Influenza virus and CNS manifestations

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Abstract

Neurological involvement during influenza infection has been described during epidemics and is often consistent with serious sequelae or death. An increasing incidence of influenza-associated encephalitis/encephalopathy has been reported in Japan, mainly in children. A variety of other clinical CNS manifestations, such as Reye's syndrome, acute necrotising encephalopathy (ANE), and myelitis as well as autoimmune conditions, such as Guillain-Barre's syndrome, may occur during the course of influenza infection. Virological diagnosis is essential and based on virusisolation, antigen detection, RNA detection by PCR, and serological analyses. Neuroimaging with CT and MRI of the brain are of prognostic value. The pathogenic mechanisms behind the influenza CNS complications are unknown. The treatment is symptomatic, with control of vital functions in the intensive care unit, antiepileptic medication and treatment against brain oedema.

Section snippets

Virology and epidemiology of influenza

Influenza viruses are important human pathogens that throughout history have caused epidemics and pandemics. Both Influenza A and B are associated with high mortality and morbidity, although Influenza B does not cause pandemics due to its antigenic stability (Nguyen-Van-Tam, 1998). New pandemic strains of Influenza A, to which the population lacks immunity, emerge either by acquisition of new gene segments in cells simultaneously infected by a human and an animal influenza A virus, or by direct

Clinical features of influenza

The spectrum of influenza may range from asymptomatic infection or mild to severe respiratory tract infection to systemic disease (“flu”) with abrupt onset of fever. The incubation period is 1–5 days. The illness, with fever and cough, sore throat, headache, anorexia, and myalgia affecting the back and limbs, may last for 1–5 days. Children often present with non-specific symptoms such as vomiting, diarrhoea in addition to high fever, cough and rhinorrhea. Paediatric influenza may provoke

CNS manifestations

CNS involvement during influenza includes a variety of syndromes, more often described in children than in adults (Nicholson, 1998). The major clinical entities are encephalitis or encephalopathy. In etiological studies of encephalitis, Influenza A and/or B have been identified in up to 8.5% of adult patients with positive virological findings (Koskiniemi et al., 2001) and in up to 10% of paediatric cases (Kolski et al., 1998). Reye's syndrome and acute necrotising encephalopathy (ANE) are

Diagnosis of CNS infection

The suspicion of CNS infection is ascertained by neuroimaging with MRI/CT of the brain, EEG pathology, and virological analyses of CSF (Table 2).

Prognosis

The outcome in encephalitis/encephalopathy depends mainly on age and presence of CT/MRI pathology. Neuroimaging studies in influenza encephalitis/encephalopathy reveal that patients with pathological CT/MRI are significantly younger and have more severe sequelae or fatal disease in comparison with patients with normal CT/MRI, the majority of whom recover or have mild sequelae (Table 1). However, severe sequelae such as choreoathetosis, altered personality, spastic quadriparesis, and persistent

Treatment

The therapy in CNS complications of influenza is supportive with supervision of vital functions in the intensive care unit including control of intracranial pressure, antiepileptic treatment against seizures, and treatment against brain oedema. Mild hypothermia (34–35 °C) therapy has been tried for suppressing brain oedema (Yokota et al., 2000, Munakata et al., 2000) in addition to corticosteroid treatment. Whether antiviral treatment in CNS complications of influenza may have beneficial effect

Conclusions

CNS complications during influenza virus infection are diverse, and the pathogenesis is mostly unknown. The phenomenon of frequent reports of influenza-associated encephalitis/encephalopathy from Japan, and infrequent reports from other parts of the world is puzzling. Virological analyses with virusisolation or detection of viral RNA by PCR from the CSF and respiratory tract, antigen detection, and serological analyses are important for establishing the diagnosis of influenza virus infection.

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