Foramen ovale electrodes can identify a focal seizure onset when surface EEG fails in mesial temporal lobe epilepsy

PURPOSE: We analyze a series of patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) submitted to presurgical investigation with scalp sphenoidal, followed by foramen ovale electrodes (FO), and, when necessary, with depth temporal electrodes. We sought to evaluate the clinical utility of FO in patients with MTLE-HS. METHODS: We included patients who had phase I investigation with bitemporal independent seizures, nonlateralized ictal onsets, or ictal onset initiating in the side contralateral to the side of hippocampal sclerosis. Patients whose implanted FO failed to demonstrate an unambiguous unilateral ictal onset were later evaluated with depth hippocampal electrodes. RESULTS: Between May 1994 and December 2004, 64 patients met our inclusion criteria: 33 female (51.5%) and 31 male subjects (48.5%). The mean age at enrollment was 37.66+/-10.6 years (range, 12-56 years). The groups with nonlateralized surface ictal EEG onsets and contralateral EEG onsets had a greater chance of lateralization with FO when compared with the group with bilateral independent seizures on surface EEG (p<0.01). Foramen ovale electrodes lateralized the seizures in 60% of patients. Seventy percent of patients became seizure free after temporal lobectomy. Five patients were implanted with depth temporal electrodes after FO video-EEG monitoring. The depth-electrode EEG onsets confirmed the results of FO video-EEG monitoring in all patients, and the surgery was refused. CONCLUSIONS: In MTLE-HS, FO is a reliable method for lateralization of seizures that are not clearly recorded by surface EEGs.     

Cerebral white matter abnormalities associated with chromosome 18q duplication

BackgroundChromosome 18q duplications are associated with a range of phenotypes often similar to complete trisomy 18, variably including poor growth, feeding difficulties, congenital malformations and dysmorphic facial features. Although 18q duplication patients may have seizures and developmental impairment, brain MRI typically shows only variable degrees of cerebral atrophy.PatientWe present a boy with a 52.2 Mb 18q duplication in whom brain MRI in the neonatal period showed striking white matter abnormalities, most notable in the frontal lobes. His clinical presentation was otherwise in keeping with trisomy 18, including characteristic facial features, hypotonia, cardiac malformation, rocker bottom feet, pectus excavatum, short and broad thumbs and halluces, and diabetes insipidus.ConclusionSince not previously reported in association with 18q duplication, the observation of cerebral white matter anomalies is particularly interesting. This radiologic pattern is a well-recognized feature of 18q deletion syndrome, hypothesized by many to occur due to haploinsufficiency of MBP, the gene encoding myelin basic protein. The mechanisms leading to the white matter anomalies in this patient remain unexplained.     

Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy

Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE).We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1–2 s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA).At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW.Our case is the first patient with BMEI reported in the literature who later developed a CAE.This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes.     

3 TESLA MR imaging in adults with focal onset epilepsy

Objective

The finding of cerebral epileptogenic lesions in magnetic resonance (MR) has demonstrated to be a relevant prognostic factor for potential surgical candidates. In a series of consecutive adults with focal onset epilepsy, we investigated the yield of 3 T MR imaging for detecting epileptogenic cerebral lesions.

Materials and methods

We prospectively recruited 161 adult patients with a diagnosis of focal epilepsy, all of whom underwent standardized MR imaging study performed with a 3 T magnet.

Results

Lesion-related epilepsy was observed in 48% of patients, and 12% of cryptogenic patients showed subtle or non-specific lesions related to the epileptogenic source. The most common findings were focal cortical dysplasia and vascular lesions, followed by mesial temporal sclerosis, tumors, and scars from previous cerebral injuries. Patients older than 72 years were more likely to have vascular epilepsy.

Conclusions

Diagnostic assessment using a standardized 3 T MR imaging protocol for focal-onset epilepsy detects lesions in nearly half the patients. Our results indicate that elders with focal epilepsy should be searched for vascular lesions.     

