Electroencephalographic Abnormalities Research Articles

BDNF, proBDNF and proBDNF/BDNF ratio with electroencephalographic abnormalities in children with attention deficit hyperactivity disorder: Possible relations to cognition and severity.

Attention deficit hyperactivity disorder (ADHD) with and without subclinical epileptogenic discharges (SED) have been suggested to negatively affect cognitive abilities of children with ADHD. The role of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in ADHD is in need of being investigated. The aims were to evaluate the levels of serum BDNF, proBDNF and the proBDNF/BDNF ratio in addition to the potential impacts of SED on the children's cognitive abilities and the severity of ADHD. The included participants with ADHD were 30 children with normal electroencephalogram (EEG) (G1) and 30 children with SED (G2), together with 30 healthy children (G3). The cognitive abilities and severity of the disorder were evaluated. The biochemical measures were determined by ELISA. The presence of coexisting SED and nocturnal enuresis has led to a deleterious effect on cognitive processes but not on the severity. The focal epileptogenic discharge was the most common among children in G2. The levels of BDNF in Groups 1 and 2 were less than those in G3. The higher proBDNF/BDNF ratio could be related to the low BDNF levels rather than high proBDNF levels. The findings of this study highlight the importance of investigating the presence of SED and nocturnal enuresis in children with ADHD. Targeting strengthening of cognitive abilities in children with coexisting ADHD and SED is advised. The role of proBDNF in the pathophysiology of ADHD needs further investigation.

EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome

BackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy. ObjectiveThis study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy. Study designEEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS. ResultsTwenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h. ConclusionsIf confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment.

Learning Disabilities and Epilepsy: About a Clinical Case

Landau-Kleffner syndrome (LKS) is an epilepsy syndrome of childhood, characterized by auditory verbal agnosia and severe electroencephalographic abnormalities. It happens between 3-7 years of age, 20% without seizures. A 6-years-old boy, with normal psychomotor development, who begins to experience difficulties in understanding the meaning of words, sometimes with incoherent speech and writing difficulties (irregular handwriting, spelling mistakes). Neurological evaluation showed loss of comprehensive language with auditory verbal agnosia, difficulties in fine motor skills and in graphomotor coordination. After clinical suspicion, the diagnosis of SLK was confirmed by night video-electroencephalogram (EEG): abundant paroxysmal activity of bilateral and independent fronto-center-temporal spikes and spike-wave activity, with an almost continuous exacerbation during sleep. Initially treated with valproate and clobazam, without improvement, he started prednisolone, with improvement in language, writing and normalization of the EEG. Knowledge of this syndrome is important for differential diagnosis with other neurological disorders, especially learning difficulties.

Exploring the correlation between serum α-synuclein and abnormal electroencephalography patterns in children with epilepsy, as well as electroencephalographic discharge index

Background This study investigates the correlation between serum α-synuclein and abnormal electroencephalography patterns as well as the electroencephalographic discharge index in children with epilepsy. Methods Fasting venous blood of 4 ml were collected from the participants, centrifuged at 3000 rpm with a centrifuge radius of 15 cm for 20 min, and stored in a −70 °C freezer for serum α-synuclein examination. Normal EEG: Exhibits symmetrical α or β rhythm primarily in the occipital region. Results The electroencephalogram (EEG) examination results showed that out of the 110 children with epilepsy, 9 had normal EEGs, 35 had mild EEG abnormalities, 46 had moderate EEG abnormalities, and 20 had severe EEG abnormalities. It is noteworthy that the control group did not exhibit any abnormalities in EEG. In the epilepsy group, serum α-synuclein levels were higher than those in the normal group, while α-wave power and θ-wave power were lower than in the normal group (p < 0.05). Among children with epilepsy, those with mild EEG abnormalities, moderate EEG abnormalities, and severe EEG abnormalities had higher serum α-synuclein levels and electroencephalographic discharge indices compared to children with normal EEGs (p < 0.05). Additionally, among children with EEG abnormalities, those with mild, moderate, and severe EEG abnormalities had progressively increasing serum α-synuclein levels and electroencephalographic discharge indices (p < 0.05). Conclusions Children with epilepsy exhibit elevated serum α-synuclein levels, and there is a positive correlation between α-synuclein levels and the grading of EEG abnormalities as well as the electroencephalographic discharge index.

