Central Nervous System Infections in Pediatric Solid Organ Transplant Recipients

Background

Solid organ transplant (SOT) recipients face a heightened risk of central nervous system (CNS) infections due to immunosuppression 1,2. The incidence of CNS infections in adult SOT recipients ranges from 0.8% to 10% 3,4, while it remains unknown in pediatric SOT recipients5. Diagnosing these infections is often delayed because of weakened immune responses and atypical symptoms 1,4,6. Mortality rates are high, ranging from 30% to 70%, with fungal infections having the worst outcomes 4,6. Data on CNS infections in SOT recipients, especially in pediatrics, are limited.

Methods

A retrospective case series of patients ≤ 21 years old who received a solid organ transplant between 2003-2023 at Texas Children’s Hospital was completed. Primary outcome was proven CNS infection, defined as pathogen isolation and the presence of signs and symptoms or clinical evidence of CNS infection (radiographic evidence and/or pleocytosis, elevated protein and/or decreased glucose on cerebrospinal fluid (CSF) analysis), as previously described 4.

Results

Among 1810 SOT recipients, 19 (1%) developed a proven CNS infection, including 7/447 (1.6%) heart, 5/625 (0.8%) liver, 4/237 (1.7%) lung, 2/458 (0.4%) kidney, and 1/42 (2.3%) multi-organ recipients. A primary CNS infection was present in 10/19 (53%), while a disseminated infection with CNS involvement was observed in 9/19(47%) SOT recipients. Presenting symptoms included fever in 9 (47%), altered mental status in 5 (26%), and nausea/vomiting in 5 (26%) patients. None presented with neck stiffness. Lumbar punctures were completed in 12/19 (63%); 10 had CSF pleocytosis (83%) and two patients had a positive CSF culture. Fungal and bacterial infections each accounted for 37% of cases, followed by viral infections at 26%. Neuroimaging was performed in 14/19 of which 9 (64%) had abnormal findings; 6 (67%) had a space occupying lesion and 3 (33%) had leptomeningeal enhancement. CNS infections occurred more commonly in the first year after transplant (11/19, 58%). 90-day mortality was 37% (7/19). Of the surviving SOT recipients with CNS infection, three (16%) required inpatient rehabilitation, one (5%) developed hearing loss, and one (5%) developed short-term memory loss secondary to their CNS infection.

Conclusions

CNS infections are an uncommon complication after SOT but are associated with high mortality and morbidity. They can have an atypical presentation; therefore, a high index of suspicion and a low threshold for evaluation is warranted.

References