Scholarly article on topic 'Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and laboratory findings'

Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and laboratory findings Academic research paper on "Clinical medicine"

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{Rabies / "Rabies survivor" / "Rabies atypical manifestations" / "Rabies diagnosis"}

Abstract of research paper on Clinical medicine, author of scientific article — Sunil Karande, Mamta Muranjan, Reeta Subramaniam Mani, Ashwini Manoor Anand, Raghavendraswami Amoghimath, et al.

Summary A 6-year-old boy from India developed an atypical form of rabies following a stray dog bite and as a consequence of not receiving the standard World Health Organization recommended post-exposure prophylaxis for category III wounds. Serial rising rabies virus neutralizing antibody titres in serum and cerebrospinal fluid by rapid fluorescent focus inhibition test helped confirm the diagnosis of rabies. The child has survived for 4 months since the onset of illness, albeit with neurological sequelae.

Academic research paper on topic "Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and laboratory findings"

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International Journal of Infectious Diseases

journal homepage www.elsevier.com/locate/ijid

Case Report

Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, croSSMark and laboratory findings

Sunil Karande a, Mamta Muranjan a, Reeta Subramaniam Manib, Ashwini Manoor Anand b, Raghavendraswami Amoghimatha, Shilpa Sankhec, Ashwin Yajaman Belludib, Shampur Narayan Madhusudana b *

a Department of Paediatrics, Seth Gordhandas Sunderdas Medical College and King Edward VII Memorial Hospital, Parel, Mumbai, India b Department of Neurovirology, WHO Collaborating Centre for Reference and Research on Rabies, National Institute of Mental Health and Neurosciences, Bangalore 560029, India

c Department of Radiology, Seth Gordhandas Sunderdas Medical College and King Edward VII Memorial Hospital, Parel, Mumbai, India

ARTICLE INFO

SUMMARY

Article history:

Received 20 March 2015

Received in revised form 29 April 2015

Accepted 1 May 2015

Corresponding Editor: Eskild Petersen,

Aarhus, Denmark.

Keywords: Rabies

Rabies survivor

Rabies atypical manifestations

Rabies diagnosis

A 6-year-old boy from India developed an atypical form of rabies following a stray dog bite and as a consequence of not receiving the standard World Health Organization recommended post-exposure prophylaxis for category III wounds. Serial rising rabies virus neutralizing antibody titres in serum and cerebrospinal fluid by rapid fluorescent focus inhibition test helped confirm the diagnosis of rabies. The child has survived for 4 months since the onset of illness, albeit with neurological sequelae. © 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-

nc-nd/4.0/).

1. Introduction

Rabies is an almost invariably fatal disease that can present as the classical furious form or as paralytic rabies. The cardinal features of furious rabies, namely fluctuating consciousness, hydrophobia/aerophobia, inspiratory spasms, and signs of auto-nomic dysfunction, are seen in most patients with this form of the disease. Conversely, paralytic rabies presents as rapidly progressing lower motor neuron ascending weakness with only motor disturbance, and consciousness may be preserved right until the pre-terminal phase.1 The average interval from clinical disease onset to death has been reported to be 5.7 days in furious rabies and 11 days in paralytic rabies.2

Approximately 60 000 people die from rabies worldwide each year, with about 20 000 human deaths occurring in India alone.3,4 Many of the dog bite victims do not receive appropriate postexposure prophylaxis, and the use of rabies immunoglobulin in patients presenting with category III exposure is abysmally low (2.1%).5

* Corresponding author. Tel.: +91-80-26995129; fax: +91-80-26564830. E-mail address: mshampur@gmail.com (S.N. Madhusudana).

The rare case of a child who developed an atypical form of rabies despite receiving rabies post-exposure prophylaxis is reported herein; the patient has survived for 4 months since the onset of illness, albeit with neurological sequelae.

2. Case report

A 6-year-old boy from a village in western India was bitten by a stray dog, sustaining category III wounds on his back and the right side of his neck. His parents took him immediately to the local primary health centre where the child's wounds were washed 'briefly' with running tap water. Within the next 6 h the child had received equine rabies immunoglobulin (ERIG) at a dose of 40 IU/ kg, half of which was locally infiltrated around the neck bite site and the other half administered intramuscularly in the gluteal region. The child also simultaneously received the first dose of purified chick embryo cell (PCEC) rabies vaccine, 0.5 ml intramuscularly in the anterolateral area of the thigh muscle. He received three subsequent doses of the PCEC rabies vaccine on days 3, 7, and 14 after the bites.

