1. Neuroimaging of Toxic Encephalopathy
Ecstasy
Sandy CY Chen, MD
Tri-Service General Hospital, Taiwan
SNR 2010 Bolongna

2. Toxic Encephalopathy Pathomechanisms Etiology Imaging approach
By etiologies: drugs
By history
Substance abuse: imaging patterns
Occupational & environmental
Suicidal attempts

3. Toxic Encephalopathy -Pathomechanisms Leukoencephalopathy:
demyelination, ischemia and
astrogliosis
Excitotoxicity
Vasculopathy
Cellular energy failure

4. Glutamate Excitotoxicity
Cellular edema
Apoptosis or
necrotic cell death
Moritani et al. AJNR 2005

5. Hyperammonemia induce low grade brain edema
by impairing glutamate-nitric oxide-cGMP pathway

6. Hyperammonemia In Hepatic encephalopathy
Impair glutamate-nitric oxide-cGMP pathway
Disrupt osmolar balance: glutamine mI & Choline
NAA Cr
GLX mI
Cho
Chronic relapsing hepatic encephalopathy

7. Excitotoxicity in Wernicke’s encephalopathy
Acetyl CoA
Krebs
cycle
Glutamate
α-Ketoglutarate
α-KGDH
Succinyl CoA
Succinate

8. NMDA –mediated excitotoxicity In Wernicke Encephalopathy
Thiamine-dependent enzyme
α-ketoglutarate dehydrogenase .

9. Serotonergic pathway Serotonergic : Memory, mood, cognitive and motor
NEJM 2005

10. Ecstasy encephalopathy
High density of 5HT Receptors
in globus pallidus
Oxidative stress, excitotoxicity, and mitochondrial dysfunction

11. ← - - - - - + + Disinhibition Basal ganglia-thalamocortical circuit
MDMA effect
( ) -
( ) +
( ) -
( ) -
( ) +
( ) -
( ) -
Disinhibition

12. Study purpose To investigate the effects of MDMA abuse on
the alterations of brain metabolites and
anatomical connectivity related to the function
of the basal ganglia-thalamocortical circuit
using 1H-MRS and DTI 12

13. Materials and Methods
31 MDMA (24 male, 7 female, aged ) abusers with positive hair and urine tests were enrolled as MDMA group, and 33 normal healthy non-abusers (17 male, 16 female, aged ) were also included as controls.
MR images were acquired at a 3.0 T MR system (Philips, Achieva, Best, Netherlands).

14. LCModel analysis for MRS
Single voxel proton MRS
LCModel analysis for MRS
3T scanner
Double spin-echo, point resolved spectroscopy (PRESS)
TR/TE 2000/40 ms, NEX=128 14

15. Diffusion tensor imaging
DTI analysis
Diffusion tensor imaging
Diffusion tensor imaging were acquired with 6 non-collinear directions with b =1000s/mm2. -- TR/TE=5890/57ms, matrix size=128x128, slice thickness=3 mm without gap, NEX=6, number of slice=40.
The FA difference was statistically compared on a voxel-by-voxel basis between normal and MDMA groups using Student’s t-test. 15

16. Whole brain FA images: normalized to an ICBM-MNI-FA template using affine registration followed by diffeomorphic demons registration
DTI
( MDMA group )
( control group ) #1 #9
#10
#28 #1 #9
#10
#28 … … … …
Average brain
Average brain 16

17. Results : MRS in frontal lobeml
Cho
NAA Cr
Glx
MDMA
5.013± 0.977
1.377 ± 0.287
7.507 ± 1.237
5.990 ± 0.994
±2.636
control
5.207 ± 1.519
1.463 ± 0.235
7.302 ± 1.054
6.095 ± 0.768
± 0.768
P-value
0.578
0.230
0.603
0.664
0.192 17

18. Results : MRS in basal ganglia* ml
Cho
NAA Cr
Glx
MDMA
4.498 ± 1.543
1.721 ± 0.346
8.122 ± 1.351
7.069 ± 1.128
± 3.242
control
3.308 ±1.149
1.638 ±0.220
8.018 ±0.688
7.223 ±0.717
±2.608
P-value
<0.001
0.11
0.382
0.362
0.265 18

19. Results voxel-wise P < 0.05 cluster > 50 voxels
MDMA > control
MDMA < control
voxel-wise P < 0.05
cluster > 50 voxels
MDMA < control
MDMA > control

20. Discussion The increased mI in the basal ganglia
raise the possibility that MDMA-induced
deficits on the basal ganglia would reduce
inhibitory effects on the thalamus, and
therefore increase the thalamocortical
activities

21. Discussion The observed ADC reduction in the
corticospinal tracts and thalamus in the
present study would likely reflect the
increased neuronal activity in the
thalamorcortical fibers

22. Discussion Study limitations 1) many MDMA users have also exposed to
other recreational drugs.
2) the causative relationships between
MDMA use and the alternations in the
basal-thalamocortical circuit can be
challenged because we did not conduct
standard motor function assessments in
MDMA subjects

23. ← - - - - - Conclusion mI + + MDMA effect ( ) ( ) ( ) ( ) ( )
( ) -
( ) +
( ) -
( ) -
( ) +
( ) -
( ) -
Disinhibition
Basal ganglia-thalamocortical circuit

24. Contributions：
Professor
Hsiao-Wen Chung
Ming-Chung Chou
Ph.D.
Nei-Yu Chuo
Hua-Shan Liu
Chao-In Wang
M.D.
Hueng-Wen Gao Chun-Jung Juan
Chun-Jen Hsueh
*National Taiwan
University
*National Defense
Medical Center
*Tri-Service General
Hospital