Cause of Seizures in Eclampsia
Eclamptic seizures result from severe cerebral autoregulation failure triggered by placental dysfunction, leading to vasogenic cerebral edema that lowers the seizure threshold. 1
Primary Pathophysiologic Mechanism
The pathogenesis follows a two-stage cascade:
Stage 1: Placental Dysfunction
- Abnormal placentation is the initiating event, characterized by shallow cytotrophoblast invasion of maternal spiral arteries 1
- Spiral arteries fail to undergo normal remodeling, remaining small muscular vessels instead of becoming distended, low-resistance channels 1
- This results in reduced placental perfusion and placental ischemia 2, 1
Stage 2: Systemic Endothelial Dysfunction and Cerebral Injury
- The ischemic placenta releases soluble factors into maternal circulation, particularly excess soluble fms-like tyrosine kinase-1 (sFlt-1), causing systemic endothelial dysfunction throughout maternal vasculature, including cerebral vessels 2, 1
- These circulating factors antagonize vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), contributing to widespread endothelial injury 2, 3
- Blood-brain barrier disruption occurs, with increased permeability allowing passage of fluid, ions, and plasma proteins into brain parenchyma 3
Cerebral Autoregulation Failure
When severe hypertension exceeds the upper limit of cerebral autoregulation, forced vasodilation occurs with further endothelial injury 1:
- This results in vasogenic cerebral edema, predominantly affecting posterior circulation territories (posterior reversible encephalopathy syndrome) 1, 3
- The cerebral edema and vascular dysfunction lower the seizure threshold, precipitating eclamptic convulsions 1, 4
- Imaging studies demonstrate cerebral edema and/or cerebral hemorrhage in eclamptic patients 4
Clinical Context
Eclampsia occurs in approximately 2% of women with severe preeclampsia who do not receive magnesium sulfate prophylaxis, compared to <0.6% in those receiving prophylaxis 1, 3:
- Warning signs indicating high seizure risk include occipital lobe blindness, hyperreflexia, clonus, severe headache, and visual disturbances 2, 1
- These symptoms reflect severe cerebrovascular involvement and impending autoregulation failure 2
Important Clinical Pitfalls
- The pathophysiology is fundamentally different from primary epilepsy—eclamptic seizures are caused by acute cerebrovascular dysfunction, not primary neuronal hyperexcitability 4
- Eclampsia can occur postpartum (up to 1 month after delivery), as circulating placental factors may persist temporarily even after delivery 5
- The only definitive treatment is delivery of the placenta, which removes the source of circulating pathogenic factors 1, 6
- Magnesium sulfate prevents recurrent seizures but does not address the underlying placental pathology 3, 7