Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral Sclerosis

Dept. of Neurology, Medical School Hannover, Hannover, Germany.
BMC Neurology (Impact Factor: 2.04). 04/2006; 6(1):17. DOI: 10.1186/1471-2377-6-17
Source: PubMed


Widespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS) has been described in neuropathological studies. The presence of cortical atrophy in conventional and scientific neuroimaging has been a matter of debate. In studies using computertomography, positron emission tomography, proton magnetic resonance spectroscopy and conventional T2-weighted and proton-weighted images, results have been variable. Recent morphometric studies by magnetic resonance imaging have produced conflicting results regarding the extent of grey and white matter involvement in ALS patients.
The authors used optimized voxel-based morphometry as an unbiased whole brain approach to detect differences between regional grey and white matter volumes. Seventeen patients with a diagnosis of ALS according to El-Escorial criteria and seventeen age-matched controls received a high resolution anatomical T1 scan.
In ALS patients regional grey matter volume (GMV) reductions were found in the pre- and postcentral gyrus bilaterally which extended to premotor, parietal and frontal regions bilaterally compared with controls (p < 0.05, corrected for the entire volume). The revised ALS functional rating scale showed a positive correlation with GMV reduction of the right medial frontal gyrus corresponding to the dorsolateral prefrontal cortex. No significant differences were found for white matter volumes or when grey and white matter density images were investigated. There were no further correlations with clinical variables found.
In ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent feature of the disease. Supporting the concept of ALS being a multisystem disorder, our study provides further evidence for extramotor involvement which is widespread. The lack of correlation with common clinical variables probably reflects the fact that heterogeneous disease processes underlie ALS. The discrepancy within all published morphometric studies in ALS so far may be related to differences in patient cohorts and several methodological factors of the data analysis process. Longitudinal studies are required to further clarify the time course and distribution of grey and white matter pathology during the course of ALS.

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    • "The involvement of the posterior limb of the internal capsule that we observed has been previously highlighted in relation to prognosis [21]. The changes in frontal areas are in line with bilateral frontal atrophy in VBM [8], [10], [12], [13], an frontally increased diffusivity [22], [23] and post mortem studies [24]. Also VBI confirms that the corpus callosum, which connects orbitofrontal and frontal cortices, is consistently involved in ALS pathology [25]. "
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons. Advanced MRI techniques such as diffusion tensor imaging have shown great potential in capturing a common white matter pathology. However the sensitivity is variable and diffusion tensor imaging is not yet applicable to the routine clinical environment. Voxel-based morphometry (VBM) has revealed grey matter changes in ALS, but the bias-reducing algorithms inherent to traditional VBM are not optimized for the assessment of the white matter changes. We have developed a novel approach to white matter analysis, namely voxel-based intensitometry (VBI). High resolution T1-weighted MRI was acquired at 1.5 Tesla in 30 ALS patients and 37 age-matched healthy controls. VBI analysis at the group level revealed widespread white matter intensity increases in the corticospinal tracts, corpus callosum, sub-central, frontal and occipital white matter tracts and cerebellum. VBI results correlated with disease severity (ALSFRS-R) and patterns of cerebral involvement differed between bulbar- and limb-onset. VBI would be easily translatable to the routine clinical environment, and once optimized for individual analysis offers significant biomarker potential in ALS.
    PLoS ONE 08/2014; 9(8):e104894. DOI:10.1371/journal.pone.0104894 · 3.23 Impact Factor
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    • "Several studies described structural neurodegenerative alterations in ALS not only within motor areas, but also across multiple frontotemporal, limbic or subcortical structures (Agosta et al., 2010; Anderson et al., 1995; Grosskreutz et al., 2006; Kato et al., 1997; Neumann et al., 2006; Takeda et al., 2009; Tsermentseli et al., 2012; Wightman et al., 1992). As for the functional results, the pattern of changes was quite inconsistent across studies, probably due to differences in the disease stages of the patient populations. "
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    ABSTRACT: Previous studies have shown that in amyotrophic lateral sclerosis (ALS) multiple motor and extra-motor regions display structural and functional alterations. However, their temporal dynamics during disease-progression are unknown. To address this question we employed a longitudinal design assessing motor- and novelty-related brain activity in two fMRI sessions separated by a 3-month interval. In each session, patients and controls executed a Go/NoGo-task, in which additional presentation of novel stimuli served to elicit hippocampal activity. We observed a decline in the patients’ movement-related activity during the 3-month interval. Importantly, in comparison to controls, the patients’ motor activations were higher during the initial measurement. Thus, the relative decrease seems to reflect a breakdown of compensatory mechanisms due to progressive neural loss within the motor-system. In contrast, the patients’ novelty-evoked hippocampal activity increased across 3 months, most likely reflecting the build-up of compensatory processes typically observed at the beginning of lesions. Consistent with a stage-dependent emergence of hippocampal and motor-system lesions, we observed a positive correlation between the ALSFRS-R or MRC-Megascores and the decline in motor activity, but a negative one with the hippocampal activation-increase. Finally, to determine whether the observed functional changes co-occur with structural alterations, we performed voxel-based volumetric analyses on magnetization transfer images in a separate patient cohort studied cross-sectionally at another scanning site. Therein, we observed a close overlap between the structural changes in this cohort, and the functional alterations in the other. Thus, our results provide important insights into the temporal dynamics of functional alterations during disease-progression, and provide support for an anatomical relationship between functional and structural cerebral changes in ALS.
    Clinical neuroimaging 07/2014; 5. DOI:10.1016/j.nicl.2014.07.007 · 2.53 Impact Factor
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    • "Their primary role is the interhemispheric integration of various brain functions, including basic sensorimotor and high-level cognitive integration.29 The involvement of the CC in ALS was first proposed in seminal histologic studies that found numerous degenerating fibers in the CC in almost all areas of ALS brains, although the pathology was most conspicuous in the middle portion of the CC.3 Atrophy of the CC with anterior predominance has been identified in several MRI studies,7,30 while others have found no size differences in patients with ALS.31,32 However, these studies were limited to the midsagittal CC cross-section either grossly or with geometric subdivisions, and thus did not address those CC fibers projecting into different cortical regions. "
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    ABSTRACT: Background and Purpose Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS. Methods Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively. Results The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs. Conclusions Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.
    Journal of Clinical Neurology 07/2014; 10(3):249-56. DOI:10.3988/jcn.2014.10.3.249 · 1.70 Impact Factor
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