9
doi:10.1684/epd.2013.0621 Epileptic Disord, Vol. 15, No. 4, December 2013 383 Correspondence: Michael Duchowny Department of Neurology, Brain Institute, Miami Children’s Hospital University of Miami Miller School of Medicine, 3200 SW 60 th Court, Miami, Florida, USA <[email protected]> Original article Epileptic Disord 2013; 15 (4): 383-91 Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia Martin Kudr 1 , Pavel Krsek 1 , Bruno Maton 2 , Stephen Malone 2 , Alena Jahodova 1 , Petr Jezdik 1 , Vladimir Komarek 1 , Ian Miller 2 , Prasanna Jayakar 2 , Trevor Resnick 2,3 , Michael Duchowny 2,3 1 Department of Paediatric Neurology, Charles University, 2 nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic 2 Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children’s Hospital, Miami, Florida, United States 3 Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, United States Received July 13, 2013; Accepted October 03, 2013 ABSTRACT Aims. To identify variables that influence the extent of ictal single-photon emission computed tomography (SPECT) findings in paediatric patients with focal cortical dysplasia (FCD). Methods. We visually evaluated 98 ictal SPECT studies from 67 children treated surgically for intractable epilepsy caused by FCD. SPECT findings were classified as “non- localised”, “well-localised”, and “extensive” and compared with parameters of injected seizures (seizure type and duration, injection time, and scalp EEG ictal pattern), presence of structural pathology on MRI, type of surgery performed after SPECT study, and histological findings. Results. A shorter injection time and duration of injected seizure was associated with more localised SPECT hyperperfusion. SPECT findings were not significantly influenced by type of injected seizure. Widespread ictal scalp EEG pat- terns were associated with extensive SPECT findings. Larger zones of hyperperfusion were more common in patients with lesional MRI and patients undergoing multilobar resections. SPECT studies demonstrating good localisation were more common in patients with mild malformations of cortical development. Conclusion. Early ictal SPECT radiotracer injec- tion is crucial for successful localisation of the epileptogenic zone. Seizure duration, type of scalp EEG findings, and presence of structural pathology on MRI may influence the extent of ictal SPECT hyperperfusion, which was associated with certain types of epilepsy surgery as well as histopathological findings. Key words: Ictal SPECT, focal cortical dysplasia, epilepsy surgery

Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

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Page 1: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

do

i:10.

1684

/ep

d.2

013.

0621

Epileptic Disord, Vol. 15, No. 4, December 2013 383

Correspondence:Michael DuchownyDepartment of Neurology,Brain Institute,Miami Children’s HospitalUniversity of Miami Miller Schoolof Medicine,3200 SW 60th Court,Miami, Florida, USA<[email protected]>

Original articleEpileptic Disord 2013; 15 (4): 383-91

Predictive factorsof ictal SPECT findingsin paediatric patientswith focal cortical dysplasia

Martin Kudr 1, Pavel Krsek 1, Bruno Maton 2,Stephen Malone 2, Alena Jahodova 1, Petr Jezdik 1,Vladimir Komarek 1, Ian Miller 2, Prasanna Jayakar 2,Trevor Resnick 2,3, Michael Duchowny 2,3

1 Department of Paediatric Neurology, Charles University, 2nd Faculty of Medicine,University Hospital Motol, Prague, Czech Republic2 Department of Neurology and Comprehensive Epilepsy Program, Brain Institute,Miami Children’s Hospital, Miami, Florida, United States3 Department of Neurology, University of Miami Miller School of Medicine, Miami,Florida, United States

