What is the workup for anterior horn cell disease?

Workup for Anterior Horn Cell Disease

Begin with needle electromyography (EMG) and nerve conduction studies as the cornerstone of diagnosis, looking specifically for denervation patterns with fibrillation potentials, positive sharp waves, and fasciculations in multiple muscles across different nerve root distributions. 1, 2

Initial Electrodiagnostic Testing

• Perform needle EMG at initial evaluation to detect denervation as evidence of anterior horn cell involvement, which characteristically shows fibrillation potentials, positive sharp waves, fasciculations, and complex repetitive discharges 1, 3
• Conduct nerve conduction studies at baseline, which typically show normal or low compound muscle action potential (CMAP) amplitudes with relatively normal conduction velocities—this distinguishes anterior horn cell disease from peripheral neuropathy 1, 3
• Sensory nerve conduction studies should be normal (except in Kennedy's disease), helping differentiate from peripheral neuropathies that affect both motor and sensory fibers 3, 2
• Document abnormalities in multiple muscles with different nerve root and peripheral nerve innervation across multiple limbs to establish widespread motor neuron involvement 3

The EMG findings will show polyphasic motor units with large amplitude and duration motor unit action potentials when disease is slowly progressive, along with reduced recruitment and abnormally rapidly firing motor units 3.

Neuroimaging Studies

• Order MRI of the head without IV contrast as the optimal initial imaging modality for suspected motor neuron disease 2, 4
• Consider MRI of the spine without IV contrast to look for the characteristic "snake eyes" appearance—abnormal T2/STIR signal in the anterior horns corresponding to lateral corticospinal tract involvement 2, 4
• Brain MRI may reveal abnormal T2/FLAIR signal in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 2

This imaging is critical to exclude mimics such as cervical spondylotic myelopathy, which can present with similar symptoms but shows upper motor neuron signs and sensory involvement 2.

Baseline Functional Assessments

• Establish baseline motor and functional assessments with repeat testing at 3-6 month intervals for children under age five years, and annually in older children and adults 1, 4
• Document specific patterns of weakness, muscle wasting, and fasciculations across different muscle groups 3, 5
• Assess for bulbar dysfunction (speech, swallowing difficulties) as this affects prognosis and management 6, 5

Specialized Testing for Specific Etiologies

• Perform hearing tests including behavioral assessment, otoacoustic emissions, tympanometry, and auditory evoked potentials (ABR/BAER) using air and bone conducted stimuli, particularly when Pompe disease is suspected 1
• Consider genetic testing when familial patterns exist or specific syndromes are suspected (Kennedy's disease is X-linked recessive; two-thirds of familial ALS and 10% of sporadic ALS have genetic explanations) 2, 5
• Evaluate for infectious causes including HTLV-1 serology if clinical context suggests (particularly in endemic areas or with associated polymyositis) 7
• Consider paraneoplastic workup if there is history of malignancy, particularly non-Hodgkin lymphoma 8

Laboratory Exclusion of Mimics

• Rule out metabolic and infectious causes that can mimic anterior horn cell disease through appropriate laboratory testing 1, 5
• Maintain low threshold for aggressive infection workup, as patients with anterior horn cell disease are at very high risk for pneumonia and respiratory failure 1

Common Pitfalls to Avoid

The most critical error is failing to perform electrodiagnostic studies early—clinical examination alone cannot definitively establish anterior horn cell involvement 1, 3. Another pitfall is confusing anterior horn cell disorders with peripheral neuropathies; remember that sensory symptoms and length-dependent patterns suggest peripheral neuropathy, while pure motor involvement with preserved sensation points to anterior horn cell disease 2. Finally, do not overlook the need for imaging to exclude structural lesions like cervical spondylotic myelopathy that can mimic motor neuron disease 2.