Ictal Discharges Research Articles

Comment on: RTTBD-like activity in association with hippocampal ictal discharges in patients with temporal lobe epilepsy by Sun et al.

Comment on: RTTBD-like activity in association with hippocampal ictal discharges in patients with temporal lobe epilepsy by Sun et al.

Reliability and availability of granger causality density in localization of Rolandic focus in BECTS.

A new method, called granger causality density (GCD), could reflect the directed information flow of the epileptiform activity, which is much closely match with excitatory and inhibitory imbalance theory of epilepsy. Here, we investigated if GCD could effectively localize the Rolandic focus in 50 patients with benign childhood epilepsy with central-temporal spikes (BECTS) from 27 normal children. The BECTS were classified into ictal epileptiform discharges (IEDs; 12 females, 15 males;age, 8.15 ± 1.68years) and non-IEDs (10 females, 13 males; age, 9.09 ± 1.98years) subgroups depending on the presence of central-temporal spikes. Multiple correlation-modality analyses (Pearson, across-voxel and across-subject correlations) were used to calculate the couplings between the GCD maps and IEDs-related brain activation map. The individual lateralization coefficient of localize IEDs and multiple regression analysis were used to identify the reliability of the GCD method in localizing the Rolandic focus. In this study, multiple correlation-modality analyses showed that the IEDs-related brain activation map and the GCD maps had highly temporal (coefficient ׀r\= 0.56 ~ 0.65) and spatial(\r\=0.53~0.91) (r\=~ couplings. The proposed GCD method and multiple regression analyses showed consistentfindings with the clinical EEG recordingsinlateralization of Rolandic focus. Furthermore, the GCD method could reflect the epilepsy-related brain activity during non-IEDs substate. Therefore, the proposed GCD method has the potential to be served as an effective and reliable neuroimaging biomarker to localize the Rolandic focus of BECTS. These findings are critical for clinical early diagnosis, and may promote the progression of treatment and management of pediatric epilepsy.

Presynaptic GABAB receptors underlie the antiepileptic effect of low-frequency electrical stimulation in the 4-aminopyridine model of epilepsy in brain slices of young rats

Low-frequency electrical stimulation (LFES) of the brain is one of the promising methods for helping patients with pharmacoresistant epilepsy. However, the mechanism of the antiepileptic effect of LFES is still unclear. We applied electrophysiological and pharmacological tools and mathematical modeling to investigate it. Using the 4-aminopyridine (4-AP) model of epileptiform activity in juvenile rat brain slices, we found that LFES increased the interval between ictal discharges (IDs) in the entorhinal cortex. The blockade of GABAA, GABAB, AMPA, or NMDA synaptic receptors strongly affected the characteristics of epileptiform discharges in slices. However, only under the blockade of GABAB receptors, LFES becomes entirely ineffective, indicating that the activation of GABAB receptors underlies the main LFES antiepileptic effect. Further experiments allowed us to suggest that LFES activates mostly presynaptic GABAB receptors, which decrease the probability of glutamate release. In line with this hypothesis is the following data: 1) LFES reduces the short-term synaptic depression of excitatory postsynaptic currents similar to the agonist of GABAB receptors SKF-97541; 2) the blockade of excitatory amino acid transporters diminishes the antiepileptic effect of LFES; 3) modeling of the effects of LFES on the probability of glutamate release with a previously proposed mathematical model of epileptiform activity Epileptor-2 also shows the increase of the interval between IDs. Our findings point out a crucial role of presynaptic GABAB receptors in the antiepileptic effect of LFES in the 4-AP model in juvenile rat brain slices.

Spatio-temporal dynamics of interictal activity in musicogenic epilepsy: Two case reports and a systematic review of the literature

ObjectiveTo explore neurophysiological features of musicogenic epilepsy (ME), discussing experimental findings in the framework of a systematic review on ME. MethodsTwo patients with ME underwent high-density-electroencephalography (hd-EEG) while listening to ictogenic songs. In one case, musicogenic seizures were elicited. Independent component analysis (ICA) was applied to hd-EEG, and components hosting interictal and ictal elements were identified and localized. Finally, the temporal dynamics of spike-density was studied relative to seizures. All findings were compared against the results of a systematic review on ME, collecting 131 cases. ResultsInterictal spikes appeared isolated in specific fronto-temporal independent components, whose cortical generators were located in the anterior temporal and inferior frontal lobe. In the patient undergoing seizure, ictal discharge relied in the same component, with the interictal spike-density decreasing before the seizure onset. ConclusionOur study shows how ICA can isolate neurophysiological features of ictal and interictal discharges in ME, highlighting a fronto-temporal localization and a suppression of spike-density preceding the seizure onset. SignificanceWhile the localization of ME activity could indicate which aspect within the musical stimulus might trigger musicogenic seizures for each patient, the study of ME dynamics could contribute to the development of models for seizure-prediction and their validation.