Autonomic seizures versus syncope in 18q- deletion syndrome: a case report

PURPOSE: The 18q- deletion syndrome (18qDS) is frequently associated with cardiac anomalies. Patients with this syndrome may also have epilepsy, which presents certain diagnostic difficulties. This case report aims to illustrate these diagnostic problems, document the usefulness of heart rate-based seizure detection algorithms in this setting, and define the epilepsy syndrome associated with 18qDS. METHODS: Closed-circuit video electroencephalogram (EEG) monitoring using a heart rate-based seizure detection software was used to identify the event in question and to establish the diagnosis of epilepsy. Chromosomal analysis and magnetic resonance imaging (MRI) were used to further define the epilepsy syndrome. RESULTS: We report on a patient with an atrial septal defect, enlargement of the right heart, and incomplete right bundle branch block, who developed episodes of tachycardia, loss of consciousness, and pallor, for which he was amnesic. Chromosomal analysis demonstrated karyotype 46,XY,del(18)(q21.3). ish del(18)(wcp18+,D18Z1+) with a loss of the gene for myelin basic protein. MRI revealed multifocal dysmyelination. Video-EEG monitoring using an electrocardiogram (ECG)-triggered seizure detection software proved to be indispensable in detecting an autonomic seizure and establishing the correct diagnosis; the procedure also allowed for the definition of the epilepsy syndrome. The patient was treated with carbamazepine and remained seizure-free. CONCLUSIONS: Video-EEG monitoring using a heart rate-based seizure detection software can be helpful in diagnostically differentiating autonomic seizures from syncope. Dysmyelination due to loss of the myelin basic protein gene on 18q and cortical dysgenesis may be of pathogenic relevance.     

伴中央颞区棘波的儿童良性癫痫典型及非典型病例探讨

目的 探讨ＢＥＣＣＴ典型与非典型特征,以提高对该病的认识。方法 分别５６例ＢＥＣＣＴ临床发作形式、ＥＥＧ表现、影像学及治疗资料。结果 ５６例中典型者２３例（４１．０７％）;不典型病例３３例（５８．９３％）,其中临床发作形式不典型１６例（２８．５７％）,ＥＥＧ不典型２５例（４４．６４％）。头ＣＴ及ＭＲＩ检查正常４６例,轻度异常１０例。卡马西平及丙戊酸对治疗典型和非典型的ＢＥＣＣＴ均有效,以卡马西平为优。结论 ＢＥＣＣＴ的诊断应建立在对发病年龄、发作时间及形式、发作间期ＥＥＧ综合分析基础上,可以有不典型的发作。曾接受ＡＥＤｓ治疗者ＥＥＧ可能不典型。     

The effect of Perampanel on EEG spectral power and connectivity in patients with focal epilepsy

ObjectiveQuantitative Encephalography (qEEG) depicts synthetically the features of EEG signal and represents a promising tool in the assessment of neurophysiological changes brought about by Anti-Seizure Medications (ASMs). In this study we characterized qEEG alterations related to add-on therapy with Perampanel (PER). PER is the only ASM presenting a direct glutamatergic antagonism, hence the characterization of PER induced EEG changes could help to better understand its large spectrum of efficacy.MethodsWe analysed standard-19 channel-EEG from 25 People with Epilepsy (PwE) both before (T0) and after (T1) the introduction of PER as add-on treatment. Normal values were obtained in 30 healthy controls (HC) matched for sex and age. EEGs were analysed using Matlab™ and the EEGlab and Brainstorm toolkits. We extracted spectral power and connectivity (Phase locking Value) of EEG signal and then compared these features between T0 and T1 and across groups (PwE, HC), we also evaluated the correlations with clinical features.ResultsPwE showed increased theta power (p = 0.036) after the introduction of PER but no significant change of EEG connectivity. We also found that PwE have reduced beta power (p = 0.012) and increased connectivity in delta (p = 0.013) and theta (p = 0.007) range as compared to HC, but no significant change was observed between T0 and T1 in PwE. Finally, we found that PwE classified as drug responders to PER have greater alpha power both at T0 and at T1 (p = 0.024) suggesting that this parameter may predict response to treatment.ConclusionsPER causes slight increase of theta activity and does not alter connectivity as assessed by standard EEG. Moreover, greater alpha power could be a good marker of response to PER therapy, and potentially ASM therapy in general.SignificanceOur results corroborate the hypothesis that pharmaco-EEG is a viable tool to study neurophysiological changes induced by ASM. Additionally, our work highlights the role of alpha power as a marker of ASM therapeutic response.     

Resting state connectivity in neocortical epilepsy: The epilepsy network as a patient-specific biomarker

ObjectiveLocalization related epilepsy (LRE) is increasingly accepted as a network disorder. To better understand the network specific characteristics of LRE, we defined individual epilepsy networks and compared them across patients.MethodsThe epilepsy network was defined in the slow cortical potential frequency band in 10 patients using intracranial EEG data obtained during interictal periods. Cortical regions were included in the epilepsy network if their connectivity pattern was similar to the connectivity pattern of the seizure onset electrode contact. Patients were subdivided into frontal, temporal, and posterior quadrant cohorts according to the anatomic location of seizure onset. Jaccard similarity was calculated within each cohort to assess for similarity of the epilepsy network between patients within each cohort.ResultsAll patients exhibited an epilepsy network in the slow cortical potential frequency band. The topographic distribution of this correlated network activity was found to be unique at the single subject level.ConclusionsThe epilepsy network was unique at the single patient level, even between patients with similar seizure onset locations.SignificanceWe demonstrated that the epilepsy network is patient-specific. This is in keeping with our current understanding of brain networks and identifies the patient-specific epilepsy network as a possible biomarker in LRE.     

