Epilepsy is highly prevalent and notoriously pharmacoresistant. New therapeutic interventions are urgently needed, both for preventing the seizures themselves as well as negative outcomes and comorbidities associated with chronic epilepsy. While the cerebellum is not traditionally associated with epilepsy or seizures, research over the past decade has outlined the cerebellum as a brain region that is uniquely suited for both therapeutic needs. This review discusses our current understanding of the cerebellum as a key node within seizure networks, capable of both attenuating seizures in several animal models, and conversely, prone to altered structure and function in chronic epilepsy. Critical next steps are to advance therapeutic modulation of the cerebellum more towards translation, and to provide a more comprehensive characterization of how the cerebellum is impacted by chronic epilepsy, in order to subvert negative outcomes.

Status epilepticus (SE) is a life-threatening emergency that can result in de novo development or worsening of epilepsy. We tested the hypothesis that the aberrant cortical output during neocortical focal status epilepticus (FSE) would induce structural and functional changes in the thalamus that might contribute to hyperexcitability in the thalamocortical circuit. We induced neocortical FSE by unilateral epidural application of convulsant drugs to the somatosensory cortex of anesthetized mice of both sexes. The resulting focal EEG ictal episodes were associated with behavioral seizures consisting of contralateral focal myoclonic activity and persisted for 2-3 h. Ten and 30 days later, brains were processed for either immunohistochemistry (IHC) or in vitro slice recordings. Sections from the center of the thalamic reticular nucleus (nRT, see methods), the ventral posterolateral nucleus (VPL), and the ventral posteromedial nucleus (VPM) from the ventrobasal nucleus (VB) were used to measure density of NeuN-immunoreactive neurons, GFAP-reactive astrocytes, and colocalized areas for VGLUT1 + PSD95- and VGLUT2 + PSD95-IR, presumptive excitatory synapses of cortical and thalamic origins. Whole-cell voltage-clamp recordings were used to measure spontaneous EPSC frequency in these nuclei. We found that the nRT showed no decrease in numbers of neurons or evidence of reactive astrogliosis. In contrast, there were increases in GFAP-IR and decreased neuronal counts of NeuN positive cells in VB. Dual IHC for VGLUT1-PSD95 and VGLUT2-PSD95 in VB showed increased numbers of excitatory synapses, likely of both thalamic and cortical origins. The frequency, but not the amplitude of sEPSCs was increased in nRT and VB neurons. SIGNIFICANCE STATEMENT: Previous reports have shown that prolonged neocortical seizures can induce injury to downstream targets that might contribute to long-term consequences of FSE. Effects of FSE in thalamic structures may disrupt normal thalamo-cortical network functions and contribute to behavioral abnormalities and post-SE epileptogenesis. Our results show that a single episode of focal neocortical SE in vivo has chronic consequences including cell loss in VB nuclei and increased excitatory connectivity in intra-thalamic and cortico-thalamic networks. Additional experiments will assess the functional consequences of these alterations and approaches to mitigate cell loss and alterations in synaptic connectivity.

In the study of epilepsy, the term semiology is used to comprise the clinical characteristics of a seizure, both subjective symptoms and objective phenomena. It is produced by activation of the symptomagenic zone, and an accurate and comprehensive understanding of the localizing value of seizure semiology is crucial for presurgical evaluation and planning. Myriad publications in epilepsy journals detail correlations between various semiological features and activation of specific cortical regions. Traditionally these studies involved scalp EEG recorded in epilepsy monitoring units. The increasing use of invasive monitoring, and specifically the use of depth electrodes and stereo-electroencephalography, has advanced our understanding of the characteristics of seizures arising from ictal foci deep to the scalp, including the cingulate, insula and operculum. However, the distinction between seizure onset and symptomogenic zones is not always clear. In 2017 the International League Against Epilepsy (ILAE) published an operational classification of seizure types based heavily on seizure semiology. The current paper provides an updated review of the current body of knowledge relating to seizure semiology, incorporating both scalp EEG studies and more recent stereo-electroencephalography discoveries in the framework of the 2017 ILAE classification.

Epilepsy is the fourth most common neurological disorder, but current treatment options provide limited efficacy and carry the potential for problematic adverse effects. There is an immense need to develop new therapeutic interventions in epilepsy, and targeting areas outside the seizure focus for neuromodulation has shown therapeutic value. While not traditionally associated with epilepsy, anatomical, clinical, and electrophysiological studies suggest the cerebellum can play a role in seizure networks, and importantly, may be a potential therapeutic target for seizure control. However, previous interventions targeting the cerebellum in both preclinical and clinical studies have produced mixed effects on seizures. These inconsistent results may be due in part to the lack of specificity inherent with open-loop electrical stimulation interventions. More recent studies, using more targeted closed-loop optogenetic approaches, suggest the possibility of robust seizure inhibition via cerebellar modulation for a range of seizure types. Therefore, while the mechanisms of cerebellar inhibition of seizures have yet to be fully elucidated, the cerebellum should be thoroughly revisited as a potential target for therapeutic intervention in epilepsy. This article is part of the Special Issue "NEWroscience 2018.

The role of the Rolandic operculum in in mesial temporal lobe epilepsy (MTLE) is to produce oroalimentary automatisms (OAAs). In insulo-opercular epilepsy (IOE), the Rolandic operculum may produce perioral muscle clonic or tonic movements or contractions. This paper aims to confirm the symptomatogenic zone of facial symptoms in IOE and to explain this phenomenon.

