Cortical demyelination and diffuse white matter injury in multiple sclerosis.

  title={Cortical demyelination and diffuse white matter injury in multiple sclerosis.},
  author={Alexandra Kutzelnigg and Claudia F. Lucchinetti and Christine Stadelmann and Wolfgang Br{\"u}ck and Helmut Rauschka and Markus Bergmann and Manfred Schmidbauer and Joseph E. Parisi and Hans Lassmann},
  journal={Brain : a journal of neurology},
  volume={128 Pt 11},
Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques… 

Cortical pathology in multiple sclerosis

Studies on the pathogenesis of cortical demyelination, cortical damage, and repair will elucidate basic principles of multiple sclerosis lesion formation, however, more sensitive imaging tools are required to study the impact of cortical lesions on clinical symptoms, disability, and disease progression.

Meningeal and cortical grey matter pathology in multiple sclerosis

Early cortical lesions in multiple sclerosis are highly inflammatory, suggesting that neurodegeneration in MS occurs on an inflammatory background and raising interesting questions regarding the role of cortical demyelination and meningeal inflammation in initiating and perpetuating the disease process in early MS.

Substantial subpial cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology?

Cases of progressive MS with substantial subpial cortical demyelination that is independent of underlying white matter lesion area support the implications that these lesions may in-part arise through different pathogenetic mechanisms.

Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron

Both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients.

Grey matter pathology in multiple sclerosis

The most common lesion type consists of purely cortical lesions extending inward from the surface of the brain, this lesion subgroup is grossly underestimated by standard histochemical myelin staining methods.

An Animal Model of Cortical and Callosal Pathology in Multiple Sclerosis

The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.

White Matter Damage in Multiple Sclerosis

Current knowledge on the interrelation between the processes of inflammation, neurodegeneration and demyelination that occurs in MS is summarized and the mechanisms that may be involved in the damage of the different cellular components of white matter are analyzed.

Widespread Demyelination in the Cerebellar Cortex in Multiple Sclerosis

It is described that the cerebellar cortex is a major predilection site for demyelination, in particular in patients with primary and secondary progressive MS, and is identified as a potential substrate of Cerebellar dysfunction in MS.

Interplay between mechanisms of damage and repair in multiple sclerosis

Remyelination represents an important mechanism of tissue repair in multiple sclerosis and already occurs at an early stage of lesion development and in both white and grey matter lesions.



Axonal changes in chronic demyelinated cervical spinal cord plaques.

The results on the cervical cord combined with other observations support the concept of slow axonal degeneration rather than acute damage as a cause of chronic disability in multiple sclerosis.

Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis.

Using formalin-fixed brains of eight multiple sclerosis patients and eight age-matched controls, the relationship between demyelinating lesion load in three volumes of the cerebral white matter and the loss of axons in NAWM of the corresponding three projection regions in the corpus callosum is examined.

In vivo evidence for axonal dysfunction remote from focal cerebral demyelination of the type seen in multiple sclerosis.

It is concluded that effects of damage or dysfunction to axons traversing inflammatory lesions can be transmitted over long distances in the normal-appearing white matter.

Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions

The hypothesis that demyelination, axonal transection, dendritic tran section, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients is supported.

Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis.

Widespread axonal pathology, largely independent of MRI-visible inflammation and too extensive to be completely reversible, occurs in patients even at the earliest clinical stage of multiple sclerosis, and argues strongly in favour of early neuroprotective intervention.

Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability.

Cerebral NAA/Cr and MTr values are diffusely decreased in MS patients with early disease, low demyelinating lesion load, and no significant disability, suggesting that axonal and/or tissue injury begins very early in the course of MS and might be at least partially independent of cerebral Demyelination.

Immunopathology of secondary‐progressive multiple sclerosis

Findings suggest that slowly expanding lesions (progressive plaques), in which ongoing myelin breakdown occurs in the absence of florid perivascular cell cuffing or other histological signs of acute inflammation, contribute to disease progression in cases of secondary‐progressive multiple sclerosis.

Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination

At a given time point of the disease, the patterns of demyelination were heterogeneous between patients, but were homogenous within multiple active lesions from the same patient, suggesting that MS may be a disease with heterogeneous pathogenetic mechanisms.

In vivo assessment of the brain and cervical cord pathology of patients with primary progressive multiple sclerosis.

The data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP multiple sclerosis patients, whose extent seems to match that of SPmultiple sclerosis patients with similar levels of disability, and suggest that the severity of multiple sclerosis pathology in the cervical cord is one of the factors contributing to neurological impairment in PPmultiple sclerosis.

MRI dynamics of brain and spinal cord in progressive multiple sclerosis.

Although the detection of new lesions by frequent cord imaging using current technology has little role in the monitoring of disease activity in progressive multiple sclerosis, the serial measurement of cord cross sectional area may be important.