Advances in Neuroimaging for Amyotrophic Lateral Sclerosis

In a review of PET imaging in ALS, researchers found that the largest study to date involved 195 ALS patients and 40 controls. FDG-PET using generalized linear discriminant model resulted in 95% sensitivity and 83% specificity in distinguishing ALS patients from healthy controls.⁹

Although advances in ALS neuroimaging have been substantial, further progress is needed in developing biomarkers for the presymptomatic period, which is currently only feasible for familial ALS.

“Ongoing research into patients with preclinical familial ALS to identify biomarkers of disease onset is very important,” Pioro said, “but may become even more useful if such indicators of pathology can reveal disease at the earliest stages of symptom onset in nonfamilial patients.”

In an opinion piece, Martin Turner of Oxford University’s John Radcliffe Hospital and Michael Benatar, of Miller School of Medicine, University of Miami, said such presymptomatic biomarkers are essential for studying both disease onset and symptom onset as well as overcoming biases inherent in studies that focus exclusively on people already affected.²

The article listed several research needs, among them the need to standardize techniques and data sharing. Such standards for sample collection, storage, and analysis are required not only for those affected, but also for relevant healthy controls in order to be able replicate findings that allow the validation essential to advancing the understanding and treatment of ALS. The authors recommended that a biomarker development arm should be a mandatory component in all future therapeutic trials. Multivariate modeling is also required because of the complex biology of ALS.²

“Hopefully we will [soon] have a palette of biomarkers, [including] blood, CSF, electrodiagnostic, and neuroimaging-based, to achieve early and accurate identification of ALS in patients who will be able to derive the greatest benefits from present and emerging therapies,” said Pioro.

Michael O’Leary is a freelance medical writer based in the greater Seattle Area. This article was medically reviewed by Pat F. Bass III, MD, MS, MPH.

References

1. Chiò A, Pagani M, Agosta F, Calvo A, Cistaro A, Filippi M. Neuroimaging in amyotrophic lateral sclerosis: insights into structural and functional changes. Lancet Neurol. 2014;13(12):1228-40.
2. Turner MR, Benatar M. Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis. Muscle Nerve. 2015;51(1):14-8.
3. ALS Association. “Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing” http://www.alsa.org/about-als/genetic-testing-for-als.html
4. ALS Association. “Diagnosing ALS” http://www.alsa.org/about-als/diagnosing-als.html
5. Foerster BR, Carlos RC, Dwamena BA, et al. Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2014;1(2):107-14.
6. Verstraete E, Foerster BR. Neuroimaging as a new diagnostic modality in amyotrophic lateral sclerosis. Neurotherapeutics. 2015;12(2):403-16.
7. Rajagopalan V, Pioro EP. Comparing brain structural MRI and metabolic FDG-PET changes in patients with ALS-FTD: ‘the chicken or the egg?’ question. J Neurol Neurosurg Psychiatr. 2014;
8. Pradat PF, El mendili MM. Neuroimaging to investigate multisystem involvement and provide biomarkers in amyotrophic lateral sclerosis. Biomed Res Int. 2014;2014:467560.
9. Quartuccio N, Van weehaeghe D, Cistaro A, Jonsson C, Van laere K, Pagani M. Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what is new?. Q J Nucl Med Mol Imaging. 2014;58(4):344-54.