Seizure-promoting effect of blood-brain barrier disruption.
OBJECTIVE
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.


CONCLUSIONS
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.
Marchi
Nicola
N
Cerebrovascular Research Center, Department of Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Angelov
Lilyana
L
Masaryk
Thomas
T
Fazio
Vincent
V
Granata
Tiziana
T
Hernandez
Nadia
N
Hallene
Kerri
K
Diglaw
Tammy
T
Franic
Linda
L
Najm
Imad
I
Janigro
Damir
D
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy; D002561:Cerebrovascular Disorders / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000706:statistics & numerical data; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007261:Infusions, Intra-Arterial; D008223:Lymphoma / Q000150:complications / Q000188:drug therapy; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000494:pharmacology; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009997:Osmotic Pressure / Q000187:drug effects; D009418:S100 Proteins / Q000097:blood; D012640:Seizures / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D013552:Swine; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015415:Biomarkers; D009418:S100 Proteins; D008353:Mannitol; D008727:Methotrexate