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  In this Article
 »  Abstract
 »  Introduction
 »  Neurological Com...
 »  Pathogenesis
 »  Encephalitis
 »  Encephalopathy
 »  Stroke Syndromes
 »  Myositis
 »  Myelitis
 »  Acute Disseminat...
 »  Hypokalemic Para...
 »  Guillain-Barr...
 »  References

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TOPIC OF THE ISSUE: REVIEW ARTICLE
Year : 2010  |  Volume : 58  |  Issue : 4  |  Page : 581-584

Neurological complications of dengue infection


Department of Neurology, the Institute of Neurological Sciences, CARE Hospital, Hyderabad, India

Date of Acceptance11-Aug-2010
Date of Web Publication24-Aug-2010

Correspondence Address:
J. M. K. Murthy
Chief of Neurology, The Institute of Neurological Sciences, CARE Hospital, Hyderabad
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.68654

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 » Abstract 

Dengue infection is endemic in more than 100 countries, mostly in the developing world. Recent observations indicate that the clinical profile of dengue is changing, and that neurological manifestations are being reported more frequently. The exact incidence of various neurological complications is uncertain. The pathogenesis of neurological manifestations is multiple and includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. In countries endemic to dengue, it will be prudent to investigate for dengue infection in patients with fever and acute neurological manifestations. There is need for understanding of the pathogenesis of various neurological manifestations.


Keywords: Dengue infections, encephalitis, encephalopathy, myositis, myelitis, Guillain-Barre syndrome


How to cite this article:
Murthy J. Neurological complications of dengue infection. Neurol India 2010;58:581-4

How to cite this URL:
Murthy J. Neurological complications of dengue infection. Neurol India [serial online] 2010 [cited 2019 Jul 18];58:581-4. Available from: http://www.neurologyindia.com/text.asp?2010/58/4/581/68654



 » Introduction Top


Dengue is caused by 4 distinct viruses (type 1 to 4) that are closely related antigenically. Humans are the main amplifying host of the virus. Recent observations indicate that the clinical profile of dengue is changing, and that neurological manifestations are being reported more frequently. The exact incidence of various neurological complications is uncertain. The reported incidence of encephalopathy and encephalitis, the most common neurological complications of dengue, has been found to vary between 0.5% [1] and 6.2%. [2]


 » Neurological Complications Top


From the pathogenesis point of view, the neurological manifestations of dengue infection can be grouped into 3 categories: (I) related to neurotrophic effect of the virus: encephalitis, [3],[4],[5],[6],[7],[8],[9],[10] meningitis, [11],[12] myositis, [13],[14],[15] rhabdomyolysis [16],[17],[18],[19] and myelitis [20],[21],[22],[23] ; (II) related to the systemic complications of dengue infection: encephalopathy, [1],[9],[10],[24],[25] stroke (both hemorrhagic and ischemic), [26],[27],[28],[29] hypokalemic paralysis [30],[31] and papilledema [32] ; and (III) post-infection: acute disseminated encephalomyelitis (ADEM), [33],[34],[35],[36],[37] encephalomyelitis, [38] myelitis, [39],[40] neuromyelitis optica, [41] optic neuritis, [42] Guillain-Barré syndrome, [43],[44],[45],[46],[47],[48],[49] probable Miller-Fisher syndrome, [50] phrenic neuropathy, [51],[52] long thoracic neuropathy, [53] oculomotor palsy, [54] maculopathy [55] and fatigue syndrome. [56]


 » Pathogenesis Top


The pathogenesis of neurological complications and the contribution of viral and host factors are not well understood and can be related to neurotrophic effect of the virus, systemic effects of the infection and can be immune mediated.