Received July 13, 2013; Accepted October 03, 2013

ABSTRACT – Aims. To identify variables that influence the extent ofictal single-photon emission computed tomography (SPECT) findings inpaediatric patients with focal cortical dysplasia (FCD). Methods. We visuallyevaluated 98 ictal SPECT studies from 67 children treated surgically forintractable epilepsy caused by FCD. SPECT findings were classified as “non-localised”, “well-localised”, and “extensive” and compared with parametersof injected seizures (seizure type and duration, injection time, and scalpEEG ictal pattern), presence of structural pathology on MRI, type of surgeryperformed after SPECT study, and histological findings. Results. A shorterinjection time and duration of injected seizure was associated with morelocalised SPECT hyperperfusion. SPECT findings were not significantlyinfluenced by type of injected seizure. Widespread ictal scalp EEG pat-terns were associated with extensive SPECT findings. Larger zones ofhyperperfusion were more common in patients with lesional MRI andpatients undergoing multilobar resections. SPECT studies demonstratinggood localisation were more common in patients with mild malformationsof cortical development. Conclusion. Early ictal SPECT radiotracer injec-tion is crucial for successful localisation of the epileptogenic zone. Seizureduration, type of scalp EEG findings, and presence of structural pathologyon MRI may influence the extent of ictal SPECT hyperperfusion, which wasassociated with certain types of epilepsy surgery as well as histopathologicalfindings.

Key words: Ictal SPECT, focal cortical dysplasia, epilepsy surgery

Page 2: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

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ctal single photon emission computed tomographySPECT) is often employed to localise the seizure onsetone in patients with focal epilepsy. Localising studiesmprove surgical outcome in subjects with focal corti-al dysplasia (FCD) by guiding the location and extentf intracranial electrode implantation and resectivepilepsy surgery (O’Brien et al., 1998a; O’Brien et al.,000; Won et al., 1999; So, 2000). When the locationf the hyperperfusion zone is concordant with otheron-invasive methods, intracranial electrode implan-

ation may not be necessary (Buchhalter and So, 2004;ascino et al., 2004; Dupont et al., 2006).

ctal SPECT is based on the localisation of increasederebral blood flow associated with increasedetabolic activity of cerebral tissue involved in

pileptogenesis (Stefan et al., 1990; Van Paesschent al., 2007). Due to the propagation of seizure activitynd “postictal switch” (Newton et al., 1992) of bloodow from hyperperfusion to hypoperfusion, early

njection of the radiotracer is recognised as beingrucial for success and accurate interpretation of ictalPECT data (O’Brien et al., 1998a; O’Brien et al., 1999a;uchhalter and So, 2004). Several other variables

or injected seizures including seizure duration andype, as well as scalp ictal EEG findings, are reportedo influence ictal SPECT findings (Van Paesschent al., 2007). However, these factors have not beenystematically studied and there are no observationsased on large cohorts of patients.he present study aimed to analyse a large num-er of SPECT studies of paediatric patients withistologically-proven mild malformation of corticalevelopment (mMCD) and FCD, who underwent ictalPECT prior to resective epilepsy surgery. For ictalPECT, we presumed that the presence of localised,ather than extensive, hyperperfusion is more infor-

ative with regards to epilepsy surgery planning, andhus sought to identify factors that might be predictivef localised ictal SPECT findings. Our ultimate goal is

o improve noninvasive presurgical diagnosis as wells surgical treatment of paediatric epilepsy surgeryatients. The predictive value of ictal SPECT for out-ome after excisional epilepsy surgery is discussed innother study (Krsek et al., 2013).

ethods

nclusion criteria

84

ata from 567 children who underwent excisionalpilepsy surgery at Miami Children’s Hospital fromarch 1986 to June 2006 were retrospectively

eviewed. We selected SPECT findings from patientsho had (1) had at least one epilepsy surgical proce-ure at the Miami Children’s Hospital; (2) definitive

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istological evidence of mMCD/FCD; (3) at least oneresurgical ictal SPECT study; and (4) available data on

njection time, length, and type, as well as scalp EEGndings, for injected seizures. A total of 173 ictal SPECTtudies were performed for 106 patients from thisohort. Data regarding injected seizures were availablerom 98 studies, corresponding to 67 patients.

