Surgical Pathology of Epilepsy


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August 2008

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Surgical Pathology of Epilepsy

  1. 1. Surgical Pathology of Epilepsy Mark Cohen Department of Pathology August 28 th , 2008
  2. 2. <ul><li>'He was thinking, incidentally, that there was a moment or two in his epileptic condition almost before the fit itself (if it occurred in waking hours) when suddenly amid the sadness, spiritual darkness and depression, his brain seemed to catch fire at brief moments....His sensation of being alive and his awareness increased tenfold at those moments which flashed by like lightning.  His mind and heart were flooded by a dazzling light.  All his agitation, doubts and worries, seemed composed in a twinkling, culminating in a great calm, full of understanding...but these moments, these glimmerings were still but a premonition of that final second (never more than a second) with which the seizure itself began.  That second was, of course, unbearable.' </li></ul>
  3. 3. Lecture Outline <ul><li>Ammon’s Horn/Hippocampal/MTL sclerosis </li></ul><ul><li>Malformations of cortical development </li></ul><ul><ul><li>Classification & subclassification (Palmini) ‏ </li></ul></ul><ul><ul><li>Pathology of extratemporal epilepsy </li></ul></ul><ul><li>Dual Pathology in TLE </li></ul><ul><li>Other epileptogenic lesions (Ganglioglioma, DNT, Rassmussen encephalitis) ‏ </li></ul>
  4. 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. 5. Control hippocampus Hippocampal sclerosis Control hippocampus Hippocampal sclerosis
  6. 6. CA2 CA1 Subiculum CA3/4
  7. 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. 8. Control CA1 (x20)
  9. 9. Hippocampal sclerosis CA1 x4 CA1 x20
  10. 10. Blumcke I, et. Al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol (Berl). 2007 Mar;113(3):235-244.
  11. 12. ++ 0/+ 3 + +++ 2 +++ +++ 1b ++ +++ 1a CA2-4 loss CA1 loss Blumcke type
  12. 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%) ‏
  13. 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 (%) ‏
  14. 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
  15. 18. Cepeda C, et. Al. Epileptogenesis in pediatric cortical dysplasia: the dysmature cerebral developmental hypothesis. Epilepsy Behav. 2006 Sep;9(2):219-35
  16. 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 (%) ‏
  17. 20. Cortical dysplasias (Palmini) ‏ <ul><li>Mild MCD </li></ul><ul><ul><li>Type I: Ectopic neurons in/near Layer 1 </li></ul></ul><ul><ul><li>Type 2: Neuronal heterotopia outside Layer 1 </li></ul></ul><ul><li>Focal Cortical Dysplasias </li></ul><ul><ul><li>Type IA: Dyslamination +/- mild MCD </li></ul></ul><ul><ul><li>Type IB: above + giant or immature neurons </li></ul></ul><ul><ul><li>Type IIA: Dysmorphic neurons sans balloon cells </li></ul></ul><ul><ul><li>Type IIB: Dysmorphic neurons avec balloon cells </li></ul></ul>Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldvary-Schaefer N, Jackson G, Luders HO, Prayson R, Spreafico R, Vinters HV. Terminology and classification of the cortical dysplasias. Neurology. 2004 Mar 23;62(6 Suppl 3):S2-8
  18. 21. FCD IA
  19. 22. FCD IB
  20. 23. FCD IIA
  21. 24. FCD IIB
  22. 25. Relevance of Balloon cells CCF UCLA
  23. 26. Pediatric FCD subtypes <ul><li>Type I </li></ul><ul><li>Perinatal risk factors more frequent </li></ul><ul><li>Lobar hypoplasia/atrophy common </li></ul><ul><li>AHS more frequent </li></ul><ul><li>Worse outcome (trend) </li></ul><ul><li>Type II </li></ul><ul><li>More localized ictal patterns & MRI changes </li></ul><ul><li>Increased cortical thickness, abnormal gyral/sulcal patterns, gray/white junction blurring, gray matter signal abnormalities on FLAIR more common </li></ul><ul><li>Better outcome (trend) </li></ul>Krsek P, et al. Different features of histopathological subtypes of pediatric focal cortical dysplasia. Ann Neurol. 2008 Jun;63(6):758-69.
