Recognition and classification of seizures in infants

PURPOSE: We wished to assess the reliability of the International League Against Epilepsy (ILAE) seizure classification system applied to infantile seizures and to test a proposed new classification. METHODS: We first analyzed 39 seizures in 20 infants (aged 1-26 months) recorded with simultaneous closed-circuit television and EEG (CCTV/EEG). EEGs and videotapes of all seizures were independently analyzed by two epileptologists blinded to clinical histories. Videotapes of each seizure were reviewed without simultaneous EEG (phase 1), and printouts of ictal EEGs were assessed without behavioral correlates (phase II). The observers classified seizures according to ILAE criteria. Interrater agreement was assessed by the kappa statistic. RESULTS: Agreement on EEG features (phase II) was moderate (= 0.54) in identifying focal ictal onsets and substantial (= 0.79) in identifying generalized onsets. In contrast, analysis of videotapes showed substantial disagreement between observers in terms of classifying seizures as partial or generalized. Therefore, agreement between observers for partial was slight (= 0.14) and fair for generalized seizures (= 0.26). Similarly, conclusions of the observers as compared with those of a consensus panel were divergent for both partial (= 0.18) and generalized seizures (= 0.30). We therefore developed an alternative classification scheme and retested interrater agreement in a review of 50 seizures in 25 other infants. With this classification scheme, there was substantial agreement between observers (= 0.72). CONCLUSIONS: With clinical observations and interictal EEGs, seizures in infants cannot be reliably classified by current ILAE criteria. In contrast, a proposed new classification scheme based solely on semiology showed substantial reliability.     

Ictal cerebral blood flow in seizures originating in the posterolateral cortex

In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS: Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS: Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION: Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.     

EEG findings in frontal lobe epilepsies

As a group, epilepsies of frontal lobe origin are thought to be poorly localized using surface EEG recordings. This finding may depend on the specific areas of frontal lobe from which the seizures originate or the pathologic substrate. We reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who underwent epilepsy surgery. The specific area of the frontal lobe where seizures originated was determined by 1) intracranial ictal EEG recordings, or 2) the presence of a structural lesion, identified by imaging studies in patients who achieved complete seizure control following surgery. We differentiated patients whose seizures began in the dorsolateral frontal convexity from those whose seizures began in the medial frontal region, and we correlated EEG findings in the interictal, postictal, and ictal states with seizure semiology, pathologic substrate, and surgical outcome. Four of nine patients had seizures originating in the dorsolateral frontal convexity and five had medial frontal onset seizures. Patients whose seizures originated from the dorsolateral convexity had focal interictal epileptiform abnormalities that localized to the region of seizure onset. Patients whose seizures began in the medial frontal region had either no interictal epileptiform abnormality or had multifocal epileptiform discharges. Patients whose seizures began in the dorsolateral convexity showed focal electrographic seizure activity that was localizing. This rhythmic fast activity did not appear to be substrate-specific. Patients whose seizure onset localized to the medial frontal region did not show focal electrographic seizure at clinical onset. We conclude that the scalp EEG recordings of frontal lobe epilepsies contain features that enable differentiation of seizures originating from two different regions of the frontal lobe.     

Ictal smile

PURPOSE: Smiling is sometimes manifested during partial seizures. Its value for localizing the epileptogenic focus is not known. We analyzed smiling as an ictal manifestation possibly useful for seizure localization. METHODS: We reviewed patients referred to the video-EEG monitoring unit who presented a smile as part of their critical symptoms. Ictal smile was defined as an accordant expression accompanied by other characteristic epileptic symptoms and ictal EEG activity. RESULTS: Five of 86 patients experienced partial seizures with an ictal smile. We observed smiling during parietal (two patients) and temporal lobe (three patients) seizures. The right hemisphere appeared to be involved with greater frequency. CONCLUSIONS: Ictal smile is an uncommon manifestation of partial seizures involving temporal or parietal lobes, localized mainly on the right hemisphere.     

Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy

To determine whether lesional neocortical temporal lobe epilepsy (NTLE) can be differentiated from mesial temporal lobe epilepsy (MTLE) during the noninvasive presurgical evaluation, we compared the historical features, seizure symptomatology, and surface EEG of 8 patients seizure free after neocortical temporal resection with preservation of mesial structures and 20 patients after anterior temporal lobectomy for MTLE. Seizure symptomatology of 107 seizures (28 NTLE, 79 MTLE) was analyzed. One hundred one ictal EEGs (19 NTLE, 82 MTLE) were reviewed for activity at seizure onset; presence, distribution, and frequency of lateralized rhythmic activity (LRA); and distribution of postictal slowing. Seizure symptomatology and EEG data were compared between groups, and sensitivity, specificity, and positive and negative predictive values were determined for variables that differed significantly. Multiple logistic regression was used to determine whether patients could be correctly classified as having MTLE or NTLE. MTLE patients were younger at onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications, or head injury. NTLE seizures lacked features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation, and postictal cough or sigh. NTLE ictal EEG recordings demonstrated lower mean frequency of LRA that frequently had a hemispheric distribution, whereas LRA in MTLE seizures was maximal over the ipsilateral temporal region. We conclude that it may be possible to differentiate lesional NTLE from MTLE on the basis of historical features, seizure symptomatology, and ictal surface EEG recordings. This may assist in the identification of patients with medically refractory nonlesional NTLE who frequently require intracranial monitoring and more extensive or tailored resections.     

Repair of traumatic orbital wall defects with nasal septal cartilage: report of five cases

PURPOSE: Arachnoid cysts are sometimes encountered in MRIs performed for a variety of reasons. In patients with epilepsy, particularly those with refractory epilepsy, arachnoid cysts are often assumed to be related to their seizure focus. We conducted a study to investigate this putative relationship. METHODS: A retrospective study on the incidence of arachnoid cysts was performed in patients seen in our Epilepsy Clinic who had CT or MRI scans, interictal EEGs or ictal EEGS. Locations of seizure foci in these patients were defined from clinical and electrophysiologic data. RESULTS: Seventeen of 867 patients had arachnoid cysts. Twelve patients had temporal lobe cysts and only 3 of them had temporal lobe seizures. Four patients had frontal lobe cysts and only 1 had frontal lobe seizures ipsilateral to the cyst. One patient had a cerebello-pontine angle cyst and frontal lobe seizures. Thus, clinical manifestations of seizures and EEG findings (interictal and/or ictal) indicated that the seizure focus was adjacent to the cysts in only 4 patients (23.5%). CONCLUSIONS: Our findings suggest that arachnoid cysts are often an incidental finding in patients with epilepsy and do not necessarily reflect the location of the seizure focus.     

Abdominal epilepsy in an adolescent with bilateral perisylvian polymicrogyria

PURPOSE: We report a patient with recurrent episodes of severe periumbilical pain accompanied by headache, pallor, dizziness, and visual hallucinations who was subsequently diagnosed as having abdominal epilepsy and a bilateral sylvian cortical malformation. METHODS AND RESULTS: During an EEG examination, the patient had a simple partial seizure, manifested as intense abdominal pain. The ictal EEG showed a focal electrographic seizure arising from the left frontotemporal region. Computed tomography scan was normal; however, magnetic resonance imaging (MRI) revealed asymmetric lesions involving both sylvian fissures compatible with polymicrogyria. Onset of treatment with sodium valproate was followed by a significant reduction of seizures. CONCLUSIONS: Abdominal epilepsy should be suspected in adolescents or adults with paroxysmal episodes of abdominal pain associated with migraine-like symptoms. EEG and MRI investigations are indicated. A developmental brain disorder should be considered as a possible etiology.     

Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.     

