Early Referral to an ALS Center Reduces Several Months the Diagnostic Delay: A Multicenter-Based Study

Abstract

Objective: To analyze those factors contributing to the diagnostic delay in ALS.Methods: Consecutive ALS patients were categorized as those studied in departmental hospitals and those studied in a referral ALS center. Demographic and clinical variables, together with data of the diagnostic pathway were collected. Multivariable models were used to assess their effect in the time between symptoms onset and the first neurologist visit (time symptoms-neurologist), in the time between the first neurologist visit and the diagnosis (time neurologist-diagnosis) and in the diagnostic delay.Results: 166 ALS patients with a median diagnostic delay of 11.53 months (IQR: 6.68, 15.23) were included. The median diagnostic delay was 8.57 months (5.16, 11.61) in the referral center vs. 12.08 months (6.87, 16.8) in departmental centers. Bulbar onset, fast progression rate, upper motor neuron predominant phenotype and an early referral to the neurologist were associated with a shorter time between symptoms–neurologist. Being studied in a referral center was associated with a shorter time between neurologist–diagnosis. Comorbidities, familial ALS, bulbar onset, early referral to the neurologist and being studied in a referral center were associated with a shorter diagnostic delay. For patients studied in departmental hospitals, fast progression rate was also strongly associated with a shorter time between neurologist–diagnosis and diagnostic delay.Conclusion: Unmodifiable factors (comorbidities, familial ALS, bulbar onset, and progression rate) as well as modifiable factors (early referral to the neurologist and the evaluation in an ALS referral center) have an independent effect in the diagnostic delay. The universalization of ALS Units is probably the most efficient measure to reduce the diagnostic delay.

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

“…In one Italian multicenter study, older patients were noted to have a shorter diagnostic delay, which authors argued was likely due to more rapid disease progression as they are also more likely to present with a bulbar phenotype than younger populations (34), as similarly noted by Yates et al (12). Interestingly, a study by Martinez-Molina et al found no association with age and length of delay (16).…”

“…In contrast, male spine-onset patients experienced a delay of 13.7 months versus 14.8 months for female spine-onset ALS patients. Martinez-Molina et al again found no significant association with gender and length of delay (16).…”

“…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).…”

“…Another factor affecting time to diagnosis is the presence of other neurological comorbidities, particularly those diseases with symptoms similar to those of ALS (16,18,23), or an overall complex medical history (39). In one study, the presence of comorbidities was associated with nearly twice the length of delay compared to patients without comorbidities, at 19.7 months and 11.1 months respectively (38).…”

“…Importantly, diagnosis and care of patients with ALS in such tertiary centers has been shown to decrease the frequency of hospital admissions, improve quality of life, and increase survival outcomes (47,48). A more recent study in 2020 found that patients referred to ALS centers also experienced a significantly shorter diagnostic delay of 8.5 months compared to 12 months for those assessed at other facilities (16).…”