title: Cliniconeuropathologic correlations show astroglial albumin storage as a common factor in epileptogenic vascular lesions.
abstract: OBJECTIVE
  Intracerebral vascular malformations including cavernous angiomas (CAs) and arteriovenous malformations (AVMs) are an important cause of chronic pharmacoresistant epilepsies. Little is known about the pathogenetic basis of epilepsy in patients with vascular malformations. Intracerebral deposits of iron-containing blood products have been generally regarded as responsible for the strong epileptogenic potential of CAs. Here, we have analyzed whether blood-brain barrier (BBB) dysfunction and subsequent astrocytic albumin uptake, recently described as critical trigger of focal epilepsy, represent pathogenetic factors in vascular lesion-associated epileptogenesis.
  
  
  METHODS
  We examined the correlation between hemosiderin deposits, albumin accumulation, and several clinical characteristics in a series of 80 drug-refractory epilepsy patients with CAs or AVMs who underwent surgical resection. Analysis of clinical parameters included gender, age of seizure onset, epilepsy frequency, duration of epilepsy before surgery, and postoperative seizure outcome classification according to Engel class scale. Hemosiderin deposits in the adjacent brain tissue of the vascular lesion were semiquantitatively analyzed. Fluorescent double-immunohistochemistry using GFAP/albumin costaining was performed to study albumin extravasation.
  
  
  RESULTS
  Our results suggest that a shorter duration of preoperative epilepsy is correlated with significantly better postsurgical outcome (p < 0.05), whereas no additional clinical or neuropathologic parameter correlated significantly with the postsurgical seizure situation. Intriguingly, we observed strong albumin immunoreactivity within the vascular lesion and in perilesional astrocytes (57.65 ± 4.05%), but not in different control groups.
  
  
  CONCLUSIONS
  Our present data on albumin uptake in brain tissue adjacent to AVMs and CAs suggests BBB dysfunction and accumulation of albumin within astrocytes as a new pathologic feature potentially associated with the epileptogenic mechanism for vascular lesions and provides novel therapy perspectives for antiepileptogenesis in affected patients.
authors.affiliation: Departments of Epileptology Neuropathology Neurosurgery Neuroradiology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Raabe
authors.forename: Ann Kristin
authors.initials: AK
authors.lastname: Schmitz
authors.forename: Katharina
authors.initials: K
authors.lastname: Pernhorst
authors.forename: Alexander
authors.initials: A
authors.lastname: Grote
authors.forename: Christian
authors.initials: C
authors.lastname: von der Brelie
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.forename: Pitt
authors.initials: P
authors.lastname: Niehusmann
mesh_terms: D000328:Adult; D000367:Age Factors; D000418:Albumins / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000473:pathology; D020785:Central Nervous System Vascular Malformations / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D004827:Epilepsy / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D000418:Albumins