What causes seizures when the brain doesn't receive enough oxygen?

Seizures During Cerebral Hypoxia: Mechanisms and Implications

Seizures occur when the brain doesn't receive enough oxygen primarily due to disruption of normal neuronal function, excitotoxicity, and energy failure in brain cells, leading to abnormal excessive and synchronous neuronal activity. 1

Pathophysiological Mechanisms of Hypoxia-Induced Seizures

• Hypoxia (low oxygen levels) causes energy failure in brain cells as oxygen is essential for ATP production through oxidative phosphorylation, leading to membrane depolarization and abnormal neuronal firing 1

• Cerebral hypoxia results in microcirculatory failure, impaired autoregulation, and metabolic derangements that directly contribute to seizure generation 1

• During hypoxic states, there is a progressive dissociation between neuronal activity, energy demand, and cerebral blood flow, creating conditions favorable for seizure development 2

• Excitotoxicity occurs when low oxygen levels lead to excessive release of glutamate, which overstimulates NMDA and AMPA/KA receptors, causing calcium influx and triggering seizure activity 3

Clinical Manifestations of Hypoxic Seizures

• Hypoxic seizures manifest as various forms including generalized tonic-clonic seizures, myoclonus, and other seizure types depending on the severity and duration of oxygen deprivation 1

• Post-cardiac arrest brain injury commonly presents with seizures, myoclonus, varying degrees of neurocognitive dysfunction, and potentially brain death 1

• In neonates, hypoxic-ischemic encephalopathy is the most common cause of seizures (46-65% of cases), with approximately 90% of infants experiencing seizure onset within 2 days after birth 1

• Hypoxemia and hypercarbia both increase the likelihood of seizures and may contribute to secondary brain injury 1

Pathological Changes During Hypoxic Seizures

• Hypoxia during seizures causes oxidative stress and damages post-ischemic neurons, particularly affecting vulnerable regions like the hippocampus, thalamus, and brainstem 4

• Brain imaging studies show that the extent of hypoxia during seizures correlates with volume loss in critical brain regions including the periaqueductal gray, thalamus, hypothalamus, cerebellum, and brainstem 4

• Hypoxic seizures can trigger a cascade of inflammatory responses and activation of immune and coagulation pathways, similar to what is seen in sepsis 1

• Significant myocardial dysfunction is common after hypoxic events and cardiac arrest, which can further compromise cerebral perfusion and oxygenation 1

Long-Term Consequences of Hypoxic Seizures

• Hypoxia-induced seizures can lead to long-term increased seizure susceptibility and epileptogenesis, particularly when the hypoxic episode is prolonged 5, 3

• Animal studies show that even brief hypoxic seizures can cause later-life behavioral changes, including anxiety-related behaviors and increased susceptibility to subsequent seizures 5

• The duration of hypoxic seizures appears to be critical in determining long-term outcomes, with longer seizures associated with greater epileptogenic potential 3

• Hypoxic seizures may contribute to neuronal damage and cognitive impairment even without visible structural damage on conventional imaging 5

Management Considerations

• Immediate oxygen supplementation is crucial for patients with hypoxemia to maintain arterial oxygen saturation between 94-98% in most cases 1, 6

• For patients at risk of hypercapnic respiratory failure, a lower oxygen saturation target of 88-92% may be appropriate 1, 6

• Positioning patients with the head of bed elevated 15-30° can help reduce the risk of aspiration and improve ventilation, particularly in patients with decreased consciousness 1

• Antiepileptic drugs may be necessary to control seizures, with some evidence suggesting that sodium channel antagonists (carbamazepine, lamotrigine) and GABA enhancers (tiagabine, vigabatrin) may be effective in hypoxia-induced seizures 7

Special Considerations

• In neonates with hypoxic seizures, MRI with diffusion-weighted imaging is the most sensitive method for detecting hypoxic-ischemic injury 1

• Phenobarbital has limited efficacy in controlling hypoxia-induced seizures in neonatal models 5

• Careful monitoring of oxygen saturation, neurological status, and vital signs is essential in patients with hypoxic seizures 1

• AMPA/KA receptor antagonists may be more effective than NMDA receptor antagonists in preventing the epileptogenic effects of hypoxic seizures, according to animal studies 3