A study of psychogenic non-epileptic seizures in an inpatient video-electroencephalography monitoring service in Tabriz, Northwest of Iran

Background: Psychogenic non-epileptic seizures (PNES) are manifested as paroxysmal alterations in motor, sensory, autonomic, and/or cognitive and behavioral signs and symptoms, without associated ictal epileptiform discharges. A misdiagnosis of PNES as epilepsy results in a prolonged and unnecessary (antiepileptic) drug treatment and social and psychological stigma of epilepsy in these patients. This study aimed to determine the epidemiology, clinical manifestations, and associated factors of PNES in hospitalized patients in the video-electroencephalography (EEG) monitoring (VEM) service of Razi Hospital, Tabriz, Iran. Methods: In this cross-sectional descriptive study, 55 patients with a final diagnosis of PNES were selected from the patients referred to the VEM unit of Razi Hospital for the evaluation of epilepsy. The study was performed from May 2017 to June 2019. Patient information included demographic data and medical history (drug history, comorbidities, trauma, and family history). The clinical manifestations (semiology and duration of attacks) and EEG findings, as recorded by VEM during hospitalization, were collected. Results: 55 patients with PNES were studied with VEM, 27 (49.1%) of which were men, and 28 (50.9%) were women. The mean and standard deviation (SD) of age of the patients was 34.16 ± 12.64 years. No significant differences were observed in the semiology of PNES between men and women. Depression was the most common psychiatric comorbidity. Conclusion: The clinical manifestations of PNES in the present study were similar to those in most previous studies from other countries. The culture and sex of the patients did not seem to be a contributing factor in PNES semiology.

The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions.

Stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome but occur in other mitochondrial disorders (MIDs) as well. The morphological equivalent of the SLE is the stroke-like lesion (SLL) on magnetic resonance imaging (MRI). The pathophysiology of SLLs is under debate, but several hypotheses have been raised to explain the phenomenon. Of these, the metabolic, epileptogenic, and vascular hypotheses are the most frequently discussed. There are several arguments for and against these hypotheses, but a consensus has not been reached which of them provides the correct explanation. A recent consensus statement generated by a panel of experts applying the Delphi method, favoured the epileptogenic hypothesis and recommended treatment of SLEs with antiepileptic drugs, irrespective if the patient presented with a seizure or epileptiform discharges on electroencephalography (EEG) or not. We disagree with this general procedure and provide the following arguments against the epileptogenic hypothesis: 1. not each SLE is associated with seizures. 2. epileptiform discharges may be absent on EEG during a SLE. 3. SLLs are not restricted to the cortex. 4. antiseizure-drugs (ASDs) may not prevent the progression or recurrence of a SLL. 5. ASDs may terminate seizures but no other phenotypic feature of a SLE. 6. patients already under ASDs are not immune from developing a SLL. 7. SLLs usually last longer than seizures. 8. no animal model supports the epileptogenic hypothesis. The strongest arguments for the metabolic hypothesis are that SLLs are not confined to a vascular territory, that the oxygen-extraction fraction within a SLL is reduced, and that there is hypometabolism within a SLL on FDG-PET. SLLs may respond to antioxidants, NO-precursors, steroids, or the ketogenic diet. ASDs should be applied only if there is clinical or electrophysiological evidence of seizure-activity.

Evaluation of a new wireless technique for continuous electroencephalography monitoring in neurological intensive care patients.

