1. 3T 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. Leonardi1
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 1

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 Ammon’s horn sclerosis, archit./cytoarchitettural temporal pole cortical dysplasia or microdysgenetic aspects.

5. MTS Right side
MTS DX

6. 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*
1H-MRS on bilateral hippocampal regions
TE 35 ms
TR 2000 ms
128 NEX
5’ 04’’ Acquisition
VOI min 1.3 cm3 - max 5.9 cm3
Data post-processing was performed by using LC-Model

7. Axial 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)

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

9. Right pathological
tNAA mI
control
tNAA
control
Left contralateral

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. …. our results don’t show
a statistically significant differences in comparison with controls
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 Petroff OA Seizure Simister RJ Epilepsya 2002
Riederer F NMR Biomed Doelken MT Seizure 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 Connely A Neurology Achten E Am J Neuroradiol 1997
Simister RJ Epilepsya Hammen T Eur J Neurol 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 Cendes F Ann Neurol Connely A Neurology 1994
Kuzniecky R Neurology Doelken MT Seizure 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 SmisterJR Epilepsya 2002
Mueller SG Epilepsya Hajek M Eur radiol 2009

13. …. our results indicate
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 Wellard Epilepsya Riederer NMR 2006
This finding, if properly confirmed, may help a correct lateralization

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

15. Conclusions
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

16. Thank you for your kind attention

18. Istologia RM TLE età, ♀/♂ Pz.
Focale deplezione neuronale ippocampo, microdisgenesia polo
STM sn
49, ♀ 20
Sclerosi corno Ammone tipo classico, displasia cort. architetturale
STM, displ. e atrofia polo dx
33, ♀ 19
STM, lieve atrofia polo
36, ♂ 18
meningoencefalocele ala sferoidale sx, microdisgenesia del polo e gliosi ippocampo
Les pluricistica con malf. grande ala sfenoide, iposviluppo polo temporale 17
Sclerosi corno Ammone tipo globale, displasia cort. architetturale
32, ♀ 16
Displasia cort. cito-architetturale del polo
Dubbia displasia polo-uncus
30, ♀ 15
Sclerosi corno Ammone tipo classico, displasia cort. citoarchitetturale, lesione amartomatosa glio-neuronale
STM, sosp. displasia polo
38, ♀ 14
Sclerosi corno Ammone, displasia corticale architetturale del polo sx 13
41, ♀ 12
Sclerosi corno Ammone tipo globale, microdisgenesia del polo
27, ♂ 11
45, ♂ 10
Sclerosi corno Ammone tipo classico, microdisgenesia del polo
STM, atrofia polo
36, ♀ 9
STM, Δ segnale sn
44, ♂ 8
Sclerosi corno Ammone tipo classico, displasia cort.citoarchitetturale
STM sn, Δ segnale dx
46, ♀ 7
Sclerosi corno Ammone tipo classico, displasia cort. architetturale 6 5
Sclerosi corno Ammone tipo classico 4
35, ♀ 3
STM, displasia polo
55, ♂ 2 1
Istologia RM
TLE
età, ♀/♂
Pz.

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 Data intervento Classe età, ♀/♂ Pz. 12 Maggio 2006
7 Settembre 2007
2 Novembre 2007
9 Ottobre 2007
16 Dicembre 2005
2 Febbraio 2007
16 Marzo 2007
19 Ottobre 2007
25 Gennaio 2008
3 Novembre 2006
13 Settembre 2006
16 Aprile 2008
13 Gennaio 2006
29 Maggio 2008
3 Ottobre 2006
28 Novembre 2007
27 Aprile 2007
2 Ottobre 2007
11 Marzo 2008
13 Dicembre 2007
Data intervento 2b
49, ♀ 20
33, ♀ 19
36, ♂ 18 17 1b
32, ♀ 16 1a
30, ♀ 15
38, ♀ 14 13
41, ♀ 12
27, ♂ 11 2a
45, ♂ 10
36, ♀ 9
44, ♂ 8
46, ♀ 7 6 5 4
35, ♀ 3
55, ♂ 2 1
Classe
età, ♀/♂
Pz.
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 Engel’s classification (Engel,
1987).
The first subgroup, Engel’s class Ia, consisted of patients
who 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 after
surgery (Engel’s 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., 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.

