Interictal spiking increases after seizures but does not after decrease in medication

In patients with focal epilepsy, EEG spike rate fluctuates considerably over time. We had previously shown that seizure occurrence played an important role in these fluctuations. We undertook this study to confirm this finding with better control of critical variables such as state of alertness and spike quantification, and to assess the spatial extent of the changes. Background activity changes and antiepileptic drug levels were also examined in relation to spiking. Spike discharge rate increased in the hours and days following seizures in widespread brain regions including, but not restricted to, the seizure focus. Spike rate did not change systematically before seizures. Postictal changes in background activity did not parallel spike fluctuations. Decreased antiepileptic drug levels did not cause increased spike rate. These results indicate that, following seizures, there is activation of interictal spiking which is not paralleled by changes in background activity. It is most often widespread and not necessarily most prominent at the site of seizure onset.     

Prediction of Surgical Outcome by Interictal Epileptiform Abnormalities During Intracranial EEG Monitoring in Patients with Extrahippocampal Seizures

PURPOSE: Ictal intracranial EEG recordings obtained during continuous preoperative monitoring are often used to localize the region of seizure onset for purposes of surgical resection in patients with extrahippocampal seizures. Whether interictal epileptiform abnormalities during long-term monitoring can predict surgical outcome in this group is not established. METHODS: Intracranial EEGs of patients who underwent extrahippocampal resective epilepsy surgery were reviewed for interictal epileptiform abnormalities before medication discontinuation or first seizure occurrence. Interictal abnormalities were categorized as within or beyond the confines of surgical resection. We correlated these findings with the region of seizure onset, the pathologic substrate, and surgical outcome (by using Engel criteria) at 1-year minimum follow-up. RESULTS: Of 13 patients with interictal epileptiform abnormalities, six patients had interictal epileptiform discharges extending beyond the confines of surgical resection. These patients all had poor surgical outcome even if the region of electrographic seizure onset was resected. Seven patients had focal interictal epileptiform discharges, the entire extent of which were resected. All had good outcomes. All patients with structural lesions had focal interictal epileptiform abnormalities and good surgical outcomes. The spatial extent of interictal epileptiform discharges varied among patients with nonstructural lesions. However, those whose regions of interictal epileptiform abnormality were included in surgical resection also had good surgical outcome. CONCLUSIONS: The presence of interictal epileptiform discharges extending beyond the area of resection correlates with poor surgical outcome in patients with extrahippocampal epilepsy. In contrast, patients with focal interictal epileptiform discharges included in surgical resection have good surgical outcomes.     

Electroencephalographic spiking activity, drug levels, and seizure occurrence in epileptic patients

We investigated the relationships among the electroencephalographic spiking rate, drug levels, and seizure occurrence in 44 patients with focal epilepsy. Seizure occurrence was continuously monitored by personnel or videorecording and spiking rate was quantified by an automatic detection method. Results indicate that drug levels do not influence spiking rate, and spiking rate does not change before seizures but increases markedly after them, particularly secondarily generalized seizures. This increase can last several days and is observed during wakefulness and sleep. High or low spiking rates do not influence the occurrence of seizures. We suggest that interictal spikes may passively reflect damage to the brain, a damage which is worsened by further seizures. Spikes may not be directly related to seizure generation.     

Topiramate: effect on EEG interictal abnormalities and background activity in patients affected by focal epilepsy

