Intermittent Rhythmic Delta Activity Research Articles

Incidence and prognosis of frontal intermittent rhythmic delta activity in King Fahad Hospital-Hofuf intensive care unit

Objective: This study aimed to verify the rate of occurrence of frontal intermittent rhythmic delta activity (FIRDA) in electroencephalograms (EEGs) of adult patients in the intensive care unit (ICU) and its correlation with either neurological or non-neurological etiologies or prognoses. Methods: A retrospective review was performed on 239 EEGs with analysis of their neuroimages and clinical data from an ICU at King Fahad Hospital, Hufof from November 2021 to October 2022. A literature review was also conducted using the PUBMED database. The search scope was covered by the keyword "FIRDA" and was limited to English-language articles. Results: A total of 239 EEGs were conducted in the ICU, 19 (7.9%) had either electrographic or clinical seizures with or without slowing and/or interictal epileptiform discharges, 6 (2.5%) EEGs had FIRDA, and the rest of the EEGs (80.5%) had only generalized slow or rarely other EEG patterns which were noted in coma. Toxic metabolic disturbances and sepsis were the acute diagnoses of all the observed cases. There were no clinical seizures in the patients who had FIRDA and no history of epilepsy. There was no significant association between FIRDA and the seizure occurrence where the p-value was 1 (Confidence interval—0, 10.28). Conclusion: This study provides valuable insights into the incidence, clinical characteristics, and outcomes of FIRDA in critically ill patients admitted to the ICU. While FIRDA remains a relatively uncommon finding, its association with toxic-metabolic disturbances and sepsis underscores the importance of comprehensive neurological monitoring in critically ill patients.

Typical absence seizures in children: Review with focus on EEG predictors of treatment response and outcome.

Typical absence seizures (TAS) occur in idiopathic generalized epilepsy (IGE) syndromes and are a common presentation to paediatric neurologists. Considerable overlap in clinical features of IGE syndromes comprising TAS often complicates prognostication. Clinical and EEG diagnostic features in TAS are well known. However, knowledge of prognostic features for each syndrome, whether clinical or EEG-related, is less clear. Perpetuated impressions in clinical practice regarding the role of EEG when used for prognostication in TAS are known. Assumed prognostic features, particularly those relating to EEG have been rarely studied systematically. Despite rapid expansion in epilepsy genetics, the complex and presumed polygenic inheritance of IGE, means that clinical and EEG features are likely to remain the main guide to management and prognostication of TAS for the foreseeable future. We comprehensively reviewed available literature and hereby summarize current knowledge of clinical and EEG characteristics (ictal and interictal) in children with TAS. The literature focuses predominantly on ictal EEG. Where studied, interictal findings reported relate to focal discharges, polyspike discharges, and occipital intermittent rhythmic delta activity, with generalized interictal discharges not thoroughly studied. Furthermore, reported prognostic implications of EEG findings are often conflicting. Limitations of available literature include inconsistent clinical syndrome and EEG finding definitions, and variable EEG analysis methods, particularly lack of raw EEG data analysis. These conflicting findings coupled with varying study methodologies cause lack of clear information or evidence on features which may influence treatment response, outcome, or natural history of TAS.

