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Epilepsy & Behavior 12 (2008) 445–455

The selective amobarbital test in the anterior choroidal artery:Perfusion pattern assessed by intraarterial SPECT and prediction

of postoperative verbal memory

S. Vulliemoz a,*, A.J. Pegna a, J.-M. Annoni a, H. Yilmaz b, J.P. Willi c,L. Spinelli a, T. Landis a, M. Seeck a

a Department of Neurology, University Hospital of Geneva, Geneva, Switzerlandb Neuro-interventional Section, Department of Clinical Neurosciences, University Hospital of Geneva, Geneva, Switzerland

c Department of Nuclear Medicine, University Hospital of Geneva and Faculty of Medicine, University of Geneva, Switzerland

Received 30 September 2007; revised 22 November 2007; accepted 26 November 2007Available online 8 January 2008

Abstract

To screen for patients at risk for memory decline after temporal lobe epilepsy (TLE) surgery, selective amobarbital procedures, suchas injection into the anterior choroidal artery (ACA-IAT), are sometimes used. We investigated the extent of the territory affected duringACA-IAT and its predictive value with respect to postoperative memory. Seventeen patients with TLE underwent ACA-IAT. In 9 of 17patients, intraarterial SPECT co-registrated to MRI allowed delineation of amobarbital-perfused structures. Another subgroup of 9 of17 patients underwent anterior temporal lobectomy. Verbal memory was tested pre- and postoperatively and during ACA-IAT. Majorvariations in the ACA-IAT perfusion pattern occurred and were not correlated with the verbal memory scores during ACA-IAT. Post-operatively, no patient experienced a severe verbal memory decline, but individual postoperative performance was not correlated withresults during ACA-IAT. Our study suggests that ACA-IAT can be used to screen for severe postoperative amnesia in inconclusive cases,but cannot predict individual outcome, even when the perfusion pattern is taken into account.� 2007 Elsevier Inc. All rights reserved.

Keywords: Temporal lobe epilepsy; Amobarbital; Anterior choroidal artery; Single-photon-emission computed tomography; Memory

1. Introduction

Temporal lobe epilepsy (TLE) is the most frequent causeof pharmacoresistant focal epilepsy in adults and adoles-cents. Resection of anterior and mesial temporal lobe struc-tures can lead to complete seizure control in well-definedcases and has become an established treatment [1]. Postop-erative impairment of memory, particularly verbal mem-ory, remains a feared complication, and several methodshave been developed to determine the risk of such an amne-sic syndrome [2,3]. The most recognized risk factors for sig-

1525-5050/$ - see front matter � 2007 Elsevier Inc. All rights reserved.

doi:10.1016/j.yebeh.2007.11.015

* Corresponding author. Address: Presurgical Evaluation Unit, Depart-ment of Neurology, University Hospital of Geneva, Micheli-du-Crest 24,1211 Geneva 14, Switzerland. Fax: +41 22 372 84 75.

E-mail address: serge.vulliemoz@hcuge.ch (S. Vulliemoz).

nificant postoperative verbal memory decline includedominant hemisphere surgery, intact preoperative interictalmemory, and absence of hippocampal sclerosis on MRI [4–6]. Older age [4,7], male gender [8,9], extent of surgicalresection [10,11], low preoperative verbal IQ, as well asthe presence of cortical dysgenesis [12], are other risk fac-tors and should all be taken into account before surgery.

The intraarterial amobarbital test (IAT), initially devel-oped to identify the language-dominant hemisphere [13],consists of injection of a short-acting barbiturate into a cere-bral artery and produces transient deactivation of the corre-sponding vascularized structure. Behavioral testing of thepatient during IAT reveals the functioning of the unanesthe-tized structures, that is, the integrity of the structures thatwill remain after the intervention. Intraarterial injection ofamobarbital into the carotid artery is a validated procedure

446 S. Vulliemoz et al. / Epilepsy & Behavior 12 (2008) 445–455

widely employed to screen for the risk of postoperativeamnesia, to predict verbal memory decline after temporallobe epilepsy (TLE) surgery, and to lateralize the seizurefocus [14,15]. It compares the cognitive performance afterinjection into the hemisphere ipsilateral and contralateralto the epileptogenic focus by using indices of hemisphericasymmetry. However, its role in memory evaluation maybe hampered by the aphasia induced after injection intothe dominant hemisphere or by confusion after injection intothe nondominant hemisphere. Furthermore, although amo-barbital injected into the carotid artery is known to producehypoperfusion in the mesial temporal structures, as deter-mined by intravenous SPECT [16–18], other reports usingintraarterial injection of 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) during IAT have reported that theanesthetic agent did not perfuse the mesial temporal struc-tures in up to 75% of the patients [16,19,20]. Repetition ofthe IAT in the same patients produces less reliable resultsfor memory than for language testing [21].