Prevalence of clinical electroencephalography findings in stroke patients with delirium

ObjectiveDelirium is an acute cognitive disorder associated with multiple electroencephalographic (EEG) abnormalities in non-neurological patients, though specific EEG characteristics in patients with stroke remain unclear. We aimed to compare the prevalence of EEG abnormalities in stroke patients during delirium episodes with periods that did not correspond to delirium. MethodsWe retrospectively analyzed clinical EEG reports for stroke patients who received daily delirium assessments as part of a prospective study. We compared the prevalence of EEG features corresponding to patient-days with vs. without delirium, including focal and generalized slowing, and focal and generalized epileptiform abnormalities (EAs). ResultsAmong 58 patients who received EEGs, there were 192 days of both EEG and delirium monitoring (88% [n = 169] corresponding to delirium). Generalized slowing was significantly more prevalent on days with vs. without delirium (96% vs. 57%, p = 0.03), as were bilateral or generalized EAs (38% vs. 13%, p = 0.03). In contrast, focal slowing (53% vs. 74%, p = 0.11) and focal EAs were less prevalent on days with delirium (38% vs. 48%, p = 0.37), though these differences were not statistically significant. ConclusionsWe found a higher prevalence of generalized but not focal EEG abnormalities in stroke patients with delirium. SignificanceThese findings may reinforce the diffuse nature of delirium-associated encephalopathy, even in patients with discrete structural lesions.

Predictors for seizure relapse in children with epilepsy after antiepileptic drug withdrawal: case-control study

Background Epilepsy is defined as a neurologic condition caused by a pathological brain condition. Epilepsy patients who have stopped treatment and are seizure-free for two years are considered to have achieved complete remission. Relapse occurs when seizures return after anti-epileptic drug (AED) withdrawal. Several studies reported that frequent seizures, prolonged duration to control seizures, number of AEDs consumed, and abnormal electroencephalography (EEG) found during AEDs tapered, were reported as predictors of relapse. Methods This retrospective, case-control study was carried out from 2012 – 2016 using multisite medical record evaluation, followed by interviews and EEG examinations. The case group included children with epilepsy who had seizure relapse, while the control group included children with complete remission of epilepsy. Bivariate and multivariate analyses were performed to identify predictors of relapse. Results Relapse predictors in bivariate analysis were symptomatic etiology epilepsy (OR 5.000; 95%CI 2.345 to 10.660; P&lt;0.001), time to seizure control ?1 year (OR 3.689; 95%CI 1.493 to 9.116; P=0.003), and worsened EEG evolution at pre-withdrawal compared to EEG at the time of diagnosis (OR 2.310; 95%CI 1.132 to 4.717; P=0.021). Statistically significant relapse predictors in multivariate analysis were symptomatic etiology epilepsy (OR 4.384; 95%CI 1.985 to 9.681; P&lt;0.001) and slow (?1 year) time to seizure control (OR 4.355; 95%CI 1.753 to 10.817; P 0.002). Conclusion Symptomatic etiology epilepsy and time to seizure control ?1 year are independent predictive factors for seizure relapse in children with epilepsy. Therefore, children with these conditions require a longer period and careful, gradual dose reduction before antiepileptic drugs withdrawal.

Electroencephalographic microstates as a potential neurophysiological marker differentiating bilateral from unilateral temporal lobe epilepsy.

