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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    • "Whole-brain based methods provide promising ways of characterizing the neural basis of the non-motor symptoms in ALS. Notably, the majority of existing morphometric studies on ALS was conducted through VBM, reporting focal loss of grey and white matter in some specific brain regions (Grosskreutz et al. 2006; Bede et al. 2013). The interpretation of VBM results can be difficult given that an actual physical characteristic is not measured directly (Singh et al. 2006). "
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscular weakness and atrophy. Several morphometric studies have been conducted to investigate the gray matter volume or thickness changes in ALS, whereas the cortical folding pattern remains poorly understood. In the present study, we applied a surface-based local gyrification index (LGI) from high resolution MRI data to quantify the cortical folding in matched samples of 25 ALS patients versus 25 healthy controls. Using resting-state fMRI data, we further conducted seed-based functional connectivity analysis to explore the functional correlate of the cortical folding changes. We found that ALS patients had significantly reduced LGI in right occipital cortex and that abnormality in this region associated with decreased functional connectivity in the bilateral precuneus. This set of findings was speculated to result from disturbed white matter connectivity in ALS. In the patient group, we revealed significant negative correlations between disease duration and the LGIs of a cluster in the left superior frontal gyrus, which may reflect the cognitive deterioration in ALS. In summary, our results suggest that LGI may provide a useful means to assess ALS-related neurodegeneration and to study the pathophysiology 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.
    Full-text · Article · Aug 2014 · PLoS ONE
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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.
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