Presentation on theme: "S. Battaglia1, A. F. Marliani1, F. Toni1, L. Albini Riccioli1, V"— Presentation transcript:
13T MR SPECTROSCOPY IN DRUG-RESISTANT TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL ABNORMALITIES S. Battaglia1, A.F. Marliani1, F.Toni1, L.Albini Riccioli1, V. Clementi2,G. Rubboli3, P. Agati4, R. Agati1, M. Leonardi11 Neuroradiology Department, Bellaria Hospital, Bologna, Italy2 GE Healthcare Technologies, GE Healthcare, Bologna, Italy3 Neurology Department, Bellaria Hospital, Bologna, Italy4 Department of Statistics, University of Bologna, Italy1
2The most common cause of temporal lobe epilepsy (TLE: 80% of partial epilepsies) is hippocampal sclerosis, followed by cortical dysplasia, from migration and gyration abnormalities, tumors, etc.The MRI study is crucial to identify the presence or absence of morphological and/or signal abnormalities, particularly in cases of drug-resistant epilepsy (20-30%), in which surgical therapy can be resolutive
3Single voxel MR Spectroscopy 1H-MRS can complete the morphological MRI study to identify metabolic abnormalities in patients affected by cryptogenic or symptomatic TLE.In both cases, metabolic abnormalities have been described either in the side identified as "pathological" with electrophysiological and morphological examinations, and in the contralateral one
4We selected 20 patients (9 ♂ 11 ♀, mean age 39 +/- 7 ys) with drug- resistant TLE surgical candidatesMRI study showed temporal lobe tissue morphological and/or signal abnormality (not tumoral) in one side (13 right and 7 left), concordant with the one suggested by clinical and electrophysiological data (almost all MTS +/- suspected dysplasia of the pole).All patients undergone surgical treatment.Histological examination confirmed classic/global type Ammon’s horn sclerosis, archit./cytoarchitettural temporal pole cortical dysplasia or microdysgenetic aspects.
63T MR Protocol Morphological examination FSPGR T1 3D and MPR ReformattedAxial FSE DP e T2Coronal FLAIR T2Coronal FSE-IRCoronal GRE T2*1H-MRS on bilateral hippocampal regionsTE 35 msTR 2000 ms128 NEX5’ 04’’ AcquisitionVOI min 1.3 cm3 - max 5.9 cm3Data post-processing was performed by using LC-Model
7Axial sequences are acquired in parallel to the course of the temporal horns and the coronal ones perpendicular to it.Rectangular VOI along the hippocampus, to minimize artifacts due to the adjacent tissue.The tNAA/Cr, tNAA/Cho, tCho/Cr, mI/Cr, Glx/Cr ratio were calculated and compared with data collected from 12 healthy volunteers (8 ♀ and 4 ♂, mean age 39 +/- 10)
10Over the past 15 years over 6000 works have been published on this topic. The results described are in part contradictory, possibly due either to the use of different 1.5 T MRI equipments or to the different procedures of analysis.By working with a 3T system, our aim was to study epileptic patients in the hope that the greater power of the magnet could give us more accurate and consistent results..
