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Table of Contents    
CASE REPORT
Year : 2017  |  Volume : 65  |  Issue : 1  |  Page : 105-107

Diagnostic dilemma—dengue or Japanese encephalitis?


Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Date of Web Publication12-Jan-2017

Correspondence Address:
Varun Dhir
Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.198194

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 » Abstract 

Dengue and Japanese encephalitis (JE) are arboviral diseases that are common in the tropical countries. JE virus is a classical neurotropic virus. The dengue virus, however, is usually not considered to be neurotropic, even though in recent years, reports of direct central nervous system involvement in dengue has been described. Here, we report a case wherein the patient had magnetic resonance imaging evidence of bilateral thalamic and brainstem involvement with positive serologies for both dengue and JE. We also discuss the diagnostic challenge in these cases.


Keywords: Dengue, Japanese encephalitis, magnetic resonance imaging
Key Messages:
The diagnosis of dengue encephalitis can be challenging because there are no well-defined diagnostic criteria and the magnetic resonance imaging findings are often nonspecific. Dengue encephalitis should be considered in the differential diagnosis of any encephalitis in tropical countries.


How to cite this article:
Sivamani K, Dhir V, Singh S, Sharma A. Diagnostic dilemma—dengue or Japanese encephalitis?. Neurol India 2017;65:105-7

How to cite this URL:
Sivamani K, Dhir V, Singh S, Sharma A. Diagnostic dilemma—dengue or Japanese encephalitis?. Neurol India [serial online] 2017 [cited 2017 Jul 25];65:105-7. Available from: http://www.neurologyindia.com/text.asp?2017/65/1/105/198194


Dengue infection has a myriad of clinical manifestations ranging from an asymptomatic course to life-threatening dengue shock syndrome. Neurological complications can be categorized into dengue encephalopathy, encephalitis, neuromuscular complications, and neuro-ophthalmic involvement.[1] Among these, the most common form of neurological involvement in dengue is usually in the form of diffuse encephalopathy caused by metabolic disturbances, hepatic or renal involvement, or hypotension.[2] Cerebrospinal fluid (CSF) analysis is usually normal in dengue encephalopathy, whereas it shows varying degrees of pleocytosis and elevated proteins in cases of dengue encephalitis. Neurotropism is a classical feature of Japanese encephalitis (JE) with classical basal ganglia and thalamic involvement on magnetic resonance imaging (MRI). In recent years, central nervous system (CNS) manifestations due to dengue have been well-recognized with evidence of viral antigens and antibodies in the CSF [3],[4] and MRI features of brain parenchymal involvement.[5],[6],[7] According to the dengue case classification published by the World Health Organization in 2009, dengue with CNS involvement has been classified as severe dengue; however, there are no standardized criteria for the diagnosis of dengue encephalitis.[8]


 » Case History Top


A 24-year-old male patient presented with complaints of fever of 7 days duration associated with loose stools and vomiting. There was associated headache for 7 days and altered sensorium for 1 day prior to presentation. The fever was intermittent and reached up to 101°F. On evaluation elsewhere, he was found to have thrombocytopenia with a platelet count of 48000 and a positive card test for dengue non-structural protein 1 (NS1) antigen. At the time of admission, the blood pressure was 110/70 mmHg, pulse rate was 92/min, temperature was 100°F, and saturation was 96% at room air. There was no pallor, icterus, or pedal edema on physical examination. Glasgow Coma Scale was E4V3M5, with the patient being disoriented but there was no neck stiffness, and bilateral plantars were withdrawal. There was bilateral sixth nerve palsy. Fundus examination did not show any papilledema. Cardiovascular and respiratory system examinations were normal. The patient was empirically started on acyclovir for probable viral encephalitis.

Investigations revealed a hemoglobin level of 15.1 gm/dL, platelet count of 41000/cu.mm and white blood cell count of 5500/cu.mm. Bilirubin was 0.8 mg/dl, SGOT 92 U/l and SGPT 82 U/L. Ultrasonography of the abdomen showed an edematous gall bladder wall with minimal ascites. Dengue IgM antibody was positive. Cerebrospinal fluid (CSF) analysis showed 20 cells which were predominantly lymphocytes with elevated protein (98 mg/dl), normal sugar, and positive JE IgM antibody. MRI brain was done [Figure 1], which showed areas of altered signal intensity in both thalami, midbrain, pons, and anterior part of medulla, which were hyperintense on T2-weighted images and fluid-attenuated inversion recovery sequence and hypointense on T1-weighted images. Diffusion weighted images showed restriction in both the thalami and pons. There were patchy areas of blooming on susceptibility weighted images in the thalami and pons, suggesting the presence of blood degradation products.
Figure 1: (a) T1-weighted image of the brain showing hypointense signal changes in bilateral thalami. (b and c) T2-weighted image showing hyperintense signal changes in thalami and pons. (d) Diffusion weighted image showing areas of diffusion restriction in both thalami

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Course and follow-up

The patient's sensorium gradually improved and he became ambulatory. His platelet count normalized. Acyclovir was stopped after CSF reports showed negative polymerase chain reaction for herpes simplex virus (HSV PCR). His Japanese encephalitis-related immunoglobulin M (JE IgM) in the blood was also positive. The patient had mild bilateral rectus palsy persisting at the time of discharge, which had improved when he came for follow-up after 2 weeks.