A total of 45 IOE patients and 15 MTLE patients were analyzed. The patients with IOE were divided into facial (+) and (-) groups according to the facial symptoms. The interictal positron emission tomography (PET) data were compared among groups. Furthermore, electroclinical correlation, functional connectivity and energy ratio (ER) were analyzed with stereo-electroencephalography (SEEG).

Intergroup PET differences were observed mainly in the Rolandic operculum. Electroclinical correlation showed that the Rolandic operculum was the only brain area showing any correlations. Compared with the facial (-) group, the facial (+) group showed stronger functional connectivity and a higher ER in the alpha 1, alpha 2 and beta sub-bands. In the Rolandic operculum, compared with those of the MTLE group, the h² and ER of the facial (+) group were higher in the high frequency sub-bands. Intergroup comparison of the ER in the seizure onset zones (SOZ) showed no significant difference.

The symptomatogenic zone of facial symptoms in IOE is the Rolandic operculum. Seizure propagation to the Rolandic operculum generates different semiologies because of the different synchronization frequencies and energies of the sub-bands depending on the site of seizure origin. This may be due to the complex spreading pathway from the SOZ to the symptomatogenic zone.

The non-invasive localisation of insular lobe epilepsy is a challenge. We aimed to determine if ictal SPECT is a reliable adjunctive test in insular cases and to explore its role in the tailoring of intracranial strategies.

From a dataset of patients who underwent SEEG between December 2012 and December 2016, we collected patients with focal insular onset epilepsy. We examined semiology, EEG, PET and SPECT hyperperfusion pattern with SISCOM. We also reviewed relevant literature.

5 patients were identified, 4 females, from a dataset of 51 patients. Median age of seizure onset was 8 years old (8 months to 10 years). All patients had an ictal SPECT during pre-surgical work-up: median injection time was 7 s (3-17 sec) from clinical onset, and median seizure duration was 42 s (11-85 sec). Insula cortex showed focal hyperaemia in four patients, all bilateral, with the greatest hyperperfusion contralateral to the ictal onset in two cases, using SISCOM threshold at 1.5 standard deviation. Other sites with hyperaemia included basal ganglia and middle temporal gyrus. The SEEG confirmed insular onset seizures in all the cases. All patients had epilepsy surgery and were seizure free at 21 to 50 months follow up. The results from the literature review showed frequent hyperperfusion in structures outside insula and frequently over the contralateral hemisphere.

This study highlights the technical limitations of SPECT when attempting to assess seizures arising from the insula. Our findings and the literature show ictal SPECT can be localising but falsely lateralising in seizures arising from the insula.

To retrospectively reappraise characteristics of the electro-clinical seizure semiology of the bilateral asymmetric tonic seizure (BATS) in the patients with supplementary sensorimotor area (SSMA) epilepsy.

From the retrospective analysis of the pre- and post-operative Magnetic Resonance Imaging (MRI) data involving 386 patients who received epilepsy surgery, 123 BATS were identified meeting the clinical criteria and included in the study. For comparison in four extremities involvement, limbs were paired and comparatively evaluated between the contralateral and ipsilateral sides, proximal and distal segments, and upper and lower limbs. For evaluation of sequential events, each tonic phase of the BATS was chronologically divided into 10 equal epochs. In each epoch, distribution of tonic events in 4 extremities and axes was visually evaluated and comparatively analyzed.

Asymmetric tonic posturing was the most constant findings in 6 patients, whose upper limbs contralateral to epileptogenic cortex were kept in abduction in all 123 (100%) seizures and extension in 118 (95.9%) seizures. This type of asymmetry became visible and remained stable in the initial three epochs of the tonic phase in 107 out of 123 (87.0%) seizures. In each epoch, especially the initial one, the contralateral upper limbs were involved more frequently than those ipsilateral to the epileptogenic cortex (p < 0.05). By pairwise comparison, an earlier involvement of the contralateral side to epileptogenic cortex was visually observed in 53 out of 280 (18.9%) limb pairs, in which the ipsilateral limbs were preceded by the contralateral ones 4.6 (0.1-16.0) seconds earlier. Both of the proximal and distal segments were simultaneously involved in 260 out of 298 (87.2%) limb pairs, although the former were 4.3 (0.5-16.0) earlier than the latter in 34 out of 298 (11.4%) limb pairs.

This study demonstrated that by studying the restricted epileptogenic lesion limited to pure SSMA, unilateral extension and abduction posturing in upper limb were the most prominent and valuable sign for the lesion lateralization in SSMA neurosurgery decision-making.

In seizures with tonic posturing, differentiation of seizures originating in SSMA from seizures originating in cortices other than SSMA and spreading to SSMA has not been previously attempted. Twenty-two patients were studied with intractable focal epilepsy with tonic limb posturing as the most prominent semiology, who underwent resective surgery and obtained favorable postoperative seizure outcomes. These 22 patients were divided into an SSMA group (N = 12) and an extra-SSMA group (N = 10), according to the location of resection. Resection area in the extra-SSMA group was located in the dorsolateral frontal or prefrontal area in four patients, the frontal operculum (insula) in two, the parietal cortex in three, and the temporoparietal cortex in one patient. Video-recorded seizures were carefully reviewed. Tonic posturing characteristics and the presence or absence of accompanying symptoms were compared between groups. Incidence of preservation of consciousness was significantly higher in the SSMA group (p < 0.001). Patients in the SSMA group demonstrated a propensity for having unilateral or bilateral asymmetrical tonic limb posturing. In contrast, patients in the extra-SSMA group had a statistically significantly higher incidence of bilateral symmetrical tonic limb posturing (p < 0.05). These findings may be helpful in identifying seizure origin.

