Off-label gabapentin masking ictal triphasic waves: case analysis of neuropsychiatric and electrographic correlates

Antiepileptic drugs (AEDs) are frequently used off-label for the treatment of psychiatric, pain, and other neurological disorders. Off-label AED use may confound the diagnosis for acute neuropsychiatric changes associated with delirium by fortuitously treating, or partially treating, underlying seizure disorders while masking ictal electrographic patterns on EEGs. Standard video/EEG monitoring includes weaning from AEDs to maximize ictal activity and better determine seizure focus. We report a case of off-label gabapentin use masking ictal electrographic activity, the neuropsychiatric and electrographic consequences of discontinuing gabapentin, and the therapeutic response when gabapentin was re-initiated and titrated to a total daily dose greater than that at time of admission. Weaning from AEDs with concurrent video/EEG monitoring is an important diagnostic tool in these complex cases.     

Clinical significance of periodic lateralized epileptiform discharges: relationship with status epilepticus

A retrospective study was carried out in 147 patients who had been found to have periodic lateralized epileptiform discharges (PLEDs). Clinical, laboratory, radiological, and pathological correlation was performed for all patients. As in previously published works, we found a high correlation with cerebrovascular accidents in our population. A large number of patients, however, had no evidence of focal central nervous system pathology. An attempt was made to find a temporal relationship between the onset of seizure activity (or neurological dysfunction in those patients without seizure activity) and the recording of an EEG with PLEDs. We found that most of the EEGs with PLEDs were obtained within the first 4 days of seizure activity or status epilepticus condition. We postulate that the EEG phenomenon of PLEDs could be considered a part of the status epilepticus condition. Suggestive of this was the fact that the first EEG record obtained in one-third of our patients showed electrographic partial status epilepticus. In a small percentage of our patients, a transitional record showed first status epilepticus and then PLEDs. We found that PLEDs usually disappeared from the EEG tracing within 9 days post-ictus flash status. They were most frequently replaced by focal slowing or random spike activity.     

Electroencephalography in neonatal seizures: comparison of a reduced and a full 10/20 montage

This study compares a reduced electrode montage (9 electrodes) with the full 10/20 electrode montage for the ability to detect and characterize neonatal seizures and background electroencephalographic (EEG) characteristics, utilizing new digital technology allowing "remontage" of previously acquired records. A total of 151 neonatal EEG records were retrospectively and blindly analyzed by two readers. Records were first analyzed for seizure number, topography, duration, and characteristics of EEG background using the reduced montage, before reanalysis with the full montage. One hundred eighty-seven seizures were identified in 31 ictal recordings using the full montage. Using the reduced montage, 166 seizures were identified in 30 records. The sensitivity and specificity of the reduced montage for detecting electrographic seizures was 96.8% and 100% respectively. In only one patient's record, the single seizure was missed altogether. For grading background abnormalities, the sensitivity and specificity of reduced montage was 87% and 80%. Although there are inherent weaknesses in reduced montages with respect to both underestimation and overestimation of seizure number, a nine-electrode reduced montage can be a sensitive tool for identification of neonatal seizures and assessment of background characteristics of neonatal electroencephalography.     

Electrographic status epilepticus in children with critical illness: Epidemiology and outcome

Electrographic seizures and electrographic status epilepticus are common in children with critical illness with acute encephalopathy, leading to increasing use of continuous EEG monitoring. Many children with electrographic status epilepticus have no associated clinical signs, so EEG monitoring is required for seizure identification. Further, there is increasing evidence that high seizure burdens, often classified as electrographic status epilepticus, are associated with worse outcomes. This review discusses the incidence of electrographic status epilepticus, risk factors for electrographic status epilepticus, and associations between electrographic status epilepticus and outcomes, and it summarizes recent guidelines and consensus statements addressing EEG monitoring in children with critical illness.This article is part of a Special Issue entitled “Status Epilepticus”.     

Beta activity in status epilepticus

Focal beta activity on scalp EEG is a rare seizure pattern that has most extensively been studied in patients undergoing evaluation for epilepsy surgery. However, ictal beta activity is uncommon beyond this population and has not been reported in human status epilepticus. We observed ictal focal beta activity as the predominant seizure pattern in a patient with refractory status epilepticus. Continuous left temporal beta activity clinically correlated with complex partial semiology on video-EEG.     

