J. Neurovirol.
DOI 10.1007/s13365-017-0516-1
CASE REPORT
Guillain-Barre syndrome complicating chikungunya
virus infection
Ayush Agarwal 1 & Deepti Vibha 1 & Achal Kumar Srivastava 1 &
Garima Shukla 1 & Kameshwar Prasad 1
Received: 3 November 2016 / Revised: 3 December 2016 / Accepted: 17 January 2017
# Journal of NeuroVirology, Inc. 2017
Abstract Chikungunya virus (CHIKV) is a mosquito-borne
alphavirus which presents with symptoms of fever, rash, ar-
thralgia, and occasional neurologic disease. While outbreaks
have been earlier reported from India and other parts of the
world, the recent outbreak in India witnessed more than 1000
cases. Various systemic and rarely neurological complications
have been reported with CHIKV. We report two cases of
Guillain-Barré syndrome (GBS) with CHIKV. GBS is a rare
neurological complication which may occur after subsidence
of fever and constitutional symptoms by several neurotropic
viruses. We describe two cases of severe GBS which present-
ed with rapidly progressive flaccid quadriparesis progressing
to difficulty in swallowing and breathing. Both required me-
chanical ventilation and improved partly with plasmapharesis.
The cases emphasize on (1) description of the rare complica-
tion in a setting of outbreak with CHIKV, (2) acute axonal as
well as demyelinating neuropathy may occur with CHIKV, (3)
accurate identification of this entity during outbreaks with
dengue, both of which are vector borne and may present with
similar complications.
Keywords Guillain-Barre syndrome . Chikungunya virus .
Plasmapharesis . Mosquito-borne diseases
* Deepti Vibha
deeptivibha@gmail.com
1
Neurosciences Center, Department of Neurology, All India
Institute of Medical Sciences, Room number 707, 7th floor,
New Delhi, India
Introduction
Chikungunya virus (CHIKV) is an RNA alphavirus
(group A arbovirus) in the family of Togaviridae. It has
an incubation period of 2–10 days. The known vectors are
Aedes aegypti and Aedes albopictus mosquitoes. Clinical
features consist of severe arthralgia, which can persist for
even several weeks or months. Apart from fever, arthral-
gia and rash, rare complications in the form of mild hem-
orrhage, myocarditis, and hepatitis have been reported
(Menon et al. 2010), (Oehler et al. 2015). Neurologic
complications are rarer (Lewthwaite et al. 2009).
CHIKV virus infection is confirmed by the identification
of genomic products in acute-phase blood specimens, (re-
verse transcription–PCR [RT-PCR]) (Oehler et al. 2015)
and/or by serum immunoglobulin (Ig) M antibodies (Priya
et al. 2014). Although CHIKV outbreaks have occurred in
India in the 1960s and early 1970s, and also reported in
other parts of the world (Handler et al. 2016), recent re-
surgence in various parts of India have been reported re-
cently (2016a).
Guillain-Barré syndrome (GBS) is an acute inflamma-
tory polyneuropathy with worldwide incidence being 1.1
to 1.8 per 100,000 persons per year (Fujimura 2013). In
two thirds of patients, GBS occurs after an infection and
putative molecular mimicry. Although GBS has been re-
ported earlier with CHIKV (Wielanek et al. 2007),
(Lebrun et al. 2009) from France, there is no report of
this feature from India in any of the recent or previous
outbreaks (Lewthwaite et al. 2009). We report two cases
of GBS which had severe presentations after a viral pro-
dromal which were diagnosed as chikungunya.
 J. Neurovirol.

Clinical description of cases
Patient 1
An 18-year-old boy without any co-morbidity had high
grade intermittent fever associated with body ache of
25 days duration. This was associated with multiple joint
pains, but not associated with rash, cough, or diarrhea.
His fever subsided after 7 days and he was asymptomatic
for the next 10 days after which he developed complains
of swelling and weakness of his both distal upper limbs
which gradually spread proximally and then progressed to
dysphagia both to solids and liquids in the next 4 to
5 days. He presented at our hospital with progressive
weakness in both the lower limbs for the past 3 days.
He was found to have neck weakness and tachypnea at
the time of admission following which he was electively
intubated. The neurologic examination revealed
quadriparesis more pronounced distally (Medical
Research Council [MRC] 2/5) than proximally (MRC
3/5), and global areflexia. The sensory examination was
normal. Electrophysiological studies were done and

