Inflammation and Neurodegeneration in Multiple Sclerosis

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Presentation transcript:

Inflammation and Neurodegeneration in Multiple Sclerosis John DeLuca, PhD Vice President for Research Kessler Foundation West Orange, New Jersey Claudia F. Lucchinetti, MD Professor of Neurology Chair, Division of Multiple Sclerosis and Autoimmune Neurology Mayo Clinic College of Medicine Rochester, Minnesota

Inflammation and Neurodegeneration in MS Brains Study objectives To determine the relationship between inflammation and axonal injury/destruction in MS brain tissue To determine whether disease progression and neurodegeneration may occur in MS in the absence of inflammation Autopsy material from 95 cases 67 MS patients (9 acute, 5 relapsing/remitting, 35 secondary-progressive, 13 primary-progressive, 5 benign/asymptomatic) 28 controls without neurologic disease or brain lesions (18 normal, 10 septic) Frischer JM, et al. Brain. 2009;132:1175-1189.

Inflammation and Extent of Axonal Injury in Pooled MS Patients Acute axonal injury T-cells r = 0.6, P <.001 B-cells r = 0.3, P <.01 Plasma cells r = 0.2, P <.05 HLA-D r = 0.7, P <.001 Neurofilament reactive end bulbs T-cells r = 0.5, P <.001 Plasma cells r = 0.3, P <.01 HLA-D r = 0.6, P <.001 Frischer JM, et al. Brain. 2009;132:1175-1189.

Inflammation and Extent of Acute Axonal Injury in Progressive MS Secondary-progressive MS and primary- progressive MS only T-cells r = 0.5, P <.001 B-cells r = 0.2, P <.05 Plasma cells r = 0.3, P <.05 HLA-D r = 0.6, P <.001 Controls HLA-D r = 0.3, P <.01 No association with number of T-cells, B-cells, and plasma cells Frischer JM, et al. Brain. 2009;132:1175-1189.

Pathologically Active (PA) vs Pathologically Inactive (PI) Disease in Patients with Progressive MS PI patients were significantly older and had longer disease duration than PA patients (76 vs 53 years, respectively; 372 vs 192 months, respectively); the extent of clinical deficit was similar in the 2 groups (EDSS 8.5 in both groups) PI patients had significantly lower inflammatory infiltrates than PA patients; levels in PI patients were similar to levels in age-matched or septic controls PI patients had significantly lower densities of acutely injured axons or neurofilament reactive end-bulbs; densities in PI patients were similar to those of age-matched controls Results indicate that MS-related neurodegeneration ceases as inflammation ceases Frischer JM, et al. Brain. 2009;132:1175-1189.

Summary Highly significant associations were seen between inflammation and axonal injury in lesions from the total MS population sampled, as well as lesions from patients with secondary-progressive MS and primary-progressive MS, demonstrating a close association between inflammation and neurodegeneration in all stages of MS In older patients with long-standing disease, inflammatory infiltrates and the extent of axonal injury declined to levels that were similar to those of age-matched controls, suggesting that the MS disease process may die out in older individuals with disease of long duration Frischer JM, et al. Brain. 2009;132:1175-1189.