Viral infections

The herpes group of viruses is the most likely cause of neurologic complications, although routine prophylaxis has greatly reduced the incidence of encephalitis due to herpes simplex virus, varicella zoster virus (VZV), and cytomegalovirus (CMV). ^{, ,}

Human herpes virus 6 (HHV-6) encephalitis after allogenic HSCT is a serious complication occurring in up to 78% of patients, usually during either early or late posttransplant phases. It causes posttransplant acute limbic encephalitis (PALE). ^{, ,} PALE manifests with anterograde amnesia, changes in mental state, headache, fever, and drowsiness. MR imaging typically shows symmetric, bilateral T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in the limbic system particularly at the medial temporal lobe, hippocampus, and amygdala. ^{, , ,}

Toxoplasma infection

Parasitic CNS infections due to Toxoplasma gondii ^, are almost always fatal, with a frequency of 0.3% to 13%. ^, Clinical symptoms are nonspecific, usually presenting with fever, seizure, headache, or altered mental status. MR imaging shows multiple lesions in the basal ganglia, ^{, ,} posterior fossa, or at the gray-white matter junction. On T2-weighted images, lesions can be hyperintense due to necrotizing encephalitis or isointense from organizing abscess.

Imaging appearance of toxoplasmosis after HSCT is different from those in the human immunodeficiency virus (HIV)-infected population. Lesions are initially hemorrhagic following HSCT, whereas in HIV infection, hemorrhages are only seen after initiating antitoxoplasma therapy. Edema and contrast enhancement may also be absent unlike in HIV infection. The lesions may have peripheral diffusion restriction due to hemorrhage within the walls but not within the center as seen in pyogenic abscesses.

Bacterial infections

Gram-positive bacterial infections also frequently occur in this period. ^{, ,} Methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis as well as Listeria monocytogenes may cause severe meningitis and ventriculitis. ^,

Meningitis presents with hyperintense extra-axial spaces with leptomeningeal enhancement on the postcontrast FLAIR images. Contrast-enhanced FLAIR sequence is more sensitive and specific than contrast-enhanced T1. For pyogenic ventriculitis, the typical MR imaging findings are hydrocephalus, abnormal ependymal enhancement, and intraventricular debris with diffusion restriction, which is highly sensitive. ^,

Cerebrovascular complications

Cerebrovascular complications most often manifest in the preengraftment or in the early postengraftment period, occurring in 3.8% to 8.8% of patients following HSCT. ^,

The most common hemorrhagic complication during bone marrow depletion is a subdural hematoma. It is usually associated with underlying acute leukemia and persistent thrombocytopenia. ^{, , ,}

Intraparenchymal hemorrhages ( Fig. 3 ) are more common in allogenic HSCT particularly when accompanied by severe graft-versus-host disease (GVHD). This is probably related to microvascular endothelial injury or vasculitis. ^{, , ,}

An 11-year-old boy with acute myelogenous leukemia, post–bone marrow transplantation. Axial nonenhanced soft tissue window setting CT image shows a large right frontal lobe intraparenchymal hematoma ( asterisk ), with intraventricular ( arrow ) and subarachnoid ( arrowhead ) extension.

Infarctions may also occur in this phase and may be the result of using dimethylsulfoxide in autologous HSCT, fungal emboli, or with prolonged neutropenia. According to a retrospective study by Coplin and colleagues, nearly one-third of strokes were caused by Aspergillus fumigatus , Staphylococcus endocarditis (5.6%), and noninfectious endocarditis (2.8%). ^,

Subdural hematomas, infarctions, and intraparenchymal hemorrhages are common complications, and imaging characteristics are similar to those seen in the general population.

Posterior reversible encephalopathy syndrome

Posterior reversible encephalopathy syndrome (PRES), also known as posterior reversible leukoencephalopathy syndrome, is the most commonly reported neurologic complication after pediatric allogenic HSCT. The incidence is 1.1% to 20%. ^, It is most common during the early posttransplant period but can occur in any stage. ^, PRES is also a known complication of pretransplant steroids and calcineurin inhibitors such as tacrolimus and cyclosporine A, used as GVHD prophylaxis. ^{, , , , , ,} PRES manifests with rapid onset of seizures primarily, but hypertension, cortical blindness, headache, vomiting, and altered mental status may follow. ^{, ,} The pathophysiology remains unclear, but theories entail a breakdown of the blood-brain barrier leading to vasogenic edema (6.8).

CT is the first-line imaging modality, mainly used to exclude hemorrhages, ^{, ,} but MR imaging is the current imaging modality of choice. The characteristic imaging appearance consists of fairly symmetric ( Fig. 4 A), bilateral vasogenic edema without diffusion restriction ( Fig. 4 B) in the cortical-subcortical gray and white matter of the parietooccipital lobes in 50% to 99%. ^{, , ,} Atypical PRES may involve the frontal and temporal lobes, cortical watershed zones, basal ganglia, brainstem, and cerebellum. ^{, , , ,} Other findings may include contrast enhancement (20%); restricted diffusion (11%–26%); and hemorrhages (5%–19%) including petechial hemorrhage (<5 mm), subarachnoid hemorrhage, and intraparenchymal hematoma. ^,

An 11-year-old boy with acute lymphocytic leukemia who presented with tonic-clonic seizures 2 months after stem cell transplantation. ( A ) Axial unenhanced FLAIR MR image shows fairly symmetric, abnormal increased signal in both frontal ( arrowheads ) and parietal lobes ( arrows ) seen in patients with posterior reversible leukoencephalopathy syndrome. ( B ) Axial unenhanced diffusion-weighted MR image demonstrates no restricted diffusion. ( C ) Axial unenhanced FLAIR MR image reveals complete resolution after 4 months.

Most of the patients with PRES resolve completely with no detectable residual abnormalities ( Fig. 4 C), but residual gliosis may happen when infarcts or hemorrhages do occur. ^{, , , ,} Complete clinical recovery usually precedes neuroimaging resolution. ^,

Wernicke encephalopathy

Metabolic encephalopathies are also common but occur less frequently than other CNS complications. They usually occur in the preengraftment or early postengraftment period. ^, Prolonged fasting, hyperemesis, and prolonged total parenteral nutrition may result in Wernicke encephalopathy. ^{, ,} The most frequent manifestation is a change in mental status. MR imaging may reveal symmetric, hyperintense T2 and FLAIR signal in the mammillary bodies, medial thalami, around the aqueduct of Sylvius and in the tectal plate. Contrast enhancement is most common in the mammillary bodies. ^{, ,}