These observations, combined with the development ofmore selective epilepsy surgery, led to the design of selec-tive amobarbital tests targeting the mesial temporal struc-tures. The mesial temporal lobe and, more specifically,the amygdaloid body and hippocampal formation are vas-cularized by the anterior choroidal artery (ACA) and theposterior choroidal artery (a branch of the posterior cere-bral artery), with anastomoses between both vessels[22,23]. IAT of the anterior choroidal artery (ACA-IAT)[24] and the posterior cerebral artery (PCA-IAT) [24–27]have been found useful in this respect.

In the present case series, we were interested in evaluat-ing the usefulness of ACA-IAT by determining exactlywhich brain regions are perfused by the test, how thisaffects memory performance (verbal and visual recogni-tion), and, ultimately, whether the procedure results inaccurate prediction of postoperative verbal memorydecline.

2. Methods

2.1. Patients

Between 1995 and 2006, 17 patients aged 15–56 years (8 women, 9men, mean age = 34.3 years) with intractable temporal epilepsy who wereconsidered candidates for resective surgery were evaluated with ACA-IAT. All except two (patients 9 and 17) were right-handed. On MRI, 14had hippocampal sclerosis and 3 had normal hippocampi (patients 7, 8and 11). Four patients had evidence of bilateral temporal dysfunctionon MRI or intracranial EEG (patients 6, 7, 8, and 11). This study wasapproved by the local ethics committee.

The indication for ACA-IAT was related to (1) the presence of domi-nant-hemisphere epilepsy or (2) a focus in the nondominant hemisphere,but significantly impaired interictal verbal memory scores. In our group,9 of 17 patients (4 women, 5 men) underwent additional assessment ofthe perfusion pattern with intraarterial SPECT. In all patients, the proce-dure was carried out ipsilaterally to the potential surgical resection, as ini-tially described by Wieser et al. [24].

Nine patients (3 patients with SPECT, 6 patients without) underwent tem-poral lobe surgery consisting of amygdalohippocampectomy and resection ofthe anterior third of the temporal lobe (anterior temporal lobectomy).

Table 1 summarizes the clinical features and the results of the patientworkups.

2.2. Selective amobarbital test in the anterior choroidal artery

Percutaneous transfemoral catheterization under local anesthesia wasperformed, and selective digital subtraction angiograms (DSAs) of theinternal carotid artery were obtained with biplanar angiography equip-ment (Philips Integris BV/BN 3000, Best, The Netherlands). The proce-dure was performed under intravenous heparin coverage (3000 IU), anda 5-French Envoy guiding catheter (Cordis Endovascular, Miami Lakes,FL, USA) was used. Depending on the size of the ACA and on the anat-omy of the carotid siphon, a previously steam-shaped microcatheter wasused (Vasco 10 microcatheter, Balt, Montmorency, France, or Fastracker18 microcatheter, Boston Scientific, Natick, MA, USA). A microguidewire (Transend Ex 14, Boston Scientific) was used to navigate throughthe carotid siphon. The previously steam-shaped microcatheter enableddirect catheterization of the ACA without the use of the microguide wire,thus avoiding the risk of arterial damage or spasm during the procedure.The microcatheter position was checked by angiographic series in theanteroposterior and lateral positions. Amobarbital (75 mg) was thenslowly and manually injected into the ACA over about 20 seconds to avoidreflux into the middle cerebral artery. Angiograms were performed afteramobarbital and 99mTc-ethyl cysteinate diethylester (99mTc-ECD) injec-tions to verify that the microcatheter remained at the same location.