Adequacy of routine EEG examinations in neonates with clinically suspected seizures.

This study identified the clinical and electroencephalographic (EEG) characteristics that distinguished neonates with EEG-confirmed seizures from those without, in order to assess the adequacy of routine short-term EEG examinations in neonates with clinically suspected seizures. Two different subgroups of tracings were analyzed: EEGs performed on therapeutically paralyzed (TP+) neonates and EEGs performed on non-therapeutically paralyzed (TP-) neonates. The rate of electrographic seizures, abnormal EEG background activity, and excessive sharp EEG transients (SETs) was significantly more common in the tracings performed on TP- neonates. In lethargic/comatose TP- neonates with clinically suspected seizures and abnormal EEG background activity, the rate of EEGs with excessive SETs (implying a "lowered seizure threshold") occurred equally in tracings with or without documented electrographic seizures. Consequently, we suspect that routine EEGs may be inadequate to electrographically confirm suspected seizures in some TP- neonates due to a large sampling error. In contrast, routine 40-minute EEGs are probably adequate to seek evidence of electrographic seizure activity in TP+ neonates because their seizure rate is low and most do not display background abnormalities or excessive SETs.     

On the prognostic value of ictal EEG patterns in temporal lobe epilepsy surgery: A cohort study

PurposeTo investigate the prognostic value of ictal scalp EEG patterns in drug-resistant temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) prior to undergoing temporal lobectomy.MethodsScalp EEGs of the first seizure recorded during presurgical long-term video-EEG monitoring of 284 patients were reviewed. Patients were divided according to seizure laterality as either unilateral, when the EEG was restricted to one cerebral hemisphere for the entire seizure, or bilateral, when there was involvement of both hemispheres during the seizure. In patients with unilateral hippocampal sclerosis (HS), seizures were subdivided according to the side of initial ictal activity in relation to the side of the HS, as concordant, non-lateralising or contralateral. Postsurgical seizure outcome, according to Engel's classification, was verified at 1, 2, and 5 years after surgery.ResultsThere was no significant association between ictal EEG characteristics and postsurgical seizure outcome. An Engel I seizure outcome was observed in 87.1% of the patients with unilateral ictal EEGs and in 79.6% of those with bilateral ictal EEGs (p = 0.092).ConclusionAnalysis of the localisation, morphology, and lateralisation of ictal EEG patterns did not provide prognostic information regarding seizure-free status in patients with MTLE-HS undergoing temporal lobectomy.     

The effect of lamotrigine on the EEGs of children and adolescents with epilepsy

Lamotrigine (LTG) is one of the newer-generation antiepileptic drugs (AEDs) with broad-spectrum efficacy against a variety of seizures and epileptic syndromes. We retrospectively evaluated the effects of LTG as add-on therapy on EEGs of children and adolescents. The EEGs of 53 patients (mean age: 12.5 years) with primarily pharmacoresistant epilepsy were reviewed prior to and after LTG add-on therapy. Multiple seizure types were seen in 25, generalized seizures in 15, and complex partial seizures in 13 of the patients. Preceding LTG therapy, the baseline EEG was abnormal because of slow background in 60.3% and localized spikes in 35.8%, generalized spikes in 28.3%, or both in 24.5%. The EEG analysis during the 2-year follow-up period showed improvement in the background in 21.9%, interictal activity in 37.8%, and ictal pattern in 41.1% of the EEG recordings. Overall, LTG resulted in improvement in electrographic features which paralleled the clinical improvement.     