Sleep and epilepsy are two well recognized conditions that interact with each other in a complex bi-directional way. Some types of epilepsies have increased activity during sleep disturbing it; while sleep deprivation aggravates epilepsy due to decreased seizure threshold. Epilepsy can deteriorate the sleep-related disorders and at the same time; the parasomnias can worsen the epilepsy. The secretion of sleep-related hormones can also be affected by the occurrence of seizures and supplementation of epileptic patients with some of these sleep-related hormones may have a beneficial role in controlling epilepsy.

We used ictal single photon emission computed tomography (SPECT) to clarify the propagation pathways of epileptic discharges in patients with supplementary motor area (SMA) seizure.

In four patients (four males, age range, 18-27 years) with SMA seizures, SPECT studies by radioisotope 99mTc-ECD were performed as a preoperative evaluation. Two of the patients remained seizure-free after complete resection of the focal cortical dysplasia on magnetic resonance (MR) images including epileptic foci. In the other two patients, MR images were normal, but subdural electrode monitoring allowed for verifying the ictal onset in the left SMA. After partial resection of the SMA including epileptic foci, these patients experienced a significant (>90%) reduction of seizure frequency. Regional cerebral blood flow (rCBF) measurements obtained under ictal and interictal conditions were compared on a voxel-by-voxel basis by means of the SPM99 paired t-test option (uncorrected p<0.001).

Significant increases in rCBF under ictal conditions were identified in the bilateral anterior cingulate cortex (ACC), the globus pallidus ipsilateral to epileptic foci and the contralateral cerebellar hemisphere. The right ACC included a cluster with a submaximum in the right primary sensorimotor area.

In patients with SMA seizures, the hyperperfusion areas of ictal SPECT did not localize within the SMA but spread to the adjacent cortex such as the ACC and sensorimotor cortex ipsilateral to epileptic foci. Additionally, the epileptic discharges propagated to the remote areas such as the globus pallidus and cerebellum. We caution that ictal SPECT localization in patients with SMA seizures is not always concordant to epileptic focus but reveals already spread seizure activities.

Developmental venous anomalies (DVAs) are associated with epileptic seizures; however, the role of DVA in the epileptogenesis is still not established. Simultaneous interictal electroencephalogram/functional magnetic resonance imaging (EEG/fMRI) recordings provide supplementary information to electroclinical data about the epileptic generators, and thus aid in the differentiation of clinically equivocal epilepsy syndromes. The main objective of our study was to characterize the epileptic network in a patient with DVA and epilepsy by simultaneous EEG/fMRI recordings. A 17-year-old woman with recently emerging generalized tonic-clonic seizures, and atypical generalized discharges, was investigated using simultaneous EEG/fMRI at the university hospital. Previous high-resolution MRI showed no structural abnormalities, except a DVA in the right frontal operculum. Interictal EEG recordings showed atypical generalized discharges, corresponding to positive focal blood oxygen level dependent (BOLD) correlates in the right frontal operculum, a region drained by the DVA. Additionally, widespread cortical bilateral negative BOLD correlates in the frontal and parietal lobes were delineated, resembling a generalized epileptic network. The EEG/fMRI recordings support a right frontal lobe epilepsy, originating in the vicinity of the DVA, propagating rapidly to both frontal and parietal lobes, as expressed on the scalp EEG by secondary bilateral synchrony. The DVA may be causative of focal epilepsies in cases where no concomitant epileptogenic lesions can be detected. Advanced imaging techniques, such as simultaneous EEG/fMRI, may thus aid in the differentiation of clinically equivocal epilepsy syndromes.

To assess the predictive value of ictal single-photon emission computed tomography (SPECT) for outcome after excisional epilepsy surgery in a large population of children with focal cortical dysplasia (FCD).

One hundred seventy-three ictal SPECT studies in 106 children with histologically proven FCD were retrospectively analyzed. The extent and location of ictal hyperperfusion and completeness of surgical removal were assessed. Completeness of resection of epileptogenic regions defined by ictal SPECT, electroencephalography (EEG), and magnetic resonance imaging (MRI) were compared and correlated with postoperative seizure outcome. In addition, subcortical activation of the cerebellum, basal ganglia, and thalamus were analyzed.

The extent of hyperperfusion was focal or lobar in 58%, whereas multilobar activations occurred in only 32%; hemispheric or bilateral findings were rare. Favorable postsurgical seizure outcome was achieved in 67% patients with nonlocalized SPECT findings, 45% with nonresected ictal hyperperfusion, 36% with partially resected ictal hyperperfusion, and 86% when the zone of ictal hyperperfusion was completely resected (p = 0.000198). The favorable postsurgical outcome after complete removal of the SPECT hyperperfusion zone surpassed the 75% rate of seizure freedom in patients with removal of MRI/EEG-defined epileptogenic region. A similar predictive value of ictal SPECT for seizure outcome was found in nonoperated patients and subjects who were undergoing reoperation. Subcortical activation conferred no predictive value.

