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260 PRACTICAL NEUROLOGY

REVIEW Lateral Medial


Precentral Precentral

Lateral Premotor Medial Premotor


Central
Prefrontal Prefrontal

Lateral-dorsal Medial-dorsal
Ventral

Lateral-ventral Medial-ventral
Classification

Medio-ventral

Frontal lobe epilepsy:


seizure semiology and
presurgical evaluation
Dr Aileen McGonigal† and Professor Patrick
Chauvel*
*Director of Neurophysiology and Neuropsychology
and †Clinical Research Fellow in Epileptology, Service de
Neurophysiologie Clinique, Hôpital de la Timone and Laboratoire
de Neurophysiologie et Neuropsychologie, INSERM EMI 9926,
Faculté de Médecine, Marseille, France;
Email: aileenmcg@hotmail.com
Practical Neurology, 2004, 4, 260–273
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OCTOBER 2004 261

INTRODUCTION no matter how sophisticated. Just as the pres-


John Hughlings Jackson reflected that the fron- ence of a right hemiparesis alerts the clinician to
tal lobe is the brain’s ‘most complex and least look for a lesion in the contralateral motor path-
organized centre’ (Jackson 1931) and, despite way, so too can the clinical features of a seizure
subsequent advances in neuroscience, even by point to the activation (or inhibition) of certain
the late 20th century the frontal lobe was still brain regions. At its simplest level, this allows us
considered to be an ‘uncharted province of the to relate a sign such as a focal clonic contraction
brain’ (Goldman-Rakic 1984). For epileptolo- in the hand with seizure activity in the contralat-
gists today, frontal lobe epilepsy (FLE) remains eral motor cortex. However, in FLE the observed
the most challenging of all the epilepsies, both symptoms or signs may be complex, subtle and
in terms of understanding how seizures are or- often occur simultaneously or in rapid succes-
ganized and how they should be treated. This sion, frequently reflecting the activation of dif-
is very evident in comparison to the now well- ferent structures within a dynamic system, with
defined syndrome of mesial temporal lobe epi- rapid and unpredictable propagation patterns.
lepsy (TLE). Not only is it challenging to determine from
Important advances have been made in re- which part of the frontal lobe the seizure arises,
cent decades, especially in correlations between but also it is often difficult to assess whether a
the clinical and electrical expression of seizures, particular attack is indeed a frontal lobe sei-
permitting better understanding of FLE. To- zure at all. Frontal lobe seizures are particularly
gether with major developments in the field of prone to misdiagnosis as psychogenic non-epi-
neuroimaging, these advances are changing the leptic seizures, due to their sometimes bizarre
approach to management, particularly in mak- or atypical appearance, as well as to the fact that
ing curative surgery a real possibility for many surface EEG does not necessarily show interictal
more patients than ever before. or ictal abnormalities (Bautista et al. 1998).
Understanding FLE, it can be argued, will Another possible misdiagnosis of FLE is of a
also help us understand more about the cer- sleep disorder, particularly as a large proportion
ebral processes that underlie normal higher of frontal seizures arise from sleep. For example,
brain functions such as the interaction between the nocturnal attack disorder originally identi-
emotion and decision making (Damasio 1995). fied as a form of movement disorder – ‘paroxys-
Indeed, frontal lobe epilepsy has been described mal nocturnal dystonia’ (Lugarasi & Cirignotta
as ‘the next frontier’ (Niedermeyer 1998). From 1981) – was subsequently recognized to have an
historical observations to futuristic develop- epileptic basis in most cases (Meierkord et al.
ments: what does all this mean for our routine 1992). The syndrome of autosomal dominant
clinical practice? nocturnal frontal lobe epilepsy (ADNFLE) was
later described; this is a monogenic disorder
AIMS OF THIS REVIEW with high penetrance, characterized by brief
We have chosen to focus on the approach to hyperkinetic nocturnal seizures.
the electroclinical diagnosis and localization Because of these diagnostic difficulties, cau-
of FLE, in other words the combined analysis tion must be exercised, and an epilepsy specialist
of the clinical features of seizures (semiology) rather than a general neurologist or general phy-
and electroencephalographic (EEG) data. This sician should ideally make the diagnosis.
approach is particularly important when assess- The localizing value of specific semiological
ing those patients who may be candidates for features is, in general, less well-understood in
epilepsy surgery: the 20% or so of all patients FLE, compared with TLE. For this reason, as well
with partial epilepsy who are pharmacoresist- as other issues related to the limitations of EEG
ant. In addition we will briefly discuss recent in FLE, diagnosis and localization are well rec-
developments in other aspects of presurgical ognized to be more difficult than in other locali-
evaluation. zation-related epilepsies (Manford et al. 1996).
Indeed, it is likely that some epilepsy ‘surgical
WHY ARE ELECTROCLINICAL failures’, including cases operated for presumed
CORRELATIONS SO IMPORTANT IN TLE that do not become seizure-free post-op-
FRONTAL LOBE EPILEPSY? eratively, reflect incorrect presurgical localiza-
In epilepsy, as in all neurological practice, the tion, rather than suboptimal resection (Walsh &
history and physical signs are of paramount im- Delgado-Escueta 1984). FLE forms the second
portance and cannot be replaced by a single test, largest group of potentially operable localiza-
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262 PRACTICAL NEUROLOGY

