Acute necrotizing encephalopathy in a young adult triggered by adenovirus: a rare etiology of a devastating neurological syndrome

Abstract

Background

Acute necrotizing encephalopathy is a rare but severe neurological disorder characterized by rapid onset of fever, altered mental status, seizures, and multifocal brain lesions, particularly involving the thalami and brainstem. Often triggered by viral infections, its pathogenesis involves a hyperinflammatory response, resulting in blood-brain barrier disruption and necrosis of neural tissue. While influenza and herpesviruses are common etiological agents, adenovirus is a less frequently reported cause.

Case presentation

A 19-year-old previously healthy male presented with a two-day history of fever, headache, altered mental status, and seizures. On admission, he was febrile, with impaired consciousness. Initial investigations showed leukocytosis, elevated C-reactive protein, and cerebrospinal fluid analysis indicative of inflammation without bacterial or fungal pathogens. Brain MRI revealed bilateral symmetrical lesions in the thalami, putamen, and brainstem, consistent with acute necrotizing encephalopathy. Polymerase chain reaction testing of cerebrospinal fluid and nasopharyngeal swabs confirmed adenovirus as the causative agent. The patient was managed with seizure control, corticosteroids for cerebral edema, and supportive care, including mechanical ventilation and physiotherapy. Follow-up imaging demonstrated regression of thalamic and pontine lesions. The patient showed partial neurological recovery but required transfer to a long-term care facility for rehabilitation, with persistent functional disability.

Conclusion

This case highlights adenovirus as a rare etiological agent of acute necrotizing encephalopathy, emphasizing the importance of molecular diagnostics in identifying atypical pathogens in severe neurological conditions.

Background

Acute necrotizing encephalopathy is a rare but severe neurologic disorder predominantly seen in children and young adults, often triggered by viral infections [1]. It is characterized by rapid onset of fever, altered mental status, seizures, and multifocal brain lesions, particularly affecting the thalami, brainstem, and other deep gray matter structures. The condition is associated with high morbidity and mortality, and survivors often face significant neurological sequelae.

The pathogenesis of acute necrotizing encephalopathy is not fully understood but is thought to involve a hyperinflammatory response to viral infections, leading to blood-brain barrier disruption, cytokine storm, and necrosis of neural tissue [1, 2]. Viral triggers commonly associated with acute necrotizing encephalopathy include influenza A and B, human herpesvirus-6, and enteroviruses [2]. Adenovirus, while a well-documented cause of respiratory and gastrointestinal infections, is a less frequently reported precipitant of acute necrotizing encephalopathy [3]. This case highlights adenovirus as a rare etiological agent in the development of this devastating neurological condition in a previousl healthy young adult.

Case presentation

A previously healthy 19-year-old male presented to the emergency department with a sudden onset of fever, headache, altered mental status, and seizures. His symptoms began two days prior to admission, starting with a high-grade fever (39.2 °C), generalized malaise, and intermittent headaches. On the day of admission, he experienced a generalized tonic-clonic seizure at home, witnessed by his mother, prompting immediate medical attention. His medical history was unremarkable, with no prior history of neurological disorders, recent travel, or sick contacts. He denied the use of illicit substances or recent alcohol consumption. Immunization history was up to date, and there was no family history of seizures, autoimmune disorders, or cerebrovascular diseases.

On arrival, the patient was febrile with a temperature of 39.5 °C, a blood pressure of 130/85 mmHg, a heart rate of 112 beats per minute, and a respiratory rate of 18 breaths per minute. Oxygen saturation was 98% on room air. His Glasgow Coma Scale score was 11 (E3V3M5), reflecting moderate impairment of consciousness. Physical examination revealed no signs of trauma or meningeal irritation. Neurological examination demonstrated a paucity of spontaneous movements bilaterally, with decreased responsiveness to noxious stimuli. Deep tendon reflexes were brisk on the right side and diminished on the left. Babinski’s sign was positive bilaterally. There were no cranial nerve deficits, and the funduscopic examination was unremarkable.

Based on the acute onset of fever, seizures, and altered mental status, along with focal neurological signs, the initial working diagnosis was viral encephalitis, with differential considerations including acute disseminated encephalomyelitis, cerebral venous thrombosis, and autoimmune encephalitis.

