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Neuromodulation through implantable pulse generators (IPGs) represents an important treatment approach for neurological disorders. While the field has observed the success of state-of-the-art interventions, such as deep brain stimulation (DBS) or responsive neurostimulation (RNS), implantable systems face various technical challenges, including the restriction of recording from a limited number of brain sites, power management, and limited external access to the assessed neural data in a continuous fashion. To the best of our knowledge, for the first time in this study, we investigated the feasibility of recording human intracranial EEG (iEEG) using a benchtop version of the Brain Interchange (BIC) unit of CorTec, which is a portable, wireless, and externally powered implant with sensing and stimulation capabilities. We developed a MATLAB/SIMULINK-based rapid prototyping environment and a graphical user interface (GUI) to acquire and visualize the iEEG captured from all 32 channels of the BIC unit. We recorded prolonged iEEG (~ 24 h) from three human subjects with externalized depth leads using the BIC and commercially available clinical amplifiers simultaneously in the epilepsy monitoring unit (EMU). The iEEG signal quality of both streams was compared, and the results demonstrated a comparable power spectral density (PSD) in all the systems in the low-frequency band (< 80 Hz). However, notable differences were primarily observed above 100 Hz, where the clinical amplifiers were associated with lower noise floor (BIC-17 dB vs. clinical amplifiers <  - 25 dB). We employed an established spike detector to assess and compare the spike rates in each iEEG stream. We observed over 90% conformity between the spikes rates and their spatial distribution captured with BIC and clinical systems. Additionally, we quantified the packet loss characteristic in the iEEG signal during the wireless data transfer and conducted a series of simulations to compare the performance of different interpolation methods for recovering the missing packets in signals at different frequency bands. We noted that simple linear interpolation has the potential to recover the signal and reduce the noise floor with modest packet loss levels reaching up to 10%. Overall, our results indicate that while tethered clinical amplifiers exhibited noticeably better noise floor above 80 Hz, epileptic spikes can still be detected successfully in the iEEG recorded with the externally powered wireless BIC unit opening the road for future closed-loop neuromodulation applications with continuous access to brain activity., (© 2024. The Author(s).)

Objective. High-frequency oscillations (HFOs) are considered a biomarker of the epileptogenic zone in intracranial EEG recordings. However, automated HFO detectors confound true oscillations with spurious events caused by the presence of artifacts. Approach. We hypothesized that, unlike pseudo-HFOs with sharp transients or arbitrary shapes, real HFOs have a signal characteristic that can be represented using a small number of oscillatory bases. Based on this hypothesis using a sparse representation framework, this study introduces a new classification approach to distinguish true HFOs from the pseudo-events that mislead seizure onset zone (SOZ) localization. Moreover, we further classified the HFOs into ripples and fast ripples by introducing an adaptive reconstruction scheme using sparse representation. By visualizing the raw waveforms and time-frequency representation of events recorded from 16 patients, three experts labeled 6400 candidate events that passed an initial amplitude-threshold-based HFO detector. We formed a redundant analytical multiscale dictionary built from smooth oscillatory Gabor atoms and represented each event with orthogonal matching pursuit by using a small number of dictionary elements. We used the approximation error and residual signal at each iteration to extract features that can distinguish the HFOs from any type of artifact regardless of their corresponding source. We validated our model on sixteen subjects with thirty minutes of continuous interictal intracranial EEG recording from each. Main results. We showed that the accuracy of SOZ detection after applying our method was significantly improved. In particular, we achieved a 96.65% classification accuracy in labeled events and a 17.57% improvement in SOZ detection on continuous data. Our sparse representation framework can also distinguish between ripples and fast ripples. Significance. We show that by using a sparse representation approach we can remove the pseudo-HFOs from the pool of events and improve the reliability of detected HFOs in large data sets and minimize manual artifact elimination., (© 2022 IOP Publishing Ltd.)

High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001.

