To determine the diagnostic value of clinical features at onset that differentiate amyotrophic lateral sclerosis (ALS) from benign brachial monomelic amyotrophy (BMA).

BMA, also known as Sobue disease, is a rare syndrome characterised by isolated lower motor neurone weakness of the upper-limbs, which can mimic ALS at onset. In contrast to ALS, following a period of slow progression, the symptoms of BMA arrest. Differential diagnosis can be challenging at first presentation.

Detailed phenotyping of baseline clinical and electrophysiological findings was retrospectively performed in patients with isolated upper-limb onset weakness, presenting to a tertiary neuroscience centre over 15 years. Diagnosis after >5 years of follow-up was recorded.

Compared to the ALS group (n=45), patients with BMA (n=13) were significantly younger (median 39 years (20-50) vs 64 years (53-70), p<0.0001) and had a longer duration of symptoms (median 18 months (10-47) vs 53 months (28-100), p=0.013) at presentation. Clinically, BMA patients more frequently presented with unilateral onset (p=0.016), distal weakness (p=0.024), fewer clinical fasciculations (p<0.0001), sensory abnormalities (p=0.038), and less frequent electrophysiological denervation outside the cervical region (p=0.0002), compared to ALS patients.

Clinical and electrophysiological differences at presentation can help differentiate between upper-limb onset ALS and BMA.