2.3. Combined intraarterial and intravenous 99mTc-ECD cerebral

SPECT

Immediately after the amobarbital injection, a maximum of 0.5 mL of99mTc-ECD, corresponding to a dose of 26.4 ± 6.3 MBq, was slowlyinjected manually into the ACA. Following intraarterial injection, a doseof 460.8 ± 163.6 MBq of 99mTc-ECD was injected intravenously to bettervisualize the brain parenchyma in six of eight patients. The first twopatients (patients 1 and 2) in the series received only intraarterial injec-tions. SPECT imaging was performed 30 to 60 minutes after completionof the angiography on a three-head Toshiba GCA-9300 A/HR camerawith fan beam collimators. Data were acquired and reconstructed in a128 · 128 matrix. A Shepp and Logan filter was used. The scatter correc-tion was applied using the FBP/Sorenson method. Whole-brain volumewas covered.

2.4. Co-registration of intraarterial and intravenous SPECT to

MRI

Nuclear medicine images were transferred on the dedicated image pro-cessing workstation in Analyze format. The images were then resampled inan isotropic set and co-registered to the patient’s own millimetric three-dimensional MRI scan using a six-parameter rigid-body algorithm. Forthis purpose, we used AIR5.2 software, a voxel-based intensity algorithmavoiding the use of external markers.

In one of the two patients (patients 1 and 7) who received only anintraarterial injection, co-registration was possible (patient 7) becausehemispheric contamination provided anatomical landmarks. In the other(patient 1), co-registration was not possible and perfused structures wereidentified from the native SPECT images alone.

2.5. Neuropsychological protocol

ACA-IAT was performed according to the following protocol, asdescribed elsewhere [24]. Sixty cards, each containing a verbal item anda visual item to memorize (dual encoding run), were presented in centralvision to the patients. Verbal and visual stimuli were positioned one underthe other on the card; on half of the cards, the visual stimulus was on top,and on the other half, on the bottom. The cards were presented in pseudo-random order. Subjects were instructed to press a button (thumb of the

Table 1Clinical data

Gender/age/handedness

ACA-IAT side

Age at onset,frequency

Clinical aspects ATCD/etiology MRI EEG I Interictal PEThypometabolism

Operation

Patient 1 F/44y/R

Ra 4 years 0–10/month

LOC, automatismsPostictal: complete amnesia

— R HS TRIctal 6/6b

Interictal 85%c

R anteriortemporal

No

Patient 2 F/16/R

L 4 years 8/month

Anxiety fi LOC, automatismsPostictal aphasia

Febrile seizures L HS TLIctal and interictal

L temporal Yes

Patient 3 M/56/R

R 5 years 1/month

Epigastric aura fi LOCPostictal: prolonged confusionOccasional GTCS

Probableneonatalhypoxia

R HS TLIctal: 8/8 withcontralateralpropagationInterictal TR>>TL

R temporal Yes

Patient 4 F/32/R

L Childhood 1/week

Nausea fi LOC, automatismsPostictal: amnesia and aphasia

Febrile seizures L HS TLIctal and interictal

L anteriortemporal

Yes

Patient 5 M/15/R

L 11 years 2–8/year

Blurred vision, nausea fi LOC,automatisms, aphasia fi occasionalGTCS

— L HS TLIctal and interictal

L anteriortemporal

Yes

Patient 6 M/41/R

R 16 yearsCPS 1/monthSPS 1/week

‘‘Deja vu,’’ olfactogustatoryhallucination fi epigastric aura fi LOC,automatisms, occasional GTCS