Objective: Convulsive status epilepticus can exert profound cardiovascular effects in adults including ventricular depolarization-repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus., Methods: We conducted a 2-year retrospective, case-control study. Children between 1 month and 21 years of age were included if they were admitted to the pediatric intensive care unit with primary diagnosis of convulsive status epilepticus and had 12-lead electrocardiogram (ECG) within 24 hours of admission. Children with heart disease, ion channelopathy, or on vasoactive medications were excluded. Age-matched control subjects had no history of seizures or epilepsy. The primary outcome was ventricular abnormalities represented by ST segment changes, abnormal T wave, QRS axis deviation, and corrected QT (QTc) interval prolongation. The secondary outcomes included QT/RR relationship, beat-to-beat QTc interval variability, ECG interval measurement between groups, and clinical factors associated with ECG abnormalities., Results: Of 317 eligible children, 59 met the inclusion criteria. History of epilepsy was present in 31 children (epileptic) and absent in 28 children (non-epileptic). Compared with the control subjects (n = 31), the status epilepticus groups were more likely to have an abnormal ECG with overall odds ratio of 3.8 and 7.0 for the non-epileptic and the epileptic groups respectively. Simple linear regression analysis demonstrated that children with epilepsy exhibited impaired dependence and adaptation of the QT interval on heart rate. Beat-to-beat QTc interval variability, a marker of ventricular repolarization instability, was increased in children with epilepsy., Significance: Convulsive status epilepticus can adversely affect ventricular electrical properties and stability in children, especially those with epilepsy. These findings suggest that children with epilepsy may be particularly vulnerable to seizure-induced arrhythmias. Therefore postictal cardiac surveillance may be warranted in this population., Competing Interests: Disclosure of Conflicts of Interest The authors do not have any conflict of interest to disclose

Epilepsy associated with cavernous malformation (CM) often requires surgical resection of seizure focus to achieve seizure-free outcome. High-frequency oscillations (HFOs) in intracranial electroencephalogram (EEG) are reported as potential biomarkers of epileptogenic regions, but to our knowledge there are no data on the existence of HFOs in CM-caused epilepsy. Here we report our experience of the identification of the seizure focus in a 3-year-old pediatric patient with intractable epilepsy associated with CM. The electrocorticographic recordings were obtained from a 64-contact grid over 2 days in the epilepsy monitoring unit (EMU). The spatial distribution of HFOs and epileptic spikes were estimated from recording segments right after the electrode placement, during sleep and awake states separately. The HFO distribution showed consistency with the perilesional region; the location of spikes varied over days and did not correlate with the lesion. The HFO spatial distribution was more compact in sleep state and pinpointed the contacts sitting on the CM border. Following the resection of the CM and the hemosiderin ring, the patient became seizure-free. This is the first report describing HFOs in a pediatric patient with intractable epilepsy associated with CM and shows their potential in identifying the seizure focus.

Objective: The coincidence of autism with epilepsy is 27% in those individuals with intellectual disability. 1 Individuals with loss-of-function mutations in SHANK3 have intellectual disability, autism, and variably, epilepsy. 2-5 The spectrum of seizure semiologies and electroencephalography (EEG) abnormalities has never been investigated in detail. With the recent report that SHANK3 mutations are present in approximately 2% of individuals with moderate to severe intellectual disabilities and 1% of individuals with autism, determining the spectrum of seizure semiologies and electrographic abnormalities will be critical for medical practitioners to appropriately counsel the families of patients with SHANK3 mutations., Methods: A retrospective chart review was performed of all individuals treated at the Blue Bird Circle Clinic for Child Neurology who have been identified as having either a chromosome 22q13 microdeletion encompassing SHANK3 or a loss-of-function mutation in SHANK3 identified through whole-exome sequencing. For each subject, the presence or absence of seizures, seizure semiology, frequency, age of onset, and efficacy of therapy were determined. Electroencephalography studies were reviewed by a board certified neurophysiologist. Neuroimaging was reviewed by both a board certified pediatric neuroradiologist and child neurologist., Results: There is a wide spectrum of seizure semiologies, frequencies, and severity in individuals with SHANK3 mutations. There are no specific EEG abnormalities found in our cohort, and EEG abnormalities were present in individuals diagnosed with epilepsy and those without history of a clinical seizure., Significance: All individuals with a mutation in SHANK3 should be evaluated for epilepsy due to the high prevalence of seizures in this population. The most common semiology is atypical absence seizure, which can be challenging to identify due to comorbid intellectual disability in individuals with SHANK3 mutations; however, no consistent seizure semiology, neuroimaging findings, or EEG findings were present in the majority of individuals with SHANK3 mutations., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Importance: Isolated sulfite oxidase deficiency (ISOD) causes severe intellectual disability, epilepsy, and shortened life expectancy. Intractable seizures are invariable in children with ISOD; however, to our knowledge, infantile spasms with a corresponding hypsarrhythmia pattern on electroencephalogram have never been reported. In addition, the nonepileptic paroxysmal movement disorder hyperekplexia has not previously been reported with ISOD., Observations: We describe an infant with ISOD who initially presented with neonatal seizures, diffusion restriction noted on magnetic resonance imaging, and elevated serum S-sulfocysteine consistent with ISOD. A homozygous mutation in the SUOX gene was identified, confirming the diagnosis. Uniquely, this patient developed a profound accentuated startle response that did not have a corresponding electrographic change on electroencephalogram consistent with hyperekplexia. This was followed by a change in the child's electroencephalogram to the chaotic pattern of hypsarrhythmia and brief tonic seizures with attenuation of the hypsarrhythmia pattern characteristic of infantile spasms., Conclusions and Relevance: The evolution of seizures associated with ISOD is poorly characterized because of the small number of patients. We report what we believe to be the first case of a child with ISOD who developed infantile spasms and hyperekplexia. This expands the phenotypes associated with ISOD and also should caution clinicians to not assume that all abnormal movements are seizures.