Electroencephalographic (EEG) microstate abnormalities have been documented in different neurological disorders. We aimed to assess whether EEG microstates are altered also in patients with temporal epilepsy (TLE) and whether they show different activations in patients with unilateral TLE (UTLE) and bilateral TLE (BTLE). Nineteen patients with UTLE, 12 with BTLE, and 15 healthy controls were enrolled. Resting state high-density electroencephalography (128 channels) was recorded for 15 min with closed eyes. We obtained a set of stable scalp maps representing the EEG activity, named microstates, from which we acquired the following variables: global explained variance (GEV), mean duration (MD), time coverage (TC), and frequency of occurrence (FO). Two-way repeated measures analysis of variance was used to compare groups, and Spearman correlation was performed to study the maps in association with the clinical and neuropsychological data. Patients with BTLE and UTLE showed differences in most of the parameters (GEV, MD, TC, FO) of the four microstate maps (A-D) compared to controls. Patients with BTLE showed a significant increase in all parameters for the microstates in Map-A and a decrease in Map-D compared to UTLE and controls. We observed a correlation between Map-A, disease duration, and spatial short-term memory, whereas microstate Map-D was correlated with the global intelligence score and short-term memory performance. A global alteration of the neural dynamics was observed in patients with TLE compared to controls. A different pattern of EEG microstate abnormalities was identified in BTLE compared to UTLE, which might represent a distinctive biomarker.

Prevalence of epileptiform electroencephalographic abnormalities in people without a history of seizures: A systematic review and meta-analysis.

Abnormal patterns identified on electroencephalogram (EEG) are one of the primary diagnostic tests for epilepsy. However, epidemiological studies have established that both benign and epileptiform abnormalities (EAs) occur on the EEG of nonepileptic, seizure-free people as well. The reported rates of EAs in nonepileptic, seizure-free populations vary, and the true prevalence is unknown. The primary objective of this systematic review and meta-analysis was to estimate the overall prevalence of EAs in the EEG of people without a history of seizures. Secondary aims were to characterize (1) the cortical localization of focal abnormalities, (2) the proportion of findings that occurred during standard EEG stimulation protocols, and (3) the persistence and implications of abnormalities at follow-up. A comprehensive electronic search of six bibliographic databases was completed: Embase, MEDLINE, PsycInfo, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register for Controlled Trials, and Web of Science. No search date restrictions were applied. Overall effect size was calculated using a generalized linear mixed-effects model. Fifty-three studies, totaling 73 990 individuals, met our inclusion criteria. The overall point prevalence of EAs was 1.74% (95% confidence interval [CI] = 1.13-2.67). Due to the risk of bias in the literature, especially from participant selection, we believe this to be an overestimate of the true prevalence. Prevalence of EAs was greater in children (2.45%, 95% CI = 1.41-4.21) and the elderly (5.96%, 95% CI = 1.39-22.13) compared with adults (.93%, 95% CI = .48-1.80). Reports of developing epilepsy after an EA-positive EEG were rare. The likelihood of subsequent positive findings on follow-up EEG may be as high as 50%. Our study has limitations in that males were overrepresented in the study samples, there is substantial heterogeneity among studies, and many studies provided insufficient detail about their exclusion criteria. Nonetheless, our estimates provide benchmark data for future studies examining EAs in clinical populations, particularly behavioral and psychiatric populations.

Treatment Options for Infantile Spasms Syndrome with SCN8A: A Case Report and Literature Review

Abstract“Infantile spasms syndrome (IS),” previously known as “West syndrome (WS),” is characterized by epileptic spasms (ES), abnormal electroencephalography (EEG) patterns such as hypsarrhythmia, and developmental stagnation or regression in infancy. IS has various etiologies, including genetic abnormalities. SCN8A variants are associated with developmental and epileptic encephalopathy, characterized by developmental delay, seizures starting from infancy, and refractory epilepsy with multiple seizure types. However, previous studies have not focused on the treatment of IS caused by SCN8A variants. We report a case of a previously healthy boy who presented ES and developmental regression at 6 months of age. His EEG revealed hypsarrhythmia, leading to the diagnosis of IS. After admission, the patient was treated with hormonal therapy using intravenous methylprednisolone pulse therapy (MPT). ES and hypsarrhythmia on EEG disappeared in the early stages of MPT administration with no observed treatment complications. Furthermore, we observed no recurrence of EEG abnormalities or seizures at 17 months of age. Genetic testing revealed a novel de novo SCN8A variant (NM_001177984.2:c.2882T &gt; G:p. M961R). The literature review confirmed that 13 patients, including our described patient, were reported to have ES owing to missense variants of SCN8A. While the previous articles do not mention intravenous MPT for ES with SCN8A, our case findings suggest that intravenous MPT therapy may be effective for short-term suppression of ES caused by the SCN8A variant in IS.