tion-related epilepsies after TLE. The reliable area) within the premotor cortex, particularly
electroclinical diagnosis of FLE, as well as the in the dominant hemisphere (area 44).
identification of subtypes, is therefore particu- • The frontal eye fields, which can contribute
larly important in terms of optimal selection of to ictal versive head and eye movement, lie
candidates for epilepsy surgery. within the dorsolateral cortex (area 8) in the
Despite the complex nature of most fron- boundary where the premotor and precentral
tal seizures, certain semiological patterns are cortex meet, and may therefore be involved in
reproducible and can help to define the likely seizures arising from either of these regions.
region(s) involved. The occurrence of localized The organization of the prefrontal cortex,
tonic posturing (face, upper limb, lower limb), which is predominantly made up of heteromo-
emotional behaviour (such as fear) and com- dal association areas, is extremely complicated
plex motor activity, may direct the clinician to- and incompletely understood. It has complicat-
wards a particular part of the frontal lobe, as will ed and long association connections with other
be discussed later. This becomes crucial when a brain regions, including limbic and paralimbic
more precise sublobar understanding of locali- areas, which involve a continuum of temporal
zation is required. and frontal lobe structures (particularly the cin-
gulate gyrus and the posterior orbital region)
FRONTAL LOBE ANATOMY AND RELATION (Fig. 2). Incoming sensory information from
TO SEMIOLOGY these areas may be processed, taking account of
The frontal lobe is the largest lobe in the brain motivational and emotional states, and used to
(accounting for about 40% of cerebral cortex) influence decision-making and many aspects of
(Fig. 1). This large size contributes to diagnostic behaviour (Pandya & Yeterian 1985). Patients
difficulties. There are multiple diverse propaga- with prefrontal epilepsy may demonstrate in-
tion patterns, and there is the problem of lim- terictal behavioural or psychiatric abnormalities,
ited EEG sampling, particularly from relatively such as lack of spontaneity and poor planning
‘hidden’ regions such as medial and basal (or- (frontal abulic syndrome), or impulsivity and
bitofrontal) cortex (Bautista et al. 1998). The socially inappropriate behaviour (frontal dis-
functional anatomical divisions of precentral, inhibition syndrome), which may improve fol-
premotor and prefrontal cortex provide a use- lowing surgery (Devinsky et al. 1995).
ful model for thinking about semiology and will
be briefly described: ATTEMPTS TO CLASSIFY FRONTAL LOBE
• The precentral region consists of primary EPILEPSY
motor cortex, Brodmann’s area 4. Although the approach of separating tempo-
• The premotor cortex consists principally of ral from extra-temporal epilepsy is now estab-
the lateral and medial components of area 6, lished, and most extra-temporal epilepsies have
the latter corresponding to the supplemen- their origin in the frontal lobe, a widely accepted
tary motor area (SMA). classification of FLE has not yet been reached.
• There is some representation of language (in- Indeed the nomenclature used by different
cluding the region formally known as Broca’s groups to describe frontal seizure types has var-

D E
Figure 1 Cytoarchitectonic 8B 4

diagram of the frontal lobe 8Ad 6 8B


9
(prefrontal cortex shown in 9
9/46d 8Av
colour), with Brodmann’s areas
(Petrides & Pandya 1994). (a)
9/46v CC 24
Lateral view, (b) Medial aspect. 6 10
46 44
Reprinted from The Frontal Lobes, 32
Computational Modelling and
45A 45B
Neuropsychology: Handbook of 10 25

