Multipe Sclerosis - Pathology

Is MS only one Disease? - updated: 16 November 2009

The pathological spectrum of CNS inflammatory demyelinating diseases

Semin Immunopathol. 2009 Sep 25.

Hu W, Lucchinetti CF.

Inflammatory demyelinating diseases of the central nervous system (CNS) occur throughout the world and are the leading cause of nontraumatic neurological disability in young adults. They represent a broad spectrum of disorders that vary in their clinical course, regional distribution, and pathology. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. Multiple sclerosis (MS), the most common inflammatory demyelinating CNS disease affecting approximately one million adults, shares the basic pathological hallmark of CNS inflammatory demyelination. Advances based on recent systematic clinicopathologic-serologic correlative approaches have led to novel insights with respect to the classification of this disorder, the pathologic substrate of disability, a better understanding of the underlying pathogenic mechanisms involved in lesion formation, as well as the clinical relevance of cortical demyelination and normal appearing white matter pathology. In addition to prototypic MS, these diseases include Marburg variant of acute MS, Balo's concentric sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, and tumefactive MS. The last decade has seen a resurgence of interest in examining the lesions of these inflammatory demyelinating CNS disorders with newer and more sophisticated immunological and molecular tools. Herein, we review the clinicopathologic features of these CNS inflammatory demyelinating disorders and discuss recent advances in understanding their immunopathogenesis.

Publication Types:

• Review

Pathological heterogeneity of idiopathic central nervous system inflammatory demyelinating disorders.

Curr Top Microbiol Immunol. 2008;318:19-43.

Lucchinetti C.

The last decade has seen a resurgence of interest in MS neuropathology. This resurgence was partly fueled by the development of new molecular and histochemical tools to examine the MS lesion microscopically, as well as technological advances in neuroimaging, which permit a dynamic assessment of lesion formation and disease progression. The heterogeneous pathology of MS in relation to stage of lesion activity, phase of disease, and clinical course is discussed. Pathological studies reveal that the immune factors associated with multiple different effector mechanisms contribute to the inflammation, demyelination, and tissue injury observed in MS lesions. While many agree that pathological heterogeneity exists in white matter demyelinated lesions, it is uncertain whether these observations are patient-dependent and reflect pathogenic heterogeneity or, alternatively, are stage-dependent with multiple mechanisms occurring sequentially within a given patient. Evidence supporting both concepts is presented. Remyelination is present in MS lesions; however, the factors contributing to the extent of repair and oligodendrocyte survival differ depending on the disease phase. A variable and patient-dependent extent of remyelination is observed in chronic MS cases and will likely need to be considered when designing future clinical trials aimed to promote CNS repair. MS is one member of a spectrum of CNS idiopathic inflammatory demyelinating disorders that share the basic pathological hallmark of CNS inflammatory demyelination. Advances based on recent systematic clinicopathologic-serologic correlative approaches have led to novel insights with respect to the classification of these disorders, as well as a better understanding of the underlying pathogenic mechanisms.

Publication Types:

• Review

Acute disseminated encephalomyelitis: study of factors involved in a possible development towards multiple sclerosis

Neurologia. 2008 Nov;23(9):546-54.

Tur C, Téllez N, Rovira A, Tintoré M, Río J, Nos C, Perkal H, Castilló J, Horga A, León A, Galán I, Sastre-Garriga J, Montalbán X.

Acute disseminated encephalomyelitis (ADEM) is an uncommon disease characterized by inflammation and demyelination of the central nervous system (CNS). It typically occurs after a viral infection or vaccination and is more frequent in children. Its immediate and longterm prognosis is expected to be good (20% of cases with sequelae). Although ADEM is typically monophasic, occasional relapses may occur. Differential diagnosis, mostly in the early phases, is established with multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the CNS that may have worse prognosis. Traditionally it has been believed that 10% of ADEM patients develop MS. However, this percentage could be higher according to several recently published clinical series. Some clinical and paraclinical patterns are considered to confer risk of developing MS when present in ADEM patients. Our study has aimed to: a) describe a series of 29 patients (22 children and 9 adults) admitted in our hospital and diagnosed of ADEM between 1990 and 2005; b) study those patients considered to have risk patterns of developing MS, and c) compare the child and adult populations of our series. After a median 55 month follow-up, 6 children (27%) and no adults developed MS. In our series, risk patterns for developing MS predicted conversion to MS more accurately in children than in adults. Eight patients (6 children and 2 adults) had sequelae, cognitive in 6 of them. Our work supports that also observed in recent publications: that both conversion to MS or presence of sequelae after an episode of ADEM are more frequent than traditionally considered.

Publication Types:

• Review

Pathogenesis of multiple sclerosis and other neural autoimmune diseases

Verh Dtsch Ges Pathol. 1996;80:109-15

Lassmann H.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Its pathological hallmark is the demyelinated plaque with reactive glial scarring. Recent neuropathological and immunopathological data suggest a pronounced pathologic heterogeneity of MS plaques. Although demyelination is present in all lesions, the extent of oligodendroglia loss, remyelination and axonal pathology is highly variable. In the present review, data are discussed on the fate of myelin forming cells in MS lesions, which suggest that fundamentally different immunological mechanisms may be involved in the formation of the lesions in different MS patients. Possible immunopathogenetic mechanisms are discussed by comparing the different types of MS lesions with those described in different experimental models of inflammatory demyelinating disease.

Publication Types:

• Review

Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis

Brain Pathol. 1996 Jul;6(3):259-74

Lucchinetti CF, Brück W, Rodriguez M, Lassmann H.

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. The hallmark of its pathology is the demyelinated plaque with reactive glial scar formation. However, a detailed analysis of the patterns of demyelination, oligodendroglia cell pathology and the reaction of other tissue components suggests that the pathogenesis of myelin destruction in this disease may be heterogeneous. In this review we present a new classification scheme of lesional activity on the basis of the molecular composition of myelin degradation products in macrophages. When these criteria are used, different patterns of demyelination can be distinguished, including demyelination with relative preservation of oligodendrocytes, myelin destruction with concomitant and complete destruction of oligodendrocytes or primary destruction or disturbance of myelinating cells with secondary demyelination. Furthermore, in some cases a primary selective demyelination may be followed by a secondary oligodendrocyte loss in the established lesions. Finally, some extraordinarily severe conditions may result in destructive lesions with loss of myelin, oligodendrocytes, axons and astrocytes. This heterogeneity of plaque pathology is discussed in the context of recent experimental models of inflammatory demyelination, which show that different immunological pathways may lead to the formation of demyelinated plaques that reveal the diverse structural aspects described above. Our data indicate, that the demyelinated plaques of multiple sclerosis may reflect a common pathological end point of a variety of different immunological mechanisms of myelin destruction in this disease.

Publication Types:

• Review

Publication Types:

• Review