Fractional Anisotropy in the Posterior Limb of the Internal Capsule and Prognosis in Amyotrophic Lateral Sclerosis

Menke, Ricarda; Abraham, Ivy; Thiel, Catherine S.; Filippini, Nicola; Knight, Stephen; Talbot, Kevin; Turner, Martin R

doi:10.1001/archneurol.2012.1122

Cited by 66 publications

(61 citation statements)

References 45 publications

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“…This idea conflicts with postmortem reports indicating that alterations in motor neuron cell bodies and axonal processes are at least as prominent as observations of demyelination (4). However, our observation of increased AD, also recently seen in ALS (34,35), could be indicative of axonal loss. Future advances in the understanding of the histologic correlates of different DTI metrics would serve well to inform this discussion.…”

Section: Discussionsupporting

confidence: 69%

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Chapman¹,

Jelsone‐swain²,

Johnson³

et al. 2014

Magnetic Resonance Imaging

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Purpose-To determine if decline in corpus callosum (CC) white matter integrity in patients with amyotrophic lateral sclerosis (ALS) is localized to motor-related areas.Materials and Methods-Twenty-one ALS patients and 21 controls participated. Diffusion tensor images (DTI) were acquired using 3 Tesla (T) MRI. Tract-based spatial statistics were used to examine whole-brain white matter damage. A segmentation schema was used to define CC volumes-of-interest (VOI). Fractional anisotropy (FA) and radial-and axial-diffusivity (RD, AD) were extracted from VOIs and compared between groups. DTI measurements in motor-related Area III were tested for correlation with symptoms and disease duration.Results-Extracted FA values from CC VOIs were reduced in ALS patients (P≤0.0001), particularly in Areas II and III (P≤0.01). Reduced FA in Area III correlated with disease symptomology (P≤0.05) and duration (P≤0.02). Between-group whole-brain comparisons (P≤0.05, corrected) showed reduced FA and increased RD throughout white matter regions including the CC, corona radiata, and internal capsule. AD was increased in the left corona radiata and internal and external capsules.Conclusion-FA in motor-related regions of the CC is more affected than other CC areas in ALS patients. Microstructural pathology of transcallosal fiber tracts may represent a future component of an imaging biomarker for ALS. AMYOTROPHIC LATERAL SCLEROSIS (ALS) is a progressive neurodegenerative disease affecting both upper-and lower-motor neurons. There are active efforts in the field of neuroimaging to discover a biomarker to aid in earlier diagnosis, improve the understanding of motor-neuron degeneration, and perhaps serve as an outcome measure for disease-modifying therapies. Unfortunately, early diagnosis of ALS has proven elusive as clinical confirmation can only occur after both upper (UMN) and lower motor neuron (LMN) involvement are detected by neurologic examination, which often occurs at a time point of advanced pathology (1). While noninvasive neurophysiologic techniques exist to detect subclinical LMN dysfunction, there is no sensitive tool that can similarly distinguish UMN dysfunction to aid in early diagnosis (2). For these reasons, much attention has turned toward neuroimaging as a means of identifying UMN involvement (3). KeywordsParticular interest in the use of diffusion tensor imaging (DTI) to identify UMN involvement in ALS has been growing. DTI research to date has largely replicated findings from postmortem studies indicating widespread microstructure deterioration along the UMNs of the corticospinal tract and corpus callosum (CC), validating this method as a valuable in vivo marker of the disease process (4-7). The CC in patients with ALS has consistently shown DTI changes, with decreased fractional anisotropy (FA) and increased radial and axial diffusivity (RD, AD) compared with control subjects (8). These changes may correspond to degeneration of transcallosal fibers passing between primary motor cortices observed at 1.5T (9). H...

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Section: Discussionsupporting

confidence: 69%

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Chapman¹,

Jelsone‐swain²,

Johnson³

et al. 2014

Magnetic Resonance Imaging

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“…While motor cortex atrophy has proven to be an inconsistent measure, 37 corpus callosum degeneration 38 and changes in the posterior limb of the internal capsule 39 have been gradually established as sensitive imaging signatures of ALS. Given the extensive involvement of subcortical structures in ALS, basal ganglia measures are likely to refine and improve the sensitivity of future diagnostic models.…”

Section: Resultsmentioning

confidence: 99%

Basal ganglia involvement in amyotrophic lateral sclerosis

et al. 2013

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ALS is associated with widespread basal ganglia involvement. Caudate nucleus, hippocampus, and nucleus accumbens atrophy are key features of ALS. Dysfunction of frontostriatal networks is likely to contribute to the unique neuropsychological profile of ALS, dominated by executive dysfunction, apathy, and deficits in social cognition. Our quantitative imaging findings are consistent with postmortem studies and indicate that subcortical gray matter structures should be included in future biomarker studies of ALS.

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“…34,35 There are also data specifically supporting a role for baseline FA in prognostication. 36,37 This raises the possibility that DTI measures might not be as simplistically related to WM tract degeneration in ALS as previously thought.…”

Section: Dti Analysis the Diffusion Toolbox Of The Fmrib (Centre Formentioning

confidence: 95%

Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS

et al. 2013

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Objective: To demonstrate the sensitivity of a recently developed whole-brain magnetic resonance spectroscopic imaging (MRSI) sequence to cerebral pathology and disability in amyotrophic lateral sclerosis (ALS), and compare with measures derived from diffusion tensor imaging.Methods: Whole-brain MRSI and diffusion tensor imaging were undertaken in 13 patients and 14 agesimilar healthy controls. Mean N-acetylaspartate (NAA), fractional anisotropy, and mean diffusivity were extracted from the corticospinal tract, compared between groups, and then in relation to disability in the patient group.Results: Significant reductions in NAA were found along the course of the corticospinal tracts on whole-brain MRSI. There were also significant changes in fractional anisotropy (decreased) and mean diffusivity (increased) in the patient group, but only NAA showed a significant relationship with disability (r 5 0.65, p 5 0.01). Conclusion:Whole-brain MRSI has potential as a quantifiable neuroimaging marker of disability in ALS. It offers renewed hope for a neuroimaging outcome measure with the potential for harmonization across multiple sites in the context of a therapeutic trial. Neurology â 2013;80:610-615 GLOSSARY ALS 5 amyotrophic lateral sclerosis; ALSFRS-R 5 Amyotrophic Lateral Sclerosis Functional Rating Scale-revised; CST 5 corticospinal tract; DTI 5 diffusion tensor imaging; FA 5 fractional anisotropy; LMN 5 lower motor neuron; MD 5 mean diffusivity; MIDAS 5 Metabolite Imaging and Data Analysis System; MRSI 5 magnetic resonance spectroscopic imaging; NAA 5 N-acetylaspartate; OR 5 optic radiation; PLS 5 primary lateral sclerosis; TBSS 5 tract-based spatial statistics; WM 5 white matter.

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Fractional Anisotropy in the Posterior Limb of the Internal Capsule and Prognosis in Amyotrophic Lateral Sclerosis

Cited by 66 publications

References 45 publications

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Basal ganglia involvement in amyotrophic lateral sclerosis

Whole-brain magnetic resonance spectroscopic imaging measures are related to disability in ALS

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