Neuropsychology, Vol 9, Boller F, 47/12


14
Spinnler H, Hendler JA, 1994, with
permission from Elsevier.
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OCTOBER 2004 263

ied markedly over the years. Trying to advance Figure 2 There are extensive functional connections between the prefrontal cortex
our understanding of all this is important, be- and other frontal lobe structures as well as other lobes of the brain. The long length of
cause FLE must be regarded as a variety of sei- these connections is a contributing factor to the highly variable propagation patterns
zure patterns originating from different regions and the diverse, complex semiology that may occur with frontal lobe seizures. The more
of the frontal lobes rather than a disease per se highly integrative (and more anteriorly situated) the association area, the longer these
(Wieser & Swartz 1992). projections are. (a) Lateral view, (b) Medial view. AS, arcuate sulcus; CC, corpus callosum;
Important progress has been made recently CF, calcarine fissure; CING S, cingulate sulcus; CS, central (Rolandic) sulcus; IOS, inferior
by the proposed system of electroclinical pat- occipital sulcus; IPS, intraparietal sulcus; LF, lateral (Sylvian) fissure; LS, lunate sulcus;
terns based on the functional anatomical divi- PS, principal sulcus) (Pandya & Yeterian 1985, permission sought.)
sions of the frontal lobe (Bartolomei & Chauvel
2000; Chauvel 2003). This recognizes central,
premotor and prefrontal seizure types with dis- video-EEG recording, enabling correlation of
tinction between predominantly dorsolateral detailed clinical observations of seizures with
and medioventral types within each of these simultaneously recorded electrophysiological
categories. This model is clinically useful be- data. The development of depth electrode EEG
cause it reflects the tendency for postural and recording, especially the technique of stereo-
tonic motor activity to be seen in the most pos- electroencephalography (SEEG), developed by
terior subtypes (central, precentral) and more the French team of Bancaud and Talairach in the
complex motor behaviours with autonomic and 1960s–1980s, has been crucially important in
emotional manifestations to be associated with this respect (Chauvel 2001). SEEG involves the
prefrontal seizures. Distinction between dorsal stereotaxic placement under general anaesthetic
and medial patterns is also possible to some ex- of depth electrodes that record EEG from deep
tent, this having been already well-documented brain structures. It has certain advantages over
in motor area seizures. There is some evidence to other intracranial recording methods (such as
suggest that prefrontal seizures may be similarly subdural grids or strips placed on the cortical
separable. This classification will be discussed surface), in that it permits simultaneous record-
later. ing from superficial and deep structures, allow-
ing better spatial definition of the likely region
ANATOMO-ELECTRO-CLINICAL of seizure onset, or epileptogenic zone (EZ).
CORRELATIONS Morbidity is also lower. Ictal and interictal SEEG
Detailed study of FLE electro-clinical corre- recording with simultaneous video is generally
lations has been possible since the advent of obtained over a period of 4–10 days, during an
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264 PRACTICAL NEUROLOGY

inpatient stay in a specialist videotelemetry unit.


The decision about where to place the electrodes
is based on the hypotheses regarding the likely
brain structures involved in the EZ. These hy-
potheses are formed by the epilepsy team and
are based on the ensemble of all the available
non-invasive data [standard EEG and video-
EEG, MRI, single photon emission computer-
ized tomography (SPECT), positron emission
tomography (PET), etc.], and including detailed
semiological observations. This technique can
be very useful in those patients with FLE who
Figure 3 Stereo electroencephalographic (SEEG) intracerebral recording of a dorsolateral are potential surgical candidates, but where
prefrontal seizure. (a) This patient had seizures characterized by semipurposeful standard non-invasive investigations are insuf-
behaviour, proximal tonic posturing and vocalization. The combination of clinical, ficient to allow localization of the EZ (for ex-
electrophysiological and imaging data suggested likely involvement of the dorsolateral ample normal or nonlocalizing MRI). Potential
prefrontal region. (b) The electrical onset of the seizure is clearly seen in his ictal SEEG contra-indications to surgery (e.g. involvement
recording, with a build-up of high amplitude rhythmic spikes (red arrows) followed by of language areas) can also be studied during
a high frequency rapid discharge (blue arrows). The electrodes involved lie within a the recording. The method is well-established
localized part of the dorsolateral prefrontal region. (c) Representation of propagation in several European countries for epilepsy pre-
patterns as recorded with SEEG, superimposed on a 3D MRI reconstruction. The surgical evaluation, but remains much less used
patient subsequently underwent localized cortical resection, with no postoperative elsewhere, including in the UK and US. An ex-
neurocognitive deficit, and remains seizure-free at 1-year follow-up. With thanks to the ample of this electroclinical approach is shown
staff of the Epilepsy Unit, Hôpital de la Timone, Marseille, France. in Fig. 3.

