Post-malaria neurological syndrome: a rare manifestation of common disease

Introduction

Several systemic and neurological complications can occur with Plasmodium falciparum malaria, of which cerebral malaria is the best known and most serious. Rarely, patients may suffer post-malaria neurological syndrome (PMNS), a neurological syndrome that occurs after complete recovery from P. falciparum infection. ¹ It is a rare and transient clinical syndrome in which a patient with symptomatic malaria infection, after parasitic clearance from the peripheral blood (in cases of cerebral malaria after regaining full consciousness), develops neurological symptoms within 2 months of recovery. It is characterized by varied clinical manifestations ranging from impaired consciousness to focal or polyneuropathy.^1,2 There have been 12 case reports of Guillain-Barré syndrome (GBS) following malarial infections ² and also a reported case of bilateral facial paresis following malaria. ³ We report a case of PMNS manifesting as bilateral common peroneal nerve palsy leading to foot drop.

Case history

A 23-year-old man presented with a high grade fever with chills and rigors. Two days after the onset of fever he developed impaired consciousness that evolved into a deep coma within the next 24 hours. A general physical examination showed mild pallor and he was febrile. The neurological assessment revealed: deep coma; pupils bilaterally normal size and reacting to light; no gaze preference; and normal fundus examination. Deep tendon reflexes were brisk in all the extremities and had bilateral extensor planter response. Meningeal signs were absent. The rest of the systemic examination was unremarkable.

A parasite lactate dehydrogenase (pLDH)-based immunochromatographic antigen detection (optiMAL) assay showed a positive result for P. falciparum. Haematological tests revealed: haemoglobin 6.4 g%; total leukocyte count 8100  cells/mm³; platelet count 100,000  cells/mm³; and normal coagulation tests. Biochemical analysis showed: blood urea 91 mg%; serum creatinine 0.9 mg%; serum bilirubin 4.0 mg% total (1.75 mg% indirect); serum glutamic oxalo-acetic transaminase (SGOT) 122 U/L; and serum glutamic pyruvic transaminase (SGPT) 45 U/L. An arterial blood gas analysis showed mild metabolic acidosis with compensatory respiratory alkalosis and normal oxygenation. A peripheral blood smear (PBS) examination detected gametocytes of P. falciparum with high parasitaemia. The patient was treated with intravenous artesunate and oral clindamycin. He gradually regained full consciousness over the next 3–4 days and remained well for one week after which he developed bilateral complete foot drop. There was no recurrence of fever. The muscle power of the ankle dorsiflexors on both sides were 0/5 (Medical Research Council grade). Deep tendon reflexes were normal and the neurological examination, including sensory examination, was normal. A nerve conduction study (NCS) showed non-recordable compound muscle action potential (CMAP) in both the common peroneal nerves which was suggestive of severe axonal involvement. NCS (motor as well as sensory) of the rest of the upper and lower limb was normal. The cerebrospinal fluid (CSF) analysis was unremarkable except for mild increase in the CSF protein (66 mg %). A repeat PBS for malaria parasite was negative. The patient was not given any specific treatment and rehabilitation therapy was advised. Follow up at 4 weeks showed partial clinical and electrophysiological improvement (motor power 2/5 MRC grade). At 3 months follow-up there was no neurologic deficit and a normal CMAP of the common peroneal nerves.

Discussion

After complete recovery from symptomatic malarial infection patients can suffer myriad neurological complications such as: delayed onset cerebellar ataxia; acute disseminated encephalomyelitis (ADEM); and acute inflammatory demyelinating polyneuropathy (AIDP). ² PMNS was first reported in 1994 from a Vietnamese study describing 21 patients with severe falciparum malaria complicated by PMNS. ¹ Impaired sensorium, drowsiness, psychosis, aphasia, seizure, myoclonus, tremor, ataxia, or peripheral neuropathies are the main manifestations that have been reported in literature.^1,2 The prevalence of PMNS in patients with malaria is 0.12% and is 300 times more common in patients with severe malaria. ¹ PMNS usually occurs in adults after complete clinical recovery and parasite clearance from severe falciparum malaria. The median onset of PMNS manifestation was 4 days in the Vietnamese study and 15 days in the other reports. There have been 12 case reports of GBS following malarial infections.^2,4,5 The aetiopathogenesis of PMNS is not clear. However, several factors suggest that PMNS may be immunologically mediated. A formerly proposed hypothesis of the cytoadherence of parasitized red blood cells in the central or peripheral nervous system microvasculature is replaced by an immunological mechanism, as the parasitized red blood cells are not present at the time of neurological involvement in PMNS. PMNS is a self-limited disorder, lasting 2–14 days, and no specific treatment is required in the majority of cases. Steroids have been tried in severe cases with good clinical outcomes. ¹

Conclusion

PMNS is a rare complication of severe falciparum malaria. The disorder must be differentiated from a relapse of infection as the treatment is different. Clinicians should be aware of this rare delayed manifestation of falciparum malaria especially in malaria prevalent regions.