Ictal SPECT helps to define the epileptogenic zone in a high proportion of children with FCD undergoing surgical evaluation. Complete removal of both SPECT and MRI/EEG-defined regions is a strong predictor of surgical success and has important implications for surgical planning.

The aim of this study was to determine whether the occurrence of unilateral ictal limb dystonia (ID) during complex partial seizures (CPS) reduces the possibility of contralateral propagation (CP) and secondary generalization (SG) in patients with temporal lobe epilepsy (TLE). We assessed 216 seizures recorded in 33 patients with pharmacoresistant TLE. All patients underwent video-EEG telemetry prior to surgical treatment with good postoperative outcomes (Engel I). Ictal limb dystonia was observed in 16 of the 33 patients (48%) and 58 of the 216 seizures (26.8%). We found highly significant differences in the frequency of SG between seizures with ID and seizures without ID (2/58 vs. 41/158; 3.45% vs. 25.95%; p<0.001). Contralateral propagation was seen in 13 of the 57 analyzed seizures with ID compared to 85 of the 158 seizures without ID (22.8% vs. 53.8%; p<0.001). Among the CPS without SG, we found that the mean duration of seizures with ID was significantly longer than the duration of seizures without ID (81.66±40.10 vs. 68.88±25.01 s; p=0.011). Our findings that CP and SG occur less often in patients with ID, yet the duration of CPS without SG is longer in patients with ID, suggest that the basal ganglia might inhibit propagation to the contralateral hemisphere but not ictal activity within the unilateral epileptic network.

Epilepsy is the most common serious brain disorder in children, occurring in all parts of the world and within every stratum of the population. Through its effects, it exerts a significant physical, psychological, economic, and social toll on children and their caregivers. Historically, the surgical treatment of epilepsy has been viewed with skepticism with regard to its indications, safety, and therapeutic benefit. However, continued refinements in diagnostic and operative techniques are helping to put to rest the antiquated notion that surgery is a last-resort procedure in the management of pediatric epilepsy. Surgery can be performed safely, even in infants and young children, with excellent patient outcomes in properly selected patients. This review focuses on the surgical treatment of pediatric epilepsy. A brief background discussion of seizures and epilepsy is followed by a substantive discussion regarding the intricacies of selecting patients for epilepsy surgery, emphasizing the important role of advanced imaging techniques in the decision-making process. The indications and outcomes of the most common epilepsy surgical procedures are then reviewed. The article ends with a discussion of the future of epilepsy surgery.

To explore the diagnostic value of intracranial electrodes in highly suspected temporal lobe epilepsy (TLE) and the value of sphenoid electrodes (PG) and the propagation patterns of ictal discharges in focus lateralization.

Intracranial electrodes were implanted in 22 probable TLE patients through bilateral temporal burr holes. Extracranial electrodes included the 10-20 international EEG system and bilateral PGs. Intracranial and extracranial EEGs (IEEG, EEEG) were synchronously recorded. The interictal epileptic discharges (IEDs) were counted for 3h of interictal preoperative long-playing video EEG. Time intervals between electrodes recording the ictus and ictus occurring were measured and the propagation patterns were deduced.

By IEEG, 18 patients with confirmed TLE had surgery; 14 were seizure-free. 3 had FLE, and 1, uncertain localization. Of the 14 TLE and postoperative seizure-free patients, the ratio (left:right) of IEDs in the 3h interictal EEG was 483:211 in the 6 left TLE and 263:654 in the 8 right TLE. In 12 of the 14 cases, the side with more IEDs at PG was the epileptic focus side. In 11 of the 14 cases the earlier PG recording side was focus side. We found that the propagation sequence of ictus followed certain rules in most attacks.

The results indicated that IEEG was useful for final diagnosis of highly suspected TLE and that PG was helpful in focus lateralization. The propagation patterns of ictus might provide a new tool in focus lateralization and localization.

Although a nonspecific cephalic sensation, the so-called "cephalic aura," is a common sensory aura, particularly in frontal lobe seizures, but is rarely is the entire sensory seizure event. The unusual presentation of cephalic sensations in isolation representing supplementary motor area (SMA) seizures, which are commonly unaccompanied by ictal electroencephalography (EEG) changes, can easily lead to misdiagnosis of nonepileptic psychogenic seizures. We illustrate the case of a 36-year-old male patient with frontal lobe epilepsy who presented with isolated cephalic auras described as a nonvertiginous sense of head movement without observable clinical signs after his habitual partial motor seizures were controlled with pharmacotherapy. Video/EEG recordings showed no recognizable epileptic discharges time-locked to the onset of the isolated cephalic auras. Ictal magnetoencephalography (MEG) with synthetic aperture magnetometry-kurtosis (SAM(g(2))) analysis demonstrated the SMA onset of the cephalic auras; thus, MEG was essential in differentiating these isolated auras from nonepileptic psychogenic events.

