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Review articleEpileptic Disord 2013; 15 (3): 221-39

Cognitive outcomesof different surgical approachesin temporal lobe epilepsy

Christoph HelmstaedterDepartment of Epileptology, University of Bonn, Germany

Received March 22, 2013; Accepted June 12, 2013

ABSTRACT – Epilepsy surgery is a successful treatment option forpharmacoresistant focal symptomatic epilepsies. However, cognitiveimpairment is very common in epilepsy patients and may be negativelyor positively affected by surgery. Amidst the long-standing discussion ofwhether a particular surgical approach for temporal lobe epilepsy patientsmay be superior with regards to seizure control, a recent meta-analysisindicated that this is the case for more extended resections. Larger tem-poral lobe resections, however, raise concerns that more unaffected andfunctional tissues may be involved, thus causing worse cognitive outcome.This review is based on published reports collected over a long period,with changing diagnostics and surgical methods, and focuses mainly onthe experiences of one epilepsy centre. The review highlights the effectsof standard versus selective surgery, the different surgical approaches inselective surgery, determinants other than surgery which may affect cog-nitive outcome, and the methodologically-important question of outcomeassessment and how neuropsychological test selection may bias the result.Overall, from a neuropsychological point of view, individual and selectivesurgery is preferred in which the aim is to achieve seizure control with min-imal effect on the functional integrity of tissues or fibre tracts. Cognition

ryday life and this should be kept inrgery is preferred.

selective surgery, standard surgery,

with temporal lobe epilepsy (TLE),successful seizure control wasachieved in 58% operated versus8% medically-treated patients in

is important for the functions of evemind, irrespective of which kind of su

Key words: temporal lobe epilepsy,outcome, cognition, memory

The cognitive outcomeof temporal lobe epilepsysurgery

pileptic Disord, Vol. 15, No. 3, September 2013 221

orrespondence:hristoph Helmstaedterepartment of Epileptology,niversity of Bonn,igmund Freud Str 25,3105 Bonn, GermanyC.Helmstaedter@uni-bonn.de>

Epilepsy surgery represents a verysuccessful treatment option forpatients with focal symptomaticepilepsies. By comparing surgicalversus conservative medical treat-ment in 80 randomised patients

a 12-month observation period(Wiebe et al., 2001). This corres-ponds to what was found in ourown non-randomised longitudinal2-10-year follow-up study of 102medically- (12% seizure-free) versus147 surgically- (63% seizure-free)

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reated patients with TLE (Helmstaedter et al., 2003). Inonclusion, and without any further characterisation,bout two thirds of operated patients with TLE mayecome (permanently) seizure-free (Tellez-Zentenot al., 2010).eizure control is clearly the primary aim ofpilepsy surgery. Successful seizure control under-tandingly reduces behavioural and mood problemsnd improves overall quality of life. However, leavingeizure control aside, brain surgery can have negativeffects on cognition and behaviour, resulting in impair-ents which quantitatively and qualitatively exceed

hose observed before surgery (Helmstaedter, 2004).able 1 provides a comprehensive overview of therequency of cognitive deficits and changes in postop-rative performance in a large cohort of 732 patientsith TLE, who received surgery in Bonn between

989 and 2007 (Helmstaedter et al., 2007). Accord-ng to categorical test results (using a point systemccording to standard deviations, whereby 0 to 4epresents severely impaired to above average perfor-

ance, and 3 represents average performance), 78%f patients with chronic pharmacoresistant TLE alreadyad cognitive impairment (values <2) of either verbalemory, figural memory, or attention/executive func-

ions before surgery. Regarding the localisation of thepileptogenic focus in brain regions relevant to memo-y processing, the most commonly affected cognitiveomains in TLE are verbal and figural memory, fol-

owed by complications in language, attention, andotor and visuo-constructive functions. Consistentith the literature, lateralisation-dependent results are

een regarding verbal memory impairment and a morerequent atypical language dominance in left sidedLE, and with more frequent impairments in figuralemory and attention in right-sided TLE. In addition to

ateralisation, factors such as the time of epilepsy onsetduring brain maturation or after), presence versusbsence and type of underlying lesion (e.g. neoplasticersus developmental), patient variables (such as age,ender, and education), and last, but not least, medi-ation and seizure situation differentially contributeo the cognitive capabilities observed in individualatients. One year after surgery, 65% of 732 patientsere completely seizure-free, i.e. they did not have

ny seizures or aura. By applying 90% reliability ofhange indices (RCI), individually significant gains andosses in the assessed domains were evident for 10-0% of the patients. According to table 1, major gains

22

oncern extratemporal non-memory functions. Lossesre prominent in memory, and here patients with left-ided temporal epilepsy are more frequently affectedhan those with right-sided temporal epilepsy. Patientsith left-sided temporal epilepsy also worsen with

egards to language functions which tend to improvefter right-sided surgery.

cFsmooH

he findings in this large cohort of patients fit wellith base-rate estimates of expected gains and losses

fter TL surgery which were published in a recenteta-study on cognitive outcomes after TL surgery

Sherman et al., 2011). Regarding 22 of 193 evaluatedtudies investigating temporal lobe surgery and takingCI or standardised regression-based (SRB) changecores into consideration, the pooled estimates ofains and losses for the assessed cognitive domains

ndicated a rate of 44% patients with verbal memoryecline after left-sided surgery, compared to 20% afteright-sided surgery. The gains for verbal memory werecarce; 7% (left side) versus 14% (right side). Losses ingural memory were not different between left-sided

15%) and right-sided (10%) surgery. The total averageate of decline in language (naming) was 34%. As inhe Bonn sample, benefits were identified for execu-ive functions after left-sided surgery (10% losses and7% gains); for right-sided surgery, the losses and gainsere 21% and 16%, respectively.ummarising the findings so far, TLE patients andhose with left TLE in particular, bear an increasedisk of cognitive decline in memory after temporalobe surgery. In some patients, improvement of cog-itive functions is possible. The role of seizure control

or the postoperative course of cognition is still aatter of debate. While Rebecca Rausch reported a

rogressive decline, independent of seizure outcome,n a long-term follow-up study, our own long termollow-up study indicated that further decline versusecovery depended on seizure control (Helmstaedtert al., 2003; Rausch et al., 2003). Recent evidence fromwo other long term follow-up studies indicates a sta-le course of memory from two years after surgery

Alpherts et al., 2006; Andersson-Roswall et al., 2010).

eterminants of cognitive outcomefter surgery

wo major factors determine the cognitive outcomef epilepsy and its treatment. The first and probablyost predictive factor is the “functionality” of brain

reas affected by epilepsy which are to be resectedChelune, 1995; Stroup et al., 2003). The second factor,losely connected to the question of “functionality”,oncerns the brain areas and functions not affected bypilepsy or surgery, referred to as the patient’s “mentaleserve capacity” (Helmstaedter, 1999). Mental reserve

Epileptic Disord, Vol. 15, No. 3, September 2013

apacities can help to compensate surgical defects.unctionality of the brain also appears to predict latereizure control (Helmstaedter, 2009). Seizure controlay be discussed as a third determinant of cognitive

utcome. Here, the principal idea is that of a releasef functions due to control of epileptic dysfunction.owever, up to now, there is only sparse evidence

E

Cognitive outcome and surgery in TLE

Table 1. Cognition in TLE before and after surgery.