A novel wireless eight-channel electroencephalography (EEG) headset specially developed for ICUs was tested in regard of comparability with standard 10/20 EEG systems. The continuous EEG (cEEG) derivations via CerebAir EEG headset (Nihon Kohden Europe, Rosbach, Germany) and internationally standardized 10/20 reference EEGs as the diagnostic standard were performed in a mixed collective on a neurointensive care unit (neuro-ICU). The derivations were verified for comparability in detection of EEG background activity, epileptiform discharges, and seizure patterns. Fifty-two patients with vigilance reduction following serious neurological or metabolic diseases were included, and both methods were applied and further analyzed in 47. EEG background activity matched in 24 of 45 patients (53%; p = 0.126), epileptiform discharges matched in 32 (68%) patients (p = 0.162), and seizure activity matched in 98%. Overall, in 89% of the patients, cEEG detected the same or additional ICU-relevant EEG patterns. The tested wireless cEEG headset is a useful monitoring tool in patients with consciousness disorders. The present study indicates that long-term measurements with the wireless eight-channel cEEG lead to a higher seizure and epileptiform discharge detection compared to intermittent 10/20 EEG derivations in the ICU setting.

1216 Markedly decreased ictal discharges with positive airway pressure (PAP) treatment in a patient with refractory epilepsy and severe obstructive sleep apnea

Abstract Introduction Individuals with epilepsy are at increased risk for obstructive sleep apnea (OSA). Treatment of OSA with positive airway pressure (PAP) can result in decreased seizure frequency in patients with epilepsy, possibly due to decreased sleep disruption and normalization of oxygenation saturation levels when using PAP. The following case report demonstrates an example in which treatment of OSA with PAP resulted in a dramatic improvement of electroencephalographic seizures. Report of Case A 32 year-old man with refractory epilepsy presented to our office complaining of loud snoring, witnessed apneas, and excessive daytime sleepiness. Despite prior left frontal and left anterior temporal lobectomy, vagus nerve stimulator treatment, and excellent treatment adherence to four different antiepileptic medications, the patient continued to have 1-3 clinical seizures per day. Physical examination was notable for obesity (BMI=39.4 kg/m2), high arched palate and Mallampati class 4 airway. Long-term eletroencephalogram (EEG) monitoring was significant for frequent interictal discharges during wakefulness and sleep, as well as frequent subclinical seizures during sleep characterized by C3/P3 polyspike bursts followed by brief rhythmic fast activity. A diagnostic polysomnogram revealed severe OSA (AHI=69/hour). The patient subsequently underwent a PAP titration study with extended EEG montage, which was notable for a marked decrease in polyspike discharges on effective PAP pressures, from an average of 24 polyspike discharges per hour on PAP pressures < 15 cm of water to an average of 3 polyspike discharges per hour on PAP pressures ≥ 15 cm of water. PAP treatment was initiated following the titration study. Conclusion This case demonstrates that effective treatment of OSA can lead to a reduction of abnormal EEG discharges in a patient with intractable epilepsy. Additional clinical follow up is needed to assess whether PAP treatment also resulted in decreased frequency of clinical seizures.

Epileptic seizure discharges in patients after open chamber cardiac surgery\u2014a prospective prevalence pilot study using continuous electroencephalography

PurposePatients undergoing cardiac surgery often develop delirium which increases the risk of postoperative morbidity and leads to a reduced quality of life. Retrospective studies show a higher incidence of delirium in patients with seizures. However, these studies do not systematically detect subclinical seizures, so the incidence of seizures after cardiac surgery remains speculative. The objective of this study is to determine the prevalence of electrographic seizures after elective open-chamber cardiac surgery.MethodsThis prospective, blinded, monocentric, observational study investigated patients scheduled for elective open-chamber valve reconstruction or replacement. Anaesthesia, surgery and postoperative treatment were standardized and not influenced by the presented observation. After surgery, all patients arrived at the ICU, and EEG monitoring started within the first hour. EEG recording was continuously performed for up to 24 h, and the results were independently analysed by two blinded EEG board-certified neurologists.Results100 patients were included. Abnormal EEG patterns were present in 33% of patients, and 9% of all patients showed electrographic seizures. The main EEG activity at the beginning of each recording was suppressed or showed a burst-suppression pattern, and at the end of recording, all patients had an alpha/theta rhythm. An association between electrographic seizures and delirium was found (pχ2 < 0.01).ConclusionThis study reveals a surprisingly high incidence of abnormal EEG patterns and electrographic seizures in patients undergoing open-chamber cardiac surgery. As electrographic seizures are associated with the incidence of delirium, this finding is a relevant phenomenon in the post-cardiac surgery ICU population.

Clinical and Electroencephalographic Features of the Seizures in Neuronal Surface Antibody-Associated Autoimmune Encephalitis.

