Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Walhout, Renée; Westeneng, Henk Jan; Verstraete, Esther; Hendrikse, Jeroen; Veldink, Jan H.; Heuvel, Martijn P. van den; Berg, Leonard H van den

doi:10.1136/jnnp-2013-306839

Cited by 96 publications

(112 citation statements)

References 39 publications

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“…Cortical changes are not seen in disorders that mimic ALS or in patients with PMA ( Fig. 1) [32]. In addition, clinical disability in particular body regions correlated with focal cortical changes in corresponding regions of the somatotopic representation in the motor cortex [32], consistent with a previous VBM study [20].…”

Section: Volumetric Imagingsupporting

confidence: 76%

“…1) [32]. In addition, clinical disability in particular body regions correlated with focal cortical changes in corresponding regions of the somatotopic representation in the motor cortex [32], consistent with a previous VBM study [20]. Newer highresolution analytic methods, such as fractal dimension analysis, are able to model alterations in the shape of white matter, providing an additional potential diagnostic biomarker [33].…”

Section: Volumetric Imagingsupporting

confidence: 65%

“…However, significant challenges remain for analyzing the imaging data and establishing sufficient diagnostic accuracy. Several phase 2 studies have evaluated the diagnostic accuracy using single neuroimaging modalities, such as DTI and cortical thickness, with encouraging results, although clinical utility is currently limited [28,30,32,58,[97][98][99][100][101]. Using different statistical approaches, two meta-analyses evaluated several DTI studies and found that a single imaging metric results in marginal diagnostic accuracy measures (Fig.…”

Section: Challenges For Analysesmentioning

confidence: 99%

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Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

Verstraete

Foerster

2015

Neurotherapeutics

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Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of upper and lower motor neurons, with variable involvement of extramotor brain regions. Currently, there are no established objective markers of upper motor neuron and extramotor involvement in ALS. Here, we review the potential diagnostic value of advanced neuroimaging techniques that are increasingly being used to study the brain in ALS. First, we discuss the role of different imaging modalities in our increasing understanding of ALS pathogenesis, and their potential to contribute to objective upper motor neuron biomarkers for the disease. Second, we discuss the challenges to be overcome and the required phases of diagnostic test development to translate imaging technology to clinical care. We also present examples of multidimensional imaging approaches to achieve high levels of diagnostic accuracy. Last, we address the role of neuroimaging in clinical therapeutic trials. Advanced neuroimaging techniques will continue to develop and offer significant opportunities to facilitate the development of new effective treatments for ALS.

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Section: Volumetric Imagingsupporting

confidence: 76%

Section: Volumetric Imagingsupporting

confidence: 65%

Section: Challenges For Analysesmentioning

confidence: 99%

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Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

Verstraete

Foerster

2015

Neurotherapeutics

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“…The subcortical hypointense line corresponding to U-fibers appears smooth, and the gray-white junction, poorly demarcated ( Fig 1A, -B). When the M1 anatomy differed from such configurations, and namely the M1 deeper layers were particularly thin 23,29 and/or hypointense 9,30 ( Fig 1D, -E), images were judged as belonging to patients with ALS. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy in distinguishing patients and HS were calculated for each reader.…”

Section: Image Analysismentioning

confidence: 99%

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis

Cosottini¹,

Donatelli

Costagli³

et al. 2015

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment.

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“…At present it is still not completely clear to what extent the factors playing a role in dysarthria are related to the neurodegeneration triggered by ALS. In fact, there are studies which found positive associations between the bulbar sub-score of the revised version of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and the anatomy of the lateral portion of the motor homunculus (11)(12). Although this sub-score estimates bulbar function, it incorporates different abilities in one single composite score, in which the assessment of speech is simply quantified with a number ranging from 0 to 4 (13).…”

Section: Introductionmentioning

confidence: 99%

Morphometric correlates of dysarthric deficit in amyotrophic lateral sclerosis

Marco

Merico²,

Berta³

et al. 2015

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Objective: To investigate the volumetric correlates of speech in Amyotrophic Lateral Sclerosis (ALS).Methods: Twenty-three ALS patients had a structural 3D MRI scan, neuropsychological, linguistic and speech assessments. Twenty-three healthy adults of comparable age, education, white-matter hyperintensities and intracranial volumes were also recruited. Between-group differences in grey matter and white matter (WM) were examined to characterise ALS patients accurately. The association between residual speech and volumetric maps was studied in these patients.Results: ALS patients showed a pattern of WM reduction, which was located in peri-cortical motor/premotor fibres bilaterally, and in a large volume extending from the pons/midbrain to the cerebellum. A speech composite score was computed, and this was positively associated with premotor/supplementary-motor WM bilaterally, right cerebellar WM, and the posterior-caudal cerebellar cortex, bilaterally. Conclusion:Variance in residual speech in ALS is associated with variance in premotor WM and cerebellar volumes. Since premotor associations were found in volumes where ALS patients showed WM reduction, this region is believed to be directly involved in speech execution in this group. Since cerebellar associations were instead found in volumes free from shrinkage, this region is interpreted as playing a modulatory role, compensating for the impact of ALS pathology.

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Cortical thickness in ALS: towards a marker for upper motor neuron involvement

Cited by 96 publications

References 39 publications

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis

Morphometric correlates of dysarthric deficit in amyotrophic lateral sclerosis

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