Neurological Complications in Chikungunya Fever
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Original Article
Neurological Complications in Chikungunya Fever
Rampal*, Meenaxi Sharda**, H Meena***
Abstract
Objective: The present prospective study was undertaken to study the clinical manifestations and mainly neurological
complication of an acute febrile illness termed chikungunya which has recently attacked india after 43 years.
Method: This prospective study has been conducted in hospitalised patients admitted in government and private
hospitals of Kota city from August 2006 to October 2006. Patients showing neurological involvement with typical
clinical picture of chikungunya infection were studied in detail and followed up for improvement and any permanent
damage or death.
Results: Apart from typical clinical triad of high grade fever, arthralgia and rash of chikungunya infection we have
observed a spectrum of neurological abnormalities in terms of altered mental functions, seizures, focal neurological
deficit with abnormal ct scan of head and altered csf biochemistry. Permanent neurological sequelae and even
death has occurred.
Conclusion: Typical clinical history of chikungunya infection, neurological complications with associated csf
abnormalities, supportive laboratory evidences, positive chikungunya igm card test, exclusion of other causes
and known predilection of arboviruses for cns infection allows us to conclude the diagnosis of study cases as
Chikungunya Encephalitis. ©
INTRODUCTION
C hikungunya is a relatively rare form of viral fever
caused by a single stranded RNA virus of the genus
alpha virus in the family Togaviridae and transmitted
2006 in French Island of Reunion in the Indian Ocean.5
Presently India is facing major outbreaks of the disease in
various states from last few months as mentioned below
to human by the bite of Aedes aegypti mosquito.1 The in sequential order.6
name ‘Chikungunya’ is derived from the Makonde word In November - December 2005 in Andhra Pradesh
meanings “that which bends up” in reference to the stooped (Hyderabad and Secunderabad) and Southern India
posture which develops as a result of arthritic symptoms (Gulbarga, Bidar, Raichur, Bellary, Chitradurga, Davanagera,
of the disease. Chikungunya virus is of African origin and is Kolar, Bijapur districts of Karnataka).
maintained among non-human primates on that continent
March 2006 Malegaon town of Nasik district of
by Aedes mosquito of subgenera stegomyia. Disease is
Maharashtra and Orissa state.
endemic in rural area of Africa.2
May 2006 A major outbreak in Bangalore and Andhra
The disease was first described by Marion Robinson
Pradesh.
and W.H.R. Lumsden in 1955, following an outbreak on the
Makonde Plateau, along the border between Tanganyika June- August 2006 New cases reported in Chennai, Salem
and Mozambique in 1952.3 The Aedes aegypti- Chikungunya and Tamilnadu.
virus transmission cycle has also been introduced into Asia Beside Southern India, MP, Maharashtra, Gujarat,
where it poses a great health problem. Chikungunya virus Rajasthan are also presently under the attack of infection
is not a stranger agent for our country also. It had caused and facing major outbreaks.
two major outbreaks, one in Calcutta during month of
July-August 1963 and another in Madras and Vellore cities MATERIAL and METHOD
of Chennai state during months of July–November 1964. Clinically suspected cases of Chikungunya fever from
Both the epidemics were short lived.4 A major epidemic various parts of Haroti region (Kota, Baran, Jhalawar,
was recently reported during March 2005 to January Bundi) of Rajasthan hospitalized in government and
private hospitals of Kota city from August 2006 to October
*Professor and Head; **Assistant Professor; ***Resident Doctor, 2006 were studied. Twenty cases (out of 60 cases) with
Department of Medicine, Medical College and Associated Group of neurological manifestations and positive chikungunya IgM
Hospitals, Kota (Rajasthan).