Spread of ictal activity in focal epilepsy

Purpose: Latencies between seizure onset, propagation of ictal activity, and initial clinical symptoms and signs are critically important for the successful implementation of detection‐based intervention systems in the treatment of epilepsy. This study analyzes intracranial EEG‐recordings for temporal characteristics of ictal spread and its dependence on focus localization. Methods: Intracerebral EEG recordings of 215 seizures from 43 patients with pharmacoresistant focal epilepsy were evaluated based on site of first propagation, latencies between EEG seizure onset, early propagation, and clinical seizure onset. Seizure onset was mesial temporal in 15 patients, neocortical temporal in 15 patients, and frontal in 13 patients. Results: Periods during which ictal activity remained confined to the seizure onset area showed significant differences between the patient groups. Median latencies between electrographic seizure onset and early propagation were significantly longer for patients with mesial temporal (5 s in seizure‐based analysis/10 s in patient‐based analysis) as compared to neocortical temporal (3 s/5 s) and frontal seizure focus (1 s/2 s; p < 0.01). Concordantly, median latencies to onset of clinical symptomatology were significantly longer for patients with mesial temporal (17 s/19 s) as compared to neocortical temporal (11 s/17 s) and frontal seizure focus (4 s in seizure‐based analysis and 6 s in patient‐based analysis; p < 0.01). Conclusions: The speed of propagation of ictal activity and the latencies until initial clinical seizure symptoms differ significantly depending on focus localization. Extended spread often occurred within the time window during which current detection systems operate. This suggests that inclusion criteria of patients suitable for testing the efficacy of detection‐based seizure intervention strategies should be based on focus localization and patient‐individual propagation patterns.     

SPECT abnormalities in Landau-Kleffner syndrome

Five right-handed children with acquired aphasia elipepsy syndrome (Landau-Kleffner, LKS), were investigated with 99^m TcHMPAO single photon emission computed tomography (SPECT) and the results were correlated with their EEGs and clinical history. The childrens' ages ranged from 2 to 5 years and the aphasia had been present for 6 to over 12 months. No clinical seizure had ever been onserved in the younger two children and their waking EEGs showed infrequent central spikes. Both children had areas of low intensity on SPECT, involving the left temporal lobe in one and the right temporal lobe in the other, which has also been reported in children with congenital dysphasia who have normal EEGs. The three older children presented with frequent generalized seizures, with the aphasia occurring 3–6 months later. The SPECT scans in these children were performed either in the ictal state, or when electrographic seizure activity was very frequent on EEG. All three children had hyperintense foci on SPECT involving the left posterior temporal region corresponding to Wernickes area. We conclude that LKS may be initially a unilateral seizure disorder of Wernickes area, with EEG discharges in the contralateral hemisphere representing propagation from the unilateral focus.     

Generalized Convulsive Status Epilepticus in the Adult

Summary: Status epilepticus (SE) is denned as recurrent epileptic seizures without full recovery of consciousness before the next seizure begins, or more-or-less continuous clinical and/or electrical seizure activity lasting for more than 30 min whether or not consciousness is impaired. Three presentations of SE are now recognized: recurrent generalized tonic and/or clonic seizures without full recovery of consciousness between attacks, nonconvulsive status where the patient appears to be in a prolonged "epileptic twilight state," and continuous/repetitive focal seizure activity without alteration of consciousness. Generalized convulsive status epilepticus (GCSE) encompasses a broad spectrum of clinical presentations from repeated overt generalized tonic-clonic seizures to subtle convulsive movements in a profoundly comatose patient. Thus, GCSE is a dynamic state that is characterized by paroxysmal or continuous tonic and/or clonic motor activity, which may be symmetrical or asymmetrical and overt or subtle but which is associated with a marked impairment of consciousness and with bilateral (although frequently asymmetrical) ictal discharges on the EEG. Just as there is a progression from overt to increasingly subtle clinical manifestations of GCSE, there is also a predictable sequence of progressive EEG changes during untreated GCSE. A sequence of five patterns of ictal discharges has been observed: discrete electrographic seizures, waxing and waning, continuous, continuous with flat periods, and periodic epileptiform discharges on a relatively flat background. A patient actively having seizures or comatose who exhibits any of these patterns on EEG should be considered to be in GCSE and should be treated aggressively to stop all clinical and electrical seizure activity to prevent further neurological morbidity and mortality.     

