Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis.

RATIONALE: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. OBJECTIVE: We addressed the role of platelets in mediating CNS inflammation in EAE. METHODS AND RESULTS: We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control nondiseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression on platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ibα (GPIbα) promotes both platelet adhesion and inflammatory actions of platelets and targeting of GPIbα attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice. CONCLUSIONS: Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment.

Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome.

BACKGROUND: Sporadic fatal insomnia is a rare prion disease that has recently been recognized. OBJECTIVE: To report a unique case of sporadic fatal insomnia in a woman with progressive cerebellar deterioration who was originally thought to have a paraneoplastic cerebellar syndrome. DESIGN: Case report describing a patient with autopsy-proven sporadic fatal insomnia. PATIENT: A 56-year-old woman with progressive cerebellar ataxia who was found to have a retroperitoneal non-Hodgkin lymphoma. RESULTS: Autopsy demonstrated marked degenerative changes in the thalamus, cerebellum, and inferior olivary nucleus. A mild spongiform change was present in the thalamus and cortical gray matter. Western blot analysis confirmed the presence of abnormal, protease-resistant prion protein (PrP(Sc)), characteristic of sporadic fatal insomnia. CONCLUSIONS: Clinicians should be aware of this rare prion disease and should strongly consider the importance of autopsy toward the investigation of unusual neurological diseases.

In vivo activation of myelin oligodendrocyte glycoprotein-specific T cells in healthy control subjects.

Autoreactive T cells are present in healthy subjects but are assumed not to induce overt disease due to lack of exposure to autoantigen or because of immune regulation. In EAE, activation of myelin protein-specific T cells is a crucial step in disease induction. In this study, we evaluated whether myelin oligodendrocyte glycoprotein (MOG)-reactive T cells had been activated in vivo using peripheral blood mononuclear cells from neurologically healthy subjects. In vitro assays used either memory, CD45RO(+), or naïve, CD45RA(+) T-cell populations. MOG-reactive T cells were isolated from 7 of 10 subjects. Unexpectedly, a substantial number of MOG-reactive T cells were isolated from the CD45RO(+), memory T-cell subset in 6 subjects. The majority of these T cells generated gamma interferon in excess of IL-4, expressed VLA-4, and produced nerve growth factor. These findings demonstrate that a substantial proportion of MOG-reactive T cells from some subjects have been activated in vivo without resulting in clinical disease.