1
Epilepsy Resea ch 2010;91:94-100.
QUANTITATIVE EEG ABNORMALITIES IN PERSONS WITH "PURE" EPILEPTIC
PREDISPOSITION WITHOUT EPILEPSY. A LOW RESOLUTION ELECTROMAGNETIC
TOMOGRAPHY (LORETA) STUDY
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Puskás S.,
2
Bessenyei
M., MD;
1
Feke e I., MD, PhD;
3
Hollódy K., MD, PhD.;
2
Clemens B., MD, PhD;
1
Uni e si y o Deb ecen, Medical and Heal h Science Cen e , Depa men o Neu ology, Deb ecen,
Hunga y
2
Kenézy Hospi al L d., Depa men o Neu ology, Deb ecen, Hunga y
3
Uni e si y o Pécs, Depa men o Pedia ics, Pécs, Hunga y
Co esponding au ho : Is án Feke e, MD, PhD, Uni e si y o Deb ecen, Medical and Heal h Science
Cen e , Depa men o Neu ology, Mó icz Zsigmond k . 22. 4032 Deb ecen, Hunga y.
TEL: +36-52-415-176
Fax: +36-52-453-590
E-mail: p o . eke [email protected]
2
Abs ac
Objec i e. Epilep ic p edisposi ion means gene ically de e mined, inc eased seizu e suscep ibili y.
Neu ophysiological e alua ion o his condi ion is s ill lacking. In o de o in es iga e „pu e epilep ic
p edisposi ion” (wi hou epilepsy) in his pilo s udy he au ho s p ospec i ely ec ui ed en pe sons
who displayed gene alized onic-clonic seizu es p ecipi a ed by 24 o mo e hou s o sleep dep i a ion
bu we e heal hy in any o he espec s.
Me hods. 21-channel EEGs we e eco ded in he mo ning, in he waking s a e, a e a nigh o
su icien sleep in he in e ic al pe iod. Fo each pe son, a o al o 120 seconds a i ac - ee EEG was
p ocessed o low esolu ion elec omagne ic omog aphy (LORETA) analysis. LORETA ac i i y
(Ampe s/ me e s squa ed) was compu ed o 2394 oxels, 19 ac i e elec odes and 1 Hz e y na ow
bands om 1 o 25 Hz. The da a we e comp essed in o ou equency bands (del a: 0.5-4.0 Hz, he a:
4.5-8.0 Hz, alpha: 8.5-12.0 Hz, be a: 12.5-25.0 Hz) and p ojec ed on o he MRI igu es o a digi ized
s anda d b ain a las. The band- ela ed LORETA esul s we e compa ed o hose o en, age- and sex-
ma ched heal hy pe sons using independen - es s. p<0.01 di e ences we e accep ed as s a is ically
signi ican .
Resul s. S a is ically signi ican dec ease o alpha ac i i y was ound in widesp ead, medial and la e al
pa s o he co ex abo e he le el o he basal ganglia. Maximum alpha dec ease and s a is ically
signi ican be a dec ease we e ound in he le p ecuneus. S a is ically no signi ican di e ences we e
del a inc ease in he medial-basal on al a ea and he a inc ease in he same a ea and in he basal
empo al a ea.
Discussion. The signi icance o alpha dec ease in he pa ien g oup emains enigma ic. Be a dec ease
p esumably e lec s non-speci ic dys unc ion o he co ex. P e on al del a and he a inc ease migh
ha e biological meaning despi e he lack o s a is ical signi icance: hese indings a e opog aphically
simila o hose epo ed in idiopa hic gene alized epilepsy in p e ious in es iga ions.
Signi icance. Quan i a i e EEG cha ac e is ics o he gene ically de e mined epilepsy p edisposi ion
we e gi en in e ms o equency bands and ana omical dis ibu ion.
Key wo ds
Epilepsy, epilep ic p edisposi ion, EEG, LORETA
In oduc ion
In his amous book William Lennox p esen ed an au og aphic illus a ion named "The Epilepsy Ri e ".