Initial laboratory investigations revealed leukocytosis with a white blood cell count of 14,800/µL (normal: 4,000–11,000/µL), predominantly neutrophilic, and elevated C-reactive protein at 12.5 mg/L (normal: <5 mg/L). Liver and kidney function tests were within normal limits. Coagulation studies showed mild elevation in prothrombin time at 15.2 s (normal: 11–14 s) and activated partial thromboplastin time at 40 s (normal: 25–35 s). Cerebrospinal fluid analysis via lumbar puncture revealed an opening pressure of 20 cm H₂O (normal: 6–20 cm H₂O), elevated protein at 78 mg/dL (normal: 15–45 mg/dL), glucose at 55 mg/dL with serum glucose of 90 mg/dL (normal CSF glucose: 45–80 mg/dL, typically 60–70% of serum glucose), and 120 white blood cells/µL, predominantly lymphocytic (normal: 0–5 cells/µL).

A non-contrast CT scan of the brain revealed bilateral hyperdensity in the thalamus (Fig. 1). The CT venogram did not show any evidence of thrombosis. An echocardiogram showed no evidence of emboli or infective endocarditis. Due to the patient’s decreased level of consciousness, he was intubated and admitted to the intensive care unit. While in the intensive care unit, the patient experienced another tonic-clonic seizure, witnessed by the nursing staff, prompting the initiation of intravenous levetiracetam for seizure management. To reduce cerebral inflammation and edema, intravenous dexamethasone at 10 mg every 6 h was started and continued for a total of 7 days, followed by a taper over 5 days. Supportive care also included antipyretics for fever and intravenous fluids for hydration.

Fig. 1.

Axial CT scan of the brain showing bilateral hyperdensity in the thalami (arrows)

Serological tests for HIV, toxoplasmosis, cytomegalovirus, and drug toxicology were negative. Influenza polymerase chain reaction and hepatic profile tests were also negative. Vasculitic screening, including antinuclear antibody (ANA), anti–double-stranded DNA (anti-dsDNA), antineutrophil cytoplasmic antibodies (both c-ANCA and p-ANCA), rheumatoid factor, complement levels (C3 and C4), and erythrocyte sedimentation rate (ESR), did not reveal any abnormalities, with all results within normal reference ranges. To further investigate the possibility of hemorrhagic leukoencephalitis or acute demyelinating encephalomyelitis, an MRI of the brain showed bilateral symmetrical multifocal lesions in the thalami, putamen, hippocampal lobes, and pons, exhibiting hyperintensity on T2 and FLAIR sequences, with associated central hypointensity. Microhemorrhagic foci were visible on susceptibility-weighted imaging, and diffusion-weighted imaging demonstrated restricted diffusion with high signal intensity (Fig. 2).

Fig. 2.

MR images of the brain demonstrating bilateral symmetrical edema in the paramedian thalami (arrowheads) and pons (arrows), with increased FLAIR signal intensity (A and B). Susceptibility-weighted imaging (C and D) reveals punctate microhemorrhages, consistent with the diagnosis of acute necrotizing encephalopathy

Polymerase chain reaction testing of the cerebrospinal fluid and nasopharyngeal swab confirmed the presence of adenovirus DNA, establishing an infectious etiology. Screening for other viral pathogens, including herpes simplex virus, enteroviruses, and arboviruses, was negative. Blood cultures and serological tests for autoimmune and paraneoplastic encephalitis, including antibodies against NMDA receptor, AMPA receptor, LGI1, CASPR2, GABA-B receptor, Hu, Yo, Ri, and Ma2/Ta, were unremarkable.

Following the diagnosis, the patient was started on appropriate supportive therapy. Gradual reduction of sedation was initiated, and he was weaned off mechanical ventilation after 10 days. Repeated MRI brain revealed an interval regression of the previously noted lesions in the thalami (Fig. 3). Physiotherapy and speech therapy were started to aid in his recovery. Despite some improvement, the patient was transferred to a nursing facility due to ongoing disability, characterized by persistent right-sided hemiparesis, moderate dysarthria, and impaired short-term memory. Over time, efforts focused on supportive care and rehabilitation to manage these long-term sequelae.

Fig. 3.

