Malaria Retinopathy and Cerebellitis in a 9-Year-Old Boy in the United States

This case report describes the first documented case of hemorrhagic cerebellitis secondary to Plasmodium falciparum malaria in the United States, occurring in a 9-year-old boy who also developed malarial retinopathy. Published in the Journal of AAPOS in 2015, the report highlights the critical role of retinal examination in diagnosing cerebral malaria and predicting disease severity.

Background

Malaria remains one of the leading causes of childhood mortality worldwide, with the Global Burden of Diseases Study estimating over 710,000 deaths in children under age 10 in 2010 alone. The pathogenesis of cerebral malaria involves sequestration of parasitized erythrocytes in the microvasculature of the central nervous system, leading to blockage of blood supply and tissue hypoxia.

The cerebellum is particularly vulnerable because of its higher vascularity and lower blood flow rate compared to the cerebral cortex. This explains why cerebellar pathology may present before classic cerebral signs such as confusion, delirium, personality changes, or paresis. While acute cerebellitis following viral infections is well recognized in the United States, hemorrhagic cerebellitis due to P. falciparum had not previously been reported domestically.

Malarial retinopathy is characterized by retinal whitening, vessel changes, and hemorrhages -- usually with a white center. The retinal findings serve as a window into the degree of microvascular sequestration throughout the central nervous system and can both confirm the diagnosis and help predict prognosis.

The Patient

A 9-year-old African American boy presented to the emergency room at Children's Memorial Hermann Hospital in Houston, Texas, with the following symptoms:

• Lethargy, nausea, and abdominal pain
• Tachypnea
• Blood pressure of 98/38 mm Hg (hypotension)
• Bilateral "fire flare hemorrhages" -- a combination of icteric sclera with overlying patchy subconjunctival hemorrhage

The patient had returned two weeks earlier from a 2-month trip to Tanzania, a country endemic for P. falciparum malaria. Blood smear analysis confirmed P. falciparum infection.

The clinical course rapidly deteriorated. He developed hypovolemic shock, respiratory distress requiring intubation for airway protection.

Diagnostic Workup

Laboratory Findings

• Blood smear: Positive for Plasmodium falciparum
• Parasitemia level: 20-22% parasite load (severely elevated)
• Peripheral blood: Thrombocytopenia, severe microcytic hypochromic anemia, leukocytosis
• Liver function tests: Abnormal
• Coagulation profiles: Abnormal

Neuroimaging

MRI of the brain performed three days after admission showed:

• Diffuse cerebellar swelling
• Edematous cerebellar cortex
• Multiple small hemorrhages within the cerebellum
• Findings consistent with hemorrhagic cerebellitis

Sagittal T1-weighted images demonstrated diffuse cerebellar edema, while axial T2-weighted sequences revealed the cerebellar hemorrhages.

Ophthalmic Examination

Retinal examination performed on day 4 of admission revealed:

• Bilateral retinal hemorrhages with white centers (Roth spot-like lesions)
• Left eye subhyaloid hemorrhage overlying the macula
• Subconjunctival hemorrhages (bilateral, later resolving)

Follow-up examination 12 days after initial evaluation showed:

• Visual acuity: 20/25 right eye, 20/70 left eye
• Retinal hemorrhages improving bilaterally
• Persistent subhyaloid hemorrhage in the left eye, partially obstructing the fovea
• Resolution of subconjunctival hemorrhages

Results

Treatment

The patient was treated with:

• Continuous intravenous quinidine infusion at 0.0125 mg/kg/min
• Clindamycin at 5 mg/kg every 8 hours

Prognostic Context from the Literature

The authors placed these findings in the context of published data on malarial retinopathy and outcomes:

• Taylor et al. found that 74% (17/23) of children with confirmed cerebral malaria at autopsy had retinal hemorrhages, compared to 0% (0/7) of those without cerebral malaria
• Beare et al. reported retinopathy in 61% (170/278) of children with cerebral malaria
• A dose-response relationship existed between hemorrhage burden and mortality:
  • 1-5 hemorrhages: 12% fatal outcome (10/85)
  • 6-20 hemorrhages: 21% fatal outcome (6/28)
  • 21-50 hemorrhages: 58% fatal outcome (7/12)
  • >50 hemorrhages: 75% fatal outcome (3/4) (P < 0.001)

Clinical Significance

This case demonstrates several critical points for clinicians:

1. Malaria should be considered in the differential diagnosis of any child presenting with fever, jaundice, and systemic illness after travel to endemic regions, even in the United States
2. Retinal examination is essential in suspected cerebral malaria -- it can confirm the diagnosis and provide prognostic information about disease severity
3. Cerebellar involvement may precede cerebral signs due to the cerebellum's vascular anatomy, making early neuroimaging important
4. The "fire flare" hemorrhage sign (scleral icterus with overlying subconjunctival hemorrhage) may be an early clinical indicator of severe malarial infection
5. With increasing globalization, physicians in non-endemic countries must be equipped to recognize and manage cerebral malaria

Citation

Hashemi N, Callon LM, Kumar KS. Malaria retinopathy and cerebellitis in a 9-year-old boy in the United States. J AAPOS. 2015;19(1):87-89.

References