American Journal of Emergency Medicine 33 (2015) 601.e1–601.e3
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case report
Paralytic rabies or postvaccination myelitis: a diagnostic dilemma☆,☆☆ Abstract Rabies is a serious health hazard in developing countries like India. Paralytic rabies is difficult to diagnose due to lack of classic manifestations. It poses diagnostic dilemma in patients who have received postexposure prophylaxis, as it is difficult to differentiate it from vaccineinduced Guillain-Barre syndrome, postvaccination myelitis, and acute disseminated encephalomyelitis. Early diagnosis of rabies in such cases is very important for adequate infection control and for institution of public health measures. We herein report a case of 55-year-old man who presented to us with features suggestive of paralytic rabies after 1 and a half month of Jackal bite, although he had received complete postexposure prophylaxis including antirabies immunoglobulin. This case report highlights the importance of identifying clinical features of paralytic rabies and possibility of postexposure prophylaxis failure. Rabies is a serious health hazard in developing countries like India, where it is endemic. The annual incidence of rabies in India is 2/100 000 population. Rabies is an almost uniformly fatal disease, and, approximately, 55 000 deaths occur in a year all over the world due to rabies; and of approximately 20 000 are from India. Paralytic form accounts for 20% of rabies [1,2]. Paralytic rabies is more common in patients who receive postexposure prophylaxis particularly in those with incomplete prophylaxis [2-4]. The possibility of paralytic rabies should always be considered in a patient who has received postexposure prophylaxis, and magnetic resonance imaging (MRI) of spine shows myelitis. However, it is difficult to differentiate it from postvaccination myelitis clinically [2]. Early diagnosis of rabies in such cases is very important for adequate infection control and for institution of public health measures such as barrier nursing, preexposure prophylaxis to relatives, and hospital staff and shifting of patient to isolation ward. We herein report an unusual case of suspected paralytic rabies in a patient even after receiving complete postexposure prophylaxis including antirabies immunoglobulin. A 55-year-old farmer presented with 3-day history of acute neurologic illness starting with moderate-grade fever for 1 day followed by progressive asymmetric weakness of both lower limbs (left more than right). There was history of Jackal bite 1 and a half month back at multiple sites on his body involving lower limbs, trunk, left upper limb, and right ear lobe (Fig. 1). He received postexposure prophylaxis in form of World Health Organization (WHO)-approved Thai Red Cross intradermal rabies vaccination schedule (2 site intra dermal injection on days 0, 3, 7, and 28). The vaccine used was purified chick embryo cell vaccine
☆ No grant was available for this case. ☆☆ No author has any conflict of interest.
0735-6757/© 2014 Elsevier Inc. All rights reserved.
(Chiron Behring). He was also given antirabies immunoglobulin locally and intramuscularly (total dose, 6.6 mL) and referred to surgery department for local wound management. On examination, vital parameters were stable, and multiple bite marks (category III) were present. There was abscess formation in left lower limb wound. Neurologic examination revealed hypotonia in left lower limb along with asymmetric paraparesis with motor power of Medical Research Council grade 3/5 in right lower limb and 1/5 in left lower limb. Deep tendon reflexes were brisk except for absent knee jerk on left side with bilateral silent plantar responses. On sensory examination, there was impairment of sensations for pinprick and crude touch below D-6 spinal level (left more than right), whereas joint position sense was intact. Diffuse fasciculations were present on tongue, both upper and lower limbs, and on trunk. Examination of other systems was unremarkable. Investigations including routine hemogram, liver and renal function tests, serum electrolytes, electrocardiogram, and chest x-ray were normal. Based on clinical presentation and history of complete postexposure prophylaxis, postvaccination myelitis was considered as the first possibility. Magnetic resonance imaging of the cervicodorsal spine including lower brainstem showed hyperintense signal on T2 weighted image involving predominantly central gray matter of spinal cord from D-5 to L-1 vertebral levels suggestive of long-segment myelitis (Fig. 2). We had planned MRI brain and cerebrospinal fluid examination for further evaluation; but patient became restless after 12 hours of admission, so we had to postpone the investigations. Subsequently, he became delirious and developed weakness in upper