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April2013 Vol.50 Issue:      2 Table of Contents
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Role of Diffusion Tensor Imaging in Mesial Temporal Lobe Epilepsy

Heba I. Ali1, Yasser A. Abbas1, Mona Noureldin2, Hany M. Zakieldine3, Ahmed A. Gaber3

Departments of Radiology; Ain Shams University1, Egypt; John Hopkins School of Medicine2, USA;

Neurology3, Ain Shams University; Egypt


Background: Imaging of epileptics frequently appears normal on conventional magnetic resonance imaging (MRI) even after performing special MR epilepsy protocol. Modern MR Techniques are helpful in assessment of patient with seizures. Objective: This study is aiming to assess the role of diffusion tensor imaging (DTI) in patients with medial temporal lobe epilepsy (MTLE). Methods: Ten patients with MTLE and 10 healthy subjects had performed conventional MRI epilepsy protocol, followed by DTI. MR tractography was then performed for fornix, cingulum and other white matter tracts. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured and then compared quantitatively as an assessment of pertinent regions. All data was correlated with the clinical and advanced EEG of the patient. Results: The patients group, however, had significantly decreased FA values and increased ADC values in the hippocampus as well as the basal ganglia ipsilateral to the seizure focus, and there were mild similar changes in the cingulum, inferior longitudinal fasciculus (ILF) and to a lesser extent in other tracts ipsilateral to seizure focus as suggested by the clinical and EEG findings. Conclusion:  DTI proved to be helpful in the evaluation of patients with MTLE. This is mainly achieved through quantitative assessment of hippocampus. It showed associated deep nuclei and white matter tracts affection in patients with MTLE explaining their clinical and EEG abnormal findings. [Egypt J Neurol Psychiat Neurosurg.  2013; 50(2): 171-176]

 Key Words: Diffusion Tensor Imaging, Mesial Temporal Lobe Epilepsy, Fractional Anisotropy, Apparent Diffusion Coefficient.

Correspondence to Heba Ibrahim Ali. Radiology department, Ain Shams University; Egypt. Tel.: +971508878210          e-mail:



Mesial temporal lobe epilepsy (MTLE) is one of the most common focal epilepsy syndromes.1,2 Seventy percent of epileptic patients can be controlled by medications however 30 % may have refractory epilepsy, predominated by MTLE.3,4 These refractory cases usually require surgical intervention. Sixty percent of surgically treated temporal lobe epilepsy (TLE) patients become seizure-free if focal pathology such as hippocampal sclerosis (HS) is identified.5 Hippocampal formation (HF) is an essential epileptogenic focus and hippocampal sclerosis is the major pathological abnormality.1 Seizure lateralization is usually accomplished through clinical and electrophysiological evaluation.

High-resolution MRI is an important imaging modality in evaluating patients with MTLE1, however diagnosis is unremarkable in 20–25% of patients with refractory focal epilepsy.6

Diffusion tensor imaging (DTI) is a non-invasive imaging technique that can indirectly evaluate the integrity of white matter tracts.2 Based on the principle of anisotropic water molecular diffusion, DTI provides quantitative analysis of the magnitude and directionality of water molecules in a 3 dimensional space, and reflects

the microstructural and functional abnormality of the brain tissues1. The two main parameters derived from DTI data are fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Apparent diffusion coefficient reflects the average magnitude of molecular displacement by diffusion. Fractional anisotropy reflects the directionality of molecular displacement by diffusion1. A disruption of brain microstructure in various neurologic conditions will lead to the changes of ADC and FA values.1,7,8 Apparent diffusion coefficient is higher in epileptogenic lesions and in the sclerotic hippocampi of patients with mesial temporal sclerosis (MTS) than in the normal hippocampi.9-11

We aimed of this study (a) to assess the role of DTI in patients with MTLE, (b) to assess its role in lateralization and/or localization of unilateral or bilateral affection, (c) to detect extra temporal involvement including the deep nuclei and white matter tracts, and (d) to correlate DTI parameters with neurological findings.




Ten patients with MTLE were included in the study. The patients were recruited from the outpatient epilepsy clinic. These patients had no history of head trauma or intracranial lesions.

After an informed consent was obtained from all subjects, full clinical evaluation was done for each patient. All cases had video EEG monitoring for at least 24 hours. Five patients had ictal EEG recording; however, an ictal recording was not required for inclusion in the study.

