Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria

Abstract

Objective: To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis.

Methods: We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation.

Results: Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA).

Conclusions: Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

Keywords:

• Amyotrophic lateral sclerosis
• ALS mimic syndromes
• early diagnosis
• phenotypes

Acknowledgements

We are indebted to the patients and caregivers for their generous collaboration in our study, as well as to the Neurological Tissue Bank of the IDIBAPS Biobank in Barcelona, Spain, for detailed neuropathological studies. The authors thank C. Newey for English language assistance.

Declaration of interest

The authors report no conflicts of interest.

Funding

This work was supported by the Fundació La Marató de TV3 under Grant 201437.10; and Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation under Grant PI15/01618.