a b

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OCTOBER 2004 265

GENERAL FEATURES OF FRONTAL Several recent FLE studies have attempted to


SEIZURE SEMIOLOGY demonstrate a consistent sublobar localization
Recent reviews have revealed the diversity of for given ictal symptoms or signs but have found
presentation of frontal seizure semiology and limited correlations (Manford et al. 1996; Jobst
some have sought to define clinical or electro- et al. 2000; Kotagal et al. 2003). This has led some
clinical subtypes (Bancaud & Talairach 1992; authors to question whether it is possible to rely
Talairach et al. 1992a; Chauvel et al. 1995; Wil- at all on semiological analysis when attempting
liamson & Engel 1997; So 1998; Swartz et al. to localize frontal seizures (Manford 1996).
1998; Bartolomei & Chauvel 2000; Jobst et al. However, such conclusions may to some de-
2000; Kotagal et al. 2003). Those (relatively few) gree reflect the limitations of using statistical
series with confirmation of frontal lobe origin by cluster analysis to try to correlate an isolated
depth studies and/or subsequent surgical cure by clinical sign with a ‘focus’ of epileptic activity,
frontal resection have been particularly useful. rather than considering patterns of clinical signs
Frontal seizure semiology is extremely di- and the concept of an epileptic ‘network’ that
verse, but certain features are agreed to suggest Seizures may involves several sites and which gives rise to ictal
frontal lobe origin. Seizures may be brief with phenomena depending on the interplay of a dy-
sudden onset and termination; often arise from be brief with namic system.
sleep; may occur in clusters; have a tendency to The underlying mechanism of the complex
rapid secondary generalization; and produce sudden onset ictal behaviour patterns seen in FLE remains an
minimal postictal confusion (Williamson et al. interesting and disputed question. One theory,
1985; Williamson & Engel 1997). Clonic activity and termination; proposed by Jackson and being revisited today,
and asymmetric tonic posturing are typical of is that epileptic activity may disrupt the con-
frontal seizures and of all the possible frontal sei- often arise from trol normally exerted by higher brain centres,
zure symptoms and signs, motor manifestations thus allowing the ‘release’ or disinhibition of
remain the most frequent and important, ob- sleep; may occur more primitive, stereotyped behaviours. Such
served in 90% of patients (Chauvel et al. 1995). release phenomena might be comparable with
Complex gestural manifestations or patterns in clusters; have the forced grasping or ‘utilization behaviour’
of behaviour seem to be particularly characteris- first described by Lhermitte (1983) in patients
tic of certain FLEs and are increasingly recognized a tendency to with bilateral frontal lesions, now recognized to
(Williamson et al. 1985; Bancaud & Talairach form part of the spectrum of abnormal motor
1992; Chauvel et al. 1995; Manford et al. 1996; rapid secondary responses that occur in the context of imbal-
Jobst 2000). Gestural automatisms include fum- ance between internally generated control of
bling or exploratory movements with the hand generalization; movement and response to environmental cues
directed toward self or environment, such as tap- (Archibald et al. 2001). The stepping reflex is
ping or grabbing of objects or bedclothes; more and produce another example of such release phenomena,
complex behaviours might include snapping the and the kicking movements or pelvic thrust-
fingers, crossing and uncrossing the legs, or more minimal postictal ing during frontal seizures may be interpreted
dramatic pedalling movements, thrashing or hit- as relating to this. Recent electrophysiological
ting. Some of these complex manifestations may confusion data supporting the role of epileptic networks in
seem to be to a greater or lesser degree adapted frontal lobe ictal phenomena argue in favour of
to the environment, indicating a degree of re- a ‘functional uncoupling’ of this nature (Wend-
tained awareness and autonomy. Although the ling et al. 2003; Gavaret et al. 2004).
term ‘hypermotor seizures’ was proposed by the This area therefore remains one of the most
Cleveland group to describe such seizures char- important for further study if we are to advance
acterized by motor agitation associated with an in our ability to understand FLE, and success-
emotional quality, this has not been uniformly fully select FLE patients for surgical treatment.
accepted as a useful description (So 1998).
ANATOMIC-FUNCTIONAL CLASSIFICATION
DIFFICULTIES OF ELECTROCLINICAL OF FRONTAL LOBE SEIZURES
CORRELATION IN FLE While the recent anatomical and functional cate-
Unlike TLE, where the sites of epileptic discharge gorization of frontal seizure subtypes proposed
likely to be responsible for certain ictal clinical by Chauvel and colleagues remains preliminary,
signs are relatively well-recognized, the neuro- it provides a useful way to consider the localizing
physiological organization of many types of value of certain patterns of seizure semiology
frontal lobe seizure remains poorly understood. (Fig. 4)
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266 PRACTICAL NEUROLOGY