— R>L HS TR>TLIctal 4/6Interictal 80%

R anteriortemporal

No

Patient 7 F/31/R

L 25 years withSE 3–6/month

Thoracic aura fi LOC, automatismsPostictal: aphasia, disorientation

— Normal ScalpInterictalbitemporalIctal: TLSEEG TL>TRIctal 5/7Interictal L>R

L temporal No

Patient 8 M/30/R

L 14 years 2/month

LOC, automatismsPostictal: amnesia

— Normal ScalpInterictal TLIctal late TLSEEG TL>TRIctal 11/15Interictal TL>TR

L temporal No

Patient 9 M/35/L

L 4 years 1/month

Epigastric aura fi LOC,automatisms fi GTCS

Early ischemiclesion

L HSL hemispheric atrophy

Interictal: LhemisphericmultifocalIctal: TL

L hemisphere No

Patient 10M/25/R

R 5 yearsSPS: 1–4/monthCPS: 2–8/month

Anxiety fi LOC, automatisms,urine loss fi GTCS

L hemiparesis andhemiatrophy

R HSR hemispheric atrophyR temporal schizencephaly

TRIctal and interictal

R temporal Yes

Patient 11M/51/R

L 16 months 4–7/week

Thoracic sensation, strange feeling fiLOC, automatismsPostictal: aphasia

Postvaccinalencephalitis(smallpox) at age 7

L temporal atrophy Scalp: TL>TRIctal late TLInterictal TL 90%SEEG: TL>TR

R temporal Yes

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Table 1 (continued)

Gender/age/handedness

ACA-IAT side

Age at onset,frequency

Clinical aspects ATCD/etiology MRI EEG I Interictal PEThypometabolism

Operation

Patient 12 F/31/R

R 5 years 1–7/week

Epigastric aura, palpitations, olfactoryhallucination fi LOC, cloni of L arm fiGTCS

Fetal distressFebrile seizures

R HSProbable L HS

TRIctal interictal

R>L temporal Yes

Patient 13 F/40/R

L 3 years 4–24/year

Thoracic aura fi LOC or motor aphasiaand R arm weaknessPostictal: aphasia

— L HS TLIctal interictal

L temporal Yes

Patient 14M/34/R

R 17 yearsSPS:15/monthCPS: 5/month

Epigastric aura fi LOC, automatisms,hypersalivation fi rare GTCSPostictal amnesia

— R HS statuspostresection of Rtemporo-parietalangioma

TR a R parietalIctal interictal

R temporal No

Patient 15M/26/R

R 13 yearsSPS:10–0/monthCPS: 5/month

Thoracic aura fi LOC, dystonia of bothhands, wandering fi rare GTCS

— R HS TRInteri l and ictalPropa tion to TL

R temporal Yes

Patient 16 F/32/R

R 3 years 10/month

Epigastric aura fi LOC, automatismsPostictal: confusion

— R HS TRIctal: 24/26Interi l: 66%

R temporal No

Patient 17 F/37/L

L 24 years 2–4/month

Nausea fi LOC, grasping Febrile seizures L HS TLInteri l TLslowiIctal: 0% late TL

L anteriortemporal

No

a R/L, right/left; TR/TL, right/left temporal lobe; LOC, loss of contact; SPS/CPS, simple/complex partial seizures; GTCS, generalized tonic–cl c seizures; HS, hippocampal sclerosis; BG, basalganglia; SE, status epilepticus.

b Ictal: numbers indicate proportion of seizures starting from the main focus.c Interictal: percentages indicate proportion of interictal spikes located at the main focus.

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S. Vulliemoz et al. / Epilepsy & Behavior 12 (2008) 445–455 449

hand ipsilateral to the side targeted by the ACA-IAT procedure) when acard was repeated. Among the 60 cards, 32 were repeated. Injection ofamobarbital started after 10–18 cards and was completed after 11–21cards (mean = 16). The display of the cards was briefly interrupted atthe end of the injection to assess language, visual field, and motor func-tions. Presentation of the cards then resumed and continued until all 60items were shown. This first session allowed us to test for the presenceof global amnesia following ACA-IAT. Five minutes after the end ofthe dual encoding run, a series of 128 cards were shown, this time witha single item (verbal or visual). These 128 cards were composed of 32 ver-bal and 32 visual items presented in the dual encoding run and 64 newstimuli. Cards were presented again in a pseudo-random order andpatients were instructed to press the button if the stimulus had been seenduring the first dual encoding run. This second session allowed us to mea-sure any asymmetry in performance between the recognition of verbal andvisual (nonverbal) material. The results were computed as a percentage ofcorrect recognition during the simple stimulation task.

The test was normalized on a group of 50 healthy subjects (25 F, 25 M,age range 20–38). Two by two correlations between verbal and nonverbalcategories were investigated and showed a positive correlation betweenverbal and nonverbal stimuli in this control group (Pearson correlationcoefficient = 0.38, P = 0.007) [28].

