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3T MR SPECTROSCOPY IN DRUG- RESISTANT TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL ABNORMALITIES S. Battaglia 1, A.F. Marliani 1, F.Toni 1, L.Albini Riccioli.

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Presentation on theme: "3T MR SPECTROSCOPY IN DRUG- RESISTANT TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL ABNORMALITIES S. Battaglia 1, A.F. Marliani 1, F.Toni 1, L.Albini Riccioli."— Presentation transcript:

1 3T MR SPECTROSCOPY IN DRUG- RESISTANT TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL ABNORMALITIES S. Battaglia 1, A.F. Marliani 1, F.Toni 1, L.Albini Riccioli 1, V. Clementi 2, G. Rubboli 3, P. Agati 4, R. Agati 1, M. Leonardi 1 1 Neuroradiology Department, Bellaria Hospital, Bologna, Italy 2 GE Healthcare Technologies, GE Healthcare, Bologna, Italy 3 Neurology Department, Bellaria Hospital, Bologna, Italy 4 Department of Statistics, University of Bologna, Italy

2 The 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

3 Single 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

4 We selected 20 patients (9 11, mean age 39 +/- 7 ys) with drug- resistant TLE surgical candidates MRI 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 Ammons horn sclerosis, archit./cytoarchitettural temporal pole cortical dysplasia or microdysgenetic aspects.

5 MTS DX MTS Right side

6 1H-MRS on bilateral hippocampal regions TE 35 ms TR 2000 ms 128 NEX 5 04 Acquisition VOI min 1.3 cm 3 - max 5.9 cm 3 Data post-processing was performed by using LC-Model 3T MR Protocol Morphological examination FSPGR T1 3D and MPR Reformatted Axial FSE DP e T2 Coronal FLAIR T2 Coronal FSE-IR Coronal GRE T2*

7 Rectangular VOI along the hippocampus, to minimize artifacts due to the adjacent tissue. Axial sequences are acquired in parallel to the course of the temporal horns and the coronal ones perpendicular to it. 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)

8 1299.5 p < 0.001 (p = 0.0001298) 1062 NN 1299.5 p < 0.001 (p = 0.000256) 996.5 mI/Cr Pathological Hippocampus Vs Contralateral Contralateral Hippocampus Vs controls Pathological Hippocampus Vs controls 2.55 p < 0.05 (p = 0.01372) 3.20 NN 2.55 p < 0.001 (p = 0.000762) 3.37 tNAA/Cho NN tCho/Cr NN Glx/Cr 913.5 p < 0.01 (p = 0.005581) 1063.5 p < 0.05 (p = 0.04824) 1198.5 913.5 p < 0.001 (p = 0.000253) 1198.5 tNAA/Cr Statistical analysis (two-sample Wilcoxon rank sum test, equivalent to the Mann-Whitney test) Median values

9 Left contralateral tNAA control Right pathological tNAA mI

10 Over 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 a statistically significant differences in comparison with controls …. our results dont show in 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 one Woermann FG Ann Neurol 1999 Petroff OA Seizure 1999 Simister RJ Epilepsya 2002 Riederer F NMR Biomed 2006 Doelken MT Seizure 2008 Simister JR Epilepsy Research 2009 of tCho/Cr ratio in both the pathological side and in the contralateral hippocampus increased tCho/Cr has been described by other authors, and it was interpreted as a sign of cell membranes damage Urenjak J Journal Neurosci 1993 Connely A Neurology 1994 Achten E Am J Neuroradiol 1997 Simister RJ Epilepsya 2002 Hammen T Eur J Neurol 2006 Doelken MT Seizure 2008

12 …. our results confirm a decrease of tNAA/Cr ratio in the pathological hippocampus as compared to the contralateral and to controls Neuronal depletion (confirmed histologically) Abnormal functionality Hugg JW Ann Neurol 1993 Cendes F Ann Neurol 1994 Connely A Neurology 1994 Kuzniecky R Neurology 1998 Doelken MT Seizure 2008 SmisterJR Epilepsy research 2009 a decrease of tNAA/Cr ratio on contralateral hippocampus compare to controls Abnormal functionality (extension of the disease? Prognostic significance? reversibility?) Woermann FG Ann Neurol 1999 SmisterJR Epilepsya 2002 Mueller SG Epilepsya 2004 Hajek M Eur radiol 2009

13 …. our results indicate This finding, if properly confirmed, may help a correct lateralization in 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 controls gliosis (confirmed histologically) induction of the cotransporter Na + /mI after epileptic activity Mueller SG Epilepsya 2003 Wellard Epilepsya 2003 Riederer NMR 2006

14 …. our next step tNAA to study, in patient treated with surgical resection of the pathological hyppocampus, metabolite modification of the contralateral side, compared to pre-op results

15 In the drug-resistant temporal lobe epilepsy 1H-MRS identifies statistically significant alterations in both the hippocampi side to be treated surgically The histological diagnosis reflects the metabolic abnormalities identified 1H-MRS can be used to monitor patients undergoing surgery Conclusions

16 Thank you for your kind attention

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19 Candidati alla chirurgia: epilessia grave (per frequenza e handicap psico-sociale e professionale) farmaco-resistente: dopo un minimo di 2 anni di trattamento zona epilettogena stabile e unica possibilità di exeresi chirurgica che non determini deficit neurologici o neuropsicologici.

