Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS)

Abstract

The objective of this study was to characterize the diagnostic timelines and their predictors in people with amyotrophic lateral sclerosis (ALS). Patients were identified through ALS billing codes. Time from presenting symptom to first doctor visit, first doctor visit to suspected ALS diagnosis, suspected to confirmed ALS diagnosis, and presenting symptom to confirmed ALS diagnosis (total diagnostic time) were collected. Regression models were used to analyze the predictors of diagnostic delay. Three hundred and four ALS patients were included in the analysis. Median total diagnostic time was 11.5 months. Diagnostic timelines were longer in patients with age > 60 years (p < 0.001), sporadic ALS (p = 0.043), and limb onset (p = 0.010). The presence of fasciculations, slurred speech, and lower extremity weakness when symptoms were first noted were independent predictors of shorter time to ALS diagnosis (p = 0.04, p = 0.02, and p = 0.04, respectively). About half of the patients (52%) received an alternative diagnosis and each patient saw an average of three different physicians before ALS diagnosis was confirmed. In conclusion, diagnostic timelines in ALS are long, and patients see many physicians and receive multiple alternative diagnoses before the diagnosis of ALS is confirmed. Older age, sporadic disease, and limb onset can delay ALS diagnosis.

Clinical Trial Designs in Amyotrophic Lateral Sclerosis: Does One Design Fit All?

“…Since the trial of riluzole in people with advanced ALS failed to demonstrate efficacy [4], most ALS trials aim to enroll patients early in the disease. Yet this remains a challenge given the relatively long diagnostic delay in ALS [5]. Beyond this, ALS trials tend to enroll without regard to clinical subtype in order to encourage rapid enrollment and unnecessary enrollment limitations.…”

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

“…Next, although unrelated to stem cell therapies directly, the diagnostic delays of around 1 year typical of ALS also hinder therapeutic windows [124]. It is likely that the microenvironment is already compromised at the time symptoms develop and even more so when ALS is diagnosed; therefore, improving the time to diagnosis as a means to achieve earlier institution of therapy is essential in order to confer the best possible opportunity for MN rescue.…”

Neuroimaging as a New Diagnostic Modality in Amyotrophic Lateral Sclerosis

“…Such changes are associated with behavioral and cognitive deficits, which are mild in up to 32 % of cases and moderate to severe in up to 19 % of cases [10]. These cognitive and behavioral deficits are similar to those found in frontotemporal dementia (FTD), which forms a clinicopathological spectrum with ALS as up to 15 % of patients with ALS meet the criteria for FTD [9]. Such deficits are currently assessed using neuropsychological testing of patients and questionnaires for caregivers.…”

“…Ideally, patients would be imaged as part of the initial diagnostic work-up. To date, the large majority of imaging studies in ALS have studied patients with a relatively long disease duration-much longer than the average diagnostic delay of 10-12 months [9]. These patients likely have more advanced disease, which may lead to overestimation of effect sizes.…”

“…Current clinical practice uses neuroimaging to exclude conditions with similar clinical presentations to ALS, but not to either confirm or facilitate the diagnosis of ALS. An objective upper motor neuron imaging marker could shorten diagnostic delay, which is still considerable in ALS, and reduce the proportion of misdiagnosed cases [9].…”