Long-term follow-up of patients with benign partial epilepsy in infancy

PURPOSE: The aim of this study was to investigate the long-term outcome of children with benign partial epilepsy in infancy (BPEI). METHODS: A telephone-interview survey using a structured questionnaire was conducted with patients who were diagnosed as having possible BPEI at age 2 years and who were 8 years or older at the time of the survey. The data from 39 of 48 patients were available. The median age at the time of the survey was 11.3 years; 18 boys and 21 girls were included. RESULTS: Three patients had a recurrence of unprovoked seizure beyond age 2 years. Four patients had cognitive problems (mild mental retardation in three and Asperger syndrome in one). An association of paroxysmal kinesigenic choreoathetosis was observed in three patients, and another three had experienced seizures associated with mild gastroenteritis. Major behavioral problems were not recognized in any patients. Four patients were excluded from having definite BPEI at age 5 years, and another two were excluded for having definite BPEI at the last follow-up. Eventually, 33 of 39 patients were categorized as having definite BPEI beyond 8 years of age. CONCLUSIONS: A large majority of patients diagnosed as possibly having BPEI at age 2 years did not have a recurrence of unprovoked seizures and cognitive problems beyond 8 years of age.     

Late EEG responses triggered by transcranial magnetic stimulation (TMS) in the evaluation of focal epilepsy

PURPOSE: To evaluate the use of EEG responses to transcranial magnetic stimulation (TMS-EEG responses) as a noninvasive tool for the diagnosis of focal epilepsy. METHODS: Fifteen patients and 15 healthy subjects were studied. TMS at an intensity set at resting corticomotor threshold were delivered at the standard EEG electrode positions. For each position, EEG responses to TMS were evaluated before and after averaging EEG recordings synchronized with the TMS pulse. RESULTS: Two types of TMS-EEG responses were seen: (A) early responses: consisting of a single slow wave seen after the TMS pulse; and (B) late TMS-EEG responses, which were subclassified into (b.1) delayed responses: waveforms resembling interictal epileptiform discharges induced by TMS; or (b.2) repetitive responses: onset of a new rhythym induced by TMS. Early responses were observed in patients and healthy subjects when stimulating at various sites and were considered normal responses to TMS. Late TMS-EEG responses were not seen in healthy subjects, whereas they were seen in 11 of the 15 epileptic patients. Late TMS-EEG responses occurred when stimulating the epileptogenic side in eight out of the nine patients who had lateralized late TMS-EEG responses. The combined use of late TMS-EEG responses and interictal scalp EEG would have suggested the diagnosis of focal epilepsy in all patients, despite the absence of late TMS-EEG responses in four patients and the presence of normal interictal scalp EEG in three. CONCLUSIONS: TMS-EEG responses can identify epileptogenic cortex and may substantially improve the diagnosis of focal epilepsy, particularly, if combined with standard EEG studies.     

Alice in wonderland syndrome in an elderly patient with focal onset epilepsy

Alice in wonderland syndrome (AIWS) is a rare perceptual disorder characterized by subjective distortions of visual and somatosensory perception. Symptoms of AIWS are attributable to functional and structural changes of the visual and somatosensory perceptual system; however, few reports have investigated the pathophysiology of AIWS with regard to epilepsy, especially ictal electroencephalogram (EEG) changes. Herein, we describe the case of an 82-year-old woman with focal onset epilepsy presenting with AIWS, whose seizures were documented by video-EEG monitoring. Video-EEG revealed multiple focal impaired awareness seizures, and ictal EEG changes arose from the right occipital region with small periodic positive discharges with evolution towards the right centro-parietal regions. Our case highlights not only a relationship between epileptic seizures and AIWS but also provides pathological insight into AIWS.     