The diagnosis of MTLE was based on clinical, electrophysiological and conventional MRI data. The diagnoses were based on the criteria of classification of epileptic syndromes according to the Commission on Classification and Terminology of the International League against Epilepsy.12 This classification was similar to that used by Arfanakis and colleagues13 for TLE diagnosis. Ten age and sex matched healthy subjects were also enrolled in the study for comparison of DTI measures.

All subjects were scanned using a 1.5T (Intera; Philips Medical System, Best, Netherlands) and a standard head coil. The MRI epilepsy protocol included 1.5-mm thick T2-weighted turbo spin echo (TSE) and T1-weighted inversion recovery slices as well as 5-mm thick (FLAIR) in the oblique coronal and axial planes. DTI was then performed with two b-values. Degree of diffusion weightening (b = 0 and bmax= 700 s/mm2) was applied in six non-collinear directions, with no interslice gap. DTI was performed in all patients when they were seizure-free for at least 24 hours. This approach was intended to ensure measurements from a baseline state as much as possible, because prior studies indicated that seizures from status epilepticus might affect diffusivity measurements.10,14-16 After image acquisition, the data were transferred to independent workstation (extended workspace) (Release Dell, Round Rock, TX).

Qualitative assessments of the conventional MR images for both hippocampi were done by two neuroradiologists, who were blinded to the EEG findings. They reported presence or absence of atrophy, signal changes, sclerosis or focal lesions.

Quantitative assessment of the FA and ADC values from symmetrical-voxel sampling regions from the anterior HF on both sides, in patients and in control subjects was done. The adjacent cerebrospinal fluid-containing pixels were avoided in region of interest (ROI) to reduce the partial volume effects. Other pertinent grey matter regions like the parahippocampus and basal ganglia bilaterally were also assessed. Blinded neuroradiologist to the clinical and EEG findings did processing.

FA and ADC values were measured and evaluated for; (1) the differences between left and right sides in the controls, (2) the differences between the HF ipsilateral and contralateral to the seizure focus which was localized by video EEG, (3) the differences between the ipsilateral HF of patients and that of the controls, and (4) the differences between the contralateral HF and that of the controls (Figure 1).

MR tractography was then performed for fornix, cingulum, uncinate fasciculus, superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), corpus callosum, middle cerebellar peduncle, and corticospinal tract. Finally, all data was correlated with the clinical, electrophysiological and conventional MRI data of the patient.


Statistical Methodology

Data was analyzed on an IBM personal computer, using Statistical Package for Special Science (SPSS) software computer program version 15. Data were described as mean ±standard deviation (SD) for quantitative (Numerical) variables and as frequency & percentage for qualitative (Categorical) variables.

The significance of the differences for quantitative variables was assessed by using the Student t test.

Significance level (P) value was as follows: P >0.05 is insignificant (NS), P ≤0.05 is significant (S), P ≤0.01 is highly significant (HS), P ≤0.001 is very highly significant (VHS).




The mean age of the patients was 26.6 years (range 9-38 years), seven males and three females. Five cases were diagnosed as MTLE based on semiology, ictal EEG and conventional MRI data while the rest were diagnosed based on interictal EEG, conventional MRI and clinical data. Conventional MRI brain using epilepsy protocol showed MTS in 4 cases; 2 were on the right side, 1 was on the left side and 1 bilateral, (Table 1).

There was no statistical difference in FA and ADC values between both hippocampi in control subjects. All patients had significantly decreased FA values and increased ADC values in the hippocampal regions ipsilateral to the seizure focus (Table 1 and Figure 2). In addition, there was a decreased FA values and increased ADC in the ipsilateral deep nuclei in all cases, but these changes were statistically significant in 4 cases (40%); (Table 1).

Reduced FA values of the white matter tracts ipsilateral to the site of the seizure focus were observed in the fornix, corpus callosum, cingulum, uncinate fasciculus, SLF, ILF, and IFOF in 4 cases (40% of cases); (Figure 3).

Conventional MRI only showed three cases of right MTS, and two cases of left MTS. However, DTI showed seven cases of right MTS and six cases of left MTS. The patients group had quantitative FA and ADC changes in the hippocampal regions with a sensitivity of 100% and specificity of 40%. P value showed a trend towards significance (p= 0.09).

Only 4 cases (40%) showed mesial temporal sclerosis on conventional MRI (total of 5 hippocampal regions). Three were unilateral and 1 was bilateral. On the other hand, semiologically and electrophysiologically the epileptic foci were localized in the mesial temporal structures and showed lateralization to one side in 9 cases and was bilateral in 1 case. DTI was able to localize the focus in 10 cases with extratemporal involvement in 4 cases (40%). DTI showed lateralization in all cases (unilateral in 7 and bilateral in 3 cases). It added contralateral involvement in 2 cases over other data collectively.