ctal SPECT examination

eriictal radioisotope injections were always per-ormed by specially-trained registered radiologyechnicians during video-EEG monitoring. The radio-racer 99mTc-HMPAO was used for all patients. Dosesf the radiotracer were calculated according to theatient’s weight. Injections were administered as soons either clinical or EEG seizure onset of a habitualeizure was observed. The radiotracer injection wasollowed by a saline flush. SPECT images were acquiredithin four hours of the radiotracer injection. The

cquisition was performed on a three-headed Multi-pect 3 Siemens’ Medical System machine (Hoffmanstate, Illinois, USA) with the following acquisitionarameters: 120-word mode, 360-degree rotations, 40tops, 120 images, 60-second-per-frame imaging, 1.28-agnification factor, and fan beam collimation. A

tandard series of axial, coronal, and sagittal imagesere created. Selected patients underwent a pae-iatric sedation protocol during image acquisitiononsisting of orally-administered chloral hydrate (50-5 mg/kg) or pentobarbital (3-6 mg/kg). Continuousonitoring of the airway and pulse oximetry was

erformed by a trained registered nurse.

eview of ictal SPECT images

n order to localise a region of greatest increasen ictal perfusion, an initial visual analysis of peri-ctal images was performed by a nuclear medicinexpert, blinded to patient data. Grey scale of the

mages was modified to achieve optimal localisationf the hyperperfused region. Ictal-interictal subtrac-

ions were not performed. For the purposes of thetudy, SPECT images were independently re-evaluatedy two reviewers (BM and AJ) who were blinded to thelinical, EEG, and MRI data. SPECT findings were clas-ified into the following groups: (1) non-localised; (2)ell-localised (i.e. focal findings confined to a regionf one or two contiguous gyri and findings limited

Epileptic Disord, Vol. 15, No. 4, December 2013

o a part of a single lobe); and (3) extensive findingsmultilobar or hemispheric). If there was disagree-

ent between the assessments from the two primaryeviewers, a third blinded reviewer (PK) analysed themages and a final assessment was based on agreementetween the third reviewer and one of the primaryeviewers.

Page 3: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

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ata for injected seizures, EEG and MRI findings

ideo/EEG recordings of all injected seizures were re-valuated from the original files. Seizure types werelassified according to the international classificationf seizures as simple partial seizures (SPS), com-lex partial seizures (CPS), and secondary generalised

onic-clonic seizures (SGTCS). Timing of injectionnd duration of injected seizures was determined asescribed previously (O’Brien et al., 1998a; O’Brient al., 1998b; O’Brien et al., 1999a). Seizure onset wasonsidered as the time of the earliest indication ofwarning (verbal or by pushing the call button) or

he presence of abnormal movements, behaviour, ormpaired awareness. The end of a seizure was defineds the time when ictal movements or behavioureased. When the start and end of the seizure couldot be confidently established based on clinical fea-

ures, the ictal EEG of the injected seizure was reviewedn order to establish the beginning and end of thehythmic seizure discharge. The time of the injectionas defined as the time when the plunger on the

yringe containing the radiotracer was fully depressed.ctal EEG patterns of injected seizures were classifieds regional (appearing exclusively over a single lober in two contiguous regions, such as centroparietalatterns), widespread (i.e. multilobar or hemispheric),nd non-localised.RI findings were re-evaluated as described previ-

usly (Krsek et al., 2008), and for the purposes of theurrent study, were classified as lesional (showing aortical malformation) or non-lesional.urgery performed after the SPECT study was iden-ified as temporal, extratemporal in a single lobe, or

ultilobar (including hemispheric cases).

europathological analysis and classification

rain tissue analysis was performed as describedreviously (Krsek et al., 2008). Neuropathologicalndings were classified according to the scheme ofalmini and Lüders (Palmini et al., 2004), since a sub-roup of patients presented with mild malformationsf cortical development (mMCD) not recognised by aecent ILAE classification of FCD (Blümcke et al., 2011).nly features definitive of mMCD/FCD were accepted.

