Upper motor neuron assessment and early diagnosis in ALS

Considerable neurologic injury has already occurred by the time the first symptom appears in amyotrophic lateral sclerosis (ALS) and, although it is one of the most rapidly progressive of the neurodegenerative diseases, the average time from symptom onset to diagnosis is approximately 9 to 12 months.1,2 Unfortunately, every month of diagnostic delay equates to worsening motor neuron damage and diminished chances that experimental therapies might be effective. The diagnosis of ALS remains a clinical one, supported by electrodiagnostic and other testing, and ALS diagnostic criteria require evidence of both upper motor neuron (UMN) and lower motor neuron (LMN) signs. Because LMN signs are often easier to detect, and UMN signs may not appear until later in the disease course, early diagnosis is challenging, and may be made more so by the fact that progressive LMN weakness can be caused by so many other pure motor disorders (e.g., motor radiculopathy, multifocal motor neuropathy, myasthenia gravis, and the inflammatory myopathies).