This widely known igu e me apho ically shows ha epilepsy is he esul o lowing oge he o se e al,
inhe i ed and acqui ed sou ces (Lennox, 1960). In ac , olde and ecen gene ic s udies ag ee ha
epilep ic p edisposi ion (in o he wo ds, inc eased seizu e p opensi y o gene ic o igin) con ibu es o
he pa hogenesis o mos , i no all so s o human epilepsy (Ande man, 1982; O man e al, 1985;
Ca alle i e al, 2007; Helbig e al, 2008). Eminen epilep ologis s who ou lined a comp ehensi e
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amewo k o epilepsy s ongly emphasized he impo ance o gene ic p edisposi ion in he e io-
pa hogenesis o he seizu e diso de s. They conside ed epilep ic p edisposi ion as a di use al e a ion
o co ical neu ochemis y esul ing in inc eased co ical exci abili y (Gloo e al, 1982). Un o una ely, i
seems ha esea ch (in pa icula , human esea ch) go s uck a his s ep and no u he e o s we e
done in o de o highligh he na u e o epilep ic p edisposi ion. Pe haps he main eason o his is ha
human gene ic and elec ophysiological s udies we e ca ied ou in pa ien s wi h epilepsy, o , a bes ,
in hei ela i es (Me akos and Me akos, 1961). In o he wo ds, no pe sons wi h "pu e epilep ic
p edisposi ion" we e in es iga ed.
Pu e epilep ic p edisposi ion (inc eased seizu e p opensi y wi hou epilepsy) can be
in es iga ed in o he wise heal hy, non-medica ed pe sons who display gene alized onic-clonic
seizu es (GTCSs) p ecipi a ed by na u al, nea -physiological e en s (Rodin, 1984). Knowledge abou
such pe sons s ems om he Second Wo ld Wa and subsequen mili a y c ises. Heal hy young
soldie s and ai c a smen who had go a GTCS p ecipi a ed by 24 o mo e hou s o sleep dep i a ion
(SD) due o long-las ing sen y o ai comba s we e epo ed by se e al au ho s (Schul e 1944;
Benne e al, 1963; Gunde sohn e al, 1973). La e , i became widely accep ed ha young, o he wise
heal hy people, mos ly in he second o hi d decades o hei li e, may su e o single o epea ed
GTCSs on occasions o SD. The a ibu e "o he wise heal hy" is suppo ed by he ac ha p o oked
GTCSs do no mean epilepsy. The GTCS is a non-speci ic esponse e lec ing he sup ac i ical load o
he b ain wi h seizu e-p omo ing in luences; in o he wo ds, he e is no eason o pos ula e any
epilep ogenic ce eb al pa hology o signi ican ne wo k dys unc ion (Ai d e al, 1984). Expe imen al
esea ch disclosed ha SD p ecipi a es seizu es by inc easing he exci abili y o he CNS a se e al
le els (Shouse, 1988). An addi i e seizu e-p o oking e ec is he dec eased and luc ua ing le el o
igilance a e SD (Ellingson, 1984).
The common neu ophysiological abno mali y in epilepsy is inc eased neu onal (EEG)
synch oniza ion in he ce eb al co ex in bo h ic al and in e ic al s a es. EEG is a p o en ool o
in es iga e neu onal synch oniza ion a la ge spa ial scales because e en a small inc ease in he
numbe o synch onized co ical EEG sou ces gi es ise o signi ican inc ease o he EEG signal
(Nunez, 1995). Animal expe imen s sugges ha epilep ic p edisposi ion migh occupy an in e media e
posi ion be ween he heal hy condi ion and he epilep ic co ex conce ning he deg ee o neu onal
synch oniza ion ( an Gelde e al, 1983; Kos opoulos, 1986). Based on he la e indings and he
o e all ole o inc eased neu onal synch oniza ion in epilepsy we pos ula ed ha pu e epilep ic
p edisposi ion is cha ac e ized by inc eased EEG synch oniza ion as compa ed o ha o comple ely
heal hy pe sons.
Pa ien s and me hods
The s udy design was app o ed by he Resea ch E hics Commi ee o Kenézy Kó ház L d. and he
Uni e si y o Deb ecen wi h he explici s a emen ha de ia ions om he accep ed diagnos ic and
ea men p o ocols a e no pe mi ed; no diagnos ic p ocedu e o ea men should be indica ed,
e u ed, o pos poned o s udy pu poses. The pa ien s we e p ospec i ely selec ed ou o hose who
we e e e ed o he Epilepsy Ou pa ien Se ices a Deb ecen o Pécs because o epilep ic seizu es.
