Author Topic: (Abst.) Association of cortical lesion burden w/cognition and disability in MS  (Read 111 times)

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Offline agate

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From JAMA Neurology, July 20, 2015:

Quote
Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis

Daniel M. Harrison, MD1,2; Snehashis Roy, PhD3; Jiwon Oh, MD2,4; Izlem Izbudak, MD5; Dzung Pham, PhD3; Susan Courtney, PhD6; Brian Caffo, PhD7; Craig K. Jones, PhD5,8; Peter van Zijl, PhD5,8; Peter A. Calabresi, MD2

Author Affiliations

1Department of Neurology, School of Medicine, University of Maryland, Baltimore
2Department of Neurology, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
3Center for Neuroscience and Regenerative Medicine, Henry Jackson Foundation, Bethesda, Maryland
4Department of Neurology, University of Toronto, Toronto, Ontario, Canada
5Department of Radiology and Radiological Science, School of Medicine, The Johns Hopkins University, Baltimore, Maryland
6Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, Maryland
7Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
8F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland


Importance

Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and the****utic trials in MS.

Objective 

To evaluate the clinical relevance of measures of CL burden derived from high-field magnetic resonance imaging (MRI) in MS.

Design, Setting, and Participants 

An observational clinical imaging study was conducted at an academic MS center. Participants included 36 individuals with MS (30 relapsing-remitting, 6 secondary or primary progressive) and 15 healthy individuals serving as controls. The study was conducted from March 10, 2010, to November 23, 2012, and analysis was performed from June 1, 2011, to September 30, 2014. Seven-Tesla MRI of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and whole-brain, 3-dimensional, 1.0-mm isotropic resolution magnetization–prepared, fluid-attenuated inversion recovery (MPFLAIR). Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented. Lesions were classified as leukocortical, intracortical, or subpial. Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm, and brain structure volumes and white matter (WM) lesion volume were reported. Volumes were normalized to intracranial volume.

Main Outcomes and Measures 

Physical disability was measured by the Expanded Disability Status Scale (EDSS). Cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery.

Results

Cortical lesions were noted in 35 of 36 participants (97%), with a median of 16 lesions per participant (range, 0-99). Leukocortical lesion volume correlated with WM lesion volume (ρ = 0.50; P = .003) but not with cortical volume; subpial lesion volume inversely correlated with cortical volume (ρ = −0.36; P = .04) but not with WM lesion volume. Total CL count and volume, measured as median (range), were significantly increased in participants with EDSS scores of 5.0 or more vs those with scores less than 5.0 (count: 29 [11-99] vs 13 [0-51]; volume: 2.81 × 10−4 [1.30 × 10−4 to 7.90 × 10−4] vs 1.50 × 10−4 [0 to 1.01 × 10−3]) and in cognitively impaired vs unimpaired individuals (count: 21 [0-99] vs 13 [1-54]; volume: 3.51 × 10−4 [0 to 1.01 × 10−4] vs 1.19 × 10−4 [0 to 7.17 × 10−4]). Cortical lesion volume correlated with EDSS scores more robustly than did WM lesion volume (ρ = 0.59 vs 0.36). Increasing log[CL volume] conferred a 3-fold increase in the odds of cognitive impairment (odds ratio [OR], 3.36; 95% CI, 1.07-10.59; P = .04) after adjustment for age and sex and a 14-fold increase in odds after adjustment for WM lesion volume and atrophy (OR, 14.26; 95% CI, 1.06-192.37; P = .045). Leukocortical lesions had the greatest effect on cognition (OR for log [leukocortical lesion volume], 9.65; 95% CI, 1.70-54.59, P = .01).

Conclusions and Relevance

This study provides in vivo evidence that CLs are associated with cognitive and physical disability in MS and that leukocortical and subpial lesion subtypes have differing clinical relevance. Quantitative assessments of CL burden on high-field MRI may further our understanding of the development of disability and progression in MS and lead to more effective treatments.

The abstract can be seen here.
« Last Edit: July 24, 2015, 01:55:38 pm by agate »
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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Re: Lesion topography matters in MS
« Reply #1 on: July 24, 2015, 02:02:37 pm »
From MedPage Today, July 21, 2015:

Quote
Lesion Topography Matters in Multiple Sclerosis

Location in cerebral cortex, more than global white matter lesion volume, tied to disability.

 
 
by Kay Jackson
Contributing Writer, MedPage Today


An observational clinical imaging study now provides in vivo evidence that cortical lesions (CLs) are associated with cognitive and physical disability in multiple sclerosis (MS), independent of white matter lesion volume. It also showed that leukocortical and subpial lesion subtypes have differing clinical relevance.