ubjects with malformations of cortical developmentther than FCD/mMCD (such as tuberous sclerosisomplex or hemimeganencephaly) were excluded.

pileptic Disord, Vol. 15, No. 4, December 2013

orrelations with ictal SPECT findings

he above-mentioned types of SPECT findings (i.e.on-localised, well-localised, and extensive) were sta-

istically compared with individual variables of injected

psswSt

Predictive factors of ictal SPECT findings

eizures; i.e. type of seizure, EEG ictal onset zone ofparticular injected seizure, injection time, and

ength of injected seizure. We further analysed SPECTndings in order to determine any correlation with theresence of MRI abnormality (MRI findings were clas-ified as lesional or non-lesional), consequent surgicalrocedure (temporal, extratemporal, and multilobar),nd finally, histological types of mMCD/FCD.

tatistical analysis

ll statistical calculations were performed usingtatistica® software. In the first step, we tested theominal variables using 2 × 2 contingency tables for

he combinations of the variable “type of SPECTnding” with other nominal variables such as “type ofeizure”, “ictal scalp EEG finding”, “type of MRI find-ng”, “surgical procedure”, and “histology”. In eachable, we compared the frequency of the presence orbsence of a particular variable with a particular SPECTnding. We used the Fisher exact test for accepting orejecting the null hypothesis of independency of theariables.he relationship between continuous variables“injection time” and “length of injected seizures”)nd “type of SPECT finding” was analysed using theon-parametric Kruskal-Wallis variance test. Next, theilcoxon test was performed in order to compare par-

icular “types of SPECT finding” with the continuousariables. Moreover, analysis of continuous variablesas calculated twice; (1) using all values (all patients

n the study) and (2) excluding extreme values usinghe Dixon’s test.

e also transformed the continuous variable “injec-ion time” into a nominal variable. We classified theariable as “early” (less than 30 seconds) or “late” injec-ion time. Independency was then tested in the sameay as for the other nominal values.

esults

haracteristics of patients and ictal SPECT studies

n total, 98 SPECT studies were performed for theohort of 40 males and 27 females, aged seven weeks to0 years at the time of (first) surgery (mean: 8.5 years).ne ictal SPECT study was evaluated for 45 patients,

385

atients, and five for 1 patient. Twenty-eight ictal SPECTtudies from 21 patients were performed after the firsturgical procedure as part of the diagnostic work-up, athich time further surgery was considered. Four ictalPECT studies from 2 patients were performed afterhe second epilepsy surgical procedure.

Page 4: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

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PECT findings were divided as described above: 27PECT findings were non-localised, 44 well-localised,nd 27 extensive. Thirty-five SPECT studies were per-ormed for 21 patients with normal MRI findings.ocalisation of surgery was temporal after 14 SPECTtudies, extratemporal in a single lobe after 36 SPECTtudies, and multilobar or hemispheric after 37 SPECTtudies. No surgery was performed after 11 SPECTtudies.

elationship between SPECT findingsnd type of seizure (table 1)

here was no statistically significant differenceetween the studied groups regarding the type of

njected seizure.

elationship between SPECT findingsnd scalp EEG pattern (table 1)

hereas widespread scalp EEG ictal onset zones (n=24)ere significantly associated with extensive SPECTndings (n=11; p=0.023), they were less frequentlyssociated with non-localised SPECT findings (n=3;=0.046). There was a non-significant trend in associa-

ion between localised EEG findings and well-localisedPECT findings (22 of 46 SPECT studies with localisedEG findings exhibited well-localised hyperperfusion).

elationship between SPECTnd MRI findings (table 1)

atients with non-lesional MRI (n=35) demonstratedPECT findings that were significantly more well-

ocalised (n=20) than extensive (n=5; p=0.022).

elationship between SPECT findingsnd type of surgery (table 1)

o surgery was performed after 11 SPECT studies.ignificantly more subjects with well-localised SPECTndings (n=38) underwent extratemporal surgery ofsingle lobe (n=23; p=0.001) than multilobar surgery

n=10; p=0.020). In patients with extensive SPECT find-ngs (n=26), multilobar surgery (n=15) was performed

ore frequently than extratemporal surgery of a singleobe (n=6; p=0.020).

