THE LANCET Summary Background Neurological signs and symptoms are common in malaria, but observations in Vietnam and Thailand have pointed to a discrete transient neurological syndrome after recovery from severe infections. Methods A prospective study of the post-malaria neurological syndrome (PMNS) was conducted at two centres in Vietnam over four years. Criteria for inclusion were recent symptomatic malaria infection with parasites cleared from blood (and in cases of cerebral malaria full recovery of consciousness), and development of neurological or psychiatric symptoms within two months after the acute illness. Half of the patients with severe falciparum malaria had been taking part in a randomised trial of antimalarials. Findings Of 18 124 patients with falciparum malaria treated (1176 of whom had severe infections) 19 adults and three children had subsequent PMNS; in one patient it followed uncomplicated malaria and in 21 it followed severe malaria. The overall incidence (95% confidence interval) of PMNS after falciparum malaria at the main study centre was 1·2 per 1000 (0·7 to 1·8 per 1000) and relative risk (95% CI) for developing PMNS after severe versus uncomplicated falciparum malaria was 299 (40 to 2223). 13 patients had an acute confusional state or psychosis, six had one or more generalised convulsions, two had generalised convulsions followed by a long period of acute confusion, and one developed a fine tremor. At the time of PMNS diagnosis all patients were aparasitaemic. The syndrome was self-limiting, median duration 60 h (range 24–240). PMNS was associated with the use of oral mefloquine. In the randomised trial 4·4% (10/ 228) of patients with severe malaria who received mefloquine after parenteral treatment developed PMNS compared with 0·5% (1/ 210) of those who received quinine; relative risk 9·2 (95% CI 1·2 to 71·3, p=0·012). Interpretation Mefloquine is not the only risk factor for PMNS but it is a strong one. Where an effective alternative drug is available, mefloquine should not be used after treatment of severe malaria. Lancet 1996; 348: 917–21 Introduction Of the many neurological manifestations and complications of malaria, the most common and important is the cerebral form of severe Plasmodium falciparum malaria. This is attributed to the sequestration of parasitised red blood cells in the brain, though how this process causes coma is incompletely understood. 1,2 In most cases recovery is complete, although cerebral malaria is fatal in 15–20% of cases and a further 10% of children and 1–3% of adults have residual neurological sequelae. 3,4 Hypoglycaemia resulting from malaria or quinine treatment can also cause coma and, if it is severe and protracted, may result in death or permanent brain damage. 5 Use of mefloquine, chloroquine, and earlier mepacrine (quinacrine) for the prophylaxis or treatment of malaria has also been associated with an acute self- limiting neuropsychiatric syndrome, 6–8 and lately a case of “central anticholinergic syndrome” associated with mefloquine treatment was described. 9 Psychosis following cerebral malaria has been reported, 10 and a delayed cerebellar syndrome following falciparum malaria has also been described, particularly in Sri Lanka. 11 After observations in Vietnam and Thailand that a discrete neurological syndrome could follow recovery from falciparum malaria a prospective study was conducted. Here we report the clinical features and associations of this post-malaria neurological syndrome (PMNS) in 22 patients. Patients and methods This prospective study was conducted over four years, to January, 1995, at the Centre for Tropical Diseases, Ho Chi Minh City, Vietnam, an infectious disease hospital which is a referral centre for much of southern Vietnam, and at the nearby Dong Nai Paediatric Centre. We included under PMNS any patient with symptomatic malaria infection (initial blood smear positive for asexual forms of malaria parasites), whose parasites had cleared from the peripheral blood and, in cerebral cases, had recovered consciousness fully, who developed neurological or psychiatric symptoms within two months after the acute illness. During part of the study period a double-blind trial of the treatment of severe adult malaria was carried out at one of the study centres, 12 and any patients presenting with PMNS after recovery were included in the present series. In this treatment trial, patients were randomised to receive either intramuscular artemether (4 mg per kg initially, then 2 mg per kg eight hourly) or quinine (20 mg of hydrochloride salt per kg initially, then 10 mg per kg eight hourly) and when they could Vol 348 • October 5, 1996 917 Centre for Tropical Diseases (N T H Mai MD, L V Chuong MD, N H Phu MD, T T Hien MD) and Wellcome Trust Clinical Research Unit (N P J Day MRCP, D Waller BM, D B Bethell MB, Prof N J White FRCP) , Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi M inh City, Vietnam; and Centre for Tropical M edicine, Nuffield Department of Clinical M edicine, John Radcliffe Hospital, Oxford OX3 9DU, UK (N P J Day, D Waller, D B Bethell, N J White) Correspondence to: Prof Nicholas J White, Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam Post-malaria neurological syndrome Nguyen Thi Hoang Mai, Nicholas P J Day, Ly Van Chuong, Deborah Waller, Nguyen Hoan Phu, Delia B Bethell, Tran Tinh Hien, Nic holas J White