limbs, dysphagia, and respiratory distress. On repeat examination, pulse rate was 110/minute, blood pressure 160/100 mmHg, and respiratory rate was 30/minute. The x-ray chest was normal, and electrocardiogram showed sinus tachycardia. Neurologic examination revealed fasciculations all over the body, generalized hypotonia, and areflexia with bilateral silent plantar responses. Nerve conduction study was suggestive of pure motor axonal neuropathy in both the lower limbs. Because of respiratory distress, patient was intubated and put on ventilatory support; but after 1 hour, he developed sudden cardiac arrest and could not be revived. Family members did not give consent for postmortem examination. In view of rapid downhill course, some unusual clinical features such as fasciculations, delirium, and autonomic dysfunction on very next day of hospitalization and MRI finding suggestive of central gray matter involvement of spinal cord, the diagnosis of postvaccination myelitis was revised, and a possibility of paralytic rabies was kept, although we could not confirm the diagnosis of rabies by serology or autopsy. Encephalitic (furious) and paralytic (silent or dumb) are the 2 forms of rabies described. Encephalitic rabies can be diagnosed easily due to its classic features such as hydrophobia, aerophobia, agitation, hypersalivation, and seizures [1-3,5]. Paralytic rabies is difficult to diagnose due to lack of classic manifestations, and problem is compounded when it occurs after postexposure prophylaxis. In postexposure prophylaxis
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R.S. Jain et al. / American Journal of Emergency Medicine 33 (2015) 601.e1–601.e3
[1,7]. High titers (more than 1:5000) of neutralizing antibody in cerebrospinal fluid and serum can help differentiate paralytic rabies from postvaccination myelitis, ADEM, or GB syndrome [8,9]. Neuroimaging in early stage may be normal; however, predominant involvement of gray matter in brain and spinal cord can be seen in MRI that is useful to differentiate it from postvaccination ADEM, in which there is prominent involvement of white matter [1,2,4,7]. Postexposure prophylaxis failure occurs rarely and is often attributed to deviation from WHO recommendations and poor quality of vaccine [5,10]. Failure may also occur if there is large viral load, direct injection of virus into the nerve, improper wound cleaning, and if antirabies immunoglobulin is not injected in all the wounds [5,11]. Our case presented as myelitis, starting with fever at onset, followed by asymmetric weakness of both lower limbs with sensory level and diffuse fasciculations. Left lower limb was more affected due to multiple and large wounds on left side; however, myoedema was absent. Magnetic resonance imaging showed the involvement of predominantly central gray matter of spinal cord from D-5 to L-1 vertebral level. The course was fulminant, as the patient developed delirium, autonomic dysfunction, aggravation of weakness, and respiratory failure on the very next day of admission. Patient died within 5 days of onset of illness. Based on clinical features and course, we considered paralytic rabies as a strong possibility, although it appeared to be postvaccination myelitis at the time of admission because our patient underwent complete postexposure prophylaxis according to WHO-recommended Thai Red Cross intradermal schedule and also received the antirabies immunoglobulin. Possible causes of failure of postexposure prophylaxis in our patient may be accounted by large injection of viral load in view of multiple, large, and deep bite; any wound might have escaped from immunoglobulin injection and poor wound management and hygiene, as the patient was from rural area and consulted in antirabies clinic next day after the bite. However, possibility of any unusual strain of rabies virus should also be considered. Although the failure of postexposure prophylaxis is very rare, paralytic rabies should always be suspected in patients who present as myelitis, ADEM, and GB syndrome with history of rabid animal bite. Prompt diagnosis of rabies is of paramount importance for institution of appropriate infection control and public health measures, although it may not affect management outcome. Rajendra Singh Jain, DM Pankaj Kumar Gupta, MD* Rahul Handa, MD Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India *Corresponding author. Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India. Tel.: +91 9166979442 E-mail address: [email protected] Shankar Tejwani, MD SMS Hospital, Jaipur, Rajasthan, India
Fig. 1. A, Photograph of patient after Jackal bite showing bite marks in left upper limb and lower limb. B, Photograph of patient after Jackal bite showing bite marks in right lower limb. C, Photograph of patient after Jackal bite showing bite mark in right ear lobe.
