Substantial advances have occurred in the understanding of someof the central mechanisms underlying the inflammation, demyelination,and neurodegeneration that occur in multiple sclerosis sincethe topic was last reviewed in the Journal.1 Accordingly, theavailable clinical strategies for the management of the diseasehave widened (Table 1).2 However, the treatment options forthe disease are most effective during the relapsingremittingphase (relapsingremitting multiple sclerosis), whichis characterized by clinical exacerbations, inflammation, andevidence of plaques within the brain and spinal cord on magneticresonance imaging (MRI). Less understood are factors that promotethe transition from relapsingremitting . . . [Full Text of this Article]
Evolution of the Multiple Sclerosis Plaque
Cells Involved in the Pathogenesis of the Multiple Sclerosis Plaque
T Cells
B Cells
Other Immune Cells
Disease Initiation and Pathogenesis
Pathogenesis of Multiple Sclerosis Lesions Revisited
Neuropathology
Classification of Lesions Stages or Types?
Axonal Dysfunction and Channelopathy
Excitatory Amino Acid Receptors and Neurodegeneration
Growth Factors
The Enigma of Remyelination
A Role for Oligodendrocyte Apoptosis?
The Plaque Edge A Fine Line
Radiographic Measures of the Lesion's Pathological Character
Prospects for Characterizing the Evolution and Progression of Multiple Sclerosis
Source Information
From the Departments of Neurology and Ophthalmology (E.M.F.), and the Department of Neurology and the Center for Immunology (M.K.R.), University of Texas Southwestern Medical Center at Dallas, Dallas; and the Division of Neuropathology, the Department of Pathology and Neurology, Albert Einstein College of Medicine, Bronx, N.Y. (C.S.R.).
Address reprint requests to Dr. Frohman at the Department of Neurology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390, or at elliot.frohman@utsouthwestern.edu.
This article has been cited by other articles:
Frohman, T. C., Galetta, S., Fox, R., Solomon, D., Straumann, D., Filippi, M., Zee, D., Frohman, E. M.
(2008). Pearls & Oy-sters: The medial longitudinal fasciculus in ocular motor physiology. Neurology
70: e57-67
[Abstract][Full Text]
Chen, J. W., Breckwoldt, M. O., Aikawa, E., Chiang, G., Weissleder, R.
(2008). Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis. Brain
131: 1123-1133
[Abstract][Full Text]
Davis, S. L., Frohman, T. C., Crandall, C. G., Brown, M. J., Mills, D. A., Kramer, P. D., Stuve, O., Frohman, E. M.
(2008). Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis. Neurology
70: 1098-1106
[Abstract][Full Text]
McCandless, E. E., Piccio, L., Woerner, B. M., Schmidt, R. E., Rubin, J. B., Cross, A. H., Klein, R. S.
(2008). Pathological Expression of CXCL12 at the Blood-Brain Barrier Correlates with Severity of Multiple Sclerosis. Am. J. Pathol.
172: 799-808
[Abstract][Full Text]
Jurynczyk, M., Jurewicz, A., Raine, C. S., Selmaj, K.
(2008). Notch3 Inhibition in Myelin-Reactive T Cells Down-Regulates Protein Kinase C{theta} and Attenuates Experimental Autoimmune Encephalomyelitis. J. Immunol.
180: 2634-2640
[Abstract][Full Text]
Minagar, A., Alexander, J. S., Schwendimann, R. N., Kelley, R. E., Gonzalez-Toledo, E., Jimenez, J. J., Mauro, L., Jy, W., Smith, S. J.
(2008). Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis: An Open-Label Trial. Arch Neurol
65: 199-204
[Abstract][Full Text]
Frohman, E. M., Costello, F., Stuve, O., Calabresi, P., Miller, D. H., Hickman, S. J., Sergott, R., Conger, A., Salter, A., Krumwiede, K. H., Frohman, T. C., Balcer, L., Zivadinov, R.
(2008). Modeling Axonal Degeneration Within the Anterior Visual System: Implications for Demonstrating Neuroprotection in Multiple Sclerosis. Arch Neurol
65: 26-35
[Abstract][Full Text]
Rejdak, K., Petzold, A., Stelmasiak, Z., Giovannoni, G.
(2008). Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis. Mult Scler
14: 59-66
[Abstract]
Nessler, S., Boretius, S., Stadelmann, C., Bittner, A., Merkler, D., Hartung, H.-P., Michaelis, T., Bruck, W., Frahm, J., Sommer, N., Hemmer, B.
(2007). Early MRI changes in a mouse model of multiple sclerosis are predictive of severe inflammatory tissue damage. Brain
130: 2186-2198
[Abstract][Full Text]
Antony, J. M., Ellestad, K. K., Hammond, R., Imaizumi, K., Mallet, F., Warren, K. G., Power, C.
(2007). The Human Endogenous Retrovirus Envelope Glycoprotein, Syncytin-1, Regulates Neuroinflammation and Its Receptor Expression in Multiple Sclerosis: A Role for Endoplasmic Reticulum Chaperones in Astrocytes. J. Immunol.