Visual and quantitative ictal EEG predictors of outcome after temporal lobectomy

PURPOSE: We investigated whether visual and quantitative ictal EEG analysis could predict surgical outcome after anteromesial temporal lobectomy (AMTL) in which mesial structures, basal, and temporal tip cortex were resected. METHODS: We retrospectively reviewed 282 presurgical scalp-recorded ictal EEGs (21- to 27-channel) from 75 patients who underwent AMTL. We examined the pattern of seizure onset (frequency, distribution, and evolution) and estimated the principal underlying cerebral generators by using a multiple fixed dipole model that decomposes temporal lobe activity into four sublobar sources (Focus 1.1). We correlated findings with a 2-year postoperative outcome. RESULTS: Sixteen patients had seizures with a well-lateralized, regular 5 to 9-Hz rhythm at onset, that most often had a temporal or subtemporal distribution. All patients became seizure free after surgery. In 51 patients, seizure onset was remarkable for lateralized slow rhythms (<5 Hz), which sometimes appeared as periodic discharges, were often irregular and stable only for short periods (<5 s), and had a widespread lateral temporal distribution. Among these a favorable surgical outcome was encountered in patients with seizures having prominent anterior-tip sources ( 16 of 17 seizure free), whereas those with dominant lateral or oblique sources had a less favorable outcome (three of 14 and 13 of 18, respectively). Irregular, nonlateralized slowing characterized seizure onsets in eight patients. Three patients became seizure free after surgery. CONCLUSIONS: Both visual and quantitative sublobar source analysis of scalp ictal EEG can predict surgical outcome in most cases after AMTL and complement non-invasive presurgical evaluation.     

Routine microbiological testing in sudden and unexpected infant death

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.     

Nonlinear dynamics of epileptic seizures on basis of intracranial EEG recordings

PURPOSE: An understanding of the principles governing the behavior of complex neuronal networks, in particular their capability of generating epileptic seizures implies the characterization of the conditions under which a transition from the interictal to the ictal state takes place. Signal analysis methods derived from the theory of nonlinear dynamics provide new tools to characterize the behavior of such networks, and are particularly relevant for the analysis of epileptiform activity. METHODS: We calculated the correlation dimension, tested for irreversibility, and made recurrence plots of EEG signals recorded intracranially both during interictal and ictal states in temporal lobe epilepsy patients who were surgical candidates. RESULTS: Epileptic seizure activity often, but not always, emerges as a low-dimensional oscillation. In general, the seizure behaves as a nonstationary phenomenon during which both phases of low and high complexity may occur. Nevertheless a low dimension may be found mainly in the zone of ictal onset and nearby structures. Both the zone of ictal onset and the pattern of propagation of seizure activity in the brain could be identified using this type of analysis. Furthermore, the results obtained were in close agreement with visual inspection of the EEG records. CONCLUSIONS: Application of these mathematical tools provides novel insights into the spatio-temporal dynamics of "epileptic brain states". In this way it may be of practical use in the localization of an epileptogenic region in the brain, and thus be of assistance in the presurgical evaluation of patients with localization-related epilepsy.     

Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.     

Pedicled and microvascular reanastomosed transplants for reconstruction in the head-neck area

In seizures starting gradually, careful examination of the background is required to determine the time and region of onset. We propose a method for displaying EEG variables which characterize seizure onset: changes in amplitude and in average frequency compared to background. These variables are displayed topographically for each EEG channel so that 1 or 2 min of EEG may be viewed on a standard screen, thus representing pre-ictal and ictal periods. We evaluated the ability of this display to indicate seizure onset, by comparing the times and regions of seizure onset indicated by traditional EEG and by the display. The comparison was performed on 30 seizures from scalp recordings and 49 seizures from depth recordings. Seizures were selected for having a gradual onset with no or minimal artefact. Onset times from traditional EEG and the computer method, examined independently, coincided (within 3 sec) in 77% of scalp seizures and 63% of depth seizures. In 14% of seizures the computer display indicated an onset more than 3 sec earlier than visual examination; upon reexamination, however, this onset was thought to be possibly correct. This quantitative display, which in practice should be used with traditional EEG, may thus be useful for computer-assisted seizure interpretation and for a condensed representation of seizures.     

Ictal single photon emission computed tomography in occipital lobe seizures

PURPOSE: Ictal single photon emission computed tomography (SPECT) has been evaluated as an adjunctive localizing technique in temporal lobe epilepsies and, to a lesser degree, in some extratemporal epilepsies. The purpose of this study was to determine whether occipital lobe seizures are associated with distinctive ictal cerebral blood perfusion (rCP) patterns. METHODS: SPECT was used with the tracer 99mTc HMPAO to image ictal rCP in 6 patients in whom clinical, EEG, and imaging data indicated occipital lobe seizures. RESULTS: Two patterns of rCP were seen. Four patients had hyperperfusion that was restricted to the occipital lobe, and two patients had hyperperfusion of the occipital lobe and the ipsilateral mesial temporal lobe, with hypoperfusion of the lateral temporal lobe. The latter 2 patients had clinical and surface EEG evidence of temporal lobe involvement in the seizure discharge. CONCLUSIONS: Ictal rCP patterns in occipital lobe seizures are distinct from those in temporal lobe seizures and may vary according to whether or not ipsilateral temporal lobe structures are involved in the ictal discharge.     

