Correlating Brain Atrophy With Cognitive Dysfunction, Mood Disturbances, and Personality Disorder in Multiple Sclerosis

Benedict, Ralph H. B.; Carone, Dominic A.; Bakshi, Rohit

doi:10.1177/1051228404266267

Cited by 131 publications

(88 citation statements)

References 99 publications

(92 reference statements)

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“…After normalization to the TICV, using Eq. [1], the mean upper cervical cord CSA in controls was 77.97 Ϯ 0.95 mm 2 . There was no statistically significant difference (P ϭ 0.670) in mean normalized CSA between the males (78.48 Ϯ 1.49 mm 2 ) and females (77.65 Ϯ 1.25 mm 2 ).…”

Section: Resultsmentioning

confidence: 90%

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Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

Mann¹,

Constantinescu²,

Tench³

2007

Magnetic Resonance Imaging

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Purpose: To measure accurately the upper cervical cord cross-sectional area (CSA) in patients with relapsing remitting multiple sclerosis (RRMS), and normal control subjects, to address the paradox that longitudinal reduction in CSA has been detected in RRMS while reduction compared to controls has not. We hypothesized that a lack of statistical power and/or measurement sensitivity due to partial volume averaging in previous studies contributed to this paradox. Materials and Methods:Using a technique that corrects for partial volume averaging, we measured the CSA in 35 normal controls and 35 RRMS patients. We used the total intracranial volume (TICV) to normalize the CSA and therefore reduce the normal variance and improve the statistical power. Results:The mean TICV did not differ between groups. Statistical power analysis indicated that a 5% reduction in CSA in the patients could be detected with an estimated power of 0.74 before normalization and 0.9 after. The mean CSA in the patients was not reduced compared to controls after (P ϭ 0.928) or before (P ϭ 0.881) normalization. Conclusion:Using a sensitive analysis method, and apparently appropriate statistical power, we did not detect reduced CSA in RRMS patients. We hypothesize that this may be due to inflammation.

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Section: Resultsmentioning

confidence: 90%

“…The relative contribution of each of these pathological features to long-term neurological deficit is unknown. Axonal loss, however, is thought to be an important factor contributing to long-term cumulative persistent dysfunction (1,2). It is also thought to contribute to atrophy of the CNS (3).…”

mentioning

confidence: 99%

Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

Mann¹,

Constantinescu²,

Tench³

2007

Magnetic Resonance Imaging

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“…However there is evidence to suggest that whole grey and white matter volume, as compared with lesion burden, is more closely related to neuropsychological performance and neuropsychiatric symptoms [2,3]. Our investigations of total white and grey matter volume in patients with type 1 diabetes revealed a relationship between cerebral white matter volume and cognitive performance [4].…”

Section: Wmhs White Matter Hyperintensitiesmentioning

confidence: 70%

Integrity of cerebral white matter in type 1 diabetes

Wessels¹

2008

Diabetologia

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Keywords Brain structure . Type 1 diabetes . White matter volume . White matter hyperintensities Abbreviation WMHs White matter hyperintensitiesTo the Editor: In a recent issue of Diabetologia, Weinger et al. [1] report evidence of only mild white matter hyperintensities (WMHs) in a sample of adults with type 1 diabetes. These WMHs were comparable to those seen in a demographically similar sample of non-diabetic adults, and no association between diabetes characteristics and WMHs was found.As stated by the authors and from what is known from the literature, there is no clear understanding of the clinical relevance of WMHs. However there is evidence to suggest that whole grey and white matter volume, as compared with lesion burden, is more closely related to neuropsychological performance and neuropsychiatric symptoms [2,3]. Our investigations of total white and grey matter volume in patients with type 1 diabetes revealed a relationship between cerebral white matter volume and cognitive performance [4]. Patients with diabetes demonstrated several subtle neuropsychological deficits, and patients with a microvascular complication (defined as proliferative retinopathy) showed a decreased white matter volume that was associated with worse cognitive performance. This suggests that cognitive decline is at least partly mediated by microvascular disease.Despite the fact that these studies differ methodologically and focus on different aspects of the brain (i.e. WMHs vs white matter volume), both aimed to elucidate the underlying mechanism of cognitive decline in type 1 diabetes. It is therefore unfortunate that Weinger et al. did not include this specific consideration in their paper.Whether WMHs are associated with white matter volume is still under debate. The results of a study by Wen et al. [5] suggest that WMHs are associated with loss of brain volume, which could presumably be the result of white matter pathology [6]. In contrast, Smith at al. [7] reported that decreased white matter volume measured from magnetic resonance imaging was associated with dementia and with lower cognitive test scores, whereas no such association was found with periventricular WMHs identified on the same images. WMHs were not related to white matter volume, stroke or dementia. Nonetheless, low white matter volume was strongly related to dementia and poor cognitive performance in this sample.In the elderly, the periventricular WMHs have been shown to be unrelated to total white matter volume loss [8]. Additional data from diffusion-weighted and magnetisation transfer (MT) imaging studies [9,10] reveal that fractional anisotropy and the magnetisation ratio (a measure of the integrity of the microstructure) in white matter significantly decrease with age. These decreases suggest that white matter volume loss may result from these microscopic structural changes, which include myelin and axonal loss, dilatation of perivascular spaces and gliosis.To understand the mechanisms by which diabetes might affect the brain, it is important to consider...

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“…The reader is referred to several recent detailed reviews on the relationship between CNS atrophy in MS and cognitive impairment, 166 physical disability, 167 disease course, 167 mood disturbances, 166 and quality of life. 167 Losseff et al 168 showed that progression of brain atrophy, but not T2-hyperintense lesions over 18 months, was related to deterioration of EDSS score.…”

Section: Atrophy Of the Cnsmentioning

confidence: 99%

“…166 One of the first studies conducted in this area demonstrated that linear measures of brain atrophy (bifrontal span, bicaudate span, and third ventricle width) were significantly correlated with cognitive impairment. 176 Subsequent work confirmed the close relationship between cognitive impairment and atrophy in central brain regions, measured by corpus callosum atrophy, 177 the bicaudate ratio, 178 and enlargement of the lateral ventricles.…”

Section: Atrophy Of the Cnsmentioning

confidence: 99%

Imaging of multiple sclerosis: Role in neurotherapeutics

Bakshi¹,

Minagar²,

Jaisani³

et al. 2005

Neurotherapeutics

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Summary:Magnetic resonance imaging (MRI) plays an everexpanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normalappearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1-or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

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Correlating Brain Atrophy With Cognitive Dysfunction, Mood Disturbances, and Personality Disorder in Multiple Sclerosis

Cited by 131 publications

References 99 publications

Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

Integrity of cerebral white matter in type 1 diabetes

Imaging of multiple sclerosis: Role in neurotherapeutics

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