Preoperative impairmentsa Postoperative changes (1 year)b

Domain n L TLE (%) R TLE (%) n L TLE (%) R TLE (%)

impairment=x<m-1.5 SD

Verbal memory 732 69 46*** 732 40 14*** 27 29

Figural memory 716 49 59** 707 31 27 28 23

Attention 717 21 29* 709 11 36*** 11 40***

Language 653 39 32 618 21 27 14 32***

Motor function 717 30 40 449 16 34*** 16 37***

Visuo-construction 602 19 21 554 10 35*** 13 31***

Vocabulary - IQ 591 8 11

Atypical language 320 41 22***

a ted fb

I psy;* p<0.

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dominance (IAT)

�2 (note that the table displays % but that statistics were calculaWilcoxon Signed Ranks Test.AT: Intracarotid Amobarbital Test; L TLE: left temporal lobe epilep<0.05; **p<0.01;***p<0.00; downward arrow=significant loss (

rom surgical studies which support this assumptionHelmstaedter et al., 2003; Tanriverdi et al., 2010).unctional integrity of the affected tissue to beesected and reserve capacity are both reflected byaseline performance. Those with a better baselineerformance are at greater risk to lose cognitive func-

ions after surgery (functionality), however, at the sameime, those with a better baseline performance willtill have better performance after surgery than thoseith a poor baseline performance (reserve). This isemonstrated by correlating the preoperative mem-ry performance (total score: verbal + figural memory)f the large sample from table 1 (left and right-sidedLE patients) with a) absolute postoperative memoryr=0.44, p=0.000) and b) loss over time calculated as theifference between pre and postsurgical performancecores (r=0.60, p=0.000).oth functionality and reserve capacity depend on

he patient’s age at the time of surgery. The criticalhases of cerebral functional plasticity are the timesf language acquisition (until age 6), puberty (untilge 15), and the time at around 30 years of age, wheneserve capacities and capabilities for compensationtart to decline with age (Helmstaedter, 1999). Methods

pileptic Disord, Vol. 15, No. 3, September 2013

o estimate functional integrity and reserve capacity,n addition to neuropsychological assessment, are:ntracranially recorded event related potentials or non-inear EEG measures of complexity (Elger et al., 1997;

runwald et al., 1998; Helmstaedter et al., 1998a),tructural and functional imaging techniques (Koeppnd Woermann, 2005), angiography with intracaroti-

srinmn(

or patient numbers).

R TLE: right temporal lobe epilepsy.1); upward arrow=significant gain (p<0.1).

al application of amobarbital, methohexital (brevital)r etomidate (Buchtel et al., 2002), and pre- or intra-perative electrocortical stimulation (Wellmer et al.,009).

elective surgical approaches versustandard anterior temporal lobectomy

he logical step following from the previous sectionn epilepsy surgery is to remove what is necessary

o control seizures and leave as much as possibleunctional tissue in order to preserve the patient’sognitive functions. According to a review on theuest for the optimal extent of resection in TLE bychramm (2008), no particular surgical approach waseported to be superior with regards to seizure con-rol. Six of 8 studies on selective surgery versusemporal lobe resections reported similar seizure out-omes and 2 reported better outcome with largeresection. This report has very recently been chal-enged by a meta-study by Josephson et al. (2013)

ho compared selective amygdalo-hippocampectomySAH) and anterior temporal lobectomy (ATL) across 15

223

tudies and found overall better outcome with largeresections in 13 studies (risk ratio: 1.32; 95% confidencenterval [CI]: 1.12-1.57; p<0.01). This study, however, didot address the question of whether one approachight be superior to the other with regards to cog-

itive outcome. According to the review by Schramm2008), 11/14 studies reported that smaller, as opposed

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o larger, resections are associated with better cog-itive outcome. In addition, taking the extent of theesial resection into consideration, an association

etween better seizure control and larger resec-ions was reported in 5/12 studies and an associationetween extent of resection and neuropsychologicalutcome was not identified in 8/9 studies. A reviewrovided in a study by Tanriverdi et al. reported that6/21 studies demonstrated better cognitive outcomefter selective surgery, compared to 5/21 studies whichhowed no difference (Tanriverdi et al., 2010).

ithin the last 20 years, surgery for TLE has becomencreasingly selective due to major improvements inigh-resolution structural and functional imaging, with

ncreased reliability for detecting subtle lesions suchs dysplasia or hippocampal sclerosis in patients withemporal lobe epilepsies. In its beginnings, selec-ive surgery was only performed for patients withross lesions and/or with evidence from intracranialEG recordings. In 1982, Wieser and Yasargil pub-ished a series of 27 patients (12 with mesial tumoursnd epileptogenic area identified by stereo or sur-ace EEG in 13 and 2 patients, respectively) whichhowed good seizure control, improved general intel-igence, and minor-to-no decline in verbal memoryfter SAH, compared to large temporal lobe resectionshich caused significant functional losses (Wieser

nd Yasargil, 1982). In 1993, Goldstein and Polkeyeported that both surgical approaches cause simi-ar decrease in delayed recall in logical memory, buthat ATL, in contrast to SAH, causes more impairmentn paired associate learning and immediate recall ofisuo-spatial material (Goldstein and Polkey, 1993). Aear before, the same authors reported that whereasatients who had undergone either selective surgeryr en-bloc resections could be distinguished basedn a traditional memory test score, this was not thease for memory measures more related to every-ay behaviour (Rivermead Behavioural Memory Test)

Goldstein and Polkey, 1992).or a long time, selective surgery was performedxclusively at a few centres. However even for ATLesections it was demonstrated that lateral extent ofesection (<3 cm) (Helmstaedter and Elger, 1996), con-ideration of cortical eloquent sites for language oremory (Ojemann and Dodrill, 1985), and the patients

athological status (presence/absence of hippocam-al pathology) (Hermann et al., 1992) were decisiveeterminants for memory decline after surgery. In a

24

etrospective study by Wolf et al., performed in 1993,o difference in memory outcome (RAVLT, WMS) waseported, taking the extent of mesial (>/<2 cm) or lat-ral (>/<4 cm) resection into consideration. Instead,lder age at seizure onset was decisive for worse out-ome (Wolf et al., 1993).