Ictal and interictal technetium-99m-bicisate brain SPECT in children with refractory epilepsy

Identification of epileptogenic foci in patients with refractory epilepsy remains a significant diagnostic challenge. Magnetic resonance imaging studies frequently fail to reveal an anatomic origin for the seizures, and scalp electroencephalography is often limited to identification of the involved hemisphere. Functional imaging modalities such as PET and SPECT are more promising tools for this application because they reflect the functional pathology associated with the seizure. These changes are more pronounced ictally, but until recently, no radiopharmaceutical was available that could be used routinely for ictal SPECT. The present study was therefore undertaken to determine whether 99mTc-bicisate could be used in ictal SPECT in pediatric patients with refractory epilepsy, to compare the patterns of ictal and interictal blood flow in these patients and to compare the localization information provided by ictal SPECT with that available from other techniques. METHODS: Technetium-99m-bicisate/SPECT was compared prospectively with scalp EEG for its ability to identify a possible seizure focus in pediatric patients with refractory epilepsy. Ictal and interictal SPECT studies were performed in 10 patients (3-19 yr old, mean age 10.9 +/- 4.3 yr; 7 female, 3 male) in whom MRI scans revealed no lesions that might be responsible for the seizures. RESULTS: Ictal SPECT was performed in all patients, and all ictal studies revealed focal perfusion abnormalities. By comparison, four of the interictal SPECT studies showed regional hypoperfusion that corresponded to the regions of hyperperfusion in the ictal studies, and three showed regional hyperperfusion corresponding to the hyperperfused regions in the ictal studies. Three interictal studies revealed no abnormal perfusion. Scalp EEG provided localization information in five patients. CONCLUSION: These initial results suggest that ictal SPECT with 99mTc-bicisate is a more promising tool for the identification of epileptogenic foci than interictal SPECT or scalp EEG in patients without focal abnormalities on MRI.     

Continuous source imaging of scalp ictal rhythms in temporal lobe epilepsy

PURPOSE: We wished to determine whether continuous EEG source imaging can predict the location of seizure onset with sublobar accuracy in temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed the earliest scalp ictal rhythms, recorded with 23- to 27-channel EEG, in 40 patients with intractable TLE. A continuous source analysis technique with multiple fixed dipoles (Focus 1.1) decomposed the EEG into source components representing the activity of major cortical sublobar surfaces. For the temporal lobe, these were basal, anterior tip, anterolateral, and posterolateral cortex. Ictal EEG onset was categorized according to its most prominent and leading source component. All patients underwent intracranial EEG studies before epilepsy surgery, and all had a successful surgical outcome (follow-up >1 year). RESULTS: Most patients with ictal rhythms having a predominant basal source component had hippocampal-onset seizures, whereas those with seizures with prominent lateral source activity had predominantly temporal neocortical seizure origins. Seizures with a prominent anterior temporal tip source component mostly had onset in entorhinal cortex. Seizures in some patients had several equally large and nearly synchronous source components. These seizures, which could be modeled equally well by a single oblique dipole, had onset predominantly in either entorhinal or lateral temporal cortex. CONCLUSIONS: Multiple fixed dipole analysis of scalp EEG can provide information about the origin of temporal lobe seizures that is useful in presurgical planning. In particular, it can reliably distinguish seizures of mesial temporal origin from those of lateral temporal origin.     

Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families

We report clinical, EEG and neuroimaging findings of three patients in two Italian families with merosin-negative congenital muscular dystrophy (CMD), drug-resistant occipital epilepsy, diffuse persistent cerebral white matter changes and focal cortical dysplasia. Clinical and epilepsy histories, EEG and neuroimaging findings were very similar in all patients. Seizures started in childhood and mainly consisted of periodic spasms, a particular type of partial seizure characterized by clusters of epileptic spasms. The motor expression of the spasms was very mild so that they had been frequently missed or misinterpreted as non-convulsive generalized absence seizures. Interictal EEG showed occipital spike-waves and bilateral synchronous slow spike-wave discharges. Ictal EEG showed prolonged periodic sequences of slow waves with associated fast rhythm complexes, characteristic of periodic spasms. Two patients had normal intelligence, one patient presented moderate mental retardation. Focal cortical dysplasia in the posterior areas of the brain, in addition to marked diffuse white matter alterations, was detected in the magnetic resonance images of all patients. Findings in these patients indicate that in merosin-negative CMD brain involvement can include cortical dysplasia, in addition to white matter changes. In such cases the brain damage can lead to a childhood-onset localization-related symptomatic occipital epilepsy. Epileptic seizures and cortical dysplasia can be, however, difficult to detect in CMD. The clinical semiology of epileptic seizures may in fact be modified because of muscular weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG-polymyographic recordings may be necessary to identify it. Similarly, cortical dysplasia may be very localized and visible by neuroimaging only if it is carefully investigated on the basis of epileptological and EEG-polymyographic findings.     

Molecular characterization of a dual endothelin-1/Angiotensin II receptor

Clinical neurophysiologic studies have an important role in the diagnosis and management of the patient with epilepsy. Epilepsy is a clinical diagnosis and the EEG is an important adjunct used to differentiate epileptic seizures from nonepileptic events, refine the diagnosis of epilepsy into specific seizure types and epileptic syndromes, and provide a measure of brain function. The value of the EEG is highly dependent on the clinical context in which it is being applied. In some epilepsies the interictal EEG may be diagnostic whereas in others an ictal recording may be necessary to obtain a specific diagnosis. Both the interictal and ictal EEG characteristics vary with specific seizure types and epilepsies and are described in detail in this review. The usefulness of the EEG in the management of epilepsy and in aiding in the decision to discontinue antiepileptic therapy is also discussed.     

The ictal electroencephalogram as a marker for the efficacy of electroconvulsive therapy

The question of how to define a therapeutically adequate electroconvulsive therapy (ECT) has been under discussion since the early days of ECT. Although convention has asserted a demand for minimum seizure times, the complex electrophysiological conditions involved in developing a generalized seizure make it problematic for therapeutic efficacy of ECT to be linked only with seizure duration. Within the framework of an open clinical study of 40 patients, selected parameters of the ictal electroencephalogram (EEG) have now been examined with respect to differentiation between therapeutically effective and ineffective treatments. For this purpose a rating scale covering both quantitative and qualitative features of the ictal EEG was used. Although this study recorded no correlations between seizure duration and clinical improvement, correlations were established between clinical improvement, on the one hand, and the frequency of epileptic discharges and their slowing during the spike-wave phase as well as the stereotypy of the discharge or a "stable" pattern of rhythmic spike-wave or sharp wave complexes, on the other. The results suggest that several of these EEG parameters might be combined to form a marker for therapeutically adequate ECT, and that treatment might be controlled accordingly.     

Seizures involving the supplementary sensorimotor area in children: a video-EEG analysis

Most reports of supplementary sensorimotor seizures have been of adults with medically refractory epilepsy. Typically, supplementary sensorimotor seizures have onset in childhood. We describe the electroclinical features in 12 children. Cases were selected from an EEG laboratory population in whom video-EEG was performed routinely on all children. Supplementary sensorimotor seizures were diagnosed when there was bilateral tonic posturing of the upper or lower extremities, preserved consciousness, and lack of postictal confusion. Sensory auras were reported by 8 of 9 children aged > 3 years who had daytime seizures. Speech arrest occurred in all patients in whom it could be assessed, and abnormal vocalization was observed in 7 children. Interictal EEGs were often normal (49% of recordings), and ictal EEG changes could be subtle. An etiology was demonstrated in only 2 children, and brain imaging studies were normal in the other 10 patients. Seizures were controlled with antiepileptic drugs (AEDs) in 6 of the 12 children. The clinical manifestations of supplementary sensorimotor seizures in children are similar to those reported in adults; misdiagnosis is common at all ages.