Clinical,radiological,immunological and pathological findings in inflammatory CNS demyelination-possible markers for an antibody-mediated process

Abstract

The present report describes immunopathological, radiologcal and serological characteristics of antibody-mediated demyelination in a multiple sclerosis (MS) case with the main findings: (1) immunoglobulin and complement deposits in areas of active demyelination accompanied by massive macrophage activation; (2) ring-enhancing lesions in T1-weighted MRI after gadolinium application; (3) high titers of serum anti-myelin antibodies; and (4) signs of macrophage activation in the serum. Plasmapheresis may be a successful treatment for the type of inflammatory demyelination shown in the present case.

Keywords

Multiple sclerosis antibody plasmapheresis

Get full access to this article

View all access options for this article.

References

Lucchinetti CF et al. (1996) Distinct patterns of Multiple Sclerosis pathology indicates heterogeneity in pathogenesis . Brain Pathol 6: 259-274 .

Linington C et al. (1992) Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody . J Neuroimmunol 40: 219-224 .

Linington C et al. (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein . Am J Pathol 130: 443-454 .

Adelmann M et al. (1995) The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat . J Neuroimmunol 63: 17-27 .

Storch MK et al. (1998) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology . Brain Pathol 8: 681-694 .

Prineas JW , Graham JS. (1981) Multiple Sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown . Ann Neurol 10: 149-158 .

Storch MK et al. (1998) Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination . Ann Neurol 43: 465-471 .

Genain CP et al. (1999) Identification of autoantibodies associated with myelin damage in multiple sclerosis . Nature Med 5: 170-175 .

Lucchinetti C et al. (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination . Ann Neurol 47: 707-717 .

10.

Reindl M et al. (1999) Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study . Brain 122: 2047-2056 .

11.

Weinshenker BG et al. (1999) A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease . Ann Neurol 46: 878-886 .

12.

Brück W et al. (1997) Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology . Ann Neurol 42: 783-793 .

13.

Poser CM et al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols . Ann Neurol 13: 227-231 .

14.

Lassmann H et al. (1998) Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna . J Neuroimmunol 86: 213-217 .

15.

Brück W et al. (1995) Monocyte/macrophage differentiation in early multiple sclerosis lesions . Ann Neurol 38: 788-796 .

16.

Breitschopf H et al. (1992) In situ hybridization with digoxigenin-labeled probes: sensitive and reliable detection method applied to myelinating rat brain . Acta Neuropathol 84: 581-587 .

17.

Bogumil T et al. (1998) Serum levels of macrophage-derived protein MRP8/14 are elevated in active multiple sclerosis . Neurosci Lett 247: 195-197 .

18.

Gay D , Esiri M. (1991) Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study . Brain 114: 557-572 .

19.

Aarli JA et al. (1975) Binding of normal human IgG to myelin sheaths, glia and neurons . Immunology 28: 171-185 .

20.

Vanguri P , Shin ML. (1986) Activation of complement by myelin: identification of C1-binding proteins of human myelin from central nervous tissue . J Neurochem 46: 1535-1541 .

21.

Karni A et al. (1999) Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis . Arch Neurol 56: 311-315 .

22.

Clanet M , Berry I. (1998) Magnetic resonance imaging in multiple sclerosis . Curr Opin Neurol 11: 299-303 .

23.

Fazekas F et al. (1999) The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis . Neurology 53: 448-456 .

24.

Powell T , Sussman JG , Davies-Jones GAB. (1992) MR imaging in acute multiple sclerosis: ringlike appearance in plaques suggesting the presence of paramagnetic free radicals . AJNR Am J Neuroradiol 13: 1544-1546 .

25.

Masdeu JC et al. (2000) Open-ring imaging sign. Highly specific for atypical brain demyelination . Neurology 54: 1427-1433 .

26.

Rodriguez M et al. (1993) Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination . Neurology 43: 1100-1104 .

27.

Radzun HJ et al. (1991) Detection of a monocyte/macrophage differentiation antigen in routinely processed paraffin-embedded tissues by monoclonal antibody Ki-M1P . Lab Invest 65: 306-315 .

28.

Piddlesden SJ et al. (1993) The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement . Am J Pathol 143: 555-564 .