86

elationship between SPECTnd histopathological findings (table 1)

o mMCD was histopathologically proven in subjectsith extensive SPECT findings (n=27; p=0.001). Exten-

ive SPECT findings significantly associated with FCDype I (n=16; p=0.048).

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elationship between SPECT findingsnd injection time (tables 1 and 2)

o significant difference in mean injection time wasdentified when the different types of SPECT findingsere analysed using the non-parametric Kruskal-Wallis

ariance test. A significant difference, however, wasbserved when the mean injection time, correspond-

ng to well-localised (25.1 seconds) and extensive (37.9econds) SPECT findings, was compared using the

ilcoxon test (p=0.034). Similar results were obtainedhen statistical evaluation was performed without

hree extreme values of injection times (SPECT studiesith 105, 180, and 202 seconds of injection time).statistically significant difference was also observedhen early and late injections were comparedetween groups of patients with well-localised andxtensive ictal SPECT findings (after transforming theontinuous variable “injection time” into a nominalariable). For 33 of 44 SPECT studies with well-localisedndings, the radiotracer injection was early (i.e. <30econds; p=0.016), in comparison to 12 of 27 studiesith extensive findings (p=0.023).

elationship between SPECT findingsnd length of seizure (table 2)

statistically significant difference in mean seizureuration was observed between the different types ofPECT findings using the Kruskal-Wallis test (p=0.002).significant difference was also observed when either

he mean seizure duration of non-localised (73.1 sec)r well-localised (68.5 seconds) SPECT findings wereompared with extensive SPECT findings (144.4 sec)sing the Wilcoxon test (p=0.004 and p=0.019, respec-

ively). Similar results were found when statisticalvaluation was performed without extreme valuesictal SPECT studies with seizure duration of 340, 660,60, 700, and 900 seconds).

iscussion

he ability to define and fully remove dysplastic cortexs the most powerful variable that influences outcomen surgical patients with mMCD/FCD (Palmini et al.,995; Paolicchi et al., 2000; Krsek et al., 2009a). It haseen demonstrated that a portion of the epileptogenicone may extend beyond the MRI-detected lesionNajm et al., 2002; Boonyapisit et al., 2003). Noninvasive

Epileptic Disord, Vol. 15, No. 4, December 2013

unctional neuroimaging techniques could thus berucial in planning epilepsy surgery in these patients.revious studies suggested that appropriately per-ormed ictal SPECT may indicate the region of seizurenset (O’Brien et al., 1998a; O’Brien et al., 1998b; So,000; Gupta et al., 2004; Dupont et al., 2006; Krsek et al.,

Page 5: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

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Predictive factors of ictal SPECT findings

Table 1. Relationship between SPECT findings and type of seizure, scalp EEG ictal onset zone, MRI findings, early(<30 seconds) and late injection time (>30 seconds), type of surgical procedure, and histopathological findings.

Ictal SPECT findingsNon-localised(n=27)

Well-localised(n=44)

Extensive(n=27)

Seizure type(n=98)

SPS (n=38) 12 16 10

CPS (n=36) 9 18 9

SGTCS (n=24) 6 10 8

Scalp EEG ictal onset zone(n=98)

Non-localised (n=28) 9 12 7

Localised (n=46) 15 22 9

Widespread (n=24) 3 (p=0.046) 10 11 (p=0.023)

MRI findings(n=98)

Non-lesional (n=35) 10 20 5 (p=0.022)

Lesional (n=63) 17 24 22 (p=0.022)

Early/late injection time(n=98)

Early 16 33 (p=0.016) 12 (p=0.023)

Late 11 11 (p=0.016) 15 (p=0.023)