Utility of the Scalp-Recorded Ictal EEG in Childhood Epilepsy

PURPOSE: To evaluate the usefulness of the scalp-recorded ictal EEGs in diagnosing childhood epilepsy. METHODS: We analyzed the ictal EEGs of 259 seizures in 183 patients who visited the department of child neurology, Okayama University Medical School, during the past 6 years. RESULTS: We divided all seizures into the following four categories, according to the diagnostic usefulness of ictal EEGs in determining the seizure type: 1. (a) Ictal EEGs confirmed the diagnosis of the seizure type based on seizure symptoms (101 seizures); (b) Ictal EEGs aided in the classification of the seizure type based on the seizure symptoms (101 seizures); (c) Ictal EEGs corrected errors in the classification (37 seizures); and (d) Ictal EEGs revealed previously unreported/undocumented seizure type (20 seizures). 2. Of the 37 misdiagnosed seizures (group C), 11 were nonepileptic seizures misdiagnosed as epileptic seizures, eight were complex partial seizures (CPS) misdiagnosed as the other seizure types, and 10 were other seizure types misdiagnosed as CPSs. 3. Of the 20 previously unreported/undocumented seizures (group D), nine were myoclonic seizures, five were absence seizures, five were CPS, and one was tonic spasms. 4. Seventy-two patients had CPS. Among them, 11 patients showed no epileptic spikes in their interictal EEG recordings. Therefore, ictal recordings confirmed the diagnosis of epilepsy. CONCLUSIONS: Ictal EEG recording is a very useful diagnostic tool not only for determining seizure types, but also for uncovering the existence of the unsuspected seizure types. It supplies the physician with useful information for the classification and the treatment of epilepsy. In particular, ictal EEGs are useful in diagnosing patients with CPS.     

Persistent Nonconvulsive Status Epilepticus After the Control of Convulsive Status Epilepticus

Summary: Purpose: Convulsive status epilepticus (CSE) is a major medical and neurological emergency that is associated with significant morbidity and mortality. Despite this high morbidity and mortality, most acute care facilities in the United States cannot evaluate patients with EEG monitoring during or immediately after SE. The present study was initiated to determine whether control of CSE by standard treatment protocols was sufficient to terminate electrographic seizures. Methods: One hundred sixty-four prospective patients were evaluated at the Medical College of Virginia/VCU Status Epilepticus Program. Continuous EEG monitoring was performed for a minimum of 24 h after clinical control of CSE. SE and seizure types were defined as described previously. A standardized data form entry system was compiled for each patient and used to evaluate the data collected. Results: After CSE was controlled, continuous EEG monitoring demonstrated that 52% of the patients had no after-SE ictal discharges (ASIDS) and manifested EEG patterns of generalized slowing, attenuation, periodic lateralizing epileptiform discharges (PLEDS), focal slowing, and/or burst suppression. The remaining 48% demonstrated persistent electrographic seizures. More than 14% of the patients manifested nonconvulsive SE (NCSE) predominantly of the complex partial NCSE seizure (CPS) type (2). These patients were comatose and showed no overt clinical signs of convulsive activity. Clinical detection of NCSE in these patients would not have been possible with routine neurological evaluations without use of EEG monitoring. The clinical presentation, mortality, morbidity, and demographic information on this population are reported. Conclusions: Our results demonstrate that EEG monitoring after treatment of CSE is essential to recognition of persistent electrographic seizures and NCSE unresponsive to routine therapeutic management of CSE. These findings also suggest that EEG monitoring immediately after control of CSE is an important diagnostic test to guide treatment plans and to evaluate prognosis in the management of SE.     

A machine-learning algorithm for detecting seizure termination in scalp EEG

Efforts to develop algorithms that can robustly detect the cessation of seizure activity within scalp EEGs are now underway. Such algorithms can facilitate novel clinical applications such as the estimation of a seizure's duration; the delivery of therapies designed to mitigate postictal period symptoms; or detection of the presence of status epilepticus. In this article, we present and evaluate a novel, machine learning-based method for detecting the termination of electrographic seizure activity. When tested on 133 seizures from a public database, our method successfully detected the end of 132 seizures within 10.3 ± 5.5 seconds of the time determined by an electroencephalographer to represent the electrographic end of seizure. Furthermore, by pairing our seizure end detector with a previously published seizure onset detector, we could automatically estimate the duration of 85% of test electrographic seizures within a 15-second error margin compared with electroencephalographer determinations. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.     