PURPOSE: To evaluate the effects of topiramate (TPM) on interictal epileptiform abnormalities (IEA) and background activity by means of a computerized EEG analysis, in adult patients affected by focal epilepsy, with or without secondarily generalization, treated with TPM as adjunctive therapy or monotherapy. METHODS: Twenty-four patients affected by symptomatic or cryptogenic focal epilepsy underwent long-term video-EEG recording before and after TPM addition (mean dose 175+/-25 mg per day). RESULTS: TPM addition induced a significant reduction of both partial and secondarily generalized tonic-clonic (SGTC) seizures; treatment responder patients (seizure reduction > or = 50%) were 19 out of 24 patients (79.1%), of whom 5 were seizure-free. Quantitative analysis of IEA showed a significant decrease in the mean number of spikes/10 min during TPM therapy ( 4.2+/-4.2 versus 2.2+/-4.4; P<0.003 ). The analysis of spatial distribution of interictal spikes showed that such reduction was more evident at the level of the epileptogenic area rather than on the spreading component. Statistical analysis revealed only a significant decrease of mean relative power of alpha band in the EEG spectral content, recorded at rest in a group of 18 out of 24 epileptic patients during TPM therapy. In addition, during TPM treatment we observed a significant reduction in alpha reactivity without any important changes of alpha indexes (peak frequency and median frequency). CONCLUSION: These findings suggest that TPM has a strong inhibitory effect on IEA, probably acting on the generating processes, and, if used at low dosage and gradually titrated, seems to have only mild interferences with EEG background activity.     

Ictal cerebral perfusion related to EEG in drug resistant focal epilepsy of childhood.

OBJECTIVES: To evaluate the EEG changes during seizures in children with drug resistant focal epilepsy who demonstrate hypoperfusion at the "seizure focus" interictally, but no perfusion change during the seizure. METHODS: Ictal EEG findings of six children with focal epilepsy who demonstrated hypoperfusion on rCBF SPECT after an interictal injection of (99)Tc(m) HMPAO concordant with the seizure focus, but who did not demonstrate rCBF change after an ictal injection (group 1) were reviewed. These were contrasted with the EEG data of six children matched as closely as possible for age, type of epilepsy, and pathology who did show hyperperfusion at the seizure focus on ictal scan when compared with the interictal study (group 2). RESULTS: The children in group 1 showed slowing of the EEG at the time of the (99)Tc(m) HMPAO injection relative to that seen at the onset of the seizure. Those in group 2 showed rhythmic activity, or sharp waves, or both on EEG at the time of injection. This last change was also seen consistently when the EEG data of a further 13 children who also showed ictal hyperperfusion at the seizure focus were reviewed. CONCLUSION: Ictal rCBF does not invariably increase at the seizure focus in patients with drug resistant focal epilepsy.     

Coexistence of focal and idiopathic generalized epilepsy in the same patient population.

PURPOSE: To review the clinical, electrographic, radiological, and pathological findings of patients with coexistent idiopathic generalized and partial epilepsy syndromes. METHODS: We performed a medical record review and a phone interview with all patients hospitalized to the Cleveland Clinic epilepsy monitoring unit (EMU) between 1992 and 2002 who fulfilled clinical and EEG criteria of coexistent partial and generalized epilepsy syndromes. RESULTS: Seven patients were identified. Two (29%) were men with a mean age of 26 years. Four had a history of febrile seizures. Family history was positive in five. Mean duration of the generalized epilepsy syndrome was 11 years, and of the focal epilepsy 18 years. An equal number of patients developed focal versus generalized epilepsy first. Interictal EEG activity was predominantly generalized. Four had video-EEG documentation of both types of seizures. In the rest, only focal seizures were recorded but interictal activity strongly suggested a coexistent generalized epilepsy. MRI showed hippocampal atrophy in all, and hippocampal dysplasia in three. Five patients had PET imaging, all with hypometabolism in areas corresponding to the ictal onset on EEG. Four patients underwent epilepsy surgery with good surgical outcome and pathological confirmation of hippocampal sclerosis in all. CONCLUSION: We found a 0.2% incidence of coexistent focal and primary generalized epilepsy. Febrile seizures and a positive family history were common. Good seizure control was achieved after temporal lobectomy, even when interictal generalized activity predominated.     

