August 2008

1. Surgical Pathology of Epilepsy Mark Cohen Department of Pathology August 28 th , 2008 http://show.zoho.com/View.do?P_ID=208287000000008001&P_STIME=0&TP=false&displayall=false&THEME=plain&USER=gliageek&DOC=Surgical%20Pathology%20of%20Epilepsy

4. Pathology of TLE Blumcke I, Thom M, Wiestler OD. Ammon's horn sclerosis: a maldevelopmental disorder associated with temporal lobe epilepsy. Brain Pathol. 2002 Apr;12(2):199-211 5% No Pathology 5% Dual Pathology 25% Focal lesions 65% Ammon’s Horn Sclerosis

5. Control hippocampus Hippocampal sclerosis Control hippocampus Hippocampal sclerosis

6. CA2 CA1 Subiculum CA3/4

7. Wyler grading of HS (1992) ‏ AR Wyler, FC Dohan, JB Schweitzer, AD Berry A grading system for mesial temporal pathology (hippocampal sclerosis) from anterior temporal lobectomy - J Epilepsy, 1992 >50% neuronal loss involving all hippocampal sectors Grade 4 >50% neuronal loss CA1, CA3, and/or CA4; CA2 spared Grade 3 10-50% neuronal loss in CA1, CA3, and/or CA4 Grade 2 0-10% neuronal loss in CA1, CA3, and/or CA4 Grade 1

8. Control CA1 (x20)

9. Hippocampal sclerosis CA1 x4 CA1 x20

10. Blumcke I, et. Al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol (Berl). 2007 Mar;113(3):235-244.

12. ++ 0/+ 3 + +++ 2 +++ +++ 1b ++ +++ 1a CA2-4 loss CA1 loss Blumcke type

13. MTS: New classification ‏ Blumcke I, et. Al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol (Berl). 2007 Mar;113(3):235-244. CA1 preserved, moderate loss in other sectors (endfolium sclerosis) ‏ MTS type 3 (5%) ‏ Severe CA1 loss, mild loss in other sectors (CA1-sclerosis) ‏ MTS type 2 (5%) ‏ Severe neuronal loss involving all sectors (= Wyler grade 4) ‏ MTS 1b (50%) ‏ “ Classic” – severe CA1 loss, moderate loss in other sectors MTS 1a (20%) ‏ Neuronal cell loss within 1 st SD compared to controls No MTS (20%) ‏

15. Surgical outcomes at 1 year 15 40 15 30 MTS type 3 10 10 10 65 MTS type 2 1 5 20 70 MTS type 1b 5 10 10 70 MTS type 1a 10 20 10 60 No MTS Engle 4 Engle 3 Engle 2 Engle 1 Score (%) ‏

17. Generalized malformations of cortical development Guerrini R, Dobyns WB, Barkovich AJ. Abnormal development of the human cerebral cortex: genetics, functional consequences and treatment options. Trends Neurosci. 2008 Mar;31(3):154-62. sporadic HME SRPX2, sporadic Polymicrogyria Filamin 1 FLNA PV nodular heterotopia Doublecortin DCX Laminar heterotopia PAF-acetylhydrolase Doublecortin Reelin LIS1 DCX(XLIS) ‏ RLN Lissencephalies Protein Genes Malformation

18. Cepeda C, et. Al. Epileptogenesis in pediatric cortical dysplasia: the dysmature cerebral developmental hypothesis. Epilepsy Behav. 2006 Sep;9(2):219-35

19. MCD pathology by MRI type 0 0 15 30 55 Immature neurons 80 35 45 20 45 Balloon cells 10 25 35 55 100 Layer I neurons 10 25 80 65 80 PMG 70 40 70 35 90 Cytomegalic neurons 100 90 90 100 90 Dysmorphic neurons 100 100 100 100 100 WM neurons Focal Lobar Multilobar Hemi CD HME Path (%) ‏

21. FCD IA

22. FCD IB

23. FCD IIA

24. FCD IIB

25. Relevance of Balloon cells CCF UCLA

28. Extratemporal FCD at CCF 10% Coexistent Tumor 10% Coexistent Ischemia 40% Dysmorphic neurons/Balloon cells 60% Increased Layer 1 Neurons 60% Neuronal Cytomegaly 90% Architectural Disorganization

29. Extratemporal FCD at CCF 50 50 35% IIB NA NA 0 IIA 10 90 25% IB 10 90 40% IA % Worse % Better Prevalence Palmini

31. Palmini grading: A personal view IIA IIB IA IB

34. What else causes epilepsy? Khalsa SS, Moore SA, Van Hoesen GW. Hughlings Jackson and the role of the entorhinal cortex in temporal lobe epilepsy: from patient A to Doctor Z. Epilepsy Behav. 2006 Nov;9(3):524-31

35. 52 patients with occipital lobe epilepsy Binder DK, Von Lehe M, Kral T, Bien CG, Urbach H, Schramm J, Clusmann H. Surgical treatment of occipital lobe epilepsy. J Neurosurg. 2008 Jul;109(1):57-69. 30 Gliosis 20 Vascular malformations (including SWD) 10 Other gliomas 20 Glioneuronal tumors 20 FCD (including TS) % of cases Histopathologic diagnosis

36. Dysembryoplastic Neuroepithelial Tumor

37. Ganglioglioma

39. RS: Pathologic staging Pan-laminar cavitation &/or gliosis 4 Pan-laminar degeneration & gliosis 3 Pan-laminar inflammation & gliosis 2 Mild focal inflammation 1 Normal cortex 0