Untreated epileptic encephalopathies in children may potentially have disastrous outcomes. Treatment with antiepileptic drugs (AEDs) often may not control the seizures, and even if they do, this measure is only symptomatic and not specific. It is especially valuable to identify potential underlying conditions that have specific treatments. Only a few conditions have definitive treatments that can potentially modify the natural course of disease. In this paper, we discuss the few such conditions that are responsive to vitamin or vitamin derivatives.

Untreated maple syrup urine disease (MSUD) leads to encephalopathy in neonates and causes abnormalities on the electroencephalogram (EEG). A case is presented of MSUD with unique features consisting of a comb-like rhythm before the therapy and its disappearance with therapy is presented. This case illustrates the potential use of the EEG in the identification of this specific cause of a neonatal encephalopathy.

To date, over 70 mutations in the TGFBR2 gene have been reported in patients with Loeys-Dietz syndrome (LDS), Marfan syndrome type 2 (MFS2), or other hereditary thoracic aortic aneurysms and dissections. Whereas almost all of mutations analyzed thus far are predicted to disrupt the constitutively active C-terminal serine/threonine kinase domain of TGFBR2, mounting evidence suggests that the molecular mechanism underlying these diseases is more complex than simple haploinsufficiency. Using exon-targeted oligonucleotide array comparative genomic hybridization, we identified an ∼896 kb deletion of TGFBR2 in a 20-month-old female with microcephaly and global developmental delay, but no stigmata of LDS. FISH analysis showed no evidence of this deletion in the parental peripheral blood samples; however, somatic mosaicism was detected using PCR in the paternal DNA from peripheral blood lymphocytes and lymphoblasts. Our data suggest that TGFBR2 haploinsufficiency may cause a phenotype, which is distinct from LDS. Moreover, we propose that somatic mosaicism below the detection threshold of FISH analysis in asymptomatic parents of children with genomic disorders may be more common than previously recognized., (Copyright © 2011 Wiley-Liss, Inc.)

Opinion Statement: Antiepileptic drugs (AEDs) are the mainstay of treatment for recurrent seizures. Uncontrolled seizures may cause medical, developmental, and psychological disturbances. The medical practitioner should thus strive to eliminate or minimize seizures. Treatment advances in epilepsy include 1) identification of the basic mechanisms of epilepsy and action of AEDs, 2) the introduction of new AEDs, and 3) the use of neurostimulation, including vagus nerve stimulation. Treatment with AEDs involves balancing each AED's efficacy against its side effects. In some patients, effective AEDs must be discontinued because of intolerable side effects. Although all AEDs have a proven efficacy, the choice of AEDs should be based on better efficacy for individual seizure types or epilepsy syndromes. Side effects also differ from drug to drug and must be taken into account. This article focuses on studies and expert opinion consensus to guide the choice of AEDs.