Electroencephalographic findings in autistic non-epileptic children

Despite the well-acknowledged link between autism spectrum disorders (ASDs) and epilepsy, the prevalence and significance of electroencephalogram (EEG) changes in epileptic children in the absence of clinical seizures remains underdetermined. Aim. The primary goal of this study is to report the prevalence of EEG abnormalities in non-epileptic or pre-epileptic autistic children, investigate their association with a set of pre-determined risk factors, speculate on their significance, and direct future research efforts. Methods. A case-based sampling for children diagnosed with autism was done. Only patients without a history of epilepsy and those under the age of 15 were included. All patients underwent an EEG study. Children with abnormal EEG findings (case group) were compared to age-matched controls with normal EEG findings using a set of pre-determined factors. Results. A total of 38 patients were enrolled in our study, of whom 31.6% (n=12) had abnormal EEG readings. Of those, the presence of the following EEG abnormalities were noted – each being present in two patients: frontal sharp waves, frontal slowing, temporal slowing, bitemporal slowing, frontal sharp waves, and generalized sharp waves, Frontal intermittent rhythmic delta activity (FIRDA). Patients with abnormal EEG findings were more likely to have a positive family history of epilepsy and/or autism, with odd ratios of 28.05, and 12.62, accordingly. Conclusion. Aberrant brain connectivity patterns have been observed in non-epileptic ASD patients, and our findings support these findings. Furthermore, we believe that gender, mother's age, mode of delivery, and speech abnormalities could all have an impact on the EEG results. However, more research is needed to expand on these findings.

Frontal Intermittent Rhythmic Delta Activity Is a Useful Diagnostic Tool of Neurotoxicity After CAR T-Cell Infusion.

Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS. Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS. Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55-74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4-8). The median ICANS grade was 2 (1-3). Higher C-reactive protein peak (146 mg/L [86-256], p = 0.004) at day 4 (3-6), lower natremia (131 mmol/L [129-132], p = 0.005) at day 5 (3-6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA (p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS (p = 0.043). FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results. This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy.

Frontal intermittent rhythmic delta activity (FIRDA) detected by bispectral index monitoring.

Frontal intermittent rhythmic delta activity (FIRDA) detected by bispectral index monitoring.

424 Clinical Translational Approach to Targeted Therapy in SLC6A1-related Neurodevelopmental Disorder

OBJECTIVES/GOALS: SLC6A1-Related Neurodevelopmental Disorder (SLC6A1-NDD) is a leading genetic cause of epilepsy and autism. Haploinsufficiency of SLC6A1 leads to reduced uptake of GABA from the synaptic cleft, and increased extracellular GABA in mice. It is a candidate for gene transfer therapy, but translational read outs are needed. EEG is a promising biomarker. METHODS/STUDY POPULATION: The SLC6A1-NDD program includes a specialty clinic and prospective cohort study run in parallel with pre-clinical gene therapy development. Characterization and pre-clinical testing of a homozygous knock-out, heterozygous knock-out, and two humanized knock-in models are on-going, including EEG analyses before and after treatment. Patients with a confirmed diagnosis of SLC6A1-NDD are seen annually in a specialty clinic and a subset participate in the cohort study which collects standardized questionnaires, EEGs, and MR Spectroscopy to measure glutamate and GABA. Gene Therapy Program investigators meet weekly to discuss progress on pre-clinical and clinical trial readiness on SLC6A1-NDD and to align efforts on translational read outs, including EEG, in both humans and the pre-clinical models. RESULTS/ANTICIPATED RESULTS: We have enrolled the full cohort of 20 participants in the prospective SLC6A1-NDD cohort study. Preliminary results have shown that all but 1 individual has a history of developmental delay, and 8 of the 24 individuals in our clinical cohort had at least one episode of developmental regression. Over 90% have epilepsy, and 17/20 in the cohort study have intermittent rhythmic delta activity on EEG. The full knock out mice have behavioral and learning deficits and abnormal electrical brain activity on telemetry, including bursts of spike trains, analogous to epileptiform activity seen in humans. Next steps include quantitative analysis of both mouse and human EEG to develop a translational brain-based biomarker. We plan to assess delta power and investigate genotype-phenotype correlations in mice and humans. DISCUSSION/SIGNIFICANCE: With targeted therapies in development for SLC6A1-NDD, translational biomarkers that demonstrate engagement with the brain are critical. With clinical heterogeneity in SLC6A1-NDD, biomarkers can objectively capture change. Collaborative translational projects may improve efficiency in rare disease research to facilitate early phase trials.