Received : 9.1.2007; Revised : 27.6.2007; Accepted : 4.10.2007
antibody test were subjected to detailed history and clinical
examination and followed up. Chikungunya IgM antibody
© JAPI • VOL. 55 • NOVEMBER 2007 www.japi.org 765detection test, routine investigations and other supportive Fever and Constitutional Symptoms: In the majority
tests such as SGOT, CRP, total platelets count were done in of the cases the onset of fever was abrupt and associated
all cases. EEG, CT scan head, CSF examination were done with chills and joint pain. Fever was moderate (100-1030F)
in patients showing neurological signs and symptoms. for first 7 days, there after; became mild (99-1000F) for next
Malaria, dengue and typhoid fever were especially ruled 3-4 days. All the cases had associated headache, bodyache,
out. Chikungunya IgM antibody negative cases were lethargy, insomnia and anorexia with fever. Duration and
excluded. range of temperature is shown in Table 1.
Details of Chikungunya Igm Card Test (Ctk Biotech) Musculoskeletal Symptoms/Signs: The most striking
It is the onsite Chikungunya IgM rapid test that is a lateral complaint with fever was joint pain, which was sudden
flow chromatographic immuno-assay for the qualitative in onset, moderate to severe in severity and had affected
detection of IgM anti Chikungunya virus “Chik–V” in more than one joint at a time. The joints involved in order
the human serum or plasma. It is a screening test. The of severity and preference were knee, ankle, wrist, small
onsite Chikungunya IgM rapid card test is an IgM capture joints of hand & feet and elbow. Because of severe pains the
immunoassay, utilizing recombinant antigen derived from most of the cases were confined to bed on 1st or 2nd day of
its structural protein. It detects IgM anti-chikungunya in fever and 10 cases developed characteristic stooped flexed
patient’s serum or plasma within 10 minutes.7 posture. Seventeen cases had joint swelling around knee
and ankle. Various musculoskeletal symptoms and signs
Test Cassette Consists of
are shown inTable 2.
Bleeding Manifestation: There was no active bleeding
in any of these cases. Five cases had conjunctival injection.
A burgundy colored conjugate pad containing of Tourniquet test was positive in 3 cases.
‘Chikungunya Antigen conjugated with colloid Dermatological Symptoms/Signs: are shown in Table 3.
gold (CHIKUNGUNYA Conjugate) & Rabbit IgG (Gold
Hypotension: Eight cases had demonstrated hypotension
Conjugate). Specimen ID Simple Well on admission in whom blood pressure was ranging between
A nitro cellulose membrane strip containing a test band 90/70 – 100/70 mm of Hg.
T & control band C. T-band is precoated with anti-human M
Git Symptoms/Signs: Almost all the cases had vomiting,
antibody & C-band is precoated with goat anti rabbit IgG.
stomatitis and oral ulceration with the onset of disease. Two
Adequate amount of specimen is dispensed into the cases had mild hepatomegaly.
sample well. Specimen migrates by capillary action. If IgM
Neurological Symptoms/Signs: Occurrence of
antibody to Chikungunya is present in the specimen it will
neurological symptoms and signs in Chikungunya cases
bind to the Chikungunya conjugates. The immuno complex
were observed early in the course of disease on 2nd or
is then captured on the membrane by the precoated anti-
3rd day of fever. All the cases had shown altered level
human IgM antibody, forming a burgundy coloured T band
of consciousness in form of confusion, disorientation,
indicating Chikungunya IgM positive result. Test contains
drowsiness and delirium. Six cases had developed psychosis.
an internal control (C conjugates) which should exhibit a
Six cases had either focal or generalised seizures. EEG was
burgundy colored band of immuno complex of goat anti
normal in these cases. Two cases had total blindness due
rabbit IgG / rabbit IgG Gold (Gold conjugates). Test will be
to retro-bulbar neuritis. One case had right hemiparesis
invalid in absence of control band.
(power 3/5) with diminished deep tendon reflexes and
Limitations flexor planter response and mild papilloedema on fundus
1. Failure to follow the procedure closely may give examination. CT scan of head revealed ring-enhancing
inaccurate result.
Table 1 : Duration and range of temperature
2. A negative result indicates either absence or low titer
of IgM antibodies but does not preclude the possibility Range/ 990F-1000F 1000F-1030F 1030F-1050 F
Duration
of exposure to Chikungunya infection.
1-4 Days 7 8 5
3. The results obtained with this test should be interpreted
5-7 Days 10 8 2
in conjunction with other diagnostic procedures and > 7 Days 18 1 1
clinical findings.