 » Encephalitis Top


Recent observations suggest that dengue encephalitis is due to direct central nervous system (CNS) infection. An autopsy study of a child with dengue encephalitis has shown histological evidence of encephalitis. [57] Dengue virus (type 2 and 3) was isolated in the cerebrospinal fluid (CSF) of patients with dengue encephalitis. [4] Dengue antigen has been detected in the brain. [5],[7],[58] Dengue virus (type 4) has been detected by immunohistochemistry and by reverse transcription polymerase chain reaction (RT-PCR) in the inferior olivery nucleus and granular layer of cerebellum. Immunoreactivity was observed in neurons, microglia and endothelial cells. [6] Animal studies have shown that the virus is known to release cytokines that could breach the blood-brain barrier, thus being capable of CNS invasion. [59]


 » Encephalopathy Top


Encephalopathy is the most common neurological manifestation of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), and the pathophysiology is multi-factorial and includes cerebral edema, cerebral hemorrhage, hyponatremia, hepatic failure, renal failure and cerebral hypoxia. [1],[9],[10],[24],[25] Pathological studies in fatal cases of dengue showed nonspecific lesions, edema, vascular congestion, focal hemorrhages. [60],[61] In patients with dengue encephalopathy, magnetic resonance imaging (MRI) brain abnormalities included edema and scattered focal lesions, hemorrhage and cerebral edema. [1]


 » Stroke Syndromes Top


Bleeding diathesis caused by vasculopathy, thrombocytopenia and platelet dysfunction can explain the intracranial hemorrhagic complications in dengue infection. Thrombocytopenia is both from decreased production and increased destruction. [62],[63] The degree of thrombocytopenia correlates with the clinical severity of DHF and also with the activation of complement system. Thus, impairment of platelet function can increase the risk of vascular fragility leading to hemorrhage. [62] Dengue-associated coagulopathy and vasculopathy can result in vascular thrombosis and ischemic stroke. [63],[64],[65] In addition, patients with dengue have high plasminogen activator inhibitor type I (PAI-I) plasma concentration, which is a procoagulant. [65]


 » Myositis Top


Direct invasion of skeletal muscle by the dengue virus has not been demonstrated. Muscle biopsy studies have revealed a range of findings - from mild lymphocytic infiltrate to foci of severe myonecrosis. [66] Myotoxic cytokines, particularly tumor necrosis factor (TNF), have been incriminated in the pathogenesis of myositis. However, recently Salgado et al.[67] have demonstrated infection of heart tissues in vivo; and of striated muscle, in vitro. Immunofluorescence confocal microscopy showed that myotubes were infected by dengue virus and had increased expression of the inflammatory genes and protein IP-10.


 » Myelitis Top


In some of the reported cases, myelitis is probably caused by direct viral invasion. In the case reported by Kunishige et al.,[21] MRI abnormalities were limited to the gray matter of the spinal cord, preferentially to the anterior horn, similar to poliomyelitis; and CSF was positive for anti-dengue virus antibodies for dengue virus type 1. In the patient described by Leao et al., dengue virus type 2 was isolated from the blood; and the CSF showed mononuclear cell response with a slight increase of protein, and MRI was negative. [20] Intrathecal synthesis of dengue IgG antibodies in patients with myelitis may be associated with the pathogenesis of the disease, indicating viral neurotropism. [23] Post-infectious myelitis, [39],[40] and neuromyelitis optica [41] have possible autoimmune basis, like in ADEM. [68]


 » Acute Disseminated Encephalomyelitis Top


ADEM following dengue infection is extremely rare; and in this issue, Sundaram et al.[37] have documented an autopsy-confirmed case of ADEM. This patient had hemorrhagic foci in the demyelinating lesions, probably related to the thrombocytopenia the patient had. Similar were the observations on the MRI in the patient reported by Gera and George. [36] These observations suggest that demyelinating lesions with foci of hemorrhage on MRI are probably pathgnomonic of ADEM following dengue infection. The existing evidence suggests that post-infectious and postvaccinial ADEM results from a transient autoimmune response towards myelin or other self-antigens, possibly via molecular mimicry or by nonspecific activation of auto-reactive T-cell clones. [68]


 » Guillain-Barré Syndrome and Mononeuropathies Top


Several cases of Guillain-Barré syndrome following dengue infection have been reported. The proposed mechanism for Guillain-Barré syndrome (GBS) is that an antecedent infection - in this case, dengue infection - evokes an immune response, which in turn cross-reacts with peripheral nerve components because of the sharing of cross-reactive epitopes (molecular mimicry). This immune response can be directed towards the myelin or the axon of peripheral nerve. [69] Similar may be the immuno-pathogenesis for mononeuropathy described following dengue infection.