Non-Convulsive Status Epilepticus as A Complication of Electroconvulsive Therapy: A Case Report

IntroductionStatus Epilepticus is defined as a condition that can have long-term outcomes involving neuronal death and injury due to the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures. Electroconvulsive therapy (ECT) is a highly effective treatment option for psychiatric disorders. Although it rarely occurs in the treatment, non-convulsive status epilepticus can be seen as a complication after ECT. Due to its rarity, this complication is not yet well understood, is challenging to diagnose, and information about treatment options is limited.ObjectivesBy sharing this case report, we aim to emphasize the importance of being careful in terms of the risk of status epilepticus in patients receiving electroconvulsive therapy.MethodsHere in we present a 29-year-old patient with no previous neurological disease and who had a history of schizophrenia. Electroconvulsive therapy was planned because the patient was resistant to antipsychotic treatment. EEG was planned for the patient who had urinary incontinence during the ninth session of ECT. Generalized slow wave activity and intermittent rhythmic delta activity were observed in the EEG, therefore it was found suspicious for NCSE, and the patient was planned to perform an EEG again by administering diazepam to confirm the diagnosis. After diazepam, the patient whose EEG tracing was clearly improved was admitted to the neurology intensive care unit. He was followed up for 48 hours with continuous 4 mg/hour/day midazolam and continuous bedside EEG in the neurology intensive care unit. Concomitant lamotrigine was started at 100 mg/day. Significant improvement in EEG, sinusoidal alpha, and beta waves with the eye open was observed at the 48th hour, and the patient was transferred back to the psychiatry service. Lamotrigine treatment was increased up to 200 mg/day and clozapine treatment was adjusted to 350 mg/day in the psychiatry service. In the patient whose EEG was requested again before discharge.ResultsThe diagnosis of NCSE post-ECT can be laborious; the symptoms may not be characteristic and clear, and usually not distinguish from symptoms of confusion, delirium, or psychiatric illness, hence the follow-up psychiatrist should be careful. In suspicious cases, EEG should be taken, especially in patients at risk for seizures. These risky conditions include previous seizure history, and lithium or clozapine use.ConclusionsThe diagnosis of NCSE after ECT is a demanding condition. Particular attention should be paid to factors that will lower the seizure threshold. In cases with ECT treatment with clozapine, intermittent clozapine blood levels can be quantified and medication interactions and smoking can be considered. When the cases are examined, the common aspect of most of them is that the treatments have good results.Disclosure of InterestNone Declared

High prevalence of electroencephalographic frontal intermittent rhythmic delta activity in patients with moderately severe COVID-19.

The aim of our study was to analyse EEG findings in patients with COVID-19 not requiring respiratory support. We reviewed EEGs performed in patients with COVID-19 between April 2020 and May 2021 at the University Hospital in Kraków, Poland. Demographic and clinical data, including comorbid conditions, discharge disposition, survival, neuroimaging findings, laboratory results, and treatment was collected. The study included 44 EEGs performed in 35 patients (51.4% females), aged 65.5 ± 13.9 years. Almost all patients had at least one comorbidity, and one-third had one or more preexisting neurological conditions. Three quarters of EEGs were abnormal. The most frequent EEG finding was background slowing (16 patients; 45.7%). Frontal findings included frontally predominant rhythmic delta (FIRDA) in 10 (28.6%) patients and focal slowing in the left frontal lobe. Patients with abnormal EEG significantly more often required oxygen supplementation (p = 0.003) and were less likely to recover (p = 0.048). Patients with COVID-19 infection may frequently manifest with an abnormal EEG. FIRDA seems to be a frequent EEG pattern in less severe cases of COVID-19 infection. Future studies are needed to establish whether COVID-19 infection increases the risk for FIRDA, and to investigate its pathogenesis.

Clinical and Electrophysiological Features Predicting Response to Antiseizure Medications in Juvenile Absence Epilepsy.

