One nerve suffices: A clinically guided nerve ultrasound protocol for the differentiation of multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS)

OBJECTIVE: To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient’s clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN). METHODS: Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development): Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation): Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II. RESULTS: 48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12) (mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p < .001; two-sided t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%). CONCLUSIONS: Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-020-10323-6.