In community healthcare, providing initial treatment for a broad range of conditions affecting individuals across all age groups, including suspected pediatric acute encephalitis, is essential. Encephalitis is a syndrome characterized by neurological dysfunction resulting from inflammation of the brain parenchyma [1]. In children, acute encephalitis presents with a variety of clinical manifestations, including fever, impaired consciousness, seizures, and respiratory failure. As this condition often progresses rapidly, leading to death or severe neurological sequelae, initial management is critical, especially in community hospitals located far from advanced medical facilities. In Japan, acute encephalitis/encephalopathy annually affects 1,000 children aged < 15 years, with a mortality rate of 5% - 10% and neurological sequelae observed in 20% - 30% of cases [2]. This report describes a case of suspected acute encephalitis in a child presenting with seizures and respiratory failure in a remote area of Japan and highlights the importance of early intervention in suspected pediatric acute encephalitis.

A previously healthy, fully immunized 13-year-old boy was transported to our hospital by emergency medical services (EMS) because of seizures and respiratory failure. Upon arrival, he was unconscious with shallow breathing and an oxygen saturation (SpO₂) of 60% on room air. Oral suctioning and assisted ventilation with oxygen were initiated using a manual resuscitator, during which he experienced a seizure lasting approximately 1 minute. He was brought to our hospital 32 minutes after the onset of symptoms. No sick contact was confirmed; however, he had been experiencing upper respiratory symptoms for several days prior to the event. He had no prior travel history and had no contact with or been bitten by any animals; he also had no exposure to mosquitoes or ticks. No family history of epilepsy was found. Previous herpes simplex virus (HSV) and varicella zoster virus (VZV) infections were not confirmed. His vital signs were as follows: body temperature, 39.0˚C; pulse, 153 beats/minute; blood pressure, 190/93 mmHg; and SpO₂, 98% under assisted ventilation with oxygen administration using a manual resuscitator. Physical examination revealed a Glasgow Coma Scale score of 10 (eye response +4, verbal response +2, motor response +4), generalized seizures, and severe respiratory distress. Intubation was attempted immediately under intravenous diazepam sedation (total doses: 10 mg); however, it was unsuccessful due to recurrent generalized seizures. The patient was subsequently sedated with intravenous midazolam (total doses: 4.5 mg) and successfully intubated 28 minutes after arrival at the hospital. No signs of meningeal irritation were observed during sedation and intubation. Blood gas analysis following intubation and mechanical ventilation (Table 1) revealed significant acidosis (pH, 7.106; partial pressure of carbon dioxide [PaCO₂], 50.3 mmHg; partial pressure of oxygen [PaO₂], 209.0 mmHg; bicarbonate [ HCO 3 − ], 15.1 mmol/L; base excess, −14.8 mmol/L; blood glucose, 251 mg/dL; lactic acid, 14.9 mmol/L), prompting the immediate administration of sodium bicarbonate. However, computed tomography (CT) of the brain revealed no abnormalities (Figure 1). Laboratory studies (Table 2) revealed a white blood cell count of 31.6 × 10³/µL with a normal differential; platelet count of 416 × 10³/µL; hemoglobin level of 14.5 g/dL; C-reactive protein of 0.05 mg/dL; blood urea nitrogen of 20.4 mg /dL; creatinine of 1.48 mg/dL; and ammonia of 147 µg/dL. Hepatobiliary enzymes, the remaining complete metabolic panel, and coagulation studies were within normal ranges. Blood gas analysis after 1 hour (Table 3) demonstrated improvement (pH, 7.428; PaCO₂, 45.9 mmHg; PaO₂, 472.4 mmHg; HCO 3 − , 29.7 mmol/L; base excess, +5.0 mmol/L, lactic acid, 6.6 mmol/L). Nasopharyngeal exudate testing was negative for severe acute respiratory syndrome coronavirus 2 and influenza virus antigens. Despite intubation, mechanical ventilation, and repeated midazolam injection, the patient continued to experience generalized seizures and involuntary movements. He was administered midazolam for continuous sedation and transferred to a specialized medical facility for further care on suspicion of acute encephalitis 2 hours after arrival at our hospital. During the two-hour stay at our hospital, the patient experienced eight seizures lasting 3 - 5 minutes each, and two more seizures during the one-hour transport, and the patient’s consciousness did not recover between seizures, which fulfilled the criteria for status epilepticus. After transfer, the patient was admitted to the intensive care unit and received mechanical ventilation with sedation using midazolam and fentanyl. No seizures were observed, and metabolic acidosis and hyperammonemia improved. Magnetic resonance imaging (MRI) of the brain performed on the day revealed no evidence of hemorrhagic lesions, encephalopathy, or encephalitis. Additionally, electroencephalography revealed no abnormalities. The patient’s respiratory condition rapidly improved, and purposeful movement was noted even under sedation, prompting extubation the following day. Cerebrospinal fluid (CSF) studies (Table 4) performed on 15 hours after the onset of symptoms indicated a high protein level of 97.8 mg/dL, increased cell counts of 51/µL with 94.1% monocytes, and normal glucose and chloride levels. Serum blood glucose level was 111 mg/dl. Gram staining and bacterial culture of the CSF did not reveal any bacterial growth, and blood culture yielded no bacterial growth. The CSF polymerase chain reaction (PCR) test did not identify any pathogens (Table 5). Because the patient’s condition improved rapidly, repeated PCR tests for herpes simplex virus were not performed. Based on the clinical course and a series of test results, the possibility of meningitis caused by some other virus was considered. After sedation was discontinued, the patient regained full consciousness and had no difficulty with daily activities. The altered mental status was not observed. The patient was discharged on day 6 and exhibited no neurological deficits at the 6-month follow up.