The relationship between interictal and ictal paroxysms in an in vitro model of focal hippocampal epilepsy

In studies of focal epilepsy it is frequently assumed that the interictal spike is the elementary form of epileptic activity and that seizure, or ictal, episodes evolve by temporal summation and spatial expansion of interictal paroxysms. We examined this hypothesis in an in vitro model of acute focal epilepsy produced by perfusing rat hippocampal slices with solutions containing moderately elevated concentrations of K+. Some of the preparations treated in this way displayed recurring electrical seizures in the CA1 field. Each seizure episode typically evolved by a seemingly smooth progression of brief interictal bursts into sustained ictal discharge. However, exposure of preparations showing electrical seizures to blockers of synaptic transmission or to cholinergic agonists abolished interictal spiking in all hippocampal fields but did not impede the initiation of ictal episodes in area CA1. Likewise, severing the connections between areas CA3 and CA1 abolished interictal spiking in area CA1 without disrupting the initiation of seizures in this region. These data clearly show that in this model, focal seizures arise independent of interictal spikes and through different cellular mechanisms. While interictal electrogenesis requires chemical synaptic excitation, ictal episodes can be initiated and maintained by nonsynaptic neuronal interactions.     

Characterization of the tetanus toxin model of refractory focal neocortical epilepsy in the rat

PURPOSE: To characterize in detail a model of focal neocortical epilepsy. METHODS: Chronic focal epilepsy was induced by injecting 25-50 ng of tetanus toxin or vehicle alone (controls) into the motor neocortex of rats. EEG activity was recorded from electrodes implanted at the injection site, along with facial muscle electromyographic (EMG) activity and behavioral monitoring intermittently for up to 5 months in some animals. Drug responsiveness was assessed by using the antiepileptic drugs (AEDs) diazepam (DZP) and phenytoin (PHT) delivered systemically, while 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), a competitive antagonist at AMPA receptors, was administered directly to the brain to investigate the potential benefits of focal drug delivery. RESULTS: Tetanus toxin induced mild behavioral seizures that persisted indefinitely in all animals. EEG spiking activity, occurring up to 80% of the time, correlated with clinical seizures consisting of interrupted behavioral activity, rhythmic bilateral facial twitching, and periods of abrupt motor arrest. Seizures were refractory to systemic administration of DZP and PHT. However, focal delivery of NBQX to the seizure site reversibly reduced EEG and behavioral seizure activity without detectable side effects. CONCLUSIONS: This study provides a long-term detailed characterisation of the tetanus toxin model. Spontaneous, almost continuous, well-tolerated seizures occur and persist, resembling those seen in neocortical epilepsy, including cortical myoclonus and epilepsia partialis continua. The seizures appear to be similarly resistant to conventional AEDs. The consistency, frequency, and clinical similarity of the seizures to refractory epilepsy in humans make this an ideal model for investigation of both mechanisms of seizure activity and new therapeutic approaches.     

Understanding Lennox–Gastaut syndrome: insights from focal epilepsy patients with Lennox–Gastaut features

To delineate the clinical and EEG features of adults with focal epilepsy associated with a generalized paroxysmal fast activity (GPFA) pattern on EEG who developed refractory seizures, notably drop attacks, but do not fulfill the classical triad for the diagnosis of Lennox–Gastaut syndrome (LGS) and provide further insight into LGS mechanisms. Among 957 patients admitted to video-EEG monitoring between 2002 and 2015, we retrospectively research adult patients with refractory focal epilepsy, drop attacks and GPFA on EEG. We collected demographic, anamnestic, and clinical data from medical records. We reviewed for all patients the interictal and ictal video-EEG recordings. We identified ten patients with focal epilepsy and electro-clinical features of LGS. As compared to classical LGS patients, our patients: (1) began epilepsy later (15.4 ± 8 years); (2) exhibited exclusively focal onset seizures, including drop attacks seizures linked to focal asymmetrical tonic posturing seizures; (3) had a stable cognition over time and (4) evolved favourably with a good secondary response to treatments in 80% of cases. Interestingly, all patients exhibited apparent diffuse interictal and ictal EEG abnormalities but a detailed analysis revealed that 50% had asymmetrical GPFA and 70% secondary bilateral synchrony processes. We may hypothesize here that a process of “secondary LGS” occurred which produced a worsening of seizures with the apparition of drop attacks and GPFA on EEG. This study brings arguments to consider that some cases of LGS could be linked to the development of a “secondary epileptic network” driven by a primary focal epileptic zone.     