Objectives: To investigate clinical and electroencephalographic features of the seizures in different types of neuronal surface antibody (NSAb)-associated autoimmune encephalitis (AE).Methods: The clinical data of the seizures were analyzed in 18 patients with NSAb-associated AEs diagnosed in the First Affiliated Hospital of Dalian Medical University.Results: From May 2013 to April 2019, a total of 18 cases of NSAb-associated AE were diagnosed, including 9 cases of leucine-rich glioma-inactivated 1 protein (LGI1) antibody-associated encephalitis, 7 cases of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, and 2 cases of anti-γ-aminobutyric acid B receptor (GABABR) encephalitis. All nine cases (100%) with LGI1 AE had seizures manifesting in three types: faciobranchial dystonia seizure (FBDS) (44.4%), mesial temporal lobe epilepsy (MTLE)-like seizure (66.7%), and focal to bilateral tonic–clonic seizure (FBTCS) (77.8%). Six of nine (66.7%) showed abnormal signal on hippocampus or basal ganglia in brain MRI. Five of seven cases (71%) with anti-NMDAR encephalitis had seizures manifesting in three types: focal aware seizure (40%), focal-impaired awareness seizure (20%), generalized tonic–clonic seizure (GTCS) (100%), and status epilepticus (SE) (40%). Three of seven (42.8%) showed abnormalities in brain MRI. Both patients with anti-GABABR encephalitis had seizures manifesting in two types: GTCS and MTLE-like seizure, one with SE. One showed abnormal signal on left hippocampus in brain MRI. All patients (100%) with three types of AE had abnormalities in electroencephalogram (EEG), showing diffuse (4/18) or focal slow waves (14/18) in background, interictal (10/18), or ictal (6/18) epileptic discharges in the temporal or other regions; two patients with anti-NMDAR encephalitis showed delta activity or rhythm in frontotemporal region. All patients with seizures showed good response to immunotherapy except one with LGI1 AE.Conclusions: Most patients with NSAb-associated AE had seizures; seizure types varied between different types of AE. In LGI1 AE, the hippocampus and basal ganglia were two main targets; the corresponding seizure type was MTLE-like seizure and FBDS, respectively. Anti-NMDAR encephalitis had more generalized than focal seizures. Delta activity or rhythm in the frontotemporal region in EEG was helpful for diagnosis. Anti-GABABR encephalitis was characterized by refractory seizures as initial symptom, mainly GTCS or MTLE-like seizure. Most seizures in NSAb-associated AE showed good response to immunotherapy, and antiepileptic drugs should be considered as an add-on symptomatic treatment.

False alarms reduction in non-convulsive status epilepticus detection via continuous EEG analysis

Objective: Frequent false alarms from computer-assisted monitoring systems may harm the safety of patients with non-convulsive status epilepticus (NCSE). In this study, we aimed at reducing false alarms in the NCSE detection based on preventing from three common errors: over-interpretation of abnormal background activity, dense short ictal discharges and continuous interictal discharges as ictal discharges. Approach: We analyzed 10 participants’ hospital-archived 127-hour electroencephalography (EEG) recordings with 310 ictal discharges. To reduce the false alarms caused by abnormal background activity, we used morphological features extracted by visibility graph methods in addition to time-frequency features. To reduce the false alarms caused by over-interpreting short ictal discharges and interictal discharges, we created two synthetic classes—‘Suspected Non-ictal’ and ‘Suspected Ictal’—based on the misclassified categories and constructed a synthetic 4-class dataset combining the standard two classes—‘Non-ictal’ and ‘Ictal’—to train a 4-class classifier. Precision-recall curves were used to compare our proposed 4-class classification model and the standard 2-class classification model with or without the morphological features in the leave-one-out cross validation stage. The sensitivity and precision were primarily used as performance metrics for the detection of a seizure event. Main results: The 4-class classification model improved the performance of the standard 2-class model, in particular increasing the precision by 15% at an 80% sensitivity level when only time-frequency features were used. Using the morphological features, the 4-class classification model achieved the best performances: a sensitivity of 93% ± 12% and a precision of 55% ± 30% in the group level. 100% accuracy was reached in a participant’s 4.3-hour recording with 5 ictal discharges. Significance: False alarms in the NCSE detection were remarkably reduced using the morphological features and the proposed 4-class classification model.

SREDA: A Rare but Confusing Benign EEG Variant.