Po en ially eligible pe sons we e designa ed a he i s isi by aking a de ailed medical his o y,
physical and neu ological in es iga ion. Inclusion c i e ia we e: age o he i s SD-p o oked seizu e
be ween 10 and 30 yea s; no mal an e- and pe ina al his o y, no mal de elopmen al miles ones and a
c edible epo o one o mo e GTCSs p ecipi a ed by 24 o mo e hou s o SD. Exclusion c i e ia we e:
ecen ly ac i e me abolic o in lamma o y disease, a his o y o p io neu ological and psychia ic
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mo bidi y, unp o oked seizu es (including o he seizu e ypes, absences o myoclonia in pa icula );
egula alcohol in ake o d ug use excep con acep i e pills; he use o exci an d ugs o comme cial
p oduc s ( o example, he so-called ene gy d inks) in he 48 hou s be o e he seizu e. Usual amoun s
o co ee o ea was pe mi ed. The pe sons who had go a seizu e in a disco heque we e excluded
because o he addi ional seizu e p o oking e ec s o licke ing ligh and because he possibili y o
consuming some unde ec ed d ugs. Finally, pa ien s wi h abno mal neu ological and/ o psychia ic
indings a in es iga ion we e excluded. The po en ially eligible pa ien s we e u he e alua ed
acco ding o he ou ine p o ocol including EEG examina ion wi h hype en ila ion and in e mi en
pho ic s imula ion, and a c anial MRI. Pe sons who showed signi ican EEG abno mali ies and/ o a
pa hological MRI inding indica ing a ocal epilep ic o non-epilep ic p ocess we e excluded a his s ep
o e alua ion. In e ic al, gene alized spike-wa e pa oxysms we e accep able because his inding was
epo ed in heal hy pe sons (Ca azu i e al, 1980) and in pa ien s wi h SD-p o oked seizu es
(Ellingson e al, 1984). Acco ding o ou ou ine p o ocol he pa ien s who we e diagnosed as ha ing
"sleep dep i a ion seizu es" did no ecei e medica ion bu we e ins uc ed o a oid SD and o en e
any u he seizu e and he suspec ed p ecipi a ing ac o in o a dia y. They we e ollowed a egula
isi s o a leas wo yea s. Follow-up was necessa y because epilepsy may begin wi h a p o oked
seizu e. Gi en ha he i s seizu e is ollowed by he second wi hin h ee mon hs in mos cases o
beginning epilepsy (Sande and Sillanpaa, 1997), he lack o o hcoming non-p o oked seizu es in he
long un is he bes a gumen agains epilepsy. Thus, he wo-yea s pe iod wi hou spon aneous
seizu es excludes epilepsy wi h high p obabili y. The pa ien s who displayed one o mo e non-
p o oked seizu es in his ime pe iod o hose who escaped ollow-up we e excluded om he s udy.
An age- and sex-ma ched con ol g oup composed o 10 heal hy pe sons was selec ed om ou
no ma i e EEG da abase. These pe sons had been ec ui ed p e iously, o he sake o p io
quan i a i e EEG s udies. They had no had any neu ological and psychia ic an eceden s, me abolic
dis u bances, addic i e habi s (alcohol o d ug use) and did no ake legal d ugs egula ly
(con acep i es we e pe mi ed).
EEG in es iga ion
As o a oid he con ounding e ec o pos ic al slowing only EEGs eco ded a leas i e days a e he
seizu e we e e alua ed. All EEGs we e ca ied ou in he mo ning, a e a nigh o su icien sleep.
Con ounding, ci cadian EEG e ec s (To h e al, 2007) and SD- ela ed in usion o slowe equencies
(Bo bély e al, 1981) we e excluded in his way. All EEGs we e eco ded wi h he same so o digi al
EEG equipmen and eco ding p o ocol: 30 minu es EEG was eco ded in elaxed-waking, eyes-closed
s a e using he 19 monopola de i a ions o he 10-20 sys em plus he ea lobes agains a sampling
e e ence a Fpz; bipola de i a ions de ec ed oculog aphic and myog aphic a i ac s. Impedances
we e < 10 kOhm; EEG was il e ed a 0.1 and 33.6 Hz. Sampling a e was 128 pe second, on-line
analog-digi al con e sion was 12 bi . Gi en he Nyquis sampling a e ( wice he maximum equency
o in e es ) and he desi able an i-aliasing e ec o low-pass il e ing hese eco ding a iables we e
app op ia e o in es iga e he 1 o 25 Hz equency ange. The ea e , all ol age di e ences we e e-
compu ed agains a so-called ma hema ical linked ea s e e ence. As o he quali y o he eco ds
ecommended s anda ds we e ollowed (Nuwe e al, 1994).
