Recent advances and opportunities for improving diagnosis of amyotrophic lateral sclerosis

ABSTRACT

Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of upper and lower motor neurons causing progressive weakness, and in nearly all cases, death. The diagnosis of ALS is currently limited to physical exam and electrodiagnostic testing, with use of diagnostic testing to exclude ALS mimics. There is growing interest in developing improved biomarkers to make an earlier and more accurate diagnosis of ALS, for use in clinical practice and for recruitment into trials. A number of promising biomarkers have been recently described, including imaging modalities, blood and CSF biomarkers, genetic testing, and electrodiagnostic techniques.

Areas covered: This review describes the current diagnostic criteria for ALS and emerging biomarkers showing promise in the diagnosis and tracking of disease progression in ALS. Types of biomarkers and testing modalities reviewed include genetic, electrodiagnostic, imaging, and blood and CSF markers.

Expert opinion: ALS currently remains a clinical diagnosis, but many emerging testing modalities and biomarkers show promise in ALS diagnosis and tracking disease progression. Some of the most promising biomarkers include genetic testing, volume based MRI modalities, and serum and CSF light chain neurofilament. The greatest challenge to ALS diagnostic testing is the broad pathogenic heterogeneity underlying a common clinical phenotype.

KEYWORDS:

• Amyotrophic lateral sclerosis
• motor neuron disease
• primary lateral sclerosis
• progressive muscular atrophy
• biomarker
• electrodiagnostic testing

Article highlights

• ALS remains at this point a clinical diagnosis made using history, physical exam, and electrodiagnostic testing to confirm upper and lower motor neuron dysfunction in multiple body segments and using Awaji or El Escorial criteria to categorize certainty of diagnosis.

• Traditional and newer electrodiagnostic techniques, including EMG, MUNIX and TMS play an important role in diagnosis of ALS and monitoring disease progression.

• There is an expanding role of genetic testing in ALS diagnosis and understanding motor neuron disease pathogenesis.

• Multiple imaging modalities show promise as biomarkers for ALS diagnosis, particularly volume based MRI modalities and metabolic imaging techniques.

• Serum and CSF biomarkers in development for ALS diagnosis include light chain neurofilament and microRNA profiles.

• The challenges of developing ALS biomarkers lie in the pathogenetic heterogeneity of a clinical phenotype and the need to develop testing methods that can be reproduced reliability in a variety of settings.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.