Improving the interpretation of ictal scalp EEG: BSS-CCA algorithm for muscle artifact removal

PURPOSE: To investigate the potential clinical relevance of a new algorithm to remove muscle artifacts in ictal scalp EEG. METHODS: Thirty-seven patients with refractory partial epilepsy with a well-defined seizure onset zone based on full presurgical evaluation, including SISCOM but excluding ictal EEG findings, were included. One ictal EEG of each patient was presented to a clinical neurophysiologist who was blinded to all other data. Ictal EEGs were first rated after band-pass filtering, then after elimination of muscle artifacts using a blind source separation-canonical correlation analysis technique (BSS-CCA). Degree of muscle artifact contamination, lateralization, localization, time and pattern of ictal EEG onset were compared between the two readings and validated against the other localizing information. RESULTS: Muscle artifacts contaminated 97% of ictal EEGs, and interfered with the interpretation in 76%, more often in extratemporal than temporal lobe seizures. BSS-CCA significantly improved the sensitivity to localize the seizure onset from 62% to 81%, and performed best in ictal EEGs with moderate to severe muscle artifact contamination. In a significant number of the contaminated EEGs, BSS-CCA also led to an earlier identification of ictal EEG changes, and recognition of ictal EEG patterns that were hidden by muscle artifact. CONCLUSIONS: Muscle artifacts interfered with the interpretation in a majority of ictal EEGs. BSS-CCA reliably removed these muscle artifacts in a user-friendly manner. BSS-CCA may have an important place in the interpretation of ictal EEGs during presurgical evaluation of patients with refractory partial epilepsy.     

Identification of the temporal components of seizure onset in the scalp EEG

BACKGROUND: The identification of the earliest indication of rhythmical oscillations and paroxysmal events associated with an epileptic seizure is paramount in identifying the location of the seizure onset in the scalp EEG. In this work, data-dependent filters are designed that can help reveal obscure activity at the onset of seizures in problematic EEGs. METHODS: Data-dependent filters were designed using temporal patterns common to selected segments from pre-ictal and ictal portions of the scalp EEG. Temporal patterns that accounted for more variance in the ictal segment than in the pre-ictal segment of the scalp EEG were used to form the filters. RESULTS: Application of the filters to the scalp EEG revealed temporal components in the seizure onset in the scalp recording that were not obvious in the unfiltered EEG. Examination of the filtered EEG enabled the onset of the seizure to be recognized earlier in the recording. The utility of the filters was confirmed qualitatively by comparing the scalp recording to the intracranial recording and quantitatively by calculating correlation coefficients between the scalp and intracranial recordings before and after filtering. CONCLUSION: The data-dependent approach to EEG filter design allows automatic detection of the basic frequencies present in the seizure onset. This approach is more effective than narrow band-pass filtering for eliminating artifactual and other interference that can obscure the onset of a seizure. Therefore, temporal-pattern filtering facilitates the identification of seizure onsets in challenging scalp EEGs.     

Clinical and electroencephalographic features of simple partial seizures

The clinical and electroencephalographic features of 87 simple partial seizures in 14 patients were studied with video-EEG telemetry. The patients were able to respond to verbal stimuli during all seizures and, later, could clearly recall ictal events. To determine whether the EEG changes in simple partial seizures could be reliably observed, a reader blindly reviewed four EEGs of equal duration for each seizure. These EEGs consisted of one ictal and three nonictal recordings obtained at predetermined times before the seizure. There were 27 motor seizures (mean duration, 86 seconds; range, 2 to 250 seconds), all involving clonic movements of the head and/or upper extremities; 8 (30%) of these had a sensory component (pain in 6, paresthesia in 2). An EEG change, usually localized spikes or sharp waves over the contralateral or both rolandic regions, was identifiable in nine (33%) of the motor seizures. The 60 nonmotor seizures (mean duration, 63 seconds; range, 8 to 375 seconds) involved a variety of symptoms, including somatosensory/special sensory (3 seizures), autonomic (26 seizures), cognitive (1 seizure), affective (14 seizures), and mixed, or more than one category of nonmotor symptoms (16 seizures). In only nine (15%) of the nonmotor seizures was there an ictal EEG change, usually localized spikes or paroxysmal theta activity over the temporal region. Overall, among the 87 simple partial seizures, only 18 (21%) revealed ictal EEG changes. Thus, a normal EEG is common during simple partial seizures and does not exclude the diagnosis.     