Amygdala interconnections with the cingulate motor cortices were investigated in the rhesus monkey. Using multiple tracing approaches, we found a robust projection from the lateral basal nucleus of the amygdala to Layers II, IIIa, and V of the rostral cingulate motor cortex (M3). A smaller source of amygdala input arose from the accessory basal, cortical, and lateral nuclei, which targeted only the rostral region of M3. We also found a light projection from the lateral basal nucleus to the same layers of the caudal cingulate motor cortex (M4). Experiments examining this projection to cingulate somatotopy using combined neural tracing strategies and stereology to estimate the total number of terminal-like immunoreactive particles demonstrated that the amygdala projection terminates heavily in the face representation of M3 and moderately in its arm representation. Fewer terminal profiles were found in the leg representation of M3 and the face, arm, and leg representations of M4. Anterograde tracers placed directly into M3 and M4 revealed the amygdala connection to be reciprocal and documented corticofugal projections to the facial nucleus, surrounding pontine reticular formation, and spinal cord. Clinically, such pathways would be in a position to contribute to mediating movements in the face, neck, and upper extremity accompanying medial temporal lobe seizures that have historically characterized this syndrome. Alterations within or disruption of the amygdalo-cingulate projection to the rostral part of M3 may also have an adverse effect on facial expression in patients presenting with neurological or neuropsychiatric abnormalities of medial temporal lobe involvement. Finally, the prominent amygdala projection to the face region of M3 may significantly influence the outcome of higher-order facial expressions associated with social communication and emotional constructs such as fear, anger, happiness, and sadness.

Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery.

One hundred ninety-three neocortical epilepsy patients, including 91 without focal lesions on MRI, were included. Sixty-one had frontal lobe epilepsy (FLE), 80 had neocortical temporal lobe epilepsy (nTLE), 21 had parietal lobe epilepsy (PLE), and 22 had occipital lobe epilepsy (OLE). The primary outcome variable was patient status >or=2 years after surgery (i.e., seizure free or not). Clinical characteristics and the recent presurgical diagnostic modalities were considered as probable prognostic factors. Univariate and standard multiple logistic regression analyses were used to identify favorable prognostic factors.

The seizure-free rate was 57.5%. By univariate analysis, a focal lesion on MRI, localized ictal onset on surface EEG, epilepsies other than FLE, localized hypometabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET), and pathologies other than cortical dysplasia were significantly associated with a seizure-free outcome (p<0.05). Multivariate analysis revealed that a focal lesion on MRI (p=0.003), correct localization by FDG-PET (p=0.007), and localized ictal onset on EEG (p=0.01) were independent predictors of a good outcome.

The presence of a focal lesion on MRI, correct localized hypometabolism on FDG-PET, or localized ictal rhythms on EEG were identified as predictors of a seizure-free outcome. Our results suggest that these findings allow the selection of better candidates for neocortical epilepsy surgery.

2-[18F]Fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), ictal single-photon-emission computed tomography (ictal SPECT), and magnetoencephalography (MEG) represent three established functional imaging tests that offer unique information toward the localization of epilepsy for surgery evaluation and treatment. When these tests are combined with high-resolution magnetic fresonance imaging (MRI), epilepsy related structure and function disturbances may be localized with a degree of confidence and understanding not possible with electroencephalography (EEG), even ictal recordings with intracranial electrodes, the mainstay of tools for seizure localization. Use of these alternative tests allows an increased percentage of patients to be considered for surgical treatment. In particular, the additional information provided by these techniques has been demonstrated to help those patients with nonlocalizing MRI or extratemporal lobe epilepsy. Studies that address optimal use of these tests (alone and in combination) will build toward the next major advancement in the surgical treatment of epilepsy by allowing better patient selection, less risk, and better surgical outcomes. Ultimately, appropriate use of these tests, combined with more comprehensive functional brain mapping (e.g., with MEG or functional MRI), may lead to completely noninvasive epilepsy surgery evaluation.

Ictal single-photon emission computed tomography (SPECT) may help localize the seizure-onset zone (SOZ) by detecting changes in regional cerebral blood flow induced by epileptic discharges. This imaging method also reveals hyperperfusions in areas of seizure propagation, including the hemisphere contralateral to the SOZ. We have studied the occurrence, the topography, and the clinical value of such contralateral ictal hyperperfusion areas (HPAs).

We examined data from presurgical evaluations of 36 consecutive patients with pharmacoresistant partial epilepsy of various localizations. Ictal and interictal SPECT examinations were made with 99mTc-ECD, and the scans were processed for coregistration, normalization, subtraction, and merging with MRI images.

Contralateral HPAs were observed in 72% of the patients: 50% of mesiotemporal epilepsy cases with hippocampal sclerosis, 85.7% of the other mesiotemporal epilepsies, 85.7% of neocortical lateral temporal epilepsies, and 87.5% of extratemporal epilepsies. Contralateral HPAs were usually symmetrical to the SOZ, forming a mirror image, observed in 57.1% of the patients. They could be slightly asymmetrical in mesiotemporal epilepsies, perhaps because of the particular anatomic pathways linking temporal lobes. In neocortical epilepsies, they were located in the cortex homotopic to the SOZ.

We show that the symmetrical nature of the mirror image usually does not disturb SPECT interpretation. It can confirm the location of the SOZ (11 patients) and even occasionally improve the precision of its definition (nine patients) by restraining several potential SOZ-related HPAs to a single one or by permitting a restricted localization of the SOZ in a large HPA.

