Review

Frontal lobe epilepsy

Pedro Beleza

, Joo Pinho
Journal of Clinical Neuroscience 1 !"#11$ %&'()##
Contents lists available at *cience+ irect
Journal of Clinical Neuroscience
, o u r n a l ho- ep a. e/ www 0 e l s e v i e r 0 co - 1 l ocat e 1 ,
o c n
2pilepsy 3roup, +epart-ent of Neurolo.y, Bra.a 4ospital, 5ar.o Carlos 6-arante, 6partado ""7", Bra.a 78#19&)%, Portu.al
a r t i c l e i n f o
6rticle history/
Received 1' January "#1#
6ccepted 8 6u.ust "#1#
:eywords/
223
Frontal lobe epilepsy
Refractory epilepsy
*P2C;
*ur.ery
;reat-ent
a b s t r a c t
6bout one9<uarter of patients with refractory focal epilepsies have frontal lobe epilepsy !F52$0 ;he typical
seizure se-iolo.y for F52 includes unilateral clonic, tonic asy--etric or hyper-otor seizures0 =nterictal
electroencephalo.ra-s !223$ usually reveal interictal epileptifor- dischar.es and rhyth-ical -idline
theta, which has localizin. value0 ;he usefulness of ictal 223 recordin.s is li-ited by fre<uent -uscle
artifacts in -otor seizures and because a lar.e portion of the frontal lobe corte> is ??hidden@@ to scalp elec9
trodes0 =ctal sin.le photon e-ission C; and positron e-ission to-o.raphy are able to localize F52 in
about one9third of patients only0 6 pre9sur.ical evaluation should include, whenever possible, a subclas9
siAcation of F52 as dorsolateral frontal, -esial frontal or basal frontal lobe epilepsy to allow a -ini-al
cortical resection0 6 review of the typical Andin.s of seizure se-iolo.y, interictal and ictal 223 re.ardin.
the different F52 subtypes is .iven0 2tiolo.y, -edical treat-ent and sur.ery are also discussed0
"#1# 2lsevier 5td0 6ll ri.hts reserved0
10 =ntroduction
Refractory epilepsy is dia.nosed when there is inade<uate sei9
zure control despite use of potentially effective antiepileptic dru.s
!62+$ at tolerable levels for 1(" years0 Bnce refractoriness is estab9
lished, sur.ical treat-ent -ust be considered0
1
Bf all patients with
refractory focal epilepsies referred to epilepsy sur.ery, "%C have
frontal lobe epilepsy !F52$0
"
;he ob,ective of resective sur.ery is
the re-oval of the entire epilepto.enic zone !2D$ without
causin. per-anent neurolo.ical deAcits0 3iven this ob,ective,
localization of the 2D is of para-ount i-portance0 ;his can be
achieved by co-binin. seizure se-iolo.y, interictal and ictal
electroencephalo9 .ra- !223$ Andin.s, as well as
Euorodeo>y.lucose !F+3$9positron e-ission to-o.raphy !P2;$,
sin.le photon e-ission C; !*P2C;$ and FR=0
'
Gnilateral clonic seizures,
7
tonic asy--etric seizures with pre9
served consciousness
%
and hyper-otor seizures,
7
while not patho9
.no-onic, are speciAc for F520 2ven thou.h abdo-inal auras -ay
occur in F52, the evolution of an abdo-inal aura into an auto-otor
seizure is typical of te-poral lobe epilepsy !;52$, which allows its
differentiation fro- F520
)
;he presence of a visual aura stron.ly ar9
.ues a.ainst an F52, since visual auras are associated with parietal,
te-poral or occipital lobe epilepsy0
8
3iven that an ictal 223 fro- a
patient with F52 is characterized by fre<uent false ne.atives and
fre<uent -uscle artifacts,

the analysis of ictal se-iolo.y is crucial
for the differential dia.nosis between F52 and psycho.enic
non9epileptic seizures !PN2*$, the -ost fre<uent ! &#C$ condition
Correspondin. author0 ;el0/ H'% 1"%'"#&###0
29-ail address/ beleza08)I.-ail0co- !P0 Beleza$0
