Frontal lobe seizures: overview and update.

Frontal lobe seizures (FLS) are debilitating for patients, highly diverse and often challenging for clinicians to evaluate. Frontal lobe epilepsy is the second most common localization for focal epilepsy, and if pharmacoresistant, can be amenable to resective surgery. Detailed study of frontal seizure semiology in conjunction with careful anatomical and electrophysiological correlation based on intracerebral recording with stereoelectroencephalography (SEEG) has allowed demonstration that ictal motor semiology reflects a hierarchical rostro-caudal axis of frontal lobe functional organization, thus helping with presurgical localization. Main semiological features allowing distinction between different frontal sublobar regions include motor signs and emotional signs. Frontal lobe seizure semiology also represents a valuable source of in vivo human behavioral data from a neuroscientific perspective. Advances in defining underlying etiologies of FLE are likely to be crucial for appropriate selection and exploration of potential surgical candidates, which could improve upon current surgical outcomes. Future research on investigating the genetic basis of epilepsies and relation to structural substrate (e.g. focal cortical dysplasia) and seizure organization and expression, could permit a "genotype-phenotype" approach that could be complementary to anatomical electroclinical correlations in better defining the spectrum of FLS. This could help with optimizing patient selection and prognostication with regards to therapeutic choices.

Female verbal memory advantage in temporal, but not frontal lobe epilepsy.

Women show better performance than men on a range of episodic memory tasks. Evidence regarding a neuroanatomical localization of this effect remains ambiguous. It has been suggested that anterior temporal lobe structures are responsible for sex differences in verbal memory, yet temporal lobe epilepsy (TLE) and TLE surgery do not affect women's verbal memory advantage. Instead, frontal lobe regions may be relevant for female verbal memory superiority, i.e. by enabling more efficient encoding and retrieval strategies in women. The aim of the present study was to investigate whether women's verbal memory advantage can be found in patients with frontal lobe epilepsy (FLE), and how patients with FLE and those with TLE differ with regard to sex differences in verbal memory. Fifty patients with unilateral FLE (26 women, 24 men) were compared with 183 patients with unilateral TLE (90 women, 93 men) on both verbal learning and delayed memory. We found that women showed better verbal memory than men in the TLE group, but not in the FLE group. In addition, we found that patients with TLE showed worse verbal learning than those with FLE. Our findings support the idea that women's advantage in verbal memory may be related to frontal lobe function.

Posterior cingulate epilepsy: clinical and neurophysiological analysis.

OBJECTIVE: Posterior cingulate epilepsy (PCE) is misleading because the seizure onset is located in an anatomically deep and semiologically silent area. This type of epilepsy is rare and has not been well described yet. Knowledge of the characteristics of PCE is important for the interpretation of presurgical evaluation and better surgical strategy. The purpose of this study was to better characterise the clinical and neurophysiological features of PCE. METHODS: This retrospective analysis included seven intractable PCE patients. Six patients had postcingulate ictal onset identified by stereotactic EEG (SEEG) evaluations. One patient had a postcingulate tumour. We analysed clinical semiology, the scalp EEG/SEEG findings and cortico-cortical evoked potential (CCEP). RESULTS: The classifications of scalp EEG were various, including non-localisible, lateralised to the seizure onset side, regional parieto-occipital, regional frontocentral and regional temporal. Three of seven patients showed motor manifestations, including bilateral asymmetric tonic seizures and hypermotor seizures. In these patients, ictal activities spread to frontal (lateral premotor area, orbitofrontal cortex, supplementary motor area, anteior cingulate gyrus) and parietal (precuneus, posterior cingulate gyrus, inferior parietal lobule (IPL), postcentral gyrus) areas. Four patients showed dialeptic seizures or automotor seizures, with seizure spread to medial temporal or IPL areas. CCEP was performed in four patients, suggesting electrophysiological connections from the posterior cingulate gyrus to parietal, temporal, mesial occipital and mesial frontal areas. CONCLUSIONS: This study revealed that the network from the posterior cingulate gyrus and the semiology of PCE (motor manifestation vs dialeptic/automotor seizure) varies depending upon the seizure spread patterns.

Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies.