Surgical treatment of cryptogenic neocortical epilepsy is challenging. The aim of this study was to evaluate surgical outcomes and to identify possible prognostic factors including the results of various diagnostic tools. Eighty-nine patients with neocortical epilepsy with normal magnetic resonance imaging (35 patients with frontal lobe epilepsy, 31 with neocortical temporal lobe epilepsy, 11 with occipital lobe epilepsy, 11 with parietal lobe epilepsy, and 1 with multifocal epilepsy) underwent invasive study and focal surgical resection. Patients were observed for at least 2 years after surgery. The localizing values of interictal electroencephalogram (EEG), ictal scalp EEG, interictal 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and subtraction ictal single-photon emission computed tomography were evaluated. Seventy-one patients (80.0%) had a good surgical outcome (Engel class 1-3); 42 patients were seizure free. Diagnostic sensitivities of interictal EEG, ictal scalp EEG, FDG-PET, and subtraction ictal single-photon emission computed tomography were 37.1%, 70.8%, 44.3%, and 41.1%, respectively. Localization by FDG-PET and interictal EEG was correlated with a seizure-free outcome. The localizing value of FDG-PET was greatest in neocortical temporal lobe epilepsy. The focalization of ictal onset and also ictal onset frequency in invasive studies were not related to surgical outcome. Concordance with two or more presurgical evaluations was significantly related to a seizure-free outcome.

Neuroimaging has important applications in the diagnosis and treatment of patients with seizures and epilepsy. Having replaced computed tomography (CT) in many situations, MRI is the preferred imaging technique for patients with epilepsy. Advances in radionuclide-based techniques such as single-photon emission CT/positron emission tomography and electromagnetic source imaging with magnetoencephalography are providing new insights into the pathophysiology of epilepsy. In addition, techniques such as magnetic resonance spectroscopy are beginning to impact treatment. In this review, I discuss how these techniques are used in clinical practice but more importantly, how imaging findings play an increasing role in neurotherapeutics.

We analyzed ictal motor symptoms in 10 patients diagnosed to have supplementary motor area (SMA) seizures based on ictal encephalographic (EEG) findings and ictal clinical semiology. Inclusion criteria were (1) EEG seizure pattern in the vertex for the scalp recording or in the area over and/or adjacent to SMA for epicortical recording and (2) ictal motor semiology characterized, as previously reported, by sudden and a brief tonic posturing of extremities and trunk mainly occurring during sleep without loss of consciousness. In 50% (5/10) of the patients, tonic posturing began in one part of the body and moved to other part(s) in 5-10s. Unlike Jacksonian march seen in seizures involving the primary sensorimotor area (S1-M1), it spread in no accordance with the somatotopy in S1-M1. The sequential propagation of tonic posturing may represent the somatotopic organization within the SMA proper.

In this study, we evaluate the diagnostic and localizing value of SPECT in three patients with nonconvulsive status epilepticus (NCSE). Our results indicate that ictal/subtraction ictal SPECT is a useful complementary noninvasive diagnostic test in patients with focal NCSE. This is especially the case when the EEG findings are inconclusive and for patients in whom surgical treatment is being considered.

Parietal lobe epilepsy (PLE) is neither common nor easily diagnosed because of its variable clinical features. To elucidate its characteristics and surgical outcome, the authors reviewed their surgical experiences.

Between September 1994 and August 2001, 38 patients with PLE received surgical treatment at the Seoul National University Hospital. All patients underwent resection, mainly involving the parietal lobe.

Preoperatively, over 60% of the cases were not considered to be PLE, even though PLE was the most common diagnosis (15/38, 39.8%). An invasive study was performed in 37 of the 38 patients. Awake operations under regional anesthesia were performed in 20 patients (52.6%). Seizure disappeared in 15 (Engel's classification I, 39.5%), and rare seizure remained in 5 (Engel II, 13.2%). Thirteen patients showed a worthwhile improvement (Engel III, 34.2%), whereas 5 exhibited no worthwhile improvement (Engel IV, 13.2%). Pathologies were diverse, the most common being cortical dysplasia (94.3%).

Since PLE is difficult to diagnose preoperatively, an invasive study covering the parietal lobe is mandatory, if PLE is suspected. Cortical dysplasia was the most common etiology, thus awake operation under regional anesthesia and intraoperative brain mapping is helpful during extensive resection in order to spare the eloquent cortex.

The goal of presurgical evaluation of intractable epilepsy is to identify epileptogenic regions in the brain. From our experience of 38 cases of resective epilepsy surgery from the last 3 years, ictal SPECT was considered the most sensitive at detecting focal changes relating to seizures compared to other neuroimaging modalities, such as MRI, FDG-PET, SPECT and MEG. At interictal state, on the other hand, FDG-PET was most sensitive, especially in cases with focal cortical dysplasia, which is often MRI-invisible. In dysplastic tumors, MRI showed the highest concordance rate to clinically verified epileptogenic regions. Activation studies using functional neuroimaging such as PET and fMRI is useful to evaluate brain functions at epileptogenic regions presurgically. The role of functional brain imaging in epilepsy surgery is considered to be: (i). case selection for resective surgery, (ii). case selection for invasive EEG monitoring, and (iii). navigation of electrode placement and cortical resection.