-isdia.nosed as epilepsy0
&
Certain characteristics of the -otor
pheno-ena are stron.ly associated with PN2*, includin. a very
.radual onset or ter-ination, pseudosleep, discontinuous !stop9
and9.o$ and irre.ular or asynchronous !out9of9phase$ activity,
side9to9side head shaJin., opisthotonic posturin., stutterin. and
weepin.0
1#
=nterictal epileptifor- dischar.es !=2+$ occur in )#C to #C of
F52 and are considered to be of less localizin. value than in ;52 be9
cause they can be bilateral, -ultilobar or even .eneralized0
11
=nter9
ictal rhyth-ical -idline theta !RF;$ is co--on ! %#C of F52
patients$ and has localizin. value in patients with F52, provided
that it can be distin.uished fro- nor-al variants occurrin. with
drowsiness and -ental activation tasJs0
1"
=ctal 223 is often .ener9
alized and localized patterns are observed in fewer than one9third
of patients !Fi.0 1$0
1'
5ocalization of seizure onset with ictal *P2C; in adults is possi9
ble in only '#C to 7'C of patients with F520
17
Kith the use of F+39
P2;, it is possible to localize a hypo-etabolic re.ion in about 8%C
of patients with unilateral F52 and abnor-al FR=,
1%
but in only
"&C to 7%C of patients with unilateral F52 and nor-al FR=0
1)
F52 should be, whenever possible, further classiAed as dorsolat9
eral frontal, -esial frontal or basal to allow -ini-al cortical
resection0
"0 +orsolateral frontal lobe epilepsy
+orsolateral F52 -ay be further subdivided into central, pre-o9
tor and prefrontal lobe epilepsy0 ;he central lobe is so-eti-es de9
scribed as the re.ion for-ed by the pri-ary -otor corte> and the
sensory corte> !Brod-ann areas 7 and '$ !Fi.0 "$0 ;he border be9
#&)89%)1L 9 see front -atter "#1# 2lsevier 5td0 6ll ri.hts reserved0
doi/1#01#1)1,0,ocn0"#1#0#0#1
" P0 Beleza, J0 Pinho 1 Journal of Clinical Neuroscience 1 !"#11$ %&'()##
Fi.0 10 =ctal electroencephalo.ra- !223$ in lon.itudinal bipolar -onta.e of a 1)9year9old fe-ale with a rin. chro-oso-e "# syndro-e0 ;he 223 shows a predo-inantly
ri.ht frontal seizure pattern occurin. durin. a dysco.nitive seizure0
tween these -otor and sensory areas was thou.ht to be the
central sulcus, but recent studies showed both -otor !tonic,
clonic or -o9
Fi.0 "0 Brain anato-y dia.ra- !upper left$ lateral, !lower left$ -esial and !ri.ht$
inferior views showin. the localization of i-portant functional areas of the
do-inant frontal lobe0
tor arrest$ and sensory responses after electrical sti-ulation of the
.yrus precentralis and .yrus postcentralis0
18
Functionally, the pre9
-otor corte> !Fi.0 "$ includes the secondary -otor area !posterior
parts of the frontal .yri$, the frontal eye Aeld !intersection of
sulcus precentralis and superior frontal sulcus$ and Broca@s
lan.ua.e area !opercular and trian.ular parts of the inferior
frontal .yrus in the do-inant he-isphere$0 ;he pre-otor corte>
pro,ects to the pri9 -ary -otor corte> and, less e>tensively, to
the -otor syste-s of the spinal cord, and there is evidence in
ani-al studies supportin. its role in -otor preparation and -otor
learnin.0
1
2>tensive fron9 tal lobe resections up to the precentral
sulcus, sparin. the supple9 -entary -otor area, do not lead to
any per-anent or even transient -otor disturbance0
1&
;he
prefrontal corte> !Fi.0 "$ is in9 volved in e-otion processin.,
-oral behaviour, e>ecutive control, -onitorin. in worJin.
