1. Epilepsy Tissue Bank Institute of Neurology Jan 2013

2. Epilepsy Tissue Bank at IoN Epilepsy is a common neurological disease. There is currently no Epilepsy Tissue Bank in the UK as a resource for donors or researchers Aim to build on existing tissue archives at IoN and promote collection to patient donors / relatives / pathologists / Coroners in UK. Further research into epilepsy, its causes and prevention, particularly SUDEP.

3. Epilepsy Tissue Bank: Tissue holdings SURGICAL AND POST MORTEM TISSUES Whole brains Frozen tissue FFPE PFF EM

4. Surgical tissues Epilepsy surgical programme at NHNN since 1992 Mainly lobectomy specimens Currently > 600 samples available for use in research

5. 1. Structural abnormality2. EEG abnormality RESECTIVE EPILEPSY SURGERY Focal/partial epilepsy syndromes Anterior temporal lobectomies & hippocampectomies Lesionectomies Lobectomies Corticetomies Frontal > temporal

6. Temporal lobectomy Fresh weight ~12g Surgical suture marks middle temporal gyrus POLE Hippocampus ~2.5cm 1.WEIGH/VOLUMES ORIENTATE, PHOTOGRAPH 2.FREEZE SAMPLES (STG,MTG, ITG, HIPPOCAMPUS) 3.EM 4.PARA FORMALDEHYDE 5.FIXED SAMPLES : Hippocampal Body Pes hippocampus Parahippocampal Gyrus Amygdala (CUSAs) Temporal Lobe TEMPORAL LOBE SURGERY Tissue in Epilepsy Bank ‘en-bloc resection’ 4.5cm

7. RANGE OF EPILEPSY PATHOLOGIES HIPPOCAMPAL SCLEROSISCORTICAL MALFORMATIONS GFAP NeuN

8. Advantages of epilepsy surgical tissue for research studies Ample, fresh tissue available Optimal preservation Short fixation times Standardised regions (Brodmann areas) collected in each case Detailed pre-operative clinical, MRI correlation (& psychometry / functional imaging) Disadvantages Patients by definition have refractory epilepsy all on multiple AED No controls Advantages of epilepsy surgical tissue for research studies Ample, fresh tissue available Optimal preservation Short fixation times Standardised regions (Brodmann areas) collected in each case Detailed pre-operative clinical, MRI correlation (& psychometry / functional imaging) Disadvantages Patients by definition have refractory epilepsy all on multiple AED No controls Gene expression Single cell electrophysiology (patch clamp recording) Proteomics Cell culture IHC MRI-correlations Gene expression Single cell electrophysiology (patch clamp recording) Proteomics Cell culture IHC MRI-correlations Studies 9.4T

9. Majority of cases from Epilepsy Society, Chalfont. POST MORTEM WHOLE BRAINS ~160 Collected since 1980 Advantage : Detailed clinical documentation Disadvantage : Selection bias of severe epilepsy cases SYNDROMES Partial epilepsy Symptomatic focal Temporal lobe epilepsy Post-traumatic Lesion-related epilepsy Idiopathic generalised Dravets PME PATHOLOGIES

10. PM tissue sampling protocols include Temporal (T1, pole) Frontal (cingulate, watershed, pole, basal) Any lesion Hippocampus (both sides, two levels) with parahippocampal gyrus Amygdala, Thalamus (Level AV nucleus) Basal ganglia Cerebellum (anterior and posterior lobe) Brainstem (midbrain pons and medulla) Essential blocks / Desirable blocks In epilepsy, both hemispheres need to be sampled as disease (causal and acquired) can be uni- hemispheric Freeze samples for research, further investigation as appropriate and where possible Royal College of Pathologists UK, Guidelines on Autopsy Practice (Scenario 6: Deaths associated with epilepsy) 2006

11. Aims of Epilepsy Tissue Bank Development of PM collection Reverse current trends in acquisition of cases Collection of both common and rarer epilepsies e.g. genetic epilepsies as SCN1A mutations Categorise and phenotype/genotype cases both clinically and pathologically according to up to date International League Against Epilepsy (ILAE) criteria Standard sampling protocols (frozen sample sets) Collections of SUDEP cases

12. SUDEP : Sudden and Unexpected death in epilepsy Epilepsy death register :https://www.sudep.org Incidence ~500 /year UK Current hurdles – collection of material 60 SUDEP cases Survey of hospital pathologists

13. Epilepsy Tissue Bank Current position & Aims Promotion of bank to all stakeholders. Support & Management structure Continued internal and external research collaborations. Potential users: Primarily for Epilepsy research (Control tissue for other neurological diseases) Link with other UK and European Epilepsy BB collections Epilepsy Tissue Bank Within Division Of Neuropathology http://www.ucl.ac.uk/ion/divisions/neuropathology/memberdetails/mt

14. Maria Thom Consultant in Neuropathology Division of Neuropathology, National Hospital of Neurology and Neurosurgery, Queen Square, London Reader, Department of Clinical and Experimental Epilepsy, UCL, Institute of Neurology M.Thom@ucl.ac.uk