Substantial Archaeocortical Atrophy and Neuronal Loss in Multiple Sclerosis

Papadopoulos, Dimitrios; Dukes, Sumayya; Patel, Ryan; Nicholas, Richard; Vora, Abhilash; Reynolds, Richard

doi:10.1111/j.1750-3639.2008.00177.x

Cited by 180 publications

(225 citation statements)

References 72 publications

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“…Furthermore, increased SMI-34 (hyperphosphorylated NF-H) immunostaining was seen in demyelinating grey matter of the cerebral cortex of MS patients [105]. Attempts have been made to correlate these pathological changes with clinical disability (EDSS score), matching neuronal loss, axonal damage, and synaptic loss in demyelinating grey matter of hippocampus to memory loss [106][107][108]. Upon 12 weeks of cuprizonemediated experimental demyelination, epileptiform spikes were measured by EEG/video monitoring [109].…”

Section: Cortical Demyelination and Atrophy -Mechanisms Governing Promentioning

confidence: 99%

Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?

Lee

Taghian

Petratos

2014

Acta Neuropathol Commun

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Axonal degeneration is a major determinant of permanent neurological impairment during multiple sclerosis (MS). Due to the variable course of clinical disease and the heterogeneity of MS lesions, the mechanisms governing axonal degeneration may differ between disease stages. While the etiology of MS remains elusive, there now exist potential prognostic biomarkers that can predict the conversion to clinically definite MS. Specialized imaging techniques identifying axonal injury and drop-out are becoming established in clinical practice as a predictive measure of MS progression, such as optical coherence tomography (OCT) or diffusion tensor imaging (DTI). However, these imaging techniques are still being debated as predictive biomarkers since controversy surrounds their lesion-specific association with expanded disability status scale (EDSS). A more promising diagnostic measure of axonal degeneration has been argued for the detection of reduced N-acetyl aspartate (NAA) and Creatine ratios via magnetic resonance spectroscopic (MRS) imaging, but again fail with its specificity for predicting actual axonal degeneration. Greater accuracy of predictive biomarkers is therefore warranted and may include CSF neurofilament light chain (NF-L) and neurofilament heavy chain (NF-H) levels, for progressive MS. Furthermore, defining the molecular mechanisms that occur during the neurodegenerative changes in the various subgroups of MS may in fact prove vital for the future development of efficacious neuroprotective therapies. The clinical translation of a combined Na + and Ca 2+ channel blocker may lead to the establishment of a bona fide neuroprotective agent for the treatment of progressive MS. However, more specific therapeutic targets to limit axonal damage in MS need investigation and may include such integral axonal proteins such as the collapsin response mediator protein-2 (CRMP-2), a molecule which upon post-translational modification may propagate axonal degeneration in MS. In this review, we discuss the current clinical determinants of axonal damage in MS and consider the cellular and molecular mechanisms that may initiate these neurodegenerative changes. In particular we highlight the therapeutic candidates that may formulate novel therapeutic strategies to limit axonal degeneration and EDSS during progressive MS.

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Section: Cortical Demyelination and Atrophy -Mechanisms Governing Promentioning

confidence: 99%

Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?

Lee

Taghian

Petratos

2014

Acta Neuropathol Commun

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“…The hippocampus is an archicortical gray matter structure that is impacted by MS and related to cognitive impairment [91]. Pathological studies show demyelination and neuronal loss throughout the hippocampal formation [92,93]. Recent evidence suggests that there may be subregional susceptibility to distinct MS disease processes linked to depression and cognitive impairment in the hippocampus [94,95].…”

Section: Fig 1 Serial Cerebral Magnetic Resonance (Mr) Images Demonmentioning

confidence: 99%

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

Sicotte

2011

Neurotherapeutics

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Summary: Imaging techniques, in particular magnetic resonance imaging (MRI), play an important role in the diagnosis and management of multiple sclerosis (MS) and related demyelinating diseases. Findings on MRI studies of the brain and spinal cord are critical for MS diagnosis, are used to monitor treatment response and may aid in predicting disease progression in individual patients. In addition, results of imaging studies serve as essential biomarkers in clinical trials of putative MS therapies and have led to important insights into disease pathophysiology. Although they are useful tools and provide in vivo measures of disease-related activity, there are some important limitations of MRI findings in MS, including the non-specific nature of detectable white matter changes, the poor correlation with clinical disability, the limited sensitivity and ability of standard measures of gadolinium enhancing lesions and T2 lesions to predict future clinical course, and the lack of validated biomarkers of long term outcomes. Advancements that hold promise for the future include new techniques that are sensitive to diffuse changes, the increased use of higher field scanners, measures that capture disease related changes in gray matter, and the use of combined structural and functional imaging approaches to assess the complex and evolving disease process that occurs during the course of MS.

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“…Moreover, in cotherapy with estrogens, progesterone counteracts not only EAE-induced spinal cord demyelination (Garay et al, 2008) but also cuprizone-induced demyelination of the corpus callosum (Acs et al, 2009) symptoms which are not circumscribed to the spinal cord. Brain atrophy and gray matter lesions are observed at early disease onset (Ellwardt and Zipp, 2014), whereas cell loss in CA1 and CA3 pyramidal cells of the hippocampus have been described by Papadopoulos et al (2009). The hippocampus abnormalities are closely bound to the memory impairment and cognitive decline of MS patients (Koenig et al, 2013;Sumowski and Leavitt, 2013).…”

Section: Introductionmentioning

confidence: 96%