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|Year : 2020 | Volume
| Issue : 3 | Page : 673-676
Enigma of Rabies: Prolonged Survival in a Boy with Rabies Brachial Plexitis and Encephalomyelitis
Kanika Goyal1, Chandana Bhagwat1, Renu Suthar1, Arushi Gahlot Saini1, Namita Ravikumar1, Paramjeet Singh2, Reeta S Mani3, Meenu Singh1
1 Department of Pediatrics, PGIMER, Chandigarh, India
2 Department of Radiodiagnosis, PGIMER, Chandigarh, India
3 Department of Neurovirology, NIMHANS, Bengaluru, Karnataka, India
|Date of Web Publication||6-Jul-2020|
Dr. Meenu Singh
Department of Pediatrics, PGIMER, Chandigarh
Source of Support: None, Conflict of Interest: None
Rabies encephalitis is a universally fatal disease. Prolonged survival in children with rabies encephalitis has only been anecdotally reported. Case report: An 11-year-old boy presented with right-handed paraesthesia followed by flaccid weakness, progressive quadriparesis and encephalopathy following an unprovoked, class III dog bite over the right wrist 1 month previously. He received five doses of the rabies vaccine as post exposure prophylaxis. Diagnosis of rabies encephalitis was supported by typical MRI brain and spine findings in addition to marked elevation of anti-rabies neutralizing antibody titers in serum and CSF. He was treated with supportive care, methylprednisolone, dexamethasone and simvastatin and was discharged after 6 weeks of hospital stay in a minimally conscious state, with tracheostomy and naso-gastric feeding tubes. At 9 months follow-up, his neurological status showed minimal improvement. Paralytic rabies with brachial plexitis and encephalomyelitis is an atypical presentation of rabies. Very few surviving cases have been reported from India. Survival from rabies is possible with effective clearing of virus with post exposure prophylaxis, but with severe neurological sequelae.
Keywords: Brachial plexitis, encephalitis, intravenous immunoglobulins, rabies survivor, rabies, simvastatin
Key Messages: Paralytic rabies with brachial plexitis and encephalomyelitis is a rare presentation. Few rabies survivors have been reported from around the world. Survival from rabies encephalitis is possible with prompt post exposure prophylaxis and good supportive care.
|How to cite this article:|
Goyal K, Bhagwat C, Suthar R, Saini AG, Ravikumar N, Singh P, Mani RS, Singh M. Enigma of Rabies: Prolonged Survival in a Boy with Rabies Brachial Plexitis and Encephalomyelitis. Neurol India 2020;68:673-6
|How to cite this URL:|
Goyal K, Bhagwat C, Suthar R, Saini AG, Ravikumar N, Singh P, Mani RS, Singh M. Enigma of Rabies: Prolonged Survival in a Boy with Rabies Brachial Plexitis and Encephalomyelitis. Neurol India [serial online] 2020 [cited 2020 Sep 25];68:673-6. Available from: http://www.neurologyindia.com/text.asp?2020/68/3/673/288993
Rabies is rapidly progressive, universally fatal, acute encephalomyelitis caused by rabies virus, a bullet shaped, negative sense, single stranded, enveloped, RNA virus from the family viridae (genus Lyssaviridae). Dogs are the most important reservoirs and account for >99% cases of human rabies in India. Typically, human rabies presents in furious furious (encephalitic) or paralytic forms, however, atypical presentations are also reported. Human rabies has been eliminated from developed countries, however in southeast Asia, rabies continues to be an important, but neglected cause of mortality. India contributes to one-third of the 60,000 deaths due to human rabies reported yearly around the globe. In India, 15 million people are annually bitten by dogs, for which they receive post are bitten by dogs, and receive post-exposure prophylaxis (PEP). Very few surviving cases of rabies have been documented world-wide. We report a surviving case of paralytic rabies with brachial plexitis and encephalomyelitis.
| » Case Report|| |
An 11-year-old boy presented to pediatric emergency with an abnormal tingling sensation in the right hand, followed by weakness of the right arm for for a 5-day duration. He had grade 3 dog over his right hand, one month previously for which he had received local wound care and five doses of intra-dermal purified chick embryo cell rabies vaccine as PEP. He did not receive rabies immunoglobulin (RIG). He remained well for 1 month in between, then he developed right upper limb paraesthesia, weakness, followed by involvement of left upper limb, and both lower limbs over the next week after his initial presentation. On examination, he was encephalopathic, with Glasgow Coma Score of 6 and with sluggishly reacting pupils. His right upper limb showed flaccid weakness; he was quadriplegic with rigidity and intermittent dystonia. He had autonomic dysfunction with bradycardia and hypertension. MRI spine with brachial plexus [Figure 1] showed presence of brachial plexitis, longitudinal extensive myelitis involving cervical spine and MRI brain showed bilateral basal ganglia, pons and hippocampal hyperintensities. Lumbar cerebrospinal fluid (CSF) examination showed 61 cells (lymphocytes 90%), protein 78 mg/dl, sugar 92 mg/dl, and CSF culture was sterile. Samples were tested at the Neurovirology laboratory, NIMHANS, Bangalore; real time PCR for detection of viral RNA in CSF was negative, paired serum samples showed rising titers of rabies neutralizing antibodies over 3 weeks, and CSF showed an antibody titer of 1:2048 by rapid fluorescent focus inhibition test (RFFIT), suggestive of rabies encephalitis. Rabies neutralizing antibody titer in CSF and serum are presented in [Table 1].
