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Maria del Pilar Martin, PhD; Petra D. Cravens, PhD; Ryan Winger; Elliot M. Frohman, MD, PhD; Michael K. Racke, MD; Todd N. Eagar, PhD; Scott S. Zamvil, MD, PhD; Martin S. Weber, MD; Bernhard Hemmer, MD; Nitin J. Karandikar, MD, PhD; B. K. Kleinschmidt-DeMasters, MD; Olaf Stüve, MD, PhD

Arch Neurol. 2008;65(12):1596-1603. Published online October 13, 2008 (doi:10.1001/archneur.65.12.noc80051).

Objective  To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS.

Design  A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining.

Subjects  A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy.

Results  The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209⁺ dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4⁺ T cells were detectable.

Conclusions  Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.

Author Affiliations: Departments of Neurology (Drs Martin, Cravens, Frohman, Eagar, and Stüve and Mr Winger), Ophthalmology (Dr Frohman), Immunology (Drs Eagar, Karandikar, and Stüve), and Pathology (Dr Karandikar), University of Texas Southwestern Medical Center at Dallas; Departments of Neurology, The Ohio State University Medical Center, Columbus (Dr Racke), University of California, San Francisco (Drs Zamvil and Weber), and Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany (Drs Weber and Hemmer); Departments of Pathology, Neurology, and Neurosurgery, University of Colorado, Denver (Dr Kleinschmidt-DeMasters); and the Neurology Section, Veterans Affairs North Texas Health Care System, Medical Service, Dallas (Dr Stüve).

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