Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing–remitting MS

Morgen, Katrin; Sammer, Gebhard; Courtney, Susan; Wolters, Tobias; Melchior, Hanne; Blecker, Carlo R.; Oschmann, Patrick; Kaps, Manfred; Vaitl, Dieter

doi:10.1016/j.neuroimage.2005.10.032

Cited by 213 publications

(196 citation statements)

References 66 publications

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“…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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Section: Comparison With Msmentioning

confidence: 99%

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

et al. 2008

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“…Indeed, while MS is characterized by WM lesions, GM atrophy is considered to be a relevant biomarker of permanent disability in MS (Bermel & Bakshi, 2006; van den Elskamp et al., 2010; Fisher et al., 2002). In fact, GM atrophy has been found to be associated with changes in all cognitive domains in MS (Morgen et al., 2006). 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.…”

Section: Introductionmentioning

confidence: 99%

“…Others have reported statistically significant slowing of brain atrophy, but only after 24 months or more (Cohen et al., 2012; Coles et al., 2012; Kappos et al., 2010; Mattioli, Stampatori, Bellomi, Scarpazza, & Capra, 2015; Miller et al., 2007; Rinaldi et al., 2012). Brain atrophy is considered predictive of progression in cognitive and/or motor disability (Bermel & Bakshi, 2006; Deloire et al., 2011; Morgen et al., 2006), emphasizing a need for early intervention to prevent brain atrophy and forestall the advance of disability. Thus, fast‐acting directly neuroprotective treatments are needed to halt GM atrophy.…”

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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“…An interesting point that should be mentioned is the presence of cortical atrophy in case two. Such fi nding is more common in secondary progressive MS, and may be related to behavioral and, occasionally, cognitive symptoms 24 .…”

Section: Discussionmentioning

confidence: 99%

Bipolar disorder and multiple sclerosis

Ybarra

Moreira

Araújo

et al. 2007

Arq. Neuro-Psiquiatr.

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-Bipolar disorder may be overrepresented in multiple sclerosis (MS) patients. Although research in this area is limited, studies assessing the nature of this association have focused on genetic aspects, adverse reaction to drugs and brain demyelinating lesions. Herein we report three patients with MS that also presented bipolar disorder. The coexistence of neurological and psychiatric symptoms in most MS relapses highlights the relevance of biological factors in the emergence of mood disorders in these patients.KEY WORDS: multiple sclerosis, bipolar disorder.Transtorno bipolar e esclerose múltipla RESUMO -O transtorno bipolar do humor parece estar super-representado em pacientes com esclerose múl-tipla (EM). Apesar de a pesquisa nessa área ser limitada, estudos acerca da natureza dessa associação têm se concentrado em aspectos genéticos, reações adversas a drogas e lesões desmielinizantes no sistema nervoso central. Relatamos, aqui, três casos de pacientes com EM que também apresentaram transtorno bipolar do humor. A coexistência de sintomas neurológicos e psiquiátricos em grande parte das recaídas de EM reforça a importância de fatores biológicos na gênese dos sintomas afetivos nesses pacientes.PALAVRAS-CHAVE: esclerose múltipla, transtorno bipolar.

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Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing–remitting MS

Cited by 213 publications

References 66 publications

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

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

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

Bipolar disorder and multiple sclerosis

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