Histopathology(n=98)

mMCD (n=18) 8 10 0 (p=0.001)

FCD type I (n=43) 12 15 16 (p=0.048)

FCD type II (n=37) 7 19 11

Non-localised(n=23)

Well-localised(n=38)

Extensive(n=26)

Type of surgery

Temporal (n=14) 4 5 5

Extra-temporal 7 23 (p=0.001) 6 (p=0.020)

S CS: sm ortic

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(n=87) (n=36)

Multilobar (n=37) 12

PS: simplex partial seizures; CPS: complex partial seizures; SGTMCD: mild malformation of cortical development; FCD: focal c

013) and this is especially valuable for MR-negativeubjects (O’Brien et al., 2000; O’Brien et al., 2004;iegel et al., 2001; Cascino et al., 2004). If the hyper-erfusion zone is concordant with results of otheron-invasive tests, intracranial electrode implantationay be avoided (Buchhalter and So, 2004; Cascino

t al., 2004; Dupont et al., 2006; Kudr et al., 2013). Recog-

pileptic Disord, Vol. 15, No. 4, December 2013

ition of factors that influence ictal SPECT findings isherefore important for appropriate interpretation ofesults.erforming ictal SPECT in paediatric patients maye complicated by certain features specific to chil-ren with epilepsy (Gupta et al., 2004): clinical onsetf seizures is often difficult to recognise, prevail-

cOohtid

10 (p=0.020) 15

econdary generalised tonic-clonic seizures;al dysplasia.

ng extratemporal seizures may be brief and spreadapidly, and it is often necessary to perform SPECTnder general anaesthesia. There are only a fewtudies concerning ictal SPECT in children with FCDKaminska et al., 2003; Gupta et al., 2004; Krsek et al.,013), however, the localising value of ictal SPECT forpileptogenic zone localisation in children appears

387

omparable to that in adult patients.ur study was based on a large population

f paediatric epilepsy surgery patients withistologically-proven mMCD/FCD and thus facili-

ated a comprehensive analysis of factors influencingctal SPECT findings. We investigated potential pre-ictors of SPECT findings, including seizure variables

Page 6: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

3

M. Kudr, et al.

Table 2. (A) Relationship between SPECT findings and mean injection time and seizure duration.(B) Statistical analysis of a comparison of SPECT findings in relation to mean injection time and seizure duration.

(A)Mean injection time (seconds) Mean seizure duration (seconds)

All (n=98) Without extremevalues (n=95)

All (n=98) Without extremevalues (n=93)

Ictal SPECTfindings

Non-localised 33.3 (n=27) 26.8 (n=26) 73.1 (n=27) 49.0 (n=26)

Well-localised 25.1 (n=44) 23.3 (n=43) 68.5 (n=44) 54.7 (n=43)

Extensive 37.9 (n=27) 32.5 (n=26) 144.4 (n=27) 83.3 (n=24)

(B)p value

All (n=98) Without extremevalues (n=95)

All (n=98) Without extremevalues (n=95)

Kruskal Wallistest

Non-localised/Well-localised/Extensive

0.168 0.177 0.002* 0.017*

Wilcoxon test

Non-localised vsWell-localised

0.149 0.228 0.581 0.469

Non-localised vsExtensive

0.292 0.424 0.004* 0.008*

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Well-localised vsExtensive

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ignificant values are depicted by asterisks and are in bold.

injection time and duration, type of injected seizurend respective scalp EEG pattern), MRI, and surgicalariables, as well as histological findings.e showed that radiotracer injection time and mean

eizure duration significantly influenced the zone ofyperperfusion on ictal SPECT. The mean injection

ime for well-localised ictal SPECT findings was signif-cantly shorter than for extensive ictal SPECT findings.

ell-localised SPECT findings were also significantlyssociated with early radiotracer injections (<30 sec).e thus confirm the observations of O’Brien et al.

