Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative neuromuscular disease with limited treatment options. The diagnosis of ALS can be challenging for numerous reasons, resulting in delays that may compromise optimal management and enrollment into clinical trials. Several studies have examined the process and challenges regarding the clinical diagnosis of ALS. Twenty-one studies that were almost exclusively from the English literature published between 1990 and 2020 were identified via PubMed using relevant search terms and included patient populations from the United States, Canada, Japan, Egypt, and several countries in South America and Europe. Probable or definitive ALS patients were identified using El Escorial or revised El Escorial/Airlie House Criteria. Time to diagnosis or diagnostic delay was defined as mean or median time from patient-reported first symptom onset to formal diagnosis by a physician, as recorded in medical records. The typical time to diagnosis was 10-16 months from symptom onset. Several points of delay in the diagnosis course were identified, including specialist referrals and misdiagnoses, often resulting in unnecessary procedures and surgeries. Bulbar onset was noted to significantly reduce time to ALS diagnosis. Future interventions and potential research opportunities were reviewed. Diagnostic delay in non-neurological ambulatory medicineDiagnostic delay is a problem broadly impacting medicine. In a 2012 study, Poon et al. examined cases of missed or delayed diagnoses of breast and colon cancer, which have the potential for good outcomes if caught early. Ninety-five percent of diagnostic delay involved

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

“…The recent literature review (10) found that the typical delay to diagnosis for ALS patients is 10-16 months reviewed studies from 1990 to 2020, which suggests the establishment of clinical diagnostic criteria and growing public awareness of ALS may not have been sufficient to significantly shorten delay (20). While this chapter has addressed the "what" and the "where" with regard to ALS diagnostic delay, there remains the question of why?…”

“…The study reporting the longest delay of 2.25 years, as mentioned in the review paper by Richards et al (10), showed a substantial difference between delays in the bulbar-onset group (1.25 years) compared to the spine-onset group (2.5 years) (18). Of note, for patients presenting with both bulbar and spine symptoms, the median time to diagnosis dropped to 0.25 years (10,18). Patients with spinal-onset presentation also receive more differential diagnoses than those with bulbar presentation (26) and are more likely to be misdiagnosed (27).…”

“…Clinical presentation plays a significant role in time to diagnosis, particularly with regards to bulbar versus spinal-onset presentation (8,13,15,16,18,19,21,22,(25)(26)(27)(28)(29)(30)(31), with the literature suggesting patients with bulbar-onset ALS experience a delay to diagnosis three to seven months shorter than those with spinal-onset ALS (21,(26)(27)(28). The study reporting the longest delay of 2.25 years, as mentioned in the review paper by Richards et al (10), showed a substantial difference between delays in the bulbar-onset group (1.25 years) compared to the spine-onset group (2.5 years) (18). Of note, for patients presenting with both bulbar and spine symptoms, the median time to diagnosis dropped to 0.25 years (10,18).…”

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

“…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.…”

Differential expression of circRNA in amyotrophic lateral sclerosis and validation of identified circRNA biomarker

“…Current diagnosis is based on clinical examination (El-Escorial criteria) [3] and neurophysiological examination (Awaji criteria) [4], while recently the ALS diagnostic index was also described [5]. Despite all this, establishing the correct diagnosis can still take one year or more [6]. Therefore, reliable and easy-to-obtain biomarkers are in desperate need for earlier and more accurate diagnoses.…”