title: The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy.
abstract: Astrogliosis and microgliosis in hippocampal sclerosis (HS) are widespread and are postulated to contribute to the pro-excitatory neuropathological environment. This study aimed to establish if seizure burden at the time of surgery or post-surgical outcome were correlated with the extent of gliosis in HS. As a secondary aim, we wanted to determine if the degree of gliosis could be predicted by pre-operative neuroimaging.Children and adults who underwent epilepsy surgery for HS between 2002 and 2011 were recruited (n = 43), and age-matched autopsy controls obtained (n = 15). Temporal lobe specimens were examined by DAB immunohistochemistry for astrocytes (glial fibrillary acidic protein (GFAP)) and microglia (CD68). Cell counting for GFAP and CD68 was performed and quantitative densitometry undertaken for GFAP. Seizure variables and outcome (Engel) were determined through medical record and patient review. Seizure frequency in the 6 months prior to surgery was measured to reflect the acute seizure burden. Duration of seizures, age at onset and age at operation were regarded to reflect chronic seizure burden. Focal, lobar and generalized atrophy on pre-operative MRI were independently correlated with the degree of cortical gliosis in the surgical specimen.In HS, both acute and chronic seizure burden were positively correlated with the degree of gliosis. An increase in reactive astrocyte number in CA3 was the strongest predictor of poor post-operative seizure outcome at 1 and 3 years post-operatively in this cohort. Changes in lower cortical astrocyte and upper cortical microglial number also correlated with post-operative outcome at 1 year. Post-surgical seizure outcome (1, 3 and 5 years) did not otherwise correlate with GFAP immunoreactivity (GFAP-IR) or CD68 immunoreactivity (CD68-IR). Increased microglial activation was detected in patients with pre-operative bilateral convulsive seizures, compared to those without convulsive seizures. Furthermore, focal, lobar and generalized atrophy on pre-operative neuroimaging were independently correlated with the degree of cortical gliosis in the surgical specimen.
authors.affiliation: Department of Neurology, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia. Alexandra.johnson@sesiahs.health.nsw.gov.au.|School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia. Alexandra.johnson@sesiahs.health.nsw.gov.au.
authors.forename: Alexandra M
authors.identifier: 0000-0003-0997-0372
authors.initials: AM
authors.lastname: Johnson
authors.affiliation: Prince of Wales Hospital, High St, Randwick, Sydney, NSW 2031, Australia.
authors.forename: Ella
authors.initials: E
authors.lastname: Sugo
authors.affiliation: Department of Neurology, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barreto
authors.affiliation: Prince of Wales Hospital, High St, Randwick, Sydney, NSW 2031, Australia.
authors.forename: Chee-Chung
authors.initials: CC
authors.lastname: Hiew
authors.affiliation: Department of Neurology, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia.|School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.affiliation: Department of Neurology, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia.|School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Connolly
authors.affiliation: Prince of Wales Hospital, High St, Randwick, Sydney, NSW 2031, Australia.|Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia.
authors.forename: Ernest
authors.initials: E
authors.lastname: Somerville
authors.affiliation: South Eastern Area Laboratory Services, Barker St, Randwick, Sydney, NSW 2031, Australia.
authors.forename: Enisa
authors.initials: E
authors.lastname: Hasic
authors.affiliation: Department of Neurology, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia.|School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia.
authors.forename: Annie Me
authors.initials: AM
authors.lastname: Bye
authors.affiliation: Department of Neurology, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia.|School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia.|Developmental Neurosciences Program, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Cunningham
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D017281:Cost of Illness; D003710:Demography; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000150:complications / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011300:Preoperative Care; D012598:Sclerosis / Q000150:complications / Q000473:pathology*; D012640:Seizures / Q000150:complications / Q000601:surgery*; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000601:surgery*; D016896:Treatment Outcome; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005904:Glial Fibrillary Acidic Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Astrocyte; Astrogliosis; Hippocampal sclerosis; Lobectomy; Microglia; Temporal lobe epilepsy