Seizure-promoting effect of blood-brain barrier disruption

Epilepsia. 2007 Apr;48(4):732-42. doi: 10.1111/j.1528-1167.2007.00988.x. Epub 2007 Feb 23.


Purpose: It is generally accepted that blood-brain barrier (BBB) failure occurs as a result of CNS diseases, including epilepsy. However, evidences also suggest that BBB failure may be an etiological factor contributing to the development of seizures.

Methods: We monitored the onset of seizures in patients undergoing osmotic disruption of BBB (BBBD) followed by intraarterial chemotherapy (IAC) to treat primary brain lymphomas. Procedures were performed under barbiturate anesthesia. The effect of osmotic BBBD was also evaluated in naive pigs.

Results: Focal motor seizures occurred immediately after BBBD in 25% of procedures and originated contralateral to the hemisphere of BBBD. No seizures were observed when BBB was not breached and only IAC was administered. The only predictors of seizures were positive indices of BBBD, namely elevation of serum S100beta levels and computed tomography (CT) scans. In a porcine model of BBBD, identical procedures generated an identical result, and sudden behavioral and electrographic (EEG) seizures correlated with successful BBB disruption. The contribution of tumor or chemotherapy to acute seizures was therefore excluded.

Conclusion: This is the first study to correlate extent of acute BBB openings and development of seizures in humans and in a large animal model of BBB opening. Acute vascular failure is sufficient to cause seizures in the absence of CNS pathologies or chemotherapy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Biomarkers / blood
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiopathology*
  • Brain / physiopathology*
  • Brain Neoplasms / complications
  • Brain Neoplasms / drug therapy
  • Cerebrovascular Disorders / chemically induced
  • Cerebrovascular Disorders / physiopathology*
  • Disease Models, Animal
  • Electroencephalography / statistics & numerical data
  • Female
  • Functional Laterality
  • Humans
  • Infusions, Intra-Arterial
  • Lymphoma / complications
  • Lymphoma / drug therapy
  • Male
  • Mannitol / administration & dosage
  • Mannitol / pharmacology
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Middle Aged
  • Osmotic Pressure / drug effects
  • S100 Proteins / blood
  • Seizures / diagnosis
  • Seizures / etiology*
  • Seizures / physiopathology*
  • Swine
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers
  • S100 Proteins
  • Mannitol
  • Methotrexate