Figure 1.Brain computed tomography displaying preserved gray-white matter differentiation with no evidence of intracranial hemorrhage, infarction, or structural abnormalities.

Table 1.Arterial blood gas analysis obtained after intubation and initiation of mechanical ventilation.

PaCO₂, partial pressure of carbon dioxide; PaO₂, partial pressure of oxygen; HCO 3 − , bicarbonate.

Table 2.Initial laboratory findings on admission.

Table 3.Arterial blood gas analysis performed 1 hour after hospital arrival.

PaCO₂, partial pressure of carbon dioxide; PaO₂, partial pressure of oxygen; HCO 3 − , bicarbonate.

Table 4.Cerebrospinal fluid analysis performed at the referral hospital.

Table 5.PCR test performed at the referral hospital on 15 hours after the onset of symptoms.

PCR; polymerase chain reaction.

We report the case of a pediatric patient with suspected acute encephalitis presenting with respiratory failure and generalized seizures in a remote area of Japan. Although acute encephalitis in children is relatively rare, the condition can progress rapidly, often leading to death or severe neurological sequelae. Clinical outcomes depend on prompt identification of the cause and initiation of appropriate treatment [3]. Therefore, physicians in community hospitals play a crucial role in the initial management of children with suspected acute encephalitis.

Pediatric acute encephalitis has diverse etiologies, including viral, autoimmune, and demyelinating causes, with initial clinical presentations and laboratory findings often being nonspecific. In immunocompetent individuals in Europe and the United States, viral encephalitis is most commonly caused by HSV types 1 and 2, VZV, and enterovirus [4][5]. In cases of suspected encephalitis at the initial visit, hypoglycemia, electrolyte imbalances, and head trauma must be considered in the differential diagnosis. In the present case, these conditions were ruled out based on laboratory data and brain CT findings.

MRI of the brain is critical for diagnosing suspected encephalitis, as the modality allows for morphological and functional studies that can identify lesions in the cerebral parenchyma, even during the hyperacute phase [6]. CSF analysis is also essential for suspected encephalitis cases. Although both examinations are valuable for diagnosis, avoiding delays in definitive diagnostic confirmation is vital in community hospitals in remote areas. If acute encephalitis is strongly suspected, priorities in a remote hospital are life support and brain function protection before transfer for further investigation at a higher-level medical institution. Therefore, pre-transfer care includes three keys: first, respiratory and circulatory management; second, suppression of seizures and increased intracranial pressure; and third, correction of metabolic disturbances, including blood gas and electrolyte abnormalities.

However, exceptions exist, particularly when HSV encephalitis cannot be ruled out. The mortality rate associated with untreated HSV encephalitis is approximately 70%, and even with antiviral therapy, the rate remains over 30%. Furthermore, nearly 60% of survivors develop neurological sequelae [7]. Prompt diagnosis and initiation of antiviral therapy are crucial for favorable outcomes in HSV encephalitis [8]. Even if initial CSF or imaging findings are normal, acyclovir should be administered within 6 hours of symptom onset if HSV encephalitis is clinically suspected [1]. As brain CT scan has a 50% detection rate for acute changes in HSV encephalitis [9], this condition could not be excluded in the present case before transfer to an advanced medical institution. Although the patient had mild renal impairment, acyclovir should have been administered with adequate fluid replacement before transfer.

Moreover, bacterial meningitis is a crucial differential diagnosis for suspected acute encephalitis. Although seizures and respiratory distress are uncommon early symptoms, bacterial meningitis necessitates urgent initial treatment similar to that for HSV encephalitis. Given the high case-fatality rate of up to 30% and the development of neurological complications in up to 66.1% of survivors, the condition should be empirically treated before a specific pathogen is identified [10]-[12]. Delays in antibiotic administration exceeding 2 hours are associated with doubled mortality [13]; thus, antibiotics should be administered as soon as bacterial meningitis is suspected, ideally within 2 hours [14]. In this case, the absence of meningeal sign and nonspecific blood laboratory findings cannot reliably exclude bacterial meningitis, particularly in a sedated and intubated condition. Empiric antibiotic administration should have been initiated before transfer to an advanced medical institution.

In suspected pediatric acute encephalitis cases in remote areas, initial management is critical. Priorities include providing ventilatory and circulatory support and protecting brain function. Only essential imaging and blood chemistry tests should be performed, and any metabolic disturbances should be corrected before the patient is promptly transferred to an advanced medical facility. However, if HSV encephalitis or bacterial meningitis cannot be ruled out, initial treatment should be administered at the community hospital prior to transfer. Physicians treating children in remote areas must understand the management of suspected encephalitis, as this can facilitate earlier diagnosis and treatment, ultimately improving outcomes.

Written informed consent for publication was obtained from the patient’s parents.

Conceptualization, T.H. and T.Y.; Investigation, T.H., T.O., T.Y., M.K., Y.O.; Writing-original draft preparation, T.H.; Writing-review and editing, T.H.; Supervision, T.O. and Y.O. All authors have read and agreed to the published version of the manuscript.