Before the child could receive his fifth dose of vaccine, he developed mild to moderate fever, a bilateral frontal headache, and occasional episodes of vomiting (~22 days after the dog bite). On

http://dx.doi.org/10.1016/j.ijid.2015.05.005

1201-9712/© 2015 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

day 5 of the febrile illness, the child developed six episodes of generalized tonic convulsions and was admitted to a local private hospital. Cerebrospinal fluid (CSF) obtained by lumbar puncture revealed 82 x 106 cells/l (all lymphocytes), proteins of 20mg/dl, and sugar of 54 mg/dl. A plain computed tomography (CT) scan of the brain was done and was reported as normal. Over the next 4 days the child continued to develop convulsions and his sensorium deteriorated progressively. The child no longer recognized his parents or responded to any stimuli, and he had lost his speech and bladder control. The parents affirmed that the child had not developed any hydrophobia or aerophobia.

The parents sought treatment for their semi-comatose child from a district hospital and later from a hospital affiliated to a medical college, where a differential diagnosis of viral encephalitis or partially treated pyogenic meningitis was considered, and the child was treated with intravenous acyclovir and ceftriaxone, along with dexamethasone and mannitol as anti-cerebral oedema treatment. The convulsions were controlled with intravenous phenytoin and phenobarbitone. However the child continued to remain semi-comatose and developed involuntary movements of both the upper limbs and lips (~58 days after the dog bite).

The parents brought their child to our institution (KEM Hospital, Mumbai) in October 2014 (~68 days after the dog bite). On examination, the child's vital parameters were normal. He presented a modified Glasgow Coma Scale score of 8 (E2 M4 V2). There was flexion contracture of both ankles. His pupils were equal and reactive bilaterally. There was no hydrophobia or aerophobia. Motor system examination revealed hypertonia of all four limbs with grade 4/5 power. All the deep tendon jerks were brisk bilaterally. Ankle clonus was present bilaterally. Both plantar responses were extensor. Dystonic movements of both upper limbs and oro-mandibular dystonia were noted.

A magnetic resonance imaging (MRI) scan of the brain done on admission (Figure 1a) was reported by a trainee radiologist as suggestive of acute disseminated encephalomyelitis (ADEM). The MRI showed T2/FLA1R hyperintensities in the bilateral basal ganglia, thalami, and cerebellum, with diffuse involvement of the deep and periventricular white matter. Mild diffusion restriction was seen in the gangliocapsular region without any post contrast enhancement. There was generalized parenchymal volume loss in the form of dilatation of the ventricular system and prominence of the sulcal spaces. An MRI of the brainstem and spine was normal. CSF examination revealed 2 x 106 lymphocytes/l, proteins of 46 mg/dl, and sugar of 76 mg/dl (corresponding to blood sugar of 88 mg/dl). CSF culture was sterile and 1gM antibodies against Japanese encephalitis virus were not detected.

A diagnosis of post-PCEC vaccine ADEM was made and a standard course of intravenous methylprednisolone (30 mg/kg/ day once daily for 3 days) followed by oral prednisolone in a rapidly tapering dose was also given. Since there was no clinical improvement, standard intravenous immunoglobulin therapy (0.4 g/kg/day once daily for 5 days) was given. Supportive therapy in the form of trihexyphenidyl for the dystonia, baclofen and diazepam for the hypertonia, and sodium valproate as an anticonvulsant was started. Physiotherapy and splinting of both lower limbs for contractures was done. Nasogastric tube feeding was continued.