Swayam Prakash, MD Sunil Kumar, MD Rakesh Agrawal, MD Mahendra S. Sisodiya, MD Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India http://dx.doi.org/10.1016/j.ajem.2014.09.026
patient, it poses diagnostic dilemma with vaccine-induced GuillainBarre (GB) syndrome, postvaccination myelitis, and acute disseminated encephalomyelitis (ADEM) [2-4]. Paralytic rabies can present as paresthesia and flaccid weakness confined to 1 extremity, quadriplegic form, transverse myelitis, and symmetrical ascending paralysis like GB syndrome [1,6]. The clinical features that favor paralytic rabies rather than GB syndrome, myelitis, or ADEM include rapid progression, greater affection of bitten extremity, fasciculations, severe paresthesia, myoedema in the extremity with bite, fever in prodromal phase, altered consciousness, autonomic dysfunction, hydrophobia, and aerophobia
References [1] Gadre G, Satishchandra P, Mahadevan A, Suja MS, Madhusudana SN, Sundaram C, et al. Rabies viral encephalitis: clinical determinants in diagnosis with special reference to paralytic form. J Neurol Neurosurg Psychiatry 2010;81(7):812–20. [2] Vaish AK, Jain N, Gupta LK, Verma SK. Atypical rabies with MRI findings: clue to the diagnosis. BMJ Case Rep 2011. http://dx.doi.org/10.1136/bcr.05.2011.4234. [3] Ghosh B, Roy M, Lahiri K, Bala AK. Acute flaccid paralysis due to rabies. J Pediatr Neurosci 2009;4(1):33–5. [4] Desai RV, Jain V, Singh P, Singhi S, Radotra BD. Radiculomyelitic rabies: can MR imaging help? Am J Neuroradiol 2002;23:632–4.
R.S. Jain et al. / American Journal of Emergency Medicine 33 (2015) 601.e1–601.e3
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Fig. 2. A, T2-weighted sagittal MRI dorsal spine showing hyperintense signal in spinal cord from D-5 to D-12 level. B, STIR image sagittal MRI dorsal spine showing hyperintense signal in spinal cord from D-5 to D-12 level. C, T2-weighted sagittal MRI lumbar spine showing hyperintense signal in spinal cord up to L-1 level.
[5] Deshmukh DG, Damle AS, Bajaj JK, Bhakre JB, Patil NS. Fatal rabies despite postexposure prophylaxis. Indian J Med Microbiol 2011;29(2):178–91. [6] Mader Jr EC, Maury JS, Santana-Gould L, Craver RD, El-Abassi R, Segura-Palacios E, et al. Human rabies with initial manifestations that mimic acute brachial neuritis and Guillain-Barré syndrome. Clin Med Insight Case Rep 2012;5:49–55. [7] Kumar S. Differentiating paralytic rabies from post antirabies vaccine polyradiculoneuropathy. Neurol India 2004;52:270. [8] Srivastava AK, Sardana V, Prasad K, Behari M. Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine. Neurol India 2004;52(1):132–3.
