Prevalence of Neuroradiological Brain Damage Patterns and Assessment of Cerebral Volumes in Children with Hypoplastic Left Heart Syndrome after Three-Staged Palliation

Objectives: The markedly improved survival of children with hypoplastic left heart syndrome (HLHS) after palliation has shifted the clinical focus toward improving outcomes. The aim of this prospective study was to assess neuroradiological features of brain injury after three-stage palliation and to identify neuroradiological risk markers in HLHS. Furthermore, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes were compared between HLHS patients and healthy controls.

Methods: Eighty-two HLHS patients (median age: 5.7; 2.4–14.6 years) underwent comprehensive brain and cardiac MRI examinations at 3 T. Neuropathological abnormalities were graded using a global score from 0 to 12 according to neuroradiological standards. Cerebral volumes were measured with a dedicated software tool (SPM8 toolbox). Cerebral volumes in HLHS patients were compared with 64 age-matched children without any neuropathological findings. Regression analysis was used to identify significant predictors for neuropathological abnormalities and low brain volumes.

Results: Out of 82, 63 patients (77%) showed cerebral lesions (periventricular leukomalacia: n = 52; infarct: n = 18; globally reduced brain volume: n = 29), resulting in predominantly mild-to-moderate global brain lesion scores (score: 0 = 23%, 1 = 32%, 2–3 = 27%, 4–7 = 18%, 8–12 = 0%). The cerebral volumes showed a significant reduction for all subcompartments compared with controls (GM 720.2 ± 72.5 vs. 748.5 ± 58.3 mL [p = 0.010]; WM 334.2 ± 52.6 vs. 399.6 ± 55.7 mL [p ≤ 0.001]; and CSF 173.2 ± 43.1 vs. 193.8 ± 58.3 [p = 0.027]). Patients with severe lesions (score >2) showed a significant larger CSF volume than patients with mild lesions. HLHS patients without any visible lesion (score 0) had reduced WM and CSF volumes (GM 729.6 ± 50.2 vs. 748.5 ± 58.3 mL [p = 0.21]; WM 341.8 ± 43.1 vs. 399.6 ± 55.71 mL [p ≤ 0.001]; and CSF 154.6 ± 29.9 vs. 193.8 ± 58.31 mL [p = 0.008]). Strong statistical predictors for severe lesions were duration of postoperative ventilation and the occurrence of seizures. Age at the time of Norwood operation, postoperative resuscitation time, microcephalus at birth, and female gender were independent predictors for low cerebral volumes.

Conclusion: Children with HLHS had reduced brain volumes (GM, WM, and CSF) and mostly mild cerebral lesions. The association of low brain volumes with later age at the time of Norwood-operation supports previous findings from neuropsychological studies and underlines the adverse role of a delayed operation.

No conflict of interest has been declared by the author(s).