 » Discussion Top


This patient presented with fever, thrombocytopenia, and symptoms of central nervous system (CNS) involvement in the month of September to our hospital. At that time, there was an ongoing occurrence of dengue fever in the community. The MRI features of bilateral thalamic involvement and brain stem involvement, as in this case, have been described only in a few other cases of dengue fever.[5],[6],[7] Borawake et al., reported a case of dengue encephalitis with MRI showing the involvement of bilateral thalami, pons, and cerebellum that is similar to that seen in JE; however, the CSF dengue IgM was positive in their case.[7] In our case, the serological tests were positive for both dengue and JE but there were no other cases of JE reported from the same area. Both dengue and JE viruses are flaviviruses and share some common antigens because of which serological cross-reactivity can occur with either infection.[9],[10] In a retrospective study by Singh et al., among 1410 patients with fever, thrombocytopenia, and suspected CNS infection, 129 patients were positive for both dengue virus and JE IgM.[9] Among these, 8 patients were positive for both dengue virus and JE RNA on polymerase chain reaction (PCR), with 6 having a positivity in the serum only, and 2 having a positivity in both CSF and serum. Incidentally, they also found the highest frequency of dual positive patients being observed in the month of September. Nuegoonpipat et al., examined the cross-reactivity in IgM responses to dengue and JE viruses in serum and CSF samples from subjects suffering from dengue and JE. They found that 9% of serum samples from dengue patients were positive for anti-JE IgM, and conversely, 13% of serum samples and 11% of CSF samples from JE patients were positive for anti-dengue IgM.[11] In this case, we could not perform the JE and dengue virus PCR in the blood and CSF due to the non-availability of the test, and hence, we cannot be certain whether he had a single infection and cross-reactivity, or a true dual infection. This case highlights the overlapping and wide spectrum of manifestations of arboviral encephalitis and the inability of tests to differentiate dengue encephalitis from JE.


 » Conclusion Top


In an endemic country where both dengue and JE are prevalent, it may not be uncommon for both diseases to be present in the community at the same time. However, given the fact that both are flaviviruses and there can be serological cross-reactivity, PCR for these viruses can determine the simultaneous occurrence of these diseases in a single individual. Although the management of both these diseases at present is largely supportive, it is important to recognize that dengue virus can also involve the CNS either directly or through immune mediated mechanisms.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Carod-Artal F, Wichmann O, Farrar J, Gascón J. Neurological complications of dengue virus infection. Lancet Neurol 2013;12:906-19.  Back to cited text no. 1
    
2.
Verma R, Sahu R, Holla V. Neurological manifestations of dengue infection: A review. J Neurol Sci 2014;346:26-34.  Back to cited text no. 2
    
3.
Solomon T, Dung NM, Vaughn DW, Kneen R, Thao LT, Raengsakulrach B, et al. Neurological manifestations of dengue infection. Lancet 2000;355:1053-9.  Back to cited text no. 3
    
4.
Lum LC, Lam SK, Choy YS, George R, Harun F. Dengue encephalitis: A true entity? Am J Trop Med Hyg 1996;54:256-9.  Back to cited text no. 4
    
5.
Rao S, Kumar M, Ghosh S, Gadpayle A. A rare case of dengue encephalitis. BMJ Case Rep 2013;2013. pii:Bcr2012008229.  Back to cited text no. 5
    
6.
Kamble R, Peruvamba JN, Kovoor J, Ravishankar S, Kolar BS. Bilateral thalamic involvement in dengue infection. Neurol India 2007;55:418-9.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.
Borawake K, Prayag P, Wagh A, Dole S. Dengue encephalitis. Indian J Crit Care Med 2011;15:190-3.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.
WHO. Dengue guidelines for diagnosis, treatment, prevention and control. Geneva: World Health Organization, 2009.  Back to cited text no. 8
    
9.
Singh KP, Mishra G, Jain P, Pandey N, Nagar R, Gupta S, et al. Co-positivity of anti-dengue virus and anti-Japanese encephalitis virus IgM in endemic area: Co-infection or cross reactivity? Asian Pac J Trop Med 2014;7:124-9.  Back to cited text no. 9
    
10.
Garg R, Malhotra H, Gupta A, Kumar N, Jain A. Concurrent dengue virus and Japanese encephalitis virus infection of the brain: Is it co-infection or co-detection? Infection 2012;40:589-93.  Back to cited text no. 10
    
11.
A-Nuegoonpipat A, Panthuyosri N, Anantapreecha S, Chanama S, Sa-Ngasang A, Sawanpanyalert P, et al. Cross-reactive IgM responses in patients with dengue or Japanese encephalitis. J Clin Virol 2008;42:75-7.  Back to cited text no. 11
    


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