ACA-IAT memory performance was compared with interictal verbaland nonverbal retrieval memory (delayed recall) that had previously beenassessed using standardized verbal (Rey auditory–verbal learning test) andvisual (Rey visual design test) memory tests [29]. Both tests contain 15items that must be memorized and recalled over five repeated trials, witha delayed recall after 40 minutes. Scores are expressed as percentages ofcorrect recall. In the operated patients, memory was tested again 3–6months after surgery using parallel versions of the preoperative interictaltests.

Although the ACA-IAT memory protocol allows simultaneous mea-surement of verbal and nonverbal memory, its clinical indication was dri-ven by the concern over possible major postoperative decline in verbalmemory. Consequently, we focused on verbal memory performance.

2.6. EEG monitoring

EEG was recorded for at least 18 hours before as well as duringACA-IAT to exclude the occurrence of subclinical seizures. EEG wasrecorded from 17 electrodes in a standard 10–20 montage with exclu-sion of the middle temporal electrodes (T7, T8), which mask visualiza-tion of the ACA on digital angiograms. Patient 7 underwent invasivemonitoring with intracerebral stereotactic electrodes in the temporal,orbitofrontal, and frontomesial lobes on both sides during ACA-IAT.No seizure occurred prior to or during the ACA-IAT procedure, exceptin patient 15, who had a brief typical complex partial seizure 10 min-utes before the procedure.

2.7. Statistics

Analysis were carried out using a nonparametric Mann–Whitney U

test which was considered significant at P < 0.05.

3. Results

3.1. Perfusion pattern using intraarterial SPECT and

memory performance

Table 2 outlines the ACA-IAT perfusion patterns andverbal and nonverbal memory scores during ACA-IAT,as well as pre- and postoperative performance, for allpatients. Fig. 1 shows relevant examples of the perfusionpattern. For three patients (patients 1–3), the distributionof 99mTc-ECD and the perfusion of amobarbital were lim-

ited to the mesial temporal lobe (Fig. 1a). In right ACA-IAT, there was a moderate decrease in verbal memory per-formance for patient 1 and a marked decline for patient 3.Patient 2 (left TLE, left-sided test) showed good memoryperformance. In patients 4 and 5, the left thalamus wasaffected as well (Fig. 1b), with a decline in verbal memoryperformance in patient 4 but not patient 5 (additional smallreflux in the middle cerebral artery leading to a discretefrontal co-perfusion).

In the remaining four patients, extended perfusion pat-terns were observed. Three patients (patients 6–8) had con-comitant perfusion of the temporal neocortex and frontallobe, due to reflux from a thin ACA into the carotid arteryor vascular variants, as assessed by the angiograms.Patients 6 and 8 had additional perfusion of the thalamus.Moreover, patient 8 had extensive temporal lobe perfusionsparing only the pole and part of the superior temporalgyrus, due to a prominent inferolateral branch from theACA (Fig. 1c). Verbal memory performance was notaffected in patient 6 (right-sided test). In patients 7 and 8(left-sided test), significant verbal memory loss was noted.

Finally, in patient 9 (left-handed, left-sided injection),there was prominent contamination of the posterior com-municating artery and the posterior cerebral artery, proba-bly because the microcatheter tip was displaced duringtransient restlessness (Fig. 1d). However, the decrease inverbal memory was only modest.

In the whole group, no significant correlation was foundbetween number and size of affected territories and ACA-IAT performance, both for verbal and for nonverbalmemory.

3.2. Memory lateralization

The decline in verbal memory during ACA-IAT did notsignificantly differ between groups with right versus leftACA-IAT (P = 0.29). The same was true for the declinein nonverbal memory (P = 0.40). In patients with left-sidedACA-IAT, the decline in verbal memory was significantlylarger than the decline in nonverbal memory (P < 0.05).There was no significant difference between verbal andnonverbal memory in right-sided ACA-IAT (P = 0.18).

3.3. Prediction of postoperative outcome

Verbal memory performance during preoperative testingand ACA-IAT is illustrated in Fig. 2, in which patients areclassified according to their perfusion pattern. Fig. 3 illus-trates memory performance pre- and postoperatively andduring ACA-IAT.

