Hastening the Diagnosis of Amyotrophic Lateral Sclerosis

Hiroshi Mitsumoto, Edward J. Kasarskis, Zachary Simmons

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disease. Neurologists generally see patients as requested and as schedules allow. This practice is part of the reason it takes approximately 12 months from onset of new progressive weakness to receive a definitive diagnosis of ALS. It is well recognized that the disease of ALS starts long before symptom onset. In mutant SOD1 transgenic mice, early loss of motor neurons and compensatory morphological changes precede a rapid loss of motor neurons that coincides with symptom onset. In a human autopsy study, anterior roots in the "presymptomatic"stage indicate that ∼20% loss of motor neurons had already occurred. Sera collected from individuals who later developed ALS and sera from presymptomatic members of families with ALS harboring pathogenic gene variants demonstrated high neurofilament (Nf) levels, again suggesting that the neurodegenerative process is already active at a clinically presymptomatic stage. Potential benefits of hastening the diagnosis of ALS include earlier initiation of therapy to slow the fundamental neurodegenerative process. Such effects are observed in treatment with riluzole, edaravone, methylcobalamin, and sodium phenylbutyrate-taurursodiol in patient care and clinical trial settings. Early initiation of multidisciplinary care results in cost savings and prolonged survival. Early diagnosis after symptom onset also seems to reduce psychological distress. Hence, how can we facilitate an earlier diagnosis of ALS? We already have the necessary tools. New and simple ALS diagnostic criteria (Gold Coast Criteria) have been introduced along with genetic testing. At least 2 studies provide Class II evidence that establishes the reliability and sensitivity of CSF and/or serum Nf levels in supporting a diagnosis of ALS. Challenges, however, still exist as to how to facilitate earlier recognition of possible ALS by primary care physicians and other nonneurologist providers and how to foster a sense of urgency among neurologists to accelerate the diagnostic process. In this article, we provide a number of recommendations that we hope will help achieve these ends.

Original languageEnglish
Pages (from-to)60-68
Number of pages9
Issue number2
StatePublished - Jul 12 2022

Bibliographical note

Publisher Copyright:
© 2022 American Academy of Neurology.

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'Hastening the Diagnosis of Amyotrophic Lateral Sclerosis'. Together they form a unique fingerprint.

Cite this