Analysis of initial slow waves (ISWs) at the seizure onset in patients with drug resistant temporal lobe epilepsy

RATIONALE: The goal of this study is to analyze initial slow waves (ISWs) at seizure onset in patients with refractory temporal lobe epilepsy. ISWs are a specific type of ictal EEG pattern characterized by a slow wave at the seizure onset followed by low voltage fast activity. METHODS: Investigations were carried out on 14 patients from the UCLA hospital (USA) and 10 from the Ghent University Hospital (Belgium) implanted with depth and grid electrodes for localization of the epileptogenic zone. RESULTS: Sixty-one seizures in the UCLA group and 30 seizures in the Ghent group were analyzed. Fourteen UCLA and seven Ghent patients had ISWs at seizure onset. The duration of ISWs varied between 0.3 to 6.0 s and maximum amplitude varied from 0.2 to 1.4 mV. ISWs in three of 14 UCLA patients (30% of seizures) had a consistent positive polarity at the deepest contacts that were located in the amygdala, hippocampus, or entorhinal cortex and reversed polarity outside of these brain areas (ISWs1). ISWs in 11 of 14 UCLA patients (70% of seizures) had negative polarity at the deepest electrodes and their amplitude increased toward the recording contacts located in the white matter or neocortex (ISWs2). All ISWs from the seven Ghent patients were negative in the depth contacts (ISWs2) and positive on grid electrodes at the cortical surface. ISWs1 were associated with EEG spikes at the onset and on increase in amplitude of 10-20 Hz sinusoidal activity. In contrast, ISWs2 were associated with suppression of EEG amplitude, an increase in frequency in the range of 20-50 Hz, and did not have EEG spikes at the onset. Multiunit neuronal activity showed strong synchronization of neuronal discharges during interictal spikes, but multiunit synchronization was not obvious during ISWs2. CONCLUSION: The existence of EEG spikes and phase reversal with ISWs1 indicates this type of seizure may be triggered by hypersynchronous neuronal discharges; however, seizures with ISWs2 at the onset may be triggered by different mechanisms, perhaps nonneuronal.     

The value of EEG-fMRI and EEG source analysis in the presurgical setup of children with refractory focal epilepsy

Purpose: In the presurgical evaluation of children and juvenile patients with refractory focal epilepsy, the main challenge is to localize the point of seizure onset as precisely as possible. We compared results of the conventional electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) analysis with those obtained with a newly developed method using voltage maps of average interictal epileptiform discharges (IEDs) recorded during clinical long‐term monitoring and with the results of the electric source imaging (ESI). Methods: Simultaneous EEG‐fMRI was recorded in nine patients (ages 1.5–17.5 years) undergoing presurgical evaluation. The postoperative outcome and resected area were compared with the following: the localizations of blood oxygen–level dependent (BOLD) signal changes associated with IEDs, which were identified by visual inspection changes using SPM5 software (Analysis I); BOLD signal changes related to IED topography, which was characterized using spike‐specific voltage maps of average IED recorded outside the MR scanner during clinical long‐term monitoring (Analysis II); as well as results of EEG source analysis based on the distributed linear local autoregressive average (LAURA) algorithm using the Cartool software by Denis Brunet (Analysis III). Key Findings: All nine patients had postoperative outcome Engel class I–IIb (postoperative time 6–26 months). The analysis I revealed an IED‐related area of activation within the resection area in 3 (33%) of 9 patients, analysis II was able to reliably localize the source of epileptic activity in 4 (44%) of 9 patients, and analysis III rendered results concordant with the postoperative resection site in all nine patients. Conclusions: The localization of seizure onset based on EEG‐fMRI may be a useful adjunct in the preoperative evaluation but also has some deficits that impair the reliability of results. In contrast, EEG source analysis is clearly a more credible method for epileptic focus localization in children with refractory epilepsies. It seems likely that the analysis based on IED topography (Analysis II) may increase sensitivity and reliability of EEG‐fMRI in some patients. However, the benefit from this innovative method in children is rather limited compared with adults.     

Role of MRI in patient selection for surgical treatment of intractable epilepsy in infancy

Epilepsy surgery is an effective treatment in selected patients with localization-related intractable epilepsy. The success of epilepsy surgery is in part dependent upon identification of a lesion on MRI. In infants, the surgical epileptogenic substrates include focal cortical dysplasia (FCD), hemimegalencephaly, tuberous sclerosis complex, Sturge Weber syndrome, hypoxic-ischemic or cerebrovascular injury and low-grade tumor. The sensitivity of MRI in identifying the epileptogenic substrate is influenced by the nature of the epileptogenic substrate, MRI technique and expertise of the interpreting physician. The MRI features of some lesions such as FCD may differ in infants compared to children and adults; the white matter adjacent to FCD may demonstrate lower T2 and higher T1 signal in some infants due to premature myelination, while in others, the white matter demonstrates higher T2 or lower T1 signal due to demyelination, dysmyelination or gliosis, similar to children and adults. The appearances of some lesions, such as FCD, may change with time, due to brain maturation or seizure related changes. MRI for patients with localization-related intractable epilepsy should have high-resolution, multiplanar and multisequence. In infants, volumetric T1 and high-resolution T2 imaging are recommended. FLAIR and proton density sequences are less helpful in infants due to lack of myelin in the white matter. The physician interpreting the scan should be familiar with the imaging appearances of epileptogenic substrates and may need to review the scan more than once if a lesion is not seen on initial inspection.     