All five patients who underwent surgery after rightACA-IAT had right TLE with unilateral hippocampal scle-rosis. Verbal memory scores were below 30% correctanswers during ACA-IAT in patient 3 (duration of epilepsy>50 years), in patient 15 (low preoperative memory, bitem-poral complex partial seizure shortly before the test), andin patient 12 (probable bilateral hippocampal lesions),

Table 2Clinical, angiographic, and memory data obtained with the ACA-IATa

Gender/age/handedness

Clinical change during test Angio-graphy Intraarterial SPECT PreopV%

PreopNV%

ACA-IAT V%

ACA-IATNV%

PostopV%

PostopNV%

Patient 1 F/44/R

Emotional reaction before injection R MTb 47 93 34 47

Patient 2 F/16/R

None L MT 80 67 69 59 40 60

Patient 3 M/56/R

None R MT 73 97 28 47 87 60

Patient 4 F/32/R

None L MT + thalamus 73 87 19 53 47 NA

Patient 5 M/15/R

None L MT + lateral thalamus + frontal 27 73 27 43

Patient 6 M/41/R

None R MT + thalamus fronto-orbital + lateral temporal

53 57 53 44

Patient 7 F/31/R

Faciobrachial weakness and hypesthesia, dysarthria L MT + temporal lateral + frontalb 73 70 6 69

Patient 8 M/30/R

None L MT + inferior temporal + thalamus+ orbitofrontal

87 100 22 50

Patient 9 M/35/L

R hemianopsia, ‘‘heavy R arm’’ Disinhibition L MT + thalamus + inferior posterior temporal+ occipital + orbitofrontal

47 37 34 59

Patient 10 M/25/R

Discrete disinhibition and psychomotor slowing R NA 87 83 75 75 93 100

Patient 11 M/51/R

None L NA 47 87 16 53 53 NA

Patient 12 F/31/R

Hypophony without dysarthria or aphasia R NA 80 40 25 28 60 37

Patient 13 F/40/R

None L NA 87 80 56 88 60 100

Patient 14 M/34/R

Moderate brachial weakness R NA 67 60 41 56 87 60

Patient 15 M/26/R

Habitual CPS 10 min before the procedureModerate brachial weakness and dystonia,hypophony

R NA 27 57 25 38 40 77

Patient 16 F/32/R

Long-lasting angiography, emotional reactionduring the test

R NA 60 70 13 50

Patient 17 F/37/L

Dysarthria, motor aphasia L NA 67 73 22 84

a Baseline memory performance is expressed as a percentage of delayed recall (15 words/figures). Preop/Postop, before/after surgery; R/L, right/left; MT, mesiotemporal; V, verbal memory; NV,nonverbal memory; CPS, complex partial seizure; NA, not available.

b No concomitant intravenous radiotracer, hence lower spatial definition.

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Fig. 1. Perfusion pattern of ACA-IAT assessed by SPECT during ACA-IAT, co-registered to MRI (left: axial view, right: coronal view). (a) Patient 2:selective perfusion of mesial temporal lobe. (b) Patient 4: additional perfusion of the thalamus. (c) Patient 8: additional extensive perfusion of the inferiorand lateral temporal lobe due to anatomical variation of ACA as well as frontal perfusion due to reflux into the internal carotid artery (arrow). (d) Patient9: additional temporo-occipital perfusion due to reflux into the posterior communicating artery.

S. Vulliemoz et al. / Epilepsy & Behavior 12 (2008) 445–455 451

Fig. 2. Verbal memory performance during the ACA-IAT (gray) forindividual patients compared with preoperative scores (white). Scores aregiven as percentages of correct answers. The vertical bar separates patientsinto two groups: selective perfusion (patients 1–3) and extended perfusion(patients 4–9). In parentheses is the side of ACA-IAT.

Fig. 3. Preoperative (white), ACA-IAT (gray), and postoperative (striped)verbal memory outcome for each patient who underwent surgery. Fromleft to right are preoperative, ACA-IAT, and postoperative. The verticalbar separates patients with a right-sided procedure (first five patients) frompatients with a left-sided procedure. In parentheses is the side of ACA-IAT.

