- “Cortical deficits in multiple sclerosis on the basis of subcortical lesions”: Douglas R Jeffery et al
-”Two of the patients underwent positron emission tomography and showed profound cortical hypometabolism adjacent to subcortical white matter lesions seen on MRI. This paper points out that neurologic deficits referable to cortical sites may be caused by subcortical white matter lesions and that cognitive dysfunction in patients with MS may progress rapidly in the absence of motoria deficits or other evidence of clinical deterioration”
- “The relevance of cortical lesions in patients with multiple sclerosis” by Olivia Geisseler et al
-””26% of the MS lesions affected the gray matter”
-”We detected cortical lesions in 32 of 42 patients (76%). The highest occurrence of cortical lesions was found bilaterally in the parahippocampal gyrus”
-”reduction of global cortical thickness in cortical lesion patients”
-”cortical lesion patients performed significantly worse in memory tests”
-”patients without cortical lesions showed normal cortical thickness and mnestic
functions when compared with a group of healthy controls”
-”That a reduction of cortical thickness can occur in MS and that this thinning is related
to global and even specific cognitive impairment has been found in previous studies”
-”We observed an uneven spatial distribution of cortical lesions over the cerebral cortex,
with a prominent accumulation in memory-relevant mesiotemporal regions,
Particularly the bilateral parahippocampal gyrus”
-”Coebergh et al described a patient with acute memory impairment, associated with
hippocampal and cortical lesions. Cortical lesions were also associated with cognitive
decline in a group of 13 MS patients…we conclude that mesiotemporal cortical lesions
are highly prevalent in RRMS patients and play a crucial role in the development of
mnestic dysfunction”
-”In all patients, including those of the CL group, the majority of MS lesions was located
subcortically….we propose that our CL group may represent a ‘cortically dominant’
subtype of MS. In these patients, pathophysiological processes might be different from
those of patients without cortical involvement”
-”Filippi and colleagues showed that the presence of at least one cortical lesion is
associated with a high risk of conversion from clinically isolated syndrome to definite MS
within a short period”
“The occurrence of cortical lesions in MS is clinically relevant insofar as it is associated
with neurodegenerative cortical thinning and mnestic dysfunction”
- “Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis” by M Filippi et al
-””The final multivariate model showed that 1 or more ICL (intracortical lesion), 1 or more infratentorial lesion, and one or more gadolinium-enhancing lesion or one or more spinal cord lesion were independent predictors of clinically-definite MS; the presence of at least 2 of these variables was the best DIS criterion in both samples”
-”The accuracy of MRI diagnostic criteria for MS is increased when considering the presence of intracortical lesions on baseline scans from patients at presentation with CIS suggestive of MS”
- “Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage: A Comparative Ultrahigh-Field Strength Magnetic Resonance Imaging Study” by Tim Sinnecker et al
-”Our results indicate structural damage beyond demyelination in every lesion depicted, which is in accordance with postmortem histopathological studies”
-”the 7T MPRAGE clearly delineated every cortical lesion that was visualized by any other MRI sequence at 1.5 or 7T”
-”These black holes are associated with clinical worsening and cerebral atrophy”
-”histopathological studies demonstrated severe tissue destruction as the morphologic correlate of black holes”
“Many cortical lesions still remain undetected in vivo”
-”Cortical lesions were characterized according to the histopathological criteria of Peterson et al into lesions affecting the white matter and at least 1 layer of the cortex (leukocortical lesions, perivascular purely cortical lesions, and subpial lesions)
-”3 subpial cortical lesions were delineated weakly by the 7T MPRAGE sequence but were much more pronounced at the 7T FLASH sequence”
-”MPRAGE visualized significantly more lesions compared with T2 (FLASH)
-”demonstrating axonal transection in each MS lesion, visualized as terminal axonal ovoids”
-”T1 hypointensity at 9.4T is a predictor of neuronal density in cortical lesions”
-”7T MPRAGE hypointense lesions do not change their appearance over the course of more than 1 year and thus may well express brain parenchymal destruction”
-”In contrast to the 7T FLASH sequence ,the T1-weighted MPRAGE sequence was not able to depict the whole subpial area of type III lesions (subpial)”
- “Subcortical lesions are common in multiple sclerosis (MS) patients. Subpial lesions are the most common type of cortical lesion in MS, making up about 65% of them. They are ribbon-like areas of demyelination that often extend over multiple gyri and sulci.”
