Malaria-associated limbic encephalitis in severe Plasmodium falciparum infection: a case series from a tertiary hospital in Tanzania

Abstract Background Neurological complications are among the most severe manifestations of Plasmodium falciparum malaria. Cerebral malaria is the best-recognized neurological syndrome; however, malaria-associated brain injury involves a broad spectrum of inflammatory, vascular, and immune-mediated processes. Limbic encephalitis is characterized by inflammation involving the medial temporal structures, and is most commonly associated with viral infections, particularly herpes simplex virus (HSV), or autoimmune disorders. Malaria-associated limbic encephalitis remains poorly characterized. Case presentation We describe two adult male patients with severe P. falciparum malaria complicated by a clinico-radiological phenotype consistent with limbic encephalitis, identified through clinical presentation, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and exclusion of alternative infectious causes; neither case fulfilled formal criteria for a definite diagnosis, as anti-neuronal antibody testing was not performed. The first patient, a 47-year-old previously healthy male, developed progressive altered sensorium, seizures, and respiratory failure requiring intensive care admission and mechanical ventilation, with acute liver injury and metabolic acidosis. EEG showed diffuse cerebral dysfunction with an electrographic seizure arising from the left posterior region. MRI demonstrated bilateral hippocampal/amygdalar T2/FLAIR hyperintensity with mild diffusion restriction on DWI and no hemorrhage. CSF was mildly inflammatory with negative multiplex PCR, including HSV. Intravenous immunoglobulin was added to antimalarial therapy given the severity of illness, and the patient achieved complete clinical recovery at hospital discharge. The second patient, a 25-year-old previously healthy male, presented with confusion and recurrent generalized seizures. MRI showed diffuse left hippocampal T2/FLAIR hyperintensity without hemorrhage or true diffusion restriction on DWI. CSF and multiplex PCR testing for bacterial, viral, and fungal pathogens were unremarkable. The patient improved with standard antimalarial and antiseizure therapy alone and achieved complete clinical recovery at hospital discharge. Conclusion Malaria-associated limbic encephalitis is an uncommon but clinically important neurological phenotype of severe P. falciparum malaria, although the diagnosis in this series remains presumptive in the absence of anti-neuronal antibody testing. Recognition of the characteristic mesial temporal MRI abnormalities and exclusion of alternative causes of encephalitis may assist clinicians in identifying such patients. Further studies are needed to clarify the mechanisms, diagnostic criteria, and potential role of immunomodulatory therapy in this condition.