-e-ory, learnin. and te-poral structurin. of behavior by
conte>t0
"#
2ven thou.h so-e hypotheses propose that
individualized tasJs are carried out by the prefrontal corte>, this
brain re.ion -i.ht be responsible for the coordination of infor9
-ation processin. and transfer, re<uired for occurrence of -ultiple
hi.h9level co.nitive operations0
"1
"010 *eizure se-iolo.y
"01010 Central lobe
6lthou.h non9speciAc auras occur in -ost patients with F52,
fo9 cal so-atosensory auras, -ore co--only unilateral
parasthesias !??tin.lin.@@, ??nu-bness@@ or ??stran.e feelin.@@
sensations$ restricted to the hand, the face1ton.ue or the foot, are
speciAc to contralateral
involve-ent of the central lobe0
7
5iJewise, unilateral -yoclonic or
clonic seizures, -ore fre<uently affectin. distal se.-ents of the
body !such as the face or ton.ue$, are .enerally also the e>pression
of the epileptic activation of the contralateral central lobe0 6s for
electrical sti-ulation of the pri-ary -otor area, it usually does
not cause tonic contractions, but rather clonic twitchin. of the af9
fected -uscles0 ;he patho.enesis of clonic seizures, which consists
pri-arily of repetitive -yoclonic ,erJs, is probably very si-ilar to
that of -yoclonic seizures0
""
;ypical seizure evolution includes/ !i$
focal clonic seizures with JacJsonian -arch without secondary
.eneralization, usually acco-panied by ipsilateral head version
and followed by postictal paresisM and !ii$ so-atosensory aura of9
ten followed by tonic posturin. and head version or clonic sei9
zuresM auto-atis-s and vocalization are rare0
7
"010"0 Pre-otor corte>
;ypical seizure evolution associated with lesions of the pre-o9
tor corte> includes early versive seizure, fre<uently followed by
other -otor -anifestations such as auto-atis-s0
!17C$, in contrast to rhyth-ical theta activity, the -ost fre<uent
seizure pattern in ;52, which was seen in only &C of the 1"8 sei9
zures0 6 study co-parin. -edial !n N %$ with dorsolateral !n N 7$
patients with F52 found that absence of focal electro.raphic sei9
zure activity e>cluded the possibility of dorsolateral frontal lobe
seizures with a ne.ative predictive value of &'C, but this conclu9
sion -ay be -isleadin. because of the s-all nu-ber of study par9
ticipants0
1'
*everal authors have reported that, althou.h scalp
electrodes showed widespread seizure onset and FR= was nor-al
or non9localizin., the use of subdural .rid electrodes that e>ten9
sively covered the frontal areas was able to localize the seizure on9
set zone in O&#C of patients0
'#
'0 Fesial frontal epilepsy
;he -esial surface of the frontal lobe includes pri-ary sensory
and -otor corte> for the lower li-b, the supple-entary sensori9
-otor area !**F6$, the anterior cin.ulate corte> and the
prefrontal
'1
Persive seizures, characterized by lateral deviation of the eyes
corte> !Fi.0 "$0 ;he **F6 e>tends anteriorly appro>i-ately to the
!tonic or saccadic$, version of the head and, fre<uently, also of
the trunJ, especially when followed by a secondary .eneralized to9
nic(clonic seizure, indicate an epileptic activation of the frontal
eye Aeld contralateral to the side of eye deviation0
"'
6phasic sei9
zures -ay occur if Broca@s lan.ua.e area is involved0 5on.9lastin.
postictal aphasia is seen in O&#C of seizures startin. in the frontal
lobe of the do-inant side that spreads to the ipsilateral te-poral
lobe0
"7
"010'0 Prefrontal corte>
level of the .enu of the corpus callosu-0 **F6 sti-ulation results
in usually bilateral and pro>i-al tonic posturin. and -otor re9
sponses, but fre<uently show predo-inance on the contralateral
side0 6dditionally, contralateral sensory pheno-ena -ay occur0
;he **F6 has a so-atotopic distribution/ the head and upper
li-bs are represented at the anterior and the lower li-bs at the
posterior surface of the interhe-ispheric re.ion0 *ti-ulation of
the anterior portion of the **F6 results in arrest or slowin. of vol9
untary -otor activity0 Further-ore, sti-ulation of the cin.ulate
.yrus near the **F6 leads to -otor responses that overlap those
'"
4yper-otor seizures were deAned by 5Qders et al0
"%
as co-ple>
occurrin. in the **F6, but auto-atis-s, na-ely oro9ali-entary,
''
-ove-ents involvin. trunJ and pro>i-al li-b se.-ents, usually
with the preservation of consciousness, and are considered
speciAc for F52, in close association with frontopolar and
orbitofrontal cor9 tical lesions0
7
;his type of seizure is fre<uently
preceded by an aura !fear, ill9deAned feelin.s, and so-atosensory
pheno-ena$ and in9 cludes bizarre .estures, repetitive
-ove-ents, bicycle peddlin., pelvic thrustin. and shoutin.,
often char.ed with e-otional and a..ressive features0
