Towards a neuroimaging biomarker for amyotrophic lateral sclerosis

Turner, Martin R; Großkreutz, Julian; Kassubek, Jan; Abrahams, Sharon; Agosta, Federica; Benatar, Michael; Filippi, Massimo; Goldstein, Laura H.; Heuvel, Martijn P. van den; Kalra, Sanjay; Lulé, Dorothée; Mohammadi, Bahram

doi:10.1016/s1474-4422(11)70049-7

Cited by 153 publications

(123 citation statements)

References 5 publications

(10 reference statements)

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Biochemical markers of underlying neuropathology phosphorylated high molecular weight neurofilament protein (pNFH) or immunological markers are also promising [86]. These methods have generated interesting data, particularly within certain disease presentations involving upper motor neuron dysfunction, but have not yet been accepted as markers applicable throughout the disease spectrum.…”

Section: Biomarkersmentioning

confidence: 99%

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Rosenfeld¹,

Strong

2015

Neurotherapeutics

View full text Add to dashboard Cite

With the acceleration in our understanding of ALS and the related motor neuron disease has come even greater challenges in reconciling all of the proposed pathogenic mechanisms and how this will translate into impactful treatments. Fundamental issues such as diagnostic definition(s) of the disease spectrum, relevant biomarkers, the impact of multiple novel genetic mutations and the significant effect of symptomatic treatments on disease progression are all areas of active investigation. In this review, we will focus on these key issues and highlight the challenges that confront both clinicians and basic science researchers.

show abstract

Section: Biomarkersmentioning

confidence: 99%

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Rosenfeld¹,

Strong

2015

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…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).…”

mentioning

confidence: 99%

Diffusion tensor MRI of the corpus callosum in amyotrophic lateral sclerosis

Chapman¹,

Jelsone‐swain²,

Johnson³

et al. 2014

Magnetic Resonance Imaging

View full text Add to dashboard Cite

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...

show abstract

“…Emergence of several disease-modifying drugs in neurodegenerative diseases has particularly highlighted the need for biomarkers of therapeutic response. Unwanted drug effects has brought additional requirement for effective biomarkers for optimal initial patient selection and timing of discontinuation (Turner et al, 2011). In the future, in search for robust biomarkes, MRI based neuroimaging techniques are a promising candidate.…”

Section: Discussionmentioning

confidence: 99%

“…MRS has been used in research but fields of clinical application are expanding i.e. longitudinal change of metabolites in therapeutic intervention (Turner et al, 2011).…”

Section: Spectroscopymentioning

confidence: 99%