rslSwt

he earlier studies performed in patients undergoingtandard ATL already implicitly hinted that differenturgical procedures within the language-dominant lat-ral temporal neo-cortex affect learning capability,ather than delayed recall, and that, based on memoryeasures (mainly RAVLT, CVLT and WMS), the patient

anguage capabilities should be taken into considera-ion in order to understand the memory impairmentsbserved in TLE (Hermann et al., 1988) (see belownder Living in a different test universe). In thejemann and Dodrill study from 1985, 80% of the mem-

ry outcomes assessed by WMS could be predictedased on the association between the resection andites essential for naming, encoding, or memory stor-ge, as identified by electrical stimulation mapping.his close relationship between verbal memory and

anguage indicates that preoperative determination ofanguage sites can be used to protect against lossesn either function (Hamberger, 2007; Hamberger et al.,010).ifferential cognitive sequelae of surgery of temporo-esial and temporo-lateral structures for different

spects of verbal learning and memory were demon-trated in a study which compared patients whonderwent cortical lesionectomy to patients withmmonshorn sclerosis who either underwent SAH orTL (Helmstaedter et al., 1996; Helmstaedter et al.,997) (figure 1). This study had been performed at aime in Bonn when selective surgery had become aew treatment option for mesial TLE. Thus, a retro-pective comparison was possible between tworoups of M-TLE patients; one group who, accord-

ng to the new treatment guidelines, underwenteft-sided SAH and another who, according to theld guidelines, received left-sided ATL, includingmygdalo-hippocampectomy. The third group witheocortical temporal lobe lesions and circumscribed

esionectomy, not affecting the mesial structures,erved as another control in order to compare betweenortical lesionectomy and cortical resection of non-esional tissue in ATL. Consistent with the presencef left TLE, patients from all groups showed impairederbal memory before surgery, but differed consider-bly with regards to postoperative memory outcome.

ith regards to average group data, least lossesi.e. unchanged performance) were observed afteresionectomy, SAH mainly caused a loss in long-term

emory aspects of verbal learning and memory, andTL, in which unaffected neocortical tissues had been

Epileptic Disord, Vol. 15, No. 3, September 2013

emoved, additionally caused a significant loss in thehort-term and working memory aspects of verbalearning and memory. The differential effects of leftAH and ATL on verbal learning and memory, whiche described in 1996 and 1997, were also observed in

he longitudinal study published in 2003 which had

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Cognitive outcome and surgery in TLE

Verbal memory and surgical approaches in left temporal lobe surgery

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igure 1. Pre- and postoperative verbal learning and memory (Vho underwent ATL versus SAH and patients with lateral lesionsefore surgery, the three groups showed similar impaired memodecrease in long-term retrieval after ATL and SAH, and a decre

ollow-up intervals of 2 to 10 years, and which alsoomprised some of the patients included in the earlynvestigation (Helmstaedter et al., 2003). Later, in 2005,oGalbo et al. confirmed the negative impact of per-orming ATL on memory in patients with exclusive AHSLoGalbo et al., 2005).ince this time, there have been several other studies

n which SAH or individually tailored temporal lobeurgery were compared with ATL. In general, selectiveurgery appears to be more favourable but this is not aonsistent finding. Continuing with controlled studies,enowden et al. reported reduced memory after SAHnd ATL, although to a greater extent, after en-blocTL. In addition, non-memory functions increased togreater extent after SAH (Renowden et al., 1995).

nterestingly, this group previously reported larger-han-expected collateral damage for selective surgicalpproaches (trans-sylvian, trans-temporal), an issuehich will be dealt with later in greater detail.

n a multicentre study from 1997 (Jones-Gotman et al.,

pileptic Disord, Vol. 15, No. 3, September 2013

997), in which 71 seizure-free patients who haduccessfully received surgery were evaluated, theemory outcomes following ATL (performed in Mon-

real, Canada), lesional neocorticectomy sparing themydgala and hippocampus (performed in Dublin, Ire-and), and SAH sparing the neocortex (performed in

mctcm2

/German AVLT) in left TLE patients with hippocampal pathologyunderwent cortical lesionectomy.

eft panel). Excellent outcome was observed after lesionectomy,learning after ATL.

ürich, Switzerland) were compared. Unfortunately,his study considered only postoperative performancen verbal and figural list learning and, in addition, theurgical procedures appeared less distinct than pre-iously planned. The results indicated impairments inatients, relative to controls, independent of the typef resection and lateralisation effects (more for ver-al than figural materials), and no advantage of one

ype of surgery over another could be discerned. Theize of mesial removal did not have a differential effectn postoperative memory. The findings were rated asnexpected but one should keep in mind that thevaluation did not take baseline differences or changever time into consideration.auli et al. (1999) compared left ATL, tailored temporo-ateral resections, and SAH and found that better

emory outcome was associated with sparing the neo-ortex for SAH and ATL and sparing the hippocampusor tailored surgery.n a review of 321 patients operated in Bonn, Clus-

225

ann et al. concluded, on the basis of gross categoricalognitive performance measures, that limited resec-ions, relative to standard ATL, resulted in better out-ome of attention, verbal memory, and a compoundeasure of cognitive performance (Clusmann et al.,

002).

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orino et al. (2006) demonstrated better preservedemory function after trans-sylvian SAH, compared

o ATL, and Paglioli et al. (2006) reported greater post-perative improvements after left SAH, as opposed to

eft ATL. Alpherts et al. (2008) showed that tailoredesections caused additional problems in attentionnd working memory whereas ATL, dependent on thextent of the resection of the superior temporal gyrus,aused greater problems with regards to verbal intel-igence and verbal comprehension.

more recent study from the Montreal groupTanriverdi et al., 2010) compared large samples ofatients who underwent left/right cortectomy, includ-

ng a comparison between AH (ATL; n=123) andelective AH (n=133). The findings indicated thateneral intelligence increased after epilepsy surgery,ut that verbal IQ was negatively affected by leftAH. Verbal memory declined and non-verbal memo-y improved after left-sided surgery, and non-verbalemory decreased after right ATL. In addition, later

urgery was associated with worse memory, andeizure freedom was associated with better memory.nterestingly, in this study, immediate logical memo-y recall significantly decreased after left-sided ATL,hereas delayed logical memory recall was similarly

ffected by both approaches after left-sided surgery.his is in line with what was previously discussed;

earning parameters are more significantly affectedy left neocortical resections than left mesial resec-

ions, and delayed memory parameters are similarlyffected following left neocortical resections usingoth approaches.

esection versus preservationf non-affected tissue

n concluding the neuropsychological findings onelective surgery versus ATL, selective surgery is clearlyreferred. From a neuropsychological point of view,

he functional integrity of brain tissue to be resected,nd thus the question of sacrificing versus preservingunctional tissue, appears to be of major impor-ance regarding cognitive loss observed after surgeryChelune, 1995; Helmstaedter, 1999; Stern, 2003).he evaluation of impact of resection of non-lesionalissue, however, is not that straightforward sinceor two-third standard temporal lobe surgery, andven more so for selective surgery, it is very diffi-