4yper-otor seizures are usually short and tend to occur
durin. sleep0 GnliJe seizures involvin. the central lobe, the
co-ple> se-iolo.y of prefrontal seizures -ay be caused by
disruption of neuronal synchrony between different brain re9
.ions rather than by e>citation of sin.le areas of the corte>0
")
"0"0 =nterictal 223
6 concordant 2D and irritative zone was found in 8"C of
patients with dorsolateral F52 co-pared to ''C with -esial F52
!Fi.0 '$0
"8
Possible reasons for this difference are the s-aller distance be9
tween lateral corte> and scalp electrodes and that the dipoles tan9
.ential to the scalp in -esial F52 cannot be detected by 2230 ;he
sensitivity of interictal 223 is hi.her in intracranial subdural than
in scalp recordin.s0 +ue to the closer distance to the corte>, sub9
dural electrodes -ay reveal a s-aller irritative zone in so-e pa9
tients, when co-pared to surfaces electrodes0 4owever, a
sa-plin. bias re-ains in invasive -onitorin. studies0
"
"0'0 =ctal 223
=ctal scalp 223 in 1"8 seizures of 1% patients with dorsolateral
F52 showed correct localization of the 2D in )%C of patients, while
")C of seizures started with .eneralized 223 activity and 'C were
-islateralized in 223 analysis0
"&
=n this study only 10%C of the sei9
zures was obscured by artifacts or did not show 223 chan.es0 ;he
-ost fre<uent 223 patterns at seizure onset were repetitive
epilep9 tifor- activity !')C$, rhyth-ic delta !")C$ and 223
suppression
have also been described0
'010 *eizure se-iolo.y
6 so-atosensory aura consistin. of ??tin.lin.@@ or a feelin. of
tension, pullin. or heaviness in a li-b or the i-pression of
i-pendin. -ove-ent of the li-b -ay precede the tonic seizure0
;he sensation -ay be relatively focal, involvin. a portion of a li-b,
lateralized with both upper and lower li-bs involved si-ulta9
neously, or a poorly deAned bilateral sensation in the head or
body0
'7
;he sy-pto-s -ay arise fro- the sensory representation
within the **F6
'"
or -ay be the awareness of tension developin.
in -uscle .roups involved in the tonic contraction0 Bilateral asy-9
-etric tonic seizures are characterized by an abrupt onset of tonic
posturin. -aintained for 1# s to 7#s and absence of any postictal
stupor or confusion0
'%
PenAeld and Jasper described ??the ar-
bein. raised and the head and eyes turned as thou.h to looJ at the
hand@@, which is called the ??fencin. posture@@0
')
Foreover, 6,-one9
Farsan and Ralston created the ter- ??F"e@@ to describe tonic
abduction and e>ternal rotation of the shoulder with Ee>ion of
the elbow0 ;hey described **F6 involve-ent if F"e posturin.
occurred with9 out loss of consciousness and without pro.ression
into a secondar9 ily .eneralized tonic(clonic seizure0
'8
6lthou.h
asy--etric tonic seizure is typically associated with -esial F52,
it is not speciAc0
'
;onic seizures arisin. fro- the **F6 preferentially affect -uscle
.roups on both sides of the body, yet, they -ore often
predo-inate in the contralateral -usculature0
'&
=n -ost patients
with focal epi9 lepsy, consciousness re-ains unclouded durin.
tonic seizures, at least at the onset of seizures0
'&
*trictly
unilateral tonic seizures have a hi.hly lateralizin. si.niAcance,
pointin. to a contralateral seizure onset0
'&
Bther distinct
se-iolo.ies -ay also be associated with -esial frontal lobe
onset, includin./ hyper-otor seizures, dialeptic seizures, focal
clonic seizures of the lower li-b and ne.9 ative -yoclonus0
4owever, hyper-otor seizures do not have a hi.hly localizin.
value in the frontal lobe, since orbitofrontal,
7#
Fi.0 '0 =nterictal electroencephalo.ra- !223$ in lon.itudinal bipolar -onta.e of a 1)9year9old fe-ale with a ri.ht frontal epilepsy due to ri.ht inferior frontal .yrus cortical
dysplasia0 ;he 223 shows sharp waves involvin. ri.ht central and -idline central re.ions0
dorsolateral frontal,
11
frontopolar and opercular(insular
71
seizure
onset have all been reported0 Khile seizure onset in several frontal
re.ions -ay produce this seizure se-iolo.y, the anterior cin.ulate
re.ion has been fre<uently proposed as the cortical re.ion respon9
sible for the clinical si.ns and sy-pto-s0 +ialeptic seizures, as de9
Aned by 5Qders et al0,
"%
consist of episodes with loss of
consciousness, durin. which a patient cannot react or reacts only
to a li-ited e>tent to e>ternal sti-uli and shows -ini-al -otor
activity0 +ialeptic seizures are rare in patients with F52 and were
ter-ed ??frontal absences@@ due to their rese-blance to dialeptic
seizures in patients with .eneralized epilepsies !??absence@@$0 =n
contrast to childhood absences, patients with frontal lobe
absences -ay have subtle repetitive vocalizations, rocJin.