452 S. Vulliemoz et al. / Epilepsy & Behavior 12 (2008) 445–455

who was the only one to show a postoperative decline.Both patients who scored higher than 30% during rightACA-IAT showed postoperative improvement of verbalmemory.

Three of the four patients who underwent surgery afterleft-sided ACA-IAT had left TLE with unilateral hippo-campal sclerosis; the fourth, patient 11, had nonlesionalbilateral TLE. Two patients (4 and 11) had verbal memoryscores below 30% correct answers during the procedure,but the scores were not predictive of postoperative decline.Postoperatively, memory scores declined for all exceptpatient 11, who had low preoperative verbal memory.Moreover, patient 2 showed a strong decline in verbal

memory that was not predicted by the ACA-IAT score.Fortunately, she could still retain 40% of items; that is,she had no postoperative amnesia.

There was no significant correlation between verbalmemory performance during ACA-IAT and pre-/postoper-ative decline whether considering the whole group or sub-groups of patients with right and left ACA-IAT. Therewas no significant correlation between preoperative andpostoperative verbal memory performance.

4. Discussion

In our institution, ACA-IAT is carried out when there isa concern about any potentially significant postoperativeverbal memory decline. Thus, only a small group ofpatients with intractable TLE undergo this procedure.Given its invasive nature, thorough evaluation of its useful-ness in terms of estimation of the postoperative memorydeficit is mandatory. Despite the modest size of the studygroup, we feel that important conclusions can be drawnregarding decisions on operability, which are always madeon an individual basis. Our study based on this series ofpatients with different types of TLE shows that:

1. Performed by experienced interventional neuroradiol-ogists, the procedure did not lead to complications.

2. The perfusion pattern of amobarbital varies greatlybetween patients.

3. No case of severe postoperative amnesia was observedin the patients screened preoperatively with ACA-IAT.Performance during the test was lower than postopera-tive performance in all except one patient; that is, ACA-IAT provides a pessimistic estimate of the postopera-tive situation in the vast majority.

4. The ACA-IAT memory test gives an insufficient esti-mate of the individual decline in postoperative verbalmemory. Underestimation and overestimation ofpostoperative decline were observed.

4.1. Perfusion pattern

The perfusion pattern during ACA-IAT has beenreported for only two patients so far, but details of theirclinical history were not given [24]. In our study, selectiveamobarbital injection into the anterior choroidal arteryled to a very variable perfusion pattern due to a combina-tion of anatomical variations and technical aspects (reflux,catheter displacement). The pattern varied from selectiveperfusion of the anterior mesial temporal structures tar-geted to widespread involvement of frontal, temporal,and parieto-occipital lobes, as well as subcortical struc-tures. This might explain, at least partially, the lack of pre-dictive value of ACA-IAT.

Amobarbital affected more than the mesial temporallobe in six of nine patients, including co-perfusion of thethalamus in five cases. In four of six patients with extended

S. Vulliemoz et al. / Epilepsy & Behavior 12 (2008) 445–455 453

perfusion, the decrease in verbal memory was significant.Interpreting significant memory decline in patients withan extensive pattern of perfusion is particularly challeng-ing: thalamic, frontal, as well lateral temporal structuresare known to be involved in memory function and theirinactivation would thus worsen memory scores [30]. Inthese cases, the memory test does not mimic selective surgi-cal resection. Consequently, knowledge of the perfusionpattern of amobarbital could be relevant in decidingwhether surgery is contraindicated in patients with a severedecrease in verbal memory during ACA-IAT.

A study of PCA-IAT found significant variability inneurological/neuropsychological deficits in patients withco-perfusion of the thalamus (11/14 patients) [31,32]. Vari-ations in the perfusion pattern are also found in intracaro-tid IAT: the mesial temporal region is perfused only inabout one-third of cases [16,18,20,33]. More data are there-fore needed to determine the influence of co-perfusion ofthe thalamus or other structures on memory performance.Other factors, such as side of TLE, presence of hippocam-pal sclerosis, and age at onset of the disease are known tobe relevant to postoperative verbal memory outcome andshould also be taken into account. Unfortunately, ourgroup was too small for multivariate analysis.

