Epilepsy Research 42 (2000) 83–88

Persistent postictal hyperperfusion demonstrated with PET

Rozet Tatlidil *Research Imaging Center, Uni6ersity of Texas Health Sciences Center, San Antonio, TX, USA

Received 10 February 2000; received in revised form 20 April 2000; accepted 23 April 2000

Abstract

Four patients with complex partial seizure disorder whose positron emission tomography (PET) scans showsustained hyperperfusion of the epileptiform focus 12–24 h after a seizure episode are presented. Three of thesepatients underwent same day Fluorine-18 (18F) deoxyglucose (FDG) PET scans, which showed hypometabolism ofthe epileptic temporal lobe. In one patient who underwent repeated blood flow and concurrent glucose metabolismscans 4 days after a seizure, hyperperfusion was not present and the FDG-PET demonstrated hypometabolism.Persistent hyperperfusion was noted in six out of 65 cases studied. Four out of six patients who were followedclinically were presented in this report. The cause of the rare occurrence of persistent postictal or interictalhyperperfusion and the differences of postictal blood flow dynamics and glucose metabolism need to be clarifiedfurther with future studies. © 2000 Elsevier Science B.V. All rights reserved.

Keywords: Blood flow; Epilepsy; 18F deoxyglucose (FDG); Lactate; Positron emission tomography (PET); Seizures

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1. Introduction

Interictally, an epileptic focus in the temporallobe characteristically shows hypoperfusion andhypometabolism (Kuhl et al., 1980). Previousstudies have indicated that the perfusion abnor-mality has been generally less profound than glu-cose metabolism (Leiderman et al., 1992). Thisobservation has been attributed to interictal un-coupling of blood flow and metabolism by laterstudies (Fink et al., 1996). Classically, during

neuronal discharges such as seizures, the glucosemetabolism and perfusion are closely coupled(Kuhl et al., 1980 and Frank et al., 1986). Thefocal glucose hypermetabolism and hyperperfu-sion is most likely related to increased glucosedemand within an active epileptic focus (Lewis etal., 1974). Hyperperfusion and hypermetabolismduring ictal activity has been demonstrated byimaging studies (Frank et al. 1986; Theodore etal., 1989; Chugani et al. 1993). Chugani et al.presented positron emission tomography (PET)scans of seven epileptic children, which showedfocal glucose hypermetabolism postictally and in-terictally when the EEG is abnormal. Blood-flowdynamics change from hyperperfusion to hypop-

* Present address: 1362 Sokak No. 14-A, 35230 Cankaya,Izmir, Turkey. Tel.: +90-232-4848851; fax: +90-232-4842936.

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R. Tatlidil / Epilepsy Research 42 (2000) 83–8884

erfusion postictally as shown by ictal SPECTstudies. This observation has been valuable forlocalization of the epileptogenic focus. The dura-tion of postictal hyperperfusion is not a constant.It has generally been reported that postictal bloodflow changes return to baseline within 10–30 minafter the seizure (Newton et al., 1992). In this caseseries, four cases of complex partial seizures(CPSs) with delayed postictal hyperperfusion arepresented.

2. Methods

15O water and 18F deoxyglucose (FDG) PETscans were performed with a GE/Scanditronix4096, a 10.6 cm field of view, 15 slice tomographwith a resolution of 6.5 mm in plane and 6.5 mmin axial full-width at half maximum. Scans wereperformed in the resting, eyes closed condition.Transmission scans with Germanium-68 sourcewere obtained to measure and correct for theattenuation. The emission images were recon-structed with a Hanning filter to a resolution of 8mm. After 2590 MBq (70 mCi) of 15O waterinjection, scans of 90 s were performed for theflow imaging of a total of three injections/scansper patient. Blood-flow scans were averaged intoa single image to improve the signal noise ratio.Subsequently, glucose metabolism image was ob-tained for a total of 20 min, after 40 min of 204MBq (5.5 mCi) intravenous FDG injection. BothFDG and blood flow scans were completed within1.5–2 h. A region of interest was drawn throughthree consecutive mid and lower temporal lobeplanes outlining the temporal lobes. Functionalasymmetry indices (FAIs), using counts were cal-culated as 100× ((left−right)/(left+right×0.5)).Normalized regional values (NRVs) were calcu-lated as the mean radioactivity of the temporalregion of interest, to the mean radioactivity of thewhole brain (Fig. 1). An average NRV and FAIvalue was calculated for three temporal slices.Data of 100 controls, who served as volunteers inother research studies, was used for calculatingmean and standard deviations (S.D.) (mean FAI:0.1, S.D.: 92.35; mean NRV: 0.92, S.D.: 90.05).