-ove-ents, s-all de.rees of head and eye turnin., report
awareness of a -otor arrest without loss of consciousness and
have brief postictal confu9 sion0
71
*tarin. -ay evolve into a
.eneralized tonic(clonic seizure via version of the head and eyes,
focal tonic posturin. of an upper li-b or bilateral tonic posturin.0
Patients with dialeptic seizures in F52 see- to have a -ore
anterior 2D than those with bilateral asy--etric tonic seizures0
71
;his clinical se-iolo.y has been as9 cribed to bilateral cin.ulate
.yrus involve-ent via the callosal route0
7"
Ne.ative -yoclonic
seizure consists of short phases of -uscle atonia !'#(7## -s$,
which are preceded by epileptifor- dischar.es in the central
re.ion !"#('# -s$0 3eneralized and focal ne.ative -yoclonic
seizures have also been reported0
7'
*everal re9 ports indicate that
these seizures are caused by the sudden inhibi9 tion of tonic
inervation of -otor neurons, as evidenced by the silent
electro-yelo.ra- !2F3$ period0 Recent studies showed that
**F6 sti-ulation induces silent periods only, re.ardless of the
sti-ulus intensity, whereas occurrence of silent periods followin.
sti-ulation of the pre-otor corte>, pri-ary -otor corte> or pri9
-ary so-atosensory area depended -ainly on the intensity of
sti-ulation0
77
3elastic seizures are seizures characterized by ictal
lau.hin., so-eti-es acco-panied by -irth, that fre<uently occur
in patients with hypothala-ic ha-arto-as0
7%
;he antero-esial
superior frontal .yrus and anterior cin.ulate .yrus have been de9
scribed as involved in -otor aspects of lau.hter,
7)
while the te-9
poral lobes, particularly the basal re.ions, see- to be -ainly
involved in the processin. of -irth0
78
'0"0 =nterictal 223
;he interictal 223 in patients with -esial F52 .enerally shows
either abundance of non9lateralised epileptifor- activity or none
at all0
7
Focal =2+ at or ad,acent to the -idline have been reported
in patients with tonic postural seizures0
'%
Blu-e and Bliver
7&
found that about %#C of patients !n N 1'$ with ??supple-entary -o9
tor area epilepsy@@ show -idline !Fz, Cz$ !Ave patients$ or frontal
!F7, F'$ !two patients$ spiJe foci0 223 analysis with transverse
-onta.es and usin. -idline electrodes Fz, Cz and Pz is essential,
as -a>i-al dischar.es at these electrodes -ay have a li-ited
Aeld0
7&
=n addition, bilateral frontal synchronous dischar.es are
characteristic, but not speciAc, of -esial F520
7#
6 recent study
showed that all -esial F52 patients !n N 7, established by invasive
223 recordin.s$ were characterised by interictal RF;, but this
Andin. was less fre<uent in other F52 patients !77C, "" of %#$, pro9
vidin. evidence that RF; -ay be a neurophysiolo.ical -arJer for
-esial frontal lobe abnor-ality0
1"
Nevertheless, replication of
these results by further studies with a lar.er cohort of patients is
needed0 RF; is seen in patients with bilateral asy--etric tonic
seizures and in patients with -idline parasa.ittal epileptic
dischar.es0
%#
'0'0 =ctal 223
Fuscle activity is pro-inent fro- the onset of bilateral asy-9
-etric tonic seizures and the 223 is fre<uently conta-inated
with considerable 2F3 and -ove-ent artifacts0 *eizure patterns
-ay still be evident at the verte>, where 2F3 activity is -ini-al0
6b9 sence of any ictal or i--ediate postictal 223 slowin. has
been re9 ported in patients with -esial F520
1'
=n the study by
Foldvary et al0, ,ust over %#C of the seizures analyzed were
obscured or showed no 223 chan.e in the -esial frontal lobe
epilepsy patients, an unco-9 -on occurrence in the other focal
epilepsy .roups0
"&
Characteristic Andin.s include an initial hi.h
a-plitude slow wave transient or -idline sharp wave, followed
by bilateral frontocentral low volt9 a.e fast activity or
electrodecre-ent0
%1
6ccordin.ly, one study re9 ported that
seizures fro- the -esial frontal lobe -ore fre<uently showed
paro>ys-al fast activity !''C$ or electrodecre-ent !"&C$ as the
initial ictal pattern0
"&
2lectrodecre-ent will usually evolve into
low volta.e fast activity and then bilateral frontocentral or
.eneralized rhyth-ic theta slowin.0
%"
;he low volta.e fast activity
and the rhyth-ic slow activity -ay be either localized in the ver9
te> or be -ore diffuse0 *ubtle lateralization of these rhyth-s -ay