1998b), who reported late injections (>45 secondsfter seizure onset) significantly more frequently inatients with non-localising or falsely localising SPECTata. The same study demonstrated that late injections

88

educed the clarity of SISCOM localisation, as showny the inability of reviewers to agree on localisationr to label the study as non-localising (O’Brien et al.,998b). Other studies have supported the view thatnjection times are later in patients with non-localisingr falsely localising ictal SPECT results (Weis et al., 1994;mith et al., 1999).

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he explanation for the association between localisedPECT findings and early radiotracer injections isased on the fact that regions of ictal hyperperfusionrimarily reflect the site of predominant seizure activi-

y at the time of radioisotope injection (Stefan et al.,000; Van Paesschen et al., 2007) and thus, for earlynjections, there is a greater probability that theredominant seizure activity will be centred focallyround the epileptogenic zone. In contrast, when thenjection is late there is more time for spread of seizurectivity (and perfusion changes) in secondary areas.lso, the “postictal switch” phenomenon (i.e. the timeoint when blood flow at the seizure focus rapidlyvolves from hyperperfusion to hypoperfusion) mightelp to account for the association between falsely

Epileptic Disord, Vol. 15, No. 4, December 2013

ocalised SPECT findings and late radiotracer injectionsRowe et al., 1991; Newton et al., 1992).xtensive SPECT findings were associated withreater mean seizure duration, compared to well-

ocalised SPECT findings. The first-pass extraction for9mTc-HMPAO is about 85% (Van Paesschen, 2004). Weypothesize that more extensive patterns of SPECT

Page 7: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

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yperperfusion in longer seizures are caused by thepread of epileptic activity to secondary areas duringubsequent radiotracer brain extractions.nother plausible explanation for differences in thextent of SPECT hyperperfusion is that extensivelyyperperfused areas simply reflect a larger (multilo-ar or hemispheric) area of dysplastic cortex. Ourata support this view since extratemporal surgicalrocedures of a single lobe were significantly more fre-uent than multilobar surgical procedures followingell-localised SPECT findings (in contrast to extensivePECT studies).owever, there was no difference in the extent ofyperperfusion zone between subjects undergoingither single temporal lobe or extratemporal surgery.rontal lobe seizures are reported to be more dif-cult to localise using ictal SPECT because of theirhorter duration and faster ictal spread, when com-ared to temporal lobe seizures (Van Paesschen et al.,007). Newton et al. (1995), nevertheless, reported aomparable yield of ictal SPECT studies in temporalnd extratemporal cases (in which correct localisationas identified in 97 and 92% of patients with a knownpileptogenic zone, respectively).e did not compare the extent of SPECT hyper-

erfusion with dysplastic cortical regions detected byRI since MRI does not reliably reflect the extent of

he epileptogenic zone in mMCD/FCD patients (Najmt al., 2002; Boonyapisit et al., 2003) and because of theignificant number of MRI-negative cases in our series36% of SPECT examinations were performed in 31%atients with non-lesional MRI). We, however, com-ared SPECT findings between subjects with a visibletructural lesion and those with no lesion and foundignificantly more zones of localised hyperperfusion inatients with normal presurgical MRI. This observation

s in accord with reports showing a high sensitivity andpecificity of ictal SPECT in patients without detectable

RI lesions (O’Brien et al., 2000; O’Brien et al., 2004;iegel et al., 2001; Cascino et al., 2004). A possiblexplanation for more restricted hyperperfusion inhese subjects is based on the fact that seizures maye caused by subtle cortical lesions associated withlimited volume of the brain tissue involved in the

eizure. It is, however, important to remember thatRI-negative FCD type I may still be associated with

arge epileptogenic zones (Krsek et al., 2009b).xtensive SPECT findings were more frequentlyeported for cases of FCD type I than type II. This

pileptic Disord, Vol. 15, No. 4, December 2013

nding might be related to the observation that FCDype I demonstrates a difficult-to-localise pathologyKrsek et al., 2008) that may extend beyond bound-ries of an MRI-visible lesion (Najm et al., 2002, Krsekt al., 2009b). We found no extensive SPECT hyper-erfusion findings in patients with mMCD (based on8 SPECT studies performed for 10 patients, three of

