Trajectory Time-to-Intervention Playground

About

Amyotrophic Lateral Sclerosis (ALS)

Background on the disease and on how this application can be used.

Application

This application lets you simulate different scenarios based on the paper titled "Joint Machine Learning Model for Longitudinal Functional Decline and Time-to-Intervention Prediction: An Application to Amyotrophic Lateral Sclerosis". It is based on the revised ALS Functional Rating Scale (ALSFRS-R), which you can calculate with the ALSFRS-R calculator.

More information on the scale: Why ALSFRS-R matters. A full background on ALS follows below.

Background

Amyotrophic lateral sclerosis (ALS) was first described by Jean-Martin Charcot in 1869 as a pure motor neuron disease, but is now recognised as a multisystem neurodegenerative disorder, which over time results in progressive muscle weakness and ultimately death[1].

Frequency

ALS is a rare disease, occurring at a frequency of about 5.2 per 100,000 in Western countries, although it is more common in certain Western Pacific populations[2].

Diagnosis

ALS is a clinical diagnosis, although various criteria have been established, including the El Escorial criteria and Awaji criteria. The mean time from symptom onset to confirmation of the diagnosis of ALS is 10–18 months[3].

Classification

Different phenotypes of ALS exist, which can be grouped based on relative involvement of the upper motor versus lower motor neurons, and the regional distribution of involvement[1].

Morbidity and mortality

Due to neuronal degeneration resulting in muscle weakness, patients experience multiple morbidities including dysphagia and respiratory muscle weakness.

Dysphagia can cause increased risk of aspiration and malnutrition. To provide enteral nutrition, patients can undergo nasogastric or percutaneous enteral gastrostomy tube insertion. Decline in respiratory function may be managed with non-invasive and invasive mechanical ventilation.

The prognosis varies between patients, with a median survival of 3 years after disease onset, with major causes of mortality being respiratory failure[1], pulmonary infections, and nutritional disorders.

Clinical predictors

Several features present at disease onset are associated with a shorter survival[1]. These include:

  • fast functional decline (e.g. revised ALS Functional Rating Scale (ALSFRS-R) decline)
  • pronounced loss of weight (or body mass index)
  • bulbar onset
  • short diagnostic delay
  • presence of fronto-temporal dementia
  • older age at the onset of symptoms
  • low forced vital capacity

References

  1. Masrori, P. and Van Damme, P. Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol (2020). PubMed. Retrieved on February 21, 2024.
  2. Wijesekera, L.C., Nigel Leigh, P. Amyotrophic lateral sclerosis. Orphanet J Rare Dis (2009). PubMed. Retrieved on February 21, 2024.
  3. Andersen, P.M. et al. EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis (MALS) – revised report of an EFNS task force. European Journal of Neurology (2012). PubMed. Retrieved on February 21, 2024.