occur but, in .eneral, the lateralizin. infor-ation fro- ictal 223 is
-ini-al0 =ndeed, it has been shown that only "%C of -esial F52
sei9 zures correctly localized or lateralized on 223 and 8%C had
non9 lateralised patterns0
"&
Khen indicated, intracranial 223 with
depth electrodes, usually placed bilaterally, provides .reater
accuracy for lateralization and localization, but also carries a
si.niAcant risJ of parenchy-al he-orrha.e0
70 Basal frontal lobe epilepsy
Bn the basal !orbital$ surface of the frontal lobes, Ave .yri can
be identiAed/ lateral orbital .yrus, anterior and posterior orbital
.yri, -edial orbital .yrus and .yrus rectus
1&
!Fi.0 "$0 ;he posterior
part of the orbitofrontal re.ion is continuous with the rostral part
of the a.ranular insula, and is hence re.arded as -ore ??li-bic@@ in
character0 4owever, the rostrally placed isocortical orbitofrontal
re.ion has features of .ranular isocorte> and blends into the
dorso9 lateral hetero-odal co-ponents of the prefrontal corte>0
%'
7010 *eizure se-iolo.y
Blfactory auras, usually described by patients as unpleasant, are
fre<uently an e>pression of epileptic activation of the orbitofrontal
part of the .yrus rectus0
%7
6utono-ic seizures -ay also occur, and
consist of ictal events durin. which the -ain abnor-ality is an
ob,ective autono-ic chan.e includin. cardiovascular !tachycardia,
bradycardia, asystole, arrhyth-ia$, respiratory !hyperventilation,
apnea, dyspnea and stridor$, .astrointestinal !epi.astric aura, vo-9
itin., spittin., defecation$, cutaneous !piloerection, pallor, Eush9
in.$, papillary !-ydriasis, -iosis$ or uro.enital !urinary ur.e,
se>ual1or.as-ic aura, .enital aura, se>ual and .enital auto-a9
tis-s$ -anifestations0 ;o docu-ent its epileptic nature, a si-ulta9
neously recorded 223 seizure pattern is usually re<uired0 =ctal
??ve.etative@@ -anifestations are thou.ht to result fro- activation
of the orbitofrontal and opercular insular re.ions0
71
4yper-otor
seizures are also co--on, althou.h not speciAcally associated
with this re.ion0
70"0 =nterictal and ictal 223
;ypically, abnor-alities detected by scalp 223 do not allow for
topo.raphic localization of foci residin. in the basal frontal lobe,
-ostly due to the inaccessibility of the basal frontal surface to
scalp electrodes0 Khen present, =2+ -ay have a re.ional distribu9
tion or appear .eneralized as a result of secondary bilateral syn9
chrony0 Case reports by 5udwi. and co9worJers hi.hli.hted the
occurrence of bilaterally synchronous epileptifor- dischar.es,
with a bifrontal or frontopolar -a>i-u-, as well as dischar.es
involvin. one anterior <uadrant, with or without evidence of addi9
tional te-poral lobe involve-ent0
%%
=n a sin.le patient with orbito9
frontal epilepsy described by Chan. et al0, the use of invasive
recordin.s showed that sphenoidal recordin.s were able to lateral9
ize the 2D, and the infraorbital scalp electrodes added to the scalp
223 revealed that the observed bisynchronous dischar.es had a
-ore basal distribution with a -a>i-u- in the infraorbital re9
.ions0
%%
False localization to the anterior te-poral re.ion is not
unco--on in patients with basal frontal epilepsies0
%)
Bccasion9
ally, propa.ated epileptifor- activity can be present over central
or frontolateral re.ions0 Foreover, epileptifor- abnor-alities
-ay have a -isleadin.ly widespread appearance because of the
lar.e distance and intervenin. cortical area that separates the 2D
fro- the scalp 223 electrodes0
%7
%0 2tiolo.y
=n a study of ) patients with F52 who underwent frontal
lesionecto-y, the histopatholo.ical Andin.s were/ tu-ors in "7
patients !'%C$ !.lioneural tu-ors, M astrocytic tu-ors, 1%M and
osteo-a, 1$, dys.enetic lesions in 1 patients !")C$ !.lioneural
ha-arto-a, 1%M cortical dysplasia, 1M cortical subcortical disor.a9
nization, 1M ectopical cortical neurons, 1$, .liosis in 17 patients
!"1C$, vascular -alfor-ations in 1# patients !1%C$ !caverno-as,
)M arteriovenous -alfor-ations, 7$, encephalitis in one patient
!10%C$ and necrosis in one patient !10%C$0
%8
;he Cleveland Clinic
series included 8# patients with F52 who underwent a frontal
lobecto-y between 1&&% and "##'0 Based on FR= and sur.ical