[9] Beckham JD, Solbrig MV, Tyler KL. Infections of the nervous system viral encephalitis and meningitis. Bradley’s neurology in clinical practice6th ed. ; 2012 1252–3. [10] Shantavasinkul P, Tantawichien T, Wacharapluesadee S, Jeamanukoolkit A, Udomchaisakul P, Chattranukulchai P, et al. Failure of rabies postexposure prophylaxis in patients presenting with unusual manifestations. Clin Infect Dis 2010;50: 77–9. [11] Wilde H, Shantavasinkul P, Hemachudha T, Tepsumethanon V, Lumlerdacha B, Wacharapluesadee S, et al. New knowledge and controversies in rabies. J Infect Dis Antimicrob Agents 2009;26:63–74.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case report
Paralytic rabies or postvaccination myelitis: a diagnostic dilemma☆,☆☆ Abstract Rabies is a serious health hazard in developing countries like India. Paralytic rabies is difficult to diagnose due to lack of classic manifestations. It poses diagnostic dilemma in patients who have received postexposure prophylaxis, as it is difficult to differentiate it from vaccineinduced Guillain-Barre syndrome, postvaccination myelitis, and acute disseminated encephalomyelitis. Early diagnosis of rabies in such cases is very important for adequate infection control and for institution of public health measures. We herein report a case of 55-year-old man who presented to us with features suggestive of paralytic rabies after 1 and a half month of Jackal bite, although he had received complete postexposure prophylaxis including antirabies immunoglobulin. This case report highlights the importance of identifying clinical features of paralytic rabies and possibility of postexposure prophylaxis failure. Rabies is a serious health hazard in developing countries like India, where it is endemic. The annual incidence of rabies in India is 2/100 000 population. Rabies is an almost uniformly fatal disease, and, approximately, 55 000 deaths occur in a year all over the world due to rabies; and of approximately 20 000 are from India. Paralytic form accounts for 20% of rabies [1,2]. Paralytic rabies is more common in patients who receive postexposure prophylaxis particularly in those with incomplete prophylaxis [2-4]. The possibility of paralytic rabies should always be considered in a patient who has received postexposure prophylaxis, and magnetic resonance imaging (MRI) of spine shows myelitis. However, it is difficult to differentiate it from postvaccination myelitis clinically [2]. Early diagnosis of rabies in such cases is very important for adequate infection control and for institution of public health measures such as barrier nursing, preexposure prophylaxis to relatives, and hospital staff and shifting of patient to isolation ward. We herein report an unusual case of suspected paralytic rabies in a patient even after receiving complete postexposure prophylaxis including antirabies immunoglobulin. A 55-year-old farmer presented with 3-day history of acute neurologic illness starting with moderate-grade fever for 1 day followed by progressive asymmetric weakness of both lower limbs (left more than right). There was history of Jackal bite 1 and a half month back at multiple sites on his body involving lower limbs, trunk, left upper limb, and right ear lobe (Fig. 1). He received postexposure prophylaxis in form of World Health Organization (WHO)-approved Thai Red Cross intradermal rabies vaccination schedule (2 site intra dermal injection on days 0, 3, 7, and 28). The vaccine used was purified chick embryo cell vaccine
☆ No grant was available for this case. ☆☆ No author has any conflict of interest.
0735-6757/© 2014 Elsevier Inc. All rights reserved.
(Chiron Behring). He was also given antirabies immunoglobulin locally and intramuscularly (total dose, 6.6 mL) and referred to surgery department for local wound management. On examination, vital parameters were stable, and multiple bite marks (category III) were present. There was abscess formation in left lower limb wound. Neurologic examination revealed hypotonia in left lower limb along with asymmetric paraparesis with motor power of Medical Research Council grade 3/5 in right lower limb and 1/5 in left lower limb. Deep tendon reflexes were brisk except for absent knee jerk on left side with bilateral silent plantar responses. On sensory examination, there was impairment of sensations for pinprick and crude touch below D-6 spinal level (left more than right), whereas joint position sense was intact. Diffuse fasciculations were present on tongue, both upper and lower limbs, and on trunk. Examination of other systems was unremarkable. Investigations including routine hemogram, liver and renal function tests, serum electrolytes, electrocardiogram, and chest x-ray were normal. Based on clinical presentation and history of complete postexposure prophylaxis, postvaccination myelitis was considered as the first possibility. Magnetic resonance imaging of the cervicodorsal spine including lower brainstem showed hyperintense signal on T2 weighted image involving predominantly central gray matter of spinal cord from D-5 to L-1 vertebral levels suggestive of long-segment