Invasive mold disease of the central nervous system in children and adolescents with cancer or undergoing hematopoietic stem cell transplantation: Analysis of 29 contemporary patients

Abstract

Background Invasive mold disease (IMD) is a severe infectious complication in immunocompromised patients. The outcome of central nervous system (CNS) IMD is poor, but contemporary data, in particular in the pediatric setting, are lacking. Procedure For this retrospective multicenter analysis, pediatric patients < 18 years with proven or probable CNS IMD receiving chemotherapy or undergoing allogeneic HSCT were reported by the local investigator. CNS IMD had to be diagnosed between 2007 and 2016. Proven CNS IMD was defined as compatible CNS imaging or macroscopic autopsy findings in conjunction with a positive microscopic or microbiological result in the brain tissue or cerebrospinal fluid. Probable CNS IMD was defined as compatible CNS imaging findings in combination with proven or probable IMD at a site outside the CNS. Results and conclusions A total of 29 patients (median age, 14 years; 14 allogeneic HSCT recipients) were diagnosed with proven (n = 12) or probable (n = 17) CNS IMD. Aspergillus spp. was the most common fungal pathogen. All but one patient had IMD sites outside the CNS and eight patients (27.6%) were neurologically asymptomatic at diagnosis of CNS IMD. Forty‐nine percent of the patients survived CNS IMD; however, 46.7% of the survivors suffered from severe long‐term neurological sequelae. Our data suggest that (1) outcome of CNS IMD has improved in children as compared with previous series, (2) half of surviving patients suffer from severe neurological sequelae, and (3) imaging of the CNS should be performed in all children with IMD irrespective of neurological symptoms.

Invasive Mold Infection of the Central Nervous System in Immunocompromised Children

“…For this retrospective study, children and adolescents diagnosed between 2007 and 2016 with CNS-IMD were identified by the recollection of local investigators. The detailed analyses of diagnostic procedures, therapy, clinical course, and outcome (e.g., death or severe neurological sequelae such as hemi-/quadriplegia, aphasia, amaurosis) have been reported previously [1,7]. For the present analysis, pediatric patients receiving chemotherapy for an underlying malignancy and patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) were included if they met the following criteria: (1) younger than 18 years at the time of diagnosis; (2) proven or probable CNS-IMD, as defined previously [1]; and (3) availability of (a) non-contrast T1-weighted images (T1-W), (b) T2-W, (c) fluid-attenuated inversion recovery sequences (FLAIR), (d) gradient-echo T2* and/or susceptibility weighted imaging (SWI), (e) diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, and (f) contrast-enhanced T1-W in at least two different planes and without severe motion artefacts.…”

“…These infections can originate from hematogenous dissemination from a distant primary focus, commonly the lung, or from local dissemination, usually from a sinus infection. Clinical symptoms are often uncharacteristic and may even be absent in a significant proportion of patients with invasive mold disease (IMD) of the CNS, which makes early diagnosis difficult [1]. On the other hand, early diagnosis and treatment of IMD of the CNS seems to be associated with better outcomes.…”

Galactomannan and PCR in the Central Nervous System to Detect Invasive Mold Disease - A Retrospective Analysis in Immunocompromised Children

“…For a retrospective study on children and adolescents suffering from CNS IMD, patients were identified by recollection of the local investigators. The clinical details and patients’ outcome have been reported elsewhere as part of a larger cohort 28 . In this analysis, children and adolescents <18 years were included if they (1) received chemotherapy for a malignant disease or underwent allogeneic hematopoietic stem cell transplantation (HSCT), (2) had been diagnosed with proven or probable CNS IMD between 2007 and 2016 and (3) GM and/or PCR was assessed in CNS samples.…”

Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment

“…Focal neurological symptoms (e.g., aphasia, diplopia) were seen in 48%, and seizures occurred in 18%. Interestingly, in a study on CNS IMD in 29 children, 21 (72%) presented with CNS related symptoms, whereas eight (28%) were neurologically asymptomatic and CNS IFD was detected by diagnostic work-up for pulmonary or liver fungal infection or during routine CNS imaging for assessing tumor response [22]. Common neurological symptoms were somnolence and cerebral palsy (each 24%), followed by headache (21%).…”

“…In a recent analysis on immunocompromised children suffering from mucormycosis, five out of eight patients (62.5%) with rhino-cerebral involvement died, but it has to be noted that the outcome of invasive aspergillosis is generally better than that of mucormycosis [10,11]. Another analysis of 29 immunocompromised children diagnosed with CNS IMD between 2007 and 2016 reported that the probability of 2-year survival was 48.9% [22]. Unfortunately, only four of 14 children undergoing HSCT were alive after 2 years, whereas this was the case in 11 out of 15 patients receiving chemotherapy.…”