Table 1 Clinical features,

electrophysiology and treatment Patient 1 Patient 2
of the two patients with Guillain-
Barre syndrome Age, year/sex 18/male 30/male
Neurological examination Flaccid quadriparesis, bulbar Flaccid quadriplegia, facial and
weakness, global areflexia bulbar weakness, global areflexia
Nerve conduction studies (motor)
Left median nerve
dCMAP (N > 5 mV) 2.8 1.1
DML (N < 3 ms) 2.9 11.7
NCV (elbow-wrist) (N > 50 m/s) 52 21
F waves latency (N < 30 ms) 24.8 NR
Left ulnar nerve
dCMAP (N > 5 mV) 2.1 1.3
DML (N < 3.5 ms) 2.8 10.6
NCV (elbow-wrist) (N > 48 m/s) 52 39
F waves latency (N < 30 ms) 29.1 NR
Left tibial nerve
dCMAP (N > 5 mV) 6.1 NR
DML (N < 5 ms) 5.2 NR
NCV (calf-ankle) (N > 40 m/s) 47 NR
F waves latency (N < 50 ms) 51 NR
Left common peroneal nerve
dCMAP (N > 2 mV) 1 NR
DML (N < 5 ms) 4.3 NR
NCV (calf-ankle) (N > 40 m/s) 50 NR
F waves latency (N < 50 ms) NR NR
Nerve conduction studies (sensory)
Left median nerve
Latency (N < 3 ms) 2.3 2.5
Amplitude (N > 5 μV) 7.6 6
Velocity (N > 50 m/s) 57 51
Left sural
Latency (N < 4 ms) 3.1 3.0
Amplitude (N > 5 μV) 7.5 6.2
Velocity (N > 40 m/s) 45 42
Treatment Plasmapharesis Plasmapharesis
Outcome Partial recovery Partial recovery

dCMAP distal compound muscle action potential, DML distal motor latency, NCV nerve conduction velocity, NR
not recordable
J. Neurovirol.
revealed a pure motor axonal neuropathy involving all
four limbs (Table 1). The patient was treated with five
cycles of plasmapharesis (3 liter per plasma exchange,
fresh frozen plasma) and improved by one MRC grade
p ow e r i n both upper and lower limbs. IgM anti-
chikungunya antibodies were found to be positive at the time
of presentation to our hospital. Serologic screening for
Campylobacter jejuni, Cytomegalovirus, Mycoplasma
pneumoniae, Epstein-Barr virus, Dengue virus, and HIV was
negative. His liver transaminase levels were also found to be
elevated which gradually normalized on conservative man-
agement during his hospital course.
The patient had a delayed extubation due to associated
aspiration pneumonitis, although the power in the limbs im-
proved by the second cycle of plasmapharesis. At 1 month of
follow-up, the patient had normal bulbar functions with grade
4-/5 power in upper limbs and grade 3/5 power in lower limbs.
Patient 2
The second patient was a 30-year-old gentleman who was
apparently well 20 days prior to admission. His complaints
started as high-grade fever with chills associated with large
joint pain. By the 12th day of fever, he started feeling
numbness involving both soles which gradually ascended
up to thigh within 2 days. Over a period of the next 4 days,
it spread to all four limbs and trunk. In the next 24 to 48 h,
he noticed flaccid weakness, first involving both lower
limbs (proximal > distal) which soon progressed to involve
both upper limb (proximal > distal). Five days prior to
admission, he developed difficulty in chewing and
swallowing food. At the time of admission, he was quad-
riplegic (MRC grade 0/5 in all limbs) with severe facial
and bulbar weakness. The sensory examination was nor-
mal. He was intubated and electrophysiological study was
done which revealed severe demyelinating neuropathy
(Table 1). He was also treated with five cycles of
plasmapharesis following which he improved and was
extubated at the end of the fourth cycle.
The patient was extubated by the end of fourth cycle of
plasmapharesis and the power in upper and lower limbs was
2/5 and 1/5 respectively at the end of therapy. His power
improved further at 1 month follow-up and was 4-/5 and 3/5
in upper and lower limbs, respectively.
Both patients presented with history of fever 2 to
3 weeks prior to the onset of weakness, which was rapidly
progressive with respiratory involvement and showed im-
provement with plasmapharesis. The diagnosis of GBS
was made on the basis of clinical history and electrophys-
iological studies, which qualifies for level 2 diagnostic
certainty according to WHO Brighton criteria for the case
definition of GBS (Sejvar et al. 2011). The absence of
other viruses in serology analysis and the epidemiologic
data showing current outbreak of chikungunya also con-
firm the diagnosis.
We conclude that these two cases of GBS were related to an
acute infection with chikungunya. Both patients showed im-
provement with plasmapharesis.
Discussion
The two described cases of GBS with chikungunya virus
infection highlight the occurrence of this neurological
complication from CHIKV from this part of the world.
Although other viral disease outbreaks with GBS as com-
plication have been described with dengue and zika virus-
es (Tilak et al. 2016), the threat of CHIKV is still less
reported (Chandak et al. 2009). For the first time it also
describes acute axonal neuropathy GBS with CHIKV
(Table 1). Earlier reported cases showed acute demyelin-
ating neuropathy (Wielanek et al. 2007), (Lebrun et al.
2009). Another important finding was an afebrile period
transcending between viral prodrome and neurological
symptoms. The current outbreak of CHIKV in India has
reported 1682 confirmed cases out of 1,369,319 suspected
cases in 188 districts (2016b). In India, major epidemics
of chikungunya fever was reported in 1963 (Kolkata),
1965 (South India) and 1973, (Maharashtra). Although
previous studies from India in pediatric population have
described encephalitis-like illness, GBS is still unreported
(Lewthwaite et al. 2009). The case reports suggest asso-
ciation of GBS with the CHIKV outbreaks. It also empha-
sizes that the complication may occur even after a self-
limited and uncomplicated chikungunya infection. The
cases had severe neurological presentation and both re-
quired ventilatory support. Also, since dengue and
CHIKV are both endemic in India, both etiologies should
be considered in patients of GBS during the outbreak
season.
Conclusion
CHIKV may present with GBS after a viral prodrome.
Suspicion of this complication should warrant timely manage-
ment as the cases were rapidly progressive. Acute axonal neu-
ropathy does not exclude CHIKV and serology and/or RT-
PCR should be done in all cases of GBS during CHIKV out-
break to know the real burden of disease.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.