Subclinical rhythmic EEG discharges in adults (SREDA) is a very rare benign EEG pattern. The electrophysiological features and atypical variants of SREDA has wide spectrum and they are poorly known. It resembles ictal discharges, and overinterpretation of SREDA may lead to misdiagnosis of epilepsy. Herein, we aimed to report patients with SREDA to identify the frequency and characterized clinical, demographic, electrophysiological features. We reviewed 22,234 EEG reports that are reported by the same experienced clinical neurophysiologists, between 2012 and 2018. The EEGs with SREDA were reevaluated blindly by three clinical neurophysiologists. The demographic, clinical characteristics, and neuroimaging features of the patients were reviewed. Subclinical rhythmic EEG discharges in adults was present in 14 EEG records (0.06%), in nine patients. The mean age of patients was 52.1 ± 17.7 (range, 21-71) years. The patients had been diagnosed with several neurologic diseases, including cerebrovascular disease, epilepsy, psychogenic nonepileptic seizures, mental retardation, Alzheimer disease, and transient global amnesia. One patient had unilateral lesion, in whom SREDA had appeared on contralateral side of the lesion, whereas other patients with normal or nonlateralized lesions had SREDA bilaterally and symmetrical. This variant had been misdiagnosed as an ictal discharge in previous EEGs in three patients. This study indicates that SREDA is difficult to associate with any specific condition. The pathophysiology of SREDA can not be explained by a single mechanism. Even if it is mostly observed in older adults, it is also observed in young adults in this study. It is important to differentiate SREDA from ictal discharge to prevent misdiagnosis of epilepsy especially in nonepileptic paroxysmal events.

Evolution in the Findings of Head-Impulse Tests During the Attacks of Menière's Disease.

To determine the vestibulo-ocular reflex (VOR) performance during the attacks of Menière's disease (MD) using video head-impulse tests (video-HITs) according to each ictal phase. Retrospective case series review. We analyzed the results of video-HITs in 24 patients with unilateral definite MD during and between the attacks. The head impulse gain of the VOR was usually normal (81%, 39 of the 48 semicircular canals [SCCs] in 16 patients) in the affected ear during the irritative or recovery phase, and did not differ from that for each SCC between the attacks (horizontal [HCs], p = 0.412; anterior [ACs], p = 0.920; posterior canals [PCs], p = 0.477). During the paretic phase, however, the head impulse gains of the VOR were equally normal (22/42, 52%) or decreased (20/42, 48%) for the affected ear (42 SCCs in 14 patients). The gains for the HCs were lower during the paretic phase than those between the attacks in the affected ear, while those for the ACs and PCs did not differ (HCs, p = 0.001; ACs, p = 0.158, PCs, p = 0.401). Covert saccades were more frequently observed even in the presence of normal VOR gains during the paretic phase as well. During the attacks of MD, HITs are usually normal during the irritative/recovery phases, but become positive in more than a half of the patients during the paretic phase. This evolution in the ictal findings of HITs may reflect characteristic ictal vestibular discharges in MD and should be considered in evaluating patients with MD according to each ictal phase during the attacks.

Electrophysiological properties and seizure networks in hypothalamic hamartoma.

ObjectiveLittle is known about the intrinsic electrophysiological properties of hypothalamic hamartoma (HH) in vivo and seizure network since only few cases using stereoelectroencephalography (SEEG) electrodes exploring both cortex and HH have been published. To elucidate these issues, we analyzed simultaneous SEEG recordings in HH and cortex systematically.MethodsWe retrospectively investigated data from 15 consecutive patients with SEEG electrodes into the HH for the treatment purpose of radiofrequency thermocoagulation treatment. Additional SEEG electrodes were placed into the cortex in 11 patients to assess extra‐HH involvement. Interictal discharges within the HH and anatomo‐electroclinical correlations during seizures of each patient were qualitatively and quantitatively analyzed.ResultsOverall, 77 electrodes with 719 contacts were implanted, and 33 spontaneous seizures were recorded during long‐term SEEG monitoring. Interictally, distinct electrophysiological patterns, including isolated intermittent spikes/sharp waves, burst spike and wave trains, paroxysmal fast discharges, periodic discharges, and high‐frequency oscillations, were identified within the HH. Notably, synchronized or independent interictal discharges in the cortex were observed. Regarding the ictal discharges, the electrical onset pattern within the HH always started with abrupt giant shifts superimposed on low‐voltage fast activity across patients. The gelastic seizure network mainly involved the HH, orbitofrontal areas, and cingulate gyrus. Seizures with automatisms and impaired awareness primarily propagated to mesial temporal lobes. Moreover, independent ictal discharges arising from the mesial temporal lobe were detected in three out of nine patients.InterpretationThis study comprehensively reveals intrinsic electrophysiological patterns and epileptogenic networks in vivo, providing new insights into the mechanisms underlying cortical and subcortical epileptogenesis.