- “Subcortical lesions in the frontal lobe can cause learning difficulties, visual-motor issues, and problems with attention. Subpial lesions can cause lower back pain, muscle tightness, numbness, tingling, weakness in the legs, and stiffness.”
- “Also known as intracortical lesions, these lesions are small and are found within the gray matter” (Type 2)
- “Also known as leukocortical lesions, these lesions extend into both the gray and white matter at the border between them” (Type 1)
- “Subcortical lesions are found in the white matter above the tentorium, while subpial lesions are found in the cortex and touch the pial surface.”
- “Meningeal and cortical grey matter pathology in multiple sclerosis” by Bogdan F Gh Popescu et al
-”cognitive impairment and seizures could be better explained by pathological processes affecting the grey matter”
-”Seven cortical demyelinated lesion types have been described based on their location relative to the venous supply of the cerebral cortex”
-”We consider lesions affecting all 6 cortical layers with only marginal involvement of the whit matter as subpial, rather than leukocortical demyelinated lesions”
-”the center of the lesion is in the grey and not in the white matter”
-”The most extensive cortical demyelination has been detected in the cingulate gyrus, frontal, temporal, insular and cerebellar cortices as well as the hippocampi of patients with progressive MS, while the paracentral lobule and the occipital lobe are less frequently affected but not spared”
-”Subpial demyelination preferentially involves the sulci”
-”Pathological studies have shown that cortical demyelination is prominent and extensive in PPMS and SPMS and in MS patients with cognitive deficits, suggesting it may be the pathological substrate of progression and an important pathologic correlate of irreversible disability and cognitive impairment”
-”cortical demyelinated lesions are less inflammatory than white matter lesions”
-”Purely cortical lesions reportedly lack the lymphocytic and macrophagic inflammatory infiltrates, complement deposition and blood-brain barrier breakdown”
-”The majority of phagocytic cells in cortical lesions have the morphology of activated ramified microglia that appear in close apposition to neurites and neuronal cell bodies. Neurons are also damaged as evidenced by neuronal atrophy and apoptosis and a mild to moderate reduction of neuronal densities in the demyelinated MS cortex”
-”cortical demyelination is devoid of inflammatory lymphocytes and macrophages and is driven in part by organized meningeal inflammatory infiltrates”
-”Corroborated with evidence for neuronal degeneration and glial loss, this has led to the suggestion that neurodegeneration in MS proceeds independent of inflammation”
-”recent histopathological studies have shown that cortical demyelination may occur spatially removed from and without obvious anatomical relationships to the white matter pathology. Therefore, it is plausible that the cortex could represent an important early and/or initial target of the MS disease process”
-”37% of patients with CIS show the presence of cortical lesions”
-”cortical lesions in early MS also show loss of oligodendrocyte and axonal and neuronal injury”
-”The presence of inflammatory cortical demyelination in early MS argues against a primary neurodegenerative process at this stage of disease”
-”Meningeal inflammation”
- “Cortical lesions uniquely predict motor disability accrual and form rarely in the absence of new white matter lesions in multiple sclerosis” by Erin S Beck, Daniel S Reich, et al
-cortical lesions are common in MS and associate with disability and progressive disease
-baseline CL volume was higher in people with worsening disability and individuals with RRMS who transitioned to SPMS
-CL but not WML burden predicts future worsening of disability, suggesting that the relationship between CL and disability progression is related to long-term effects of lesions that form in the earlier stages of disease rather than to ongoing lesion formation
-CLs are associated with disability and progression possibly to a greater extent than white matter lesions
-CLs and in particular subpial CLs, which involve the superficial cortical layers, have been hypothesized to form via a partially distinct mechanism from other MS lesions that is related to inflammation in the overlaying meninges
-suggesting that the relationship between cortical lesions and disability progression is related to long-term effects of lesions that formed earlier in the earlier states of disease rather than to ongoing lesion formation
-2 people in the active RRMS had relapses with new lesions in the WM, spinal cord and cortex
-2 people with clinical relapses in the stable RRMS group; neither had new lesions
-NECESSARY TO STOP CORTICAL LESION FORMATION EARLY IN THE DISEASE!
