Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis

Tekok-Kılıç, Ayda; Benedict, Ralph H. B.; Weinstock‐Guttman, Bianca; Dwyer, Michael G.; Carone, Dominic A.; Srinivasaraghavan, Bhooma; Yella, Viritha; Abdelrahman, Nadir; Munschauer, Frederick E.; Bakshi, Rohit; Zivadinov, Robert

doi:10.1016/j.neuroimage.2007.04.017

Cited by 111 publications

(111 citation statements)

References 42 publications

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“…corticospinal pathway for motor function). Localized measurement of FD might provide complimentary information or identifying more selectively damaged cortical regions, since cortical atrophy does not appear to be a uniform process throughout the GM [23,[33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Fractal dimension analysis of grey matter in multiple sclerosis

Esteban

Sepulcre

Miras

et al. 2009

Journal of the Neurological Sciences

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The fractal dimension (FD) is a quantitative parameter that characterizes the morphometric variability of a complex object. Among other applications, FD has been used to identify abnormalities of the human brain in conventional magnetic resonance imaging (MRI), including white matter abnormalities in patients with Multiple Sclerosis (MS). Extensive grey matter (GM) pathology has been recently identified in MS and it appears to be a key factor in long-term disability. The aim of the present work was to assess whether FD measurement of GM in T1 MRI sequences can identify GM abnormalities in patients with MS in the early phase of the disease. A voxel-based morphometry approach optimized for MS was used to obtain the segmented brain, where we later calculated the three-dimensional FD of the GM in MS patients and healthy controls. We found that patients with MS had a significant increase in the FD of the GM compared to controls. Such differences were present even in patients with short disease durations, including patients with first attacks of MS. In addition, the FD of the GM correlated with T1 and T2 lesion load, but not with GM atrophy or disability. The FD abnormalities of the GM here detected differed from the previously published FD of the white matter in MS, suggesting that different pathological processes were taking place in each structure. These results indicate that GM morphology is abnormal in patients with MS and that this alteration appears early in the course of the disease.

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Section: Discussionmentioning

confidence: 99%

Fractal dimension analysis of grey matter in multiple sclerosis

Esteban

Sepulcre

Miras

et al. 2009

Journal of the Neurological Sciences

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“…Since then, we and others have shown the tests to be reliable (Benedict 2005), predictive of multiple forms of brain pathology (Benedict et al 2006b;Christodoulou et al 2003;Tekok-Kilic et al 2007), and associated with vocational disability Parmenter et al 2007b Delis et al 2001). Most often, the Total Learning and Delayed Recall indices from the CVLT2 and BVMTR are emphasized.…”

Section: Comparison With Msmentioning

confidence: 99%

“…More recently, measures reflecting brain atrophy have been more strongly correlated with cognitive impairments, such as reduced whole brain volume (Zivadinov et al 2001), enlargement of the ventricles (Benedict et al 2004a, c;Bermel et al 2002;Christodoulou et al 2003), and reduction in cortical volume (Amato et al 2004;Benedict et al 2006b). The clinical relevance of regional cortical volume is beginning to be explored (Morgen et al 2006;Prinster et al 2006;Sepulcre et al 2006;Tekok-Kilic et al 2007). …”

Section: Comparison With Msmentioning

confidence: 99%

Neuropsychological Impairment in Systemic Lupus Erythematosus: A Comparison with Multiple Sclerosis

et al. 2008

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In this manuscript, we review literature describing the neuropsychological and brain imaging characteristics of systemic lupus erythematosus (SLE) patients. The findings are compared and contrasted with multiple sclerosis (MS) studies, revealing similarities and differences of interest to clinicians and researchers. While cognitive impairment is somewhat less common in SLE than MS, the diseases share a similar cognitive profile with deficits most prominent on tests emphasizing the speed of information processing, working memory, and visual/spatial learning, and memory. In early or more mildly affected patients, diffuse white matter damage, which may not be apparent on conventional brain imaging, plays a major role in clinical presentation and cognitive testing. The causes of white matter damage are very different, however, and in later stages of the disease MS and SLE appear to give rise to different forms of cerebral pathology. MS may be characterized by increasing brain atrophy affecting especially the cortical and deep gray matter, at least after conversion to secondary progressive course. There is less evidence for neurodegenerative changes in SLE, but patients are increasingly at risk for cerebrovascular disease. We conclude by offering some suggestions for future clinical and imaging research. KeywordsSystemic lupus erythematosus; Multiple sclerosis; Cognition; Memory; Processing speed; MRI; Effect size Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease with wide ranging organ involvement and clinical symptoms varying from mild and transient symptoms to death. Cognitive impairment is reported in SLE, even among those patients without documented or overt signs of central nervous system (CNS) involvement. Presumably, cognitive disorder is the result of underlying brain disease although the precise mechanisms remain to be elucidated. The prevalence and degree of cognitive impairment is also uncertain.In this article we will endeavor to evaluate the evidence for neuropsychological impairment in SLE, and to compare the findings with that of MS, another immunological disorder whose symptoms wax and wane and which affects women more than men. Unlike SLE, MS is a disease that always impacts the CNS, and the causes of cognitive disorder in MS are better understood.

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“…This is not surprising as several pathological (Kutzelnigg et al., 2005; Peterson, Bo, Mork, Chang, & Trapp, 2001) and MRI (Calabrese, Atzori, et al., 2007; Calabrese, De Stefano, et al., 2007; De Stefano et al., 2003) studies have shown that the cerebral cortex is profoundly affected in MS. Indeed, cortical atrophy has been proposed as one of the major underlying substrates of cognitive impairment in MS (Amato et al., 2004; Benedict et al., 2004; Tekok‐Kilic et al., 2007). Which regions within the cerebral cortex undergo atrophy and align with impairments in which cognitive domains is only beginning to be investigated (Wen et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

et al. 2018

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IntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty‐two estriol‐ and forty‐nine placebo‐treated RRMS patients underwent clinical evaluations and brain MRI. Voxel‐based morphometry (VBM) was used to evaluate voxelwise GM sparing from high‐resolution T1‐weighted scans.ResultsA region of treatment‐induced sparing (TIS) was defined as the areas where GM was spared in estriol‐ as compared to placebo‐treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability‐specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol‐treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability‐specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

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Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis

Cited by 111 publications

References 42 publications

Fractal dimension analysis of grey matter in multiple sclerosis

Fractal dimension analysis of grey matter in multiple sclerosis

Neuropsychological Impairment in Systemic Lupus Erythematosus: A Comparison with Multiple Sclerosis

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

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