26

ult to determine the proportion of functional andesional/epileptogenic tissues with regards to cog-itive outcome. Resection of non-lesional tissueequires clinical and ethical justification. The negativeffects of resection of unaffected lateral cortex in ATLerformed in patients, with AHS as the sole pathology,ere reported in the previous section (Helmstaedter

adbnhoe

t al., 1996; LoGalbo et al., 2005). In contrast to this,urgery, which is confined to neocortical temporalobe lesions, appeared to be associated with very goodognitive outcome.ery recently, Hamberger et al. (2010) demonstrated

hat resection of a structurally intact hippocampusesulted in loss of visual naming ability, despite pre-perative mapping of the cortical naming sites.s a proof of principle that resection of pre-umably unaffected brain tissue worsens cognitiveutcome in TLE, we recently compared memory out-ome after temporal lobe surgery in 15 MRI- andistopathologically-negative patients and 15 pairwise-atched patients with MRI and histopathologically-

roven lesions. Clinical (e.g. side and site of surgery,ype of surgery, and onset and duration of epilepsy)nd neuropsychological performance, other thanemory (e.g. IQ, attention), were considered as theatching criteria. As for the question of whether

esected tissues were involved in epilepsy, it is impor-ant to note that 12/15 non-lesional patients showed noostoperative response with regards to seizures. It wasypothesized that preoperative differences in mem-ry outcome should reveal the impact of the lesionn memory, whereas postoperative differences shouldeveal the impact of resection of non-lesional tissuesn memory. The results impressively showed that for

he truly non-lesional TLE patients, memory is mostlynimpaired before surgery and drops to a postoper-tive level which is also observed in lesional patientsfter surgery (Helmstaedter et al., 2011a) (figure 2).

ow selective is selective surgery?

AH is a procedure aimed at the specific resectionf pathological mesial brain tissue whilst preservingon-affected lateral cortex which, to a varying degree,

s included in standard ATL. However, the selecti-ity of TLE surgery is limited by the fact that it mayause collateral neocortical damage due to the sur-ical approach. In this regard, we demonstrated thatamage of neocortical tissues adjacent to trans-sylvianurgery should be considered as a decisive determi-ant for postoperative decline of the more neocorticalspects of verbal learning and memory (learning, shorterm, and working memory). This observation was

ade independent of side of surgery. An effect of theide of surgery became evident only with regards to

Epileptic Disord, Vol. 15, No. 3, September 2013

measure of verbal, long-term consolidation (verbalelayed recall) which was affected, to a greater extent,y left-sided surgery. The size of mesial resection,egatively assessed by measurement of the residualippocampus after surgery, was of no relevance forutcome in verbal learning or memory (Helmstaedtert al., 2004). With this study, we identified one of

E

Cognitive outcome and surgery in TLE

Memory Executive ExecutiveMemory

Resecting non-lesional tissues in temporal lobe epilepsy

Surgical group

MRI/Histo negative MRI/Histo positive

60

70

80

90

100

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Pre Post Pre Post Pre Post Pre Post

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Figure 2. Differential pre- and postoperative combined memory (verbal/nonverbal: VLMT German AVLT, DCS-R) and executive score( secte1N nts ap er surw

tcaAvmitsgattantaca

maBisopiewlt

letter cancellation/verbal fluency) for 10 left- and 5 right-sided re5 matched lesional controls.ote the group difference in memory disfavouring lesional patieatients, and the similar memory performance in both groups afthich may by part be due to a practice effect.

he possible reasons for inconsistent memory out-omes reported by studies which compared surgicalpproaches in the literature.nother factor may be the dissection versus preser-ation of fibre tracts. At present, there are threeajor approaches to access the mesial structures

n selective AH; the trans-sylvian, trans-cortical/trans-emporal, and sub-temporal approach. The trans-ylvian approach may affect the superior temporalyrus and the adjacent frontal lobe, the trans-temporalpproach may affect the middle temporal gyrus, andhe sub-temporal approach may affect the inferior

pileptic Disord, Vol. 15, No. 3, September 2013

emporal gyrus. Another difference between thesepproaches is whether the temporal stem, which con-ects the temporal lobe to frontal lobe structures, is

ransected (trans-sylvian approach) or spared (trans-nd sub-temporal approaches). In 1978, Horel dis-ussed the potential role of the temporal stem in theppearance of amnesia in a study in which lesional

uVmrasm

d patients with MRI and histopathologically-negative TLE versus

t baseline, the highly significant drop in memory in non-lesionalgery. Non-memory functions tended to improve in both groups,

odels of amnesia were compared between humansnd animals (Horel, 1978).y comparing trans-sylvian and trans-cortical surgery

n a randomised trial of 80 patients who receivedurgery, we were unable to find a difference inutcome with regards to memory, however, betterostoperative recovery of executive functions follow-

ng the trans-temporal approach was observed (Lutzt al., 2004). We were surprised to find no differenceith regards to learning or memory, however, in the

ight of what is discussed below, it cannot be excludedhat the effects were overlooked by the memory test

227

sed (German AVLT).ery positive cognitive outcomes, i.e. almost noemory decline or improvements, have been

eported in two studies on SAH using a sub-temporalpproach (Hori et al., 2003; Hori et al., 2007). In a thirdtudy, Takaya et al. (2009) furthermore found thatemory, assessed using the Wechsler Memory Scale

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WMS), improved to a larger extent than attention afterominant side resections. At the same time, increasedlucose metabolism in extratemporal regions wasbserved. However, the latter observation was made

n only 7 patients. Unfortunately, a control conditionanother type of surgery) was not used in any ofhese studies, nor was the eventual effect of basalemporal lesions on language taken into considera-ion (Trebuchon-Da Fonseca et al., 2009). A study by

ikuni et al. (2006), in which the potential functionalelevance of the basal language area was considered,ocused only on memory. In this study, the basalanguage area, defined by strip electrodes, was sparedy entering the temporal horn via the collateralulcus, and verbal memory was found to be improvedfter surgery. However, it should be kept in mindhat all these studies were uncontrolled and thathe WMS was chosen for memory assessment ataseline and follow-up without explicitly controlling

or practice effects. The WMS is highly confounded byon-memory functions (IQ, language, and executive

unctions) (Helmstaedter et al., 2009a). Thus, it can-ot be excluded that postoperative improvement of

rontal lobe functioning, which is commonly observedfter temporal lobe surgery, had a beneficial effect onerformance in the WMS. Taking this into account,e very recently compared cognitive outcomes in

linically- and demographically-matched patientsho underwent subtemporal versus trans-sylvian

urgery (von Rhein et al., 2012). In this evaluation, bothurgical approaches caused a comparable decline inerbal learning and memory performance. Differentialffects became evident with regards to decline inerbal recognition memory (more affected by leftrans-sylvian SAH), as well as in verbal semanticuency and figural memory (more affected by sub-

emporal SAH) (for memory outcomes independentf side of surgery; see figure 3). The findings wereiscussed and thought to be probably due to the effectn the basal language area which is involved in lexicalrocessing and the effect on the inferior temporalyrus and ventral stream which have significant roles

n visual perception, imagery, and memory (Hamamet al., 2012; Hitomi et al., 2013).he temporal stem is not only preserved using therans-cortical or sub-temporal approach, but also pre-erved after surgery towards the mesial structuresollowing removal of the tip of the temporal pole untilhe mesial structures are visually accessible. By com-

