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Its Correlation With Clinical Parameters, Evoked Potentials, and Intra-Blood-Brain Barrier IgG Synthesis

Robert W. Baumhefner, MD; Wallace W. Tourtellotte, MD, PhD; Karl Syndulko, PhD; Victor Waluch, MD, PhD; George W. Ellison, MD; Lawrence W. Meyers, MD; Stanley N. Cohen, MD; Meredith Osborne; Paul Shapshak, PhD

Arch Neurol. 1990;47(1):19-26.

Abstract
• Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24(46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF. Factor analysis of the data showed that the major plaque burden in the cerebrum of patients with MS as demonstrated on the MRI had a strong relationship with neuropsychological functioning (SDMT) and the intra-BBB IgG synthesis rate, while most clinical assessments in MS seemed to be related primarily to noncerebral plaques in the brain stem and cerebellum. We conclude that the intra-BBB IgG synthesis rate, neuropsychological functioning, and cerebral MRI abnormalities should be investigated further as possible objective outcome measurements in future clinical treatment trials of MS.

Author Affiliations
From the Neurology and Research Services, Veterans Administration West Los Angeles Medical Center, Wadsworth Division (Drs Baumhefner, Tourtellotte, Syndulko, and Shapshak and Ms Osborne), Department of Neurology, UCLA School of Medicine, Reed Neurological Research Center (Drs Baumhefner, Tourtellotte, Syndulko, Ellison, Myers, Cohen, and Shapshak), and St Vincent's Hospital (Dr Waluch), Los Angeles, Calif.

Footnotes
Accepted for publication May 1, 1989.

Reprint requests to Neurology Service (W127A), VA Medical Center West Los Angeles, Wilshire & Sawtelle boulevards, Los Angeles, CA 90073 (Dr Baumhefner).

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