Epoch selec ion and LORETA analysis
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EEGs o he pa ien s and he con ol pe sons we e eco ded and analyzed in he same way. 30 x 2-
sec epochs o spon aneous, waking ac i i y cha ac e ized by con inuous alpha hy hm wi h pos e io
ol age maximum we e selec ed. Epochs con aining any so o ansien s, a i ac s, o EEG pa e ns
indica ing shi s o he le el o igilance we e excluded. Epoch selec ion was ca ied ou by one o us
and con olled by he senio au ho . Spli -hal eliabili y and es - e es eliabili y we e checked and only
samples wi h a leas 95 pe cen o hese measu es we e analyzed. Fas Fou ie T ans o m o he
selec ed samples was ca ied ou by means o he Neu oGuide 2.5.6. so wa e
(h p://www.appliedneu oscience.com). The ea e , he da a we e p ocessed o he joined Low
Resolu ion Elec omagne ic Tomog aphy (LORETA) so wa e in o de o quan i a i ely assess
synch onized co ical ac i i y in e ms o equency and he h ee-dimensional dis ibu ion o he
sou ces.
LORETA is a ecen ly de eloped me hod o localizes mul iple dis ibu ed co ical sou ces o
EEG ac i i y in he h ee-dimensional space (Pascual-Ma qui e al, 1994). The consis ency o LORETA
wi h physiology and localiza ion has been alida ed o a lo o no mal and pa hological condi ions
(Pascual-Ma qui e al, 2002). The scien i ic basis and comp ehensi e e alua ion o LORETA can be
ound a he abo e speci ied websi e whe e ee download o a lo o ele an pape s is allowed. In
b ie , LORETA compu es squa e oo ans o m o he squa ed sou ce cu en ec o s (Ampe s/
me e s squa ed) o 2394 oxels and o each e y na ow band (VNB) om 1 o 30 Hz along he
equency axis. Fo he sake o b e i y, his is called "ac i i y" in his pape . LORETA p ojec ed hese
alues on o s uc u al magne ic esonance images acco ding o he coo dina e sys em o he Talai ach
B ain A las (Talai ach and Tou noux, 1988) digi ized a Mon eal Neu ological Ins i u e. Indi idual
LORETA esul s we e a e aged ac oss he pa ien s. The a e aged esul s we e comp essed in o
equency bands (del a: 0.5-4.0 Hz, he a: 4.5-8.0 Hz, alpha: 8.5-12.0 Hz, be a: 12.5-25.0 Hz). The
pa ien s and he con ols we e compa ed by independen - es s. T- alues co esponding o p<0.01
we e labelled as s a is ically signi ican . Co ec ion o mul iple compa isons was no done because i
assumes ha each oxel is independen o all o he oxels and i is known ha he Laplacian ope a o
smoo hs oxels hus ende ing hem as "dependen " and no independen . The ou pu o LORETA
analysis was a omog aphically a anged se ies o colo -coded pic u es displaying he algeb aic
di e ence and he s a is ical di e ence be ween he wo g oups. Localiza ion was gi en in ana omical
e ms, he name o he gy us, numbe o he B odmann a ea, and he h ee-dimensional coo dina es
on he abo e men ioned b ain a las.
Resul s
Due o he mul iple exclusion c i e ia only en pa ien s who we e eligible in all espec s we e collec ed
du ing a pe iod o h ee yea s (2 males, 8 emales, age limi s: 18 and 29 yea s, a e age age: 21.7
yea ). They we e s uden s o wo ke s who missed a nigh o sleep because o lea ning o nigh wo k.
Ou o hem, ou pa ien s had a single GTCS a e SD while six pa ien s had go 2 o 4 seizu es on
epea ed occasions o SD. EEG backg ound ac i i y was o alpha ype and was wi hin he no mal
limi s in all he pa ien s. B ie , in e ic al, gene alized spike-wa e pa oxysms we e eco ded in wo
cases. Video eco ding o pe sonal obse a ion o one o us ensu ed ha hese pa oxysms we e no

6
accompanied by sub le seizu e phenomena. The a e age age o he con ol pe sons was 21.1 yea s;
he age di e ence be ween he wo g oups was s a is ically no signi ican (p=0.6).
