Postmalarial Neurological Syndrome Revisited
Postmalarial Neurological Syndrome Revisited
Abstract & Commentary
Synopsis: Observations of those patients recovering from Plasmodium falciparum malaria in Vietnam and Thailand who developed a discrete neurological syndrome led to a prospective study, which described the clinical features and associations of postmalarial neurological syndrome (PMNS). A fascinating report of a PMNS case from Baylor College of Medicine, published in Clinical Infectious Diseases (CID), represents the first patient identified with PMNS in the United States.
Source: Falchook GS, et al. Postmalarial neurological syndrome after treatment of Plasmodium falciparum malaria in the United States. Clin Infect Dis. 2003;37:e22-e24.
Neurological infections and their complications, particularly the cerebral form of severe Plasmodium falciparum malaria, are perhaps among most feared entities known to physicians who take care of travelers. The postinfectious syndrome described by this recent CID case report is consistent with the other such cases described by Nguyen and associates in 1996.1 These cases were specifically noted as not due to cerebral malaria. Common features among the 1996 Asian cases included: 1) having a negative malaria blood smear at the onset of neurological or neuropsychiatric symptoms; 2) a preceding severe case of malaria infection; 3) a recent complete recovery from P falciparum malaria; and 4) complete recovery from PMNS without specific treatment within 10 days.
The most recently described patient was a 50-year-old Ghanaian woman who was visiting friends and relatives in the United States and presented with intermittent dyspnea during physical exertion. Her examination was consistent with pulmonary edema. She was treated with quinine sulfate and doxycycline when her peripheral blood smear revealed P falciparum parasites at a 0.2% level of parasitemia. Her hemoglobin was 5-6 g/dL, and other pertinent admission labs were serum sodium level of 122 meq/L and serum potassium of 6.4 meq/L and creatinine of 2.5 mg/dL. These values were corrected. However, on day 5 of treatment, this antimalarial regimen was altered when her blood sugar level decreased to 31 mg/dL. Malaria treatment was completed with a 3-day course of atovaquone/proguanil. Following treatment, P falciparum was no longer detected in peripheral blood smears. The patient required endotracheal intubation on day 6 to treat pulmonary edema, which was not responding to large doses of loop diuretics. Echocardiogram showed mild concentric LVH with normal ejection fraction and normal LVEDP, and the pulmonary edema was felt to be noncardiac in origin but secondary to P falciparum infection.
Eleven days following resolution of parasitemia and 9 days after completing antimalarial therapy, the patient was found to have an abnormal mental status and the new onset of upper and lower extremity myoclonus, jerking, and tremors. She was awake but disoriented, unable to answer questions or follow commands. Verbal response consisted only of incomprehensible responses to pain. She was neither hypoxic, nor hypoglycemic, and there were no acute changes noted on head CT scan although multiple old lacunar infarcts were seen. Subsequent brain MRI showed nonspecific increased signal in the pons, posterior internal capsule, thalamus, corona radiata, and periventricular areas. CSF analysis was normal, and CSF cultures for bacteria, fungi, and mycobacteria were all unrevealing. All potentially offending medications were discontinued the day after symptoms developed; yet the patient’s abnormal mental state became progressively worse. Eight days later, she developed both visual and auditory hallucinations, but within 2 days her mental status began to improve; she was able to both understand and answer questions, and her mental status returned to normal. Although she exhibited a slight expressive aphasia, this resolved 2 days later and she subsequently had no further neurological episodes or complications.
Comment by Maria D. Mileno, MD
The mechanism(s) and reasons for the development of PMNS are unknown. The brain sequestration of parasitized RBCs in persons with cerebral malaria has been documented in several necropsy series and remains the accepted pathogenesis of neurological syndromes occurring during falciparum-associated cerebral malaria. This finding is not limited to persons who die with cerebral malaria and could be a factor in the development of PMNS. Cerebral malaria is fatal in 15-20% of cases; in most other cases, recovery from coma is complete. Additional factors contributing to neurological symptoms can include hypoglycemia as well as use of mefloquine or chloroquine for prophylaxis or treatment. Both have been associated with an acute self-limited neuropsychiatric syndrome. Clinically significant neurological events have also been described with use of artemisinin compounds for the treatment of malaria.
Importantly, the patient who was reported in CID did not receive mefloquine, an agent that has been associated with neuropsychiatric side effects such as seizures and psychosis. Nor did she receive any other antimalarials commonly associated with adverse neurological events. One-fourth of the patients in Nguyen et al’s study also had not received mefloquine. The combination atovaquone/proguanil has rarely been associated with neuropsychiatric effects, largely among patients with predisposing neuropsychiatric medical histories. There has been speculation about whether PMNS is a distinct clinical entity and not simply a consequence of either cerebral damage from malaria or the adverse effects of anti-malarial therapy; this case report offered no evidence of cerebral malaria or drug-induced adverse events. It appears to be a disturbing, yet self-limited, syndrome characterized by bizarre derangement in mental status without long-term sequelae. More cases of what is a fairly recently described neurological syndrome will probably be recognized if travel medicine practitioners are simply aware of it. They are likely to be the major source of additional cases.
Dr. Mileno is Director, Travel Medicine, The Miriam Hospital, Assistant Professor of Medicine, Brown University, Providence, RI.
References
1. Nguyen THM, et al. Lancet. 1996;348:917-921.
2. Miller LG, Panosian CB. N Engl J Med. 1997;336:1328.
Observations of those patients recovering from Plasmodium falciparum malaria in Vietnam and Thailand who developed a discrete neurological syndrome led to a prospective study, which described the clinical features and associations of postmalarial neurological syndrome (PMNS).Subscribe Now for Access
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