20 Follow-Up Classification of seizure outcome Seizure freedom outcome was assessed at the last follow-up with at least 1 year elapsing before the final evaluation and according to Engels classification (Engel, 1987). The first subgroup, Engels class Ia, consisted of patients who reported no seizures after their surgery. The second subgroup, Engels 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, Engels class II patients, included patients who were not seizure-free but had a substantial improvement, exhibiting still only rare seizures. The fourth subgroup, Engels 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 after surgery (Engels class Ia patients) o those that had been free from seizures for at least 1 year at the time of assessment – the persistence of seizures and the importance of the reduction in seizure frequency: o patients who had rare seizures (i.e., Engels class II patients) o patients with frequent and disabling seizures (i.e., Engels 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.

21 Ippocampo controlaterale Ippocampo patologico Controlli 2084,51299,53572,55913,5 22051062363,53,201063,5 2382,5996,53443,371198,5 Glx/CrmI/CrtCho/CrtNNA/ChotNAA/Cr 2.2 +/- 0.4 2.2 +/- 0.5 2.2 +/- 0.8 Glx/Cr 1.1 +/- 0.2 1.4 +/- 0.2 1 +/- 0.3 mI/Cr 0.3 +/- 0.04 0.3 +/- 0.05 0.3 +/- 0.06 tCho/Cr 3 +/- 0.5 2.7 +/- 0.6 3.6 +/- 0.9 tNNA/Cho 1 +/- 0.2 Ippocampo controlaterale 0.9 +/- 0.2 Ippocampo patologico 1.2 +/- 0.2 Controlli tNAA/Cr Media +/- SD Mediana

22 Controlli 2,4620,0252,1511,866 7,6670,06810,9174,575 Media +/- DS 80,076109,9 50,096104,6 90,076124,9 60,067114,3 130,067124,3 60,115154,4 70,03372,8 60,043102,6 50,057145,3 110,067113,9 70,029104,6 90,08693,3 S/NFWHMLWvolume patologiciControlaterali

23 NNmI/Cr Ippocampo patologico Vs Ippocampo controlaterale Ippocampo controlaterale Vs controlli Ippocampo patologico Vs controlli NNtNNA/Cho NN tCho/Cr NN Glx/Cr tNAA/Cr Analisi statistica

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25 0.00066508 (p<0.01 ) 0.2220644770.00278617 (p<0.01) mI/Cr Ippocampo patologico Vs Ippocampo controlaterale Ippocampo controlaterale Vs controlli Ippocampo patologico Vs controlli 0.1164948830.030525889 (p<0.05) 0.003564292 (p<0.01) tNNA/Cho 10.9964017480.996623558tCho/Cr 0,8488647090,8267393770,917377921Glx/Cr 0.0904444860.005160921 (p<0.01) 0.000196105 (p<0.01) tNAA/Cr Analisi statistica: Test t di Student ATTenzione su 12 pazienti

26 Analisi Statistica: dati significativi Misura di sintesi adoperata per ogni parametro: MEDIANA Test usato: two-sample Wilcoxon rank sum test (equivalente al Mann-Whitney test) PATOLOGICO p < 0.001 (p = 0.000762) NORMALE p < 0.001 (p = 0.000253) p < 0.001 (p = 0.000256) NAA+NAAG/Cho NAA+NAAG/Cr mI/Cre 913.51198.5 2.55 3.37 1299.5 996.5

27 CONTROLATERALE NORMALE p < 0.05 (p = 0.04824) NAA+NAAG/Cr 1063.5 1198.5 Analisi Statistica: dati significativi Misura di sintesi adoperata per ogni parametro: MEDIANA Test usato: two-sample Wilcoxon rank sum test (equivalente al Mann-Whitney test)

28 Analisi Statistica: dati significativi Misura di sintesi adoperata per ogni parametro: MEDIANA Test usato: Wilcoxon matched-pairs signed rank test PATOLOGICO p < 0.05 (p = 0.01372) CONTROLATERALE p < 0.01 (p = 0.005581) p < 0.001 (p = 0.0001298) NAA+NAAG/Cho NAA+NAAG/Cre mI/Cre 913.51063.5 2.553.20 1299.5996.5


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