1. 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

2. 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:

3. 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:

4. 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:

5. 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:

6. 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: