Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ
J NeuroPathol Exp Neurol 2003 Jul;62(7):723-32
Haukeland Hospital, Department of Neurology, Bergen, Norway
The extent and pattern of DeMyelination in the Cerebral Cortex was determined in 78 tissue blocks from the Brains of 20 Multiple Sclerosis (MS) patients and 28 tissue blocks from 7 patients without Neurological Disease.
Tissue blocks from 4 predetermined areas (Cingulate Gyrus, Frontal, Parietal, and Temporal Lobe) were studied, irrespective of macroscopically evident MS plaques.
All tissue blocks contained Cerebral Cortex and PeriVentricular and/or SubCortical White Matter.
One hundred and nine DeMyelinating lesions were detected in the Cerebral Cortex, of which 92 (84.4%) were purely IntraCortical and 17 (15.6%) were lesions extending through both White and Gray Matter areas.
In 5 of the 20 MS Brains, SubPial DeMyelination was extensive in the 4 widely spaced Cortical areas studied, thus considered to represent a general Cortical SubPial DeMyelination.
The percentage of DeMyelinated area was significantly higher in the Cerebral Cortex (mean 26.5%, median 14.1%) than in White Matter (mean 6.5%, median 0%) (p = 0.001).
Both Gray and WhiteWhite Matter DeMyelination was more prominent in the Cingulate Gyrus than in the other areas examined (p < 0.05).
These results indicate that the Cerebral Cortex is likely to be a predilection site for MS lesions and identify general Cortical SubPial DeMyelination as a distinct pattern occurring in a significant subpopulation of MS patients.
Cortical Lesions In Multiple Sclerosis: Combined Postmortem MR Imaging And Histopathology
Geurts JJ, Bo L, Pouwels PJ, Castelijns JA, Polman CH, Barkhof F
AJNR Am J NeuroRadiol 2005 Mar;26(3):572-7
VU University Medical Center, Department of Radiology, Amsterdam, the Netherlands
Background And Purpose
Cortical lesions constitute a substantial part of the total lesion load in Multiple Sclerosis (MS) Brain.
They have been related to NeuroPsychological deficits, Epilepsy, and Depression. However, the proportion of purely Cortical lesions visible on MR images is unknown.
The aim of this study was to determine the proportion of IntraCortical and mixed Gray Matter (GM)-White Matter (WM) lesions that can be visualized with postmortem MR imaging.
We studied 49 Brain samples from nine cases of chronic MS. Tissue sections were matched to dual-echo T2-weighted Spin-Echo (T2SE) MR images.
MS lesions were identified by means of Myelin Basic Protein ImmunoStaining, and lesions were classified as IntraCortical, mixed GM-WM, deep GM, or WM.
Investigators blinded to the HistoPathologic results scored postmortem T2SE and 3D Fluid-Attenuated Inversion Recovery (FLAIR) images.
ImmunoHistoChemistry confirmed 70 WM, eight deep GM, 27 mixed GM-WM, and 63 purely Cortical lesions.
T2SE images depicted only 3% of the IntraCortical lesions, and 3D FLAIR imaging showed 5%.
Mixed GM-WM lesions were most frequently detectable on T2SE and 3D FLAIR images (22% and 41%, respectively).
T2SE imaging showed 13% of deep GM lesions versus 38% on 3D FLAIR. T2SE images depicted 63% of the WM lesions, whereas 3D FLAIR images depicted 71%.
Even after side-by-side review of the MR imaging and HistoPathologic results, many of the IntraCortical lesions could not be identified retrospectively.
In contrast to WM lesions and mixed GM-WM lesions, IntraCortical lesions remain largely undetected with current MR imaging resolution.
IntraCortical Lesions In Multiple Sclerosis: Improved Detection With 3D Double Inversion-Recovery MR Imaging
Geurts JJ, Pouwels PJ, Uitdehaag BM, Polman CH, Barkhof F, Castelijns JA
Radiology 2005 Jul;236(1):254-60
VU University Medical Center, MR Center for MS Research, Department of Radiology, Neurology, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands
To prospectively compare the depiction of IntraCortical lesions by using multislab Three-Dimensional (3D) Double Inversion-Recovery (DIR), multislab 3D Fluid-Attenuated Inversion-Recovery (FLAIR), and T2-weighted Spin-Echo (SE) Magnetic Resonance (MR) imaging in patients with Multiple Sclerosis.
Materials And Methods
Local ethics review board approval and informed consent were obtained.
Conventional T2-weighted SE and multislab 3D FLAIR and DIR images were acquired in 10 patients with Multiple Sclerosis (five women, five men) and 11 age-matched healthy control subjects (seven women, four men).
Mean age was 40 years (range, 25-54 years) in patients and 34 years (range, 24-55 years) in control subjects.
Lesions were classified according to seven anatomic regions: IntraCortical, mixed White Matter-Gray Matter, JuxtaCortical, deep Gray Matter, PeriVentricular White Matter, deep White Matter, and InfraTentorial lesions.
The numbers of lesions per category were compared between techniques (Dunnett-corrected analysis of variance).
Gain or loss (with 95% Confidence Intervals [CIs]) of numbers of lesions detected at 3D DIR imaging was calculated in comparison with those detected at T2-weighted SE and 3D FLAIR imaging.
Total number of lesions did not differ between 3D DIR and 3D FLAIR sequences, but the 3D DIR sequence showed a gain of 21% (95% CI: 4%, 41%) in comparison with the T2-weighted SE sequence.
Because of high Gray Matter-White Matter contrast, DIR images depicted more IntraCortical lesions (80 lesions in 10 patients) than both SE (10 lesions) and FLAIR (31 lesions) images.
Gains with DIR were 538% (95% CI: 191%, 1297%) and 152% (95% CI: 15%, 453%) compared with SE and FLAIR, respectively.
Only four IntraCortical lesions were detected in control subjects. Also, DIR imaging enabled a better definition of mixed White Matter-Gray Matter lesions because of greater contrast between the lesion and its surroundings.
MR imaging with 3D DIR enables increased IntraCortical lesion detection in the Multiple Sclerosis Brain, as well as improved distinction between JuxtaCortical and White Matter-Gray Matter lesions.
Copyright RSNA, 2005
The Ependymal "Dot-Dash" Sign: An MR Imaging Finding Of Early Multiple Sclerosis
Lisanti CJ, Asbach P, Bradley WG Jr
AJNR Am J NeuroRadiol 2005 Sep;26(8):2033-6
Wilford Hall Medical Center Lackland AFB, Department of Radiology, TX, USA
Background And Purpose
Corpus Callosum lesions are of specific interest in the evaluation of suspected Multiple Sclerosis in Brain MR imaging.
Using thin-section sagittal Fluid-Attenuated Inversion Recovery images, researchers have shown that the finding of "SubCallosal striations" correlates significantly with the diagnosis of Multiple Sclerosis.
Using the same MR imaging technique, we describe a finding of Ependymal irregularity that we call the "Dot-Dash" sign, which we believe to be associated with early Multiple Sclerosis.
Sagittal 2-mm fast Fluid-Attenuated Inversion Recovery images were obtained in 70 patients. Thirty-five patients had Multiple Sclerosis according to the Poser criteria, and 35 were age-matched controls.
The images were reviewed in a blinded fashion by an experienced NeuroRadiologist for the presence or absence of the Dot-Dash sign.
The correlation between the Dot-Dash sign and definite clinical Multiple Sclerosis is highly significant (P < .001), with a sensitivity of 91.4% and a specificity of 65.7%.
In the age group of < or =50 years, the sensitivity was 95.7% and the specificity, 71.9%.
The Dot-Dash sign of Ependymal irregularity on thin-section sagittal Fluid-Attenuated Inversion Recovery images is an early marker for Multiple Sclerosis, which is particularly useful in the younger patient.
This finding appears to be more sensitive for early lesion detection than any other Multiple Sclerosis imaging finding yet described in the literature.
Determinants of Cerebral Atrophy rate at the time of diagnosis of Multiple Sclerosis
Jasperse B, Minneboo A, de Groot V, Kalkers NF, van Helden PE, Uitdehaag BM, Barkhof F, Polman CH
Arch Neurol 2007 Feb;64(2):190-4
VU University Medical Center, Department of Neurology, Boelelaan 1117, 1007 MB Amsterdam, the Netherlands
To identify determinants visible on Magnetic Resonance Imaging of the Brain that explain the subsequent rate of Cerebral Atrophy in patients with recently diagnosed Multiple Sclerosis.
Magnetic Resonance Imaging of the Brain was performed at baseline and after 2 years.