Next-generation sequencing testing in children with epilepsy reveals novel clinical, diagnostic and therapeutic implications.

Introduction: Epilepsy is one of the commonest diseases in children, characterized by extensive phenotypic and genetic heterogeneity. This study was conducted to determine the diagnostic utility and to identify novel clinical and therapeutic implications of genetic testing in pediatric patients with epilepsy. Methods: Large multigene panel and/or exome sequencing was performed in 127 unrelated Polish and Ukrainian patients with suspected monogenic epilepsy. Diagnostic yields were presented for five phenotypic subgroups, distinguished by seizure type, electroencephalographic abnormalities, anti-seizure treatment response, and neurodevelopmental deficits. Results: A definite molecular diagnosis was established in 46 out of 127 cases (36%). Alterations in six genes were detected in more than one patient: SCN1A, MECP2, KCNT1, KCNA2, PCDH19, SLC6A1, STXBP1, and TPP1, accounting for 48% of positive cases. 4/46 cases (8.7%) were mosaic for the variant. Although the highest rates of positive diagnoses were identified in children with developmental delay and generalized seizures (17/41, 41%) and in developmental end epileptic encephalopathies (16/40, 40%), a monogenic etiology was also frequently detected in patients with solely focal seizures (10/28, 36%). Molecular diagnosis directly influenced anti-seizure management in 15/46 cases. Conclusion: This study demonstrates the high diagnostic and therapeutic utility of large panel testing in childhood epilepsies irrespective of seizure types. Copy number variations and somatic mosaic variants are important disease-causing factors, pointing the need for comprehensive genetic testing in all unexplained cases. Pleiotropy is a common phenomenon contributing to the growing phenotypic complexity of single-gene epilepsies.

Electroencephalographic abnormalities in children with type 1 diabetes mellitus: a prospective study.

The aim herein was to investigate epileptiform discharges on electroencephalogram (EEG), their correlation with glutamic acid decarboxylase 65 autoantibody (GAD-ab) in newly diagnosed pediatric type 1 diabetes mellitus (T1DM) patients and interpret their medium-term utility in predicting epilepsy. Children presenting with T1DM between July 2018 and December 2019 were included in this prospective longitudinal study. Patients with a history of head injury, chronic illness, neurological disorder, seizure, autism, or encephalopathy were excluded. EEGs were obtained within the first 7 days of diagnosis and later reviewed by a pediatric neurologist. All of the children were clinically followed-up in pediatric endocrinology and neurology clinics for 2 years after their diagnosis. A total of 105 children (46 male, 43.8%) were included. The mean age at the time of diagnosis was 9.6 ± 4.1 years (range: 11 months-17.5 years). At the time of admission, 24 (22.9%), 29 (27.6%), and 52 (49.5%) patients had hyperglycemia, ketosis, and diabetic ketoacidosis, respectively. GAD-ab was positive in 55 children (52.4%). No background or sleep architecture abnormalities or focal slowing were present on the EEGs. Of the patients, 3 (2.9%) had focal epileptiform discharges. The mean GAD-ab levels of the remaining 102 patients were 7.48 ± 11.97 U/mL (range: 0.01-50.54) (p = 0.2). All 3 children with EEG abnormality had higher levels of GAD-ab (3.59 U/mL, 31.3 U/mL, and 7.09 U/mL, respectively). None of the patients developed epilepsy during the follow-up, although 1 patient experienced Guillain-Barré syndrome (GBS). The prevalence of epileptiform discharges in the patients was similar to those of previous studies, in which healthy children were also included. No relationship was found between the epileptiform discharges and GAD-ab, and none of the patients manifested seizures during the first 2 years of follow-up of T1DM. These data support the findings of previous studies reporting that T1DM patients with confirmed electroencephalographic abnormalities do not have an increased risk of epilepsy. On the other hand, GBS might be considered as another autoimmune disease that may be associated with T1DM in children.