28

aring memory outcomes after left/right trans-sylvianAH with those after temporal pole resections andH in 97 postsurgically seizure-free patients, an asso-iation between material (verbal/figural) and side ofurgery (left/right) was revealed (Helmstaedter et al.,008). For left-sided surgery, verbal memory outcomeas better after temporal pole resection and AH, com-

wn(Tttw

ared to trans-sylvian SAH; for right-sided surgery,gural memory outcome was better after the trans-ylvian approach, compared to the pole resection andH. The results were discussed in terms of different

mportance of the temporal stem and temporal poleor verbal and figural memory processing, respectively.n concluding this section, no single surgical approach

ay be discerned to be the safest with regards toognition, irrespective of seizure control. According tohe surgical approach, different tissues and fibre tractshat hinder the surgical procedure or locate to adja-ent areas may be affected and, either way, this hasonsequences for cognition.

ariation of the extent of mesialippocampal resection

n 1995, Wyler and colleagues published the first reportf a randomised study of mesial resection length inatients who underwent ATL (Wyler et al., 1995). In

his study, a maximal mesial resection to the levelf the superior colliculus led to a better outcomeith regards to seizure freedom (69%), in compari-

on to a smaller resection to the anterior edge of theerebral peduncle (38%). No effect of the resectionength on memory outcome (assessed by the Califor-ia Verbal Learning Test, CVLT) was obtained. However,hen hippocampal sclerosis was additionally taken

nto account, adverse memory outcome was associat-d with resection of non-sclerotic left hippocampus. Inontrast to the findings of Wyler et al., an early studyy Katz et al. in 1989 reported greater losses in WMSerformance (percent retained), related to the extentf the medial resection (Katz et al., 1989). Similarly,etention (%) of visual material was correlated to the

edial extent of the resection of the right temporalobe. Both studies did not account for the covaria-ion of lateral resections. A study by Joo et al. in 2005,or example, reported an association between verbal

emory decline and only larger resection of the infe-ior and basal temporal gyrus in regression analysisJoo et al., 2005). In the above-mentioned study of Wolft al. (1993), an association between either the lateralr mesial extent of resection and memory outcomeas not identified when patients were categorised intoroups with larger versus smaller resections. In ourwn study on memory outcome after SAH, as a func-

ion of collateral surgical damage, memory change

Epileptic Disord, Vol. 15, No. 3, September 2013

as not correlated with hippocampal remnants, as aegative indicator for the mesial extent of resection

Helmstaedter et al., 2004).hus, based on studies that address mesial resec-ion length, there is no consistent result regardinghe question of whether sparing hippocampal tissueill cause better memory outcome or not. With this

E

Cognitive outcome and surgery in TLE

Surgical approach

-10

Transsylvian Subtemporal

-5

0

5

10

95%

Cl

Verbal learning

Figural learning

Verbal loss over time

Verbal recognition

F -R) osD rd vag figurac ningp

podeppoanrtv

pssac

igure 3. Verbal (VLMT: German AVLT) and figural memory (DCSubtemporal).ifference in scores (postoperative minus preoperative; standaains) for verbal learning, memory (loss), and recognition and foromparable negative effects of surgical approaches on verbal leararticularly after subtemporal surgery, is noted.

remise, we performed an analysis on a subgroupf patients recruited for a large multicentre ran-omised trial on mesial resection length (Schrammt al., 2011). This trial originally comprised all epilepsyatients from three centres in whom the hippocam-

pileptic Disord, Vol. 15, No. 3, September 2013

us was resected, independent of pathology and typef surgery. In order to evaluate memory outcome asfunction of hippocampal resection length, it was

ecessary to exclude possible alternative influenceselated to different pathologies, different lateral resec-ions, surgical approaches, and combinations of theseariables. Focussing on a homogeneous subgroup of

rbloo2r

utcome as a function of surgical approach (trans-sylvian versus

lues: one SD=10; negative values are losses and positive valuesl learning are presented, independent of the side of surgery. The

and the differential effect on figural learning, which deteriorated

atients, who all had mesial pathology and underwentelective surgery, the mesial resection length (2.5 ver-us 3.5 cm), which was determined under surgery usingruler, did not correlate with seizure or memory out-

ome, a year after surgery. However, when considering

229

esected hippocampal volumes (MRI volumetry), ver-al memory outcome was worse after resection of

arger left hippocampal volumes and figural memoryutcome was worse following larger resected volumesn either side (Gross et al., 2008; Helmstaedter et al.,011b). The respective findings for the left temporalesected group are presented in figure 4. Similar to

2

C. Helmstaedter

Effects of lenght and volume of mesial resection on memory

Verbalmemory

Figurallearning

Figurallearning

Verbalmemory70

80

90

75

85

95

100

Stan

dart

val

ues

100+

/- 1

0 [9

5% C

l]

Pre Post Pre Post Pre Post Pre Post

Small Large

Intent-to-treat resection length

Verbalmemory

Figurallearning

Figurallearning

Verbalmemory70

80

90

75

85

95

Stan

dart

val

ues

100+

/- 1

0 [9

5% C

l]

Pre Post Pre Post Pre Post Pre Post

Small Large

Hippocampal volume difference

F -R) oi e reS sectet mory

t1tichsTtotaor(ItpooItbvts

a2bHit2toaevmi2afpd

igure 4. Verbal (VLMT: German AVLT) and figural memory (DCSntended hippocampal resection length (2.5 versus 3.5 cm) and thcores represent standard scores with mean=100, SD=10. The rehe intended resection length, is related to verbal and figural me

hat of Wyler’s randomised study of ATL (Wyler et al.,995), the major message from this study, with regardso SAH, was that consideration of resection length isrrelevant if the pathology at baseline is not taken intoonsideration. Thus, a large resection of an atrophiedippocampus will have fewer consequences than ahort resection of a non-atrophied hippocampus.he importance of removal of functional hippocampalissue is in line with Baxendaleı̌s finding that shrinkagef the hippocampal remnant after surgery is relevant

o memory outcome (Baxendale et al., 2000) and islso in line with recent findings on the dependencyf memory outcomes on functionality of the poste-ior hippocampus, as determined by functional MRIBaxendale et al., 2000; Bonelli et al., 2010).n conclusion, we face the same situation with regardso hippocampal resections as we have done for tem-oral neocortical resections, i.e. postoperative declinef learning and memory mostly results from resection

30

r dissection of non-affected functional brain tissues.n this regard, the degree of preservation of functionalissue, which can be achieved with radiosurgery, maye of future interest. Radiosurgery is claimed to pro-ide high spatial resolution with the aim of changinghe intrinsic epileptic characteristics of radiated tis-ue. First reports on the neuropsychological outcome

ttdpsrm

utcome in patients with left M-TLE after SAH as a function of thesected hippocampal volume (median split).d volume, taking preoperative pathology into account but notoutcome.

