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ORIGINAL ARTICLE
Year : 2009  |  Volume : 57  |  Issue : 2  |  Page : 177--180

Neurological complications of Chikungunya virus infection

Nitin H Chandak1, Rajpal S Kashyap1, Dinesh Kabra1, Poornima Karandikar1, Sonali S Saha1, Shweta H Morey1, Hemant J Purohit2, Girdhar M Taori1, Hatim F Daginawala1,  
1 Biochemistry Research Laboratory, Central India Institute of Medical Sciences, Nagpur - 440 010, India
2 Environmental Genomic Unit, National Environmental Engineering Research, Institute, Nehru Marg, Nagpur - 440 020, India

Correspondence Address:
Hatim F Daginawala
Biochemistry Research Laboratory, Central India Institute of Medical sciences, 88/2, Bajaj Nagar, Nagpur - 440 010
India

Abstract

Background: In May 2006, there was a large Chikungunya virus infection (CHIKV) outbreak in the Nagpur district of Maharashtra, a province in western India. Usually, CHIKV is a self-limiting febrile illness. However, neurological complications have been described infrequently. Aim: To study the clinical characteristics of various neurological complications associated with CHIKV infections. Materials and Methods: Patients with neurological complications following CHIKV infection during the outbreak were the subjects of the study. On the basis of clinical features and investigative findings, patients were grouped into various neurological syndromes: Encephalitis, myelopathy, peripheral neuropathy, myeloneuropathy, and myopathy. Cerebrospinal fluid (CSF) samples were also collected for biochemical and serological studies. Results: Of the 300 patients with CHIKV infection seen during the study period, June-December 2006, 49 (16.3%) [M : F: 42:7] had neurological complications. The neurological complications included: Encephalitis (27, 55%), myelopathy (7, 14% ), peripheral neuropathy (7, 14%), myeloneuropathy (7, 14%), and myopathy (1, 2%). Reverse Transcriptase polymerase chain reaction (RT-PCR) and real-time PCR was positive in the CSF in 16% and 18%, respectively. Conclusion: Recent CHIKV infection was associated with various neurological complications, suggesting neurotropic nature of the virus. The outcome of the neurological complications is likely to be good.



How to cite this article:
Chandak NH, Kashyap RS, Kabra D, Karandikar P, Saha SS, Morey SH, Purohit HJ, Taori GM, Daginawala HF. Neurological complications of Chikungunya virus infection.Neurol India 2009;57:177-180


How to cite this URL:
Chandak NH, Kashyap RS, Kabra D, Karandikar P, Saha SS, Morey SH, Purohit HJ, Taori GM, Daginawala HF. Neurological complications of Chikungunya virus infection. Neurol India [serial online] 2009 [cited 2019 Mar 20 ];57:177-180
Available from: http://www.neurologyindia.com/text.asp?2009/57/2/177/51289


Full Text

 Introduction



Chikungunya is a relatively rare and benign form of viral infection caused by a RNA-virus belonging to genus Alphavirus of Togaviridae family and is transmitted from primates to humans by Aedes aegypti mosquito. The first outbreak of Chikungunya virus infection (CHIKV) occurred in East Africa (Tanzania and Uganda) in 1952 and 1953. [1] In 1999, an outbreak occured in Port Klang in Malaysia. [2] Subsequent epidemics have been reported from Austral Africa (Zimbabwe and South Africa), West Africa (Senegal and Nigeria), Central Africa (Central African Republic, and Democratic Republic of the Congo), [3],[4],[5] Southeast Asia (Philippines, Malaysia, Cambodia), and the Indian subcontinent (Pakistan and southern India). The first documented Asian outbreak was in 1958. In India, the first outbreak was reported in 1963 in Calcutta [6] Subsequent epidemics have been reported from other parts of India, Kolkata, Vellore, Barsi, and Nagpur. [7],[8],[9],[10] The recent epidemic started in December 2005, [6] affecting a large population in southern and central India (Tamil Nadu, Karnataka, Kerala, Andhra Pradesh, Maharashtra). Over 2,000 cases of CHIKV fever were reported from Malegaon town in Nasik district of Maharashtra between February and March 2006. [11] In May 2006, a large outbreak occurred in Nagpur district of Maharashtra.

Neurological complications of CHIKV infection are infrequent and have been reported only recently. [12] In the present study our experience of neurological complications in CHIKV infection in the recent epidemic in Nagpur district of Maharastra is reported.

 Materials and Methods



Three hundred patients of clinically suspected CHIKV infections were enrolled for the study from July-December 2006 and followed up for any neurological complications until April 2007 at the Central India Institute of Medical Sciences (CIIMS), Nagpur, India. All of the patients had typical clinical features of CHIKV infection fever, headache, body ache, myalgia, and joint pains with or without swelling and without hemorrhagic rash. The study had the approval of Institutional Ethics Committee, CIIMS, Nagpur.

