Influenza virus and CNS manifestations
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.
References (72)
- Prevention and control of influenza: recommendations of the Advisory Committee on Immunization practices (ACIP),...
- et al.
Reye's syndrome in the United States from 1981 through 1997
New Engl. J. Med.
(1999) - et al.
Influenza—a infection in children
Lancet
(1972) - et al.
A nationwide outbreak of Reye's syndrome. Its epidemiologic relationship to influenza B
Am. J. Med.
(1976) - et al.
Reye's syndrome: clinical progression and evaluation of therapy
Pediatrics
(1977) Diagnosis and treatment of acute encephalitis
Neurologist
(2000)- et al.
Experimental influenza causes a non-permissive viral infection of brain, liver and muscle
J. Neurovirol.
(2000) - et al.
Influenza A virus associated with acute encephalopathy
Am. J. Dis. Child.
(1979) - et al.
Influenzal encephalopathy and postinfluenzal encephalitis
Lancet
(1958) - et al.
Type A influenza: postmortem virus isolations from different organs in human lethal cases
Arch. Virol.
(1977)
MRI and SPECT in influenzal encephalitis
Pediatr. Neurol.
PCR on cerebrospinal fluid to show influenza-associated acute encephalopathy or encephalitis
Lancet
Influenza A virus encephalopathy with symmetrical thalamic lesions
Eur. J. Pediatr.
A pregnant woman with influenza A encephalopathy in whom influenza A/Hong Kong virus (H3) was isolated from cerebrospinal fluid
Arch. Intern. Med.
Reye's syndrome: an association with influenza A infection
Ky. Med. Assoc.
Computed tomography in postinfluenzal encephalitis
Brain Dev.
Two cases of influenza B encephalitis
J. Neurol. Neurosurg. Psychol.
Influenza virus
Probable post-influenza cerebellitis
Intern. Med.
Neurologic disorders after Asian influenza
New Engl. J. Med.
Detection of influenza virus RNA by reverse transcription-PCR and proinflammatory cytokines in influenza-virus-associated encephalopathy
J. Med. Virol.
The spectrum of antecedent infections in Guillain-Barre's syndrome: a case–control study
Neurology
Neurological and hepatic disorders associated with influenza
Br. Med. J.
Proved viremia in Asian influenza (Hong Kong variant) during incubation period
Br. Med. J.
Serial magnetic resonance imaging in post-infectious focal encephalitis due to influenza virus
J. Neurol. Sci.
Clinical and radiological variability of influenza-related encephalopathy or encephalitis
Acta Paediatr. Jpn.
Etiology of acute childhood encephalitis at the hospital for sick children, Toronto, 1994–1995
Clin. Infect. Dis.
Therapeutic brain concentrations of the NMDA receptor antagonist amantadine
Neuropharmacology
Infections of the central nervous system of suspected viral origin: a collaborative study from Finland
J. Neurovirol.
Periodic lateralized epileptiform discharges in influenza B-associated encephalopathy
Intern. Med.
Antiviral agents for treating influenza
Clevel. Clin. Med. J.
Influenza RNA not detected in archival brain tissues from acute Encephalitis lethargica cases or in postencephalitic Parkinson cases
J. Neuropathol. Exp. Neurol.
Influenza B virus encephalitis
Clin. Infect. Dis.
Outbreak of influenza in a neonatal intensive care unit
J. Pediatr.
Isolated lesions limited to the bilateral substantia nigra on MRI associated with influenza A infection
Eur. Neurol.
Cited by (172)
New onset status epilepticus in influenza associated encephalopathy: The presenting manifestation of genetic generalized epilepsy
2021, Epilepsy and Behavior ReportsOlfactory immune response to SARS-CoV-2
2024, Cellular and Molecular ImmunologyBibliometric analysis of publication trends and topics of influenza-related encephalopathy from 2000 to 2022
2023, Immunity, Inflammation and DiseaseOlfactory immunology: the missing piece in airway and CNS defence
2023, Nature Reviews Immunology