Central Nervous System (CNS) Manifestations in Chronic Granolomatous Disease (CGD): Single Pediatric Center Experience

CNS involvement in CGD reflects a complex aspect of the disorder. We retrospectively reviewed 70 pediatric CGD patients (<18 years) diagnosed between 1987 and 2024 in our institutional database. Eight male patients (11.4%)—seven with X-linked CGD (CYBB) and one with autosomal recessive CGD (NFC2)—presented with CNS manifestations, identified through ICD-10 codes (G00–G09) with a documented follow-up at our center. The median time from CGD diagnosis to CNS involvement was 3 years. Notably, in three patients, neurologic symptoms preceded CGD diagnosis by 1–5 years, and these patients had substantial residual oxidative burst activity on dihydrorhodamine testing. In contrast, those who developed CNS manifestations after CGD diagnosis were already under antimicrobial prophylaxis and/or treatment for systemic or concurrent infections. CNS presentations included status epilepticus (n = 3), lower limb spastic diplegia with paresthesia (n = 1), chronic progressive demyelinating disease (n = 2; siblings), and incidental asymptomatic neuroimaging findings (n = 2). MRI revealed intracranial abscess (n = 1), spinal/paravertebral lesions (n = 1), nodular inflammatory/infectious lesions (n = 4), and demyelinating processes (n = 2). Abnormal EEGs were observed in three patients. CSF microbiology analyses were uniformly negative. CNS biopsies (n = 5; 2 patients) identified Aspergillus fumigatus in one case. Additional fungal pathogens (Scedosporium apiospermum and Aspergillus fumigatus) were isolated from non-CNS tissues (n = 2) and unknown etiology remained in two others. Antifungal therapy was administered in four patients, with voriconazole resistance reported in two; long-term posaconazole was the preferred alternative. Corticosteroids and granulocyte transfusions were used selectively. Clinical outcomes ranged from full recovery to persistent neurological deficits; no deaths related to CNS complications were observed. CNS involvement in CGD, while uncommon, was linked to active systemic infections in 62.5% of cases—mostly fungal—and likely driven by a hyperinflammatory process in the remaining 37.5% (patients with residual oxidative burst activity). Early diagnosis and personalized multidisciplinary management are critical. Limitations Data affected by underreporting and transition to digital records after 2014.