Perinatal characteristics and longer-term outcomes in Brazilian children with confirmed or suspected congenital Zika infection: ZIKAction Paediatric Registry.

Despite growing scientific knowledge of Zika virus (ZIKV) infection, questions remain regarding ZIKV infection in pregnancy and congenital ZIKV syndrome (CZS). The ZIKAction Paediatric Registry is an international registry of children with documented ZIKV exposure in utero and/or with confirmed or suspected CZS. Its aim is to characterize these children (i.e., clinical, radiological, neurodevelopmental features) and describe outcomes, longer-term sequelae and management through retrospective case note review. This analysis described the maternal and perinatal characteristics of children in the Registry's Bahia arm, assessed their neuroimaging, ophthalmic, hearing and electroencephalography abnormalities by microcephaly classification and reported on hospitalisations. Children born in 2015-2018 and enrolled 2020-2021 in three public health facilities in Salvador were included. Of 129 (57% female) children, 15 (11·6%) had laboratory-confirmed congenital ZIKV infection and 114 (88·4%) suspected CZS. At delivery, 15 (11·6%) were normocephalic, 30 (23·3%) moderately microcephalic, and 84 (65·1%) severely microcephalic. Median birth head circumference z-score was -3·51 [IQR, -4·69,-2·73]. During follow-up, all children had abnormal neuroimaging, 80·3% (94/117) abnormal electroencephalogram, 62·2% (77/120) ophthalmic abnormalities, and 27·4% (34/124) hearing impairment. Microcephaly classification was significantly associated with gestational age, and ophthalmological and electroencephalography abnormalities. Of 125 children with hospitalisation data, 52 (41·6%) had been hospitalised by most recent follow-up, at median age of 15·8 [4·0, 34·4] months; infections were the leading cause. Congenital ZIKV infection is an emerging disease with a varied and incompletely understood spectrum. Continued long-term follow-up is essential to understand longer-term prognosis and to inform future health and educational needs.

Prediction of Seizure Onset with Machine Learning: A Treatment Option for Landau Kleffner Syndrome

Landau Kleffner Syndrome (LKS) is a rare genetic disorder that presents in the form of auditory verbal agnosia and aphasia (loss of ability to interpret and express language) as well as electroencephalographic abnormalities, which present in children from the ages of 2 to 8. The disorder is classified as developmental/epileptic encephalopathy with spike wave activation on sleep (DEE-SWAS), with 70% of affected patients having epileptic seizures. The disorder is diagnosed based on language regression in addition to severe EEG abnormalities during non-REM sleep. Sometimes patients with epileptiform disorders can sense when a seizure is imminent and alert caretakers of the situation so they can be safely situated when the seizure occurs. This period is called the preictal period or prodrome in which patients can sometimes detect changes in mood and behavior. However, in disorders such as LKS, the loss of verbal expression proves difficult for expression of needs, and could lead to dangerous situations along with a constant need for such patients to be monitored. In this study, machine learning techniques are utilized to analyze several hours of ictal and preictal EEG data from 23 patients in order to predict the onset of a seizure. This study aims to promote patient safety and reduce need for constant monitoring by predicting when a seizure will occur. Several machine learning models have been constructed and their accuracies have been analyzed and compared to those of other studies to create an optimized program which can accurately interpret EEG data.

Hemimegalencephaly: A Systematic Comparison of Functional and Anatomic Hemispherectomy for Drug-Resistant Epilepsy.

Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches. PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome. Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101). We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes.