ppear optimistic (Bartolomei et al., 2008; Barbaro et al.,009). Comparably, the cognitive outcomes of deeprain stimulation will be of interest in the future.owever, it should be established whether stimulation

ndeed preserves function or whether it interferes withhe functionality of the stimulated area (Benabid et al.,002; Boon et al., 2007; Velasco et al., 2007). In addition,he possible effects of acute or chronic implantationf depth electrodes need to be systematically evalu-ted. For example, we previously described negativeffects of bilateral depth electrode implantation onerbal memory, which were still evident after threeonths of postoperative follow-up, in patients follow-

ng right-sided selective TLE surgery (Gleissner et al.,002). As an example, verbal learning and memory of30-year-old female patient of this series, who suf-

ered from right TLE with hippocampal sclerosis, isresented on the left of figure 5. Displayed are the stan-ardised values of learning (sum across five learning

Epileptic Disord, Vol. 15, No. 3, September 2013

rials), free recall after a 30-minute delay, and recogni-ion memory, at baseline, after implantation of bilateralepth electrodes (implanted posteriorly along the hip-ocampal axis), postoperatively. The patient becameeizure-free. Following implantation, verbal memo-y significantly dropped with regards to long-termemory. After surgery, the patient partly recovered

E

Cognitive outcome and surgery in TLE

- Memory and hippocampal depth electrodes -

50

60

70

80

90

100

110

Learning Delayed recall Recognition50

60

70

80

90

100

110

Learning Delayed recall Recognition

NormNorm

Pre-and three months postop. verbal memoryin a 30-year-old right temporal patient with presurgical

bilateral hippocampal depth electrodes1,2

Pre-and ½ year postimplantation verbal memoryin a 38-year-old right temporal patient

with right hippocampal DBS

Preop. Implanted Postop. Preop. Implanted

F ectrot ient wi cogn

fAbtlasuaoilphpcrsIohspipscsanh

ouoc

Sh

UltTiashhvtdpia

igure 5. Left panel: impact of bilateral hippocampal depth elion (VLMT: German AVLT: standardised values 100±10) in a patmplantation and stimulation on verbal learning, memory, and re

rom this impairment, but baseline was not reached.fter one year of follow-up, however, the effects ofilateral depth electrode implantation observed in

he group of right temporal patients in 2002 was noonger present (Gleissner et al., 2004). Verbal learningnd memory performance of a patient who becameeizure-free due to right hippocampal deep brain stim-lation is presented on the right of figure 5. Displayedre the performances at baseline and six months afternset of stimulation, showing losses in verbal learn-

ng and recognition. In addition, the error rate duringearning and memory increased significantly (not dis-layed in the figure). These are examples not only ofow selective injury of the hippocampi affects memoryerformance, but also of how differences in presurgi-al work-up between centres (using depth electrodeecordings or not) may affect cognitive outcome afterurgery.n a recent publication by Bowles et al. (2010)n different effects of sparing versus resecting theippocampus, a group of patients who underwenttereotactic amygdalo-hippocampectomy was com-ared with patients who received tailored surgery,

ncluding the entorhinal cortex but not the hippocam-

pileptic Disord, Vol. 15, No. 3, September 2013

us. The major aim of this study was to describe dis-ociated impairment between recollection in hippo-ampectomised patients, irrespective of the side ofurgery versus impairment of familiarity judgementsfter removal of the entorhinal cortex. Unfortunately,o pre- to postsurgical data were presented andealthy subjects served as a reference. If this type

ldms1td

des and right SAH on verbal learning, memory, and recogni-ith right M-TLE. Right panel: effect of chronic depth electrode

ition (standardised values 100±10) in a patient with right M-TLE.

f surgery represents an alternative to commonlysed surgical approaches, a more detailed knowledgef neuropsychological outcomes under controlledonditions would be highly appreciated.

urgery within the right non-dominantemisphere

p to now, this review has mainly addressed verbalearning and memory, and this focus can be discernedhroughout the literature with regards to memory inLE. There is good reason for this bias. Verbal memory,

n contrast to figural memory, is relatively regularlyffected when the dominant temporal lobe and itsubstructures are involved. Superficially, left and rightemispheric differences appear to be easily explained,owever, although deficits in semantic and episodicerbal memory or language are associated with leftemporal lobe epilepsies, it is in fact very difficult toetermine specific deficits associated with right tem-oral lobe epilepsies. The literature attributes deficits

n figural, visual-spatial memory, object processing,llocentric object location, face memory, rhythm, and

231

earning musical associations to right temporal lobeysfunction (Saling, 2009). Unfortunately, more experi-ental tests on object location which appear to show

pecific impairment in right TLE (Abrahams et al.,997) have not been elaborated or are too complexo be used in clinical practice. Some researchers haveemonstrated lateralisation-dependent impairment

2

C

irodssiclSole1eostben(dvHdavtpllowotgtioenTrlmrolbcFtomn

s(SbispsecMhsTtntodd“sem(maiv(Awrtdtt

L

Ttgtepu1

. Helmstaedter

n visual spatial memory in patients with TLE whoeceived surgery (Smith and Milner, 1989). The valuef these results for monitoring surgery is difficult toetermine since the pathological condition beforeurgery is not taken into consideration. Similarly,tudies are difficult to rate which show differencesn performances in right temporal lobe patients whenompared to healthy subjects, rather than left temporalobe patients (Saling, 2009).tandard tests of figural and visual spatial memorynly partially show the expected differences between

eft and right temporal lobe epilepsies (Hampsteadt al., 2010; Helmstaedter et al., 1991; Piguet et al.,994). More often, they fail to show differences (Barrt al., 2004; Barr et al., 1997; McConley et al., 2008)r require different evaluations in order to gainpecificity (Helmstaedter et al., 1995). Moreover, evenhough establishing right temporal lobe dysfunctionefore surgery is possible, monitoring the effects ofpilepsy surgery within the right temporal lobe mayot necessarily be possible with such tests (see table 1)

Gleissner et al., 1998a). Two of the few studies thatemonstrated dissociated surgical outcome (left/righterbal/figural) have already been cited (Katz et al., 1989;elmstaedter et al., 2008). Right temporal lobe surgeryoes cause decline in verbal and also figural memory,nd this is often overseen. To sum up losses in eithererbal or figural memory, 45% of 365 patients with rightemporal lobe resections in our series (see table 1)resented with memory loss and 8% presented with

oss in both performances. For the 351 patients witheft temporal lobe resections, 54% presented with lossf either verbal or figural memory and 16% presentedith loss of both. These figures, although evaluatedn the basis of gross test-wise categorisations, parallel

he outcome reported on a test score level in our lon-itudinal study (Helmstaedter et al., 2003). The facthat, unlike left temporal lobe surgery, losses follow-ng right temporal lobe surgery are often balanced orutweighed by gains (see table 1) easily leads to therroneous conclusion that losses in this group can beeglected.aken together, it is difficult to reliably relate figu-al/spatial memory performance to the right temporalobe or right mesial structures, and it appears even

ore difficult to specifically relate impairments toight-sided surgery. We recently concluded, basedn a long-term study of patients aged 6-68, that