myelitis (Fig. 2). We had planned MRI brain and cerebrospinal fluid examination for further evaluation; but patient became restless after 12 hours of admission, so we had to postpone the investigations. Subsequently, he became delirious and developed weakness in upper limbs, dysphagia, and respiratory distress. On repeat examination, pulse rate was 110/minute, blood pressure 160/100 mmHg, and respiratory rate was 30/minute. The x-ray chest was normal, and electrocardiogram showed sinus tachycardia. Neurologic examination revealed fasciculations all over the body, generalized hypotonia, and areflexia with bilateral silent plantar responses. Nerve conduction study was suggestive of pure motor axonal neuropathy in both the lower limbs. Because of respiratory distress, patient was intubated and put on ventilatory support; but after 1 hour, he developed sudden cardiac arrest and could not be revived. Family members did not give consent for postmortem examination. In view of rapid downhill course, some unusual clinical features such as fasciculations, delirium, and autonomic dysfunction on very next day of hospitalization and MRI finding suggestive of central gray matter involvement of spinal cord, the diagnosis of postvaccination myelitis was revised, and a possibility of paralytic rabies was kept, although we could not confirm the diagnosis of rabies by serology or autopsy. Encephalitic (furious) and paralytic (silent or dumb) are the 2 forms of rabies described. Encephalitic rabies can be diagnosed easily due to its classic features such as hydrophobia, aerophobia, agitation, hypersalivation, and seizures [1-3,5]. Paralytic rabies is difficult to diagnose due to lack of classic manifestations, and problem is compounded when it occurs after postexposure prophylaxis. In postexposure prophylaxis
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R.S. Jain et al. / American Journal of Emergency Medicine 33 (2015) 601.e1–601.e3
[1,7]. High titers (more than 1:5000) of neutralizing antibody in cerebrospinal fluid and serum can help differentiate paralytic rabies from postvaccination myelitis, ADEM, or GB syndrome [8,9]. Neuroimaging in early stage may be normal; however, predominant involvement of gray matter in brain and spinal cord can be seen in MRI that is useful to differentiate it from postvaccination ADEM, in which there is prominent involvement of white matter [1,2,4,7]. Postexposure prophylaxis failure occurs rarely and is often attributed to deviation from WHO recommendations and poor quality of vaccine [5,10]. Failure may also occur if there is large viral load, direct injection of virus into the nerve, improper wound cleaning, and if antirabies immunoglobulin is not injected in all the wounds [5,11]. Our case presented as myelitis, starting with fever at onset, followed by asymmetric weakness of both lower limbs with sensory level and diffuse fasciculations. Left lower limb was more affected due to multiple and large wounds on left side; however, myoedema was absent. Magnetic resonance imaging showed the involvement of predominantly central gray matter of spinal cord from D-5 to L-1 vertebral level. The course was fulminant, as the patient developed delirium, autonomic dysfunction, aggravation of weakness, and respiratory failure on the very next day of admission. Patient died within 5 days of onset of illness. Based on clinical features and course, we considered paralytic rabies as a strong possibility, although it appeared to be postvaccination myelitis at the time of admission because our patient underwent complete postexposure prophylaxis according to WHO-recommended Thai Red Cross intradermal schedule and also received the antirabies immunoglobulin. Possible causes of failure of postexposure prophylaxis in our patient may be accounted by large injection of viral load in view of multiple, large, and deep bite; any wound might have escaped from immunoglobulin injection and poor wound management and hygiene, as the patient was from rural area and consulted in antirabies clinic next day after the bite. However, possibility of any unusual strain of rabies virus should also be considered. Although the failure of postexposure prophylaxis is very rare, paralytic rabies should always be suspected in patients who present as myelitis, ADEM, and GB syndrome with history of rabid animal bite. Prompt diagnosis of rabies is of paramount importance for institution of appropriate infection control and public health measures, although it may not affect management outcome. Rajendra Singh Jain, DM Pankaj Kumar Gupta, MD* Rahul Handa, MD Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India *Corresponding author. Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India. Tel.: +91 9166979442 E-mail address: [email protected] Shankar Tejwani, MD SMS Hospital, Jaipur, Rajasthan, India
Fig. 1. A, Photograph of patient after Jackal bite showing bite marks in left upper limb and lower limb. B, Photograph of patient after Jackal bite showing bite marks in right lower limb. C, Photograph of patient after Jackal bite showing bite mark in right ear lobe.
