Use FDA approved disease modifying therapies exist for ALS, common ALS mimics and their distinguishing clues, and clinical red flags suggest an ALS mimic rather than ALS to frame the working diagnosis and next step; let it drive treatment choice rather than habit. Make common ALS mimics and their distinguishing clues the checkpoint that determines whether you escalate testing, narrow the differential, or change treatment.

Riluzole, edaravone, and tofersen are the current disease-modifying options; Symptomatic multidisciplinary care remains essential even when disease-modifying therapy is used; Common ALS mimics include multifocal motor neuropathy, Kennedy disease, CIDP, neuralgic amyotrophy, and inclusion body myositis; Early onset, sensory/autonomic features, or long clinical plateaus argue more for a mimic than ALS; Bulbar and thoracic EMG sampling is important when motor neuron disease is suspected