2.1. Case 1

The patient was a 34-year-old right-handed fe-male with medically refractory CPSs beginning atage 19, with the frequency of seizures rangingfrom 4 to 20/month. Seizures began with bilateralopening and closing of her fists, simultaneoushead turning to the left and progressed to unre-sponsiveness with postictal confusion lasting sev-eral min. Clinical seizures were not detected using24-h video EEG monitoring, but some phase re-versing, sharp slow wave epileptiform discharges,predominantly over the left F7-T3 electrodes,were observed within a week prior to PET scan.Left hippocampal atrophy was evident on MRI.An 15O water and FDG-PET scan, performed onthe same day, showed increased perfusion anddecreased glucose metabolism of the epileptic fo-cus in the left temporal lobe (Fig. 2). Averagetemporal lobe FAIs were −8.9 for FDG and 6.81for blood flow. Temporal, to all brain, NRV ratiofor blood flow was elevated (1.05). The patient’slast clinical seizure was 24 h prior to PET scan.The scalp EEG recorded during the PET scansdid not demonstrate epileptiform activity. Sheunderwent left temporal lobectomy and remainsseizure free after 4 years follow-up. The patho-logic diagnosis was left temporal lobe gliosis.

2.2. Case 2

The second patient was a 45-year-old righthanded male with a history of medically in-tractable complex partial epilepsy since the age of23, with seizure frequency ranging from 10 to20/month. The seizures were preceded by a sensa-tion of lightheadedness, headache followed byunresponsiveness and postictal confusion for 10min. Video EEG monitoring was performed usingthe standard and sphenoidal electrode placement.Baseline and sleep deprivation EEGs demon-strated intermittent slowing in the right temporalregion maximum at the T4 electrode with occa-sional epileptic discharges, 1–2/min at the F8 andT4 electrodes. Video-EEG recorded a total ofeight seizures with localization to mesial and pos-terior regions of right temporal lobe. MRI wasnormal. The patient’s last seizure was 12 h prior

R. Tatlidil / Epilepsy Research 42 (2000) 83–88 85

Fig. 1. Illustration of the regions of interest (ROI) method. A 30% threshold of maximum value of the whole brain is selected towrap the brain contour. After thresholding, the slices were manually edited to exclude non-temporal regions. Temporal regions weredrawn on three consecutive temporal planes. NRYs and FAIs were calculated from regions of interest.Fig. 2. Reversal of asymmetry indices of blood flow and FDG images are seen. Note left temporal lobe hypometabolism (arrow).15O water image demonstrates hyperperfusion of left temporal lobe evidenced by elevated NRV (1.05). (FAI for FDG: −8.9, bloodflow: +6.81).

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to the PET scan while he was in the VEEGmonitoring unit. PET showed right temporal lobeglucose hypometabolism. Focal hyperperfusionwas noted within the right temporal lobe(NRV:1.04) (Fig. 3). FAI was 3.5 for FDG and−4.5 for the blood flow scan. EEG monitoringwas not performed during the PET scan. After aright temporal lobectomy, he has been seizure freeat his 5 months follow-up. Pathologic diagnosiswas gliosis of the right hippocampus.

2.3. Case 3

The patient was a 46-year-old right handedmale who had a history of seizures beginning atage of 11, which have been refractory to multipleregimens of anticonvulsant therapy. His seizurefrequency was approximately 20/month. The pa-tient was evaluated with video-EEG monitoringfrom scalp, foramen ovale and sphenoidal elec-trodes with no clear-cut lateralization for onset of

Fig. 3. Note hypometabolism of the right temporal lobe. Note reversal of this pattern on perfusion images. Focal hyperperfusionis apparent in mesial temporal region. (NRV: 1.04; FAI for FDG: +3.5, blood flow: −4.5).Fig. 4. Right temporal hyperperfusion (NRV: 1.04, FAI: −10) (lower row) Reversal of asymmetry index (FAI for FDG: +5.3)(upper row).Fig. 5. Note hyperperfusion of the left temporal lobe (FAI: 12; NRV: 1.06) 24 h after a seizure (left). Non-lateralizing blood-flowPET 4 days postictally. FAI (−2) insignificant. (NRV: 0.92) (middle). Lateralizing FDG-PET scan 4 days postictally. Note glucosehypometabolism of the left temporal lobe. (FAI: −8; NRV: 0.80) (right).

