Overdiagnosis and underdiagnosis of amyotrophic lateral sclerosis: a retrospective study

Abstract Background The diagnosis of amyotrophic lateral sclerosis (ALS) is sometimes challenging, and misdiagnosis is frequent. The aim of this study was to determine the frequency and pitfalls of overdiagnosis and underdiagnosis of ALS over a period of 1 year in Egypt. This is a retrospective study in Egyptian patients referred to specialized ALS clinics between July 2024 and June 2025 with either a diagnosis of ALS or another diagnosis that was revised to ALS. Patients were classified into 3 groups: overdiagnosis, underdiagnosis, and confirmed ALS. Results Twenty-six patients were included. The diagnosis of ALS was confirmed in 11/18 (61.1%) and changed from ALS to another diagnosis in 7/11 (38.9%; overdiagnosis). Of 19 patients diagnosed with ALS, 8 (42.1%) were referred with a different diagnosis (underdiagnosis); neuropathy was the most common initial diagnosis. Underdiagnosed patients presented at an early stage of the disease at the time of their initial diagnosis (median ALSFRS-R was 32 compared to 15 at presentation to the specialized ALS clinics ( p < 0.01). Compared to confirmed ALS patients, underdiagnosed patients had greater diagnostic delay ( p = 0.03) and more disability at the time of final diagnosis ( p < 0.01). Most underdiagnosed patients were treated initially with immunotherapies. Conclusion Over- and underdiagnosis of ALS was common and resulted in a significant diagnostic delay. Underdiagnosed patients had greater diagnostic delay and more disability at the time of final diagnosis compared to confirmed ALS patients. Additionally, underdiagnosed patients received unnecessary immunotherapies. Underdiagnosis occurred at earlier stages of the disease. Other factors contributing to misdiagnosis included poor adherence to diagnostic criteria of ALS and unfamiliarity of physicians with ALS hallmarks.