a Premotor areas
including SMA
(BA 6): Frontal eye
Precentral (primary asymmetric tonic fields (BA 8):
Dorsolateral
motor) area (BA 4): posturing,
clonic jerks, sometimes version of gaze prefrontal
sometimes more
tonic posturing or complex motor
and/or head region:
version
cortical myoclonus phenomena complex
automatisms,
semi-
purposeful
behaviour,
“forced acting”;
also frontal
absences

Expressive language
areas
(BA 44, 45)

Frontal operculum:
facial contraction,
hypersalivation

Frontal eye Premotor region: SMA (BA 6) Precentral


b asymmetric tonic posturing,
fields (BA 8): (primary motor)
version of sometimes more complex motor area (leg
gaze and/or phenomena representation):
head version clonic jerks,
sometimes tonic
posturing or
cortical myoclonus

Ventromesial
Figure 4 Summary of elements prefrontal
of frontal seizure semiology in region:
relation to precentral, premotor hyperkinetic
and prefrontal regions. (a) motor
dorsolateral view (b) medial behaviour, ictal
view. BA, Brodmann’s area; SMA,
expression of
emotion (fear)
supplementary motor area.
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OCTOBER 2004 267

Pre-central seizures been shown by stereo-electroencephalography


The best-defined frontal seizure type was rec- (SEEG) and by scalp-EEG using back averaging
ognized by Jackson over 100 years ago (in Jack- techniques. The underlying cause in some is an
son 1931). His description of focal seizures with autoimmune process, which is now recognized
contralateral clonic movements arising from to be the mechanism for Rasmussen’s encepha-
the precentral (primary motor) region remains litis; vascular lesions and tumours may also be
valid today. The characteristic feature is the slow responsible.
progression from one body part to another ad-
jacent segment – the ‘Jacksonian march’. The Premotor seizures
body part involved in the seizure indicates the This region includes the supplementary motor
region of motor cortex activity according to the area (SMA). Seizures arising in the SMA were
somatotopic representation in the motor cortex, originally described on the basis of the results
so that it is possible to distinguish dorsal from of electrical stimulation of normal cortex.
medial precentral seizures. However, the spectrum of semiology for sei-
In the light of depth electrode data, it is now zures involving the SMA is now recognized to
recognized that seizures arising from the pre- be wider than originally suggested (Bancaud &
central cortex may also appear rather different Talairach 1992; Chauvel et al. 1992). Premotor
to the classical Jacksonian focal clonic seizure. seizures are characterized by postural and tonic
For example, contralateral clonic movements signs, which are predominantly proximal, usu-
may be accompanied by more complex bilateral ally bilateral and asymmetrical. The upper limbs
tonic posturing, or predominantly distal partial are most often involved, producing the classical
myoclonus (Chauvel et al. 1992). ‘fencing posture’ or a variety of other tonic pos-
Another form of epilepsy associated with tures (Fig. 5). Adversion (turning) of the head
the Rolandic (central) region, in other words and eyes is often associated with this, due to in-
motor (frontal precentral) and also sensory volvement of the frontal eye fields. The direction
(parietal postcentral) areas, is reflex epilepsy. of adversion may be ipsilateral or contralateral
(Vignal et al. 1998). This rare phenomenon to the site of epileptic activity, depending on its
(about 1% of partial epilepsies) manifests as timing within the seizure, and is therefore not
seizures that are triggered by cutaneous stim- a consistently reliable guide to lateralization of
ulation or movement of a specific body part.
They may manifest as tonic posturing (often
asymmetric), clonic jerks or a combination of
both; sometimes there is also a sensory compo-
nent (e.g. tingling in the arm followed by clonic
jerks in the same territory). The aetiology may
be related to hyperexcitability of the sensori-
motor Rolandic cortex.
In the related but separate entity of startle sei-
zures, a sudden or unexpected sensory stimu-
lus, usually a noise, can provoke a motor startle
response characterized by tonic motor signs,
such as bilateral upper and lower limb postur-
ing, that is often asymmetric. Such seizures were
classically described in the context of infantile
hemiplegia due to a cortical lesion involving the
motor area, and their cortical origin in the pre-
central and premotor region has been demon-
strated (Chauvel et al. 1992).
Another specific type of seizure more rarely
arising from central regions is epilepsia partialis
continua, a form of ‘partial somatomotor sta-
tus epilepticus’. This can remain focal for hours,
days, weeks or even months because of long-loop Figure 5 This patient has seizures arising from the left supplementary motor area in the
reflex mechanisms in the sensorimotor cortex premotor frontal region. Note the characteristic asymmetric tonic posturing of upper limbs
(Biraben & Chauvel 1997). Its cortical origin has during one of her typical seizures. With thanks to Dr JP Vignal, Nancy, France.
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268 PRACTICAL NEUROLOGY