11…. our results don’t show a statistically significant differences in comparison with controlsin literature, however, its increase is related to epileptic activity (increase in the epileptogenic focus, mainly in cryptogenic TLE)of Glx/Cr ratio in both the pathological side and in the contralateral oneWoermann FG Ann Neurol Petroff OA Seizure Simister RJ Epilepsya 2002Riederer F NMR Biomed Doelken MT Seizure Simister JR Epilepsy Research 2009of tCho/Cr ratio in both the pathological side and in the contralateral hippocampusincreased tCho/Cr has been described by other authors, and it was interpreted as a sign of cell membranes damageUrenjak J Journal Neurosci Connely A Neurology Achten E Am J Neuroradiol 1997Simister RJ Epilepsya Hammen T Eur J Neurol Doelken MT Seizure 2008
12…. our results confirma decrease of tNAA/Cr ratio in the pathological hippocampus as compared to the contralateral and to controlsNeuronal depletion (confirmed histologically) Abnormal functionalityHugg JW Ann Neurol Cendes F Ann Neurol Connely A Neurology 1994Kuzniecky R Neurology Doelken MT Seizure SmisterJR Epilepsy research 2009a decrease of tNAA/Cr ratio on contralateral hippocampus compare to controlsAbnormal functionality (extension of the disease? Prognostic significance? reversibility?)Woermann FG Ann Neurol SmisterJR Epilepsya 2002Mueller SG Epilepsya Hajek M Eur radiol 2009
13…. our results indicatein all patients a statistically significant increase (p<0.01) of the mI/Cr ratio as a characteristic feature of the pathological side compared to contralateral hyppocampus and to controlsgliosis (confirmed histologically)induction of the cotransporter Na+/mI after epileptic activityMueller SG Epilepsya Wellard Epilepsya Riederer NMR 2006This finding, if properly confirmed, may help a correct lateralization
14…. our next steptNAAtNAAto study, in patient treated with surgical resection of the pathological hyppocampus, metabolite modification of the contralateral side, compared to pre-op resultstNAA
15ConclusionsIn the drug-resistant temporal lobe epilepsy 1H-MRS identifies statistically significantalterations in both the hippocampiside to be treated surgicallyThe histological diagnosis reflects the metabolic abnormalities identified1H-MRS can be used to monitor patients undergoing surgery
18Istologia RM TLE età, ♀/♂ Pz. Focale deplezione neuronale ippocampo, microdisgenesia poloSTMsn49, ♀20Sclerosi corno Ammone tipo classico, displasia cort. architetturaleSTM, displ. e atrofia polodx33, ♀19STM, lieve atrofia polo36, ♂18meningoencefalocele ala sferoidale sx, microdisgenesia del polo e gliosi ippocampoLes pluricistica con malf. grande ala sfenoide, iposviluppo polo temporale17Sclerosi corno Ammone tipo globale, displasia cort. architetturale32, ♀16Displasia cort. cito-architetturale del poloDubbia displasia polo-uncus30, ♀15Sclerosi corno Ammone tipo classico, displasia cort. citoarchitetturale, lesione amartomatosa glio-neuronaleSTM, sosp. displasia polo38, ♀14Sclerosi corno Ammone, displasia corticale architetturale del polosx1341, ♀12Sclerosi corno Ammone tipo globale, microdisgenesia del polo27, ♂1145, ♂10Sclerosi corno Ammone tipo classico, microdisgenesia del poloSTM, atrofia polo36, ♀9STM, Δ segnale sn44, ♂8Sclerosi corno Ammone tipo classico, displasia cort.citoarchitetturaleSTM sn, Δ segnale dx46, ♀7Sclerosi corno Ammone tipo classico, displasia cort. architetturale65Sclerosi corno Ammone tipo classico435, ♀3STM, displasia polo55, ♂21IstologiaRMTLEetà, ♀/♂Pz.
19Candidati alla chirurgia: epilessia grave (per frequenza e handicap psico-sociale e professionale)farmaco-resistente: dopo un minimo di 2 anni di trattamentozona epilettogena stabile e unicapossibilità di exeresi chirurgica che non determini deficit neurologici o neuropsicologici.
