Abstract
Japanese encephalitis (JE) is a mosquito-borne viral infection of the central nervous system, while tuberculous meningitis (TBM) is another major CNS infection in endemic regions. The co-occurrence of these conditions is extremely rare and presents significant diagnostic and therapeutic challenges. We report a 13-year-old boy who presented with fever, respiratory distress, and neurological symptoms, progressing to respiratory failure that required intubation and intensive care. MRI findings of bilateral thalamic involvement suggested JE, while cerebrospinal fluid analysis confirmed CNS tuberculosis. He was managed with intensive antitubercular therapy, antibiotics, and supportive ICU care. Despite prolonged hospitalization and mechanical ventilation, he developed quadriplegia, reflecting the severity of these dual infections. Concurrent JE and CNS TB complicate both diagnosis and treatment, necessitating early recognition, multidisciplinary management, and intensive supportive care. This first documented case underscores the importance of awareness and further research to guide strategies for managing rare coexisting CNS infections.
Keywords
Key Clinical Message
A 13-year-old male exhibited fever, respiratory distress, and neurological deterioration, culminating in quadriplegia. MRI findings suggested Japanese Encephalitis (JE), with cerebrospinal fluid analysis confirming concurrent central nervous system tuberculosis (CNS TB). Intensive antitubercular therapy and multidisciplinary ICU management underscore the critical need for prompt diagnosis and comprehensive care in this unprecedented co-infection.
Introduction
Japanese encephalitis (JE), caused by the Japanese encephalitis virus (JEV) from family of flavivirus, is one of the most significant viral encephalitis infections affecting children in Asia. 1 The primary vector, Culex tritaeniorhynchus, is nocturnal and predominantly found in agricultural regions, particularly rice fields, during the rainy season. Waterfowl and pigs serve as the main reservoir hosts. Less than 1% of infections present with symptoms, typically starting with nonspecific flu-like signs. However, the condition can advance to encephalitis, leading to seizures, psychosis, meningism, coma, and various neurological complications. Fatal outcomes occur in up to one-third of symptomatic cases. 2 Myelitis with flaccid paralysis is an exceptionally rare clinical manifestation, even in regions where the disease is endemic. 3 The majority of cases of JEV-associated acute flaccid paralysis (AFP) met the diagnostic criteria for Guillain–Barré syndrome (GBS), while a few were suspected to have myelitis. 4 Mycobacterium tuberculosis infection of the central nervous system (CNS) is prevalent in regions where tuberculosis is endemic and can lead to seizures or acquired epilepsy, contributing to increased disability and mortality among affected individuals. However, the causes of seizures in CNS tuberculosis are multifaceted. 5 Consequently, it is crucial to assess each patient who experiences seizures to determine the need for supportive care, long-term antiseizure medication. Here we present a case report of 13 years male with Japanese Encephalitis with concurrent CNS tuberculosis.
Case History and Examination
A 13 years, Male, sixth standard student, academically and extracurricularly active. No significant illness in the past. With no history of pulmonary tuberculosis or asthma in the family presented to tertiary care center with history of fever for 4 days, followed by difficulty in breathing for 1 day and slurring of speech. He initially received symptomatic treatment with antipyretics and fluids at a local hospital on day 1 of fever. By day 4, worsening respiratory distress and slurred speech prompted referral to our tertiary center for suspected neurological involvement.
Differential Diagnosis
Investigations and Treatment
He was intubated in the Pediatric Emergency Room (ER) and subsequently shifted to the Pediatric Intensive Care Unit (PICU). A tracheostomy was performed due to prolonged ventilatory dependence. MRI findings were suggestive of Japanese Encephalitis (JE) neuroparenchymal involvement as shown in Figures 1 and 2. RT PCR which was done from the previous center had shown JE. He was treated with ceftriaxone, amikacin, and other supportive therapies. Bronchoalveolar lavage (BAL) cultures revealed Pseudomonas spp., indicating a secondary bacterial infection. The CSF analysis showed raised protein and albumin with mild increase in lymphocytes. CSF analysis confirmed CNS tuberculosis through positive Ziehl-Neelsen (ZN) staining for acid-fast bacilli and polymerase chain reaction (PCR) for Mycobacterium tuberculosis.
Thalamic changes demonstrated by yellow arrow in MRI.
Thalamic changes as compared to other structures in MRI.
The patient was kept in Intensive HRZE followed by maintenance HRE therapy. Investigations were sent which is listed in Table 1. CBC showed leukocytosis and ABG showed respiratory acidosis, Infectious work up of Malaria, Leptospirosis, Scrub Typhus were negative. Respiratory acidosis was managed following mechanical ventilation. After about 30 days of ICU stay the patient developed grade IV bed sore for which debridement and ointment mupirocin was given. The would culture was negative and air mattress was used to prevent further injury. Also Levetiracetam was given as an antiepileptic drug for seizure prevention and pyridoxine for neuropathy prevention. After 40 days of ICU stay, the patient mental status was improving however, quadriplegia still persisted.
Investigations Relevant to the CNS Involvement.