the epilepsy. Speech arrest or vocalization (char- frontal origin, although whether it was possible
acteristically palilalia) may also occur if there is to distinguish them electroclinically from tem-
involvement of the speech area in the frontal poral lobe seizures was disputed for a decade
operculum. Spread to involve the operculum or so. A frontal lobe origin for this pattern of
and the lower central region may also give rise seizure was later confirmed by depth EEG re-
to facial clonic jerks and salivation. More com- cordings (Williamson et al. 1985). Subsequent
plex movements of all four limbs can follow workers developed distinctions between those
these main signs. Initial subjective sensations or with a dorsal origin from those arising from an-
‘auras’ occur infrequently in this seizure type, terior cingulate, orbitofrontal, and frontopolar
but some patients describe sensory symptoms areas (Bancaud & Talairach 1992).
such as ill-defined tightness or tingling, which Currently available data suggest that the clear-
may be generalized or localized (Williamson & est differentiation can be made between ventral
Engel 1997). Secondary generalization is infre- and dorsal patterns.
quent.
Ventro-medial prefrontal seizures
The direction of adversion Seizures arising from ventral or ventro-medial
regions appear to correspond to those initially
may be ipsilateral or described as ‘complex partial seizures of fron-
tal lobe origin’ (Williamson et al. 1985), as de-
contralateral to the scribed above. Some begin with what appears to
be a dramatic reaction to fear, with a frightened
site of epileptic activity, facial expression, screaming and abrupt agita-
tion (Fig. 6). This intense behavioural reac-
depending on its timing tion to fear is very different from the pattern of
temporal lobe seizures that include a subjective
within the seizure, sensation of fear. There may be complex, appar-
ently purposeful gesticulation, such as kicking
and is therefore not a or punching, bipedal cycling movements or
attempts to escape. Autonomic signs such as
consistently reliable guide mydriasis, tachycardia and facial flushing are
common, as well as peri-ictal urination. It ap-
to lateralization of the pears that a consistent role for a ventro-medial
epilepsy network can be demonstrated for those
epilepsy seizures involving ictal fear-related behaviour
(Biraben et al. 2001).
Prefrontal seizures
Prefrontal seizures remain the least well-charac- Dorso-lateral prefrontal seizures
terized of all frontal seizures. In fact distinguish- Certain clinical features suggest the involvement
ing between prefrontal and premotor origin can of the dorsal prefrontal region, notably tonic de-
be difficult, as seizures may involve both areas. viation of the eyes preceding head version, and
Seizure patterns that arise from the prefrontal gestural automatisms that may be directed to-
region reflect its highly complex organization, wards the same location as the gaze. These move-
so that in comparison with the relatively simple ments may appear semipurposeful, for example
elements of more posterior frontal seizures, pre- a patient may appear to be reaching towards
frontal semiology is extremely diverse and may something in their visual field. There may also be
be highly idiosyncratic. a compulsive element to the behaviour (‘forced
The first observations of prefrontal seizures acting’). Motor patterns in this seizure type are
were published in the 1970s (Tharp 1972; Lud- usually complex, such as semirhythmic tapping
wig et al. 1975). These were described as brief of the hands or feet, or grasping motions. They
attacks typically occurring in clusters, often at are often associated with asymmetrical tonic or
night, and characterized by a frightened ap- dystonic posturing of upper and/or lower limbs.
pearance, agitation, repetitive semipurposeful Vocalization may occur; unlike the pattern seen in
behaviour and vocalizations that could be non- medioventral seizures, this often does not appear
verbal (screaming) or verbal (expletives). It was to have an initial emotional modification. Such
initially speculated that these were of orbito- vocalizations may be non-verbal (e.g. groaning,
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OCTOBER 2004 269