 » Hypokalemic Paralysis Top


The exact mechanism for hypokalemic paralysis in dengue infection is not known. Viral infections can precipitate hypokalemic paralysis. [30] Jha and Ansari [31] have discussed the possible mechanisms for hypokalemia in dengue infection and suggested that hypokalemia could be either due to redistribution of potassium in cells or transient renal tubular abnormalities leading to increased urinary potassium wasting.

In conclusion, in countries endemic to dengue, it will be prudent to investigate for dengue infection in patients with various above-mentioned neurological manifestations. There is also need to understand the pathogenesis of various neurological manifestations.

 
 » References Top

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15 Post-dengue parkinsonism
Azmin, S. and Sahathevan, R. and Suehazlyn, Z. and Law, Z.K. and Rabani, R. and Nafisah, W.Y. and Tan, H.J. and Norlinah, M.I.
BMC Infectious Diseases. 2013; 13(1)
[Pubmed]
16 Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis
Nguyen Tien Huy,Tran Van Giang,Dinh Ha Duy Thuy,Mihoko Kikuchi,Tran Tinh Hien,Javier Zamora,Kenji Hirayama,Scott B. Halstead
PLoS Neglected Tropical Diseases. 2013; 7(9): e2412
[Pubmed] | [DOI]
17 Lateral rectus palsy in a case of dengue fever
Avinash Mishra,Siddharth Shukla,Somesh Aggarwal,B. Chaudhary
Medical Journal Armed Forces India. 2013;
[Pubmed] | [DOI]
18 Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
Ma Isabel Salazar,Marissa Pérez-García,Marisol Terreros-Tinoco,María Eugenia Castro-Mussot,Jaime Diegopérez-Ramírez,Alma Griselda Ramírez-Reyes,Penélope Aguilera,Leticia Cedillo-Barrón,María Martha García-Flores
The Scientific World Journal. 2013; 2013: 1
[Pubmed] | [DOI]
19 Post-dengue parkinsonism
Shahrul Azmin,Ramesh Sahathevan,Zainudin Suehazlyn,Zhe Kang Law,Remli Rabani,Wan Yahya Nafisah,Hui Jan Tan,Mohamed Ibrahim Norlinah
BMC Infectious Diseases. 2013; 13(1): 179
[Pubmed] | [DOI]
20 Acute disseminated encephalomyelitis associated with dengue infection: A case report with literature review
Meena Gupta,Rajeev Nayak,Geeta A. Khwaja,Debashish Chowdhury
Journal of the Neurological Sciences. 2013;
[Pubmed] | [DOI]
21 Secondary Mania as a Possible Neuropsychiatric Complication of Dengue Fever
J. Harder,S. Sharma,D. Gitlin
Psychosomatics. 2013;
[Pubmed] | [DOI]
22 Paralytic squint due to abducens nerve palsy : a rare consequence of dengue fever
Mitrakrishnan C Shivanthan,Eranda C Ratnayake,Bandula C Wijesiriwardena,Kalum C Somaratna,Lakmal KGK Gamagedara
BMC Infectious Diseases. 2012; 12(1): 156
[Pubmed] | [DOI]
23 In vivo infection by a neuroinvasive neurovirulent dengue virus
Myriam Lucia Velandia-Romero,Orlando Acosta-Losada,Jaime E. Castellanos
Journal of NeuroVirology. 2012; 18(5): 374
[Pubmed] | [DOI]
24 Neuroinvasive flavivirus infections
Gregorius J. Sips,Jan Wilschut,Jolanda M. Smit
Reviews in Medical Virology. 2012; 22(2): 69
[Pubmed] | [DOI]
25 Dengue: A new challenge
Puccioni-Sohler, M. and Orsini, M. and Soares, C.N.
Neurology International. 2012; 4(3): 65-70
[Pubmed]
26 In vivo infection by a neuroinvasive neurovirulent dengue virus
Velandia-Romero, M.L. and Acosta-Losada, O. and Castellanos, J.E.
Journal of NeuroVirology. 2012; 18(5): 374-387
[Pubmed]
27 Paralytic squint due to abducens nerve palsy : a rare consequence of dengue fever
Shivanthan, M.C. and Ratnayake, E.C. and Wijesiriwardena, B.C. and Somaratna, K.C. and Gamagedara, L.K.G.K.