PURPOSE: Deep brain stimulation (DBS) of the thalamus is an emerging surgical option for people with medically refractory epilepsy that is not suitable for resective surgery, or in whom surgery has failed. Our main aim was to evaluate the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure control in generalized epilepsy and frontal lobe epilepsy with a two-center, single-blind, controlled trial. METHODS: Participants were adults with refractory generalized or frontal lobe epilepsy. Seizure diaries were kept by patients/carers prospectively from enrollment. The baseline preimplantation period was followed by a control period consisting of a blind stimulation-OFF phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month unblinded stimulation-ON phase. The control period was followed by an unblinded long-term extension phase with stimulation-ON in those patients in whom stimulation was thought to be effective. KEY FINDINGS: Eleven patients were recruited at King's College Hospital (London, United Kingdom United Kingdom) and at University Hospital La Princesa (Madrid, Spain). Among the five patients with frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, two patients with frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients with generalized epilepsy had >50% improvement in seizure frequency during the blind period. In the long-term extension phase, five of the six patients showed >50% improvement in the frequency of major seizures (one became seizure free, one had >99% improvement, and three had 60-95% reduction in seizure frequency). Among patients with generalized epilepsy, the DBS implantation itself appears to be effective, as two patients remained seizure free during 12 and 50 months with DBS OFF, and the remaining four had 50-91% improvement in the initial 3 months with DBS OFF. SIGNIFICANCE: DBS implantation and stimulation of the CMN appears to be a safe and efficacious treatment, particularly in patients with refractory generalized epilepsy. CMN stimulation was not as effective in frontal lobe epilepsy, which requires further studies. DBS of the CMN should be considered as a treatment option, particularly in patients with refractory generalized epilepsy syndromes.

Frontal lobe seizures.

BACKGROUND AND OBJECTIVE: Frontal lobe epilepsy is the second most common localization-related or focal epilepsy. Frontal lobe seizures are challenging to diagnose as the clinical manifestations are diverse due to the complexity and variability of the patterns of epileptic discharges, and the scalp electroencephalograph (EEG) can often be normal or misleading. This review focuses on the clinical and EEG features of seizures arising from the frontal lobe. REVIEW SUMMARY: The clinical manifestations in patients with frontal lobe epilepsy are varied. Frontal lobe seizures can be divided into perirolandic, supplementary sensorimotor area, dorsolateral, orbitofrontal, anterior frontopolar, opercular, and cingulate types. Seizures originating from the perirolandic and supplementary sensorimotor areas are clinically distinct, characterized by motor activity or asymmetric tonic posturing with preserved awareness. Seizures arising from dorsolateral, orbitofrontal, frontopolar, and cingulate areas are not as well characterized and have more variable clinical manifestations. Scalp EEG recording is sometimes helpful in localization but is usually normal or misleading in frontal lobe epilepsy. The treatment is similar to other localization-related or focal epilepsies. Medications are the first line of therapy, and surgery is considered for patients who fail to respond to medications. The surgical outcome in frontal lobe resections is less favorable than in anterior temporal lobectomies due to the challenge in locating the epileptogenic zone and the presence of functional areas (eloquent cortex) that can limit the resection. CONCLUSIONS: Frontal lobe seizures are characterized by diverse behavioral manifestations. Only a few well-described frontal lobe syndromes exist. The variety of clinical manifestations reflects both the varying sites of seizure origin and propagation routes that seizures may take. Although this review provides a framework for the understanding of these seizures, one should remain cautious in diagnosing seizure localization based on clinical or EEG description. Only a few patients have well-described syndromes and can be diagnosed with confidence. For most patients, new diagnostic methods and genetic testing may help improve our ability to diagnose and treat the conditions discussed in this study.

Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a familial partial epilepsy syndrome characterized by seizures suggesting a frontal lobe origin occurring predominantly during sleep. Up to a third of patients may have refractory seizures, with repeated episodes of status epilepticus, intellectual disability of variable degree and psychiatric disturbances. We report a patient with ADNFLE, refractory seizures and repeated episodes of life-threatening convulsive status epilepticus who underwent prolonged video-EEG monitoring and was implanted with a vagal nerve stimulator. At 3.5 years of follow-up, a decrease of more than 80% in seizure frequency was achieved, episodes of status were completely controlled and he displayed improved mood and alertness. Vagal nerve stimulation may be considered as therapy for patients with refractory epilepsies of genetic cause, as well as repeated status epilepticus.

Efficacy of and morbidity associated with stereoelectroencephalography using computerized tomography--or magnetic resonance imaging-guided electrode implantation.