patholo.y, patients were divided into the followin. etiolo.ical sub9
.roups/ !i$ -alfor-ation of cortical develop-ent !FC+$ with
abnor-al FR= !71C of patients$M !ii$ FC+ with nor-al hi.h9resolu9
tion FR= !18C$M !iii$ tu-or !1&C$M !iv$ vascular -alfor-ation !'C$M
!v$ crypto.enic with nor-al FR= and histolo.y !1#C$M and !vi$
encephalo-alacia followin. stroJe or trau-a !1#C$0
%
FR=9ne.a9
tive FC+ as a disease etiolo.y proved to be an independent predic9
tor of seizure recurrence after frontal lobecto-y0
%
6nother study
found that of a total of "1 patients with refractory nocturnal F52
sub-itted to sur.ery, "# !&%C$ patients had focal cortical dysplasia
detected on histolo.ical e>a-ination !includin. one patient with
fa-ilial pedi.ree su..estive of autoso-al do-inant nocturnal
F52$ and only 11 !%"C$ patients showed frontal lobe abnor-alities
on FR=0 =nvasive recordin. by stereo9223 was perfor-ed in 1
!)C$ patients0
%&
;he -ain .enetic cause of F52 is autoso-al do-9
inant nocturnal F52 !6+NF52$, a channelopathy inherited with
inco-plete !8#C$ penetrance resultin. fro- -utations in .enes
codin. for subunits of the nicotinic acetylcholine receptor0
)#
Clini9
cally available -olecular .enetic testin. reveals -utations in
C4RN67 or C4RNB" in appro>i-ately 1#C to "#C of individuals
with a positive fa-ily history and in fewer than %C of individuals
with a ne.ative fa-ily history of 6+NF520
)#
Rin. chro-oso-e "#
should be suspected in patients with recurrent frontal status and
nor-al FR=0
)1
*li.ht -ental retardation or dys-orphis- -ay
also be found0
)"
6 recent report described a patient with a rin.
chro-o9 so-e 18 who presented with an epileptic syndro-e
si-ilar to the
rin. chro-oso-e "# syndro-e, raisin. the <uestion of overlap of
rin. chro-oso-e epileptic syndro-es0
)'
)0 6dditional and e>peri-ental -ethods
+espite its low spatial resolution, FR spectroscopy -ay help to
lateralize and even to localize epilepto.enic frontal and central
lobe lesions by detection of reduced N9acetylaspartate levels0
)7
;he area of decreased N9acetylaspartate concentration fre<uently
e>ceeds the epilepto.enic lesion as seen in FR=0
)%
+iffusion tensor
i-a.in. -ay be helpful for detection of the epilepto.enic lesion in
patients without structural chan.es on conventional FR=, espe9
cially in patients with focal cortical dysplasia0
))
Further-ore, -ul9
tiplanar reconstruction and curvilinear refor-attin. have been
shown to i-prove the localization of focal cortical dysplasias in
the frontal lobe0
)8
80 ;reat-ent of refractory F52
8010 *ur.ery
;he al.orith- used in our institution for pre9sur.ical evaluation
of patients with F52 is outlined in Fi.0 70 6 F52 patient with a lesion
not ad,acent to the elo<uent corte>, with a con.ruent 223 !ictal
and interictal$, seizure se-iolo.y, and neuropsycholo.y evaluation
-ay be sub-itted to resective sur.ery without the need for inva9
sive -onitorin. if/ !i$ ictal 223 reveals a lateralized or localized
sei9 zure patternM or !ii$ ictal 223 is nor-al or contains artifacts
but P2; or ictal *P2C; is localized0 =nvasive -onitorin. is
reco--ended when there is/ F52 without a lesionM a lesion
ad,acent to an elo9 <uent corte>M no con.ruence between the
different zonesM or con9 .ruence but the ictal 223 is nor-al and
the P2; and ictal *P2C; are not localized0
'
2>trate-poral lobe sur.ery for focal epilepsy accounts for less
than %#C of all epilepsy sur.eries0
)
=n F52 sur.ery the probability
of beco-in. seizure9free is %%08C at 1 year, 7%01C at ' years, and
'#01C at % years0
%
Fesial te-poral lobe epilepsy !F;52$ associ9
ated with hippoca-pal sclerosis is the -ost co--on for- of
focal epilepsy, with around )#C of patients havin. anterior
te-poral lobe resections, of who- )#(8#C are seizure free at 1("
years of follow9up
)&
but only %C are seizure free at 1# years0
8#
Patients with F52 and favorable pro.nostic factors !FR= lesion
restricted
Fi.0 70 6l.orith- of investi.ations used in our institution for the pre9sur.ical
evaluation of patients with frontal lobe epilepsy0
to one frontal lobe, co-plete resection, re.ional or lateralized ictal
scalp 223 pattern$ show a seizure9free outco-e co-parable to
F;52 patients after te-poral lobecto-y, with %#C to )#C bein.