Table 2 : Musculoskeletal symptoms and signs
RESULTS
Twenty adults (out of 60 cases) in the age group (12-84 S.No. Signs and Symptoms No. of cases
years) affected with Chikungunya infection and showing 1 Arthralgia 20
positive Chikungunya IgM antibody test having neurological 2 Joint swelling 17
complications were included in the study group. The study 3 Limitation of activity 20
4 Myalgia 20
group is composed of 18 males and 2 females. Detailed signs
5 Backache 17
and symptoms observed in the cases were as follow:
766 www.japi.org © JAPI • VOL. 55 • NOVEMBER 2007Table 3 : Dermatological symptoms and signs oriented but had total blindness due to retro-bulbar neuritis.
S. No. Signs and Symptoms No. of
Temporal pallor of optic disc seen on direct fundoscopy.
cases Final outcomes of the study cases are shown in Table 7.
1 Macules/ Maculopapular rash 5 Laboratory Investigations: All the cases were investigated
2 Pruritus 14 in detail for complete blood counts, clotting time, bleeding
3 Bilateral lymphedema 20 time, Hb, ESR, blood sugar, CRP, electrolytes, urine complete,
4 Facial erythema /pigmentation 14 MP, widal, renal function tests, liver function test, Chik IgM
5 in oral cavity card test, dengue IgM & IgG antibody test, ultrasound of
Aphthous like ulcers
abdomen and pleural space, X-ray chest PA view, ECG,
over scrotum, axilla, groin 74
6 Petechiae/ Haemorrhage 0 CT scan head, EEG, CSF analysis and HLA-B27 in 02 cases.
Various laboratory parameters are shown in Table 6.
lesion in left basal ganglia. Patient improved and discharged
In all twenty cases hemoglobin was within normal range,
on sixth day with mild weakness. Three cases had lower
ESR was raised, CRP was positive. They were positive for
motor neuron type paraplegia. Diminished deep tendon
Chikungunya IgM antibody & negative for dengue IgM &
reflexes without any focal neurological deficit were found
IgG, widal and malaria parasite test. ECG, X-ray chest PA
in 7 cases. Involuntary movements in upper limbs were
view, EEG and ultra sonography of abdomen and pleural
seen in 4 cases. Various neurological symptoms and signs
spaces were normal. CT scan was normal in eighteen cases.
are shown in Table 4.
CT scan head of two cases had shown following abnormality
All the cases were treated symptomatically, no specific - multiple small hemorrhages with diffuse cerebral edema
treatment was given. During next 4-5 days period 14 cases in one case and ring enhancing lesion in left basal ganglia
gradually improved, became fully conscious and had no region in other case. The cost factor of MRI and EMGNC
neurological deficit. They were discharged with mild fever prohibited us for inclusion of these tests in our cases.
and mild to moderate degree of joint pain. Remaining 6 cases
CSF Analysis
deteriorated from the onset of neurological complications.
Out of these 6 cases, one young patient aged 45 yrs died CSF analysis revealed raised protein (50-112 mg/dl) in
early on 8th day of illness. CT scan of brain showed multiple 17 cases. Sugar was normal (40-70 mg/dl) in all 20 cases.
small hemorrhages with diffuse cerebral edema. Three out Nine cases had shown total counts more than 5 cells/
of these six cases, aged 70-80 yrs had associated other cumm, predominantly lymphocytes or mononuclear cells.
systemic disease, such as diabetes mellitus, hypertension Eleven cases had cell count ≤ 5 cells/cumm. There is no
and died on 30th - 40th days of illness. One out of these specific correlation between neurological findings and CSF
three cases required mechanical ventilation and died after abnormality. Table 5 shows case wise neurological findings
3 days. One female patient aged 65 yrs admitted with and CSF analysis.