Jeavons syndrome existing as occipital cortex initiating generalized epilepsy

Purpose: Jeavons syndrome (JS) is one of the underreported epileptic syndromes characterized by eyelid myoclonia (EM), eye closure–induced seizures/electroencephalography (EEG) paroxysms, and photosensitivity. JS has been proposed as idiopathic generalized epilepsy (IGE) because of normal posterior dominant background activity and paroxysmal generalized ictal epileptiform discharges (EDs). However, we noticed subtle occipital EDs preceding EM and interictal posterior EDs using digital video‐EEG. We studied clinical and EEG findings in JS to determine the specific occipital lobe relation to this “eye closure–induced” reflex IGE. Methods: We identified 12 children who met the diagnostic criteria of JS from January 2004 to April 2009 at the Hospital for Sick Children, Toronto, Canada. All patients had EM captured by video‐EEG. We reviewed and described ictal EEG patterns, interictal abnormalities, and demographics, clinical, and neuroimaging findings. Key Findings: All patients but one were female (92%). Age at seizure onset ranged from 1.5 to 9 years, with a mean age of 4.9 years. Six patients (50%) were previously diagnosed as having absence epilepsy and 10 patients were on antiepileptic medications. All 12 patients had normal posterior dominant alpha rhythm, reactive to eye opening and closure. Spiky posterior alpha activity was noted with sustained eye closure in six patients (50%). Interictally, there were generalized EDs found in 10 patients (83%); four of them also had focal interictal EDs over the posterior head region. Eleven patients (92%) had evidence of focal posterior ictal EDs. EM and/or paroxysmal EDs were induced by photic stimulation in 9 (75%) and hyperventilation in 7 (58%). Significance: We observed two neurophysiologic findings in JS: (1) focal interictal EDs from posterior head region; and (2) predominant focal posterior ictal EDs preceding generalized EDs. Further clinical observations of seizures induced by eye closure, photic stimulation, and hyperventilation along with EEG paroxysms would raise the possibility of the occipital cortex initiating generalized epilepsy network involving the brainstem, and thalamocortical and transcortical pathways in JS.     

EEG changes induced by vigabatrin monotherapy in focal epilepsy

The effect of vigabatrin (GVG) monotherapy on EEG interictal abnormalities and on background activity recorded at rest and during mental tasks was studied in 14 patients suffering from focal epilepsy. A long-term EEG monitoring was performed in each patient before and 3 months after the beginning of GVG therapy. Ictal and interictal EEG abnormalities (IEA) were quantified by specific computer programs. Background activity was evaluated by spectral analysis at rest with eyes closed (EC), during blocking reaction (BR) and during fixation of cartoons (FIX). During treatment, IEA was either decreased or unmodified independently from seizure occurrence, which clearly improved in the majority of patients. The only EEG modifications induced by GVG monotherapy were a more pronounced slowing of the background activity at rest with EC and a reduced responsiveness to BR. EEG data suggest a GVG monotherapy induced mild "sedative" action on attentive tasks rather than on cognitive function.     

EEG analysis with simulated neuronal cell models helps to detect pre-seizure changes.

