Pathological Heterogeneity of Idiopathic Central Nervous System Inflammatory Demyelinating Disorders C. Lucchinetti 1 Introduction . 20 2 Heterogeneity of Multiple Sclerosis White Matter Lesions . 21 2.1 Stages of Lesions . 21 2.2 MS Plaque Types . 22 2.3 Inflammation and Immune Effector Heterogeneity in MS . 24 2.4 Evidence for Immunopathogenic Heterogeneity in Multiple Sclerosis . 27 2.5 Immunopathologic Heterogeneity May Be Stage-Dependent . 30 3 Remyelination in MS . 31 4 The Clinicopathologic Spectrum of CNS Idiopathic Inflammatory Demyelinating Disorders . 32 4.1 Acute Disseminated Encephalomyelitis . 33 4.2 Marburg Variant of Acute MS . 34 4.3 Tumefactive MS . 35 4.4 Balo Concentric Sclerosis. 35 4.5 Neuromyelitis Optica . 36 Conclusions . 38 References . 38 Abstract The last decade has seen a resurgence of interest in MS neuropathology. This resurgence was partly fueled by the development of new molecular and histochemical tools to examine the MS lesion microscopically, as well as technological advances in neuroimaging, which permit a dynamic assessment of lesion formation and disease progression. The heterogeneous pathology of MS in relation to stage of lesion activity, phase of disease, and clinical course is discussed. Pathological studies reveal that the immune factors associated with multiple differ- ent effector mechanisms contribute to the inflammation, demyelination, and tissue injury observed in MS lesions. While many agree that pathological heterogeneity exists in white matter demyelinated lesions, it is uncertain whether these observa- tions are patient-dependent and reflect pathogenic heterogeneity or, alternatively, C. Lucchinetti Mayo Clinic College of Medicine , 200 First St. SW, Rochester, MN 55905, USA e-mail:
[email protected] M.