ObjectiveThe aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI).MethodsA prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment. Patients were randomly assigned to a training (75%) and a test (25%) cohort. The ALSDI was developed in the training cohort and its diagnostic utility was subsequently assessed in the test cohort.ResultsA total of 407 patients were recruited, with 305 patients subsequently diagnosed with ALS and 102 with a non-ALS mimicking disorder. The ALSDI reliably differentiated ALS from neuromuscular disorders in the training cohort (area under the curve 0.92, 95% confidence interval 0.89–0.95), with ALSDI ≥4 exhibiting 81.6% sensitivity, 89.6% specificity, and 83.5% diagnostic accuracy. The ALSDI diagnostic utility was confirmed in the test cohort (area under the curve 0.90, 95% confidence interval 0.84–0.97), with ALSDI ≥4 exhibiting 83.3% sensitivity, 84% specificity, and 83.5% diagnostic accuracy. In addition, the diagnostic utility of the ALSDI was confirmed in patients who were Awaji negative at recruitment and in those exhibiting a predominantly lower motor neuron phenotype.ConclusionThe ALSDI reliably differentiates ALS from mimicking disorders at an early stage in the disease process.Classification of evidenceThis study provides Class I evidence that for patients with suspected ALS, the ALSDI distinguished ALS from neuromuscular mimicking disorders.
Cortical hyperexcitability may precede the onset of familial amyotrophic lateral sclerosis