What are the neurological complications of influenza?

From the Guidelines

Neurological complications of influenza can range from mild to severe and potentially life-threatening conditions, and early antiviral treatment with neuraminidase inhibitors like oseltamivir is recommended to reduce the risk of complications. The most common neurological manifestations include febrile seizures, encephalopathy, encephalitis, and Guillain-Barré syndrome. Influenza-associated encephalopathy typically presents with altered consciousness, seizures, and neurological deficits within a few days of flu symptom onset, with children being particularly vulnerable 1. Encephalitis involves direct viral invasion of the brain tissue, causing inflammation. Guillain-Barré syndrome, an autoimmune disorder affecting peripheral nerves, can develop 1-3 weeks after influenza infection, causing ascending paralysis. Other less common complications include transverse myelitis, acute necrotizing encephalopathy (particularly in children), and exacerbation of existing neurological conditions. These complications occur due to direct viral invasion, immune-mediated responses, or metabolic disturbances.

Some key points to consider:

• Influenza-associated encephalopathy can present with altered consciousness, seizures, and neurological deficits within a few days of flu symptom onset 1.
• Encephalitis involves direct viral invasion of the brain tissue, causing inflammation, and can be associated with respiratory illnesses in children, including influenza viruses, paramyxoviruses, and the bacterium M. pneumoniae 1.
• Guillain-Barré syndrome can develop 1-3 weeks after influenza infection, causing ascending paralysis 1.
• Annual influenza vaccination remains the most effective preventive measure against these potentially serious neurological complications 1.
• Antiviral treatment with neuraminidase inhibitors like oseltamivir is recommended for all persons with suspected or confirmed influenza who are at higher risk for influenza complications, including children aged <2 years, adults aged ≥65 years, and persons with chronic pulmonary, cardiovascular, renal, hepatic, hematological, or metabolic disorders 1.

From the FDA Drug Label

Influenza can be associated with a variety of neurologic and behavioral symptoms which can include events such as seizures, hallucinations, delirium, and abnormal behavior, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease There have been postmarketing reports of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors (NAIs), including RELENZA. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon based on usage data for RELENZA These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of RELENZA to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior. If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient.

Neurological complications of influenza can include seizures, hallucinations, delirium, and abnormal behavior, which may result in fatal outcomes.

• These events may occur with or without encephalitis or encephalopathy.
• Postmarketing reports have shown delirium and abnormal behavior leading to injury in patients with influenza taking neuraminidase inhibitors, including RELENZA.
• The contribution of RELENZA to these events is unknown.
• Patients with influenza should be closely monitored for signs of abnormal behavior, and the risks and benefits of continuing treatment should be evaluated if neuropsychiatric symptoms occur 2.

From the Research

Neurological Complications of Influenza

• Neurological complications associated with influenza infection are rare but can be severe and underappreciated, as noted in a study published in 2012 3.
• The most common neurological complications include seizures, encephalopathy, and other conditions such as stroke, focal neurologic deficits, Guillain-Barré syndrome, acute disseminated encephalomyelitis, and transverse myelitis, as reported in studies from 2012 and 2013 3, 4.

Treatment and Management

• Neuraminidase inhibitors (NAIs) are the only class of antiviral agent recommended for the treatment of currently circulating strains of influenza, with evidence suggesting they can reduce the duration of illness and possibly the rate of complications and hospitalization, as shown in studies from 2018 and 2001 5, 6.
• Early use of NAIs, such as oseltamivir, is crucial for optimal clinical outcomes, and strategies to improve early widespread utilization are needed, as highlighted in a study from 2018 5.
• Supportive care, including optimizing respiratory failure through ventilatory strategies, is also essential in the management of influenza, particularly in critically ill patients, as discussed in a study from 2020 7.

Specific Neurological Complications

• Seizures are the most common neurological complication, occurring as febrile seizures, exacerbations in patients with epilepsy, or symptoms of other influenza-induced neurologic disorders, as noted in a study from 2012 3.
• Encephalopathy is the second most common neurological complication, with a wide spectrum of conditions ranging from coma to mild altered mental states, as reported in studies from 2012 and 2013 3, 4.