Neurological manifestations following cured malaria: don’t forget
post-malaria neurological syndrome
Foued Bellazreg1,3, Dorsaf Slama1, Nadia Ben Lasfar1,3, Maha Abid1,3, Houneida Zaghouani2,3,
Sana Rouis1,3, Wissem Hachfi1,3, Amel Letaief1,3
1. Department of Infectious Diseases, Farhat Hached University Hospital, 4000 Sousse, Tunisia.
2. Department of Radiology, Farhat Hached University Hospital, 4000 Sousse, Tunisia.
3. University of Sousse, Faculté de Médecine Ibn Al Jazzar, 4000 Sousse, Tunisia.
Emails:
Dorsaf Slama: dorssaf.slama@gmail.com, Nadia Ben Lasfar: benlasfar.nadia@yahoo.fr, Maha Abid:
maha_abid@hotmail.fr, Houneida Zaghouani: houneida7@yahoo.fr; Sana Rouis: sanarouis@yahoo.fr,
Wissem Hachfi: wissemhachfi@gmail.com, Amel Letaief: ameletaief@gmail.com
Abstract:

Introduction: Cerebral malaria which occurs during the active infection is the most common neurological complication of
malaria. Other complications including post-malaria neurological syndrome (PMNS) can rarely occur following complete
recovery from the disease. We report a case of post-malaria neurological syndrome in a Tunisian patient.
Case presentation: A 26-year-old Tunisian man with no past medical history was admitted in 2016 for a muscle weakness
of the 4 limbs, seizures, tetraparesis and myoclonus which appeared after he returned from Côte d’Ivoire where he had been
treated three weeks ago for Plasmodium falciparum malaria with favorable outcome. Blood smears for malaria were negative.
Brain MRI showed multiple hypersignal cerebral lesions. Investigations didn’t show any infectious, metabolic, toxic, vascular
or tumoral etiology. Thus, the diagnosis of PMNS was considered. The patient was treated with methylprednisolone with
favorable outcome. Two years later, he was completely asymptomatic.
Conclusion: PMNS should be considered in patients with neurological symptoms occurring within two months of cured
acute disease in which blood smears for malaria are negative and other etiologies have been ruled out. In most cases, the
disease is self-limited while in severe cases corticosteroid therapy should be prescribed with favorable outcome.
Keywords: Post-malaria neurological syndrome; immunologic; corticosteroid.
DOI: https://dx.doi.org/10.4314/ahs.v21i1.35
Cite as: Bellazreg F, Slama D, Lasfar NB, Abid M, Zaghouani H, Rouis S, et al. Neurological manifestations following cured

malaria: don’t forget post-malaria neurological syndrome. Afri Health Sci. 2021;21(1):273-6. https://dx.doi.org/10.4314/ahs.
v21i1.35
Introduction
In 2018, the World Health Organization (WHO) estimated that 228 million cases of malaria occurred worldwide and caused 405 000 deaths. Plasmodium falciparum,
the most prevalent malaria parasite, is most commonly associated with severe disease namely neurological
Corresponding author:
Foued Bellazreg,
Department of Infectious Diseases,
Farhat Hached hospital, 4000 Sousse, Tunisia.
University of Sousse, Faculté de Médecine Ibn
Al Jazzar, 4000 Sousse, Tunisia.
Telephone: 00216 73 10 25 56;
Fax: 00216 73 10 25 16
Email: fouedbellazreg@yahoo.fr
African
Health Sciences

complications and mortality 1. Among the neurological
complications, cerebral malaria is by far the most common. It occurs during the active infection and can lead
to death or to residual neurological sequelae in 15-20%
and 1-3% of treated patients respectively 2. Other neurological complications can rarely occur following complete recovery from malaria. They include post-malaria
neurological syndrome (PMNS), acute disseminated
encephalomyelitis, delayed cerebellar ataxia and acute
inflammatory demyelinating polyneuropathy3. In Tunisia, malaria has been eradicated since 1979 but imported cases from travelers returning from endemic countries continue to be observed. We report here a case of
PMNS in a Tunisian patient after his return from Côte
d’Ivoire.

© 2021 Bellazreg F et al. Licensee African Health Sciences. This is an Open Access article distributed under the terms of the Creative commons Attribution
License (https://creativecommons.org/licenses/BY/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly cited.

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Case presentation
A 26-year-old Tunisian man with no past medical history, who worked in Côte d’Ivoire since September 2015,
was admitted in July 2016 for a 48-hour history of
tetraparesis tonic-clonic generalized seizures and myoclonus . These signs appeared after he returned from
Côte d’Ivoire where he had been treated three weeks
ago for Plasmodium falciparum malaria with favorable
outcome.
Medical history didn’t reveal any alcohol or illicit drugs
consumption. Physical examination showed tetraparesis and was unremarkable otherwise, namely there were
no dysarthria, cranial nerve palsies, ataxia, pyramidal
signs or sensory deficits. Laboratory data including
blood sugar, sodium, calcium, creatinine, blood cell
count, prothrombin time and cerebrospinal fluid (CSF)
analysis were normal, and blood toxicologic analysis was
negative. Peripheral blood smears were both negative
for Plasmodium. Brain CT scan was normal but brain
and spine magnetic resonance imaging (MRI) showed
multiple T2-flair hypersignal cerebral lesions predomi-