OBJECTIVES: To test if a method for real-time detection of epileptic seizures based on electroencephalographic (EEG) analysis with simulated neuronal cell models can be modified to identify pre-seizure changes. METHODS: Our EEG analysis method consists of two simulated leaky integrate and fire units (LIFU) connected to a signal preprocessing stage that marks parts of the EEG signals with slopes larger than a preset threshold Hth with unit pulses. The LIFUs change their spiking frequency depending on the rate and the synchrony of the impinging pulse trains. Here, we use our method in a high-sensitivity mode by setting Hth to low values, which causes the LIFUs to continuously spike during the interictal state. We test if the LIFUs spiking rates change before seizure onset. RESULTS: We used 9 long-term EEGs (16+/-7 h) of 7 patients with drug resistant epilepsy. Fifteen seizures were analyzed and all were preceded by an increase of the time-averaged spiking rates SR(av) of the LIFUs. We defined a function F(Sz), which quantifies the changes of SR(av). F(Sz) increased and stayed above an individually set and fixed threshold 83+/-91 min (range: 4-330 min) before EEG seizure onset. Only two false alarms occurred. CONCLUSIONS: We conclude that EEG analysis with simulated neuronal cell models may be used to detect pre-seizure changes with high sensitivity and specificity.     

Partial Epilepsies in Infancy: A Study of 40 Cases

Forty patients with partial epilepsy that began before they were aged 3 years were recorded at the Centre Saint-Paul between 1981 and 1986 with a follow-up ranging from 1 year 9 months to 20 years. We analyzed the following data: age at onset, clinical features of seizures at onset and during the follow-up period, ictal and interictal EEG features, etiologic circumstances, evolution of the epilepsy, and psychomotor development. The age of onset was mostly between 2 months and 2 years (more than two thirds of cases). Most had partial symptomatic epilepsy. In nine cases, epilepsy was preceded by febrile convulsions. Seizures at onset were of the following type (in order of decreasing occurrence): unilateral seizures, complex partial seizures, elementary partial seizures, and other seizures, often difficult to classify. A few patients with infantile spasms associated with focal or multifocal EEG abnormalities, differing from West's syndrome, were included in this study. We discuss the problem arising from the classification of infantile seizures and epilepsies.     

Consistent localization of interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex

PURPOSE: We addressed consistent localization of focal interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex (TSC) and epilepsy. METHODS: Twenty-one patients with TSC with a 10-year history of epilepsy and interictal epileptiform activity in three or more EEG recordings were included. None of the patients had undergone epilepsy surgery. Local maxima of interictal epileptiform activity were measured from 76 EEG traces and 33 EEG reports. Information about the patients' clinical course was extracted from their medical records. Magnetic resonance imaging (MRI) and neuropsychological examinations were performed. Statistical analysis was performed with the Mann-Whitney U test. RESULTS: In eight patients, interictal epileptiform activity was consistently detected in one or two regions (group 1), and in 13 patients, epileptiform activity was detected in three or more regions (group 2). The number of foci increased throughout the disease course in both groups. Age at seizure onset and IQ were significantly higher in group 1. Complex partial seizures occurred more often in the patients of group 1. In 19 of the 21 patients, the most consistent epileptiform activity was localized in the frontotemporal region. CONCLUSIONS: Ninety percent of patients with TSC showed at least one region of consistent interictal epileptiform activity. Patients with one or two regions of epileptiform activity were older at seizure onset, often experienced complex partial seizures, and had mild or no mental deficits. These patients may be candidates for epilepsy surgery.     

Generalized onset seizures with focal evolution (GOFE) — A unique seizure type in the setting of generalized epilepsy