References
Chandak NH, Kashyap RS, Kabra D et al (2009) Neurological compli-
cations of chikungunya virus infection. Neurol India 57:177–180.
doi:10.4103/0028-3886.51289
Facts about Chikungunya17806 - pdf. (2016b) http://nvbdcp.gov.
in/Doc/Facts%20about%20Chikungunya17806.pdf. Accessed 3
Nov 2016
Fujimura H (2013) The Guillain-Barré syndrome. Handb Clin Neurol
115:383–402. doi:10.1016/B978-0-444-52902-2.00021-7
Handler MZ, Handler NS, Stephany MP et al (2016) Chikungunya fever:
an emerging viral infection threatening North America and Europe.
Int J Dermatol. doi:10.1111/ijd.13439
Lebrun G, Chadda K, Reboux A-H et al (2009) Guillain-Barré syndrome
after chikungunya infection. Emerg Infect Dis 15:495–496.
doi:10.3201/eid1503.071482
Lewthwaite P, Vasanthapuram R, Osborne JC et al (2009) Chikungunya
virus and central nervous system infections in children, India. Emerg
Infect Dis 15:329–331. doi:10.3201/eid1502.080902
Menon PR, C K, Sankar J, et al. (2010) A child with serious chikungunya
virus (CHIKV) infection requiring intensive care, after an outbreak.
Indian J Pediatr 77:1326–1328. doi: 10.1007/s12098-010-0174-2
J. Neurovirol.
NVBDCP (2016a), National Vector Borne Disease Control Programme.
In: Httpnvbdcpgovinchik-Cdhtml. http://nvbdcp.gov.in/chik-cd.
html. Accessed 2 Nov 2016
Oehler E, Fournier E, Leparc-Goffart I et al (2015) Increase in cases of
Guillain-Barré syndrome during a chikungunya outbreak, French
Polynesia, 2014 to 2015. Euro Surveill Bull Eur Sur Mal Transm
Eur Commun Dis Bull 20:30079. doi:10.2807/1560-7917.
ES.2015.20.48.30079
Priya R, Khan M, Rao MK, Parida M (2014) Cloning, expression and
evaluation of diagnostic potential of recombinant capsid protein
based IgM ELISA for chikungunya virus. J Virol Methods 203:
15–22. doi:10.1016/j.jviromet.2014.03.005
Sejvar JJ, Kohl KS, Gidudu J et al (2011) Guillain-Barré syndrome and
Fisher syndrome: case definitions and guidelines for collection,
analysis, and presentation of immunization safety data. Vaccine
29:599–612. doi:10.1016/j.vaccine.2010.06.003
Tilak R, Ray S, Tilak VW, Mukherji S (2016) Dengue, chikungunya
and the missing entity—Zika fever: a new emerging threat.
Med J Armed Forces India 72:157–163. doi:10.1016/j.
mjafi.2016.02.017
Wielanek AC, Monredon JD, Amrani ME et al (2007) Guillain-Barré
syndrome complicating a chikungunya virus infection. Neurology
69:2105–2107. doi:10.1212/01.wnl.0000277267.07220.88