T2 HyperIntense lesion load, black hole lesion load, presence of contrast-enhancing lesions, and normalized Brain Volume were derived from the baseline Magnetic Resonance Imaging.
And considered as possible explanatory variables for the subsequent annualized Percentage of Brain Volume Change (PBVC/y) using forward stepwise multiple linear regression analysis.
MS Center Amsterdam, Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.
Patients & Main Outcome Measure
Eighty-nine patients recently diagnosed as having Multiple Sclerosis were included at the time of diagnosis from our outpatient clinic. Annualized percentage of Brain Volume change.
The mean (SD) annualized rate of Cerebral Atrophy was -0.9 (0.8) PBVC/y.
Baseline normalized Brain Volume (standardized coefficient, 0.426; P = .001) and baseline T2 lesion load (standardized coefficient, -0.244; P = .02) were identified as explanatory variables for subsequent PBVC/y and yielded a regression model that explained 31.2% of the variance in PBVC/y.
In patients with recently diagnosed Multiple Sclerosis, the extent of accumulated Brain Tissue loss and overall lesion load partly explain the subsequent rate of Cerebral Atrophy.
Zarei M, Chandran S, Compston A, Hodges J
J Neurol NeuroSurg Psychiatry 2003 Jul;74(7):872-7
University of Cambridge, Addenbrooke's Hospital, Department of Neurology, Cambridge, UK
Although NeuroPsychiatric complications are well recognized, the presentation of Multiple Sclerosis with Cognitive or NeuroPsychiatric symptoms has generally been considered a rare occurrence and to reflect SubCortical pathology.
To document the clinical, NeuroPsychological, and Radiological features of six cases of Cognitive presentation of Multiple Sclerosis, to review the relevant literature, and to propose a possible Cortical basis for this clinical presentation.
Six patients (five women; age range 38 to 60 years) presented to the Memory and Cognitive Disorders clinic in Cambridge with an initially undiagnosed Cognitive/NeuroPsychiatric Syndrome.
All underwent NeuroPsychological evaluation, Brain imaging, and ancillary investigations to establish a diagnosis of Multiple Sclerosis.
The six cases all had a progressive Dementia Syndrome with prominent Amnesia (partial or total Memory loss), often accompanied by classic Cortical features including Dysphasia, Dysgraphia, or Dyslexia.
Mood disturbance was ubiquitous and in three patients there was a long history of preceding severe Depression. All six developed characteristic physical signs on follow up, with marked disabilities.
A review of 17 previously reported cases highlighted the prominence of Memory impairment and Depression in the early stages.
On clinical, pathological, and radiological grounds, the NeuroPsychiatric presentation of Multiple Sclerosis may represent a ClinicoPathological entity of "Cortical Multiple Sclerosis."
Failure to recognize this will delay diagnosis and may expose patients to potentially dangerous and invasive investigation.
Because the NeuroPsychiatric features of Cortical Multiple Sclerosis are a major cause of handicap, their early recognition may be particularly important in view of emerging treatments.
Cortical Pathology In Multiple Sclerosis
Stadelmann C, Albert M, Wegner C, Brück W
Curr Opin Neurol 2008 Jun;21(3):229-34
University Medical Centre, Institute of NeuroPathology, Göttingen, Germany; University of Tübingen, Department of General Neurology, Tübingen, Germany
Purpose Of Review
Multiple Sclerosis is the most common chronic, disabling Central Nervous System disease in young adults, characterized by Inflammatory DeMyelinating White Matter lesions with Glial Scar formation and Axonal Loss.
Lately, evidence has accumulated that large areas of Gray Matter are affected in Multiple Sclerosis patients.
Findings in post-mortem Brain Tissue support the notion that Cortical DeMyelination is frequent and extensive, especially in patients with Chronic Multiple Sclerosis.
Cortical Lesions differ from White Matter lesions with respect to inflammatory cell infiltration, Gliosis, and ReMyelination.
Thus, differences in Cortical and White Matter lesion pathogenesis have been proposed. Experimental models suggest a decisive role for AntiMyelin AntiBodies in Cortical DeMyelination.
Topical studies focus on damage to Neurons, Dendrites, and Synapses in Cortical Multiple Sclerosis lesions.
Improved imaging techniques for the detection of Cortical Lesions are currently developed and will provide the basis for future ClinicoPathological correlative studies.
In summary, recent years have opened our eyes to the extensive Gray Matter involvement 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.