Acute encephalopathy in a child caused by infl uenza A virus

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version

Dear Editor,

Influenza viruses A, B, and C from the genus Influenza, family Orthomyxoviridae, typically cause highly contagious respiratory diseases accompanied by fever, chills, headaches, and muscle and joint pain. They are transmitted by droplet infection [1]. The diagnosis is most often made based on an assessment of clinical symptoms. The polymerase chain reaction (PCR) method is used to detect influenza nucleic acid. Treatment is usually only symptomatic. Antiviral and immunomodulatory therapy is available in indicated cases. However, its effectiveness has not yet been well documented. Oseltamivir can be used orally as an antiviral agent, administered for 5 days, with treatment extended in cases of high risk of complications and severe disease. However, the total duration of administration is not precisely specified. Zanamivir is available for inhalation. Peramivir is intended for intravenous administration and is administered once within 2 days of the onset of symptoms. The most effective preventive measure is vaccination. Inactivated trivalent or tetravalent vaccines are available. Influenza is a specific disease characterized by the evolution of its causative agent. The antigenic composition of the vaccine is therefore adjusted annually according to the recommendations of the World Health Organization and the European Commission. Infants as young as 6 months of age can be vaccinated. The goal is to achieve 70-75% vaccination coverage of at-risk population groups [1,2]. Complications of influenza can be primary, caused by the direct action of the influenza virus, or secondary, caused by bacterial superinfection. Patients with chronic diseases, immunodeficiency or immunosuppressive medication, and obesity are particularly at risk. The most common complication is pneumonia, but any system can be affected. Gastrointestinal problems such as vomiting or diarrhea are common, especially in children and during influenza B. The kidneys and liver may be affected, and thromboembolic disease may develop. In children, hemolytic-uremic syndrome rarely develops. Cardiovascular complications include peri-/myocarditis, which can lead to secondary heart failure or the development of acute coronary syndrome. Influenza rarely causes eye damage, but in 3% of cases, optic neuritis may develop [1].

Neurological complications are rare. Their diagnosis is complex, and there are no clear or validated criteria. Clinical symptoms vary in severity and are very diverse. Brain MRIs are positive in up to 62% of cases. In contrast, the influenza virus, or rather its RNA, is rarely detected in cerebrospinal fluid, and according to the literature, diagnosis is successful in only 16% of cases [3].

Neurological involvement is more common in the pediatric population, especially in children younger than 5 years of age [2–7]. According to Goenka et al., influenza A (H1N1) virus is detected in up to 81% of cases [8]. They include acute, subacute, and chronic forms [2,3,5,6]. Neurological symptoms usually appear in the first days of influenza [1]. In encephalitis, a change in consciousness is expressed in 100% of cases, and convulsions (80%) or vomiting (25%) may be present [6]. The disease is fatal in up to one-third of cases [5]. It can leave permanent sequelae in 68% of patients [8]. Any area of the CNS can be affected. Damage to the CNS is caused by the direct action of the virus and immunopathological processes that arise from the action of pro-inflammatory cytokines (interleukin-6, interleukin-10, tumor necrosis factor, and others) [5,6]. Histologically, we find edema, nonspecific inflammatory changes, and hemorrhagic and thrombotic involvement of the vascular endothelium [2,4,5].

The most serious entity is acute encephalitis. It can be fulminant, presenting as necrotizing encephalopathy (ANE), with multifocal hemorrhagic-necrotic changes in the brain that occur symmetrically, bilaterally, and often affect the thalamus. It was first described in Japan in 1995 [7]. This also includes acute encephalopathy with biphasic seizures and late diffusion restriction on MRI (AESD). Here, the subcortical white matter is typically affected. Clinically, it manifests itself as a biphasic course of seizures, with prolonged febrile paroxysms at the onset of the disease. Another form is encephalitis/encephalopathy with reversible spleen involvement. These patients have a more favorable prognosis and neurological outcome. The spectrum of influenza-associated encephalopathies also includes PRES (posterior reversible encephalopathy syndrome), which can manifest days or weeks after the initial symptoms of the virus. Hemorrhagic leukoencephalopathy (AHLE) has a fulminant course [4,6].

Subacute disorders include cerebellitis, acute disseminated encephalomyelitis (ADEM), and Guillain-Barré syndrome [2,4–6]. In rare cases, children may also develop Rey syndrome or narcolepsy [1,4]. Autoimmune dysregulation also plays a role in the pathogenesis of these conditions, and antibodies against glutamate receptors can be detected. A certain genetic predisposition is also assumed, and the literature mentions a connection with a pathogenic variant on chromosome 2q in the RANBP2 gene. These patients are more likely to have neuroinfections, including neurological complications during influenza [6].

In February 2025, we hospitalized a 17-year-old previously healthy boy. He had not been vaccinated against influenza. He had been ill for 6 days. The day before admission, he was unusually tired, and that same night he was found unconscious at home. Upon admission, the boy had severe impaired consciousness (Glasgow Coma Scale 5) but no convulsions. CT, including CTA of the brain, showed no pathology. Blood count showed leukopenia, iontogram, renal and hepatic parameters were normal, inflammatory markers were negative. Toxicological examination was negative. Blood culture was negative. SARS-CoV-2 testing was negative. Influenza A H1N1 (PCR) was positive in respiratory tract samples. Cytological examination of cerebrospinal fluid was normal, biochemically hyperproteinorachia 0.728 g/l, lactate was low. Bacteriological and virological tests were subsequently negative. We also considered autoimmune etiology in the differential diagnosis, but this was not proven. MR + MRA showed bilateral thalamic involvement (Fig. 1).

We assessed the clinical condition as acute encephalopathy in influenza A. The boy was placed on a non-aggressive ventilation regimen. Due to the serious condition and unclear diagnosis at the beginning of hospitalization, antibiotics (ceftriaxone in a single dose) and acyclovir were prescribed pending the results of culture tests. Oseltamivir was administered via a nasogastric tube for 10 days, and the boy also received pulses of methylprednisolone (5× 1 g). Due to the serious course of the disease, immunoglobulins were administered at a total dose of 2 g/kg.

Artificial lung ventilation was discontinued after 132 hours. Despite the severe initial clinical findings, there was a rapid improvement in neurological findings. A follow-up brain MRI performed 12 days later showed significant regression of the findings, with only mild hypersignal areas persisting bilaterally in the dorsomedial thalamus, in a diffusion-weighted image without pathological diffusion restriction (Fig. 2). An EEG was performed on the 7th day of hospitalization, revealing a mild diffuse nonspecific abnormality.

The boy was discharged on the 13th day. The neurological findings described positive pyramidal symptoms in the lower limbs, but without motor deficit, and mild inhibitory psychoorganic syndrome. Six weeks after discharge, he returned to high school.

Although the influenza virus is not a typical neurotropic virus, neurological complications must be considered. Early diagnosis of the disease and the chosen course of treatment led to an excellent clinical outcome, although there are no clear recommendations for therapy.

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study.