The EEG in nonepileptic seizures.

Nonepileptic seizures are episodes that resemble seizures but are not epileptic. The importance of EEG in the diagnosis of NES is that misread (overread) EEGs are an important contributor to the misdiagnosis of epilepsy. About 20% to 30% of patients with refractory "seizures" seen at epilepsy centers have been misdiagnosed, and the vast majority have psychogenic nonepileptic seizures (PNES). Many such patients have had previous EEGs interpreted as epileptiform. These misdiagnoses based on EEG are easily perpetuated, complicate management, and adversely affect outcome. The reasons for the overinterpretation of EEGs include the common misconception that phase reversals indicate abnormalities and not applying strict criteria to make sharp transients epileptiform. The diagnosis of PNES typically begins with a clinical suspicion and then is confirmed with EEG-video monitoring. However, ictal EEG may be negative in some partial seizures and may be uninterpretable because of artifacts. Movements can generate rhythmic artifacts that mimic an electrographic seizure. Analysis of the ictal semiology (i.e., video) is at least as important as the ictal EEG. Provocative techniques, activation procedures, or "inductions" can also be useful for the diagnosis of PNES.     

Assessment of hairline EEG as a screening tool for nonconvulsive status epilepticus

PURPOSE: Because of the high incidence of nonconvulsive status epilepticus (NCSE), the attraction of a "quick and easy" screening electroencephalogram (EEG) is obvious. Previous studies have shown utility of hairline EEG in diagnosing epilepsy. However, this technique has not been evaluated as a screening tool for NCSE. We wanted to provide proof of principle that a screening hairline EEG has sufficient sensitivity to use as a screening tool for diagnosing NCSE. METHODS: A total of 120, 2- to 3-min EEG samples of normal and various abnormal digital EEG studies were reformatted in three six-channel montages (A, longitudinal bipolar; B, referential to ipsilateral ear; C, referential to contralateral ear) that mimicked a hairline recording and were interpreted by five neurophysiologists. The test data interpretation was compared with the original EEG interpretation. RESULTS: Performance was best with montages A and B; 71% and 70.5% of the samples were interpreted correctly by using these montages. Only 65% of the samples were correctly interpreted by using montage C. With the best montage (A), the sensitivities ranged from 91% for normal EEG to 54% for periodic lateralized epileptiform discharges (PLEDs). The sensitivity for seizures was only 72%. Seizures were frequently misinterpreted as more benign patterns such as normal and diffuse slowing. CONCLUSIONS: EEG data reformatted to resemble a hairline EEG had low sensitivity for detecting seizures. As a result, we do not recommend further pursuit of hairline EEG as a "quick and easy" screening tool for NCSE.     

A long‐term follow‐up study of Dravet syndrome up to adulthood

Purpose : We intended to elucidate the whole clinical course of Dravet syndrome (DS) comprehensively, from infancy through adulthood. Methods : Subjects were 31 patients with DS (14 with typical DS, and 17 with borderline DS) who were followed from childhood to at least 18 years of age. Their seizures, abilities, and electroencephalography (EEG) findings were investigated and statistically analyzed. Results : The clinical findings of the patients with typical DS and those with borderline DS became largely similar in adolescence and adulthood. Seizures were intractable in childhood in all patients, but suppressed in five (16.1%) during follow‐up. Thirty‐five (87.5%) of the 40 apparently generalized convulsive seizures that were captured by ictal EEG recording at 7 years of age or later were of focal origin. The seizure‐free outcomes were significantly correlated with the experience of <3 episodes of convulsive status epilepticus, and also with disappearance of spikes on the follow‐up EEGs. Mental outcomes involving less severe intellectual disability were correlated with the presence of occipital alpha rhythms in the background activity of the follow‐up EEGs. Mean age at the recording of the follow‐up EEGs was 23.8 years. Discussion : Prevention of the occurrence of convulsive status epilepticus was indicated to be critically important for the improvement of seizure prognosis in DS.