The aim of the investigation was to evaluate the ictal EEG in the putamen and the temporal and frontal lobes during contralateral ictal limb dystonia (ID). Ten epilepsy surgery candidates participated in the study. All of them were investigated using intracerebral and/or subdural electrodes. In four of the patients, the putamen was investigated with diagonal depth electrodes (patients 1-4), in six of the patients, both the temporal and frontal lobes were investigated (patients 5-10). All of the investigated contacts were located contralateral to the side of the ictal dystonia. All of the patients suffered from temporal lobe epilepsy (TLE); in patient 10, both temporal and frontal seizure types were recorded. A total of 20 complex partial seizures (CPS) were analysed. ID was never an early symptom in the course of CPS. Slow activity was recorded in the putamen in all 10 seizures of the four patients in whom the putamen was investigated (patients 1-4). In five of these seizures, there was a time-locked change in the ictal EEG in relation to the ID (slowing of activity in three seizures; acceleration in two seizures). At the time of the onset of ID, several cortical regions were involved in the ictal discharge, within both the contralateral temporal and frontal lobes. In all 10 seizures of the six patients in whom both the temporal and frontal lobes on the contralateral side were evaluated (patients 5-10), the ictal paroxysmal discharge was noted in both lobes (i.e. frontal and temporal) at the time of ID onset. We can conclude that ID is a late symptom in TLE. Widespread activation of the contralateral temporal and frontal lobes is needed for the appearance of ID; however, the critical region responsible for the genesis of ID was not revealed. Although there are some non-specific changes in the putamen contralateral to ID, the changes were never epileptic in type. The putamen probably collaborates in the genesis of ID, but it does not generate the epileptic discharge during its course.

Truly simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) were registered in curarized rats injected with convulsive doses of pentylenetetrazol (PTZ, 65 mg/kg, sc). Rigorous control of physiological parameters like body temperature and ventilation with control of blood gasses helped to avoid potential interference between systemic parameters, and central PTZ-induced blood oxygenation level-dependent (BOLD) changes. Simultaneous EEG/fMRI recordings demonstrated progressive epileptiform EEG discharges with concomitant BOLD changes, the latter gradually affecting most of the fore- and midbrain. Approximately 15 min after PTZ injection, the first BOLD contrast changes mainly occurred in neocortex, and coincided with the first minor EEG alterations. Most regions that displayed BOLD changes were regions with reportedly high GABA(A) receptor densities. Full-blown epileptiform discharges occurred on the EEG tracing, approximately 30 min after PTZ injection, and coincided with bilateral positive and/or negative BOLD contrast changes in cortical and subcortical regions. Behavioral observations demonstrated the first of several generalized clonic or clonic-tonic seizure episodes to occur also around this time. Approximately 90 min after injection, the electrographic paroxysms gradually decreased in amplitude and duration, whereas the BOLD signal changes still extended with alternating positive and negative traces, and spread to subcortical regions like caudate-putamen and globus pallidus.

Like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. Although the cortex is often emphasized as the site of seizure origin, accumulating evidence points to a crucial role for subcortical structures in behavioral manifestations, propagation, and, in some cases, initiation of epileptic seizures. Extensive previous studies have shown the importance of subcortical structures in animal seizure models, but corresponding human studies have been relatively few. We review the existing evidence supporting the importance of the thalamus, basal ganglia, hypothalamus, cerebellum, and brain stem in human epilepsy. We also propose a "network inhibition hypothesis" through which focal cortical seizures disrupt function in subcortical structures (such as the medial diencephalon and pontomesencephalic reticular formation), leading secondarily to widespread inhibition of nonseizing cortical regions, which may in turn be responsible for behavioral manifestations such as loss of consciousness during complex partial seizures.

The interictal and ictal EEG activity in the basal ganglia in patients with temporal lobe epilepsy were studied during invasive EEG monitoring.

Eight epilepsy surgery candidates, each with a proven mesiotemporal seizure-onset zone, participated in the study. We used two invasive EEG methods to determine the seizure-onset zone. In both methods, diagonal electrodes were targeted into the amygdalohippocampal complex via a frontal approach and were passed through the basal ganglia with several leads. We analyzed 16 partial epileptic seizures, four of which became secondarily generalized.

No epileptic interictal or ictal discharges were noticed in the basal ganglia. The interictal activity in the basal ganglia was a mixture of low-voltage beta activity and medium-voltage alpha-theta activity. When the ictal paroxysmal activity remained localized to the seizure-onset zone, the activity of the basal ganglia did not change. The spread of epileptic activity to other cortical structures was associated with the basal ganglia EEG slowing to a theta-delta range of 3-7 Hz. This slowing was dependent on the spread of ictal discharge within the ipsilateral temporal lobe (related to the investigated basal ganglia structures); alternatively, the slowing occurred in association with the regional spread of ictal activity from the mesiotemporal region to the temporal neocortex contralaterally to the investigated basal ganglia. Secondary generalization was associated with a further slowing of basal ganglia activity.

The basal ganglia do not generate specific epileptic EEG activity. Despite the absence of spikes, the basal ganglia participate in changing or reflect changes in the distribution of the ictal epileptic activity.

We report on a 26-year-old woman with subacute sclerosing panencephalitis (SSPE) who presented with frequent paroxysmal dystonic posturing. Electroencephalogram demonstrated generalized 5 to 10-second episodes of high-amplitude (150-300 microV) delta activity alternating with 10 to 20-second periods of theta activity (40-50 microV). The patient experienced episodes of dystonic posturing coinciding with the periods of delta activity. Ictal Tc-99m Ceretec SPECT demonstrated marked increased activity in the bilateral caudate (R>L). The frequency and amplitude of the episodes initially markedly improved after the addition of carbamazepine. We suggest that the movements seen in this case of SSPE may represent basal ganglia ictal activity.