Respective Contribution of Ictal and Inter-ictal Electrical Source Imaging to Epileptogenic Zone Localization.

Interictal electrical source imaging (ESI) encompasses a risk of false localization due to complex relationships between irritative and epileptogenic networks. This study aimed to compare the localizing value of ESI derived from ictal and inter-ictal EEG discharges and to evaluate the localizing value of ESI according to three different subgroups: MRI lesion, presumed etiology and morphology of ictal EEG pattern. We prospectively analyzed 54 of 78 enrolled patients undergoing pre-surgical investigation for refractory epilepsy. Ictal and inter-ictal ESI results were interpreted blinded to- and subsequently compared with stereoelectroencephalography as a reference method. Anatomical concordance was assessed at a sub-lobar level. Sensitivity and specificity of ictal, inter-ictal and ictal plus inter-ictal ESI were calculated and compared according to the different subgroups. Inter-ictal and ictal ESI sensitivity (84% and 75% respectively) and specificity (38% and 50% respectively) were not statistically different. Regarding the sensitivity, ictal ESI was never higher than inter-ictal ESI. Regarding the specificity, ictal ESI was higher than inter-ictal ESI in malformations of cortical development (MCD) (60% vs. 43%) and in MRI positive patients (49% vs. 30%). Within the ictal ESI analysis, we showed a higher specificity for ictal spikes (59%) and rhythmic discharges > 13Hz (50%) than rhythmic discharges < 13Hz (37%) and (ii) for MCD (60%) than in other etiologies (29%). This prospective study demonstrates the relevance of a combined interpretation of distinct inter-ictal and ictal analysis. Inter-ictal analysis gave the highest sensitivity. Ictal analysis gave the highest specificity especially in patients with MCD or a lesion on MRI.

A simple model of epileptic seizure propagation: Potassium diffusion versus axo-dendritic spread.

The mechanisms of epileptic discharge generation and spread are not yet fully known. A recently proposed simple biophysical model of interictal and ictal discharges, Epileptor-2, reproduces well the main features of neuronal excitation and ionic dynamics during discharge generation. In order to distinguish between two hypothesized mechanisms of discharge propagation, we extend the model to the case of two-dimensional propagation along the cortical neural tissue. The first mechanism is based on extracellular potassium diffusion, and the second is the propagation of spikes and postsynaptic signals along axons and dendrites. Our simulations show that potassium diffusion is too slow to reproduce an experimentally observed speed of ictal wavefront propagation (tenths of mm/s). By contrast, the synaptic mechanism predicts well the speed and synchronization of the pre-ictal bursts before the ictal front and the afterdischarges in the ictal core. Though this fact diminishes the role of diffusion and electrodiffusion, the model nevertheless highlights the role of potassium extrusion during neuronal excitation, which provides a positive feedback that changes at the ictal wavefront the balance of excitation versus inhibition in favor of excitation. This finding may help to find a target for a treatment to prevent seizure propagation.

Electro-clinical and neurodevelopmental outcome in six children with early diagnosis of tuberous sclerosis complex and role of the genetic background

BackgroundSeizures in individuals affected by tuberous sclerosis complex (TSC) commonly develop in the first year of life, are often preceded by a progressive deterioration of the electroencephalogram (EEG), and likely influence developmental outcome. Although early diagnosis of TSC has offered a tremendous opportunity to monitor affected patients before seizure onset, reports of the neurological manifestations of TSC in infants before seizure onset are still scarce. Here we describe early EEG activity, clinical and genetic data and developmental assessment in a group of TSC infants, with the aim of identifying possible prognostic factors for neurodevelopmental outcome.MethodsWe report on six infants diagnosed with TSC pre- or perinatally, who underwent serial Video-EEG recordings during the first two years of life. EEGs were classified based on distribution and intensity of interictal epileptiform discharges, and Vigabatrin was introduced in case of ictal discharges. Psychomotor development, cognitive functioning and behavioral problems were assessed through standardized scales. Molecular testing included analysis for point mutations and deletions/duplications in TSC1 and TSC2.ResultsEEG abnormalities appeared at a mean age of 4 months. Four of the six patients developed seizures. EEG abnormalities preceded the onset of clinical seizures in all of them. The two individuals with good seizure control showed normal development, while the other two exhibited psychomotor delays. The patients who did not develop seizures had normal development. A pathogenic variant in the TSC2 gene was detected in all patients but one. The one without a mutation identified did not develop seizures and showed normal neurodevelopment. Of note, the two patients presenting with the worst outcome (that is, poor seizure control and intellectual/behavioral disability) both carried pathogenic variants in the GAP domain of TSC2.ConclusionOur report supports the importance of EEG monitoring before seizure onset in patients with TSC, and the correlation between prompt seizure control and positive neurodevelopmental outcome, regardless of seizure type. Our results also indicate a possible role of the genetic background in influencing the outcome.