seizure free at ' years0 Re.ardin. etiolo.y, patients with low9.rade
tu-ors have the best outco-e !)"C$ followed by patients with
FR= visible -alfor-ations of cortical develop-ent !%"C$0
80"0 Palliative interventions
Co-plete seizure control is virtually unachievable for so-e pa9
tients, but useful palliation can so-eti-es be achieved with tech9
ni<ues such as va.al nerve sti-ulation or -ultiple subpial
transections0
Pa.al nerve sti-ulation is indicated in adults with focal epilep9
sies who are not sur.ical candidates or who have had sur.ery per9
for-ed without success0 Bn avera.e, a %#C reduction of seizure
fre<uency has been reported in about one9third of patients, the
sa-e ran.e of e>pected beneAt if a new 62+ is added, with the
advanta.e of lower adverse effects0 4owever, seizure freedo- is
rare0
81
Fultiple subpial transections use radially oriented incisions in
the .rey -atter at 79-- intervals to li-it propa.ation of epileptic
activity within elo<uent corte> and to reduce seizure spread
with9 out disturbin. functional inte.rity0 6 si.niAcant seizure
reduction has been reported0
8"
6 Jeto.enic diet, hi.h in fat and low in carbohydrate, is -ainly
used in pediatric patients !due to <uestions of tolerability$ as a sec9
ond line treat-ent in focal non9sur.ical refractory epilepsy0 6 re9
cent rando-ized controlled trial showed a reduction of seizure
fre<uency of -ore than %#C in 'C of children with dru.9resistant
epilepsy0
8'
=n chronic epilepsies !-ore than % years$ the addition of a pre9
viously unused 62+ provided seizure freedo- in 18C and a %#C to
&&C seizure reduction for "%C0 For non9responders to the Arst trial,
a si-ilar beneAt -i.ht be e>pected for at least two -ore trials0 6t
the end, "C of patients were seizure free0
87
Donisa-ide !1##(
7## -. id$, levetiraceta- !1###('### -. id$, la-otri.ine !'##(
%## -. id$, topira-ate !'##(1### -. id$ and .abapentine !)##(
1## -. id$ have de-onstrated efAcacy !evidence level 6$ as
add9on therapy in patients with refractory focal epilepsy0
8%
2ven
thou.h the -ethodolo.y was si-ilar for all studies, a direct co-9
parison between outco-es does not allow deter-ination of the
relative efAcacy, because populations differed and so-e dru.s
were not used in -a>i-u- doses, whereas others appear to have
been ad-inistered above the ideal dose0 For essentially all dru.s,
efAcacy as well as side effects increased with increasin. doses0
8%
=n refractory epilepsy it is convenient to -ana.e 62+ by/ !i$
increasin. the dosa.e up to the -a>i-u- tolerable doseM !ii$ if
the patient is non9responsive, then replace the 62+M if the patient
responds partially, then add on an 62+ chosen accordin. to the
-echanis- of action of the Arst 62+ !e0.0 la-otri.ine and valpro9
ate are syner.istic$, efAcacy and adverse effects0
8)
0 Conclusion
F52 is an i-portant cause of refractory focal epilepsy and repre9
sents a substantial .roup of patients referred for epilepsy sur.ery0
*eizure se-iolo.y, FR=, ictal 223, interictal 223 and P2;1*P2C;
should be ,udiciously analyzed to further classify the F52 as central,
pre-otor, prefrontal, frontal -esial or frontal basal epilepsy0 6ccu9
rate localization of the 2D and reco.nition of pro.nostic factors
fur9 ther contribute to the success in F52 sur.ery0 6ntiepileptic
dru.s, va.al nerve sti-ulation, a Jeto.enic diet and -ultiple
subpial tran9 sections are beneAcial in patients not eli.ible for
resective sur.ery0
6cJnowled.e-ent
;he authors acJnowled.e +r0 60 *0 Costa for helpful 2n.lish lan9
.ua.e editin. assistance0
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