Triage of Amyotrophic Lateral Sclerosis Patients during the COVID-19 Pandemic: An Application of the D50 Model

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, the management of which requires the continuous provision of multidisciplinary therapies. Owing to the novel coronavirus disease (COVID-19) pandemic, regular contact with ALS patients at our center was severely restricted and patient care was at risk by delay of supportive therapies. We established a triage system based on the D50 disease progression model and were thus able to identify a prospective cohort with high disease aggressiveness (D50 < 30). Thirty-seven patients with highly aggressive disease were actively offered follow-up, either via telephone or on-site, depending on their disease-specific needs and abilities. We describe here the procedures, obstacles, and results of these prescient efforts during the restrictions caused by COVID-19 in the period between March and June 2020. In conclusion, four patients with highly aggressive disease were initiated with non-invasive ventilation and two received a gastrostomy. We could show that a comparable amount of advanced care was induced in a retrospective cohort within a similar time period one year prior to the COVID-19 outbreak. Our workflow to identify high-risk patients via D50 model metrics can be easily implemented and integrated within existing centers. It helped to maintain a high quality of advanced care planning for our ALS patients.

Keywords: COVID-19; D50; SARS-CoV-2; amyotrophic lateral sclerosis; assisted ventilation; disease progression; gastrostomy; triage.

Figure 1

Consort diagrams for A) the prospective and B) the retrospective cohort under active follow-up. Patients were identified based on milestone-related entries in the neuromuscular database. Patients were then stratified based on their individual D50 values as either having high disease aggressiveness (D50 < 30 moths) or low aggressiveness (D50 ≥ 30 months). In the bottom-last row the numbers of events that occurred before the cut-off day (1^st March) are given for prior death, gastrostomy or initiation of assisted ventilation. Abbreviations: ALS = Amyotrophic Lateral Sclerosis; ALSFRS-R = ALS Functional Rating Scale (Revised); D50 = estimated time in months for an individual to lose 50% of functionality.

Figure 2

D50 disease progression model. (A) Patient with high (depicted in red, D50 = 22.8 months) and another with lower disease aggressiveness (depicted in yellow, D50 = 63.3 months). The individual disease curve is modelled based on all available ALSFRS-R scores (squares). The vertical lines mark the acute position in the disease course at March 2020. (B) Normalization with rD50, which describes individual disease course covered in reference to D50, allows for comparability between patients who all proceed through similar Phases (I-IV) of functional decline, despite vastly differing disease aggressiveness. (C) D50 and dx (time constant of ALSFRS-R total score decline) correlate linearly in all 651 patients who were available in the database and the prospective cohort respectively. (D) Modelling data for the prospective cohort (left column) and for all ALS patient data available at our neuromuscular center. From top to bottom, the number of obtained ALSFRS-R scores per patient, the minimum ALSFRS-R score (red), the maximum ALSFRS-R score (blue), and the calculated D50 (red) and dx (blue) values, and the offset between model data and scores do not differ between the cohorts.

Figure 3

Type of follow-up in the period between 1^st March and 31^st May 2020 for the 38 patients with highly aggressive ALS.

Figure 4

Results of the active follow-up for the prospective cohort from March until June 2020, concerning (A) the status of assisted ventilation or (B) the status of gastrostomy. For comparison purposes, the same situation is illustrated for the retrospective cohort, regarding the status of (C) ventilation and (D) gastrostomy.

Figure 5

Retrospective stratification of patients via D50 for the cumulative probability of the initiation of therapies after symptom onset. Patients were divided in subgroups of high disease aggressiveness (D50 < 30 months, slim graphs) and low disease aggressiveness (D50 ≥ 30 months, bold graphs). The time is calculated from symptom onset until (A) initiation of assisted ventilation (invasive or non-invasive), (B) implantation of a feeding-tube. Notably, both events occurred significantly earlier in the group with a lower D50 (Log Rank p < 0.001).