a

nantly in the white matter of the frontal and the occipital lobes (Figure 1) without myelitis or radiculitis.
The diagnosis of infectious encephalitis was initially
considered and the patient was treated with intravenous
aciclovir associated to anticonvulsant therapy. Serologic tests for West Nile virus, human immunodeficiency
virus, cytomegalovirus, Ebstein-Barr virus, hepatitis B,
hepatitis C, Brucella, Rickettsia and Coxiella burnetii were
all negative, and echocardiography was normal.
At day 5 of aciclovir, the patient has not improved
and PCR for HSV1 and HSV2 in the CSF was negative. Aciclovir was then stopped and the diagnosis of
PMNS was considered. The patient was treated with
oral methylprednisolone 1 mg/kg daily with progressive improvement of the neurological deficits. At day
15 of methylprednisolone he was discharged. Six weeks
later, he had no neurological deficit or other complaints
and brain MRI was without abnormalities (Figure 2).
The corticosteroid therapy was discontinued after a total duration of 8 weeks and the patient returned to his
job in Côte d’Ivoire. Two years later, he was completely
asymptomatic.

a

b
b
Figure 1. Initial T2-flair MRI showing hypersignal cerebral lesions (arrows)
predominantly in the white matter of the frontal (a) and the occipital lobes (b).

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Figure 1. Initial T2-flair MRI showing hypersignal cerebral lesions (arrows)
predominantly in the white matter of the frontal (a) and the occipital lobes (b).

Figure 2. End-of-therapy MRI, without abnormalities

Discussion
Among the four neurological complications reported after full recovery of malaria, our patient had no
signs of delayed cerebellar ataxia, acute inflammatory
demyelinating polyneuropathy or acute disseminated
encephalomyelitis. Thus, he was considered to have
PMNS. PMNS, first reported in 1996 by Nguyen et al.
in 22 Vietnamese patients, was defined by the occurrence of neurological or psychiatric symptoms after
a symptom-free period within two months following
cured acute malaria with a negative blood smear and no
alternative diagnosis 4. It is a rare condition with an incidence of 1.2-1.7 per 1000 malaria cases 4,5. Until February 2020, only 54 cases of PMNS were reported including 28 of them were isolated case reports 3,5,6. In two
recent systematic reviews, most cases of PMNS were
observed in young adult males (mean age, 33 years) and
preceded by severe Plasmodium falciparum malaria. They
occurred within a mean duration of 9 days (0-60) after
the malaria recovery. A wide range of clinical signs were
reported including impaired consciousness, fever, seizures, motor deficits, myoclonus, tremor and ataxia 3,5.
CSF analysis showed lymphocytic meningitis in 60% of
cases and high protein levels in 77% of cases while glucose level was normal in all patients 5. Among imaging
techniques, CT scan was normal in all cases, while MRI
revealed brain abnormalities in 43% of cases. These
abnormalities consisted of nonspecific hypersignals
sometimes associated with gadolinium enhancement
in different localizations including sub-cortical and
periventricular areas, iternal capsule, corpus callosum,
thalamus, brain stem and cerebellum 3,5.
Based on clinical severity, Schnorf et al. classified the

syndrome into three categories: a mild form with isolated cerebellar ataxia or postural tremor, a diffuse mild
encephalopathy with confusion or seizures, and a severe encephalopathy with motor aphasia, generalized
myoclonus, postural tremor and cerebellar ataxia 7.
In our patient, neurological manifestations which consisted of seizures, tetraparesis and myoclonus appeared
3 weeks after full recovery of Plasmodium falciparum malaria. CSF and CT scan were normal while MRI showed
multiple T2-flair hypersignal cerebral lesions predominantly in the white matter of the frontal and the occipital lobes. Peripheral blood smears were negative for
Plasmodium and infectious, metabolic, toxic, vascular and
tumoral etiologies were ruled out by laboratory and imaging investigations. Based on these findings, the diagnosis of PMNS in its mild encephalopathy form with
seizures has been established.
The pathogenesis of PMNS is not well understood.
The delayed-onset after a 2-3 weeks symptom-free
period the negativity of blood smears, the high CSF
concentrations of pro-inflammatory cytokines and the
beneficial effect of corticosteroid therapy are highly
suggestive of the immunological mechanism of this
disease 3,5,7,8. The cerebral microvasculature where parasites are sequestered due to cytoadherence could be
the locus of immunization process. The cytoadherence
is less frequent and less significant in Plasmodium vivax
infection which could explain why most PMNS cases
follow Plasmodium falciparum infections 9,10.
PMNS is usually self-limited and does not require specific treatment. However, in severe cases which occur
in almost 25% of patients, corticosteroids have been
used to hasten recovery 3,7. In our patient, based on MRI

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data which showed multiple brain lesions and on the
absence of spontaneous improvement, corticosteroid
therapy with methylprednisolone was prescribed during
8 weeks and the outcome was favorable.
Conclusion
PMNS should be considered in patients with neurological symptoms occurring within two months of cured
acute disease in which blood smears for malaria are
negative and other etiologies have been ruled out. In
most cases, the disease is self-limited while in severe
cases corticosteroid therapy should be prescribed with
favorable outcome.
Conflicts of interest
None.
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