Clinical Neurology and Neurosurgery 150 (2016) 89–91

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Clinical Neurology and Neurosurgery

journal homepage: www.elsevier.com/locate/clineuro

Case report

Dengue encephalitis presenting with nonconvulsive status

epilepticus: A case report
F. Assenza a , M. Tombini a , G. Assenza a , C. Campana a , A. Benvenga a , N. Brunelli a ,
M. Ulivi a , A. Cascio Rizzo a , A. Corpolongo b , M.L. Giancola b , E. Nicastri b , V. Di Lazzaro a,∗
a
Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Università Campus Bio-Medico di Roma, via Álvaro del Portillo 21, 00128
Rome, Italy,
b
UOC Malattie Infettive e Tropicali, Clinical Department, National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, Via Portuense, 292, 00149
Rome, Italy

a r t i c l e i n f o

Article history:
Received 21 January 2016
Received in revised form 13 June 2016
Accepted 26 August 2016
Available online 28 August 2016

Keywords:
Nonconvulsive status epilepticus
Dengue
Encephalitis

1. Introduction 2. Case report

Dengue fever is endemic in tropical/sub-tropical areas of the
world and the global incidence is increasing. It is an infective
disorder caused by one of the 4 serotypes of Dengue virus (fam-
ily Flaviviridae), transmitted by mosquitoes of the genus Aedes.
It is characterised by a wide spectrum of clinical manifesta-
tions, ranging from asymptomatic infection to life-threatening
dengue haemorrhagic fever and dengue shock syndrome, which
includes overt central neurological dysfunction, with encephalitis
and seizures. Here we report a case of dengue encephalitis with
an unusual clinical manifestation: a nonconvulsive status epilep-
ticus (NCSE). To our knowledge, the association between dengue
encephalitis and NCSE has not been previously described. Our
observation shows that sometimes the early manifestations of the
infection could be mild and subtle, also in the case of direct CNS
involvement, making diagnosis very challenging.
∗ Corresponding author.
E-mail address: v.dilazzaro@unicampus.it (V. Di Lazzaro).
A 79-year-old patient, coming back from holidays in Brazil, was
admitted to our Department for stupor and fever (Tmax = 38 ◦ C).
Some days before admission, he had developed gradually a con-
fusional status. Blood pressure, heart rate and blood oxygen
saturation were in the normal range.
On admission, he was drowsy and confused. Neurological exam-
ination showed marked psychomotor slowing, central left facial
weakness, absence of rigor nucalis.
Total-body-CT-scan was normal. Blood-exams revealed mild
pancytopenia (RBC: 3.78 × 106̂/uL, Haemoglobin 11.4 g/dL, PLTs
84.00 × 103̂/uL, WBC: 2.97 × 103̂/uL, Neu 1.65 × 103̂/uL, Linf
0.94 × 103̂/uL). Serological test for HIV was negative, serologi-
cal assays for Rickettsia Conorii, Borrelia Burgdorferi, EBV, CMV,
HSV-1/2, Brucella, Salmonella Typhi, excluded an acute infection.
Brain-MRI was not executed because the patient had an MRI-
incompatible pacemaker.
The electroencephalogram (EEG) (Fig. 1) performed the day
after admission showed diffuse, continuous epileptic discharges
prevailing on bilateral frontotemporal regions, suggesting an elec-
troclinical picture of nonconvulsive status epilepticus (NCSE).
Diazepam was administered and soon after Levetiracetam therapy
was introduced (up to 2000 mg/day), with a progressive decrease
of epileptic abnormalities in the next three days, and a simultane-