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his seizures. MRI study was normal. The patient’slast clinical seizure was 20 h prior to the PETscan. EEG was not recorded during the PET scan.The PET scan revealed hyperperfusion and mildhypometabolism of the right temporal lobe (Fig.4). These changes were mild, not as apparentvisually and were clarified with quantitative analy-sis. FAIs were 5.3 for FDG and −10 for 15Owater scan. NRV on blood flow image was in-creased (1.04) within the right temporal lobe.Subsequently, stereotactic depth electrodes wereplaced into orbitofrontal areas, amygdala andhippocampus bilaterally and demonstrated righthippocampal onset of seizures. The patient under-went right anterior temporal lobectomy and hasbeen significantly improved with three seizures in5 years after the surgery. The pathologic diagnosiswas right hippocampal microdysgenesis.

2.4. Case 4

A 32-year-old right handed female had CPSsbeginning at the age of 2 years. Her seizures wereaggravated by fatigue and stress and became in-creasingly refractory to medications. They hadincreased tenfold in frequency, occurring almostevery day and in clusters within the month priorto presurgical evaluation. MRI scan showed lefthippocampal sclerosis. Video EEG monitoringclearly showed a left temporal onset with wavescharacterized by bursts of spikes and frequentgeneralized slow wave activity. The first PET scanwas performed 24 h following a seizure free inter-val. Scalp EEG monitoring was performed duringthe PET scan showed intermittent generalizedbackground slowing, and no evidence of seizureactivity during the EEG. An 15O water PET scanshowed left temporal lobe hyperperfusion (FAI:+12, NRV: 1.06) (Fig. 5). The imaging was re-peated 4 days after her last seizure, both withblood flow and FDG tracers. EEG monitoringwith findings similar to the earlier one, was againperformed during the PET study and demon-strated no evidence of epileptiform activity. Bloodflow scan did not demonstrate hyperperfusion(NRV: 0.92, FAI: −2). The FDG FAI was −8(Fig. 5). A left anterior temporal lobectomy wasperformed. She remains seizure free after 15

months of follow-up. The pathologic diagnosiswas diffuse gliosis of inferior and mesial temporallobe.

3. Discussion

Postictal and interictal glucose hyperme-tabolism and hyperperfusion has been reportedpreviously (Lang et al., 1988; Leiderman et al.,1994; Franceschi et al., 1995; Rubin et al., 1995;Sperling et al., 1995; Devous et al., 1998). Interic-tal hyperperfusion of an epileptic focus has beenseen up to 7 days after a seizure (Lang et al.,1988). In some cases, hyperperfusion has beenattributed to EEG activity during the uptakephase of the SPECT radioligand. In the majorityof cases, the cause of focal hyperperfusion withinthe epileptic focus has not been clear. Therefore,there may be additional factors, which can causesustained postictal hyperperfusion. It has longbeen recognized that during the epileptic dis-charges, the increased neural activity causes anincrease in the tissue lactate and lactate/pyruvateratio (Siesjo, 1978). Comair et al. (1994) demon-strated sustained elevation of lactate up to 6.5 hafter a seizure in a patient utilizing 1H-CSI imag-ing. One explanation of the slow recovery of postictal blood flow to baseline would be due toaccumulation of products of the anaerobic glycol-ysis. Lactate being an important index of anaero-bic cerebral metabolism may be responsible forthis postictal enhancement of blood flow. A recentstudy reported simultaneous changes in the lactatelevel and regional blood flow (rBF) in the brain ofan anesthetized rabbit by using localized protonmagnetic resonance spectroscopy (1H MRS) andlaser Doppler flowmetry. Increased lactate wasfound to prolong the period of enhancement ofrBF during the recovery from hypoxia (Yanai etal., 1997). It is also possible that temporary tonicelevation of neuronal activity or occasional sub-clinical epileptiform discharges of the epilepticfocus during the PET scan unrecognized by thescalp EEG scan may have caused this hyperperfu-sion. Although unlikely, another explanationwould be uncoupling of flow and glucosemetabolism of an active epileptic focus (Bruehl etal., 1998 and Bittar et al., 1999).

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PET studies in conjunction with the depth elec-trode monitoring and spectroscopic studies will benecessary to better understand the underlyingmechanisms of persistent postictal hyperperfusionand differences between flow and metabolismpostictally.

Acknowledgements

The author acknowledges Frank Zamarrip fortechnical assistance in image processing, and thestaff of medical records of the University Hospitaland Methodist Hospital in San Antonio, Texasfor providing the clinical information on cases.

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