OBJECT: The purpose of this paper was to define the general efficacy of and morbidity associated with stereoelectroencephalography using modem methods of imaging and to particularize the risks related to specific lobes of the brain. METHODS: All patients admitted to the Montreal Neurological Institute who had undergone either computerized tomography- or magnetic resonance imaging-guided electrode implantation by one surgeon (A.O.) were reviewed. The procedure was considered efficient if the obtained information was sufficient to make a decision either in support of or against surgery. Two hundred seventeen patients underwent 224 implantations with 3022 electrodes. Complications related to each lobe were as follows: temporal lobe, two abscesses (0.54%); frontal lobe, one abscess and three hematomas (1.4%); and occipital lobe, one hypointense lesion found 1 week after electrode explantation (2.6%). Significant risk factors associated with hematomas were implantation in the frontal lobe (p < 0.05) and the use of four or more implanted electrodes (p < 0.025). General complications included the following: 26 patients, psychiatric symptoms during monitoring; one patient, meningitis; four patients, scalp cellulitis; and two patients, hemiparesis during angiography in the early 1980s. One of these latter patients maintained a mild hemiparesis and represents the only case of permanent neurological sequela in the entire series. Data obtained during recordings supported an indication for surgery in 178 patients (79.5%), excluded a surgical option in 37 patients (16.5%), and were unsatisfactory in nine patients (4%). Thus, the overall efficacy as defined previously was 96%. CONCLUSIONS: Stereoelectroencephalography is an efficient procedure with low associated morbidity. Bilateral exploration of the temporal lobes has a morbidity rate of approximately 1%. A higher risk of hematomas occurs with the implantation of four or more electrodes in the frontal lobes.

Effect of chronic deep brain stimulation of the subthalamic nucleus for frontal lobe epilepsy: subtraction SPECT analysis.

OBJECTIVES: Experimental data and case reports of patients with intractable epilepsy treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) suggest a considerable anticonvulsant effect. However, no satisfactory mechanisms of action have yet been elucidated. We investigated the putative therapeutic mechanisms of DBS from cerebral perfusion changes as measured by subtracting the SPECT image of the pre-DBS period from that of the chronic post-DBS state. METHODS: Two patients who had previous resective surgery on their right frontal cortices with or without anterior callosotomy were selected for DBS of the STN. Both of them showed frequent bilateral asymmetric tonic seizures (left > right) with rare drop attacks, and 1 patient's seizure frequency was more than 15/month during the pre-DBS period. They had both taken more than four antiepileptic agents for more than 10 years. After video-EEG monitoring, the irritative zones of the brain were delineated. The regional cerebral blood flow (rCBF) changes between the two SPECT images (pre-DBS and post-DBS after at least 6 months) were analyzed by SPECT subtraction with the volumetric MRI coregistration method using Analyze 5.0 software. RESULTS: After chronic STN DBS (18 months, case 1; 6 months, case 2), both patients experienced markedly reduced seizure frequencies (86.7% reduction in patient 1, 88.6% in patient 2). In patient 1, the increased rCBF was observed in the right frontal areas (dorsolateral and inferior frontal area), which corresponded to the irritative zones as confirmed by previous EEG recording. Unexpectedly, there was definite hyperperfusion in the right superior and inferior temporal areas as well as rCBF increase in the right superior frontal area (SMA) in patient 2. CONCLUSIONS: We demonstrated that the cerebral perfusion increase in the irritative zones of epilepsy patients is associated with favorable seizure reduction after STN DBS in 2 cases of frontal lobe epilepsy. Although the exact mechanism remains unknown, our findings suggest that the perfusion changes after STN DBS in frontal lobe epilepsy patients are quite different from those in subjects with Parkinson's disease. Our preliminary data suggest the clinical relevance of subtraction SPECT imaging in assessing the postprocedural outcome as well as the characteristics of SPECT perfusion patterns in other epilepsy syndromes.

Frontal lobe epilepsy in childhood.

Frontal lobe epilepsy is poorly understood and often unrecognized by health care workers caring for children. We sought to better characterize frontal lobe epilepsy in childhood and help delineate this condition from other nonepileptic events. We reviewed pediatric patients admitted to the Comprehensive Epilepsy Program at the University of Alberta Hospitals with a proven diagnosis of frontal lobe epilepsy. Twenty-two patients, 13 males and 9 females, were studied. Age of onset was variable from 10 months to 16 years (mean 7.5 years). Seizures were brief (30 seconds to 2 minutes), stereotypic, nocturnal (17/21), and frequent (3-22/night). Clinical features included explosive onset, screaming, agitation, stiffening, kicking or bicycling of the legs, and incontinence. The diagnosis of frontal lobe epilepsy was not made in any child before referral. The referring diagnosis was sleep disturbance (10), psychiatric problems (6), or other seizure types (6). Interictal electroencephalogram was usually normal (18/21). Long-term video electroencephalographic monitoring demonstrated frontal (9) or bifrontal (13) epileptic discharges. Magnetic resonance imaging was normal in most patients (18/21). Seizure control was difficult, with only half (11/21) the patients being controlled on medication. Three intractable patients went on to epilepsy surgery and became seizure-free. Frontal lobe epilepsy in childhood is a distinct epilepsy syndrome with characteristic features. The seizures are brief, stereotypic, nocturnal, and frequent. Electroencephalogram and magnetic resonance imaging are usually normal. The condition is often misdiagnosed as a sleep disorder or psychiatric problem. Seizures are difficult to control but may respond to carbamazepine, valproic acid, or epilepsy surgery.