We aimed to evaluate the clinical findings and electroencephalographic (EEG) characteristics of patients with juvenile absence epilepsy (JAE) and to determine the factors that predict response to antiseizure medications (ASMs) in JAE. We reviewed the medical records of 29 patients with JAE. The patients who were seizure-free during the last 12 months of their follow-up and who did not have generalized spike waves on their last EEG were considered as the treatment-responsive group, and the patients whose clinical seizures persisted during the last 12 months of their follow-up or who had generalized spike waves on their follow-up EEGs were considered as patients who did not respond to ASMs. There were 29 patients, 20 girls and nine boys, with a mean age of 13.34 ± 2.17 years and a follow-up time of 32.1 ± 11.9 months. Twenty-two cases (75.8%) were evaluated as responsive to treatment. Generalized tonic-clonic seizures (GTCS) were statistically more common in patients who did not respond to ASM. Epileptic seizures began at a younger age in the group that responded to medication. Occipital intermittent rhythmic delta activity (OIRDA) in EEG was significantly higher in the group that responded to the medication. Our study shows that concomitant GTCS may predict poorer response to ASMs in JAE. Younger age at diagnosis and OIRDA on EEG may be associated with better response to treatment. Our findings need to be confirmed by further prospective and long-term studies.

Two Cases of Isolated Neurofilament Heavy Chain Antibody Syndrome

Objective Novel clinical and laboratory findings in anti-neurofilament heavy chain encephalitis Background Antibodies to mature components of neuronal intermediate filament (NIF) have been implicated in several neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and more recently, various autoimmune encephalitides. The components include a-internexin, light chain and heavy chain. In the largest case series of anti-NIF syndromes (McKeon et al, 2021), patients' cell-based assays revealed antibodies to one, two or all three components. Heavy chain antibodies (anti-NfH) were present in most, including three out of four patients with encephalopathy and cerebellar involvement. One was due to a paraneoplastic phenomenon. Anti-NfH was also elevated in two cases of encephalopathy with spasticity. It was the lone autoantibody in one of the six aforementioned cases. Design/Methods N/A. Results Case 1: 37-year old female with a history of ovarian carcinoma, treated in 2016. Cognitive impairment started in fall 2019, with significant worsening to the point of catatonia and coma in October 2020. Though encephalopathy improved, severe ataxia and nystagmus persisted. Two MRI brain studies and an EEG were unremarkable, and no radiological evidence of cancer recurrence. Oligoclonal bands (in both CSF and serum) and serum anti-NfH were elevated. Case 2: 59 year-old female with gradual cognitive decline since March 2018, followed by rapid cognitive deterioration in Oct 2020. There was limb weakness, severe rigidity, clonus and a witnessed seizure. EEG showed intermittent rhythmic delta activity. MRI brain indicated severe bilateral hippocampal atrophy. CSF Protein and CSF anti-NfH were elevated. Conclusions This case series contains the first reported paraneoplastic encephalopathy with cerebellar involvement from isolated anti-NfH. Also presented is the first reported case of PERMS from any NIF antibody. Further research is needed on quantitative and qualitative factors of anti-NIF syndromes. Specifically, the clinical relevance of the number of antibodies, and associations between phenotype and specific antibody combination.

Temporal intermittent rhythmic theta activity (TIRTA): A marker of epileptogenicity?

To describe a novel EEG rhythm, temporal intermittent rhythmic theta activity (TIRTA), and its potential association with epilepsy. We report TIRTA on scalp EEG in a series of 12 patients, all of whom were found to have epilepsy. The clinical and electroencephalographic characteristics of each patient were reviewed. In addition, features that may distinguish TIRTA from benign EEG patterns, including rhythmic temporal theta bursts of drowsiness (RTTBD), were identified. TIRTA was unilateral in all cases. For all patients, TIRTA was seen in the awake and drowsy states. Eight patients also had TIRTA observed during N2 sleep. The average frequency of TIRTA was 5.5Hz and the average duration of a train of TIRTA was 5.25s. In seven cases the morphology was notched in appearance. Temporal intermittent rhythmic delta activity (TIRDA) was seen in seven patients on the same side as TIRTA. Eleven patients also had ipsilateral temporal sharp waves. Abnormal MRI (6/12) and or PET (5/5) findings were ipsilateral to TIRTA. In this preliminary report we suggest that TIRTA may be a novel marker of potential epileptogenicity, possibly representing a higher frequency variant of TIRDA.