Semiological seizure classification is classified according to Luders17. The findings show correlation between the clinical, EEG findings and the DTI data.


Table 1. Showing the clinical, EEG, MRI and DTI findings of the patients.





Semiology (Clinical picture)







Dialeptic, right upper limb automotor, bilateral version, no generalization.

Ictal Right anterior temporal spikes



ADC and ↓  FA of right hippocampus




Dialeptic and buccoral automatisms.

Right anterior temporal spikes



↑ ADC and ↓ FA of right hippocampus and right basal ganglia.




Psychoemotional aura and generalization.

Bilateral independent anterior temporal spikes

Normal MRI

↑ ADC and ↓ FA of both hippocampal regions.




Dialeptic seizures and buccoral automatisms.

Ictal right anterior temporal discharge

Bilateral MTS

↑ ADC and ↓ FA of both hippcampal regions, right basal ganglia and white matter.




Dialeptic, bimanual and buccoral autmomatisms.

Ictal right anterior temporal discharge

Normal MRI

↑ ADC and ↓ FA of right hippocampus.




Dialeptic and psycho-emotional seizures.

Ictal left anterior temporal discharge

Normal MRI

↑ ADC and ↓ FA of left hippocampus.




Dialeptic, buccoral automatism, rare generalization.

Ictal left anterior temporal discharge

Normal MRI

↑ ADC and ↓ FA of right hippocampus.  




Dialeptic and bimanual automatisms.

Left anterior temporal spikes

Normal MRI

↑ ADC and ↓ FA in left hippocampus.




Epilepsia partialis continua right upper limb.

Left hemispheric slowing and spikes



↑ ADC and ↓  FA in left hippocampus  and left basal ganglia.




Dialeptic and buccoral automatisms.

Right anterior temporal spikes

Normal MRI

↑ ADC and ↓  FA in both hippocampal regions and left basal ganglia.

ADC Apparent diffusion coefficient, DTI Diffusion tensor imaging, F female, FA Fractional Anisotropy, M male, MTS mesial temporal sclerosis.


Table 2. FA and ADC values of both hippocampi, left lentiform and fornix in patient presented in Figure 3 as compared to controls.










Hippocampus FA

0.67 ´ 10-3

0.54 ´ 10-3

0.25 ´ 10-3

0.18 ´ 10-3

Hippocampus ADC

0.67 ´ 10-3

0.65 ´ 10-3

0.87 ´ 10-3

0.91 ´ 10-3

Lentiform FA

0.53 ´ 10-3

0.49 ´ 10-3

0.46 ´ 10-3

0.35 ´ 10-3

Lentiform ADC

0.97 ´ 10-3

0.88 ´ 10-3

0.86 ´ 10-3

0.99 ´ 10-3

Fornix FA

0.45 ´ 10-3

0.44 ´ 10-3

0.45 ´ 10-3

0.33 ´ 10-3

Fornix ADC

1.20 ´ 10-3

1.23 ´ 10-3

1.27 ´ 10-3

1.43 ´ 10-3



Figure 1: Plotting the ROIs for FA and ADC values measurement, in 19 years old male patient.




Figure 2. Ninteen year old male with epilepsy. Conventional brain MRI was unremarkable (not shown). a) DTI color map overlaid on axial FLAIR, b) DTI tractography of the cingulum overlaid on the axial image. ROIs were plotted on the hippocampus on both sides. There is decreased FA and increased ADC values on the left hippocampus compared to the right side (0.24 ´ 10-3 and 2.32 ´ 10-3 respectively) and left cingulum as compared to the right suggestive of left mesial temporal sclerosis. These findings were consistent with the EEG findings.


Figure 3. Twenty seven year old female with epilepsy. (A) Conventional coronal brain MRI was unremarkable. (B) DTI color map overlaid on coronal and (C) axial FLAIR showing lentiform nucleus (D) Axial DTI tractography showing fornix. ROIs were plotted on the hippocampus, lentiform nucleus and fornix on both sides. There are changes of the FA and ADC values in both hippocampal regions compared to the control subject, with decreased FA and increased ADC values on the left basal ganglia and white matter tracts.  Findings are suggestive of bilateral mesial temporal sclerosis and associated left basal ganglia and white matter tracts affection, the findings at the basal ganglia and white matter tracts explained the clinical and EEG findings in those patients (Table 2).



