General

In addition to the TL, the regions involved in the EZ of TPE include the orbitofrontal cortex, insula, frontal and parietal operculum and temporo-parieto-occipital junction (Figure 2). ^{Reference Kahane, Isnard and Guénot4,Reference Barba, Barbati, Minotti, Hoffmann and Kahane8–Reference Barba, Rheims and Minotti10,Reference Barba, Minotti, Job and Kahane16,Reference Barba and Lenge17} Three tentative TPE subgroups have been described (Table 1): temporo-frontal, temporo-perisylvian (includes insula) and temporo-parietal-occipital; however, their EZs and therefore their electro-clinical features may overlap, ^{Reference Barba, Barbati, Minotti, Hoffmann and Kahane8–Reference Barba, Rheims and Minotti10,Reference Barba, Minotti, Job and Kahane16,Reference Barba and Lenge17} and EZs can be considered to be patient-specific. The overlap is exemplified by some of the cases in the series of Sarkis et al., Serletis et al. and Kogias et al. ^{Reference Sarkis, Jehi, Najm, Kotagal and Bingaman5–Reference Kogias, Bast and Schubert-Bast7}

Figure 2.

(Reproduced from Barba et al. 2016; reference # 10).*Brain regions involved in the epileptogenic zone of temporal plus epilepsy. Temporal lobe: blue; orbitofrontal cortex: violet; suprasylvian operculum: brown; insula (hidden within the lateral sulcus; hence shown in the inset figure): red; temporo-parieto-occipital junction: green. Percentages refer to the percentage of patients with involvement of the respective brain regions in the study of Barba et al. (2016); please see reference # 10 for further details. *Figure reproduced in accordance with a University of Saskatchewan library license agreement with Oxford University Press (https://library.usask.ca/copyright/authors-and-creators/re-using-figures.php).

Figure 2 Long description

The diagram illustrates various brain regions involved in the epileptogenic zone of temporal plus epilepsy. The temporal lobe is highlighted in blue, the orbitofrontal cortex in violet, the suprasylvian operculum in brown, the insula in red, and the temporo-parieto-occipital junction in green. Percentages indicate the involvement of each region in patients, with the temporal lobe at one hundred percent, the orbitofrontal cortex at one point two percent, the suprasylvian operculum at two point four percent, the insula at four point two percent, and the temporo-parieto-occipital junction at three percent. An inset figure shows a detailed view of the insula.

Table 1.

Seizure semiology and scalp video-EEG in temporal plus epilepsy (TPE) subgroups

Table 1 Long description

The table compares key features of temporo-frontal, temporo-perisylvian/insula, and temporo-parieto-occipital subgroups of TPE. It has five columns: Key features, Temporo-frontal, Temporo-perisylvian/insula, and Temporo-parieto-occipital. The rows detail various aspects such as onset, aura, impaired awareness, motor, autonomic, duration, and scalp V-EEG. For instance, the onset for temporo-frontal is often in sleep and in clusters, while for temporo-perisylvian/insula, it is often in sleep and may be reflex induced. The temporo-parieto-occipital subgroup has no data for onset. The aura for temporo-frontal includes none or nonspecific sensations, while temporo-perisylvian/insula includes gustatory, nausea, throat/laryngeal constriction, breathlessness, orofacial paresthesia, and painful paresthesia. The temporo-parieto-occipital subgroup includes vestibular, example rotation, vertigo, auditory, visual, and somatosensory auras. Impaired awareness involves focal seizures with and without impaired awareness for both temporo-frontal and temporo-parieto-occipital subgroups, while temporo-perisylvian/insula involves focal seizures with impaired awareness. Motor features for temporo-frontal include hypermotor seizures, complex motor behaviors, and focal to bilateral tonic-clonic seizures. Temporo-perisylvian/insula includes facial or faciobrachial jerks with or without focal and/or bilateral generalized tonic-clonic seizures. There is no data for motor features in the temporo-parieto-occipital subgroup. Autonomic features for temporo-frontal include urinary urge and possible changes in heart rate/respiratory rhythm. Temporo-perisylvian/insula includes hypersalivation, nausea, facial blush, sweaty hands, piloerection, changes in heart rate/respiratory rhythms, and urinary urge. Autonomic features are uncommon in the temporo-parieto-occipital subgroup. Duration is relatively short for temporo-frontal, variable for temporo-perisylvian/insula, and no data for temporo-parieto-occipital. Scalp V-EEG for temporo-frontal includes ipsilateral frontal abnormalities, for temporo-perisylvian/insula includes ipsilateral temporal, temporo-frontal temporo-central, fronto-central interictal or ictal abnormalities rapidly spreading to the other side, and for temporo-parieto-occipital includes ipsilateral temporo-parietal interictal or ictal abnormalities.

V-EEG = video-electroencephalography; TPE = temporal plus epilepsy. Information from references 8, 11,14, 16–18. *No data: there was no information about these features in the references; **limited information. Please note: the distinctions between the subgroups are likely to be imprecise in clinical practice, reflecting inter-patient variations in the epileptogenic zones.