Frontal intermittent rhythmic delta activity (firda) detected by bispectral index monitoring

Frontal intermittent rhythmic delta activity (firda) detected by bispectral index monitoring

Modified lateral orbitotomy approach for resection of anterior temporal cavernous malformation

Background: The lateral orbitotomy approach (LOA) provides a direct and minimally invasive corridor to orbital apex, cavernous sinus, and middle cranial fossa (MCF) lesions. Removal of the lateral orbital wall and retraction of the orbital contents, as performed with a traditional LOA, can cause diplopia and enophthalmos and affect visual acuity. The modified LOA (mLOA) preserves the lateral orbital wall to limit this morbidity.Case Description: A 58-year-old man experienced new-onset headaches and anxiety attacks that improved with anti-seizure medication. He was neurologically intact on examination. Magnetic resonance imaging demonstrated a 2-cm right anterior temporal cavernous malformation with an associated hemosiderin ring. Electroencephalogram revealed right temporal intermittent rhythmic delta activity suspicious for anterior temporal lobe epilepsy. He underwent an endoscopic-assisted keyhole mLOA for resection of the cavernoma and hemosiderin-stained brain. Key steps included a Y-shaped incision in the upper eyelid/lateral canthus, removal of a 1.5-cm segment of the lateral orbital rim, drilling of the lateral orbital wall with preservation of the medial cortex, drilling the lateral sphenoid ridge to access the anterior temporal lobe, resecting the cavernoma with endoscopic assistance for removal of all potentially epileptogenic abnormal brain, and plating the orbital rim as part of a layered closure. Postoperatively, he remained neurologically intact. He was discharged on postoperative day 4 after resolution of a cerebrospinal fluid leak with lumbar drainage. On follow-up, his anxiety attacks had completely resolved, and his incision was well-healed.Conclusion: The mLOA is an ideal keyhole technique for selected lesions of the MCF.

Frontal intermittent rhythmic delta activity steroid responsive (FIRDAS) as biomarker of neurotoxicity after CAR T-cells infusion

Les CAR-T cells améliorent le pronostic des patients ayant une maladie hématologique réfractaire ou en rechute. Plus de la moitié des patients traités présenteront un ICANS (Immune effector cell-associated neurotoxicity syndrome). L’objectif de cette étude était d’évaluer l’électroencéphalogramme (EEG) comme outil diagnostique de l’ICANS. Nous avons mené une étude monocentrique et prospective. Tous les patients traités par CAR T-cells au CHRU Montpellier entre septembre 2020 et juillet 2021 ont été inclus. Une évaluation neurologique (clinique, EEG et par résonance magnétique) a été réalisée entre le 6 e et le 8 e jour après injection et contrôlée à un mois en cas d’anomalies. 38 patients (14 femmes) ont été inclus, l’âge médian était de 65 ans (55, 74). 17 patients avaient un ICANS (44 %). Les trois variables les plus précoces et significativement associées à l’ICANS étaient: un EEG pathologique (N = 15/17, p < 0,001), un pic de CRP plus haut (146 [86,256] p = 0,004) et une natrémie au nadir plus basse (131 [129,132] p = 0,005). Les EEG pathologiques montraient la présence constante d’activités rythmiques intermittentes frontales (FIRDA, n = 15/15). Notre étude montre que les FIRDA sont un biomarqueur sensible de l’ICANS. Elle révèle qu’il existe une corrélation entre la neurotoxicité, l’hyponatrémie et l’élévation de la CRP. Certaines études ont pu démontrer que l’IL6 (dont la CRP est un témoin) était capable d’induire une sécrétion d’hormone anti-diurétique. L’hyponatrémie entraînerait alors un œdème cérébral osmotique objectivé par la présence de FIRDA. L’EEG est un outil diagnostique sensible de l’ICANS. Il permet la détection de FIRDAS, témoins de l’hypertension intracrânienne induite par les CAR-T cells.

