Diagnostic Testing for Suspected Amyotrophic Lateral Sclerosis (ALS)

Primary Diagnostic Tests

Electromyography (EMG) and nerve conduction velocity (NCV) studies are the cornerstone tests for diagnosing ALS, as they can detect lower motor neuron degeneration and help distinguish ALS from other conditions 1, 2
MRI of the brain without IV contrast is usually appropriate for initial imaging to exclude other conditions with similar clinical presentations 1, 2, 3
MRI of the spine without IV contrast may be appropriate in certain cases to exclude structural, infectious, or neoplastic etiologies that can mimic motor neuron disease 3, 4

Complete blood count (CBC) to evaluate for infectious or inflammatory conditions 5
Blood chemistry profile including glucose, electrolytes, kidney function, and liver enzymes to exclude metabolic causes 5
Thyroid function tests to rule out thyroid disorders that can cause weakness 6
Vitamin B12, folate, and vitamin E levels to exclude deficiencies that can cause neurological symptoms 6
Serum protein electrophoresis to rule out paraproteinemic neuropathies 5
Anti-ganglioside antibodies (GM1, GD1a, GD1b) to exclude immune-mediated motor neuropathies 5
Paraneoplastic antibody panel to exclude paraneoplastic syndromes 6
Anti-acetylcholine receptor and anti-MuSK antibodies to rule out myasthenia gravis 5

CSF analysis including cell count, protein, glucose, IgG index, oligoclonal bands, and cytology to exclude infectious, inflammatory, or neoplastic causes 5, 6
CSF protein may be normal or mildly elevated in ALS, but marked pleocytosis (>50 cells/μl) suggests alternative diagnoses 5

Genetic testing for ALS-associated genes (e.g., C9orf72, SOD1, FUS, TARDBP) should be considered, especially in cases with family history 7

The most common MRI brain findings include abnormal T2/FLAIR signal in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 3, 4
T2*-weighted or susceptibility-weighted imaging may show abnormal hypointensity in the precentral gyrus and gray matter, which can be highly sensitive and specific for ALS 4
Spine MRI may show abnormal T2/STIR signal in the anterior horns ("snake eyes" appearance), though this finding is not specific for ALS and may only appear later in the disease course 1, 3