Sepsis is a life-threatening medical emergency that arises when the body’s response to an infection becomes dysregulated, causing damage to its own tissues and organs. A seizure is a sudden, uncontrolled electrical disturbance in the brain, resulting from abnormal neuronal firing. This can cause temporary changes in movement, sensation, behavior, awareness, or consciousness.
The Link Between Sepsis and Seizures
Sepsis can lead to seizures through physiological mechanisms that affect brain function. The systemic inflammation associated with sepsis causes a release of inflammatory mediators, such as cytokines, which can have excitatory effects on the central nervous system. These cytokines can increase the extracellular concentration of glutamate, a neurotransmitter that promotes neuronal activity, and decrease its reuptake by astrocytes.
The blood-brain barrier (BBB), which normally protects the brain from harmful substances, can become disrupted during sepsis. Increased vascular permeability allows inflammatory mediators and other harmful substances to enter the brain, intensifying neuroinflammation and increasing seizure risk. This breakdown in the BBB can also lead to brain edema, which may compress brain tissue and impair cerebral perfusion.
Sepsis-associated encephalopathy (SAE), a brain dysfunction in sepsis patients, often presents with neurological symptoms, including seizures. This encephalopathy involves disruptions in neurotransmitters, abnormal brain signal transmission, and oxidative stress. Changes in neurotransmitters like acetylcholine and dopamine, which are important for normal brain function, can lead to cognitive impairment and contribute to seizure activity.
Metabolic disturbances in sepsis can also contribute to seizures. These include imbalances in electrolytes such as sodium, calcium, and magnesium, and blood glucose levels, specifically hypoglycemia (low blood sugar). Both very high and very low blood glucose levels can cause neurocognitive disorders.
Reduced cerebral blood flow and microcirculatory disturbances in the brain occur during sepsis. Systemic inflammation causes vasodilation and fluid leakage, leading to inadequate blood supply. Impaired cerebral vascular contractile function and increased vascular resistance compromise blood flow, leading to brain tissue hypoxia and neuronal injury, triggering seizures.
Identifying Sepsis-Related Seizures
Seizures in patients with sepsis can manifest in various ways, ranging from subtle changes in consciousness to generalized convulsions. Up to 20% of critically ill patients, including those with sepsis, may experience seizures. These can be convulsive, such as generalized tonic-clonic seizures, or nonconvulsive seizures (NCS), which are more common in sepsis-associated encephalopathy, accounting for about 90% of cases.
Generalized tonic-clonic seizures involve loss of consciousness and widespread muscle contractions, while focal seizures affect specific areas of the brain and may present with localized twitching, sensory disturbances, or changes in behavior. In critically ill patients, particularly the elderly, seizures might present atypically, with symptoms like prolonged confusion, memory lapses, or inattention. Nonconvulsive seizures can be particularly challenging to identify because they lack overt motor symptoms.
To diagnose sepsis-related seizures, healthcare providers use electroencephalography (EEG). EEG measures the electrical activity in the brain and can detect abnormal patterns indicative of seizure activity, even in patients who do not show obvious clinical signs. EEG abnormalities in septic patients can include diffuse slow waves, periodic discharges, or electrographic seizures.
Imaging tests like computed tomography (CT) or magnetic resonance imaging (MRI) are performed to rule out other causes of altered mental status or seizures, such as stroke, intracranial hemorrhage, or central nervous system infections like meningitis or encephalitis. Blood tests are also used to identify metabolic disturbances, such as electrolyte imbalances or blood glucose abnormalities, which can provoke seizures.
Treating Sepsis-Induced Seizures
Treatment for seizures in sepsis involves a two-pronged approach: controlling the seizure activity and addressing the underlying infection and systemic response. Rapid intervention is important to prevent further brain damage.
Anti-seizure medications manage seizures. Benzodiazepines, such as midazolam or lorazepam, are often first-line due to rapid onset. If seizures continue despite benzodiazepine therapy, longer-acting anti-seizure medications like phenytoin, valproic acid, or levetiracetam are used. In cases where seizures are resistant to initial treatments (status epilepticus), anesthetic agents like propofol or thiopental are used to induce burst suppression, to interrupt pathological electrical activity in the brain.
Alongside seizure management, treatment of the underlying sepsis is important. This involves prompt administration of broad-spectrum antibiotics, given intravenously. Intravenous fluids are given to maintain adequate blood flow to organs and prevent dangerously low blood pressure. If blood pressure remains low despite fluid resuscitation, vasopressor medications are used to constrict blood vessels and increase blood pressure.
Supportive care measures are implemented to manage organ dysfunction from sepsis. This can include oxygen therapy for oxygen delivery, mechanical ventilation for breathing difficulties, or dialysis if kidney function is impaired. Monitoring blood glucose levels and administering insulin if hyperglycemia occurs is part of sepsis management.
Recovery and Aftermath
Recovery from sepsis, especially when complicated by seizures, can be a challenging process. While many individuals with sepsis fully recover, those who experience severe complications like septic shock may require support and rehabilitation. The prognosis can depend on the degree of brain dysfunction and the presence of any prior neurological disorders.
Some individuals experience persistent neurological deficits after sepsis-induced seizures. These can include cognitive impairments affecting memory, attention, and executive functions. Long-term risks, such as recurrent seizures, are higher in sepsis survivors. Sepsis may lead to permanent neurological consequences.
Rehabilitation begins in the hospital, focusing on regaining physical abilities like sitting, standing, and walking. This gradual increase in activity, combined with adequate rest, supports the healing process. Cognitive rehabilitation and psychological counseling can address issues such as memory problems, anxiety, or depression.
The need for long-term anti-seizure medication after a sepsis-induced seizure depends on the risk of recurrence. If risk factors for epilepsy are identified, such as abnormalities on an EEG or structural brain lesions, medication is considered. However, the specific risk factors for chronic epilepsy following sepsis and optimal therapy duration are still being investigated.