AD in acute optic neuritis was associated with a worse 6-month visual outcome and correlated with VEP and RNFL measures of axon and myelin injury. Axial diffusivity may serve as a marker of axon injury in acute white matter injury.