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

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Abstract

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.

Introduction

Magnetic resonance imaging (MRI) with its new developments is the most important imaging technique today in the diagnosis of multiple sclerosis (MS) [18], [36], [42]]. A more reliable and reproducible analysis of MRI lesions can be now obtained with new computer-assisted quantitative MRI techniques [41]. The process of detecting and delineating objects in images referred to as image segmentation embodies a vast amount of literature [7]. The use of various segmentation techniques has become an important part in the accurate quantitative analysis of MS lesions in various treatment trials.

Most earlier MR studies have been focused on the assessment of MS plaques and their correlations with neurological disability [3], [10], [14], [24]. It was observed that hyperintense lesions on T2-weighted images (T2-plaques) cannot differentiate the separate pathological stages of MS lesion development and represent both active and inactive disease [1]. They display overall lesion load. The degree of hypointensity of MS plaques on T1-weighted images (T1-plaques) correlated with the extent of axonal damage, extracellular edema and the degree of demyelination or remyelination [4]. The gadolinium-enhanced plaques on T1-weighted images were found to display the currently active MS plaques [29]. The appearance of new enhancing or non-enhancing lesions or the re-enhancement of the old lesions on MRI was reported to be 5 to 10 times greater than could be expected clinically [30].

The correlations between the number, size, volume and site of MS plaques on conventional MRI examination and neurological disability have been disappointingly weak and only apparent in relapsing-remitting MS [10], [15], [16]. In general visualization of MS plaques on MRI increased the understanding of the disease, but the objective marker to evaluate disability and the efficacy of the treatment aimed at preventing disability were highly needed.

Cerebral and spinal atrophy are important new findings that represent global tissue loss and seem to be correlated with disability measures [26], [27], [11], [12], [13]. Progressive cerebral atrophy correlates with worsening disability when analyzed on conventional MRI technique [5], [19], [27], [34]. This observation indicates that the measurement of atrophy provides an objective marker by which to evaluate the effect of treatment on neurological disability. With the use of new volumetric techniques, estimation of cerebral atrophy is becoming more accurate and less time consuming than the earlier use of linear indices.

The purpose of the present study was to correlate the segmented volumes of intracranial cerebrospinal fluid (CSF) spaces representing brain atrophy and the volumes of MS plaques with neurological disability expressed in expanded disability status scale (EDSS) [25] and regional functional scoring system (RFSS) scores [31], [35] in secondary progressive MS. Correlations between MRI volumetric measurement and RFSS scores are reported for the first time. All volume determinations were performed by using a new microcomputer applicable semiautomatic MRI segmentation technique.

Section snippets

Subjects

Twenty-eight patients (14 males and 14 females, age range 35–58 years, mean age 46) with secondary progressive MS underwent a detailed neurological and neuroradiological examination. All studied patients had definitive MS and fulfilled the Poser's criteria A1 or A2 [33].

Detailed examination of the neurological disability included evaluation of EDSS scores (range 3.5–6.5, mean 4.8) and total RFSS scores (range 5.6–23.7, mean 13.9). The duration of the relapsing–remitting (the time from the

Results

Using Anatomatic™ segmentation technique we estimated that the median total lesion volumes of the brains of our MS patients for T2- and T1-weighted plaques were 5.21 cm3 and 0.60 cm3, respectively. In the assessment of brain atrophy we found that the median volume for total intracranial CSF spaces (total volumes of ventricles and peripheral cerebrospinal fluid spaces) was 131.9 cm3. The relation of total intracranial CSF space volumes to total brain volume was on average 0.18.

In the

Discussion

In this study, using computerised semiautomatic quantification of MRI parameters in patients with secondary progressive MS we found that an increasing total and relative intracranial CSF volumes indicative of brain atrophy were associated with worsening neurological disability as expressed by EDSS.

Progressive cerebral atrophy which represents axonal loss has been reported in patients with MS [32], [27]. Axonal injury has been explained by an inflammation [39], [9], but recent studies have shown

Acknowledgements

The authors thank Pertti Ryymin for skillful technical assistance. The study was supported by Medical Research Fund of the Tampere University Hospital, The Finnish Foundation of Cardiovascular Research, The Elli and Elvi Oksanen Fund of the Pirkanmaa, Regional Fund under the auspices of the Finnish Cultural Foundation, Emil Aaltonen Foundation, Wihuri Foundation, Ulla Tuominen Foundation, Instrumentarium Science Foundation, Ragnar Granit Foundation, The Finnish Radiological Association and

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