Seizure Semiology and Presurgical Evaluation on October 1, 2021 by Guest

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260 PRACTICAL NEUROLOGY Pract Neurol: first published as 10.1111/j.1474-7766.2004.00244.x on 1 October 2004. Downloaded from

REVIEW Lateral Medial Precentral Precentral

Lateral Premotor Medial Premotor Central Prefrontal Prefrontal

Medial-dorsal Lateral-dorsal Ventral

Lateral-ventral Medial-ventral Classification

Medio-ventral

Frontal lobe epilepsy: http://pn.bmj.com/ seizure semiology and presurgical evaluation on October 1, 2021 by guest. Protected copyright.

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: [email protected] Practical Neurology, 2004, 4, 260–273

INTRODUCTION no matter how sophisticated. Just as the pres- John Hughlings Jackson refl ected 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 refl ecting the activation of dif- is very evident in comparison to the now well- ferent structures within a dynamic system, with defi ned 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 diffi cult 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 fi eld 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). fi ed 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 http://pn.bmj.com/ 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 diffi culties, cau- of FLE, in other words the combined analysis tion must be exercised, and an epilepsy specialist on October 1, 2021 by guest. Protected copyright. 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 specifi c 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 briefl y discuss recent in FLE, diagnosis and localization are well rec- developments in other aspects of presurgical ognized to be more diffi cult 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, refl ect 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-

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). identifi cation of subtypes, is therefore particu- • The frontal eye fi elds, 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 defi ne 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 cingulate 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) infl uence decision-making and many aspects of (Fig. 1). This large size contributes to diagnostic behaviour (Pandya & Yeterian 1985). Patients diffi culties. 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 briefl y 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- http://pn.bmj.com/ • 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). classiﬁ cation 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- on October 1, 2021 by guest. Protected copyright.

D E Figure 1 Cytoarchitectonic 8B 4 8Ad diagram of the frontal lobe 6 8B 9 (prefrontal cortex shown in 9 8Av colour), with Brodmann’s areas 9/46d (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.

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 ﬁ ssure; 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) ﬁ ssure; 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 http://pn.bmj.com/ 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 refl ects the tendency for postural and recording, especially the technique of stereo- on October 1, 2021 by guest. Protected copyright. 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 classifi cation will be discussed surface), in that it permits simultaneous record- later. ing from superfi cial and deep structures, allowing better spatial defi nition 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

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 hypotheses 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, ﬁ cient 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 deﬁ cit, 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.

ab http://pn.bmj.com/ on October 1, 2021 by guest. Protected copyright.

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 defi ne 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 refl ect the limitations of using statistical series with confi rmation 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- fi rst 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 http://pn.bmj.com/ directed toward self or environment, such as tap- (Archibald et al. 2001). The stepping refl ex 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- fi ngers, 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 on October 1, 2021 by guest. Protected copyright. 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)

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

Expressive language areas (BA 44, 45)

Frontal operculum: facial contraction, hypersalivation http://pn.bmj.com/

b Frontal eye Premotor region: SMA (BA 6) Precentral fields (BA 8): asymmetric tonic posturing, (primary motor) version of sometimes more complex motor area (leg gaze and/or phenomena representation):

head version clonic jerks, on October 1, 2021 by guest. Protected copyright. 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.

Pre-central seizures been shown by stereo-electroencephalography The best-defi ned 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 fi elds. The direction (parietal postcentral) areas, is refl ex 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 specifi c body part. They may manifest as tonic posturing (often asymmetric), clonic jerks or a combination of

both; sometimes there is also a sensory compo- http://pn.bmj.com/ nent (e.g. tingling in the arm followed by clonic jerks in the same territory). The aetiology may be related to hyperexcitability of the sensorimotor Rolandic cortex. In the related but separate entity of startle seizures, a sudden or unexpected sensory stimu- on October 1, 2021 by guest. Protected copyright. lus, usually a noise, can provoke a motor startle response characterized by tonic motor signs, such as bilateral upper and lower limb posturing, 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 precentral and premotor region has been demonstrated (Chauvel et al. 1992). Another speciﬁ c 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 reﬂ ex 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.

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 confi rmed 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-defi ned 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 frontal 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 agitation (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 fl ushing 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 http://pn.bmj.com/ 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- on October 1, 2021 by guest. Protected copyright. be diffi cult, 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 refl ect 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 fi eld. There may also be be highly idiosyncratic. a compulsive element to the behaviour (‘forced The fi rst 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 modifi cation. Such initially speculated that these were of orbito- vocalizations may be non-verbal (e.g. groaning,

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’ http://pn.bmj.com/ 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 on October 1, 2021 by guest. Protected copyright. discharge, which manifests clinically as a ‘frontal 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 nature 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 expression, with a longer duration and/or the presence of associated features such as automatisms. The ‘atypical absences’ of the Lennox–Gastaut syndrome could be included in this category. As in other seizure types, propagation patterns affect the clinical manifestations of the seizure. When there is posterior spread towards

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 classifi cation 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 identifi cation 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 diffi culties 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 refl ect 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 identifi ed. 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 confi dent 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 11 MRI with expert review, and others with dual highlighted the potential importance of [ C] http://pn.bmj.com/ or multifocal pathology. Moreover, even when a fl umazenil 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) on October 1, 2021 by guest. Protected copyright. Coronal FLAIR, (c) Axial T2. a b c

sensitivity and speciﬁ city in detecting metabolic abnormalities than 2-[11F] ﬂ uoro-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-electroencephalography (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 promising (Gavaret et al. 2004) (Fig. 8).

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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 ﬁ gure 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.

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- REFERENCES rior and dorso-ventral gradients. Archibald SJ, Mateer CA & Kerns KA (2001) Utilization • There can be few treatments for chronic Behaviour. Clinical Manifestations and Neurological disease with the potential to make as huge Mechanisms. Neuropsychology Review, 11, 177–30. Bancaud J & Talairach J (1992) Clinical Semiology of an impact on an individual’s quality of life Frontal Lobe Seizures. Advances in Neurology, 57, as curative epilepsy surgery. This treat- 3–59. ment has the potential to transform a Barkley GL & Baumgartner C (2003) MEG and EEG young person’s life from one with intrac- in epilepsy. Journal of Clinical Neurophysiology, 20, table seizures and the inevitably associated 163–78. risks of increased mortality, social disad- Bartolomei F & Chauvel P (2000) Seizure symptoms and cerebral localization. frontal lobe and rolandic vantage and psychological vulnerability,

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