Pathogenesis and presentation of ALS: examining reasons for delayed diagnosis and identifying opportunities for improvement

Abstract

Amyotrophic lateral sclerosis (ALS), or Lou Gehrig disease, is a progressive, always-fatal neuromuscular disease characterized by motor neuron degeneration in the brain and spinal cord. As upper and lower motor neurons fail, inability to transmit messages to the muscles causes muscle stiffness, atrophy, and wasting. The incidence of this incurable disease is increasing in the United States, and its prognosis is grim. On average, patients survive about 3 to 5 years from symptom onset. Until recently, few risk factors were known, but some are newly emerging. About 10% of cases are related to genetic variants. Patients who develop ALS often experience diagnostic delays (10-16 months on average), and its heterogeneity contributes to that delay. Diagnosis is based primarily on clinical signs and symptoms and exclusion of other causes of motor neuron dysfunction. Reliable, accessible biomarkers are needed to aid early ALS diagnosis, differentiate from ALS-mimicking diseases, predict survival, and monitor disease progression and treatment response. Misdiagnosing ALS can have devastating consequences, including unnecessary emotional burden, delayed and/or inappropriate treatment, and undue financial burden. The grim prognosis and sure progression to death creates considerable burden and reduces quality of life for patients and caregivers.