psychosis, restlessness, altered sensorium, incontinence of
urine, and had motor power of 4/5 in lower limbs and brisk DISCUSSION
deep tendon reflexes with equivocal planter response on Alpha viruses are known to give rise to a spectrum
examination. Patient improved after seven days and was of disease in humans ranging from silent asymptomatic
discharged. After eight days patient developed paraplegia infections, undifferentiated febrile illness to devastating
and was readmitted and treated for 5 days, patient did not encephalitis.1 Chikungunya virus, belonging to same genus
improve and had left the hospital against medical advice is causing current epidemic with spectrum of diseases
and expired after 5 days. One case became fully conscious, ranging from a self limiting febrile illness to crippling acute
and lingering arthritis and sometimes serious complication
Table 4 : Neurological symptoms and signs like encephalitis and death. Chikungunya disease, which
S.No. Signs and Symptoms No. of cases was not even known and read by many doctors and medical
personnel, suddenly became popular in the community
1 Altered level of Consciousness 20
(e.g. confusion, drowsiness delirium)
in affected states of India during “Chikungunya season”
2 Psychosis 6 because of affection of multiple families / more than one
3 Coma 0 member of family simultaneously.
4 Focal Popular and readily diagnosable mosquito born diseases
Seizures
Generalized 15
such as malaria and dengue, are reportable diseases for
5 Optic Nerve which free tests are available in the government institutions,
Cranial Nerve deficit so that their magnitude can be assessed. But present
Other cranial nerves 20 mosquito born disease chikungunya is not a reportable
6 Hemiparesis 1 disease and timely unavailability of the tests for confirmation
7 Paraparesis/Paraplegia 3
of the diagnosis underestimated the affected number of
8 Decreased deep tendon reflexes
without motor deficit 7 population but this is definitely true that the disease in
9 Involuntary movements 4 southern states and our state also was more rampant than
malaria and dengue during the “Chikungunya season.”
© JAPI • VOL. 55 • NOVEMBER 2007 www.japi.org 767Table 5 : Csf analysis and neurological findings
S. No. Csf examination Neurological findings
Cells Protein Sugar
TLC/cumm (mg/dl) (mg/dl)
1 L-2 74 50 Altered sensorium
2 L-5 105 46 Altered sensorium, GTCs, right hemiparesis, (3/5), DTR diminished, planter-↓,
mild papilloedema
3 L-100 48 68 Altered sensorium, GTCs, paraplegia(0/5), DTR absent, planter-↓
4 L-4 78 46 Altered sensorium, psychosis
5 L-4 86 44 Altered sensorium, psychosis
6 L-3 72 46 Altered sensorium, psychosis, involuntary movements
7 L-3 90 58 Altered sensorium, involuntary movements, paraplegia (0/5), DTR absent, planter-↓
8 L-3 88 78 Altered sensorium, irritability
9 L-15 71 45 Altered sensorium, psychosis
10 L-4 41 36 Altered sensorium, blindness due to retro-bulbar neuritis,
(fundus-temporal pallor of optic disc)
11 L-0 64 38 Altered sensorium psychosis, impaired vision (fundus-NAD)
12 L-40 109 87 Altered sensorium
13 L-55 46 49 Altered sensorium psychosis
14 L-220 108 75 Altered sensorium, paraplegia(0/5), DTR absent, planter-↓
15 L-29 110 40 Altered sensorium, focal seizures in right upper limb
16 L-5 92 52 Altered sensorium, GTCs
17 L-6 110 46 Altered sensorium, GTCs, involuntary movements
18 L-3 86 70 Altered sensorium, GTCs, involuntary movements
19 L-28 70 50 Altered sensorium
20 L-8 112 70 Altered sensorium, GTCs
GTCs- generalized tonic clonic seizure, L-lymphocytes. DTR- deep tendon reflexes, ↓- flexor planter reflex.
Table 6 : Range of various laboratory parameters Table 7 : The final outcomes of the study cases
S. Tests Range No. of cases S. No. Outcomes No. of cases
No.
1 Improved and discharged 14
1 TLC 4000-6000 cells/cumm 1 2 Not improved & left the hospital against
6000-8000 8 medical advise with paraplegia and expired 1
8000-11000 4 3 Blindness due to retro-bulbar optic neuritis 2*
> 11000 7 4 Death 6
2 Platelates < 50,000/cumm 1
* One of them died and other survived. Total death -6.