Previous DTI studies showed increased diffusivity and decreased FA in cerebral tissue ipsilateral to the epileptic focus whether temporal or extra temporal, lesional or non lesional, compared to the contralateral side and to healthy controls.7,10,11

Our study shows the role of DTI in mesial temporal lobe epilepsy compared not only to the conventional MRI but to other parameters of the epileptogenic zone including the semiology, the interictal and ictal EEG. Our measurements were not restricted to the temporal structures, but to the extra temporal structures that are suspected to be involved in such conditions. The choice of the extra temporal structures involved in DTI was based on previous studies that denoted evidence of involvement of these structures in MTLE.18-25,27-31

The primary finding is that DTI could accurately detect the site of epileptic focus even if there is bilateral involvement, furthermore, our study shows associated ipsilateral deep nuclei affection and white matter tracts involvement in some cases, findings were in agreement with the clinical data and EEG findings.

These results are in agreement with those of previous studies.7,10 Our study showed that diffusion tensor imaging was more in agreement with the electrophysiological and clinical data than the conventional MRI with a sensitivity of 100% and specificity of 40%. P value was 0.09 (not significant) and could be due to low number of cases included in the study.

Our DTI findings did not concur with MRI data as those of Rugg-Gun and colleagues.7 However, they concurred more with the clinical and electrophysiological localization of epileptogenic zone. This adds to the value of DTI in epilepsy.

This study as well as other studies7,10,14,16 indicates a potential role of DTI in localizing and lateralizing the epileptogenic zone. High-resolution brain MR imaging is still the standard neuroimaging technique for lateralizing the seizure focus in TLE, but negative MR imaging results can be encountered in cases of unilateral MTLE. Our study supports a complementary role of these two imaging modalities, although a study in larger patient sample may be needed to satisfactorily address this issue. This potential complementary role of DTI may be explained by the fact that each imaging technique is used to measure a relatively different aspect of the seizure focus. We believe that the improved technical design and understanding of the pathophysiology of DTI measurements may further improve the role of this imaging technique in evaluating patients with TLE.

Our study evaluated as well other seizure variables as semiology, ictal and interictal EEG to add to the validity of the outcome of MRI data. MRI alone cannot define the epileptogenic zone; clinical, electrophysiological and anatomical correlation, are mandatory.26

The high involvement of grey and white matter in our study (40%) is concordant with those of Bonilha and colleagues.27 His explanation to this extrahippocampal grey and white matter loss is due to remote deafferentiation and neuronal damage to the structure connected to the hippocampus secondary to neuronal loss in the hippocampus. A second postulated mechanism is direct spread of seizure activity to these structures with seizure toxicity and degeneration of these structures.

Limitations of this study include low number of patients included in the study and it highlights the need to study the associated extra temporal involvement on a wide scale by using other modalities.  



In conclusion, DTI of the brain coupled with MR tractography provides essential information in challenging cases of MTLE in which conventional MRI and EEG show no abnormality. Moreover, DTI could evaluate the associated deep nuclei and white matter tracts affection. The added quantitative value of DTI tractography is useful in proper evaluation, therapy and follow-up of these cases.


[Disclosure: Authors report no conflict of interest]




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الملخص العربى


دور الرنين الطيفي  فى مرضى صرع الفص الصدغى


يلعب الرنين المغناطيسيي دوراً كبيراً في تشخيص حالات الصرع وخاصةً باستخدام التطبيقات الحديثة للرنين المغناطيسي، مثل الرنين الطيفي، التي تمكننا من دراسة التغيرات الوظيفية التي تحدث في المخ حتي مع عدم وجود تغير تشريحي يمكن رؤيته بالعين.  كان هدف هذا البحث هو دراسة دور الرنين الطيفي فى مرضى صرع الفص الصدغى. شملت الدراسة عشره مرضي وعشرة أشخاص متماثلين في العمر والنوع كمقارنة. تم عمل رنين مغناطيسي ورنين طيفي وتخطيط بعض المسارات العصبية لجميع المرضي والأصحاء المشتركين في الدراسة مع مقارنة النتائج برسم المخ والحالة الاكلينيكيه. وقد تبين من النتائج وجود تغيرات في المرضي بالمقارنة بالاصحاء وهذه النتائج جاءت مطابقة لنتائج رسم المخ والحالة الاكلينيكيه. وعليه، يمكن استنتاج أن استخدام الرنين الطيفي ورسم المسارات العصبية قد ساعد في التشخيص وبالتالي في العلاج.


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