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Review article
Department of Medicine, Santosh Medical College and Hospital, No. 1, Ambedkar Road, Ghaziabad UP, India
Department of Medicine, Lady Hardinge Medical College, New Delhi, India
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 13 September 2016
Accepted 14 September 2016
Available online xxx
Dengue, an acute febrile illness caused by Flavivirus, is among the most frequent arbovirus in tropical
regions. Mostly infections are asymptomatic, but disease manifestations may range from minimal
symptoms to death. For the rst time in 2009, WHO has given importance to neurological manifestations
and considered this as criteria for severe dengue infection. Neurological complications are being seen
more frequently nowadays which were not seen during previous dengue virus outbreaks. Increasingly,
lot of unusual case reports, case series, and studies on neurological manifestations have been published
in the existing literature. The present review focuses on the recent insights on the neurological
manifestations and the pathogenesis of neural involvement of dengue virus. Neurological complications
of dengue virus infection can be categorised into dengue encephalopathy, encephalitis, immunemediated syndromes, muscle dysfunction, and neuro-ophthalmic disorders. The neurological
manifestations in dengue infection are primarily caused by DENV-2 and DENV-3. The neurological
involvement in dengue can be due to possible four mechanisms: (a) metabolic imbalance; (b)
haemorrhagic disturbance; (c) post-infectious autoimmune reaction; (d) direct infection by virus. There
is no specic treatment for dengue, but supportive and symptomatic management is essential with
emphasis on prompt uid resuscitation, along with early recognition of dengue and its complications.
2016 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Indian Journal of Medical
Specialities.
Keywords:
Dengue
Neurological manifestations
Arboviruses
1. Introduction
Dengue is a viral infection caused by members of the genus
Flavivirus and family Flaviviridae. These small viruses contain
single-strand RNA as genome. The virion consists of a nucleocapsid
with cubic symmetry enclosed in a lipoprotein envelope. There are
four virus subtypes known as DENV-1, DENV-2, DENV-3 and
DENV-4. The principal vectors of dengue virus are Aedes aegypti
and Aedes albopictus. As per WHO approximately 2.5 billion people
two fths of the worlds population in tropical and subtropical
countries are at risk [1]. Dengue fever is one of the leading causes
of hospitalisation and death among children [1,2]. Epidemics of
dengue are being seen in almost all countries located within the
tropical belt [3]. The relationship between haemorrhagic dengue
fever and neurological manifestations was rst described in
1976. In 1983, Gubler and others recorded neurological disorders
associated with dengue from 25 different countries across Asia, the
Pacic rim, the Americas, Mediterranean regions, and Africa [4].
For the rst time in 2009, the WHO endorsed guidelines for
clinical case denitions of dengue, included neurological manifestations for severe dengue [1]. However, from the time dengue was
recognised as a clinical entity, neurological manifestations of the
disease have been described [5,6]. Factors that might contribute to
neurological manifestations include prolonged shock, hyponatraemia, hepatic failure, or intracranial bleeding [5,7].
Why do most dengue virus infections lead to asymptomatic or
mild self-limiting disease, and some infected people develop severe
dengue? Subsequent (secondary or tertiary) infection with a
heterologous dengue virus serotype has been postulated to be
the main factor associated with severe disease, via antibodydependent enhancement [8,9]. According to this hypothesis, nonneutralising antibodies from a previous dengue virus infection
facilitate cell invasion, enhance viraemia, and initiate a selfamplifying cascade that can lead to release of cytokines and other
proinammatory mediators [10].
2. Neurological complications
* Corresponding author.
E-mail address: dr_ashk2006@yahoo.co.in (A. Kumar).
http://dx.doi.org/10.1016/j.injms.2016.09.009
0976-2884/ 2016 Published by Elsevier, a division of RELX India, Pvt. Ltd on behalf of Indian Journal of Medical Specialities.
Please cite this article in press as: Kumar A, Margekar SL. Neurological manifestations in dengue. Indian J Med Spec. (2016), http://
dx.doi.org/10.1016/j.injms.2016.09.009
G Model
A. Kumar, S.L. Margekar / Indian Journal of Medical Specialities xxx (2016) xxxxxx
mediated syndromes, dengue muscle dysfunction, and neuroophthalmic disorders. However, there is no strict classication and
some overlap does exist [11].
Please cite this article in press as: Kumar A, Margekar SL. Neurological manifestations in dengue. Indian J Med Spec. (2016), http://
dx.doi.org/10.1016/j.injms.2016.09.009
G Model
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Please cite this article in press as: Kumar A, Margekar SL. Neurological manifestations in dengue. Indian J Med Spec. (2016), http://
dx.doi.org/10.1016/j.injms.2016.09.009