LORETA esul s
S a is ically signi ican dec ease o alpha ac i i y was ound in he pe sons wi h epilep ic disposi ion (as
compa ed o he con ols) in he medial and la e al pa s o he co ex abo e he le el o basal ganglia
(Fig. 1). These alpha di e ences we e dis ibu ed asymme ically a he co ical con exi y, being mo e
widesp ead in he igh hemisphe e han in he le . Howe e , maximal alpha di e ence was ound in
he le p ecuneus, BA 7. In e es ingly, he only s a is ically signi ican be a di e ence was localized o
he same a ea (Fig. 1) albei s a is ically no signi ican dec ease o be a ac i i y was ound e e ywhe e
in he empo o-pa ie o-occipi al co ex.
No s a is ically signi ican di e ence be ween he wo g oups eme ged in he del a and he a
bands. Howe e , an o e all endency o bila e ally inc eased del a and he a ac i i y was ound in he
pe sons wi h epilep ic p edisposi ion as compa ed o he con ols. G ea es del a di e ences we e
ound bila e ally in he medial and basal p e on al co ex (gy us ec us, o bi o- on al gy us, an e io -
basal pa s o he medial and middle on al gy i, an e io cingula e, subcallosal gy us).These a eas
co espond o BAs 10, 11, 34. G ea es he a di e ences we e ound in abou he same pa s o he
on al co ex and in he nea by basal empo al co ex (uncus, pa ahippocampal gy us; BAs 20, 28, 36)
and he an e io edge o he igh insula, BA 13 (Fig 2).
Discussion
Alpha and be a equency bands
This is he i s quan i a i e EEG in es iga ion o pe sons wi h "pu e epilep ic p edisposi ion" as de ined
in he In oduc ion o he pape . The main indings o his s udy we e ha epilep ic p edisposi ion is
cha ac e ized by a s a is ically signi ican dec ease o alpha ac i i y in a conside able pa o he
co ical man le, and a s a is ically signi ican dec ease o be a ac i i y in a ci cumsc ibed pa o he le
pa ie al co ex, as compa ed o he con ol g oup. The le p ecuneus (BA 7) was he si e o he
maximal alpha and be a di e ences. Howe e , hese indings we e like he op o he icebe g because
smalle , s a is ically no signi ican bu di use alpha dec ease was ound in he en i e co ex and
di use be a dec ease was ound in he empo o-pa ie o-occipi al pa s i i . The neu ophysiological
in e p e a ion o dec eased alpha and be a ac i i y in he con ex o seizu e liabili y is no easy. As a
as is known, he ela ionship be ween alpha a iables and seizu e p opensi y has ne e been
in es iga ed. Be a dec ease is usually in e p e ed as a non-speci ic sign o impai ed co ical unc ion
(Kozelka and Pedley, 1990). Be a powe was p oposed as a biological ma ke o GABA-media ed
an icon ulsi e d ug e ec s (Lopes da Sil a, 2002) hus indi ec ly sugges ing ha be a dec ease migh
be associa ed wi h inc eased seizu e p opensi y. Howe e , also opposi e esul s we e published
(P e smann e al, 1993) and, in any case, d ug-modi ied co ical GABA-e gic unc ion is only one
componen o seizu e liabili y.
Simila ly, he signi icance o maximal alpha and be a dec ease in he le p ecuneus emains
unce ain. Conco dan ly wi h his inding, in e ic al dys unc ion o he p ecuneus and pos e io
cingula e co ex in pa ien s wi h gene alized seizu es was demons a ed in a unc ional MRI s udy (Lui
7
e al, 2008). The s a egic ole o his a ea in egula ing physiological a ousal p ocesses and pe haps
also epilep ic ac i i y a gues o u he , a ge ed in es iga ions.
Del a and he a equency bands
We ound ha del a ac i i y was inc eased in he medial and basal on al a eas, he a ac i i y was
inc eased in he same a eas and also in he basal empo al a ea in he pe sons wi h epilep ic
p edisposi ion as compa ed o he con ols. These di e ences we e s a is ically no signi ican .
