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Postmalaria neurological syndrome: a case of acute disseminated encephalomyelitis?
  1. A H MOHSEN,
  3. M L SCHMID,
  4. S T GREEN
  1. Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, UK
  2. Department of Clinical Neurology
  3. Department of Neuroradiology
  1. Dr Abdul H Mohsen, Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2JF, UK Abdul.Mohsen{at}
  1. Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, UK
  2. Department of Clinical Neurology
  3. Department of Neuroradiology
  1. Dr Abdul H Mohsen, Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2JF, UK Abdul.Mohsen{at}
  1. Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, UK
  2. Department of Clinical Neurology
  3. Department of Neuroradiology
  1. Dr Abdul H Mohsen, Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield S10 2JF, UK Abdul.Mohsen{at}

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We report on a 30 year old woman presenting with neurological dysfunction 8 weeks after complete recovery fromPlasmodium falciparum malaria. Magnetic resonance imaging during her illness showed multifocal white matter abnormalities. She made a full recovery without any specific treatment. Repeat MRI 6 months after her acute illness showed complete resolution of all lesions. Although the term postmalaria neurological syndrome has been used to describe such cases, the clinical and radiological findings are indistinguishable from those seen in acute disseminated encephalomyelitis.

The term postmalaria neurological syndrome (PMNS) was first introduced in 1996.1 The syndrome has been defined as the acute onset of neurological or neuropsychiatric symptoms in patients recently recovered from Plasmodium falciparum malaria who have negative blood films at the time of onset. This therefore distinguishes it from cerebral malaria, which occurs during parasitaemia. The time from eradication of the systemic parasitaemia to the development of this syndrome can be up to 9 weeks (median 4 days).1 The prevalence of PMNS in patients withPlasmodium falciparum malaria is 0.12%. PMNS is 300 times more common in patients with severe rather than uncomplicated malaria.1 The reported clinical features include generalised convulsions, acute confusional state, acute psychosis, and tremor. The range of neurological manifestations of PMNS is probably wider and includes cerebellar ataxia (first reported in 1986),2 motor aphasia, and generalised myoclonus.3 Most cases made a complete recovery without specific treatment.

We report a case of PMNS where MRI was performed during and 6 months after the period of acute neurological dysfunction. The similarities between PMNS and acute disseminated encephalomyelitis (ADEM) are discussed.

A 30 year old woman was admitted to hospital after returning from a holiday in Kenya. She complained of rigors, sore throat, and shortness of breath. On the day of admission she had become jaundiced. She had not taken any malaria prophylaxis before or during the holiday. A blood film showed 29% falciparum malaria parasitaemia.

She was treated with intravenous quinine, doxycycline, exchange transfusion, and, subsequently, erythrocytophoresis. She remained conscious throughout the acute illness and there was no clinical evidence of cerebral malaria. Her illness was complicated by myocarditis and transient renal impairment. She was discharged 24 days after admission having made a full clinical recovery.

Two months after discharge she was readmitted. Her partner reported that she had apparently been normal since discharge up until 3 weeks previously. She had become increasingly lethargic and was sleeping for up to 18 hours per day. She had also become agitated, exhibited odd behaviour, and at times experienced language difficulties. Twenty four hours before her admission she had woken up with a severe headache associated with nausea, profound confusion, and inability to recognise her long term partner or her parents.

Initial assessment on admission showed the severe confusion to have largely resolved although she still exhibited inappropriate behaviour and was very apprehensive and restless. Neurological examination disclosed brisk reflexes with no focal neurological deficit. Soon after admission she had a tonic-clonic convulsion. She was treated with phenytoin, intravenous acyclovir, and broad spectrum antibiotics.

Full blood count, blood film, urea and electrolytes, and random blood glucose were normal. Liver function tests showed slightly raised transaminases. A cranial CT showed no significant abnormalities. Examination of the CSF showed 200x106/l cells, 22 of which were white cells (all lymphocytes) and no xanthochromia. Protein in CSF was raised at 1.4 g/l (normal <0.4 g/l). Brain MRI was performed on a 1.5 Tesla Siemens magnetic system. T2 weighted images of the brain showed areas of high signal in the subcortical white matter of the right frontal and posterior portion of the right temporal lobes (figure A). These were not associated with a mass effect. There was also increased signal in the white matter of the left cerebellar hemisphere (figure B). After intravenous gadolinium DTPA there was contrast enhancement of all areas with white matter signal change (figure C). An EEG showed a large excess of background activity with frequent runs of high voltage rhythmic slow/sharp activity, in keeping with an encephalopathy. Bacterial, viral, and mycobacterial cultures of the CSF and polymerase chain reaction for herpes virus were negative. Autoimmune and vasculitis screens were also negative.

(A) Axial T2 weighted image showing high signal in right frontal white matter (white arrow). (B) Coronal T2 weighted image showing high signal in white matter of right temporal lobe (small white arrow) and left cerebellar hemisphere (white arrow-head). (C) T1 weighted coronal image following intravenous gadolinium DTPA showing enhancement in the white matter of the right temporal lobe (curved white arrow) and left cerebellum (open white arrow).

As there was clinical evidence of improvement after the MRI she was not given steroids. She gradually improved over the next week and was discharged home 14 days after admission with no neurological deficit and with complete resolution of her confusional state.

Neurological assessment 6 months after this admission showed her to be normal. Repeat MRI with intravenous contrast on this occasion showed complete resolution of the abnormal findings.

Changes in MRI in PMNS have been reported to date only once, in a case that responded to steroid treatment.3 The MRI findings in this patient, as in the case previously reported, suggest a multifocal white matter inflammation. This explains the wide range of neurological manifestations reported so far. The aetiology of PMNS is unclear. In cerebral malaria sequestration of knob bearing parasitised red cells within the cerebral vessels can result in local ischaemic damage.4 This mechanism however cannot be implicated in PMNS where, by definition, no parasitised red cells are present. Plasma and CSF concentrations of cytokines (tumour necrosis factor and interleukins 2 and 6) are raised in patients with severe malaria.5 Tumour necrosis factor has been implicated in neurotoxicity.6 These cytokines may persist within the circulation even after eradication of the parasites but, more importantly, they can be found in higher concentrations in the serum samples of patients with PMNS compared with concentrations present during the recovery period.5 The observed time to neurological dysfunction after eradication of the parasite and the reported response to steroid treatment3 are supportive evidence of an immunological mechanism. There are no reports in the literature of acute disseminated encephalomyelitis (ADEM) in association with the use of quinine, doxycycline, or after erythrocytophoresis.

There are some similarities between PMNS and ADEM. ADEM is a multifocal, monophasic, demyelinating disease characteristically occurring 1 to 3 weeks after a viral or, occasionally, bacterial infection or vaccination. Most patients with ADEM make a full recovery. In severe cases corticosteroids can be of help. Brain MRI usually shows widespread lesions in the white matter of the brain or the spinal cord. Distinction from multiple sclerosis can be difficult at the onset but the clinical history, the course of the disease, the lack of relapses, and the resolution of the lesions on repeat MRI are useful distinguishing features. The similarities between PMNS and ADEM are striking: latency from infection to neurological dysfunction, multifocal neurological deficits, response to steroids, good prognosis, identical MRI findings, and now evidence of complete resolution of such lesions on MRI.

This is the first case report of PMNS showing spontaneous and complete resolution of not only the clinical but also the MRI abnormalities. There are no identifiable clinical or radiological features that can distinguish PMNS from ADEM. Plasmodium falciparummalaria should therefore be added to the list of infections able to precipitate ADEM.


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