New-Onset Seizures as an Acute Presentation With Atypical EEG Findings in a Previously Healthy Child With Asymptomatic COVID-19 Infection

Coronavirus disease 2019 (COVID-19) infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This infection usually presents with upper respiratory symptoms; however, it can also present with a wide variety of other multisystem and neurological symptoms, including seizures. There are several proposed mechanisms by which COVID-19 can cause systemic signs of infections, including neurological complications and seizures.This case report describes a pediatric patient without a previously documented history of epilepsy who was admitted for new-onset focal seizures with impaired consciousness. No other cause and triggers of seizures were found, and the child was tested positive for COVID-19 infection. The patient had six electroclinical seizures during EEG. Video EEG findings showed atypical features of onset of intermittent rhythmic delta activity (IRDA) slowing over the left hemisphere with evolution/generalization of rhythmic delta/theta activity and without clear typical generalized epileptiform discharges. These EEG findings correlated with a clinical change of behavior arrest, staring, and yawning. Similar spells were reported multiple times a day prior to the admission, and past EEG was normal. A review of current literature on COVID-19 and neurological manifestations in children, including new seizures and prior diagnosis of epilepsy, is also provided in this case report.The clinical experience in children with newly diagnosed or chronic epilepsy suggests that exacerbation of seizures, especially from systemic effects such as those caused by severe COVID-19 infection, will be a major concern.

EEG abnormalities indicating the genetic determination of epilepsies

Genetic and acquired factors contribute to epileptogenesis in all epilepsy syndromes and patients. A comprehensive evaluation of both components of etiology is essential in every patient. In this review, the authors enumerate the EEG abnormalities indicating the genetic determination of epilepsy. The authors briefly describe generalized spike-and-wave paroxysms, focal spikes and sharp waves, photosensitivity, 4-7 Hz theta rhythm, 2-4 Hz occipital intermittent rhythmic delta activity, phi rhythm, and generalized monomorphic alpha EEG background activity. For each abnormality, the authors review prior knowledge and add recent research results. The neurophysiological meaning of the abnormalities, age distribution, the relationship to epilepsy, the role of the EEG patterns in epileptogenesis, clinical presentation, and prognosis in the individual patient are the main aspects of description and discussion. These EEG abnormalities may shape the typical, syndrome-specific phenotype, forecast severity of the disease and difficulty of treatment or pharmacoresistance, and modify the syndrome-specific general prognosis of the syndrome. Relationship to epilepsy and heritability data of the EEG abnormalities can help to estimate the risk of epilepsy in the offspring. Epilepsy syndromes are taxonomic diagnostic categories that might be enriched with neurobiological meaning and heritability relations.

EEG findings in patients with angelman syndrome. Notched slow waves and age-specific characteristics of the main EEG patterns

Angelman syndrome (AS) is a genetic disorder caused by a mutation in the maternal copy of the UBE3A gene and characterized by typical clinical manifestations (such as mental retardation, difficulty walking, and laughter) and specific changes on the electroencephalogram (EEG).The aim of this study was to analyze age-specific characteristics of the main EEG patterns, including high-amplitude frontal delta activity with spikes, slow-wave delta-theta activity with spikes in the posterior regions, and diffuse continuous rhythmic theta activity. In addition to that, we assessed the frequency of a rare and highly specific for AS EEG pattern: notched slow waves.We have identified and described additional criteria for EEG during sleep: high index of pathological slow-wave activity and the ratio of pathological slow-wave activity index to epileptiform activity index during sleep. We also analyzed all EEG patterns at the age most significant for the detection of this syndrome (up to 3 years) and their age-specific dynamics.We covered the frequency and characteristics of EEG patterns rare in AS patients, such as three-phase bifrontal delta waves, reactive pathological activity in the posterior areas, EEG patterns of focal seizures originating from the posterior areas, benign epileptiform discharges of childhood, and migrating continuous slow-wave activity.We analyzed the differences between main EEG patterns in AS and frontal and occipital intermittent rhythmic delta activity (fIRDA and OIRDA patterns).