We investigated whether ictal single photon emission computed tomography (SPECT) with 99Tcm-ethyl cysteinate dimer (ECD) could differentiate between temporal (TE) and extratemporal epilepsy (ETE) in 30 consecutive patients (n = 21 for TE, n = 9 for ETE), all of whom had excellent postoperative seizure control (class I according to Engel's classification). Ictal SPECT showed isolated temporal hyperperfusion in 90% (19 out of 21) of the TE patients and normal perfusion in two patients. All the ETE patients had ictal SPECT findings consistent with extratemporal seizure onset. The sensitivity of ictal ECD-SPECT for correct localization of the seizure onset zone was 80% in all patients, 86% in TE patients and 66% in ETE patients. Although ictal ECD-SPECT has a lower sensitivity in ETE than in TE, it can be used to clearly distinguish between TE and ETE. It provides non-invasive imaging information for use in further diagnostic and treatment strategies in patients with drug-resistant focal epilepsy.

To determine whether the clinical features of tonic seizures (TSZ) are useful for lateralization of epileptic syndromes and the differential diagnosis of focal epileptic syndromes.

From a group of 481 patients, 123 patients with TSZ (44 females; mean age, 22.9 years; mean age at onset, 7 years; mean duration of epilepsy, 16 years) were selected. A total of 1595 epileptic seizures, documented during videoelectroencephalographic monitoring, were analyzed. Patients who had had surgery for epilepsy previously were excluded. Seizures were classified using a semiological seizure classification. Epilepsy syndromes were classified using all test data (electroencephalography, magnetic resonance imaging, computed tomography, positron emission tomography, and single-photon emission tomography). Data were compared using chi2 analysis or the Fisher exact test.

More patients with TSZ had extratemporal than temporal lobe epilepsies (79% vs. 1.7%; p < 0.0001) among those with an epilepsy localized to one lobe (n = 306). In the 123 patients, TSZ were part of 170 different seizure evolutions. Seizure evolutions began with TSZ as the first seizure type more often in patients with frontal lobe epilepsy (FLE) compared with patients with parieto-occipital lobe epilepsy (POLE) (40% in POLE vs. 67% in FLE; p < 0.05). In contrast, TSZ in POLE were more likely to be preceded by auras (50% in POLE vs. 26% in FLE; p < 0.05). TSZ were bilateral in 129 (76%) and unilateral in 41 (24%) seizure evolutions. Unilateral TSZ correctly lateralized the epilepsy syndrome to the contralateral hemisphere.

Analysis of seizure semiology and evolution in patients with TSZ is helpful for differentiating between focal epilepsies of temporal, frontal, and parieto-occipital origin. Unilateral TSZ provide useful information for the lateralization of the epileptic syndrome.

The goal of this report is to demonstrate the utility of ictal brain single photon emission tomography (SPECT) in a 39-year-old man with complex partial seizures arising from the anterior cingulate gyrus. Seizures originating from the anterior cingulate gyrus are difficult to localize because they have variable ictal semiology, are usually brief, and have rapid cortical propagation.

Clinical neurologic examination, electroencephalography, extended video-electroencephalography with scalp and sphenoidal electrodes, magnetic resonance imaging, computed tomography, and ictal brain SPECT with Tc-99m HMPAO were performed to identify the seizure focus. The patient's regional cerebral blood flow (rCBF) findings were compared with those of eight normal controls, and changes in rCBF were assessed by comparing the patient's ictal scan with those of normal controls at rest by using statistical parametric mapping (SPM).

Clinical and neurologic evaluations failed to demonstrate the epileptogenic focus. Ictal rCBF brain SPECT showed a focal region of hyperperfusion in the anterior cingulate gyrus. By using SPM, the ictal blood flow increase in the right anterior cingulate gyrus (x, y, z, -6, 42, 24 mm) was found to be statistically significant when compared with normal controls (z score, 4.88, p < 0.001). Subdural EEG recordings with intracranial electrodes positioned over this location confirmed that the cingulate gyrus was the origin of the seizures, and surgical resection resulted in >90% seizure reduction.

We concluded that ictal brain SPECT localization in conjunction with subdural electrode confirmation is a useful test in the presurgical evaluation of difficult to localize cingulate epilepsy.

To report on the use of near-infrared spectroscopy (NIRS) to examine the changes in cerebral oxygenation in the periictal period in patients with seizures.

Cerebral hemoglobin oxygen availability was monitored continuously and noninvasively with NIRS in three patients (one in the pediatric intensive care unit (ICU) and two in epilepsy-monitoring units) in conjunction with continuous EEG monitoring. Ictal events were recorded and compared with the pre-, intra-, and postictal periods for cerebral oxygen availability, as defined by oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and the redox state of cytochrome oxidase (cytox).

Several important preliminary observations were made by using this technology. First, a preictal increase in cerebral oxygenation began between 1 and 2 h and >10 h before the ictal event. Second, despite adequate perfusion, based on an observed increased HbO2, reduction in cytox indicates a perfusion-metabolism mismatch during seizure activity. Third, continued seizure activity and even isolated ictal events were associated with decreased cerebral oxygen availability. Fourth, differences in cerebral oxygen availability were noted between different types of seizures (e.g., electrographic seizures were accompanied by rapid reductions in HbO2 and cerebral blood volume without reduction of cytox, whereas electroclinical seizures were characterized by marked increases in HbO2 with or without reduction of cytox).

In this preliminary report on the use of NIRS for patients with seizures, we believe that NIRS allows continuous and noninvasive monitoring of changes in cerebral oxygenation periictally, thereby permitting investigations into the pathophysiology of seizures and the exploration of the potential of cerebral oximetry as a tool for seizure localization.