Central Nervous System Complications in Children Receiving Chemotherapy or Hematopoietic Stem Cell Transplantation

Abstract

Therapy-related neurotoxicity greatly affects possibility of survival and quality of life of pediatric patients treated for cancer. Central nervous system (CNS) involvement is heterogeneous, varying from very mild and transient symptoms to extremely severe and debilitating, or even lethal syndromes. In this review, we will discuss the broad scenario of CNS complications and toxicities occurring during the treatment of pediatric patients receiving both chemotherapies and hematopoietic stem cell transplantation. Different types of complications are reviewed ranging from therapy related to cerebrovascular with a specific focus on neuroradiologic and clinical features.

Keywords: aspergillosis; central nervous system toxicity; chemotherapy; methotrexate; neuroradiologic; neurotoxicity; posterior reversible encephalopathy syndrome; thrombosis.

Figure 1

Posterior reversible encephalopathy syndrome in a 5-year-old boy affected by neuroblastoma in treatment with vincristine, etoposide, and carboplatine. (A,B) Axial T2 and FLAIR T2 images, respectively, display iuxtacortical hyperintensities that involve, bilaterally, frontal and parietal parasagittal watershed regions. (C) Diffusion study confirms they represent vasogenic edema. (D,E) Axial T2* and axial T1 post-gadolinium sequences, respectively, reveal microbleeds and faint signs of blood–barrier disruption within the cortex of affected regions. (F) Axial FLAIR T2 image acquired 1 month later shows complete resolution of the vasogenic edema.

Figure 2

Methotrexate-induced leukoencephalopathy in a 13-year-old girl with acute lymphoblastic leukemia. (A,B) Axial FLAIR T2 and coronal T2-weighted images, respectively, reveal focal areas of hyperintensities within the deep cerebral white matter. (C) Diffusion study shows no cytotoxic edema.

Figure 3

Brain aspergillosis in a 15-year-old girl with acute lymphoblastic leukemia. (A,B,D,E) Axial T2 and coronal post-gadolinium T1-weighted images, respectively, showed ring-enhancing lesions with mass effect, surrounded by abundant edema, on the right side, within the frontal lobe and cerebellar hemisphere. (C,F) Diffusion study reveals marginal hyperintensities representing peculiar intracavitary fungal hyphae projections.

Figure 4

Multiple brain hemorrhage in a 12-year-old girl affected by acute myeloid leukemia. Axial computed tomography images show multiple hemorrhagic foci involving mainly the subcortical areas of the cerebral hemispheres, more evident in the left temporo-parieto-occipital region.

Figure 5

Venous sinus thrombosis in a 4-year-old boy with acute lymphoblastic leukemia treated with l-asparaginase. (A–C) Sagittal T1, axial FLAIR T2-weighted, and coronal angio-MR images display thrombosis of the distal portion of the superior sagittal and left transverse sinuses. (D–F) Sagittal T1, axial FLAIR T2-weighted, and coronal angio-MR images acquired 3 weeks later reveal resolution of the thrombosis with almost complete restoration of flow signal within the previously thrombosed sinuses.