21. Ippocampo controlaterale Ippocampo controlaterale
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
Ippocampo controlaterale
Ippocampo patologico
Controlli
2084,5
1299,5
357
2,55
913,5
2205
1062
363,5
3,20
1063,5
2382,5
996,5
344
3,37
1198,5
Glx/Cr
mI/Cr
tCho/Cr
tNNA/Cho
tNAA/Cr
Mediana

22. Media +/- DS Media +/- DS Media +/- DS Controlli patologici
1,997
0,021
1,316
1,011
5,900
0,065
8,789
2,680 5
0,067 9 2
0,057
3,2 7 10
3,6 8
0,048
2,8 4
1,7
3,4 6
0,086
2,4
3,1
0,01
1,4 3
0,096
0,076
4,2
1,9
2,3
2,2
1,6 11
5,5
0,105 12
S/N
FWHM LW
volume
 Media +/- DS
2,634
0,019
2,668
1,153
6,900
0,065
9,684
2,695 6
0,067 8
1,8 7 9
2,9
0,057
4,2 10
2,8 4
0,048
1,3
3,4
0,076
2,4
2,3
3,1 5
1,4
0,096 11
3,8 13
1,9
1,7
2,2
1,6 19
5,9
0,115
S/N
FWHM LW
volume
2,462
0,025
2,151
1,866
7,667
0,068
10,917
4,575
 Media +/- DS 8
0,076 10
9,9 5
0,096
4,6 9 12
4,9 6
0,067 11
4,3 13
0,115 15
4,4 7
0,033
2,8
0,043
2,6
0,057 14
5,3
3,9
0,029
0,086
3,3
S/N
FWHM LW
volume
Controlli
patologici
Controlaterali

23. Ippocampo controlateraleNN
mI/Cr
Ippocampo patologico Vs
Ippocampo
controlaterale
Ippocampo controlaterale
controlli
Ippocampo patologico
tNNA/Cho
tCho/Cr
Glx/Cr
tNAA/Cr
Analisi statistica

25. Ippocampo controlaterale Analisi statistica: Test t di Student
ATTenzione su 12 pazienti
(p<0.01)‏
(p<0.01)‏
mI/Cr
Ippocampo patologico Vs
Ippocampo
controlaterale
Ippocampo controlaterale
controlli
Ippocampo patologico
(p<0.05)‏
(p<0.01)‏
tNNA/Cho 1
tCho/Cr 0, 0, 0,
Glx/Cr
(p<0.01)‏
(p<0.01)‏
tNAA/Cr
Analisi statistica: Test t di Student

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  
  NORMALE 
NAA+NAAG/Cr 
p < 0.001  
(p = )‏
913.5
1198.5
p < 0.001  
(p = )‏
NAA+NAAG/Cho
2.55
3.37
p < 0.001  
(p = )‏
996.5
mI/Cre  
1299.5

27. 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)‏
CONTROLATERALE  
  NORMALE 
NAA+NAAG/Cr
p < 0.05  
(p = )‏
1063.5
1198.5

28. Analisi Statistica: dati significativi
Misura di sintesi adoperata per ogni parametro: MEDIANA
Test usato: Wilcoxon matched-pairs signed rank test
PATOLOGICO  
  CONTROLATERALE
NAA+NAAG/Cre 
913.5
p < 0.01  
(p = )
1063.5
NAA+NAAG/Cho
2.55
p < 0.05  
(p = )
3.20
mI/Cre  
1299.5
p < 0.001 
(p = )  
996.5