Characterization of a novel monoclonal anti-myelin basic protein antibody: use in immunoblotting and immunohistochemical studies

Monoclonal antibodies (MAbs) to the myelin basic protein (MBP) were produced in CAF1 (BALB/c x A/J) mice immunized with intact bovine MBP. A number of MAbs were obtained, one of which was characterized in detail with respect to its isotype, antigenic determinant on the MBP, the spectrum of antigens with which it reacted in mouse brain, and its immunohistochemical staining characteristics. This monoclonal, GB-1 (an IgG1), recognized an epitope within residues 30-51 of bovine MBP. It also reacted with a family of MBP-related proteins present in brain homogenates of mice from 7-35 days. Immunohistochemically, GB-1 stained myelinated fibers and oligodendrocytes in the rodent CNS. A second monoclonal (GB-2, and IgM) was partially characterized. It reacted with intact MBP when it was immobilized to plastic or nitrocellulose, but it was not found to be useful for immunoblots or immunohistochemistry.     

Hemodynamic correlates of epileptiform discharges: an EEG-fMRI study of 63 patients with focal epilepsy

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.     

Peri-ictal broadband electrocorticographic activities between 1 and 700 Hz and seizure onset zones in 18 patients

ObjectiveWe investigated the relationship between locations of broadband peri-ictal electrocorticographic activities determined by a semi-automatic detection method and seizure onset zones in medically intractable epilepsy patients.MethodsWe included 18 patients. Peri-ictal periods (−15 to +5 s from the ictal onset) were divided into 4 periods of 5 s duration each in bandwidth from 1 to 700 Hz divided into 11 bins. Thereafter, we calculated the mean overlapping percentage of the maximum amplitude activity electrodes with the seizure onset zone in the total number of seizures in each patient. Significance was considered at an adjusted p-value of 0.05.ResultsBy the maximum amplitude method with the Bonferroni correction, only high-frequency activities (>60 Hz) during −5 to 0 s from the ictal onset were significantly related to seizure onset zones. In post hoc analyses, bands in 60–139 Hz and 4–7 Hz were significantly related to seizure onset zones in the Bonferroni correction. However, after the less conservative Benjamini–Yekutieli correction and with the epileptogenicity index, other bands and periods after −10 s from the ictal onset were also related with seizure onset zones.SignificanceDetailed bands, timings and analytic methods of peri-ictal activities with high relationships to seizure onset zones were identified.     

Dense array EEG estimated the epileptic focus in a patient with epilepsy secondary to tuberous sclerosis complex

Purpose

Tuberous sclerosis complex (TSC) is a leading cause of epilepsy, with seizures affecting almost 80–90% of children. We used the concordance between magnetic resonance imaging (MRI) and dense array electroencephalography (dEEG) findings to detect epileptic focus in a patient with TSC.

Growing up with epilepsy: a two-year investigation of cognitive development in children with new onset epilepsy

Purpose: To characterize patterns and determinants of normal and abnormal cognitive development in children with new onset epilepsy compared to healthy controls. Methods: Longitudinal (2‐year) cognitive growth was examined in 100 children, age 8–18 years, including healthy controls (n = 48) and children with new onset epilepsy (n = 52). Cognitive maturation was examined as a function of the presence/absence of two neurobehavioral comorbitiies (attention deficit hyperactivity disorder and/or academic problems) identified at the time of epilepsy diagnosis. Groups were compared across a comprehensive neuropsychological battery assessing intelligence, academic achievement, language, memory, executive function, and psychomotor speed. Results: Children with new onset epilepsy without neurobehavioral comorbidities were comparable to healthy controls at baseline, rate of cognitive development, and follow‐up assessment across all neuropsychological domains. In contrast, the presence of neurobehavioral comorbidities was associated with significantly worse baseline and prospective cognitive trajectories across all cognitive  domains, especially executive functions. Conclusion: The presence of neurobehavioral comorbidities at the time of epilepsy onset is a major marker of abnormal cognitive development both prior to and after the onset of epilepsy.