PurposeWe report clinical and electrographic features of generalized onset seizures with focal evolution (GOFE) and present arguments for the inclusion of this seizure type in the seizure classification.MethodsThe adult and pediatric Epilepsy Monitoring Unit databases at Vanderbilt Medical Center and Children's Hospital were screened to identify generalized onset seizures with focal evolution. We reviewed medical records for epilepsy characteristics, epilepsy risk factors, MRI abnormalities, neurologic examination, antiepileptic medications before and after diagnosis, and response to medications. We also reviewed ictal and interictal EEG tracings, as well as video-recorded semiology.ResultsTen patients were identified, 7 males and 3 females. All of the patients developed generalized epilepsy in childhood or adolescence (ages 3–15 years). Generalized onset seizures with focal evolution developed years after onset in 9 patients, with a semiology concerning for focal seizures or nonepileptic events. Ictal discharges had a generalized onset on EEG, described as either generalized spike-and-wave and/or polyspike-and-wave discharges, or generalized fast activity. This electrographic activity then evolved to focal rhythmic activity most commonly localized to one temporal or frontal region; five patients had multiple seizures evolving to focal activity in different regions of both hemispheres. The predominant interictal epileptiform activity included generalized spike-and-wave and/or polyspike-and-wave discharges in all patients. Taking into consideration all clinical and EEG data, six patients were classified with genetic (idiopathic) generalized epilepsy, and four were classified with structural/metabolic (symptomatic) generalized epilepsy. All of the patients had modifications to their medications following discharge, with three becoming seizure-free and five responding with > 50% reduction in seizure frequency.ConclusionGeneralized onset seizures may occasionally have focal evolution with semiology suggestive of focal seizures, leading to a misdiagnosis of focal onset. This unique seizure type may occur with genetic as well as structural/metabolic forms of epilepsy. The identification of this seizure type may help clinicians choose appropriate medications, avoiding narrow spectrum agents known to aggravate generalized onset seizures.     

SECTION D: NEUROSURGERY & NEUROPATHOLOGY

Comparison of surgical and medical treatment for partial epilepsy. Medical and social implications of the treatment
Procedures in Pediatric Epilepsy Surgery
The possible need for intra-cranial EEG in surgery for temporal lobe epilepsy
Consistency of lateralisation in intracranial record-ings of seizures of temporal lobe origin
Comparison of lateralising capability of 99Tc^m HM-PAO-SPECT, neuropsychology, interictal and ictal EEG in the pre-surgical evaluation of patients with intractable epilepsy
Convergence of CT/MRI, "FDG-PET, intracarotid amobarbital procedure and D.EEG in presurgical evaluation of refractory partial epilepsy
Surgery for epilepsy in the United Kingdom
Anterior 2/3 callosotomy for the treatment of in-tractable epilepsy
Pre-surgical EEG evaluation
A simplified technique for epidural recording of epi-leptiform activity and seizure patterns
Discrepancy between interictal and ictal EEG-find-ings - the use of subdural electrodes may solve the problem
Temporal mesiolimbic versus temporal neocortical complex partial seizures; electroclinical correlates recorded by combined depth and subdural electrodes
Verifying electrical dipole localization in patients with epilepsy undergoing depth EEG recordings in the presurgical evaluation of intractable epilepsy
A current dipole tracing method locating interictal epileptiform activity in patients with focal epilepsy
PET-studies on distribution of glia in patients with focal epilepsy
Relationship of pre-operative neuropsychological test to the sodium amytal test - results on an empiri-cal study
Amygdalohippocampectomy in complex partial epi-lepsy     

Multifocal independent epileptiform discharges in children: ictal correlates and surgical therapy

We obtained continuous EEG/video recordings on four children who had the interictal EEG pattern of multifocal independent epileptiform discharges (MIED). The prominent feature of their evaluation was the evidence that their clinical seizures appeared to be of focal origin; 42/44 seizures were manifested by "fencing postures." Three patients subsequently underwent epilepsy surgery: one focal resection of superior frontal-parietal cortex and two hemidecorticectomies. Seizure control improved in all three patients, and one patient is now seizure-free. Our patients differ from those previously reported in that they had a predominance of tonic seizures and had no history of infantile spasms or Lennox-Gastaut syndrome. Some patients, such as ours, with MIED may have clinical seizures of more focal origin than might be expected from their interictal EEG and, therefore, may benefit from resective epilepsy surgery.     