Forty-nine patients who developed neurological symptoms within two months of CHIKV infections were hospitalized. All had detailed neurological evaluation and blood investigations, Depending on the neurological syndrome, patients were further investigated: CSF analysis, electrodiagnostic tests, electroencephalography (EEG), evoked potential studies, and neuroimaging, computerized tomograpy (CT) and/or magnetic resonance imaging (MRI). Molecular tests Reverse Transcriptase polymerase chain reaction, [RT-PCR], real-time PCR) and virus isolation were done in patients for whom CSF study was done.

On the basis of clinical features and investigation findings patients were grouped into various neurological syndromes: Encephalitis, myelopathy, peripheral neuropathy, myeloneuropathy, and myopathy. Patients with entrapment neuropathy were not included in the study. Patients were given supportive care as per the clinical syndrome and the course of the illness. Some received a course of methylprednisolone 1g daily for 3-5 days.

 Results



Of the 300 patients with CHIKV infection seen during this epidemic, 49 (16.3%) patients developed neurological complications There were 42 males and 7 females and the age was above 20 years in all except one. The neurological syndromes observed include: Encephalitis (27, 55.1%), myelopathy (7, 14.3%), neuropathy (7, 14.3%), myeloneuropathy (7, 14.3%), and myopathy (1, 2%) [Table 1]. Majority of the patients developed neurological complications within 20 days of onset of CHIKV infection. RT-PCR and real-time PCR was positive in eight (16%) and nine (18%) cases, respectively. However, positivity for virus isolation was only noted in one case. Of the 27 patients with encephalitis, 16(59%) presented with abnormal behavior and 6 (22%) each with impaired level of consciousness and extrapyramidal features [Table 2]. EEG was done on all patients of the encephalitic group. It did not reveal any specific information except generalized intermittent slow wave dysrhythmia. Of the 14 patients with myelopathy and myeloneuropathy, only in 3 signal alterations on MRI suggestive of demyelination were seen in the cord [Table 3]. In the 14 patients who had electrodiagnostic studies, all had demyelinating neuropathy. CT brain was done in 20 patients with encephalitis and was essentially normal in all the patients. Of the 4 patients who had MRI brain, one had white matter signal changes.

CSF analysis was done in 38 patients [Table 4], Of the 20 patients with encephalitis, proteins were raised in 14, sugar was low in 3, and cells were increased in 6. Of the six patients with myelopathy, proteins were raised in two. Of the six patients with neuropathy group, five had raised proteins. Of the six patients with myeloneuropathy, five had raised proteins and two had reduced sugar.

The outcomes were good. Of the 49 patients, there were three deaths, two with encephalitis and one with myeloneuropathy and 37 (75.5%) patients had good outcome [Table 1]. Of the patients 49 patients, 34 (69.4%) were given corticosteroid treatment and the remaining 15 patients were given supportive treatment. Of the 34 patients given corticosteroids, 25 (73.5%) improved whereas of the patients receiving only supportive treatment, 12 (80%) patients improved.

 Discussion



This study is probably the first report of large series of neurological complications following CHIKV infection from India.Neurological complications were seen in 16.3% of 300 patients with CHIKV infection registered in our institute during the 2006 epidemic. This high frequency of neurological complications may be related to referral bias. Our institute is the primary referral center for neurological diseases from Vidarbha, part of Maharastra and adjoining parts of Madhya Pradesh Chhatisgarh, and Andhra Pradesh.

Most often, CHIKV infection is a self-limiting illness. Neurological complications are infrequent and have been reported during the first Indian outbreak as well as during the recent French Reunion islands outbreak. [13] It remains uncertain whether neurological symptoms are due to persistence of the virus or inappropriate immune response. [14],[15] The severity of the disease in the 2006 outbreak, in particular the associated neurological complications may be related to the mutated CHIK. [16] In our series 46.5% of patients with neurological complications were above 60 years of age. The time interval between CHIKV infection and neurological complication was quite variable. 47% presented within one week and 6% after one month. Of the neurological complications, encephalitis was the common presenting syndrome in 55% of patients. In our series the neuropathy was predominantly demyelinating type. Only in 3 of the 14 patients with myelopathy/myeloneuropathy, MRI showed signal changes in the spinal cord suggestive of demyelinating pathology. Similar signal changes were also seen the study by Wadia. [12] Most of the patients (75, 5%) showed good neurological recovery at 3 months of follow-up and 9 patients had no much improvement in the neurological deficits. There was no difference in the outcomes between patients treated conservatively and patients treated with steroids. There were 3 (6%) deaths and all the deaths were attributable to the medical complications. Our study suggests that the outcome of the neurological complications following CHIKV infections are likely to be good and the mortality is more related to the systemic complications.

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