Follow-up axial MR image showing a reduction in the swelling of the paramedian thalami (arrows), with residual signal abnormalities indicative of partial resolution

Discussion

Acute necrotizing encephalopathy is a rare but devastating neurological disorder, typically triggered by viral infections, with a predilection for children and young adults. While influenza viruses, human herpesvirus-6, and enteroviruses are well-established etiological agents, adenovirus remains an infrequent but significant cause of acute necrotizing encephalopathy [4]. This case highlights adenovirus as the underlying pathogen in a previously healthy 19-year-old male, emphasizing the need for awareness of atypical viral triggers and the complex clinical presentation of this disease.

The pathophysiology of acute necrotizing encephalopathy is thought to involve a hyperinflammatory response to viral infection, resulting in blood-brain barrier disruption, widespread cytokine release, and subsequent necrosis of neural tissue [1, 5]. The hallmark MRI findings of acute necrotizing encephalopathy—bilateral, symmetric lesions primarily affecting the thalami, brainstem, and deep gray matter structures—are crucial for diagnostic recognition. The clinical course is typically characterized by rapid onset of fever, altered mental status, seizures, and progressive neurological deterioration [4]. The high morbidity and mortality associated with acute necrotizing encephalopathy are exacerbated by delayed diagnosis and the lack of effective antiviral therapies, as in this case, where no specific treatment exists for adenovirus infections.

In the present case, the patient presented with acute onset of fever, headache, altered mental status, and seizures, all of which are characteristic features of acute necrotizing encephalopathy. Initial imaging revealed hyperdensity in the thalami, which, in combination with the patient’s clinical presentation, prompted further investigation. The subsequent MRI revealed bilateral thalamic lesions, consistent with acute necrotizing encephalopathy. The absence of bacterial, fungal, or parasitic pathogens in cerebrospinal fluid analysis, alongside the negative results of serological tests for common viral infections, was critical in narrowing down the differential diagnosis.

The confirmation of adenovirus as the causative agent through PCR testing of both cerebrospinal fluid and nasopharyngeal swabs was pivotal in establishing the diagnosis. Although adenovirus is widely known for causing respiratory and gastrointestinal infections, its involvement in acute necrotizing encephalopathy has been less frequently documented in the literature [3]. This highlights a potentially underrecognized role of adenovirus in the pathogenesis of acute necrotizing encephalopathy, particularly in immunocompetent individuals.

The management of acute necrotizing encephalopathy is primarily supportive, as there is no antiviral therapy specifically targeted at adenovirus [5]. In this case, the patient received intravenous levetiracetam for seizure control, dexamethasone to reduce cerebral edema, and intensive monitoring in the intensive care unit. The prognosis of acute necrotizing encephalopathy varies depending on the severity of initial neurological involvement, the extent of brain damage, and the timeliness of intervention [4]. While some patients may experience full recovery, the majority have residual neurological deficits, including cognitive impairments, motor dysfunction, and speech difficulties. Rehabilitation plays a crucial role in the long-term care of these patients, as seen in this case, where the patient required ongoing physiotherapy and speech therapy. In severe cases, the risk of irreversible neurological damage remains high, and patients may face prolonged disability or death [5, 6].

Conclusion

This case demonstrates that adenovirus, although uncommon, can trigger acute necrotizing encephalopathy, a rapidly progressive and potentially devastating neurological complication. The characteristic imaging findings and swift clinical deterioration highlight the need for early recognition, molecular diagnostic confirmation, and prompt supportive management. By expanding the spectrum of known viral triggers, this report reinforces the importance of considering atypical pathogens in severe encephalopathy and the ongoing need for research into targeted therapies and long-term outcomes.

Authors’ contributions

SA was solely responsible for the conception, data collection, analysis, and writing of the manuscript. The author reviewed and approved the final version of the manuscript.

Funding

This research received no specific funding from any external source. All the authors contributed their time and resources voluntarily.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

The study was conducted in strict adherence to the principles outlined in the Declaration of Helsinki, with ethical clearance obtained from the Institutional Review Board at King Abdulaziz University. The informed consent process included a comprehensive explanation of the voluntary nature of participation, with a particular emphasis on measures taken to ensure the confidentiality of participant information

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.