Diagnosing amyotrophic lateral sclerosis (ALS) can be difficult, particularly in the early stage of disease; therefore, we evaluated the use of transcranial stem sonography (TCS) to improve early detection of the disease. In this cross-sectional study, 94 patients with sporadic ALS and 46 age- and gender-matched healthy controls were evaluated by TCS according to a standardized protocol used to diagnose Parkinson's disease. Approximately half (48%) of the patients with ALS showed a clear (> 0.25 cm(2)) mesencephalic hyperechogenic structure, 20% showed a possible (< 0.25 cm(2)) hyperechogenic structure and 24% patients showed no hyperechogenic structure in the brainstem. TCS findings were not correlated with gender, disease onset (spinal, bulbar), disease duration, ALSFRS-R scores, motor-evoked potentials and signal hyperintensities in conventional MRI. In 70% of the ALS patients these hyperechogenicities were found at the anatomical site of the substantia nigra. In terms of location and structure, hyperechogenicities in 30% of ALS patients were more heterogeneous than those in Parkinson's disease with pronounced extensions both rostrally and laterally. In conclusion, although the neuropathological correlation to hyperechogenicity remains unclear, TCS is an easy, feasible and reproducible technique that could serve as an additional diagnostic tool and as a surrogate biomarker in ALS.