179: 1210-1224
[Abstract][Full Text]
Lunemann, J. D., Kamradt, T., Martin, R., Munz, C.
(2007). Epstein-Barr Virus: Environmental Trigger of Multiple Sclerosis?. J. Virol.
81: 6777-6784
[Full Text]
Ransohoff, R. M.
(2007). Natalizumab for Multiple Sclerosis. NEJM
356: 2622-2629
[Full Text]
Frohman, E. M., Kerr, D.
(2007). Is Neuromyelitis Optica Distinct From Multiple Sclerosis?: Something for "Lumpers" and "Splitters". Arch Neurol
64: 903-905
[Full Text]
Roach, E. S.
(2007). Is Neuromyelitis Optica a Distinct Entity?. Arch Neurol
64: 906-906
[Full Text]
Rossi, C., Padmanaban, D., Ni, J., Yeh, L.-A., Glicksman, M. A., Waldner, H.
(2007). Identifying Druglike Inhibitors of Myelin-Reactive T Cells by Phenotypic High-Throughput Screening of a Small-Molecule Library. J Biomol Screen
12: 481-489
[Abstract]
Forte, M., Gold, B. G., Marracci, G., Chaudhary, P., Basso, E., Johnsen, D., Yu, X., Fowlkes, J., Rahder, M., Stem, K., Bernardi, P., Bourdette, D.
(2007). Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc. Natl. Acad. Sci. USA
104: 7558-7563
[Abstract][Full Text]
Lawson, B. R., Manenkova, Y., Ahamed, J., Chen, X., Zou, J.-P., Baccala, R., Theofilopoulos, A. N., Yuan, C.
(2007). Inhibition of Transmethylation Down-Regulates CD4 T Cell Activation and Curtails Development of Autoimmunity in a Model System. J. Immunol.
178: 5366-5374
[Abstract][Full Text]
Magliozzi, R., Howell, O., Vora, A., Serafini, B., Nicholas, R., Puopolo, M., Reynolds, R., Aloisi, F.
(2007). Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain
130: 1089-1104
[Abstract][Full Text]
Benito, C., Romero, J. P., Tolon, R. M., Clemente, D., Docagne, F., Hillard, C. J., Guaza, C., Romero, J.
(2007). Cannabinoid CB1 and CB2 Receptors and Fatty Acid Amide Hydrolase Are Specific Markers of Plaque Cell Subtypes in Human Multiple Sclerosis. J. Neurosci.
27: 2396-2402
[Abstract][Full Text]
Aktas, O., Ullrich, O., Infante-Duarte, C., Nitsch, R., Zipp, F.
(2007). Neuronal Damage in Brain Inflammation. Arch Neurol
64: 185-189
[Abstract][Full Text]
Jurewicz, A., Matysiak, M., Raine, C. S., Selmaj, K.
(2007). Soluble Nogo-A, an inhibitor of axonal regeneration, as a biomarker for multiple sclerosis. Neurology
68: 283-287
[Abstract][Full Text]
Kel, J., Oldenampsen, J., Luca, M., Drijfhout, J. W., Koning, F., Nagelkerken, L.
(2007). Soluble Mannosylated Myelin Peptide Inhibits the Encephalitogenicity of Autoreactive T Cells during Experimental Autoimmune Encephalomyelitis. Am. J. Pathol.
170: 272-280
[Abstract][Full Text]
Patrikios, P., Stadelmann, C., Kutzelnigg, A., Rauschka, H., Schmidbauer, M., Laursen, H., Sorensen, P. S., Bruck, W., Lucchinetti, C., Lassmann, H.
(2006). Remyelination is extensive in a subset of multiple sclerosis patients. Brain
129: 3165-3172
[Abstract][Full Text]
Zhang, Y., Taveggia, C., Melendez-Vasquez, C., Einheber, S., Raine, C. S., Salzer, J. L., Brosnan, C. F., John, G. R.
(2006). Interleukin-11 Potentiates Oligodendrocyte Survival and Maturation, and Myelin Formation.. J. Neurosci.
26: 12174-12185
[Abstract][Full Text]
Stuve, O., Marra, C. M., Bar-Or, A., Niino, M., Cravens, P. D., Cepok, S., Frohman, E. M., Phillips, J. T., Arendt, G., Jerome, K. R., Cook, L., Grand'Maison, F., Hemmer, B., Monson, N. L., Racke, M. K.
(2006). Altered CD4+/CD8+ T-Cell Ratios in Cerebrospinal Fluid of Natalizumab-Treated Patients With Multiple Sclerosis.. Arch Neurol
63: 1383-1387
[Abstract][Full Text]
Amend, B., Doster, H., Lange, C., Dubois, E., Kalbacher, H., Melms, A., Bischof, F.
(2006). Induction of Autoimmunity by Expansion of Autoreactive CD4+CD62Llow Cells In Vivo. J. Immunol.
177: 4384-4390
[Abstract][Full Text]
Gold, R., Hohlfeld, R.
(2006). Multiple sclerosis therapy: new agents carry new risks. PN
6: 248-251
[Full Text]
(2006). Two-Year Benefit from Natalizumab for MS. JWatch Neurology
2006: 1-1
[Full Text]