Figure 6 Some prefrontal seizures may manifest as extreme motor agitation and emotional behaviour during
the ictal period. This pattern appears to be associated with a ventromedial epileptic network, as in this
patient who had epilepsy affecting the left ventromedial prefrontal region. With thanks to staff of the Epilepsy
Unit, Hôpital de la Timone, Marseille, France.

humming) or verbal (e.g. palilalia, jargon, swear-


ing, singing). Visual hallucinations may also be
reported in seizures from this region; these can
include dimming or blurring of vision and more
rarely actual hallucinations, either simple, such
as coloured shapes, or what have been described
as ‘psychical’ illusions (e.g. images of a familiar
person) (Chauvel et al. 1995). ‘Forced thinking’
may occur, consisting of a recurrent intrusive
thought or an overwhelming impulse to per- As in other seizure
form a certain act (e.g. to open the eyes, or to
grab something). types, propagation
Another form of dorsolateral seizure is that
associated with a spike-wave, rather than a tonic patterns affect the clinical
discharge, which manifests clinically as a ‘fron-
tal absence’ with arrest of activity (Bancaud & manifestations of the
Talairach 1992). This seizure type may appear
electroclinically similar to the classical ‘petit seizure
mal’ absence seizures that occur in the context of
idiopathic generalized epilepsy; indeed the na-
ture of the differences between the two has been
the topic of some debate. The absences of FLE
tend to be more variable in their clinical expres-
sion, with a longer duration and/or the presence
of associated features such as automatisms. The
‘atypical absences’ of the Lennox–Gastaut syn-
drome could be included in this category.
As in other seizure types, propagation pat-
terns affect the clinical manifestations of the
seizure. When there is posterior spread towards
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270 PRACTICAL NEUROLOGY

premotor and motor regions, secondary gener- single lesion is seen on MRI, it is necessary to un-
alization is frequent. derstand its relation to the epileptogenic zone,
This proposed classification remains some- as the two do not necessarily fully overlap (Ta-
what theoretical and is the subject of ongoing lairach et al. 1992b). Anatomo-electro-clinical
study but progress in the identification of elec- correlation carried out using SEEG as devised
troclinical patterns has the potential to greatly by Talairach, which was developed well before
advance the surgical treatment of FLE. the era of MRI, does not necessarily depend on
the presence of a visible lesion on neuroimaging.
DEVELOPMENTS IN THE PRESURGICAL In addition, some series have reported good out-
EVALUATION OF FRONTAL LOBE comes in patients with normal imaging, based
EPILEPSY on presurgical evaluation incorporating semi-
When considering the overall evolution of sur- ological analysis and intracerebral recording as
gery for epilepsy, the importance of develop- well as other noninvasive data (Talairach et al.
ments in neuroimaging over the past 15 years 1992a; Zentner et al. 1996; Swartz et al. 1998;
cannot be overestimated – these have revolu- Siegel et al. 2001).
tionized the optimum selection and treatment Much current research is therefore being
of potential epilepsy surgical candidates (Dun- directed towards the detection of focal lesions
can 1997). Given the difficulties in the diagno- that are not visible with currently optimal MRI
sis and localization of FLE as described above, (Knowlton 2004). It seems likely that the small
imaging plays an extremely important role. surgical series reporting successful outcomes
Magnetic resonance imaging (MRI), including despite normal imaging reflect those patients
techniques such as diffusion tensor imaging, has with ‘invisible’ focal lesions, many of which are
developed to the point where the great major- focal cortical dysplasias, and which the ensem-
ity of patients with localization-related epilepsy ble of clinical data including intracerebral EEG
can be shown to have an underlying cortical le- have correctly identified. It is clear that develop-
sion (Fig. 7). Many authors emphasize the cor- ment of less invasive methods that might per-
relation between the presence of a visible focal mit the confident detection of such lesions is an
lesion and good surgical outcome (Mosewich important area for future work. Such methods
et al. 2000). include functional imaging, of which positron
However, there remain around 20% of pa- emission tomography (PET) appears particu-
tients with localization-related epilepsy who larly promising. Although most work relates
have no lesion visible on current optimum to medial temporal epilepsy, a recent study has
MRI with expert review, and others with dual highlighted the potential importance of [11C]
or multifocal pathology. Moreover, even when a flumazenil PET, which appears to have better