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90 F. Assenza et al. / Clinical Neurology and Neurosurgery 150 (2016) 89–91
Fig. 1. The EEG in the picture shows subcontinuous and diffuse epileptiform discharges, prevailing in amplitude on frontotemporal regions, compatible with non-convulsive
status epilepticus.
ous clinical improvement: the patient was alert, oriented and able
to normally interact with other people.
Rachicentesis, at first, was not performed because the patient
was on oral anticoagulant therapy, because of thrombocytope-
nia and mainly because of the pronounced clinical improvement.
Assuming an occult infection, an empirical antibiotic therapy
was introduced (Vancomycin 2 g/day, Piperacillin/Tazobactam
13.5 g/day, Clarithromycin 1000 mg/day). One week later, the
patient presented an acute and dramatic worsening of neurological
conditions with drowsiness and more confusion.
Cerebrospinal fluid (CSF) analysis revealed a mild increase of
proteins (713 mg/L) with normal values of glucose (65 mg/dl),
and cells (2/uL, mainly lymphocytes). Blood culture was sterile.
Research of neurotropic viruses, culture and cytology of CSF all
resulted negative. However, considering the recent journey to
Brazil an infective etiology, including Dengue virus, was still con-
sidered among the possible hypotheses, and, for this reason, he
was transferred to a hospital specialized in infectious diseases.
Here, further investigations revealed: Dengue serology (IgM and
IgG antibodies) positive on admission and an increasing of IgG titre
and decreasing of IgM titre in the subsequent serological exam
performed some days later. IgG antibodies for Dengue were also
detected in CSF by immunoabsorbent assay (titre 1:8). PCR for
Dengue resulted negative in serum and CSF while it was positive
for urine sample. Blood rapid test for Dengue resulted negative
for antigen (NS1) and positive for IgG and IgM antibodies. PCR for
Cytomegalovirus (CMV), Herpes Simplex virus (HSV)-1 and HSV-2,
Virus JC (JCV), Human Herpesvirus (HHV)-6 and HHV-8, Varicella
Zoster Virus (VZV), Enterovirus on CSF were negative; assays for
detection of Trypanosoma Cruzi, Listeria, Leishmania, Malaria on
blood were negative.
The patient received antibiotic, antiviral therapy, and support-
ive treatments. Over 4 weeks he had a progressive deterioration
of vigilance and respiratory functions. Levetiracetam was replaced
with Valproate and Phenobarbital without interrupting seizures,
referred as complex partial seizures with/without secondary gen-
eralization. After an initial improvement he developed pneumonia
and acute hypoxemic respiratory failure and he was admitted to
the intensive care unit. Despite intensive supportive care he died
three months later.
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3. Discussion
The altered mental state is a very common presentation in the
elderly admitted to the emergency department. The spectrum of
differential diagnosis is wide, but about 16% of patients aged 60 or
older with confusion of unknown origin have NCSE [1].
Mostly in the elderly, the diagnosis of NCSE requires the clinical
experience of neurologists and epileptologists and a high degree
of suspicion, since the presence of superimposed medical condi-
tions or pre-existing cognitive impairment may divert the correct
diagnosis. The causes of NCSE in the elderly can be cerebrovascular
disorders (acute or remote), neurodegenerative diseases, exacer-
bation of earlier epilepsy, tumours, trauma, metabolic or infectious
precipitants superimposed on an already fragile brain. Diagnosis
can usually be established using a prolonged EEG recording in most
cases, but sometimes a continuous monitoring is required.
Neurological manifestations of dengue fever are increasingly
recognized and they can range from myelitis, Guillain-Barré syn-
drome, myositis to encephalitis. Dengue encephalitis, a direct
neuronal infiltration by the dengue virus, is a rare but important
complication of dengue infection. Fever, headache, and reduced
consciousness are the core features, not explained by other causes
(acute liver failure, shock, electrolyte derangement, intracranial
haemorrhage), and corroborated by laboratory findings and neu-
roimaging findings (Brain CT scan or Brain MRI suggestive of viral
encephalitis).
Laboratory findings include several possible approaches with
different sensibility and specificity: a) Detection of virus (Viral cul-
ture, PCR amplification of viral RNA, Immunocytochemistry for viral
antigens); b) Detection of host immune response (MAC-ELISA for
anti-dengue IgM/IgG). The choice of one of these methods should
be performed according to the time of infection onset [2].
Seizures are common, typically generalized tonic-clonic
seizures; only one case manifesting as epilepsia partialis continua
has been previously reported [3]. Our case adds NCSE to the possible
spectrum of manifestations in Dengue encephalitis and shows that
the early manifestations of the infection could be mild and subtle
also in case of direct CNS involvement, making the diagnosis of this
serious and life-threatening condition very challenging.
In conclusion, we believe that dengue infection should be
considered and investigated as a potential pathogen in patients
 F. Assenza et al. / Clinical Neurology and Neurosurgery 150 (2016) 89–91 91

presenting with an encephalitis picture or confusional status, [2] A. Varatharaj, Encephalitis in the clinical spectrum of dengue infection, Neurol.
especially those ones coming from endemic areas, even if classic India 58 (Jul–Aug (4)) (2010) 585–591.
[3] R. Verma, A. Varatharaj, Epilepsia partialis continua as a manifestation of
features are missing. dengue encephalitis, Epilepsy Behav. 20 (Feb (2)) (2011) 395–397.

References

[1] S. Cheng, Non-convulsive status epilepticus in the elderly, Epileptic. Disord. 16

(Dec (4)) (2014) 385–394.

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