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
<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>
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>
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
Control hippocampus Hippocampal sclerosis Control hippocampus Hippocampal sclerosis
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
Blumcke I, et. Al. A new clinico-pathological classification system for mesial temporal sclerosis. Acta Neuropathol (Berl). 2007 Mar;113(3):235-244.
++ 0/+ 3 + +++ 2 +++ +++ 1b ++ +++ 1a CA2-4 loss CA1 loss Blumcke type
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%)
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 (%)
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
Cepeda C, et. Al. Epileptogenesis in pediatric cortical dysplasia: the dysmature cerebral developmental hypothesis. Epilepsy Behav. 2006 Sep;9(2):219-35
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.
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
Extratemporal FCD at CCF 50 50 35% IIB NA NA 0 IIA 10 90 25% IB 10 90 40% IA % Worse % Better Prevalence Palmini
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>
Palmini grading: A personal view IIA IIB IA IB
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
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>
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
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
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.
<ul><li>" 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." </li></ul>