Artikel
Clinico-neuropsychological profiles suggest hippocampal “gliosis only” as temporal lobe epilepsy syndrome distinct from hippocampal sclerosis
Die isolierte hippocampale Gliose als eigenständige Entität bei Temporallappenepilepsie
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Autoren
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Alexander Grote
- Evangelisches Krankenhaus Bethel, Neurochirurgie, Bielefeld, Deutschland
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Albert Becker
- Medizinische Hochschule der Universität Bonn, Klinik für Neuropathologie, Bonn, Deutschland
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Christoph Helmstaedter
- Medizinische Hochschule der Universität Bonn, Klinik für Epileptologie, Bonn, Deutschland
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Dieter Henrik Heiland
- Medizinische Hochschule der Universität Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
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Johannes Schramm
- Universität Bonn, Medizinische Fakultät, Bonn, Deutschland
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Daniel Delev
- RWTH Aachen University, Klinik für Neurochirurgie, Aachen, Deutschland
| Veröffentlicht: | 8. Mai 2019 |
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Gliederung
Text
Objective: Mesial temporal lobe epilepsy (mTLE) caused by hippocampal sclerosis (HS) represents a major epileptic disease condition eligible for surgical treatment in pharmacoresistant patients. In approximately 20–30% of the cases, however, the neuropathological examination uncovers hippocampus gliosis without significant neuronal loss. We hypothesized that “gliosis only” (GO) represents a distinct syndrome in the TLE spectrum, which was scrutinized by comprehensive demographic, neuropathological, molecular, neuropsychological and epileptological analyses.
Methods: We evaluated 635 consecutive patients with temporo-mesial resections revealing HS in 562 cases and GO in 73 patients.
Results: Detailed demographic and seizure outcome data were available for all cases with a mean follow-up of 42 months. RNA sequencing of representative GO versus HS cohorts (n=10) followed by machine learning based prediction model identified distinct signature gene profiles and pathway activation, confirming abundant differences between both groups. While HS subgroup showed pronounced transcriptional activation of oxidative phosphorylation and MAPK pathway, GO hippocampi were characterized by specific alterations of genes involved in the complement system and neuroinflammation. The demographic analysis revealed that patients with GO develop epilepsy significantly later in age (16,1 years vs.12,3 years; p=0.0073). Complete pre- and postoperative neuropsychological evaluation was analyzed for 59 patients with GO and 46 patients with HS matched for sex, age, type and side of surgery. Patients with GO had less impaired preoperative neuropsychological performance and significantly worse postoperative verbal and visual memory outcomes. Most importantly GO was associated with significantly higher risk of not becoming seizure free after surgery (p=0.0002, RR=1.7, CI=1.2–2.2), which was confirmed by multivariate analysis after correcting for other confounders, known to influence seizure outcome.
Conclusion: In concert, these findings suggest that GO represents rather a distinct disease entity than a variant of HS. Patients with GO present worse seizure outcome and show greater neuropsychological impairment after epilepsy surgery, which has important implications for the consultation and treatment of those patients.
