A 3-year-old previously healthy Malawian boy presented with nausea, fatigue, and headache followed by fever, loss of consciousness, and recurrent brief generalized seizures for one day. He was brought to a local health center where his malaria rapid diagnostic test was positive. He received intramuscular artesunate and was transported to a local referral hospital.

On examination, he was pale, febrile (39°C), tachycardic (150 beats per minute [bpm]), and comatose (Blantyre Coma Score [BCS] 1), with generalized hypotonia and hyperreflexia. Pupils were 3 mm bilaterally and slowly reactive. His resting gaze was deconjugate. Fundoscopic exam revealed macular whitening, flame hemorrhages, and papilledema ( Fig. 41.1 ). His liver was palpable 2 cm below the right costal margin. Treatment with intravenous artesunate was continued. He was begun on intravenous ceftriaxone, and placed on maintenance fluids and supportive care.

Malarial retinopathy. (A) White-centered hemorrhages. (B) Vessel color changes in branching veins. (C) Perimacular whitening ( oval ).

(Reproduced with permission from Taylor et al.)

Thick and thin blood smears showed Plasmodium falciparum asexual parasites with a density of 60,500/mm ³ . White blood cell count was 13.5 × 10 ^-19 /liter, hematocrit 20%, and platelet count 49 ×10 ^-19 /liter. Both hyperlactatemia (9 mmol/liter) and hypoglycemia (2.1 mmol/liter) were present. Lumbar puncture opening pressure was 210 mm H ₂ O with clear CSF and white cell count of 2/high-power field (HPF). Cerebrospinal fluid protein and glucose were normal. Rapid HIV assay was negative.

Brain MRI revealed diffuse cerebral edema with cerebellar tonsillar herniation and effaced subarachnoid spaces ( Fig. 41.2 ). Thirty-minute routine EEG showed an unreactive slow background with no sleep elements.

Spectrum of brain MRI in cerebral malaria. (A) 14-month-old girl one month after infection. Sagittal T1 shows mild global volume loss and ex vacuo dilation of the prepontine cistern and fourth ventricle ( arrows ). (B) Axial T2 shows patchy edema in the bifrontal subcortical white matter ( arrows ), with crowding of sulci and basal cisterns. (C) Sagittal T1 with severe cerebral edema causing cerebellar tonsillar herniation ( circle ), effacement of prepontine cistern, compression of the fourth ventricle, and empty sella ( arrows ). (D) Follow-up axial T2 showing progression of cerebral edema with cortical swelling ( arrows ) and effacement of sulci and basal cisterns. (E) Involvement of the cortex is more severe posteriorly with swelling of the parieto-occipital cortex and (F) thalami ( arrows ).

(Reproduced with permission from Seydel et al.)

In endemic areas, cerebral malaria (CM) is the most common cause of febrile coma or acute febrile encephalopathy in children. Rapid diagnostic tests are typically used for screening tests, with peripheral blood smears performed to confirm asexual malaria parasitemia. People living in high-transmission areas may acquire partial immunity, with some eventually developing a state of asymptomatic parasitemia. It is therefore possible for a comatose febrile child to have a chronic asymptomatic parasitemia, followed by systemic or CNS coinfection (usually bacterial or viral) causing acute illness.

Malarial retinopathy is a confirmatory sign, as two-thirds of children with clinical CM have malarial retinopathy. However, recent studies show that many children without signs of malarial retinopathy (retinopathy-negative CM) can also be infected.

Other causes of non-malaria febrile coma in Africa include viral or bacterial meningoencephalitis, TBM, toxoplasmosis, and brucellosis. Bacterial meningoencephalitis usually manifests with elevated CSF white count. Focal findings on neurological examination can raise the possibility of focal abscess, tuberculoma, or empyema.

In the absence of fever, subacute-chronic neurologic symptoms can be seen with NCC and fungal infections, as well as tumors and autoimmune disorders.