In addition, the study points to high-field MRI as a highly effective tool for quantifying cortical pathology in MS, something which could eventually lead to more effective treatments, Daniel M. Harrison, MD, department of neurology, University of Maryland School of Medicine in Baltimore, and colleagues reported online in JAMA Neurology.


"Our finding that CL volume predicts cognitive impairment independent of WM lesion volume or atrophy supports the notion that assessments of inflammatory WM pathology alone provide an insufficient appraisal of the pathology responsible for disability in MS," said Harrison.

"Furthermore, our findings of CL volume as an independent predictor of cognitive impairment highlights the need to determine whether current disease-modifying drugs reduce CL formation."

If these drugs do not modify CL formation, he added, "...this research may spur the development of novel therapeutics capable of reducing CLs and their associated disability."

Since the low sensitivity of 1.5-T and 3-T MRI techniques for identification of CLs has been established, high-field MRI should be integrated into future MS research and clinical trials, emphasized Harrison. "Although the availability of 7-T MRI at present limits this approach," he acknowledged, "our data show it is feasible to perform clinical-quality, whole-brain imaging in reasonable scan time and to quantify clinically relevant pathology."

To evaluate the clinical relevance of measures of CL burden derived from high-field MRI in MS, 36 patients with MS (30 relapsing-remitting, six secondary or primary progressive) were recruited from the Johns Hopkins Multiple Sclerosis Center. Fifteen healthy participants served as controls.

Data were collected from March 2010 to November 2012; the analysis was completed last year.

High-field MRI (7 T) of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and whole-brain, three-dimensional, 1.0-mm isotropic resolution magnetization-prepared, fluid attenuated inversion recovery (MPFLAIR), said the investigators.

Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented and classified as leukocortical, intracortical or subpial (SP). Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm.

Physical disability was measured using the Expanded Disability Status Scale (EDSS) while cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery.

Of the 36 participants, cortical lesions were noted in 35 (97%), with a median of 16 lesions per participant (range 0-99). One patient had 99 CLs. Leukocortical lesion volume correlated with WM lesion volume (ρ=0.50; P=.003) but not with cortical volume, the investigators reported.

Subpial lesion volume inversely correlated with cortical volume (ρ=−0.36; P=.04) but not with WM lesion volume. Total CL count and volume were significantly increased in participants with EDSS scores of 5.0 or more versus those with scores less than 5.0 (count: 29 [11-99] vs 13 [0-51]; volume: 2.81×10-4 [1.30×10-4 to 7.90×10-4] versus 1.50×10-4 [0 to 1.01×10-4]) and in cognitively impaired versus unimpaired individuals (count: 21 [0-99] versus 13 [1-54]; volume: 3.51×10-4 [0 to 1.01×10-4] versus 1.19× 10-4 [0 to 7.17×10-4]).

Cortical lesion volume correlated with EDSS scores more robustly than did WM lesion volume (ρ=0.59 versus 0.36), said Harrison.
In an accompanying editorial, "Cortical Lesions in Multiple Sclerosis: Clinical Relevance for Hidden Disease Burden," Robert T. Nasmith, MD, department of neurology, Washington University, St. Louis, pointed out that in the last decade, advances have been made in the management of long-term disability and treatment in MS. But clinicians are still grappling with a lack of certainty about what's in store for each patient.
"[A]ny physician who treats MS and reviews MRI scans understands that the clinic-radiological paradox is at the individual patient level, which has left physicians managing the patient's risk for a worse outcome instead of an absolute truth of future disability," said Nasmith. "White matter lesions are important in MS; however, there is more that we cannot observe in clinical practice."

Based on the study results, said Nasmith, phase II/III clinical trials should assess CLs to determine the effect of therapies on different clinical subtypes.

"From a [treatment] standpoint, we need to understand whether we are treating just one disease process common to both gray and white matter or, potentially, multiple disease processes that are independent and dissociated from the beneficial effect observed for white matter lesions," he wrote.

___________________
This study was supported in part by National Institutes of Health supplemental grants 5P41RR15241-09S1 and 5P41EB15909 and Bayer Neurosciences. Data analysis was supported by National Institutes of Health-mentored grant K23NS072366.

Harrison reported relationships with Bayer Schering Pharma and EMD Serono as well as EMD Serono, Genzyme, Mallinckrodt Pharmaceuticals, and MedImmune. Four of his co-authors report relationships with Biogen-Idec, EMD Serono, Genzyme, Novartis, Phillips Medical Systems, Bayer, MedImmune, Novartis, Vertex, Abbott, Merck, Prothena, and Vaccinex.

Naismith reported consulting relationships with Acorda Therapeutics, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Novartis, and Questcor and is on the speakers' bureau for Acorda and Genzyme.

This article can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.