Sepsis is a life-threatening medical emergency defined as the body’s dysregulated response to an infection. This response causes widespread inflammation that can rapidly lead to organ dysfunction. Among the most serious consequences of sepsis are the neurological complications, and sepsis can cause seizures. These seizures represent a severe form of acute brain dysfunction that frequently complicates the course of a septic illness.
Defining Sepsis-Associated Encephalopathy
The umbrella term for the neurological dysfunction that results from a systemic infection like sepsis is Sepsis-Associated Encephalopathy (SAE). SAE is a common complication, affecting up to 70% of patients with severe sepsis or septic shock. It is characterized by diffuse brain dysfunction that is not caused by a direct infection of the central nervous system, such as meningitis or a brain abscess.
Seizures are one of the most serious manifestations of SAE, alongside symptoms like delirium, confusion, and reduced consciousness. The development of seizures is associated with a worse prognosis for the patient. While delirium is the most common sign of SAE, the occurrence of seizures indicates a higher level of neuronal hyperexcitability and disturbance.
Biological Mechanisms of Brain Injury
Systemic Inflammation and the Blood-Brain Barrier
The mechanisms by which sepsis triggers seizures are complex and involve multiple biological pathways. One primary factor is the overwhelming systemic inflammation, often referred to as a cytokine storm. Pro-inflammatory molecules like TNF-α and interleukins are released, and these can directly affect brain cells. These inflammatory mediators also promote damage to the blood-brain barrier (BBB), which normally protects the brain. When the BBB integrity is compromised, cytokines and other inflammatory cells can cross into the brain tissue, leading to neuroinflammation and heightened neuronal excitability. This inflammatory cascade can interfere with neurotransmitters, such as increasing the excitatory neurotransmitter glutamate, which contributes to the electrical instability that causes seizures.
Metabolic and Circulatory Stress
Metabolic disturbances resulting from systemic illness also play a role in brain injury and seizure risk. Sepsis can lead to systemic low oxygen delivery (hypoxia) and poor blood flow (hypoperfusion), which starves brain cells of necessary nutrients. Furthermore, imbalances in electrolytes and blood sugar (hypoglycemia) can disrupt the normal electrical signaling of neurons, making them prone to erratic firing. Microcirculatory dysfunction is another mechanism, where reduced blood flow occurs within the brain’s smallest vessels. This can cause localized areas of ischemia, or tissue damage from lack of blood, which can act as a focus for seizure activity.
Recognizing and Managing Seizures
Diagnosis
Recognizing seizures in a critically ill patient with sepsis can be challenging because the manifestations are often subtle, especially in patients who are sedated or receiving mechanical ventilation. While generalized convulsions are sometimes seen, non-convulsive seizures (NCS) are highly prevalent and can easily be missed without specialized monitoring. Non-convulsive seizures involve electrical discharges without the dramatic, visible muscle jerking, instead presenting as unresponsiveness, subtle eye fluttering, or unexplained fluctuations in consciousness. The primary diagnostic tool for confirming seizures, particularly the non-convulsive type, is continuous electroencephalography (cEEG). Other imaging tests, such as a CT scan or MRI, may be performed to rule out other possible causes of altered mental status.
Acute Management
Acute management of seizures requires immediate pharmacological intervention with anticonvulsant medications to stop the electrical activity. Benzodiazepines, such as lorazepam or midazolam, are typically the first-line treatment to rapidly halt the seizure. Following this immediate step, other anti-seizure medications are used to prevent recurrence while simultaneously stabilizing the underlying sepsis through antibiotics, fluid resuscitation, and blood pressure support.
Recovery and Prognosis
The outcome for a patient who experiences seizures during sepsis depends on the severity of the underlying infection and the promptness of care. Seizures are a marker of more severe brain involvement and are associated with increased mortality during the acute hospitalization. Patients who survive the episode may still face long-term neurological consequences.
Survivors of sepsis, especially those who experienced SAE, frequently report persistent cognitive impairment affecting memory, attention, and executive function. Functional rehabilitation and psychological support are often required to address these deficits after discharge. Studies suggest that survivors of sepsis face a significantly higher long-term risk of developing future non-sepsis related seizures compared to the general population. This elevated risk suggests that the septic episode causes permanent neurological changes, creating a vulnerability to later seizure development.