  24. 27. Extratemporal FCD at CCF <ul><li>Present in 52/135 resections = ~40% </li></ul><ul><li>Male: Female = 1.0 </li></ul><ul><li>Mean age at surgery 15 years (<1 – 44 yrs) ‏ </li></ul><ul><li>Mean seizure duration ~10 years </li></ul>Prayson RA, Frater JL. Cortical dysplasia in extratemporal lobe intractable epilepsy: A study of 52 cases. Ann Diagn Pathol. 2003 Jun;7(3):139-46
  25. 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
  26. 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
  27. 30. Fauser S, et. al. Factors influencing surgical outcome in patients with focal cortical dysplasia. J Neurol Neurosurg Psychiatry. 2008 Jan;79(1):103-5 <ul><li>A total of 120 patients with histologically proven focal cortical dysplasias (FCD) were retrospectively analysed for prognostic factors for successful epilepsy surgery. Multivariate data analyses showed that older age at epilepsy surgery, occurrence of secondarily generalised seizures and a multilobar extent of the dysplasia were significant negative predictors. In univariate analyses, longer duration of epilepsy, need for intracranial EEG recordings and incomplete resection of the FCD were factors which significantly reduced the chance of becoming seizure free. Histological subtype of the FCD and age at epilepsy onset had no significant predictive value. These findings strongly suggest early consideration of epilepsy surgery in FCD patients. </li></ul>
  28. 31. Palmini grading: A personal view IIA IIB IA IB
  29. 32. Dual Pathology: HS + FCD <ul><li>12 male patients </li></ul><ul><ul><li>Age of onset 10 years (<1 – 29) ‏ </li></ul></ul><ul><ul><li>Age at invasive EEG 30 years (6 – 50) ‏ </li></ul></ul><ul><li>113 seizures + interictal data from depth electrodes in HC & subdural electrodes over temporal neocortex </li></ul><ul><li>40% of seizures from AHC, 35% from TN, and 25% from both </li></ul>Fauser S, Schulze-Bonhage A. Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings. Brain. 2006 Jan;129(Pt 1):82-95
  30. 33. Dual Pathology: HS + FCD <ul><li>Quantitative contribution of HC correlated strongly with Wyler grade of HS </li></ul><ul><li>FCD subtypes did not affect relative contribution to ictal activity (including even mMCD) ‏ </li></ul><ul><li>FCD interictal patterns similar to those of extratemporal FCDs </li></ul>
  31. 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
  32. 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
  33. 36. Dysembryoplastic Neuroepithelial Tumor
  34. 37. Ganglioglioma
  35. 38. Rasmussen syndrome <ul><li>45 patients (27F, 18M) ‏ </li></ul><ul><li>Age at onset 7 +/- 3 years </li></ul><ul><li>Age at hemispherectomy 9.5 +/- 4 years </li></ul><ul><li>Duration of symptoms 0.5 – 14 years </li></ul>Pardo CA, Vining EP, Guo L, Skolasky RL, Carson BS, Freeman JM. The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia. 2004 May;45(5):516-26.
  36. 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
  37. 43. <ul><li>&quot; For several instants I experience a happiness that is impossible in an ordinary state, and of which other people have no conception.  I feel full harmony in myself and in the whole world, and the feeling is so strong and sweet that for a few seconds of such bliss one could give up ten years of life, perhaps all of life. </li></ul><ul><li>I felt that heaven descended to earth and swallowed me.  I really attained god and was imbued with him.  All of you healthy people don't even suspect  what happiness is , that happiness that we epileptics experience for a second before an attack.&quot; </li></ul>