4.2. Memory lateralization

In our series of patients, nonverbal memory was lessaffected by the ACA-IAT procedure than verbal memory,consistent with evidence that nonverbal memory is less welllateralized and, thus, less severely affected after surgery[34,35]. This asymmetrical decline was largest in the groupwith left-sided ACA-IAT, confirming the importance of theleft-sided mesial temporal structures in our group of right-handed patients. Postoperative tests on our patients withright-sided ACA-IAT (all right-handed) confirmed thatverbal memory function did not strongly rely on the righthippocampus, despite doubts cast by the preoperative non-invasive workup.

4.3. Prediction of postoperative verbal memory outcome

The predictive value of amobarbital distribution in ver-bal memory decline during the test appears to be modest.Its main usefulness thus appears to be as an additionalscreening tool for patients at risk of global postoperativeamnesia, rather than as a predictor of the extent of thepostoperative deficit. In their study, Wieser et al. foundno statistically significant difference between ACA-IATverbal memory and postoperative verbal memory, but thecorrelation between the two is not given [24]. In our study,the extent of decline in verbal memory was not correlatedwith individual ACA-IAT performance. In patients withgood preoperative verbal memory, ACA-IAT scores below30% were associated with a postoperative decline in patient12 (right TLE) and patient 4 (left TLE), However, inpatient 3 (right TLE), ACA-IAT scores overestimated the

postoperative decline. In another patient (patient 2, lefthippocampal sclerosis), postoperative neuropsychologicaltesting revealed a major verbal memory decline (assessedpsychometrically but not as severely noted by the patient),which was not suspected by ACA-IAT results (underesti-mation). The two patients with low preoperative verbalmemory (patient 11 with left TLE and patient 15 with rightTLE) had low ACA-IAT scores but no postoperativedecline.

Knowledge of the whole clinical picture and of the per-fusion pattern could help in understanding the discrepantcases. Patients 7 and 8 had bilateral TLE with left-sidedpredominance and no hippocampal sclerosis. They hadgood preoperative verbal memory but very low verbalmemory during the test, in the context of an extended pat-tern of amobarbital perfusion. These results, in addition tothe known elevated risk of verbal memory decline in theabsence of hippocampal sclerosis [5], were interpreted asa contraindication to epilepsy surgery. As no operationwas performed, we do not know if the extended patternof amobarbital perfusion turned these patients into false-positive cases. Patient 9 had early ischemic lesions as wellas early epileptogenic activity, reportedly associated withatypical localization of language and memory functions[36,37]. This might explain the discrepancy between theextended territories revealed by SPECT and the moderateneuropsychological deficits, so that the clinical pictureappears more relevant than the perfusion pattern revealedby SPECT.

4.4. Clinical implications

Established clinicoradiological predictive factors ofpoor verbal memory outcome are surgery on the dominanthemisphere, intact preoperative memory, absence of ipsi-lateral hippocampal sclerosis [5], older age [4,7], male gen-der [8,9], extent of surgical resection [10,11], lowpreoperative verbal IQ, as well as the presence of corticaldysgenesis [12]. These should all be taken into accountbefore surgery.

Although less validated and technically more difficultthan the carotid IAT, ACA-IAT is sometimes envisagedwhen there is a risk of severe postoperative verbal memorydecline or when global amnesia is feared. Although it maybe valid for these purposes, the test seems to be insufficientin providing a good estimate of the degree of postoperativeverbal memory decline. The results should always be inter-preted with all relevant clinical data, to prevent incorrectjudgments concerning the operability of an individualpatient.

With respect to carotid IAT, two recent studies foundthat noninvasive tests (neuropsychology, volumetricMRI) were as reliable as carotid IAT in predicting postop-erative decline in verbal memory [38,39]. These observa-tions, as well as the ongoing development of functionalMRI using memory tasks [40,41], will certainly reduce

454 S. Vulliemoz et al. / Epilepsy & Behavior 12 (2008) 445–455

the importance of amobarbital procedures for TLE surgeryin the future.

Acknowledgments

The authors thank Nicolas Ruffieux and Boris Pimonowfor their help in gathering the neuropsychological data.

This study was supported by SNF Grants IB74B0-111086, 3200B0-104146, 3200-068105, and 3200-113766.Serge Vulliemoz is supported by the Fonds de Perfectionn-ement of the University Hospital of Geneva.

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