Epilepsy Frequency and Risk Factors Three Years After Neonatal Seizures

BackgroundNeonatal seizures, one of the main risk factors for the development of epilepsy, remain a clinical concern. In children with neonatal seizures, early recognition of risk factors is important for the early diagnosis and appropriate treatment of epilepsy and for improving prognosis. In this study, we aimed to determine the frequency of and the risk factors for the development of epilepsy in patients with neonatal seizures. MethodsThe hospital files of 228 children who experienced seizures in the neonatal period were reviewed. The frequency of epilepsy and risk factors for the development of epilepsy were determined at age 36 months. ResultsEpilepsy was diagnosed in 40.8% of the cases. Univariate analysis revealed family history of epilepsy, parental consanguinity, abnormal neurological examination findings, microcephaly, unresponsiveness to antiepileptic drugs or antiseizure medication, use of more than one antiepileptic drugs to antiseizure medication at discharge, status epilepticus, electroencephalography abnormalities, abnormal neuroimaging findings, invasive ventilation requirement, myoclonic seizures, central nervous system malformation, and congenital metabolic disease as risk factors for the development of epilepsy. Of these, a family history of epilepsy, abnormal neurological examination findings at discharge, and use of at least two antiepileptic drugs to antiseizure medication at discharge were found as independent risk factors in multivariate analysis. ConclusionsNeonatal seizures appear to be associated with epilepsy in more than one-third of the patients. Of the newborns with seizures, those with a family history of epilepsy, abnormal neurological examination findings at discharge, and those using at least two antiepileptic drugs to antiseizure medication at discharge should be monitored more carefully for the development of epilepsy.

Long-term effectiveness and seizure recurrence risk factors of ketogenic diet for pediatric refractory epilepsy: Experience from a tertiary care center in China.

This study aimed to assess the long-term effectiveness and seizure recurrence risk in children with drug-resistant epilepsy who achieved seizure freedom on a ketogenic diet (KD). Predictors associated with seizure recurrence were also evaluated. Patients with drug-resistant epilepsy who received KD therapy for at least 3 months between May 2011 and April 2020 were included. The clinical efficacy of the KD was evaluated. Patients who achieved seizure freedom for at least 3 months on the KD were focused. Multivariate Cox regression models were used to explore the risk factors of seizure relapse in patients who achieved seizure freedom. This study included 288 patients (163 males, 125 females). The seizure-free rates of the KD at 3, 6, 12, and 24 months were 9.7%, 16.7%, 14.2%, and 9.0%, respectively. Additionally, the seizure reduction rates between 50% and 99% were 46.5%, 39.9%, 30.2%, and 20.5%, respectively. Patients with Angelman syndrome (AS) showed the highest efficacy rate, followed by those with Dravet syndrome (DS). 51 patients achieved at least 3 months of seizure freedom on the KD. Seizures recurred in 24 (47.1%) patients. None of the patients with AS relapsed, while those with DS had the highest recurrence rate. The etiology of epilepsy, KD maintenance treatment period, and electroencephalography (EEG) abnormalities during follow-up differed significantly between patients with and without recurrence. However, multivariate Cox regression analysis indicated that a KD maintenance treatment period of less than 12 months and the presence of EEG abnormalities during follow-up were significantly correlated with a higher risk of relapse. Epilepsy control was restored in 3 of the 24 (12.5%) patients who experienced relapse. KD appears to be effective in children with various types of drug-resistant epilepsy. A short KD maintenance treatment period and EEG abnormalities during follow-up were associated with an increased risk of seizure recurrence.