|Figure 1: MRI brain at first week of the disease: axial T2-FLAIR MRI images (a-c) of brain showing hyperintensities in the bilateral caudate, putamen, and thalamus, basal ganglia, midbrain, hypothalamus and bilateral hippocampus. T2 sagittal MRI spine (d) showing swollen cord with T2 hyperintensities in the cervical spine|
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He required intubation, mechanical ventilation, antihypertensives and antibiotics for health care associated infection. At his third week of hospital stay he was tracheostomized for upper airway protection. Barrier nursing was done by isolating the patient, and he received intravenous ceftriaxone, meropenem, methylprednisolone and intravenous immunoglobulins at 400 mg/kg/day for 5 days. High dose dexamethosone (@4 mg/kg/day) was given for 1 week duration followed by slow tapering. CSF analysis for autoantibodies (NMDA, AMPA1, AMPA2, CASPER, LG1, GABA receptor B1, B2) was negative. Anti-MOG (Myelin Oligodendrocyte Glycoprotein) antibody was not tested. He also received high dose vitamins, and 80 mg Simvastatin per day with expert advice. He remained admitted for 6 weeks duration. He was discharged in a minimal conscious state, with dystonia, rigidity, quadriparesis, with tracheostomy, nasogastric tube in situ, high dose multivitamins, clonidine and simvastatin. He remained on regular follow-up, with 3 monthly visits. Repeat MRI after 4 months follow-up showed extensive cystic necrotic changes in the bilateral basal ganglia, and atrophy of thalamus, hippocampus and cerebral cortex [Figure 2]. During his recent follow-up (12 months post-onset of illness), his neurological status showed minimal improvement with response to sound, pain, touch with persistent rigidity and dystonic quadriplegic state.
|Figure 2: Follow-up MRI Brain at 4 months of the illness: Axial T2 weighted MRI images (a and b) showing marked atrophy of cerebrum, caudate heads, sclerotic and cystic changes in the bilateral putamen and thalamus, and periventricular white matter hyperintensities with gliotic changes|
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| » Discussion|| |
Rabies encephalitis is an inevitably fatal disease with only few surviving cases reported till date. Rabies is a neglected pediatric disease, as 40–50% of the cases are <15 years of age., Smaller size, frequent interaction with dogs and bites on extremities, head and neck predispose to a shorter incubation period and fatal outcome.
De Souza et al. compiled 12 cases of rabies survivors from all over world in 2014, including two cases from India. Subsequently few individual cases have been reported.,,,,, Mani et al. in 2019 reported eight more cases of rabies survivors from different parts of India. In the last 6 years, a total 14 rabies survivors have been reported in India, something that was unheard before 2010. Details of these 15 cases including ours are summarized in [Table 1]. All these surviving rabies cases from India had WHO grade 3 dog bite, 86% were children, lacked typical features of hydrophobia and aerophobia, five (33%) treated with RIG and 14 (93%) received PEP. High titers neutralizing antibodies were present in serum and CSF in all these cases. Delayed and incomplete PEP, lack of RIG and inappropriate or injection technique may have contributed to PEP failure in these cases.
The index patient had paralytic rabies with initial local symptoms of pain, tingling and numbness followed by flaccid paralysis of the arm and subsequent progression to rabies encephalomyelitis in 7 days. Diagnosis was clinical, supported by MRI brain and spine findings, progressively rising titers of rabies neutralizing antibodies in serum and high CSF neutralizing antibody titers. An inverse correlation has been noted between the rabies neutralizing antibodies and the of rabies virus RNA in the CSF, which can possibly explain the negative CSF real time PCR results. Rabies vaccine also produces rabies neutralizing antibodies in the serum, however paired sera demonstrating four-fold or higher rise in titres and presence of CSF antibodies are considered diagnostic in patients who have received rabies vaccination.
Management of rabies encephalomyelitis is conservative, with neurological, respiratory support and barrier nursing. The initial success of intravenous ribavarin, ketamine and interferon (Milwaukee regimen) could not be replicated in subsequent cases. Corticosteroid and immunoglobulin have been used variably in all rabies survivors to reduce the inflammation or for suspicion of acute disseminated encephalomyelitis. Although the Milwaukee regimen was not successful in subsequent cases, it has sensitized the clinicians for a possibility of surviving this deadly virus. Subsequently after year 2005 only, surviving cases have been reported due to improved awareness among clinicians and advancement in supportive care. Most of the survivors had received antirabies vaccination on the same day of bite, prior to development of symptoms and had early presence of neutralizing antibodies in serum and CSF, possibly had some role in viral clearance. Only one third survivors have received rabies immunoglobulins (RIG). Lack of RIG administration can be associated with PEP failure in some cases. However, most of these survivors have been left with severe neurological sequelae. The extensive injury to the white matter and deep gray matter nuclei of the brain could be mediated through direct neurotropism or immune dysregulation. The index patient was treated with methylprednisolone, intravenous immunoglobulin and high dose dexamethasone during acute phase. We also investigated for autoimmune antibodies for their potential role in pathogenesis. However, among the known antibodies, none were positive, suggesting the role of unknown antibodies or cell mediated toxicity in pathogenesis. Simvastatin is a known drug for anti-inflammatory action and has some role in re-myelination previously being used in patients with multiple sclerosis.
Follow-up MRI at 4 months showed marked cortical atrophy and cystic necrotic changes in bilateral basal ganglia. All rabies survivors from India had severe neurological sequelae, and mostly remained in vegetative or minimal conscious state., Only five cases of rabies have been reported with near complete recovery and two cases with mild neurological sequelae.
To conclude, there is an increasing number of rabies survivors are being reported from India in recent years. The lack of adequate antirabies vaccination and RIG contributes to PEP failure. Prompt PEP and early appearance of rabies neutralizing antibodies has a role in clearing the deadly virus from the brain tissue. Aggressive immuno-modulation could have a role in improving the quality of survival in these patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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