Discussion
The coexistence of JE and CNS TB is extremely rare. Acute encephalitis is the most common clinical presentation of Japanese encephalitis (JE). Following an incubation period of 5 to 15 days, initial symptoms are typically nonspecific and may include fever, diarrhea, and chills, progressing to headache, vomiting, and generalized weakness. In the subsequent days, patients may develop altered mental status, focal neurological deficits such as paresis, hemiplegia, quadriplegia, or cerebral palsy, as well as motor impairments. In severe cases, patients may progress to a comatose state, with some requiring ventilatory support. The clinical presentation of Japanese encephalitis (JE) is often nonspecific, with acute manifestations such as behavioral abnormalities, seizures, disorientation, coma, and spastic paralysis, which can complicate diagnosis. Laboratory confirmation via JEV-specific IgM antibodies in CSF or serum is essential, though detectable after seven days. 6 However, IgM titers become fully detectable only after 7 days of infection, potentially delaying diagnosis. JE primarily affects the diencephalon and mesencephalon, with characteristic MRI findings 7 showing abnormal signals in the thalamus (94%), basal ganglia (35.5%), midbrain (58%), cerebellum (25.8%), pons (19%), and cerebral cortex (19%). A key imaging feature of JE is the initial involvement of the posterior thalamus, which may later extend to the entire thalamus and basal ganglia. Bilateral thalamic involvement on imaging is considered a highly suggestive indicator of JE. 8
Tuberculous meningitis (TBM) and CNS tuberculomas are intracranial manifestations of tuberculosis, frequently associated with seizures and epilepsy. TBM is the most prevalent and severe form of CNS tuberculosis, accounting for 5.4% of all extrapulmonary TB cases, with a mortality rate of 23% and a 29% risk of neurological complications. 9 Mycobacterium tuberculosis reaches the CNS via hematogenous spread from the lungs, forming small subpial and subependymal lesions known as Rich foci, which can lead to structural and functional damage to the meninges and cerebral parenchyma. 10 Diagnosis was confirmed by CSF analysis showing raised protein, lymphocytic pleocytosis, and positive ZN staining for acid-fast bacilli. Diagnostic challenges include overlapping symptoms with JE, potentially delaying identification. Management challenges encompass overlapping therapies (eg, antitubercular drugs with supportive care for JE), prolonged ICU care, and secondary infections like Pseudomonas from BAL, increasing morbidity. Despite aggressive supportive care, severe neurological sequelae such as quadriplegia occurred.
The literature on JE reveals diagnostic confusions and treatment challenges in various presentations, which could be exacerbated in co-infections where one pathology masks the other, leading to delays.
A rare case of JE encephalitis following liver transplantation 11 was reported which was managed with acyclovir, assisted mechanical ventilation along with methylprednisolone. The patient was extubated on 27th post op day and was shifted to ward on 32nd post op day. A 11 year female suffering from Dystonic storm 12 was diagnosed with JE infection who was managed with assisted mechanical ventilation with Midazolam as an antiseizure medication. The symptoms improved after 3 weeks of admission and was discharged on fourth week. A 18 year male suffering from JE developed GBS 13 on 27th day of admission. The patient however denied mechanical ventilation and IVIG administration and despite broad spectrum administration and sputum clearance with bronchoscopy expired on 36th day after illness. A rare case of 52 year male with left sided limb weakness suspected to be stroke was diagnosed with JE when symptoms 14 didn’t improve following ischemic stroke medication. The patient was managed with Ribavirin and was discharged on 17th day of admission. A 71 year woman with multiple intracranial hemorrhages 15 was diagnosed with JE and was treated with multiple antiviral medications along with mechanical ventilation with tracheostomy and was discharged on 38th day of admission. A 7 year male was diagnosed with anti-NMDRe 16 following JE and was managed with Acyclovir, methylprednisolone, IVIG and cyclophosphamide. The patient was discharged after 3 weeks of admission on oral steroid which was gradually tapered over 11 months. These cases highlight potential delays if symptoms overlap with TB, complicating antiviral and antitubercular regimens in resource-limited settings.
There is no literature that described JE with CNS TB. Hence, our case is unique and aims to provide new insights into management of JE with CNS TB in the ICU setting.
Clinicians in endemic regions should consider dual CNS infections when a child presents with atypical neurological deterioration. For optimal outcomes, early MRI, CSF testing and multidisciplinary ICU care are essential.
Conclusion and Results
This case highlights the rare co-occurrence of Japanese encephalitis (JE) and central nervous system tuberculosis (CNS TB), a combination not previously described in the literature. This case underscores the importance of early identification and a multidisciplinary approach in managing dual CNS infections. The patient had not received the Japanese Encephalitis vaccine, highlighting the critical role of vaccination in endemic regions. Timely laboratory confirmation, aggressive supportive care, and targeted antimicrobial therapy remain essential for optimizing outcomes. Additionally, this report sheds light on the need for heightened awareness in endemic regions, as well as the importance of vaccination and TB prevention strategies. Given the rarity of this presentation, further studies are warranted to better understand its pathophysiology and improve therapeutic strategies for patients with concurrent JE and CNS TB. It is important because it is the first case of JE and CNS TB coinfection to be reported.
Footnotes
Abbreviations
Ethical Considerations
Ethical Approval was not taken as it is a Case Report.
Consent to Participate
Written informed consent was obtained from the patient’s parents for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
Author Contributions
All the authors contributed in writing, supervising, writing original draft and correction of the report.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.