Cerebral Malaria and Cytotoxic Lesions of the Corpus Callosum.

Abstract

To the Editors: Malaria is a common cause of morbidity and mortality worldwide. According to the WHO, 229 million cases and 409,000 deaths were reported worldwide in 2020.1 Children account for a high burden of malaria-related mortality and are at a higher risk of developing cerebral malaria (CM).1 A 12-year-old, previously healthy female from Guinea-Bissau was admitted 1 day after arriving in Portugal with a 2-day history of headache, generalized myalgia, and high-grade fever. Physical examination was unremarkable, except for pallor, icteric sclerae, and nontender hepatomegaly (4 cm). The patient was hemodynamically stable (BP, 101/52 mmHg; HR, 111 bpm), but shortly after admission, vomiting, lethargy, and impaired consciousness were observed (Glasgow coma score 11). She presented with anemia (hemoglobin, 10.0 g/dL; normal reference [NR]: 12.0–16.0), thrombocytopenia (78 × 109/L; NR: 150–450) and significant elevation of inflammatory markers (C-reactive protein, 301.0 mg/L; NR, <5; and procalcitonin, >100 ng/mL; NR, <0.1). No electrolyte disturbances, hypoglycemia, or acidosis. Plasmodium falciparum blood smear was positive, and severe malaria was diagnosed due to high parasitemia (28.5%/erythrocytes–11.872.000 parasites/µL) and central nervous system (CNS) involvement other infections were excluded. The cerebrospinal fluid revealed pleocytosis (15 cells), generalized slowing on the electroencephalogram, and a lesion in the splenium of the corpus callosum with T2 hypersignal and restricted diffusion (Fig. 1), compatible with a cytotoxic lesion of the corpus callosum (CLOCCs) on brain magnetic resonance imaging (MRI). CM was diagnosed based on severely impaired consciousness, CLOCCs, and no other identifiable causes of coma.FIGURE 1.: MRI axial images T2 weighted (A), DWI (B) and ADC map (C): oval lesion in the splenium of the corpus callosum (arrow) with T2 hypersignal and diffusion restriction with DWI hypersignal and ADC map hyposignal, corresponding to cytotoxic edema.The patient was treated with parenteral quinine and clindamycin, due to the immediate unavailability of artesunate, plus ceftriaxone. She became afebrile with progressive improvement in neurological status after 48 h and complete parasite clearance on day 3. Artemether-lumefantrine was initiated on day 5, and the patient was discharged on day 8. CM is defined as a disturbance of consciousness in a patient with Plasmodium parasitemia and no other identifiable cause.2 Despite the reported low mortality rate of pediatric imported malaria in Europe (<1%), CM entails a risk of life-threatening acute CNS effects with diffuse encephalopathy and often rapidly progressive coma, as observed in our patient.3 Distinctive brain MRI features involving both white and gray matter structures have been reported in a large cohort of Malawian children with CM. Increased volume, T2 hyperintensity, and Diffusion-weighted imaging (DWI) abnormalities affecting the cortical area (61.7%), subcortical and periventricular white matter (71.7%), basal ganglia (84.2%) and the corpus callosum (49.2%) were the most frequent features.4 CLOCCS was a common MRI finding in CM, as suggested by DWI/Apparent diffusion coefficient mismatch with DWI increased signal and Apparent diffusion coefficient low signal,4 as observed in our patient (Fig. 1). The corpus callosum, mostly the splenium, is a region vulnerable to inflammatory cytokinopathy, driven by malaria, seizures or other causes.5 The higher density of cytokines and glutamate receptors in this area leads to high extracellular glutamate levels, inducing cytotoxic edema upon infection, which is frequently reversible.5 CM in children is the most severe complication of P. falciparum infection and needs a high suspicion index in nonendemic countries. Altered MRI and CLOCCs, although unspecific, are associated with CM.