Swayam Prakash, MD Sunil Kumar, MD Rakesh Agrawal, MD Mahendra S. Sisodiya, MD Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India http://dx.doi.org/10.1016/j.ajem.2014.09.026
patient, it poses diagnostic dilemma with vaccine-induced GuillainBarre (GB) syndrome, postvaccination myelitis, and acute disseminated encephalomyelitis (ADEM) [2-4]. Paralytic rabies can present as paresthesia and flaccid weakness confined to 1 extremity, quadriplegic form, transverse myelitis, and symmetrical ascending paralysis like GB syndrome [1,6]. The clinical features that favor paralytic rabies rather than GB syndrome, myelitis, or ADEM include rapid progression, greater affection of bitten extremity, fasciculations, severe paresthesia, myoedema in the extremity with bite, fever in prodromal phase, altered consciousness, autonomic dysfunction, hydrophobia, and aerophobia
References [1] Gadre G, Satishchandra P, Mahadevan A, Suja MS, Madhusudana SN, Sundaram C, et al. Rabies viral encephalitis: clinical determinants in diagnosis with special reference to paralytic form. J Neurol Neurosurg Psychiatry 2010;81(7):812–20. [2] Vaish AK, Jain N, Gupta LK, Verma SK. Atypical rabies with MRI findings: clue to the diagnosis. BMJ Case Rep 2011. http://dx.doi.org/10.1136/bcr.05.2011.4234. [3] Ghosh B, Roy M, Lahiri K, Bala AK. Acute flaccid paralysis due to rabies. J Pediatr Neurosci 2009;4(1):33–5. [4] Desai RV, Jain V, Singh P, Singhi S, Radotra BD. Radiculomyelitic rabies: can MR imaging help? Am J Neuroradiol 2002;23:632–4.
R.S. Jain et al. / American Journal of Emergency Medicine 33 (2015) 601.e1–601.e3
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Fig. 2. A, T2-weighted sagittal MRI dorsal spine showing hyperintense signal in spinal cord from D-5 to D-12 level. B, STIR image sagittal MRI dorsal spine showing hyperintense signal in spinal cord from D-5 to D-12 level. C, T2-weighted sagittal MRI lumbar spine showing hyperintense signal in spinal cord up to L-1 level.
[5] Deshmukh DG, Damle AS, Bajaj JK, Bhakre JB, Patil NS. Fatal rabies despite postexposure prophylaxis. Indian J Med Microbiol 2011;29(2):178–91. [6] Mader Jr EC, Maury JS, Santana-Gould L, Craver RD, El-Abassi R, Segura-Palacios E, et al. Human rabies with initial manifestations that mimic acute brachial neuritis and Guillain-Barré syndrome. Clin Med Insight Case Rep 2012;5:49–55. [7] Kumar S. Differentiating paralytic rabies from post antirabies vaccine polyradiculoneuropathy. Neurol India 2004;52:270. [8] Srivastava AK, Sardana V, Prasad K, Behari M. Diagnostic dilemma in flaccid paralysis following anti-rabies vaccine. Neurol India 2004;52(1):132–3.
[9] Beckham JD, Solbrig MV, Tyler KL. Infections of the nervous system viral encephalitis and meningitis. Bradley’s neurology in clinical practice6th ed. ; 2012 1252–3. [10] Shantavasinkul P, Tantawichien T, Wacharapluesadee S, Jeamanukoolkit A, Udomchaisakul P, Chattranukulchai P, et al. Failure of rabies postexposure prophylaxis in patients presenting with unusual manifestations. Clin Infect Dis 2010;50: 77–9. [11] Wilde H, Shantavasinkul P, Hemachudha T, Tepsumethanon V, Lumlerdacha B, Wacharapluesadee S, et al. New knowledge and controversies in rabies. J Infect Dis Antimicrob Agents 2009;26:63–74.