50000-150000 8
> 150000 11 but have their own limitations to perform at point of care
3 B. urea 50-140 mg/dl 13 and are not available commercially.
S. creatinine 1.5-2.2 mg/dl 12
4 S. bilirubin > 2.0 mg/dl 0
Arbo viruses are known to cause viral encephalitis in
SGOT 64-153 IU/L 18 many epidemics in the past.8 In 15 cases (out of 2424
SGPT 50-75 IU/L 8 seropositive), meningoencephalitis has been reported in
5 Urine microscopy > 5 cells/HPF 0 chikungunya out break in Reunion island from March 2005-
and albumin Trace to 100 mg/dl 20 January 20065 and also in 1963 outbreak of haemorrhagic
6 Electrolytes Na+ < 135 mmol/L 13 fever in Calcutta.4 In our study 20 cases had shown the
K < 3.5 mmol/L
affection of CNS at various levels in the form of encephalitis
(in 15 cases), encephalomyelitis (in 03 cases) and optic
The prototypic clinical picture in more than one/
neuritis (in 02 cases). After ruling out other causes of CNS
whole family members is a triad of fever, joint pain and
involvement with detailed history, clinical examination and
rash. Exclusion of other common causes of arthritis and
relevant investigations, we conclude that these are due
supportive lab tests strongly support the diagnosis.
to chikungunya infection. Probable reasons of increased
In present study the cases were labelled Chikungunya on neurological involvement in our series can be: a) some
the basis of positive chik IgM card test. The cost of card test mutation in virus, b) being a tertiary level hospital patients
was a major limiting factor and could not be employed for with severe form of illness are referred here and study
screening the whole affected population. Rapid card tests are was conducted in these hospitalised patients only, c) total
the useful assay techniques for detection of IgM antibodies number of chikungunya positive cases is less in comparison
against any infectious agent without any additional to the quantum of epidemic as we have excluded Chik IgM
requirement of instrumentation. Virus isolation, polymerase card negative cases and cases in whom Chik test was not
chain reaction (PCR) and ELISA are the confirmatory tests, done, d) there are some limitations of Chik IgM card test.
768 www.japi.org © JAPI • VOL. 55 • NOVEMBER 2007Apart from morbidity due to articular involvement, infection by the virus Chikungunya: an emergent disease in the
the neurological complications lead to prolonged Reunion island. Eur J Emerg Med 2006;13:A 7-8.
hospitalisation and secondary complications in form of 6. Saxena S.K, Singh M, Mishra N, Lakshmi V. Resurgence of chikungunya
virus in India: an emerging threat. Euro Surveill 2006;11:E060810.2.
electrolytes imbalance, secondary infection, bedsores,
7. Thin S, La Linn, Aoskov J, Aung MM, Aye M, Zaw A, Myint A.
urinary tract infection, altered renal parameters and Development of a single indirect enzyme linked immuno sorbent
aspiration pneumonia. No case per se died of electrolyte assay for the detection of immunoglobulin M antibody in serum
imbalance or altered renal parameters as they were mildly from patients, following an out break of chikungunya virus infection
deranged. Old persons more often succumbed to disease in Yangon, Myanmar. Trans Royal Society Trop Med Hyg 1992;86:438-
42.
because of secondary infections and associated systemic
8. Chatterjee SN, Chakrawarti SK, Mitra AC, Sarkar JK. Virological
illness like diabetes, hypertension, renal disease etc.
investigation of case with neurological complications during the
outbreak of haemorrhagic fever in Calcutta. J Indian Med Assoc
CONCLUSION 1965;45:314-6.
Typical clinical history of Chikungunya infection,
neurological complications with associated CSF
abnormalities, supportive laboratory evidences, positive
Chikungunya IgM card test, exclusion of other causes and
known predilection of arboviruses for CNS infection allows
us to conclude the diagnosis of study cases as Chikungunya
Encephalitis. Being a hospital based study high proportion
of complications are expected as hospitalized patients were
comparatively more sick.
Acknowledgement
We are thankful to Sudha Hospital, Baheti Hospital and
Jaiswal Hospital of Kota city for providing the study cases.
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3. Robinson Marion. An Epidemic of Virus Disease in Southern Province,
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