Relationships between triggered seizures, spontaneous seizures, and interictal spiking in the kindling model of epilepsy

Cats were kindled in the amygdala. After completion of kindling, their EEG was monitored almost continuously by a computer system which allowed the detection of spontaneous seizures and the quantification of interictal spikes. The relationships between seizures triggered by stimulation, spontaneous seizures, and interictal spikes in kindled and contralateral amygdalas were examined. Very few spontaneous seizures were observed; their occurrence appeared facilitated by a few triggered seizures after a long seizure-free interval. Stimulation-triggered seizures were followed first by a decrease in spiking activity during a few hours and then by an increase which could take 3 to 8 days to return to baseline. Spontaneous seizures were also, but less systematically, followed by such a sequence. Spontaneous seizures could occur when the interictal spiking rate was high as well as when it was low. It is concluded that, in the fully kindled cat, interictal spiking appears to be mainly regulated by the occurrence of seizures; the rate of spiking appears to have no bearing on the probability of occurrence of spontaneous seizures. Hence, seizures and interictal spiking could be generated by separate pathophysiologic mechanisms, the seizure-generating mechanism influencing the spike-generating mechanism but not the reverse.     

Pharmacologic evidence for abnormal thalamocortical functioning in GABA receptor beta3 subunit-deficient mice, a model of Angelman syndrome

PURPOSE: gamma-Aminobutyric acid receptor (GABA(A)r) subunit beta3-deficient mice model Angelman syndrome by displaying impaired learning, abnormal EEG with interictal spikes and slowing, myoclonus, and convulsions. The beta3-subunit deficiency causes a failure of intrathalamic reticular nucleus inhibition, leading to abnormally synchronized thalamocortical oscillations. We postulated that this pathophysiology underlies the abnormal cortical EEG and triggers interictal spikes and seizures, but extrathalamic regions also contribute to interictal spikes and seizures, so that the EEG slowing should reveal an absence-like response profile, whereas spikes and seizures have dual responsiveness to absence and partial-seizure drugs. METHODS: Recording electrodes were implanted over the parietal cortices of wild-type, heterozygotes, and homozygous null mice. In each experiment, EEG was recorded for 45 min, either drug or vehicle administered, and EEG recorded for another 3 h. Each EEG was scored for slow-wave activity, interictal spikes, and seizures by a reader blinded to treatments. RESULTS: Interictal spiking and percentage of time in EEG slowing in heterozygotes were increased by the proabsence drug baclofen (GABA(B)-receptor agonist), whereas CGP 35348 (GABA(B)-receptor antagonist) had the opposite effect. The antiabsence drug ethosuximide markedly suppressed EEG slowing and interictal spiking in heterozygote and null mice. Broad-spectrum clonazepam and valproate were more effective on interictal spiking than on EEG slowing, and fosphenytoin suppressed only interictal spiking. CONCLUSIONS: The results suggest that this model of Angelman syndrome, although not expressing typical absence seizures, is characterized by hypersynchronous thalamocortical oscillations that possess absence-like pharmacologic responsiveness and promote EEG slowing, interictal spikes, and convulsive seizures.     

Frontal lobe epilepsy

About one-quarter of patients with refractory focal epilepsies have frontal lobe epilepsy (FLE). The typical seizure semiology for FLE includes unilateral clonic, tonic asymmetric or hypermotor seizures. Interictal electroencephalograms (EEG) usually reveal interictal epileptiform discharges and rhythmical midline theta, which has localizing value. The usefulness of ictal EEG recordings is limited by frequent muscle artifacts in motor seizures and because a large portion of the frontal lobe cortex is “hidden” to scalp electrodes. Ictal single photon emission CT and positron emission tomography are able to localize FLE in about one-third of patients only. A pre-surgical evaluation should include, whenever possible, a subclassification of FLE as dorsolateral frontal, mesial frontal or basal frontal lobe epilepsy to allow a minimal cortical resection. A review of the typical findings of seizure semiology, interictal and ictal EEG regarding the different FLE subtypes is given. Etiology, medical treatment and surgery are also discussed.