Inflammatory Cortical Demyelination in Early Multiple Sclerosis Background Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease. Methods We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and a topographic association between cortical demyelination and meningeal inflammation. Diagnoses were ascertained in a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5 years). Results Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination. Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study. Conclusions In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. (Funded by the National Multiple Sclerosis Society and the National Institutes of Health.) Supported by grants from the National Multiple Sclerosis Society (NMSS RG3185-B-3, to Dr. Lucchinetti) and the National Institutes of Health (1R01NS049577, to Dr. Lucchinetti, and P50NS38667, to Dr. Ransohoff). Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank Patricia Ziemer for technical assistance, Linda Linbo for assistance in patient recruitment, and Dr. Gabriele DeLuca for editorial input on an earlier draft of the manuscript. Origen:

La desmielinización inflamatoria en el cortex comienza en estadios tempranos de la esclerosis múltiple Las lesiones corticales desmielinizantes son comunes en etapas tempranas de la esclerosis múltiple (EM), según se publica recientemente en la revista The New England Journal of Medicine. Utilizando el tejido cortical obtenido durante la biopsia cerebral de enfermos de EM, los investigadores encontraron que las lesiones corticales eran frecuentes y estaban fuertemente asociadas con la inflamación meníngea. Este hallazgo sugiere que el proceso inflamatorio que conduce a la EM en la materia blanca también se produce en la materia gris. De 563 muestras, la desmielinización cortical estaba presente en el 38% de los pacientes. Veinticinco pacientes con desmielinización cortical mostraban EM definida, lo que representa el 81% de 33 pacientes, y 33 pacientes que no mostraban desmielinización cortical si tenían EM definida. El equipo encontró que el 82% de las lesiones mostraron células T CD3 + infiltradas, y el 41% de las lesiones macrófagos asociados a la desmielinización. También encontraron que la inflamación de las meninges se asoció con desmielinización cortical en los pacientes de los que se disponía de suficiente tejido meníngeo para el estudio. La presencia de inflamación meníngea está fuertemente asociada con una mayor probabilidad de desmielinización, de casi 45 veces una mayor probabilidad. Origen: