Diagnostic shifts in ALS? From clinical specter to imaging spectra

From the Florey Institute for Neuroscience and Mental Health (A.B.), University of Melbourne, Melbourne
Neurology (Impact Factor: 8.29). 01/2013; 80(7). DOI: 10.1212/WNL.0b013e318281cd27
Source: PubMed


Paradigm shifts are occurring across the realm of amyotrophic lateral sclerosis (ALS). In the past, we instructed medical students that ALS was solely a clinical diagnosis; that careful clinical examination raised the specter of this devastating condition, and neurophysiologic testing provided confirmation. We taught that ALS was an isolated clinical syndrome; that neuroimaging was not helpful for the diagnosis, other than to exclude mimic syndromes; that patients did not have significant dementia; and finally, that little could be done to predict or alter an individual patient's course.

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    ABSTRACT: Introduction: Magnetic resonance spectroscopy (MRS) will continue to play an ever increasing role in drug discovery because MRS does readily define biomarkers for several hundreds of clinically distinct diseases. Published evidence based medicine (EBM) surveys, which generally conclude the opposite, are seriously flawed and do a disservice to the field of drug discovery. Areas covered: This article presents MRS and how it has guided several hundreds of practical human 'drug discovery' endeavors since its development. Specifically, the author looks at the process of 'reverse-translation' and its influence in the expansion of the number of preclinical drug discoveries from in vivo MRS. The author also provides a structured approach of eight criteria, including EBM acceptance, which could potentially re-open the field of MRS for productive exploration of existing and repurposed drugs and cost-effective drug-discovery. Expert opinion: MRS-guided drug discovery is poised for future expansion. The cost of clinical trials has escalated and the use of biomarkers has become increasingly useful in improving patient selection for drug trials. Clinical MRS has uncovered a treasure-trove of novel biomarkers and clinical MRS itself has become better standardized and more widely available on 'routine' clinical MRI scanners. When combined with available new MRI sequences, MRS can provide a 'one stop shop' with multiple potential outcome measures for the disease and the drug in question.
    No preview · Article · May 2013 · Expert Opinion on Drug Discovery