Beta to theta power ratio in EEG periodic components as a potential biomarker in mild cognitive impairment and Alzheimer’s dementia

BackgroundAlzheimer’s dementia (AD) is associated with electroencephalography (EEG) abnormalities including in the power ratio of beta to theta frequencies. EEG studies in mild cognitive impairment (MCI) have been less consistent in identifying such abnormalities. One potential reason is not excluding the EEG aperiodic components, which are less associated with cognition than the periodic components. Here, we investigate whether aperiodic and periodic EEG components are disrupted differently in AD or MCI vs. healthy control (HC) individuals and whether a periodic based beta/theta ratio differentiates better MCI from AD and HC groups than a ratio based on the full spectrum.MethodsData were collected from 44 HC (mean age (SD) = 69.1 (5.3)), 114 MCI (mean age (SD) = 72.2 (7.5)), and 41 AD (mean age (SD) = 75.7 (6.5)) participants. Aperiodic and periodic components and full spectrum EEG were compared among the three groups. Receiver operating characteristic curves obtained via logistic regression classifications were used to distinguish the groups. Last, we explored the relationships between cognitive performance and the beta/theta ratios based on the full or periodic spectrum.ResultsAperiodic EEG components did not differ among the three groups. In contrast, AD participants showed an increase in full spectrum and periodic relative powers for delta, theta, and gamma and a decrease for beta when compared to HC or MCI participants. As predicted, MCI group differed from HC participants on the periodic based beta/theta ratio (Bonferroni corrected p-value = 0.036) measured over the occipital region. Classifiers based on beta/theta power ratio in EEG periodic components distinguished AD from HC and MCI participants, and outperformed classifiers based on beta/theta power ratio in full spectrum EEG. Beta/theta ratios were comparable in their association with cognition.ConclusionsIn contrast to a full spectrum EEG analysis, a periodic-based analysis shows that MCI individuals are different on beta/theta ratio when compared to healthy individuals. Focusing on periodic components in EEG studies with or without other biological markers of neurodegenerative diseases could result in more reliable findings to separate MCI from healthy aging, which would be valuable for designing preventative interventions.

Multiple cross-frequency coupling analysis of resting-state EEG in patients with mild cognitive impairment and Alzheimer's disease.

Electroencephalographic (EEG) abnormalities are seen in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance. We recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function. Multiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.

Later onset focal epilepsy with roots in childhood: Evidence from early learning difficulty and brain volumes in the Human Epilepsy Project.

Visual assessment of magnetic resonance imaging (MRI) from the Human Epilepsy Project 1 (HEP1) found 18% of participants had atrophic brain changes relative to age without known etiology. Here, we identify the underlying factors related to brain volume differences in people with focal epilepsy enrolled in HEP1. Enrollment data for participants with complete records and brain MRIs were analyzed, including 391 participants aged 12-60 years. HEP1 excluded developmental or cognitive delay with intelligence quotient <70, and participants reported any formal learning disability diagnoses, repeated grades, and remediation. Prediagnostic seizures were quantified by semiology, frequency, and duration. T1-weighted brain MRIs were analyzed using Sequence Adaptive Multimodal Segmentation (FreeSurfer v7.2), from which a brain tissue volume to intracranial volume ratio was derived and compared to clinically relevant participant characteristics. Brain tissue volume changes observable on visual analyses were quantified, and a brain tissue volume to intracranial volume ratio was derived to compare with clinically relevant variables. Learning difficulties were associated with decreased brain tissue volume to intracranial volume, with a ratio reduction of .005 for each learning difficulty reported (95% confidence interval [CI] = -.007 to -.002, p = .0003). Each 10-year increase in age at MRI was associated with a ratio reduction of .006 (95% CI = -.007 to -.005, p < .0001). For male participants, the ratio was .011 less than for female participants (95% CI = -.014 to -.007, p < .0001). There were no effects from seizures, employment, education, seizure semiology, or temporal lobe electroencephalographic abnormalities. This study shows lower brain tissue volume to intracranial volume in people with newly treated focal epilepsy and learning difficulties, suggesting developmental factors are an important marker of brain pathology related to neuroanatomical changes in focal epilepsy. Like the general population, there were also independent associations between brain volume, age, and sex in the study population.

Proposed anti-seizure medication combinations with rufinamide in the treatment of Lennox-Gastaut syndrome: Narrative review and expert opinion.

Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such "rational polytherapy" involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors' clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS.