Abstract Details

Title Multimodal Characterization of Delayed Diagnosis in ALS

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S13 - Behavioral and Cognitive Neurology: Behavioral Neurology, Aging, and Dementia (2:28 PM-2:39 PM)

Poster/Presentation
Number 009

Background There is significant heterogeneity in the phenotypic expression of ALS including site of onset, relative degree of upper (UMN) and lower motor neuron (LMN) dysfunction, and presence of genetic mutations. As a result, it can take over a third of the overall disease duration to accurately diagnose ALS and initiate clinical care or trials enrollment. We performed a multimodal characterization of ALS patients with long diagnostic delay to identify features facilitating an earlier diagnosis.

Objective

To investigate the clinical, genetic, cerebrospinal fluid (CSF) and MRI features of ALS patients with a long diagnostic delay in an effort to facilitate earlier diagnosis.

Design/Methods A retrospective assessment of 934 patients who eventually met criteria for probable or definite ALS. Linear regression models were applied to test the role of clinical and genetic features in predicting diagnostic delay (time from symptoms onset to diagnosis). Patients were subsequently divided into “short” (N=551) and “long” (N=383) diagnostic delay groups (defined with a median split of 12 months) and clinical, CSF (including total tau (tTau) and neurofilament light chain (NfL)) and cortical thickness MRI measurements were acquired and compared between the two groups.

Results Significant predictors for a longer diagnostic delay included: spinal onset, selective UMN dysfunction, an initial suspected El Escorial diagnosis and the absence of a genetic mutation. Patients with a long diagnostic delay relative to cases with short diagnostic delay had a slower clinical progression rate and a longer survival. CSF tTau, CSF NfL, and cortical thinning in primary motor and fronto-temporal regions were significantly reduced in the longer relative to shorter diagnostic delay group.

Conclusions While altered biomarkers can identify shorter diagnostic delay patients, cases with longer delay may exhibit spinal onset, UMN dysfunction, and sporadic disease. Clinicians should consider these factors in an effort to accelerate a confirmed ALS diagnosis.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Katerina Placek	No disclosure on file
Murray Grossman, MD, FAAN (University of Pennsylvania)	Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
Colin Quinn, MD (University of Pennsylvania)	Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Quinn has received personal compensation in the range of $0-$499 for serving as a Consultant for Amicus. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta Therapeutics. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Quinn has received personal compensation in the range of $0-$499 for serving as a Consultant for Clene Nanomedicine. Dr. Quinn has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Quinn has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Partners Health Care. Dr. Quinn has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Robins Kaplan.
Leo McCluskey, MD (Atrium Health Neurosciences Institute)	No disclosure on file
Lauren B. Elman, MD	Dr. Elman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Elman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Elman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Edgewise Therapeutics. Dr. Elman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for PTC Therapeutics. Dr. Elman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apellis Pharamaceuticals. Dr. Elman has received publishing royalties from a publication relating to health care.
Corey McMillan, PhD (University of Pennsylvania)	Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. McMillan has received research support from Biogen. The institution of Dr. McMillan has received research support from NIH.

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