The diagnostic value of midbrain hyperechogenicity in ALS is limited for discriminating key ALS differential diagnoses

Background: Hyperechogenicity of the substantia nigra was recently reported in patients with sporadic ALS with a frequency similar to PD. Data on the diagnostic utility compared to key differential diagnoses of ALS do not exist yet. Methods: We prospectively enrolled 43 patients with ALS, 29 with myasthenia gravis, 25 patients with inflammatory neuropathy, and 13 with cervical canal stenosis. All patients were examined by a blinded investigator using transcranial B-mode sonography planimetrically measuring hyperechogenic areas of the midbrain representing the substantia nigra. Results: Mean midbrain hyperechogenic area was increased in ALS compared to non-ALS differentials. ROC analysis revealed only small area under the curve for detecting ALS (AUC: 0.669 [95%CI: 0.56-0.78]; p = 0.006). Highest Youden index was observed for area size of <0.14 cm(2) (Youden index: 0.28). Using this cut-off score and that generated from normative data of healthy controls, area size measurements provided a sensitivity of only 46-58% and specificity of 69-83% for detecting ALS. No correlations of hyperechogenic area sizes in ALS patients were found to age, gender, ALS subtype (bulbar versus spinal form), disease duration or ALS-FRS-R score. Conclusions: Midbrain hyperechogenicity is reproducibly found in ALS patients, but its diagnostic value for discriminating ALS from its key differentials is limited.