Elsevier

NeuroImage

Volume 24, Issue 1, 1 January 2005, Pages 101-110
NeuroImage

Cerebral perfusion changes in mesial temporal lobe epilepsy: SPM analysis of ictal and interictal SPECT

https://doi.org/10.1016/j.neuroimage.2004.08.005Get rights and content

Abstract

We examined cerebral perfusion changes in mesial temporal lobe epilepsy (mTLE) by the statistical parametric mapping of brain single photon emission computed tomography (SPECT) images of 38 mTLE patients and 19 normal controls. Ictal and interictal SPECTs were compared with control SPECTs by independent t test, and ictal and interictal SPECTs by paired t test. We evaluated the number of heterotopic neurons in temporal lobe white matter, white matter changes of the anterior temporal lobe (WCAT) and ictal hyperperfusion of the temporal stem (IHTS). Left mTLE showed interictal hypoperfusion in the ipsilateral hippocampus, bilateral thalami, and paracentral lobules. Right mTLE showed hypoperfusion in bilateral hippocampi, contralateral insula, bilateral thalami, and paracentral lobules. Both mTLEs showed ictal hyperperfusion in bilateral temporal lobes with ipsilateral predominance, and in the anterior frontal white matter bilaterally. By paired t test, ictal hyperperfusion was found in the ipsilateral temporal lobe, temporal stem, hippocampus, thalamus, putamen, insula, and bilateral precentral gyri, whereas ictal hypoperfusion was found in bilateral frontal poles and middle frontal gyri. Fifteen patients showed WCAT and 19 showed IHTS, a weak correlation was observed between WCAT and IHTS (r = 0.377, P = 0.02). WCAT was found to correlate with an early seizure onset age. In 35 patients, heterotopic neurons were found in the white matter of the resected temporal lobe, but the number of heterotopic neurons did not correlate with WCAT or IHTS. In summary, the cerebral perfusion patterns of mTLE suggest interictal hypofunction and ictal activation of the cortico-thalamo-hippocampal-insular network and ictal hypoperfusion of the anterior frontal cortex.

Introduction

Mesial temporal lobe epilepsy (mTLE) is the most common type of intractable partial epilepsy, and hippocampal sclerosis (HS) is the most frequent pathological finding (Williamson et al., 1993). Moreover, temporal lobectomy leads to complete or almost complete seizure control in 70% to 80% of appropriately selected patients (Engel, 1987).

Brain single photon emission-computed tomography (SPECT) has been used to localize epileptogenic foci and to investigate regional cerebral blood flow (rCBF) in the epileptic brain, and increased rCBF has been detected during seizures by SPECT (Bonte et al., 1983). Meta-analysis showed that the sensitivities of brain SPECT for seizure localization in patients with temporal lobe epilepsy were as follows: 44% (32.3–55.3%) for interictal SPECT, 75% (63.1–85.2%) for postictal SPECT, and 97% (88.7–99.6%) for ictal SPECT (Devous et al., 1998).

Subtracted ictal–interictal SPECT co-registered with MRI (SISCOM) is useful for the further localization of epileptic foci (Lee et al., 2000, O'Brien et al., 1998, Zubal et al., 1995) and for studying the pathophysiology of epilepsy (Shin et al., 2001, Shin et al., 2002, Joo et al., 2003, Lee et al., 2002). And, Statistical Parametric Mapping (SPM) is a proven and effective method for the voxel-by-voxel analysis of functional images (Friston et al., 1995). The advantage of this approach lies in its promise of fully automated neurophysiological imaging analysis throughout the whole brain using various statistical approaches.

The ipsilateral temporal lobe, thalamic hypoperfusion in the interictal period (Yune et al., 1998), and ictal hyperperfusions of the ipsilateral temporal lobe, basal ganglia, frontal lobe, and contralateral cerebellum have been demonstrated in TLE (Shin et al., 2001). In addition, these various perfusion patterns in epilepsy are related with the structural and functional connections of the neural network in the human brain (Spencer, 2002).

The aim of the present study was to investigate rCBF changes during ictal and interictal periods and the neural network of unilateral mTLE using voxel-based SPM. Although many SPECT studies concerning mTLE have been reported, well-designed voxel-based studies are scarce. Furthermore, many studies have been performed without consideration of the functional asymmetry of the hemispheres, as achieved by flipping the images to the side of the epileptic focus. Although no asymmetry was found between left and right mTLE in one study (Van Paesschen et al., 2003), we compared left and right mTLE groups separately with normal controls, and left with right mTLE to find functional asymmetry. Clinical findings were compared to rCBF changes, such as heterotopic neurons in temporal lobe white matter, white matter change of the temporal lobe (WCAT) in T2-weighted MRI and ictal hyperperfusion of the temporal stem (IHTS) in SISCOM.

Section snippets

Subjects

Thirty-eight patients (22 left mTLE, 16 right mTLE) with the unilateral mTLE were enrolled. Inclusion criteria were; (1) unilateral hippocampal sclerosis by MRI and hippocampal sclerosis by pathological examination, (2) radiotracer injection during CPS for ictal SPECT during scalp EEG monitoring, and an (3) excellent surgical outcome (Engel class I) after anterior temporal lobectomy with amygdalohippocampectomy at Samsung Medical Center from 1996 to 2001.

All subjects received long-term

Results

Sex and age were not significantly different among left mTLE, right mTLE, and normal controls. In addition, age of seizure onset, duration of disease, tracer injection time for ictal SPECT, and duration of seizure were not different between the left and right mTLE groups (Table 1).

All patients (38/38) showed complex partial seizure (CPS) at the time of tracer injection. Four left mTLEs progressed into generalized tonic–clonic seizures (GTC) after tracer injection. The left mTLE group showed

Cortico-thalamo-hippocampal-insular network

Compared to normal controls, left mTLE showed interictal hypoperfusion in the ipsilateral hippocampus, insula, and in bilateral thalami and pericentral cortices (Table 2, Fig. 1, Fig. 3). This result indicates functional impairment of the cortico-thalamo-hippocampal network and anterior insular cortex. Previous studies have suggested that the thalamus participates in the initiation or propagation of temporal lobe seizure, and that it is related to the interictal cognitive dysfunction of

Conclusions

This study demonstrates that cerebral perfusion changes of the cortico-thalamo-hippocampal-insular network in unilateral mTLE. Moreover, perfusion changes were found in ictal hyperperfusion and in interictal hypoperfusion, and an asymmetric pattern of interictal cerebral perfusion was observed in left and right mTLE groups in the hippocampus contralateral to the epileptic side. Although no significant correlation was deduced between heterotopic neuron numbers and ictal hyperperfusion in

Acknowledgments

We thank Tomas E. Nichols (Department of Biostatistics, University of Michigan, USA) for reviewing the statistical SPM approach, and Lucy L. Brown (Neurology, Department of Neuroscience, Albert Einstein College of Medicine, USA) and Alexander Hammers (Clinical Science Center, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, UK) for advising on rCBF increases in white matter.

This study was supported by a grant no. HMP-03-PJ1-PG3-21300-0033 of the Good Health R and D

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