The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions.

Stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome but occur in other mitochondrial disorders (MIDs) as well. The morphological equivalent of the SLE is the stroke-like lesion (SLL) on magnetic resonance imaging (MRI). The pathophysiology of SLLs is under debate, but several hypotheses have been raised to explain the phenomenon. Of these, the metabolic, epileptogenic, and vascular hypotheses are the most frequently discussed. There are several arguments for and against these hypotheses, but a consensus has not been reached which of them provides the correct explanation. A recent consensus statement generated by a panel of experts applying the Delphi method, favoured the epileptogenic hypothesis and recommended treatment of SLEs with antiepileptic drugs, irrespective if the patient presented with a seizure or epileptiform discharges on electroencephalography (EEG) or not. We disagree with this general procedure and provide the following arguments against the epileptogenic hypothesis: 1. not each SLE is associated with seizures. 2. epileptiform discharges may be absent on EEG during a SLE. 3. SLLs are not restricted to the cortex. 4. antiseizure-drugs (ASDs) may not prevent the progression or recurrence of a SLL. 5. ASDs may terminate seizures but no other phenotypic feature of a SLE. 6. patients already under ASDs are not immune from developing a SLL. 7. SLLs usually last longer than seizures. 8. no animal model supports the epileptogenic hypothesis. The strongest arguments for the metabolic hypothesis are that SLLs are not confined to a vascular territory, that the oxygen-extraction fraction within a SLL is reduced, and that there is hypometabolism within a SLL on FDG-PET. SLLs may respond to antioxidants, NO-precursors, steroids, or the ketogenic diet. ASDs should be applied only if there is clinical or electrophysiological evidence of seizure-activity.

Novel CDKL5 mutations were found in patients in China: retrospective investigation in cases of CDKL5-related disorders

ObjectiveCDKL5-related disorders (CDD) is an epileptic encephalopathy resulted of gene mutations of CDKL5. This study aimed to explore the development process of CDD and to expand its mutation spectrum.MethodsClinic datawas collected about three infantile epileptic encephalopathy cases diagnosed at Xinhua Hospital Affiliated to Shanghai Jiaotong University, School of Medicine. Next generation sequencing technology was used to find three de novo mutations of CDKL5. We searched published literatures about CDKL5 in pubmed and made an analysis about our clinic data and the related literatures.ResultsThe three patients were all girls. Their average onset age of seizures was around 2 months, and all of them have intractable epileptic seizures, severe intellectual disability, and hypotension. Among them, two presented infantile spasm and high arrhythmia in EEG, and the other manifested clonic seizure and broad epileptiform discharge in EEG. Extracerebral space widening in cranial MRIs was demonstrated in two cases. Visual evoked potential was abnormal in two cases. Seizures were resistant to all kinds of antiepileptic drugs (AEDs). Gene tests showed three de novo mutations of CDKL5: one was a truncated mutation (c.2254A > T,P.R752X, stop279), which was pathogenic according to the ACMG guide, the other two were missense mutations (c.377G > T,p.Cys126Phe) and a frameshift mutation (c.362-362insG(p.Ala122GlyfsTer7), which were likely pathogenic according to the ACMG.ConclusionsAll three de novo mutations are first reported. Based on the combined related literature and the manifestations observed, we diagnosed the three children as CDKL5-related disorders, and concluded that the de novo CDKL5 mutations are the reason for their epilepsy.

Predictors of Nonconvulsive Seizure and Their Effect on Short-term Outcome.

Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs. We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled. Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197-2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027-2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1). Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.