Since there was no clinical improvement, an MRI scan of the brain was done on day 18 after admission (Figure lb). The MRI showed an increase in the confluent FLAIR and T2 hyperintensities involving the deep paraventricular as well as subcortical white matter of both cerebrum and cerebellum. There were persistent T2 hyperintensities involving the bilateral basal ganglia, anterolateral nuclei of the thalamus, corona radiata, and internal capsule, with shrinkage of the deep grey structures. Persistent diffusion restriction was seen in the bilateral gangliocapsular region. On perfusion study, the entire white matter, deep grey matter, and cortex were hypoperfused. MRI of the brainstem and spine continued to show a stable (normal) appearance. Both the MRI scans of the brain were reviewed by an experienced radiologist and a revised radiological diagnosis of 'probable' rabies encephalitis was made. A third MRI scan of the brain done at 26 days after admission (Figure lc) showed further atrophy of the superficial as well deep grey matter, with persistent high signal in the supra- and infratentorial white matter. At this time a radiological diagnosis of rabies encephalitis was made.

Rabies virus neutralizing antibody (RVNA) was assessed by rapid fluorescent focus inhibition test (RFFIT), performed at the Neurovirology Laboratory of the World Health Organization Collaborating Centre for Reference and Research on Rabies, NIMHANS, Bangalore, using a method described previously.6 The titre on day 64 of illness was 262 144 in serum and 4096 in CSF. Repeat RVNA titres by RFFIT obtained on day 75 of illness were >262 144 (end-point not determined) in serum and 8192 in CSF. This confirmed the diagnosis of rabies encephalitis, as the presence of RVNA in the CSF is considered diagnostic of rabies regardless of immunization status.7 However, saliva, nuchal skin biopsy, and CSF samples obtained on day 75 of illness were negative for rabies viral RNA by real-time TaqMan PCR.

After a month's stay in our centre, the patient was discharged after educating the parents about caring for a semi-comatose patient and providing nasogastric tube feeding. A telephone

Figure 1. Serial axial T2 images of the patient showing worsening of hyperintensities involving the bilateral basal ganglia and periventricular and deep white matter. (a) On admission, showing T2 hyperintensity in the bilateral basal ganglia, thalami, and deep and periventricular white matter. (b) At 18 days after admission. (c) At 26 days after admission, showing subsequent progressive worsening of the lesions with increasing parenchymal volume loss in the form of dilatation of the ventricular system.

follow-up done 7 weeks after discharge, on day 128 of illness, found the child's condition to have remained unchanged.

3. Discussion

The present case did not show any typical features of either furious or paralytic rabies. Based on the initial MRI scan of the brain, a diagnosis of an extremely rare condition viz. post-PCEC vaccine ADEM was considered. However, subsequent MRI scans of the brain showed progressive grey matter changes characteristic of rabies encephalitis.8

There were serious deviations from the World Health Organization recommendations, namely (1) ERIG was not infiltrated in the wound on the back, and (2) the dose of PCEC rabies vaccine administered on days 0, 3, 7, and 14 was half the recommended dose.3

A recent article has reported that only six patients have survived rabies encephalitis that has developed after a dog bite (during the years 1976-2013).9 All six patients had received incomplete post-exposure prophylaxis treatment for rabies and none of these patients had exhibited the classical signs of furious rabies.9 Of these, three patients survived with severe neurological sequelae, as in the present case.9 Rabies viral RNA could not be demonstrated in the present case. This could be because of the presence of high levels of neutralizing antibodies in the patient. An inverse correlation between the detection of RVNA and the presence of rabies viral RNA in clinical samples has been reported.

The diagnosis of rabies in the present case was based on the history of exposure, a compatible clinical syndrome and imaging findings, and the detection of RVNA in serum and CSF in high titres incompatible with vaccination, as seen in most of the reported survivors.9

This report highlights the lack of awareness, especially in rural India, of the need for timely, adequate, and appropriate postexposure management of human cases exposed to rabies. There is a need for health authorities to focus more attention on training rural medical practitioners in prophylactic measures for this

almost invariably fatal disease, which is almost 100% preventable with appropriate post-exposure prophylaxis.

Acknowledgements

The authors wish to thank the Dean, Seth Gordhandas Sunderdas Medical College and King Edward VII Memorial Hospital, for granting permission to publish this case report. We also thank the patient's father for giving us written informed consent to publish details of his child's clinical illness for the larger benefit of mankind, so that no person bitten by a rabid dog in the future develops this preventable illness.

Ethics approval: Not required.

Conflict of interest: The authors report no conflict of interest. References

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2. Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, Laothamatas J. Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurol 2013;12:498-513.

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9. de Souza A, Madhusudana SN. Survival from rabies encephalitis. J Neurol Sci 2014;339:8-14.