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.

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, Italy3 Neurology Department, Bellaria Hospital, Bologna, Italy

4 Department of Statistics, University of Bologna, Italy

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

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

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.

MTS DXMTS Right side

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

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*

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)

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

NNNNNN tCho/Cr

NNNNNNGlx/Cr

913.5

p < 0.01

(p = 0.005581)

1063.5

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

Left contralateral

tNAA

control

control

Right pathological

tNAAmI

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..

a statistically significant differences in comparison with controls

…. our results don’t 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

…. 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

…. 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 activityMueller SG Epilepsya 2003 Wellard Epilepsya 2003 Riederer NMR 2006

…. our next step

tNAAtNAA

tNAA

to study, in patient treated with surgical resection of the pathological hyppocampus, metabolite modification of the

contralateral side, compared to pre-op results

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

ConclusionsConclusions

Thank you for your kind attention

Focale deplezione neuronale ippocampo, microdisgenesia poloSTMsn49, ♀20

Sclerosi corno Ammone tipo classico, displasia cort. architetturale

STM, displ. e atrofia polodx33, ♀19


STM, lieve atrofia polo sn36, ♂18

meningoencefalocele ala sferoidale sx, microdisgenesia del polo e gliosi ippocampo

Les pluricistica con malf. grande ala sfenoide, iposviluppo polo temporale

sn36, ♂17

Sclerosi corno Ammone tipo globale, displasia cort. architetturale

STMdx 32, ♀16

Displasia cort. cito-architetturale del polo Dubbia displasia polo-uncus

dx30, ♀15

Sclerosi corno Ammone tipo classico, displasia cort. citoarchitetturale, lesione amartomatosa glio-neuronale

STM, sosp. displasia polodx38, ♀14

Sclerosi corno Ammone, displasia corticale architetturale del polo

STM, sosp. displasia polo sx38, ♀13


STMdx41, ♀12

Sclerosi corno Ammone tipo globale, microdisgenesia del poloSTMdx27, ♂11


STMdx45, ♂10

Sclerosi corno Ammone tipo classico, microdisgenesia del polo STM, atrofia polosn36, ♀9


STM, Δ segnale sndx44, ♂8

Sclerosi corno Ammone tipo classico, displasia cort.citoarchitetturale

STM sn, Δ segnale dxsn46, ♀7


STM, atrofia polosn33, ♀6

Sclerosi corno Ammone tipo classico, microdisgenesia del poloSTMdx45, ♂5

Sclerosi corno Ammone tipo classicoSTM, sosp. displasia polodx44, ♂4

Sclerosi corno Ammone tipo classico, microdisgenesia del poloSTMdx35, ♀3


STM, displasia polodx55, ♂2

Sclerosi corno Ammone tipo classico, microdisgenesia del poloSTMdx45, ♂1

IstologiaRMTLE età, ♀/♂

Pz.

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.

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

2b49, ♀20

33, ♀19

36, ♂18

36, ♂17

1b32, ♀16

1a30, ♀15

1a38, ♀14

38, ♀13

41, ♀12

1a27, ♂11

2a45, ♂10

36, ♀9

1a44, ♂8

46, ♀7

1a33, ♀6

45, ♂5

1a44, ♂4

35, ♀3

55, ♂2

45, ♂1

Classeetà, ♀/♂

Pz.

Follow-UpClassification 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.

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


0.9 +/- 0.2


1.2 +/- 0.2

Controlli

tNAA/Cr

Media +/- SD

Mediana

Controlli

2,4620,0252,1511,866

7,6670,06810,91

74,575

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

Media +/- DS

1,9970,0211,3161,011

5,9000,0658,7892,680

50,06792

90,05793,2

70,067103,6

80,04882,8

40,04871,7

100,04893,4

60,086102,4

60,05772

80,05793,1

40,0171,4

30,09692,4

80,07694,2

40,05781,9

70,05782,3

40,06781,7

50,05782,8

40,07692,2

40,086 1,6

70,076115,5

50,105123,4

S/NFWHMLWvolume

patologici

Media +/- DS

2,6340,0192,6681,153

6,9000,0659,6842,695

60,06781,8

70,06792,9

70,05794,2

100,067102,8

40,04881,3

100,057103,4

60,07682,4

70,06792,3

100,06793,1

50,05781,4

60,096113,8

130,067104,2

40,05781,9

90,057112,3

50,04871,7

70,05782,8

40,07692,2

40,076 1,6

100,019195,9

40,115131,9

S/NFWHMLWvolume

Controlaterali

NNmI/Cr


VsIppocampo

controlaterale


Vs controlli


Vs controlli

NNtNNA/Cho

NNNNNN tCho/Cr

NNNNNNGlx/Cr

tNAA/Cr

Analisi statistica

0.00066508 (p<0.01)

0.2220644770.00278617 (p<0.01)

mI/Cr


VsIppocampo

controlaterale


Vs controlli


Vs controlli

0.1164948830.030525889 (p<0.05)

0.003564292 (p<0.01)

tNNA/Cho

10.9964017480.996623558 tCho/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

Analisi Statistica: dati significativiMisura 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

913.5 1198.5

2.55 3.37

1299.5

996.5

CONTROLATERALE NORMALE

p < 0.05 (p = 0.04824)NAA+NAAG/Cr 1063.5

1198.5


Test usato: two-sample Wilcoxon rank sum test (equivalente al Mann-Whitney test)


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

913.5

1063.5

2.55 3.20

1299.5

996.5

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.

Documents

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contralateral tnaa control