Neuroimaging findings in children with retinopathy-confirmed cerebral malaria

Abstract

Purpose: To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria.

Materials and methods: In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT. All children had ophthalmological examination to confirm the presence of the retinopathy specific for cerebral malaria. Independent interpretation of CT images was provided by two neuroradiologists.

Results: Acute brain CT findings in three children included diffuse oedema with obstructive hydrocephalus (2), acute cerebral infarctions in multiple large vessel distributions with secondary oedema and herniation (1), and oedema of thalamic grey matter (1). One child who was reportedly normal prior to admission had parenchymal atrophy suggestive of pre-existing CNS injury. Among 56 survivors (9-84 months old), 15 had adverse neurologic outcomes-11/15 had a follow-up head CT, 3/15 died and 1/15 refused CT. Follow-up head CTs obtained 7-18 months after the acute infection revealed focal and multifocal lobar atrophy correlating to regions affected by focal seizures during the acute infection (5/11). Other findings were communicating hydrocephalus (2/11), vermian atrophy (1/11) and normal studies (3/11).

Conclusions: The identification of pre-existing imaging abnormalities in acute cerebral malaria suggests that population-based studies are required to establish the rate and nature of incidental imaging abnormalities in Malawi. Children with focal seizures during acute cerebral malaria developed focal cortical atrophy in these regions at follow-up. Longitudinal studies are needed to further elucidate mechanisms of CNS injury and death in this common fatal disease.

Figure 1

Fundus of child with cerebral malaria. Note the macular whitening. Hemorrhages with whitening in the center are also evident.

Figure 2

Fundus of a child with cerebral malaria. Papilledema with patches of peripheral retinal whitening.

Figure 3

Fundus of a child with cerebral malaria. Peripheral retinal whitening and white retinal vessels evident. White vessel have sequestered, parasitized red blood cells. The hemoglobin has been consumed by the p. falciparum.

Figure 4. Case 3 - Five days status post coma onset in this patient with severe retinopathy confirmed cerebral malaria

a and b: Diffuse prominence of the supratentorial subarachnoid spaces consistent with diffuse cerebral atrophy sparing the posterior fossa suggests this brain abnormality preceded the acute cerebral malaria infection. The presence of ventriculomegaly, including the 4^th ventricle, out of proportion to sulcal prominence suggests hydrocephalus. The lack of mass effect or transependymal reabsorption of cerebral spinal fluid could be compatible with long standing hydrocephalus, although central atrophy greater then cortical atrophy could also be considered. Both would represent a preexisting condition. Note that this patient was reportedly developmentally normal prior to admission. This underscores the challenge presented by the unknown incidence of imaging abnormalities in this pediatric population potentially exposed to multiple infections and environmental factors prior to their acute episode of cerebral malaria.

Figure 4. Case 3 - Five days status post coma onset in this patient with severe retinopathy confirmed cerebral malaria

a and b: Diffuse prominence of the supratentorial subarachnoid spaces consistent with diffuse cerebral atrophy sparing the posterior fossa suggests this brain abnormality preceded the acute cerebral malaria infection. The presence of ventriculomegaly, including the 4^th ventricle, out of proportion to sulcal prominence suggests hydrocephalus. The lack of mass effect or transependymal reabsorption of cerebral spinal fluid could be compatible with long standing hydrocephalus, although central atrophy greater then cortical atrophy could also be considered. Both would represent a preexisting condition. Note that this patient was reportedly developmentally normal prior to admission. This underscores the challenge presented by the unknown incidence of imaging abnormalities in this pediatric population potentially exposed to multiple infections and environmental factors prior to their acute episode of cerebral malaria.

Figure 5. Case 5 - Followup scan seven months after acute retinopathy confirmed cerebral malaria

a. and b: Diffuse prominence of the supratentorial cisterns and sulci with ventriculomegaly. There were no clinical signs to suggest obstructive hydrocephalus, making supratentorial atrophy and hydrocephalus ex vacuo the favored interpretation. This is the most common imaging finding on follow-up imaging in pediatric patients who survived retinopathy confirmed cerebral malaria.

Figure 5. Case 5 - Followup scan seven months after acute retinopathy confirmed cerebral malaria

a. and b: Diffuse prominence of the supratentorial cisterns and sulci with ventriculomegaly. There were no clinical signs to suggest obstructive hydrocephalus, making supratentorial atrophy and hydrocephalus ex vacuo the favored interpretation. This is the most common imaging finding on follow-up imaging in pediatric patients who survived retinopathy confirmed cerebral malaria.

Figure 6. Case 2 - Acute imaging of retinopathy confirmed cerebral malaria

Acute images were restricted to patients in prolonged coma and therefore likely reflect findings in the most severe cerebral malaria infections. Acute hydrocephalus with mass effect and cerebral edema were common findings in patients with prolonged coma from acute retinopathy confirmed cerebral malaria.

Figure 7. Case 1 - Imaging at two separate time points was available in one pediatric patient with retinopathy confirmed cerebral malaria and prolonged coma

a. The initial scan three days after the onset of coma showed subacute cortical infarcts most notable in the left frontal region (gray arrow) with a small hemorrhagic component near the left frontal horn (white arrow). b. The second scan eleven days later demonstrated worsening hydrocephalus. Note the prominent temporal tips and 4^th ventricular enlargement consistent with a communicating form. c. Also evident is evolution of the left frontal infarct (gray arrow) and interval development of additional infarcts including the right frontal lobe (white arrow). Evolution of the previously indentified acute hemorrhage in the left frontal lobe is also evident. No additional acute hemorrhages are noted.

Figure 7. Case 1 - Imaging at two separate time points was available in one pediatric patient with retinopathy confirmed cerebral malaria and prolonged coma

a. The initial scan three days after the onset of coma showed subacute cortical infarcts most notable in the left frontal region (gray arrow) with a small hemorrhagic component near the left frontal horn (white arrow). b. The second scan eleven days later demonstrated worsening hydrocephalus. Note the prominent temporal tips and 4^th ventricular enlargement consistent with a communicating form. c. Also evident is evolution of the left frontal infarct (gray arrow) and interval development of additional infarcts including the right frontal lobe (white arrow). Evolution of the previously indentified acute hemorrhage in the left frontal lobe is also evident. No additional acute hemorrhages are noted.

Figure 7. Case 1 - Imaging at two separate time points was available in one pediatric patient with retinopathy confirmed cerebral malaria and prolonged coma

a. The initial scan three days after the onset of coma showed subacute cortical infarcts most notable in the left frontal region (gray arrow) with a small hemorrhagic component near the left frontal horn (white arrow). b. The second scan eleven days later demonstrated worsening hydrocephalus. Note the prominent temporal tips and 4^th ventricular enlargement consistent with a communicating form. c. Also evident is evolution of the left frontal infarct (gray arrow) and interval development of additional infarcts including the right frontal lobe (white arrow). Evolution of the previously indentified acute hemorrhage in the left frontal lobe is also evident. No additional acute hemorrhages are noted.