Seizure semiology

Children and the cognitively impaired may not be able to describe an aura or the onset. Both focal aware and impaired awareness seizures have been reported. ^{Reference Bottan, Suller Marti and Parrent11,Reference Khoja, Albaradei and Alsulami14} The features described in the Table 1 should be considered as “red flags,” their sensitivity and specificity being unknown. ^{Reference Kahane, Barba, Rheims, Job-Chapron, Minotti and Ryvlin9} Another potential “red flag” may be the occurrence of two distinct seizures types, one with features of TL origin and the other suggesting origin in an adjacent lobe (e.g., cases 1 and 5 in Bottan et al.). ^{Reference Bottan, Suller Marti and Parrent11} Postictally, dysphoria may be more common in TPE patients than in those with just TL involvement. ^{Reference Barba, Barbati, Minotti, Hoffmann and Kahane8,Reference Kahane, Barba, Rheims, Job-Chapron, Minotti and Ryvlin9}

The involvement of the insula-orbito-frontal or frontal-opercular regions in TPE may be associated with ictal changes in cardiac and respiratory rhythms and risk of unexpected death. ^{Reference Barba, Minotti, Job and Kahane16,Reference Barba, Rheims and Minotti18}

Scalp (video-) electroencephalographic features

Inter-ictal and ictal findings depend on the region(s) involved in the EZ (Table 1). ^{Reference Barba, Barbati, Minotti, Hoffmann and Kahane8,Reference Kahane, Barba, Rheims, Job-Chapron, Minotti and Ryvlin9,Reference Bottan, Suller Marti and Parrent11,Reference Khoja, Albaradei and Alsulami14,Reference Barba, Minotti, Job and Kahane16,Reference Barba and Lenge17} Ictally, scalp EEG may suggest lateral temporal or extratemporal onset or early extratemporal spread. ^{Reference Ryvlin and Kahane19}

Neuroimaging

Brain MRI may be unremarkable in TPE but can show hippocampal sclerosis (HS), ^{Reference Barba, Barbati, Minotti, Hoffmann and Kahane8–Reference Bottan, Suller Marti and Parrent11} focal cortical dysplasia (FCD), ^{Reference Martire, Wong and Workewych13,Reference Tsuboyama, Harini, Liu, Zhang and Bolton15,Reference Garganis, Kokkinos, Zountsas, Dinopoulos, Coras and Blümcke20} etc. Malformations of cortical development are particularly important associations in children. ^{Reference Martire, Wong and Workewych13,Reference Tsuboyama, Harini, Liu, Zhang and Bolton15,Reference Garganis, Kokkinos, Zountsas, Dinopoulos, Coras and Blümcke20,Reference Najm, Lal and Alonso Vanegas21}

Techniques such as 3-D MP-RAGE (Magnetization Prepared Rapid Gradient Echo) may help to differentiate between TPE and TLE. ^{Reference Yin, Yan and Gao22}

Positron emission tomography (PET) and other noninvasive investigations

In one study using PET, patients with TPE showed ipsilateral hypometabolism involving temporal and adjacent extratemporal structures. ^{Reference Guedj, Bonini and Gavaret23} Sample sizes were inadequate to compare findings in patients with TPE with those who had mesial TLE (MTLE), neocortical TLE (NTLE) and bilateral TLE. ^{Reference Guedj, Bonini and Gavaret23}

In addition to video-EEG, MRI and PET, the evaluation of pharmacoresistant TPE (and other multilobar epilepsies) has included (in various combinations) the Wada test, functional MRI (fMRI), interictal and ictal single photon emission computed tomography (SPECT), subtraction ictal SPECT co-registered to MRI and MEG. ^{Reference Serletis, Bulacio, Alexopoulos, Najm, Bingaman and González-Martínez6,Reference Kogias, Bast and Schubert-Bast7,Reference Barba, Rheims and Minotti10–Reference Khoja, Albaradei and Alsulami14}

Currently, the information on simultaneous EEG and fMRI (EEG-fMRI) is insufficient to opine on its role in the diagnosis and management of multilobar epilepsies. ^{Reference Ikemoto, von Ellenrieder and Gotman24} On the basis of a single post hoc case report, Gong et al. suggested that multimodal and neurophysiological integration might be useful in the presurgical evaluation of patients with pharmacoresistant epilepsy. ^{Reference Gong, Bickel and Tostaeva25}

Neuropsychological testing and findings

Predominant dysfunction in aspects other than memory should raise suspicion for temporal neocortical or extratemporal involvement; fMRI may provide complementary information in TPE and other multilobar epilepsies. Multilobar epilepsies in children are associated with a high probability of cognitive impairment. ^{Reference Moorhouse, Cornell and Gerstl26}

Intracranial electroencephalography (IEEG)

IEEG can complement noninvasive evaluation in TPE and other multilobar epilepsies when surgical treatment is a consideration. ^{Reference Jayakar, Gotman and Harvey27} In this situation, the individual patient-specific objectives include (1) differentiating between unifocal, lobar and multilobar epilepsies, especially when noninvasive data are ambiguous, (2) mapping the extent of the EZ and (3) delineating eloquent cortex. ^{Reference Jayakar, Gotman and Harvey27} Further details on IEEG are beyond the scope of this communication.