eft/right temporal lobe differences in verbal memory

32

ecome evident only in the mature brain and not inhildren or the elderly (Helmstaedter and Elger, 2009).igural memory appears to be organised differentlyo verbal memory. This is indicated by observationsf “crowding” or the “suppression” of figural-visualemory in the presence of atypical language domi-

ance and the differential impact of lateralised epilep-

trbseas

ies on material-specific memory in men and womenHelmstaedter et al., 1994; Helmstaedter et al., 1999).imilar effects on language functions have not yeteen described. On discussing the “crowding” effect

n 1994, we suggested that it would be better to con-ider two hemisphere-specific styles of informationrocessing rather than material specificity. Material-pecific tasks represent an expression and not anquivalent of the respective type of information pro-essing (Helmstaedter et al., 1994). In this respect,ichael Saling in 2009 made the statement that

emispheric lateralisation is task- rather than material-pecific (Saling, 2009).aking into account the large number of left and rightemporal lobe patients who are not left-side domi-ant for language (see table 1), it comes as no surprise

hat lateralisation via material-specific memory testingften fails. This is particularly true for atypical languageominance in left temporal lobe epilepsies which,ue to “plasticity”, often show unimpaired verbal andunexpected” figural memory impairment. One rea-on why right temporal patients often do not show thexpected impairment is verbalisation of the non-verbalaterial. Verbalisation almost always interferes with

or supports?) figural/visual spatial memory assess-ent and this should be controlled either by choosing

bstract and hard-to-verbalise material or by increas-ng the complexity of the material in such a way thaterbal memory fails to compensate for the impairmentHelmstaedter et al., 1995).s a more general consideration, one may discusshether the common concepts of testing which are

elevant in the investigation of left hemisphere func-ion (i.e. mental reasoning) are appropriate to furtherelineate right hemisphere functions. The identifica-

ion and assessment of right hemisphere functionsherefore remains a challenge.

iving in a different test universe

he discussion in the previous section demonstrateshat neuropsychological assessment, like other dia-nostic tools, opens a window with a view intohe nature of cognitive impairment associated withpilepsy and after epilepsy surgery. However, neuro-sychological outcomes much depend on the testssed. As already demonstrated by Jones-Gotman in993, different epilepsy centres use different tests or

Epileptic Disord, Vol. 15, No. 3, September 2013

est batteries (Jones-Gotman et al., 1993) and recenteviews suggest that this has not changed since then. Atest, one can make recommendations as to which testshould be used for neuropsychological assessment inpilepsy patients. A recent evaluation of tests whichre currently used in epilepsy centres in German-peaking countries showed that over 200 different

E

tmsHadftwt2fatiiaatnfatdiSmushocctdCcbtBefsidfdoAciapnr

mbobeecp

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AgfagfaTlcwrfIaiHwpfdTtp(lgaDnsmrweOl

ools were in use and that there was, at best, some com-on sense with regards to which functional domains

hould be addressed (Witt and Helmstaedter, 2009a).ence, discussing the outcomes of epilepsy surgery

nd different surgical approaches also requires aiscussion of the tests in use and their psychometric

eatures. Focusing on memory tests in TLE, differentests appear to have different sensitivity and specificityith regards to differentially lateralised and localised

emporal lobe lesions and epilepsies (Loring et al.,008). A comparison of the Logical Memory subtestrom the WMS-R, the California Verbal Learning Test,nd the Verbal Learning and Memory Test showedhat although the three tests provided overlappingndicators for TLE or mesial pathology, they are barelynterchangeable (Helmstaedter et al., 2009b). The testsddressed different aspects of semantic processingnd memory organisation, and thus were differen-ially sensitive to performance and impairments inon-memory domains. This is indicated by the dif-

erent correlations between the three memory testsnd non-memory functions which are reported inable 2. Accordingly, confounding memory testing byemands on language, attention, intelligence, order-

ng, or semantic memory can easily bias the findings.pecific temporal or temporo-mesial memory impair-ent may be overlooked or the memory test may pick

p impairments in extratemporal executive functions,emantic memory, and language functions (compre-ension, fluency). Postoperatively, for example, theften observed improvements in executive functionsan support short-term and working memory whichan compensate for additional problems with long-erm retention. Thus, study results obtained withifferent tests must be compared with great caution.entres differ not only with regards to neuropsy-hological tests in use. For example, we comparedaseline and outcome data obtained using the same

ests at different surgical centres (Zürich, Freiburg,erlin) and in each case, a highly significant centreffect was obtained (Helmstaedter, 2004). Differentactors may contribute to centre effects and thesehould be controlled for when comparing or merg-ng data from different centres. Recruited patients mayiffer (collection bias), presurgical diagnoses may dif-

er (drug withdrawal, provoked seizures, subdural orept electrodes), and only some patients are placedn a postoperative drug schedule, preoperatively.dditional scientifically-motivated neuropsychologi-

pileptic Disord, Vol. 15, No. 3, September 2013

al evaluations (e.g. in fMRI or EEG/ERP studies) mightnterfere with routine neuropsychological testing. Inddition, there is not yet a full consensus on inter-retation of imaging and neuropathological data andeurologists/patients may be willing to take differentisks with regards to referral for surgery, also surgeons

anddij

Cognitive outcome and surgery in TLE

ay follow an individual approach. Further factors maye added, but the major message is that neuropsychol-gists (although not exclusively) are very likely biasedy their own view and procedures, and that a greaterxchange of knowledge and a common language aressential to achieve further progress in order to dis-ern the best treatment for the individual patient withharmacoresistant epilepsy.

oes memory impairment matter?

s discussed in the previous sections, patients under-oing epilepsy surgery have an increased risk ofurther memory impairment after surgery. The explicitim of this article was to discuss whether there is areater preservation of patients’ cognitive capabilitiesollowing different individual and selective surgicalpproaches, relative to extended standard resections.he answer to this is yes, however, for neuropsycho-

ogists, this is a legitimate question since it may not belear whether subtle differences in memory outcome,hich are assessed using sophisticated tests in a labo-

atory, have any relevance for the patient who wantsoremost to become seizure-free.n this regard, it has been demonstrated that patientsre, in part, willing to risk some cognitive declinen order to become seizure-free (Langfitt et al., 2007;

elmstaedter, 2008). In our long term follow-up study,e discussed so called “double losers”, referring toatients who, in the long run, do not become seizure-

ree and, in addition, experience significant memoryecline (Helmstaedter et al., 2003). Of the group of 732LE patients presented in table 1, about 15% belong tohis group (verbal memory decline >2 SD). Includingatients who are not seizure-free with milder losses

decline >1 SD), the group increases to 37%. In theong-term, follow-up study of Langfitt et al. (2007), aroup of double losers (only 8%) were identified to bet a particular risk of losing quality of life over time.ependent on aetiology, chronic epilepsy does notecessarily cause mental decline. Temporal lobeurgery, in contrast, often does, and there is the legiti-ate fear that every additional loss poses an increased

isk of later acceleration of mental/memory declineith normal or even pathological aging (Helmstaedtert al., 2002).ne should bear in mind that patients with long-

asting epilepsies, particularly with early onset, have

233

lready adapted to their impairments in a way that cog-itive losses due to surgery will probably not affectomains which are of major importance for their everyay life. However, patients postoperative performance

s still often considerably below that of healthy sub-ects, and patients often are still aware of, and suffer

234 Epileptic Disord, Vol. 15, No. 3, September 2013

C. Helmstaedter

Tab

le2.

