Time to Diagnosis and Factors Affecting Diagnostic Delay in Amyotrophic Lateral Sclerosis

Abstract

At present, disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain limited, with early intervention crucial for maximum potential benefit. A majority of patients will develop dysphagia during the course of their disease, and most will die within three years of the first symptom onset due to respiratory complications. Therefore, early diagnosis is vital to ensure the patient receives appropriate multidisciplinary care and resultant improved longevity as well as quality of life. However, a recent literature review found that ALS patients experience a diagnostic delay of 10-16 months from symptom onset. This chapter examines the factors that contribute to diagnostic delay and potential interventions to decrease time to diagnosis.

Prediction Model of Amyotrophic Lateral Sclerosis by Deep Learning with Patient Induced Pluripotent Stem Cells

“…Attempts to create new diagnostic criteria 22 and the development of biomarkers 23,24 are promising, but they have as yet not predicted ALS diagnosis. 25 Thus, by combining our model, which is expected to be a supportive tool for ALS diagnosis, and clinical biomarkers including blood/spinal fluid neurofilament levels, it may be possible to classify ALS with even greater accuracy. Furthermore, for ALS patients with progressed stage, there may be a possibility of applying this model to prognosis prediction and the stratification of patients for treatment selection in the future.…”

“…Progression of the disease in patients is considered to be one of the causes of clinical trial failure, because motor neurons start to disappear, and the urgency for diagnosis is increasingly emphasized. Attempts to create new diagnostic criteria 22 and the development of biomarkers 23,24 are promising, but they have as yet not predicted ALS diagnosis 25 . Thus, by combining our model, which is expected to be a supportive tool for ALS diagnosis, and clinical biomarkers including blood/spinal fluid neurofilament levels, it may be possible to classify ALS with even greater accuracy.…”

Role of plasma phosphorylated neurofilament heavy chain (pNfH) in amyotrophic lateral sclerosis

“…However, due to the clinical heterogeneity of the disease and its insidious onset, the time between symptom appearance and confirmed diagnosis is still too long. 4,5 There are still no validated diagnostic biomarkers which can be expression of the underlying pathology, and can improve the diagnostic process. Currently, the most promising candidate biomarkers for ALS are neurofilaments (NFs), particularly the neurofilament light chain (NfL) and the phosphorylated neurofilament heavy chain (pNfH), which are main components of the neuronal cytoskeleton.…”

Early and progressive dysfunction revealed by in vivo neurite imaging in the rNLS8 TDP-43 mouse model of ALS

“…Symptom onset is often insidious and with no pathognomonic test for ALS, and a broad spectrum of mimicking disorders, diagnosis remains challenging ( Chio, 1999 , Palese et al, 2019 ). A review of 21 retrospective studies published between 1990 and 2020 found a typical diagnostic delay of 10–16 months following symptom presentation with misdiagnosis occurring in 13–68.4% of cases ( Richards et al, 2020 ).…”

“…Prompt diagnosis reduces the potential for unnecessary and often invasive procedures, inappropriate or adverse therapeutic avenues, and reduces the associated psychological impact to patients. It also expedites appropriate and supportive interventions, and earlier enrolment into clinical trials of potential disease modifying therapies allowing for both timely initiation of treatment, and extended monitoring of outcomes ( Richards et al, 2020 ). A diagnosis of ALS is made on the widely-accepted El-Escorial revised criteria, which requires both the presence of upper and lower motor neuron degeneration and the progressive spread of symptoms ( Brooks et al, 2000 ).…”