Midbrain morphology reflects extent of brain damage in Krabbe disease

To study the relationships between midbrain morphology, Loes score, gross motor function, and cognitive function in infantile Krabbe disease. Magnetic resonance imaging (MRI) scans were evaluated by two neuroradiologists blinded to clinical status and neurodevelopmental function of children with early or late infantile Krabbe disease. A simplified qualitative 3-point scoring system based on midbrain morphology on midsagittal MRI was used. A score of 0 represented normal convex morphology of the midbrain, a score of 1 represented flattening of the midbrain, and a score of 3 represented concave morphology of the midbrain (hummingbird sign). Spearman correlations were estimated between this simplified MRI scoring system and the Loes score, gross motor score, and cognitive score. Forty-two MRIs of 27 subjects were reviewed. Analysis of the 42 scans showed normal midbrain morphology in 3 (7.1 %) scans, midbrain flattening in 11 (26.2 %) scans, and concave midbrain morphology (hummingbird sign) in 28 (66.7 %) scans. Midbrain morphology scores were positively correlated with the Loes score (r = 0.81, p < 0.001) and negatively correlated with both gross motor and cognitive scores (r = -.84, p < 0.001; r = -0.87, p < 0.001, respectively). The inter-rater reliability for the midbrain morphology scale was κ =.95 (95 % CI: 0.86-1.0), and the inter-rater reliability for the Loes scale was κ =.58 (95 % CI: 0.42-0.73). Midbrain morphology scores of midsagittal MRI images correlates with cognition and gross motor function in children with Krabbe disease. This MRI scoring system represents a simple but reliable method to assess disease progression in patients with infantile Krabbe disease. (orig.)