Co

rrel

atio

ns

bet

wee

nve

rbal

mem

ory

test

san

dte

sts

on

IQ,e

xecu

tive

,an

dla

ngu

age

fun

ctio

ns

(on

lyst

atis

tica

llysi

gnifi

can

tres

ult

sar

ed

isp

laye

d).

Voca

bu

lary

WA

IS-R

IQD

igit

sSp

eed

Flex

ibili

tySi

mila

riti

esC

om

pre

-h

ensi

on

Flu

ency

Nam

ing

VLM

Tto

tall

earn

ing

rN

A0.

444**

0.41

7**0.

268*

NA

0.31

6*0.

419**

0.49

3**N

Asi

g.0.

002

0.00

10.

040

0.04

10.

002

0.00

0

VLM

Td

elay

edfr

eere

call

rN

A0.

348*

NA

NA

NA

NA

0.40

2**N

A0.

299*

sig.

0.01

50.

003

0.03

5V

LMT

loss

ove

rti

me

rN

AN

AN

AN

AN

AN

AN

AN

AN

Asi

g.

VLM

Tre

cogn

itio

nr

NA

0.53

4**N

AN

AN

A0.

347*

0.53

4**0.

306*

0.35

2*

sig.

0.00

00.

024

0.00

00.

018

0.01

2

CV

LTto

tall

earn

ing

r0.

295*

0.42

4**0.

391**

0.34

2**0.

388**

0.43

1**0.

407**

0.51

6**0.

410**

sig.

0.04

40.

003

0.00

20.

008

0.00

30.

004

0.00

30

0.00

3

CV

LTd

elay

free

reca

llr

0.31

7*0.

474**

0.32

4*0.

470**

0.42

3**0.

393**

0.56

2**0.

554**

0.46

3**

sig.

0.03

00.

001

0.01

10.

000

0.00

10.

010

0.00

00.

000

0.00

1

CV

LTlo

sso

ver

tim

er

NA

NA

NA

0.37

2**N

AN

A0.

400**

0.34

0**0.

292*

sig.

0.00

40.

004

0.00

90.

04

CV

LTre

cogn

itio

nr

NA

NA

NA

NA

0.29

6*N

AN

AN

AN

Asi

g.0.

026

Logi

calM

emo

ryI

P0.

329*

0.33

1*N

AN

A0.

376**

0.40

4**N

A0.

268*

0.36

9**

sig.

0.02

40.

022

0.00

40.

008

0.04

00.

008

Logi

calM

emo

ryII

P0.

298*

0.35

6*0.

371**

NA

0.30

7*0.

387*

0.29

9*0.

258*

0.50

3**

sig.

0.04

20.

013

0.00

30.

020

0.01

10.

033

0.04

90.

000

VLM

T:G

erm

anA

VLT

;CV

LT:C

alif

orn

iaV

erb

alLe

arn

ing

Test

;WM

S:W

ech

sler

Mem

ory

Scal

e;W

AIS

:Wec

hsl

erA

du

ltIn

telli

gen

ceSc

ale

revi

sed

;NA

:no

tap

plic

able

;r:c

orr

elat

ion

coef

fici

ent;

sig:

sign

ifica

nce

leve

l.**

Co

rrel

atio

nis

sign

ifica

nta

tth

e0.

01le

vel(

2-ta

iled

);*C

orr

elat

ion

issi

gnifi

can

tatt

he

0.05

leve

l(2-

taile

d).

E

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S

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aminHaon(sdist2

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AKe2

Bpme

Bri1

BBr

rom, their impairments. Contrary to what one mayxpect, a study addressing the relationship betweenerformance and complaint showed that lower cogni-

ive demands were associated with stronger, ratherhan weaker, subjective complaints (Gleissner et al.,998b). Other studies indicate that there is no reli-ble correlation between subjective complaints andemory performance, and that complaints aboutemory problems after surgery are better consid-

red as a marker of depression (Sawrie et al., 1999;axendale and Thompson, 2005). Different findingsnd positions on the ecological validity issue demon-trate that more research, as well as presumably moreeliable ways for the assessment of the consequencesf memory impairment and loss on everyday func-

ioning in TLE, are needed. In any case, quality of lifeuestionnaires do not appear to be sufficient.ith regards to the memory tests in use, we have

reviously demonstrated that they not only providelinical but also ecological validity (Helmstaedter et al.,998b). In addition, we were repeatedly able to demon-trate a correlation between surgical memory outcomend psychosocial socioeconomic outcome (Lendtt al., 1997; Helmstaedter et al., 2003). Thus, memory

mpairment and change in memory are important.

ummary

urgery is a very successful treatment option for phar-acoresistant TLE, however, 30% to 50% of surgery

atients face a risk of additional postoperative memorympairment. The patients’ mental reserve capacities ataseline, seizure outcome, and, most importantly, the

unctional integrity of the brain tissues to be resectedre major determinants of surgical cognitive outcome.here is now converging evidence that individuallyailored and standard selective surgical approachesave a superior functional outcome, compared toxtended standard ATL (including mesial structures).owever, even with selective approaches, collateralrey and white matter damage should be consid-red. Whether cognitive losses can be further reducedy superselective treatments such as radiosurgery oreep brain stimulation is yet to be determined.s already mentioned, this article focuses on thexperiences, development, and observations prima-ily from one centre in Bonn/Germany over a periodf more than 20 years, and is referenced accordingly.

pileptic Disord, Vol. 15, No. 3, September 2013

he different views and opinions of others are acknow-edged and the ongoing discourse and initiation ofurther studies is highly appreciated.

f major concern is how neuropsychology may con-ribute to improvements in surgical outcome. Qualitynd outcome control, however, require instrumentshich reliably reflect patients’ functionality at baseline

E

Bce

Bau

Cognitive outcome and surgery in TLE

s well as changes in intervention-related perfor-ance. A consensus regarding assessments is required

n order to enable better comparison and commu-ication across centres (Witt et al., 2009; Witt andelmstaedter, 2009b; Helmstaedter and Witt, 2012). In

ddition, measures that are more valid than qualityf life questionnaires or depression inventories areeeded to assess the everyday functioning of patients

Helmstaedter et al., 2011c). Finally, the long-term con-equences of (additional) cognitive impairments in theeveloping and aging brain remain to be determined

n more detail as well as the role of uncontrolledeizures, interictal epileptic activity, and antiepilepticreatment for cognitive outcomes (Helmstaedter et al.,011d). �

isclosures.. Helmstaedter declares that there are no conflicts of interestith regard to the contents of this article.

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