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The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy

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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.

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Notes

  1. The larger cohort with TLE is reported in Johnson et al. [28].

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Acknowledgments

We have received support from Leica Biosystems with immunostaining. We acknowledge the support of Westfield Research Laboratories and Professor Jenny Peat (statistician). We thank Professor Ingmar Blümcke and Dr. Roland Coras (Neuropathologishes Institut, Univeresitatskilinkum Erlangen) for kindly providing us with control tissue for the project.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Sydney Children’s Hospital, High St, Randwick, Sydney, NSW 2031, Australia

    Alexandra M. Johnson, Daniela Barreto, John A. Lawson, Anne M. Connolly, Annie ME Bye & Anne M Cunningham

  2. School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia

    Alexandra M. Johnson, John A. Lawson, Anne M. Connolly, Annie ME Bye & Anne M Cunningham

  3. Developmental Neurosciences Program, School of Women’s and Children’s Health, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia

    Anne M Cunningham

  4. South Eastern Area Laboratory Services, Barker St, Randwick, Sydney, NSW 2031, Australia

    Enisa Hasic

  5. Prince of Wales Hospital, High St, Randwick, Sydney, NSW 2031, Australia

    Ella Sugo, Chee-Chung Hiew & Ernest Somerville

  6. Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, NSW 2052, Sydney, Australia

    Ernest Somerville

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  1. Alexandra M. Johnson
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Correspondence to Alexandra M. Johnson.

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Johnson, A.M., Sugo, E., Barreto, D. et al. The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy. Mol Neurobiol 53, 5446–5456 (2016). https://doi.org/10.1007/s12035-015-9465-y

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