BMC Infectious Diseases. 2012; 12(156)
[Pubmed]
28 Changing clinical profile of Dengue infection: A newer perspective in the pediatric population
Mukherjee, S. and Mitra, S. and Samanta, M. and Roy, P. and Sarkar, M. and Chatterjee, S.
Journal of Pediatric Infectious Diseases. 2012; 7(1): 1-7
[Pubmed]
29 Clinical profile of dengue infection at a teaching hospital in North India
Karoli, R. and Fatima, J. and Siddiqi, Z. and Kazmi, K.I. and Sultania, A.R.
Journal of Infection in Developing Countries. 2012; 6(7): 551-554
[Pubmed]
30 Dengue encephalitis in children
Arora, S.K. and Aggarwal, A. and Mittal, H.
Journal of Neurosciences in Rural Practice. 2012; 3(2): 228-229
[Pubmed]
31 Neuroinvasive flavivirus infections
Sips, G.J. and Wilschut, J. and Smit, J.M.
Reviews in Medical Virology. 2012; 22(2): 69-87
[Pubmed]
32 A fatal combo of dengue shock syndrome with acute subdural hematoma
Jain, N. and Gutch, M. and Kumar, V. and Naik, A.K.
Neurology India. 2012; 60(1): 105-106
[Pubmed]
33 Dengue encephalitis associated with hydrocephalus: A case report
Kamble, R.B. and Venkataramana, N.K. and Raghunath, C.N.
Neuroradiology Journal. 2011; 24(6): 833-837
[Pubmed]
34 Profile of dengue patients admitted to a tertiary care hospital in Mumbai
Joshi, R. and Baid, V.
Turkish Journal of Pediatrics. 2011; 53(6): 626-631
[Pubmed]
35 Neurological complications of dengue fever: Experience from a tertiary center of north India
Verma, R. and Sharma, P. and Garg, R.K. and Atam, V. and Singh, M.K. and Mehrotra, H.S.
Annals of Indian Academy of Neurology. 2011; 14(4): 272-278
[Pubmed]
36 Neuralgic amyotrophy associated with dengue fever: Case series of three patients
Verma, R. and Sharma, P. and Khurana, N. and Sharma, L.N.
Journal of Postgraduate Medicine. 2011; 57(4): 329-331
[Pubmed]
37 Spectrum of acute dengue virus myositis
Garg, R.K., Paliwal, V.K.
Journal of the Neurological Sciences. 2011; 307(1-2): 180-181
[Pubmed]
38 Hypokalaemic quadriparesis: An unusual manifestation of dengue fever
Gupta, D.K., Vaish, A.K., Arya, R.K., Chaudhary, S.C.
BMJ Case Reports. 2011;
[Pubmed]
39 Spectrum of acute dengue virus myositis
Ravindra Kumar Garg,Vimal Kumar Paliwal
Journal of the Neurological Sciences. 2011; 307(1-2): 180
[Pubmed] | [DOI]
40 Epilepsia partialis continua as a manifestation of dengue encephalitis
Rajesh Verma,Aravinthan Varatharaj
Epilepsy & Behavior. 2011; 20(2): 395
[Pubmed] | [DOI]
41 Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré Syndrome) following dengue fever | [Polirradiculoneuropatia desmielinizante inflamatória aguda (síndrome de Guillain-Barré) após dengue]
Gonçalves, E.
Revista do Instituto de Medicina Tropical de Sao Paulo. 2011; 53(4): 223-225
[Pubmed]
42 Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) following dengue fever
Eduardo Gonçalves
Revista do Instituto de Medicina Tropical de São Paulo. 2011; 53(4): 223
[Pubmed] | [DOI]
43 Dengue Encephalitis Associated with Hydrocephalus
R.B. Kamble,N.K. Venkataramana,C.N. Raghunath
The Neuroradiology Journal. 2011; 24(6): 833
[Pubmed] | [DOI]
44 Epilepsia partialis continua as a manifestation of dengue encephalitis
Verma, R., Varatharaj, A.
Epilepsy and Behavior. 2011; 20(2): 395-397
[Pubmed]
45 Paraplegia in a patient with dengue
Singh, P., Joseph, B.
Neurology India. 2010; 58(6): 962-963
[Pubmed]



 

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Online since 20th March '04
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