Howe e , he opog aphical simila i y o inc eased del a and he a ac i i y in hese pe sons and in
pa ien s wi h idiopa hic gene alized epilepsy should be emphasized. F om he clinical poin , pe sons
wi h SD- ela ed GTCSs a e mos closely ela ed o hose who ha e idiopa hic epilepsy exclusi ely wi h
unp o oked GTCSs (Panayio opoulos, 2005). A sub ype o his epilepsy synd ome is labeled as
"epilepsy wi h g and mal seizu es on awakening", abb e ia ed he e as EGMA (Janz, 1994). In hese
pa ien s insu icien sleep is a equen seizu e-p o oking ac o hus unde pinning he neu obiological
simila i y be ween hem and he pe sons p esen ing wi h SD-p o oked seizu es only. Topog aphic
analysis o he po en ial ield indica ed inc eased del a and he a ac i i y in he p e on al and pa ie o-
occipi al a eas o unmedica ed EGMA pa ien s as compa ed o heal hy con ols (Clemens e al, 2000).
Albei he localizing p ecision o a classic opog aphic s udy and LORETA is limi edly compa able,
p e on al del a- he a excess seems o be a common ea u e o EGMA pa ien s and pe sons wi h pu e
epilep ic disposi ion. Fu he mo e, a LORETA s udy disclosed ha unmedica ed idiopa hic gene alized
epilepsy pa ien s display i e co ical egions o inc eased del a- he a ac i i y (Clemens e al, 2007).
One o hese a eas, he so-called "p e on al clus e " co esponds o he p e on al del a and he a
inc ease in he pe sons wi h pu e epilep ic p edisposi ion. Howe e , he deg ee o he abno mali y was
a he dissimila . EGMA and o he , idiopa hic gene alized epilepsy pa ien s showed s a is ically
signi ican inc ease o del a and he a synch oniza ion in he p e on al co ex and o he co ical a eas
(Clemens e al, 2000, 2007). In con as , he pe sons wi h pu e epilep ic p edisposi ion showed
s a is ically no signi ican del a and he a inc ease in he same co ical a eas. This sugges s ha ,
conce ning he amoun o slow (del a, he a) EEG ac i i y, pe sons wi h epilep ic p edisposi ion a e
nea e o heal hy pe sons han o he pa ien s wi h gene alized epilepsy. This is in acco d wi h he
o e all expe ience ha pe sons wi h SD- ela ed seizu es only emain pe manen ly seizu e- ee i sleep
dep i a ion is a oided.
Acknowledgemen s
Suppo ed by g an om he Hunga ian Minis y o Heal h No. ETT 238/2006.
8
Re e ences
Ai d, R.B., Masland, R.L., Woodbu y D.M., 1984. The epilepsies. A c i ical e iew. Ra en P ess,
New Yo k.
Ande mann, E., 1982. Mul i ac o ial inhe i ance o gene alized and ocal epilepsy. In: Gene ic basis o
he epilepsies. Ande son V.E., Hause , W.A., Pen y J.K., Sing C.F. (Eds.), Ra en P ess, New Yo k,
pp. 355- 375.
Benne , D.R., 1963. Sleep dep i a ion and majo mo o con ulsions. Neu ology 13, 953-958.
Bo bély, A.A., Baumann, F., B andeis, D., S auch, I., Lehmann, D., 1981. Sleep dep i a ion: e ec on
sleep s ages and EEG powe densi y in man. Elec oencephalog Clin Neu ophysiol 51, 483-495.
Ca alle i, G.L., Weale, M.E., Shianna, K.V., Singh, R., Lynch, J.M., G in on, B., Szoeke, C.,
Mu phy, K., Kini ons, P., O'Rou ke, D., Ge, D., Depond , C., Claeys, K.G., Pandol o, M., Gumbs,
C., Walley, N., McNama a, J., Mulley, J.C., Linney, K.N., She ield, L.J., Rad ke, R.A., Ta e, S.K.,
Chissoe, S.L., Gibson, R.A., Hos o d, D., S an on, A., G a es, T.D., Hanna, M.G., E iksson, K.,
Kan anen, A.M., Kal iainen, R., O'B ien, T.J., Sande , J.W., Duncan, J.S., Sche e , I.E., Be ko ic,
S.F., Wood, N.W., Dohe y, C.P., Delan y, N., Sisodiya, S.M., Golds ein, D.B., 2007. Mul icen e
sea ch o gene ic suscep ibili y loci in spo adic epilepsy synd ome and seizu e ypes: a case-con ol
s udy. Lance Neu ol 6, 970-980.
Ca azzu i, G.B., Cappella, L., Nalin, A., 1980. Longi udinal s udy o epilep i o m EEG pa e ns in
no mal child en. Epilepsia 21, 43-55.
Clemens, B., Szige i, G., Ba a, Z., 2000. EEG equency p o iles o idiopa hic gene alised epilepsy
synd omes. Epilepsy Res 42, 105-115.
Clemens, B., Bessenyei, M., Pi os, P., Tó h, M., Se ess, L., Kondáko , I., 2007. Cha ac e is ic
dis ibu ion o in e ic al b ain elec ical ac i i y in idiopa hic gene alized epilepsy. Epilepsia 48, 941-
949.
Ellingson, R.J., Wilken, K., Benne , D.R., 1984. E icacy o sleep dep i a ion as an ac i a ion
p ocedu e in epilepsy pa ien s. J Clin Neu ophysiol 1, 83-101.
Gloo , P., Me akos, J., Me akos, K., Ande mann, E., an Gelde , N., 1982. Neu ophysiological,
gene ic and biochemical na u e o he epilep ic dia hesis. In: Hen y Gas au and he Ma seilles
School's con ibu ion o he neu osciences. B ough on, R.J. (Ed.), Else ie Biomedical P ess,
Ams e dam, pp. 45-56.
9
Gunde son, C.H., Dunne, P.B., Feye , T.L., 1973. Sleep dep i a ion seizu es. Neu ology 23, 678-686.
Helbig, I., Sche e , I.E., Mulley, J.C., Be ko ic, S.F., 2008. Na iga ing he channels and beyond:
un a elling he gene ics o he epilepsies. Lance Neu ol 7, 231-245.
Janz, D., 1994. Pi alls in he diagnosis o g and mal on awakening. In: Epilep ic seizu es and
synd omes. Wol , P. (Ed.) John Libbey. Co. L d., pp. 213-220.
Kos opoulos, G., 1986. Neu onal sensi i i y o GABA and glu ama e in gene alized epilepsy wi h spike
and wa e discha ges. Exp Neu ol 92, 20-36.
Kozelka, J.W., Pedley, T.A., 1990. Be a and mu hy hms. J. Clin. Neu ophysiol. 7:191.
Lennox, W.G., 1960. Epilepsy and ela ed diso de s. Li le, B own and Co, Bos on.
Lopes da Sil a, F., 2002. Pha maco-EEG: om cellula o ne wo k le el. EEGβ spec al powe as a
bioma ke o GABAe gic inhibi ion and i s ole in he assessmen o AEDs. Me h. Find. Exp. Clin.
Pha macol., 24, Suppl. D, pp.3.
Lui, S., Ouyang, L., Chen, Q., Huang, X., Tang, H., Chen, H., Zhou, D., Kemp, G.J., Gong, Q., 2008.
Di e en ial in e ic al ac i i y o he p ecuneus/ pos e io cingula e co ex e ealed by es ing s a e
unc ional MRI a 3T in gene alized s. pa ial seizu e. J. Magne ic Resonance Imaging 27, pp. 1214-
1220.
Me akos, K., Me akos, J.D., 1961. Gene ics o con ulsi e diso de s. II. Gene ic and
elec oencephalog aphic s udies in cen encephalic epilepsy. Neu ology 11, 474-483.
Nunez, P.L., 1995. Quan i a i e s a es o neoco ex. In: Neoco ical dynamics and human EEG
hy hms. Nunez, P.L. (Ed.) Ox o d Uni e si y P ess, pp.1-18.
Nuwe , M.R., Lehmann, D., Lopes da Sil a, F., Ma suoka, S., Su he ling, W., Vibe , J.F., 1994.
IFCN guidelines o opog aphic and equency analysis o EEGs and EPs. Repo o an IFCN
commi ee. In e na ional Fede a ion o Clinical Neu ophysiology. Elec oencephalog Clin Neu ophysiol
91, 1-5.
O man, R., Hause , W.A., Susse , M., 1985. Gene ic and ma e nal in luences on suscep ibili y o
seizu es. An analy ic e iew. Am J Epidemiol 122, 923-939.
Panayio opoulos, C., 2005. Idiopa hic gene alized epilepsies. In: The epilepsies. Seizu es, synd omes,
and managemen . Panayio opoulos, C. Bladon Medical Publishing, pp. 271-348.
Pascual-Ma qui, R.D., Michel, C.M., Lehmann, D., 1994. Low esolu ion elec omagne ic omog aphy:
a new me hod o localizing elec ical ac i i y in he b ain. In J Psychophysiol 18, 49-65.