Figure 7 Brain MRI demonstrating the presence of a small dysplasia (arrow) in the left
medial frontal lobe (prefrontal region). (a) Coronal inversion-recovery sequence, (b)
Coronal FLAIR, (c) Axial T2.

a b c

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OCTOBER 2004 271

sensitivity and specificity in detecting metabolic


abnormalities than 2-[11F] fluoro-2-deoxy-d-
glucose (FDG) PET in neocortical epilepsy and
Much current research is which may be useful in helping to detect extra-
temporal epileptogenic zones even when MRI is
being directed towards normal (Hammers et al. 2003).
Developments in non-invasive neurophysi-
the detection of focal ological techniques include magneto-elec-
troencephalography (MEG), which, though
lesions that are not visible limited to a few centres, seems to be particularly
useful in neocortical compared with temporal
with currently optimal MRI epilepsy and has been validated by intracranial
comparison studies (Barkley & Baumgartner
2003). Source localization techniques using
high-resolution scalp EEG also appear promis-
ing (Gavaret et al. 2004) (Fig. 8).

b
a

1 sec
Figure 8 High resolution EEG can be superimposed on a patient’s MR scan to represent the region of greatest
interictal activity and this can be particularly useful where imaging is non-localizing. This figure shows
interictal spikes recorded from a 27-year-old woman with medioventral frontal lobe epilepsy. (a) Interictal
spikes occurred in brief runs with maximal amplitude over electrodes FP1, F7 and FPZ (left fronto-polar
region), (b) Source localization was then performed using a technique called MUSIC (Mosher et al. 1992),
which showed the maximal contribution to be in the anterior part of the left cingulate gyrus. This localization
was later validated during a depth EEG recording that demonstrated both interictal and ictal epileptic activity
arising from this region. Cortectomy was subsequently performed and histopathology showed Taylor’s
dysplasia. The patient was seizure-free at 2 years post-operatively. With thanks to Dr Martine Gavaret,
Hôpital de la Timone, Marseille, France.
© 2004 Blackwell Publishing Ltd
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272 PRACTICAL NEUROLOGY

The notion of ‘totally non-invasive presurgi- CONCLUSIONS


cal epilepsy evaluation’ in the future (Knowl- • The study of the semiology and electro-
ton 2004) is also supported by the potential of clinical correlation of frontal seizures
functional MRI for localization of language and continues to hold an important place in
memory function prior to deciding on surgical the understanding of frontal epilepsy and
resection. This may eventually be able to replace cerebral function.
tests such as the WADA and mapping by direct • This type of detailed study has been made
cortical stimulation. possible largely because of modern video-
EEG techniques, especially those using
ACKNOWLEDGEMENTS depth recording, and those that have cor-
This paper was reviewed by Dr Richard Roberts, related electroclinical data with postop-
Dundee, Scotland. erative outcome.
Aileen McGonigal gratefully acknowleges • Recent years have seen major advances in
support from the European Federation of classifying FLE: by establishing the ten-
Neurological Sciences and the Glasgow Neuro- dency for frontal seizure types to be related
science Foundation. to functional divisions of the frontal lobe
and to be organized along antero-poste-
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Frontal Lobe Epilepsy: Seizure Semiology


and Presurgical Evaluation
Aileen McGonigal and Patrick Chauvel

Pract Neurol2004 4: 260-273


doi: 10.1111/j.1474-7766.2004.00244.x

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