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Predictive factors of ictal SPECT findings

hom had confirmed MRI features typical of corticalalformations). This observation is difficult to recon-

ile as our knowledge of mMCD is limited to oneeport of a large series of patients (Krsek et al., 2008)nd mMCD is not included in the new classificationystem of FCD (Blümcke et al., 2011). We speculate thatinor structural pathology, such as mMCD, is asso-

iated with more localised epileptogenic zones with aore restricted ictal zone of hyperperfusion.e did not find an association between SPECT findings

nd type of seizure, according to the internationallassification (SPS, CPS, SGTCS). Van Paesschen et al.2000) reported lowest sensitivity of ictal SPECT inimple partial seizures, with no information reportedn 40% of cases. The greatest sensitivity in complexartial seizures was reported in a series of temporal

obe epilepsy patients (Shin et al., 2002). We suggesthat these different results might be explained by thege of our cohort. Previous reports include mainlydults, whereas in this study, we focused on paediatricases. It is well known that the international classi-cation of seizures is difficult to apply for childrenounger than 3 years (Troester and Rekate, 2009).egarding the extent of SPECT hyperperfusion and

ctal scalp EEG pattern during injected seizures, webserved that widespread EEG findings were more fre-uently associated with extensive SPECT findings thanith non-localised SPECT findings. There was a non-

ignificant trend in association between well-localisedPECT findings and more localised scalp EEG ictal onsetones. These data are in accord with the study of Leet al. (2006) who showed a trend in accurate ictal SPECT

ocalisation in patients with localising ictal scalp EEG.he same study, nevertheless, reported the correct

ocalisation of the seizure onset zone even in patientsith non-localising EEG and suggested that imaging of

he cerebral hyperperfusion zone might be indepen-ent of neuronal activity detected by scalp EEG (Leet al., 2006).limitation of our report is the retrospective nature

f the study and the fact that ictal-interictal subtrac-ions and the SISCOM technique was not performed.owever, in our previous study, we evaluated the pre-ictive value of ictal SPECT for outcome after excisionalpilepsy surgery in the same group of patients (Krsekt al., 2013) and the results were comparable to studiessing the SISCOM technique.he radioligand used in our study was 99mTc-HMPAO.he 99mTc-HMPAO radioligand has been replaced in

389

ome institutions by 99mTc-ECD due to some tech-ical advantages. After brain uptake, 99mTc-ECD istable for 6-8 hours and 99mTc-HMPAO for four hours.9mTc-ECD is cleared from the body more rapidly than9mTc-HMPAO (Van Paesschen, 2004). The sensitivitynd specificity of 99mTc-ECD was greater than that ofnstabilised 99mTc-HMPAO in patients with partial

Page 8: Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia

3

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ntractable epilepsy (O’Brien et al., 1999b). Léveillét al. (1992) described factors that make images using9mTc-ECD “easier to interpret”. However, Lee et al.2002) reported that stabilised 99mTc-HMPAO and9mTc-ECD demonstrate a similar level of sensitivityn temporal lobe epilepsy, moreover, sensitivity to9mTc-HMPAO was superior in neocortical epilepsy.ome differences in cerebral distribution of bothadioligands have been described (Asenbaum et al.,998). We therefore cannot exclude a minor effectased on the differences between the radioligandsn SPECT findings, however, we do not expect this toignificantly alter the overall results of our study. �

cknowledgements and disclosures.his study was supported by grants GAUK 17010 (Martin Kudr),ontakt Program ME09042 (Pavel Krsek) and CZ.2.16/3.1.00/24022

Pavel Krsek), and by the Ministry of Health, Czech Republic;onceptual Development of Research Organization, Universityospital Motol, Prague, Czech Republic 00064203 (Pavel Krsek).one of the authors have any conflict of interest to disclose.

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