Association of neocortical volume changes with cognitive deterioration in relapsing-remitting multiple sclerosis

Department of Neurology, University of Florence, Viale Morgagni, 85-50134 Florence, Italy.
JAMA Neurology (Impact Factor: 7.01). 08/2007; 64(8):1157-61. DOI: 10.1001/archneur.64.8.1157
Source: PubMed

ABSTRACT We previously reported selective decreases of neocortical volumes in patients with early relapsing-remitting (RR) multiple sclerosis (MS) with mild cognitive impairment, with a good correlation between cortical volumes and cognitive measures.
To assess the relevance of gray matter changes over time to changes in cognition in RRMS.
A longitudinal survey after 2.5 years. Each patient underwent a magnetic resonance imaging (MRI) protocol identical to that performed at baseline; cognitive performance was reassessed with the Rao Brief Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis.
Two university MS clinics.
Of 41 patients with RRMS who participated in the original cross-sectional study, 28 were available for the follow-up evaluation (18 women; mean +/- SD age, 37.1 +/- 8.9 years; mean +/- SD MS duration, 7.3 +/- 2.9 years; mean +/- SD Expanded Disability Status Scale score, 1.8 +/- 1.5).
We measured the percentage of brain volume changes, normalized cortical volume (NCV) changes, and normalized deep gray matter volume changes on conventional T1-weighted MRIs and changes in lesion load on T2-weighted MRIs. The number of tests failed on the Rao Brief Repeatable Battery were used to classify the patients as cognitively deteriorating or stable or improving.
We identified 12 of 28 cognitively deteriorating and 16 of 28 stable or improving patients. These subgroups did not differ in the mean +/- SD percentage of brain volume changes (-2.1% +/- 1.2% vs -1.3% +/- 1.3%; P = .11), normalized deep gray matter volume changes (-2.1 +/- 2.8 mL vs -0.6 +/- 3.1 mL; P = .60), and changes in lesion load on T2-weighted MRIs (1.9 +/- 2.6 mL vs 1.6 +/- 2.3 mL; P = .73). However, NCV changes were significantly higher in deteriorating than in stable or improving patients (-43.0 +/- 18.9 mL vs -17.8 +/- 26.6 mL; P = .007). In deteriorating patients, NCV changes were correlated with performance in a verbal fluency test (r = 0.73; P < .001). In a regression model, only NCV changes were significantly associated with deteriorating cognitive performance (odds ratio, 0.8; 95% confidence interval, 0.7-0.9).
Progressive neocortical gray matter loss is relevant to MS-associated cognitive impairment and may represent a sensitive marker of deteriorating cognitive performance in RRMS.

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    • "In one study, a positive correlation between cortical volume values and performance in verbal memory, verbal fluency, and attention/concentration testing in cognitively impaired MS patients were reported (Amato et al., 2004). In a later study, patients with cognitive impairment displayed less cortical volume compared with cognitively preserved MS patients (Amato et al., 2007). Thus, progressive neocortical grey matter loss is likely to be relevant for MS-associated cognitive impairment. "
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    ABSTRACT: In multiple sclerosis (MS), gray matter pathology is characterized by less pronounced inflammation when compared with white matter lesions. Although regional differences in the cytoarchitecture may account for these differences, the amount of myelin debris in the cortex during a demyelinating event might also be contributory. To analyze the association between myelin debris levels and inflammatory responses, cortical areas with distinct and sparse myelination were analyzed for micro- and astrogliosis before and after cuprizone-induced demyelination in mice. In postmortem tissue of MS patients, leucocortical lesions were assessed for the type and level of inflammation in the cortical and white matter regions of the lesion. Furthermore, mice were injected intracerebrally with myelin-enriched debris, and the inflammatory response analyzed in white and grey matter areas. Our studies show that the magnitude of myelin loss positively correlates with microgliosis in the cuprizone model. In MS, the number of MHC class II expressing cells is higher in the white compared with the grey matter part of leucocortical lesions. Finally, direct application of myelin debris into the corpus callosum or cortex of mice induces profound and comparable inflammation in both regions. Our data suggest that myelin debris is an important variable in the inflammatory response during demyelinating events. Whether myelin-driven inflammation affects neuronal integrity remains to be clarified.
    Glia 10/2012; 60(10):1468-80. DOI:10.1002/glia.22367 · 6.03 Impact Factor
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    • "Decreased cerebral volume at 1 year of progression is correlated with the existence of cognitive impairment at 5 years (Summers et al., 2008). In addition, there is a distinct correlation between overall cortical thickness and cognitive impairment (Amato et al., 2007; Calabrese et al., 2010). "
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    ABSTRACT: The aim of the Multiple Sclerosis Think Tank (Groupe de réflexion sur la sclérose en plaques [GRESEP]) is to prescribe recommendations following a systematic literature search and using a Rand Corporation and California University (RAND/UCLA) appropriateness derived method, in response to practical questions that are raised in the management of patients with multiple sclerosis (MS). The topics of this working program were chosen because they were not addressed in the French recommendations and because of the few data in the literature that enabled practices to be based on validated data. Following the theme on useful serum testing with suspected multiple sclerosis, the subjects of the present work concern the detection and management of cognitive impairment in the beginning stages of the disease course. Two clinical questions were asked: which complementary exams (besides physical examination and neuropsychological tests) would help in the screening of cognitive impairment at the beginning of the disease? What care management should the person with MS and cognitive impairment be offered (treatments and neurocognitive rehabilitation)? The recommendations are the result of a consensus amongst a working group, a rating group and a reading group comprised of hospital neurologists involved in the management of patients with multiple sclerosis. Each recommendation is presented with the degree of consensus that it was accorded.
    Revue Neurologique 06/2012; 168(11). DOI:10.1016/j.neurol.2012.02.009 · 0.60 Impact Factor
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    • "Neuropsychological performance of patients with cognitive decline has been documented to correlate with cortical brain volume (Amato et al., 2004; Benedict et al., 2006a; Morgen et al., 2006), as well as cortical thickness (Calabrese et al., 2010). GM volume assessed longitudinally decreased more progressively in MS patients with deteriorating cognitive performance compared to patients with stable or improving cognitive state (Amato et al., 2007). The relevance of cortical damage in cognitive dysfunction of MS patients has been highlighted by studies of regional cortical atrophy (Calabrese et al., 2010; Morgen et al., 2006; Tekok-Kilic et al., 2007). "
    Neuroimaging - Clinical Applications, 03/2012; , ISBN: 978-953-51-0200-7
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