Classification of amyotrophic lateral sclerosis cases at presentation in epidemiological studies

Amyotrophic lateral sclerosis (ALS) diagnosis is based exclusively on clinical grounds because of the absence of biological markers and of specific neuroradiological and neurophysiological diagnostic features. A clinical classification system of cases has been introduced (El Escorial Criteria, EEC) and then revised after the inclusion of the neurophysiologic assessment (Airlie House Criteria, AHC) for enrollment of patients in clinical trials. The aim of this study is to present cases at presentation in the early stages of the disease that have difficult allocation both in EEC and AHC. All cases were subjects enrolled through SLAP, a population-based registry based in Puglia, Southern Italy. Although differential diagnosis excluded ALS-mimic syndromes, we identified four cases (out of 130 cases, 3.1%) that did not meet the EEC and AHC at the first visit. Even though the number of unclassifiable cases is small, both EEC and AHC may be restrictive. This precludes the enrollment of ALS cases at an early stage both in observational studies and clinical trials.