Genetic mosaicism, intrafamilial phenotypic heterogeneity, and molecular defects of a novel missense SLC6A1 mutation associated with epilepsy and ADHD

BackgroundMutations in SLC6A1, encoding γ-aminobutyric acid (GABA) transporter 1 (GAT-1), have been recently associated with a spectrum of neurodevelopmental disorders ranging from variable epilepsy syndromes, intellectual disability (ID), autism and others. To date, most identified mutations are de novo. We here report a pedigree of two siblings associated with myoclonic astatic epilepsy, attention deficit hyperactivity disorder (ADHD), and ID. MethodsNext-generation sequencing identified a missense mutation in the SLC6A1 gene (c.373G > A(p.Val125Met)) in the sisters but not in their shared mother who is also asymptomatic, suggesting gonadal mosaicism. We have thoroughly characterized the clinical phenotypes: EEG recordings identified features for absence seizures and prominent bursts of occipital intermittent rhythmic delta activity (OIRDA). The molecular pathophysiology underlying the clinical phenotypes was assessed using a multidisciplinary approach including machine learning, confocal microscopy, and high-throughput 3H radio-labeled GABA uptake assays in mouse astrocytes and neurons. ResultsThe GAT-1(Val125Met) mutation destabilizes the global protein conformation and reduces transporter protein expression at total and cell surface. The mutant transporter protein was localized intracellularly inside the endoplasmic reticulum (ER) in both HEK293T cells and astrocytes which may directly contribute to seizures in patients. Radioactive 3H-labeled GABA uptake assay indicated the mutation reduced the function of the mutant GAT-1(Val125Met) to ~30% of the wildtype. ConclusionsThe seizure phenotypes, ADHD, and impaired cognition are likely caused by a partial loss-of-function of GAT-1 due to protein destabilization resulting from the mutation. Reduced GAT-1 function in astrocytes and neurons may consequently alter brain network activities such as increased seizures and reduced attention.

Electroclinical features and outcome of ANKRD11-related KBG syndrome: A novel report and literature review

Electroclinical features and outcome of ANKRD11-related KBG syndrome: A novel report and literature review

Source Imaging of Triphasic Waves and Other Encephalopathies.

Triphasic waves (TWs) are defined as high-amplitude positive waveforms with preceding and after-going negative waves, typically seen in medically ill patients. TWs manifest in similar clinical presentations as other EEG encephalopathies; however, electrographically, they appear different. To better understand the difference, the authors used two different source localization software programs to find a reproducible and unique signature for TW. EEGs performed at Johns Hopkins Hospital and Duke University Hospital were retrospectively analyzed. EEG samples of TW, Delta, Theta-Delta, and Frontal Intermittent Rhythmic Delta Activity were selected. The authors did source localization via Commercial Curry 8 and open-source Brainstorm software. A minimum of 10 stereotypical waveforms per subject were selected. The authors used the Boundary Element Method for the head model, which was derived from the Montreal Neurological Institute averaged imaging data set. Dipole and current density analyses were performed. Twenty-eight patients were selected (10 TW, 4 Frontal Intermittent Rhythmic Delta Activity, 6 Theta-Delta, and 8 Delta). The findings suggest the activation of anterior frontal and midline structures for TW. Frontal Intermittent Rhythmic Delta Activity had a similar localization but without a moving dipole. In comparison, the Delta and Delta-Theta appeared to have a more diffuse origin. Source analysis of TW via two different software suggests the anterior midline location of TW with anterior to posterior propagation. These findings correlate with the previous hypotheses of TW origin. Retrospective analysis, low number of recording electrodes, and difficult analysis of slow waves limit the interpretation of these results. Nonetheless, this article opens the prospect of future studies in this field.