Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis

Dastidar, Prasun; Heinonen, T.; Lehtimäki, Terho; Ukkonen, M.; Peltola, Jukka; Erilä, Terttu; Laasonen, E. M.; Elovaara, Irina

doi:10.1016/s0022-510x(99)00071-4

Cited by 56 publications

(39 citation statements)

References 38 publications

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“…56 Decreases in brain volume over time have been documented to be objective and reliable markers for the destructive pathologic processes associated with MS. [63][64][65][66] The course of the brain atrophy may be influenced by prior inflammatory disease activity, but this has not been observed in all studies. 65,67 A continued loss of brain parenchyma from axonal degeneration as a consequence of chronic demyelination in the ); and -, patients with less than 24 months of follow-up.…”

Section: Discussionmentioning

confidence: 99%

High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

Nash

Bowen

McSweeney

et al. 2003

Blood

208

167

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There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (> 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy.

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Section: Discussionmentioning

confidence: 99%

High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

Nash

Bowen

McSweeney

et al. 2003

Blood

208

167

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“…Cross-sectional [4,5,7,9,18,23,31] and longitudinal studies [11,12,14,20,29, 30] show brain volume or brain volume changes to be correlated with the level or changes in disability. It has also been reported [13,29] that measuring brain volume changes over time is a sensitive approach to determine the treatment effect in MS clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, several crosssectional and longitudinal studies with magnetic resonance imaging (MRI) [4, 5, 7, 9, 11-14, 18, 20, 23, 24, 29, 30, 31] have investigated the magnitude of the correlation between brain volume and MS clinical findings. These studies showed that brain atrophy can develop in the early phases of MS [29,30], and that the amount of tissue loss is more pronounced in patients with more severe disability [4,5,12,14,18,20,31]. Since conventional MRI measures, such as the load of hyperintense lesions on T2-weighted images, lack pathological specificity [28] and are modestly correlated with patients' disability [28], the measurement of brain volume has been proposed as an objective marker of MS severity with the potential to monitor the disease course accurately [15].…”

Section: Introductionmentioning

confidence: 99%

Sensitivity and reproducibility of volume change measurements of different brain portions on magnetic resonance imaging in patients with multiple sclerosis

Rovaris¹,

Inglese²,

Schijndel

et al. 2000

Journal of Neurology

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The course of multiple sclerosis (MS) can be monitored by measuring changes in brain volume, but consensus is still lacking on the best strategy to be adopted. We compared the reproducibility and sensitivity of volume measurements from different brain portions for detecting changes on magnetic resonance imaging (MRI) in patients with MS. T1-weighted MRI of the brain was performed in 50 patients with relapsing-remitting MS at study entry and after an average follow-up of 18.4 months. Using a semiautomated technique for brain parenchyma segmentation, the volumes of the following brain portions were measured: (a) the whole brain (whole-brain volume, WBV), (b) the seven slices rostral to the velum interpositum (seven-slice volume, SSV), (c) the central slice of the image set (central-slice volume, CSV) and (d) the infratentorial regions (infratentorial-brain volume, IBV). All these measurements were carried out by a single observer and were repeated twice on ten randomly selected scans to test the intra-observer reproducibility using the four strategies. At follow-up there was a significant decrease in all the measures of brain volume (P ranged from 0.002 to < 0.001). The univariate correlations between changes in WBV, SSV, CSV and IBV were all statistically significant, with the exception of that between changes in CSV and IBV; r values ranged from 0.34 (for the WBV/IBV correlation) to 0.80 (for the WBV/SSV correlation). The mean intra-observer coefficient of variations were 1.9% for WBV, 1.5% for SSV, 2.9% for CSV and 2.2% for IBV measurements. The measurement of volume on a portion of brain selectively including the regions in which MS pathology is more diffuse is as reliable and sensitive to disease-related changes as that on the whole brain, with significant time saving for processing.

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“…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. Dastidar et al 169 showed that brain atrophy was associated with EDSS score, whereas T2-hyperintense and T1-hypointense lesion volumes were not. Bermel et al 170 showed that whole brain atrophy was the best predictor of EDSS disability when compared with other cerebral lesion measures (R 2 ϭ 0.204, p Ͻ 0.001).…”

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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Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis

Cited by 56 publications

References 38 publications

High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis

Sensitivity and reproducibility of volume change measurements of different brain portions on magnetic resonance imaging in patients with multiple sclerosis

Imaging of multiple sclerosis: Role in neurotherapeutics

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