TPE and mesial temporal lobe epilepsy (MTLE)

Unrecognized TPE is an important cause of failures of standard anterior temporal lobectomy in MTLE. ^{Reference Kahane, Isnard and Guénot4,Reference Barba, Rheims and Minotti10} Clinical and scalp EEG features in TPE and MTLE may be similar, with seizures arising from juxtatemporal regions mimicking those arising from mesial temporal structures. ^{Reference Kahane, Barba, Rheims, Job-Chapron, Minotti and Ryvlin9,Reference Bottan, Suller Marti and Parrent11} Additionally, HS can be associated with both TPE and MTLE. ^{Reference Barba, Barbati, Minotti, Hoffmann and Kahane8–Reference Bottan, Suller Marti and Parrent11} Since the TL is always involved in the EZ of TPE, it is not surprising that TPE can mimic TLE, explaining why preoperatively unrecognized TPE is an important cause of TLE surgery failures. ^{Reference Wirrell, Nabbout and Scheffer2–Reference Sarkis, Jehi, Najm, Kotagal and Bingaman5,Reference Kahane, Barba, Rheims, Job-Chapron, Minotti and Ryvlin9,Reference Barba, Rheims and Minotti10} These observations lead to two inter-linked conclusions: (1) MTLS-HS may not be as specific an electro-clinical epilepsy syndrome as implied in the current ILAE classification, ^{Reference Wirrell, Nabbout and Scheffer2,Reference Riney, Bogacz and Somerville28} and (2) TPE must always be considered in the differential diagnosis of MTLE with or without HS. IEEG is often necessary to distinguish TPE from MTLE, especially when noninvasive data are inconclusive. ^{Reference Bottan, Suller Marti and Parrent11,Reference Jayakar, Gotman and Harvey27}

Other multilobar epilepsies

Multilobar epilepsies other than TPE include (1) “orbitofrontal plus temporal polar” epilepsy ^{Reference Serletis, Bulacio, Alexopoulos, Najm, Bingaman and González-Martínez6} and the less well characterized “frontal plus epilepsy”; ^{Reference Rasmussen3} both may overlap with the temporo-frontal subgroup of TPE, and (2) “occipital plus” and “posterior cortex” epilepsies, ^{Reference Sarkis, Jehi, Najm, Kotagal and Bingaman5,Reference Jacobs29} which may overlap with the temporo-parieto-occipital subgroup of TPE. Their onset is often in childhood. ^{Reference Sarkis, Jehi, Najm, Kotagal and Bingaman5,Reference Serletis, Bulacio, Alexopoulos, Najm, Bingaman and González-Martínez6,Reference Jacobs29}

Serletis et al. emphasized the importance of differentiating between “orbitofrontal plus frontal” (a “lobar” epilepsy) and “orbitofrontal plus temporal polar” epilepsy (a “multilobar” epilepsy); in their series, the former responded to tailored frontal lobar excision and the latter to tailored multilobar orbitofrontal and temporal polar resection. ^{Reference Serletis, Bulacio, Alexopoulos, Najm, Bingaman and González-Martínez6}

Etiologies

MRI and post-surgery specimens have shown the following associations with TPE and other multilobar epilepsies: HS, gliosis, cavernous angioma, abnormalities of cortical development including mild malformations of cortical development with oligodendroglial hyperplasia (MOGHE) tubers, perinatal and postnatal ischemic lesions, benign tumors, Sturge–Weber syndrome, etc. ^{Reference Sarkis, Jehi, Najm, Kotagal and Bingaman5–Reference Kogias, Bast and Schubert-Bast7,Reference Bottan, Suller Marti and Parrent11,Reference Tsuboyama, Harini, Liu, Zhang and Bolton15,,Reference Garganis, Kokkinos, Zountsas, Dinopoulos, Coras and Blümcke20,Reference Najm, Lal and Alonso Vanegas21,Reference Riney, Bogacz and Somerville28–Reference Sugano, Iimura and Suzuki30} Early childhood onset is frequently associated with FCDs. ^{Reference Sarkis, Jehi, Najm, Kotagal and Bingaman5–Reference Kogias, Bast and Schubert-Bast7,Reference Bottan, Suller Marti and Parrent11–Reference Tsuboyama, Harini, Liu, Zhang and Bolton15,Reference Garganis, Kokkinos, Zountsas, Dinopoulos, Coras and Blümcke20,Reference Najm, Lal and Alonso Vanegas21,Reference Jacobs29}

Gene defects and multilobar epilepsies

Multilobar epilepsies, including TPE, have been reported with mild malformations of cortical development and oligodendroglial hyperplasia in epilepsy (MOGHE) linked with brain somatic SLC35A2 mutations. ^{Reference Najm, Lal and Alonso Vanegas21,Reference Barba, Blumcke and Winawer31} Temporo-parietal-occipital epilepsy occurred in a family with genetic epilepsy febrile seizures plus syndrome (GEFS+) associated with SCN1A mutation. ^{Reference Riva, Coppola and Balagura32}