- “Cortical lesion hotspots and association of subpial lesions with disability in MS” by Erin S Beck, Daniel S Reich, et al
-cortical lesions were found in 94% of RRMS
-highest lesion burden in supplementary motor cortex and highest prevalence in superior frontal gyrus
-subpial lesion burden is not strongly correlated with WMLs, suggesting differences in inflammation and repair mechanisms
-86% of those in study had at least one subpial lesion
-cortical lesion number was higher in progressive than RRMS
-leukocortical lesion number and volume; subpial lesion number; and spinal cord lesion number were higher in progressive MS; intracortical lesion number and WM and cortical (except leukocortical) lesion volumes were not
-the average percentage of cortex occupied by cortical lesions was highest in the parietal lobe
-lesion number was higher in progressive MS in the cuneus, middle occipital gyrus and precentral gyrus
-no correlation between leptomeningeal enhancement number and cortical lesion number, cortical lesion volume or white matter lesion number
-total and subtype cortical lesion volumes correlated with EDSS, 25TW, 9HPT and MSS; also a correlation between cortical lesion volume and SDMT
-there was a significant relationship between cortical lesion volume and EDSS, 25TW and SDMT
-all subtypes of cortical lesions are more common in progressive MS and cortical lesion volumes are correlated with measures of disability
-pathology studies demonstrate few inflammatory cells in chronic cortical lesions eve in leukocortical lesions in which there are macrophages/microglia in the WM portion of the lesion
-each cortical lesion subtype was associated with multiple measures of disability
- “Contribution of new and chronic cortical lesions to disability accrual in MS” by Erin S Beck, Daniel S Reich, et al
-cortical lesions are common in MS and are associated with disability and progressive disease
-new cortical lesions were not associated with greater change in any individual disability measure or in a composite measure of disability worsening
-baseline cortical lesion volume was higher in people with worsening disability and in individuals with RRMS who converted to SPMS
-cortical but not WM lesion burden predicts disability worsening, suggesting that disability progression is related to long-term effects of cortical lesions that form early in the disease rather than to ongoing cortical lesion formation
-limited data exist on whether cortical lesions detected with sensitive 7T MRI methods continue to form in people on moderate and high-efficacy DMTs and if so whether new cortical lesions contribute to ongoing accrual of disability
-DMT did not differ between people with new vs no new cortical lesions; 2 on Ocrevus and 1 on Tysabri got new cortical lesions; 1 on Ocrevus formed a new WML
-no intracortical lesions or subpial lesions expanded into the white matter
-baseline cortical lesion is associated with worsening disability over time
-change in subpial lesion volume was higher in people with progression of disability
-at baseline, individuals who transitioned to SPMS had higher total cortical lesion volume
-no difference in leukocortical lesion volume, WML volume or spinal cord lesion number between those who transitioned to SPMS or didn’t, nor did baseline brain volume differ between the groups
-baseline cortical lesion volume was higher in people who had subsequent worsening of motor disability
-activated microglia/macrophages within chronic cortical lesions are rare; chronic inflammation in cortical and in particular, subpial lesions may be related to overlying meningeal inflammation. Our data are consistent with a potential shared mechanism underlying inflammation in chronic active white matter lesions and cortical lesions
-cortical lesion burden predicts disability progression and transition to SPMS
-cortical lesions form early in disease and then exert long-term effects on disability
-more consistent correlations of cortical lesion burden with subsequent changes in motor disability than with cognitive disability change
-cortical and WML burden are not well correlated and the factors determining which patients develop cortical vs WML are unclear
-the association we find between cortical lesion burden and subsequent worsening of disability may be useful for prognostication
- “Asociation between subcortical lesions and behavioral and psychological symptoms in patients with Alzheimer’s disease” by Sebastian Plamqvist et al
-”Lacunes in the basal ganglia were associated with delusions and hallucinations”
-”Lacunes in the right basal ganglia were associated with depression”
-Lacunes in the basal ganglia resulted in a 2-3 fold increased risk of delusions, hallucinations and depression when adjusting for cognition and atrophy”
- “Cortical involvement determines impairment 30 years after a clinically isolated syndrome”: Lukas Haider
-”Many studies report an overlap of MRI and clinical findings between patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), which in part is reflective of inclusion of subjects with variable disease duration and short periods of follow-up. To overcome these limitations, we examined the differences between RRMS and SPMS and the relationship between MRI measures and clinical outcomes 30 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis. Sixty-three patients were studied 30 years after their initial presentation with a clinically isolated syndrome; only 14% received a disease modifying treatment at any time point. Twenty-seven patients developed RRMS, 15 SPMS and 21 experienced no further neurological events; these groups were comparable in terms of age and disease duration. Clinical assessment included the Expanded Disability Status Scale, 9-Hole Peg Test and Timed 25-Foot Walk and the Brief International Cognitive Assessment For Multiple Sclerosis. All subjects underwent a comprehensive MRI protocol at 3 T measuring brain white and grey matter (lesions, volumes and magnetization transfer ratio) and cervical cord involvement. Linear regression models were used to estimate age- and gender-adjusted group differences between clinical phenotypes after 30 years, and stepwise selection to determine associations between a large sets of MRI predictor variables and physical and cognitive outcome measures. At the 30-year follow-up, the greatest differences in MRI measures between SPMS and RRMS were the number of cortical lesions, which were higher in SPMS (the presence of cortical lesions had 100% sensitivity and 88% specificity), and grey matter volume, which was lower in SPMS. Across all subjects, cortical lesions, grey matter volume and cervical cord volume explained 60% of the variance of the Expanded Disability Status Scale; cortical lesions alone explained 43%. Grey matter volume, cortical lesions and gender explained 43% of the variance of Timed 25-Foot Walk. Reduced cortical magnetization transfer ratios emerged as the only significant explanatory variable for the symbol digit modality test and explained 52% of its variance. Cortical involvement, both in terms of lesions and atrophy, appears to be the main correlate of progressive disease and disability in a cohort of individuals with very long follow-up and homogeneous disease duration, indicating that this should be the target of therapeutic interventions.”
- “Juxtacortical Lesions and Cortical Thinning in Multiple Sclerosis”:
-”Juxtacortical lesion volume in relapsing-remitting MS was double that of patients with clinically isolated syndrome. The insula showed the highest density of juxtacortical lesions, followed by the temporal, parietal, frontal, and occipital lobes. Patients with relapsing-remitting MS with juxtacortical lesions showed significantly thinner cortices overall and in the parietal and temporal lobes compared with those with clinically isolated syndrome with normal brain MR imaging. The volume of subcortical structures (thalamus, pallidum, putamen, and accumbens) was significantly decreased in relapsing-remitting MS with juxtacortical lesions compared with clinically isolated syndrome with normal brain MR imaging. The spatial distribution of juxtacortical lesions was not found to overlap with areas of cortical thinning.”
-”Cortical thinning and subcortical gray matter volume loss in patients with a clinically isolated syndrome or relapsing-remitting MS was related to the presence of juxtacortical lesions, though the cortical areas with the most marked thinning did not correspond to those with the largest number of juxtacortical lesions.”
- “Early CNS neurodegeneration in radiologically isolated syndrome”:
-Our data provide novel evidence of thalamic atrophy in RIS and are consistent with previous reports in early MS stages. Thalamic volume loss is present early in CNS demyelinating disease and should be further investigated as a metric associated with neurodegeneration.
- “Imaging Cortical Damage and Dysfunction in Multiple Sclerosis”: Massimo Filippi, MD et al
-The notion that multiple sclerosis (MS) is a white matter (WM) disease of the central nervous system has been challenged by several pathological and magnetic resonance imaging (MRI) studies that have consistently revealed both focal and diffuse damage in the cerebral cortex of patients with MS.1–3 The clinical relevance of measures of cortical damage has been shown by several studies demonstrating that its extent differs between the principal MS disease phenotypes and that it correlates better with clinical disability and cognitive impairment than do measures of focal T2 lesion load or normal-appearing WM damage.1–3 Furthermore, some symptoms of the disease, such as epilepsy and fatigue, are likely to be related to cortical involvement
- “Association between retinal layer thickness and cortical lesions at the onset of clinically isolated syndrome (P11-3.012)”: Kyriakoula Varmpompiti et al
-We found that a thinner combined ganglion cell-inner plexiform layer (GCIPL) was associated with higher juxtacortical lesion numbers and volumes. A thinner peripapillary retinal nerve fiber was associated with higher leukocortical, juxtacortical and total cortical lesion volumes. A thinner GCIPL was correlated with greater disability as measured by the expanded disability status scale. A reduced thickness of GCIPL and inner nuclear layer were associated with MS diagnosis at presentation.
-This study provides support for a relationship between increased cortical damage and retinal layers thinning in CIS suggesting a common pathological process behind these alterations. The association between greater retinal damage and disability confirms the role of GCIPL as a possible biomarker of neurodegeneration even at this early stage of the disease.
- “Cortical atrophy is relevant in multiple sclerosis at clinical onset” by Massimiliano Calabrese MD et al
-We found a significant global cortical thinning in p-MS (2.22 ± 0.09 mm), RR-MS (2.16 ± 0.10 mm) and SP-MS (1.98 ± 0.11 mm) compared to CIS (2.51 ± 0.11 mm) and HV (2.48 ± 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = )0.393, p = 0.03) and absent in p-MS (r = )0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas.
-Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.
- “Subcortical Deep Gray Matter Pathology in Patients with Multiple Sclerosis Is Associated with White Matter Lesion Burden and Atrophy but Not with Cortical Atrophy: A Diffusion Tensor MRI Study”: R. Cappellani et al
-DTI measures were significantly different in whole brain, normal-appearing white matter, and normal-appearing gray matter among the groups (P < .01). Significant differences in DTI diffusivity of total subcortical deep gray matter, caudate, thalamus, and hippocampus (P < .001) were found. DTI diffusivity of total subcortical deep gray matter was significantly associated with normalized white matter volume (P < .001) and normalized cortical volume (P = .033) in healthy control patients. In both relapsing and progressive MS groups, the DTI subcortical deep gray matter measures were associated with the lesion burden and with normalized white matter volume (P < .001), but not with normalized cortical volume.
-These findings suggest that subcortical deep gray matter abnormalities are associated with white matter lesion burden and atrophy, whereas cortical atrophy is not associated with microstructural alterations of subcortical deep gray matter structures in patients with MS.
- “Imaging Cortical Damage and Dysfunction in Multiple Sclerosis” by Massimo Filippi et al
-both focal and diffuse damage in the cerebral cortex of patients with MS
-cortical damage correlates better with clinical disability and cognitive impairment than do measures of focal T2 lesion load or NAWM damage
-type 3 lesions (subpial) are most common in the neocortex of those with chronic MS
-compared with WM plaques, cortical plaques are characterized by fewer inflammatory infiltrates, less gliosis, and milder tissue loss, which is mainly due to synaptic and axonal pathology
-cortical demyelination is frequently oriented toward meningeal inflammatory infiltrates composed of B cells and dendritic cells, suggesting cytokine diffusion into the underlying cortex that might lead to microglial activation
-early onset of cortical pathology in MS
-global cortical thinning of around 10% has been found in patients with MS compared with controls
-suggesting that diffuse cortical pathology is present outside such lesions
-mitochondrial injury has been suggested as an important contributor
-oxidative damage as well
-cortical lesions develop early in MS and increase in number and size with the progression of the disease
-CLs are very important in explaining both locomotor disability and cognitive impairment; their presence is associated with other MRI indicators of damage such as T2 lesion load and WM and GM atrophy; Cls are sparse in benign and pediatric forms of MS
-the accuracy of MRI diagnostic criteria for MS increases when considering CLs on baseline scans in patients who present with a clinically isolated syndrome suggestive of MS
-high-field MRI systems seem to be especially useful for detecting subpial CLs which are notoriously difficult to detect at standard field strengths
-the location of WM lesions was not necessarily related to that of CLs and the 2 may therefore differentially influence clinical measures over the course of the disease
-cortical atrophy was found to be present throughout the entire cortex in MS and was partly independent of the presence of CLs
-several studies have demonstrated reduced MT ratio and increased mean diffusivity in the cortex of patients with different MS phenotypes including those at the earliest clinical stages of the disease
-diffuse cortical damage is not stable but tends to worsen over time, independent of the progression of damage within the WM
-a longitudinal study showed an increased rate of cortical tissue loss in patients with progressing disability compared to those with stable disease, whereas another study demonstrated that progressive neocortical loss is relevant to MS-associated cognitive impairment
-in patients with CIS, GM atrophy involves the thalamus, hypothalamus, putamen and caudate nucleus
-in patients with MS with long-standing disease or severe disability, focal thinning of the primary sensorimotor cortex has been reported
-in patients with RRMS, GM MT ratio was found to be an independent predictor of the accumulation of disability over the subsequent 8 years, while in PPMS, GM mean diffusivity predicted the accumulation of disability over a 5-year period
-fMRI abnormalities in patients with MS occur relatively early in the disease, including CIS, and tend to vary over the course over the disease, not only after an acute relapse but also in clinically stable patients
-the analysis of brain function at rest has shown a reduced activity of of the anterior regions of the default-mode network in patients with progressive MS, which correlates with cognitive impairment
-all of these abnormalities become more severe over time and are only partially associated with the location and extent of WM pathology
-the cortex has great potential to aid recovery by synaptic reorganization following injury, thus helping to counteract the progressive accumulation of structural damage due to disease; however, this ability to d and its reorganize is likely limited and its exhaustion might be an additional factor in the clinical manifestation of disease progression
- “Can white matter lesion burden predict involvement of normal appearing thalami in multiple sclerosis? Study using 3D FLAIR and DTI”: Mohamed D Homos
-the thalamus, as a relay organ, is involved in motor, sensory, integrative functions as well as sleep, memory, etc
-thalamus is vulnerable to early involvement in MS and its microscopic damage can occur before detecting thalamic lesions by conventional MRI; such microscopic damage and the microstructural integrity of the tissues can be assessed using diffusion tensor imaging (DTI) which is not included in the standardized imaging protocol for MS
-significant correlation between the volume of the WMLs in the corticothalamic pathway and the thalamic volume; this relation could be explained by the microstructural damage occurring in the thalami secondary to retrograde degeneration of the white matter fibres that pass within the white matter MS plaques
-the degree of correlation between the WML burden and thalamic diffusivity was found to be a moderate and not strong correlation; this can point to the presence of other factors affecting the diffusivity of the thalami besides the retrograde degeneration
-the thalamic diffusivity can be affected by the widespread microstructural changes occurring in the NAWM in MS patients that are probably relapted to demyelination, axonal degeneration, and secondary adaptive changes of already existing brain MS lesions that is in turn reflected upon the thalamic diffusivity
-anisotrophy is a measure of fibre integrity and directionality where water molecules move more easily paralle to white matter tracts than perpendicular to them
-no association between FA of the subcortical deep grey matter and T2 lesion load
-WML burden detected using the highly sensitive 3D FLAIR sequence does not always correlate with the microstructral damage in the normal appearing thalami
-the standardized protocol of MR examination of MS patients is not sufficient if the pathological damage in normal appearing thalami needs to be assessed; DIT needs to be added to the examination protocol in such cases to assess thalamic damage
- “Subcortical Deep Gray Matter Pathology in Patients with Multiple Sclerosis is Associated with White Matter Lesion Burden and Atrophy but not with Cortical Atrophy: A Diffusion Tensor MRI Study” by R Cappellani et al
-cortical and subcortical deep gray matter (SDGM) atrophy occurs in the early stages of MS and disability progression is significantly influenced by the neuronal loss of the gray matter
-atrophy of the SDGM structures is associated with disability progression and cognitive dysfunctions and can also predict the conversion to CDMS
-secondary Wallerian degeneration is certainly implicated in neuronal damage of gray matter structures; however, it seems unlikely to be the sole cause of gray matter pathology
-global and tissue-specific brain volumetric assessment showed a significant decrease of normalized gray matter volume, normalized brain parenchymal volume, normalized cortical volume and a significant increase of normalized lateral ventricular volume in the MS group; these patients also showed decreased total SDGM, caudate, globus pallidus, thalamus, putamen and hippocampus and nucleus accumbens
-it has been shown that development of gray matter pathology is associated with the progression of physical and cognitive disability in both cross-sectional and longitudinal studies
-widespread DTI alternations in the global and tissue-specific brain structures among patients in the RRMS and PMS groups
-point toward the thalamus as one of the most affected SDGM structures
-spatial and temporal relationship between T2 lesion burden and gray matter volume loss
-relationship between lesion burden and SDGM diffusivity: at best, these associations explained 20-30% of the variance
-studies showed that an increase in thalamic DTI diffusivity and in myo-Inositol also correlated with T2 lesion volume in patients with MS
-We did not detect a significant correlation among SDGM DTI measures and lesion burden in the HC group; these results support the hypothesis that the structural damage of white matter connections could lead to trans-synaptic axonal degeneration and retrograde degeneration of neurons with alteration of the microstructural architecture of SDGM structures
-SDGM DIT diffusivity associations with white matter atrophy in MS groups but not with cortical atrophy
-DTI alterations of the SDGM structures seem to be more influenced by degeneration of the white matter network exemplified by accumulation of lesion burden but not by the neuronal loss of the cortical gray matter
-SDGM DTI alterations are not associated with gray matter atrophy
-SDGM DTI alternations were present in different MS clinical phenotypes of the disease and were more pronounced in patients with PMS
- “Inflammatory Cortical Demyelination in Early Multiple Sclerosis” by Claudia F Lucchinetti et al
-in this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory and strongly associated with meningeal inflammation
–cortical disease is associated with disease progression and cognitive impairment
-cortical demyelination contributes to disability in patients with progress MS, occurs independently of white matter lesions, is driven by organized meningeal inflammatory infiltrates and is devoid of parenchymal lymphocytes and macrophages, suggest that neurodegeneration proceeds independently of parenchymal inflammation
-little is know about cortical demyelination in early MS bc conventional MRI does not reveal most lesions
-suggesting that the cortex may be damaged near the disease onset-a concept further supported by recent case reports of cortical-onset MS
-leukocortical lesions were the most common (50%) followed by subpial lesions (34%) and intracortical lesions (16%)
-we detected activated microglia in all 78 cortical lesions
-90% probability that moderate to marked meningeal inflammation was topographically associated with cortical demyelination, esp for subpial plaques as compared with intracortical plaques and leukocortical plaques with respect to diffuse meningeal inflammation
-among confirmed cases of MS or CIS, robust associations between meningeal inflammation and cortical demyelination were noted
-nearly 40% of early stage MS patients had cortical demyelination
-MRI studies showed cortical lesions in approx 30% of CIS patients
-the spatial separation of intracortical and subpial lesions (which together represented about 50% of the lesions detected) from the biopsy specimens of white matter lesions suggests intrinsic cortical demyelinating disease
-cognitive impairment correlates positively with gray matter atrophy, cortical lesion burden and reduced cortical thickness
-cortical lesion volume is an independent predictor of disability progression at follow up and cortical lesions are less common in patients with benign MS
-cortical demyelination is common in early MS
-subpial cortical demyelination showed a strong topographic relation to meningeal inflammation, suggesting that meningeal infiltrates may contribute to early cortical demyelination
-underscoring the potential of cortical demyelination to cause irreversible injury
- “Cortical/Subcortical Disease Burden and Cognitive Impairment in Patients with Multiple Sclerosis” by Marco Rovaris et al
-total and critical subcortical RARE/fast-FLAIR hyperintense and T1 hypointense lesion loads were significantly greater in the group of cognitively impaired patients; patients with cognitive deficits also had significantly lower MTR histographic values for all the variables
-a multivariable regression model showed that average cortical/subcortical brain MTR was the only factor that was significantly associated with cognitive impairment
-the extent and severity of MS disease in the cortical and subcortical regions significantly influence the cognitive functions of MS patients
- “A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes”: Karen K Chung
-The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year.
Multiple Sclerosis Research Repository 