20Follow-Up Data intervento Classe età, ♀/♂ Pz. 12 Maggio 2006 7 Settembre 20072 Novembre 20079 Ottobre 200716 Dicembre 20052 Febbraio 200716 Marzo 200719 Ottobre 200725 Gennaio 20083 Novembre 200613 Settembre 200616 Aprile 200813 Gennaio 200629 Maggio 20083 Ottobre 200628 Novembre 200727 Aprile 20072 Ottobre 200711 Marzo 200813 Dicembre 2007Data intervento2b49, ♀2033, ♀1936, ♂18171b32, ♀161a30, ♀1538, ♀141341, ♀1227, ♂112a45, ♂1036, ♀944, ♂846, ♀765435, ♀355, ♂21Classeetà, ♀/♂Pz.Classification of seizure outcomeSeizure freedom outcome was assessed at the lastfollow-up with at least 1 year elapsing before the finalevaluation and according to Engel’s classification (Engel,1987).The first subgroup, Engel’s class Ia, consisted of patientswho reported no seizures after their surgery. The second subgroup, Engel’s class I, included both seizure free patients and those who have experienced simple partial seizures, or “brief auras” and “neighborhood” seizures and drug-withdrawal seizures.The third subgroup, Engel’s class II patients, included patients who were not seizure-free but had a substantial improvement, exhibiting still only rare seizures.The fourth subgroup, Engel’s class III–IV patients, included patients with frequent seizures and a truly unsatisfactory outcome.We separated four categories of patients according to– the seizure freedom with two definitions:o patients who were completely seizure-free aftersurgery (Engel’s class Ia patients)o those that had been free from seizures for atleast 1 year at the time of assessment– the persistence of seizures and the importance ofthe reduction in seizure frequency: o patients who had rare seizures (i.e., Engel’s class II patients)o patients with frequent and disabling seizures(i.e., Engel’s class III–IV patients).Engel J Jr. (1987) Outcome with respect to epileptic seizures. In Engel J Jr (Ed) Surgical treatment of the epilepsies. 2nd ed. Raven Press, New York, pp. 553–571.Engel JJ,Wiebe S, French J, Sperling M,Williamson P, Spencer D, Gumnit R, Zahn C,Westbrook E, Enos B. (2003) Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology 60:538–547.Engel JJ. (1996) Surgery for seizures. New England Journal of Medicine 334:647–652.
22 Media +/- DS Media +/- DS Media +/- DS Controlli patologici 1,9970,0211,3161,0115,9000,0658,7892,68050,067920,0573,27103,680,0482,841,73,460,0862,43,10,011,430,0960,0764,21,92,32,21,6115,50,10512S/NFWHMLWvolume Media +/- DS2,6340,0192,6681,1536,9000,0659,6842,69560,06781,8792,90,0574,2102,840,0481,33,40,0762,42,33,151,40,096113,8131,91,72,21,6195,90,115S/NFWHMLWvolume2,4620,0252,1511,8667,6670,06810,9174,575 Media +/- DS80,076109,950,0964,69124,960,067114,3130,115154,470,0332,80,0432,60,057145,33,90,0290,0863,3S/NFWHMLWvolumeControllipatologiciControlaterali
25Ippocampo controlaterale Analisi statistica: Test t di Student ATTenzione su 12 pazienti(p<0.01)(p<0.01)mI/CrIppocampo patologicoVsIppocampocontrolateraleIppocampo controlateralecontrolliIppocampo patologico(p<0.05)(p<0.01)tNNA/Cho1tCho/Cr0,0,0,Glx/Cr(p<0.01)(p<0.01)tNAA/CrAnalisi statistica: Test t di Student
26Analisi Statistica: dati significativi Misura di sintesi adoperata per ogni parametro: MEDIANATest usato: two-sample Wilcoxon rank sum test (equivalente al Mann-Whitney test)PATOLOGICO NORMALE NAA+NAAG/Cr p < 0.001 (p = )913.51198.5p < 0.001 (p = )NAA+NAAG/Cho2.553.37p < 0.001 (p = )996.5mI/Cre 1299.5
27Analisi Statistica: dati significativi Misura di sintesi adoperata per ogni parametro: MEDIANATest usato: two-sample Wilcoxon rank sum test (equivalente al Mann-Whitney test)CONTROLATERALE NORMALE NAA+NAAG/Crp < 0.05 (p = )1063.51198.5
28Analisi Statistica: dati significativi Misura di sintesi adoperata per ogni parametro: MEDIANATest usato: Wilcoxon matched-pairs signed rank testPATOLOGICO CONTROLATERALENAA+NAAG/Cre 913.5p < 0.01 (p = )1063.5NAA+NAAG/Cho2.55p < 0.05 (p = )3.20mI/Cre 1299.5p < 0.001 (p = ) 996.5