[Problems of diagnosis and treatment in frontal epilepsies]. / Problemas diagnósticos y tratamiento de las epilepsias frontales.

OBJECTIVE: In this paper we review the anatomy, clinical features, problems of diagnosis and alternative treatment of the frontal epilepsies. DEVELOPMENT: A knowledge of the functional anatomy of the frontal lobe, the largest in the brain, is essential to understanding the varied features of the epileptic seizures arising in it. Unlike seizures arising in the temporal lobe in which the anatomicoclinical correlation is clearer since the rhinencephalum and especially the amygdala are almost always involved, in frontal seizures it is very difficult to systematize the relationship between the clinical signs and the organization of the discharge since there is wide cortico subcortical propagation, both homolateral and contralateral. There are therefore various types of frontal seizures which we define from a clinical point of view. They are the ones causing the greatest problems of differential diagnosis with epileptic pseudo seizures. A continuous video EEG recording is often necessary to differentiate them. Resonance imaging has meant a major advance in making an aetiological diagnosis of this type of seizure. It can show cortical dysplasia, heterotopia and small tumours or vascular malformations which are not visualized by other means. We give a brief description of the newly discovered genetic frontal epilepsies. Finally we review the different types of treatment indicated for them. CONCLUSIONS: Between 20% and 30% of all partial epilepsies start in the frontal lobe, and they form 30% of all surgical operations. The correct diagnosis of frontal seizures is still a challenge for the neurosurgeon. Advances in neurophysiology, neuro radiology and genetics have been, and still are, very important in better understanding of the disorder.

Vagus nerve stimulation activates central nervous system structures in epileptic patients during PET H2(15)O blood flow imaging.

OBJECTIVE: To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS: We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS: The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS: VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Frontal and central lobe focal dysplasia: clinical, EEG and imaging features.

The authors studied 11 patients with developmental malformations and seizures originating from the frontal and central regions. Patients with centrally located seizures had primary involvement of the face or mouth; clonic activity involving the limb was also seen. Seizures among those with frontal lesions were primarily unilateral or bilateral tonic motor. Secondary generalized tonic-clonic seizures preceded by focal manifestations occurred infrequently in those with central localization, but were not rare in the frontal group. MRI revealed abnormalities in 10 patients, nine of whom underwent surgical resection with good results. Focal cortical dysplasia may be the underlying epileptogenic abnormality in young patients with clinical features suggestive of central or frontal cortical involvement.

Lateralizaçäo da área epileptogênica através de ressonância magnética na epilepsia do lobo temporal / Lateralization of the epileptogenic area by magnetic resonance imaging in temporal lobe epilepsy

Métodos especiais de MRI foram utilizados em 5 pacientes com epilepsia do lobo temporal refratários ao tratamento clínico, com a finalidade de localizar a área epileptogênica. Imagens coronais com espessura de 5mm foram obtidas da borda posterior do tronco cerebral até a base do lobo frontal, utilizando-se as sequências "Inversión Recovery T1" (TR=2500 msec, TE=26 msec, T1=600 msec) para avaliar perda de estrutura interna e atrofia do hipocampo e morfologia do lobo temporal; Spin-echo T2w (TR=2500 msec, TE=120 msec) visando a avaliar sinais de alta intensidade anormais. Em 2 casos com focos esquerdos no EEG, a MRI mostrou atrofia, perda de estrutura interna e aumento de sinal no hipocampo, e atrofia do lobo temporal anterior, ipsilateralmente. Um caso com focos bilaterais independentes no EEG teve atrofia, perda da estrutura interna e aumento de sinal no hipocampo direito. Um caso com EEG focal direito mostrou atrofia em ambos os lobos temporais anteriores. Outro caso näo mostrou anormalidades. Concluimos que esta metodologia pode facilitar a indicaçäo cirúrgica em epilepsia do lobo temporal