EEG Abnormalities Research Articles

Differences in the clinical presentations of anti-NMDAR (anti-N-methyl-D-aspartate receptor) encephalitis with status epilepticus: a retrospective case series

Literature on anti-NMDAR (anti-N-methyl-D-aspartate receptor) encephalitis is limited in developing countries, including Indonesia. This retrospective observational case series explored the impact of early diagnosis and treatment on patient outcomes in four distinct cases of anti-NMDAR encephalitis with status epilepticus, and other related conditions, of patients referred to Dr. Sardjito General Hospital, Yogyakarta. Clinical data from May 2021 to August 2023 were collected through the review of medical records, encompassing demographic information, clinical presentation, history, laboratory results, imaging studies, EEG reports, interventions, and the progression of the disease. Four cases were reported, three of whom were diagnosed with anti-NMDAR and one with bacterial encephalitis, each presenting a variety of neuropsychiatric clinical symptoms, leading to hospitalization, extensive testing, and interventions to establish the definitive diagnosis. Cases 1 and 4 have a childhood history of seizures. The cases analyzed factors including the impact of childhood versus adulthood onset and the adherence to taking medicine regularly leading to exacerbation symptoms and relapses. Distinguishing anti-NMDAR encephalitis from related conditions, such as bacterial encephalitis, was further complicated in patients with varied neuropsychiatric presentations (seizures, hallucinations, irritable behavior, headaches) and responses to the treatment. Supporting investigation finds positive NMDAR testing and abnormal CT, MRI, and EEG results, contributed to definitive diagnoses. It could be concluded that comprehensive diagnostic investigations are important for prompt recognition of clinical characteristics, and early initiation of immunomodulatory therapy in managing anti-NMDAR encephalitis and related conditions in Yogyakarta, Indonesia.

Natural history and outcome of nonketotic hyperglycinemia in China.

Nonketotic hyperglycinemia (NKH) is a rare, life-threatening genetic disorder. The patients usually show heterogeneous and nonspecific symptoms, resulting in diagnosis challenges using conventional approaches. Here, the clinical presentation and genetic features of 20 Chinese patients were examined and reported in order to clarify the natural history and prognosis of NKH in China. The Human Gene Mutation Database and literature regarding NKH in China were reviewed. Age of onset, clinical characteristics, genetic analysis, cranial magnetic resonance imaging (MRI) and electroencephalography (EEG) examinations, and outcome of the patients were analyzed. Natural history experiences and follow-up assays for five patients who were followed in our center were described. Among all 20 NKH patients, 17 (85%) had the neonatal type and 3 (15%) had the infantile type, no late-onset cases were detected. Patients showed up for admission with a history of seizures (15/20), lethargy (14/20), hypotonia (11/20), apnea (9/20), and feeble sobbing (4/20). Brain MRI findings included abnormal signals in the internal capsule, cerebellum, or brainstem (6/14), dysplasia of the corpus callosum (5/14), and white matter abnormalities (3/14). EEG evaluations showed anomalies such as burst suppression (4/8) and hypsarrhythmia and/or epileptic activity (6/8). Median values of cerebrospinal fluid (CSF) glycine levels, plasma glycine levels and CSF/plasma glycine ratios were135.2 (range, 6.3-546.3) μmol/L, 998.2 (range,75-3,084) μmol/L, 0.16 (range, 0.03-0.60) respectively. Genetic analyses revealed four new variations and GLDC, AMT gene abnormalities in 13 (65%), 7 (35%) case, respectively. Prognosis information was available for 18 cases: nine patients died, eight in the neonatal period. Among the nine survivors, varying developmental disorders were observed. Different disease processes and outcomes were found in Chinese NKH patients, according to this study. The initial clinical presentations, CSF glycine levels and CSF to plasma glycine ratios do not reliably predict prognosis, while MRI and EEG abnormalities may indicate a poor outlook. NKH diagnosis should be considered for neonates presenting specific symptoms. The present survey provides clinical data that support the development of a standardized protocol for diagnosing and treating NKH in China.

Generalizability of electroencephalographic interpretation using artificial intelligence: An external validation study.

The automated interpretation of clinical electroencephalograms (EEGs) using artificial intelligence (AI) holds the potential to bridge the treatment gap in resource-limited settings and reduce the workload at specialized centers. However, to facilitate broad clinical implementation, it is essential to establish generalizability across diverse patient populations and equipment. We assessed whether SCORE-AI demonstrates diagnostic accuracy comparable to that of experts when applied to a geographically different patient population, recorded with distinct EEG equipment and technical settings. We assessed the diagnostic accuracy of a "fixed-and-frozen" AI model, using an independent dataset and external gold standard, and benchmarked it against three experts blinded to all other data. The dataset comprised 50% normal and 50% abnormal routine EEGs, equally distributed among the four major classes of EEG abnormalities (focal epileptiform, generalized epileptiform, focal nonepileptiform, and diffuse nonepileptiform). To assess diagnostic accuracy, we computed sensitivity, specificity, and accuracy of the AI model and the experts against the external gold standard. We analyzed EEGs from 104 patients (64 females, median age = 38.6 [range = 16-91] years). SCORE-AI performed equally well compared to the experts, with an overall accuracy of 92% (95% confidence interval [CI] = 90%-94%) versus 94% (95% CI = 92%-96%). There was no significant difference between SCORE-AI and the experts for any metric or category. SCORE-AI performed well independently of the vigilance state (false classification during awake: 5/41 [12.2%], false classification during sleep: 2/11 [18.2%]; p = .63) and normal variants (false classification in presence of normal variants: 4/14 [28.6%], false classification in absence of normal variants: 3/38 [7.9%]; p = .07). SCORE-AI achieved diagnostic performance equal to human experts in an EEG dataset independent of the development dataset, in a geographically distinct patient population, recorded with different equipment and technical settings than the development dataset.

Electroencephalographic outcomes and predictors of epilepsy in autoimmune encephalitis

BackgroundAn abnormal EEG is pivotal in diagnosis, exclusion of mimickers and prognosticating epilepsy in Autoimmune Encephalitis (AE). However, little is known about the short and long term electroencephalographic outcomes and predictors of epilepsy in AE. This study aims to describe the seizure characteristics and electrophysiological markers of various AE subtypes and assess the clinical and electrophysiological predictors of autoimmune epilepsy. MethodsClinical features and EEGs in 74 patients (acute phase=39 and post-acute phase defined after a minimum eight weeks after acute phase=35) of AE fulfilling the proposed criteria were reviewed in their respective acute phases and at six months follow-up. ResultsThe mean age of presentation (N = 74, 45 females) was 21.8 (21.8 ± 17.0) years. 38 (51 %) patients were <18 years. Seizures were present in 55 (74 %) patients with poor response to ASMs (p = 0.039). 39 (52.7 %) EEGs were abnormal in acute phase. Anti-NMDAR AE had most frequently abnormal EEG (63.4 %). Poor background reactivity and theta range slowing were most common abnormalities. FIRDA, EDB and delta range slowing were seen in seropositive AE (P = 0.003). Mutism, psychiatric features and incontinence correlated with abnormal EEG (p = 0.013, p = 0.028 and p = 0.025). Background slowing and epileptiform discharges predicted worse cognitive scores at follow-up (p = 0.012). Eight (11.9 %) patients developed epilepsy. Status epilepticus at presentation (p = 0.009), seronegative status (p = 0.0020), delayed initiation of immunotherapy (p = 0.012), abnormal MRI (p = 0.003) and abnormal EEG (p = 0.004) at onset indicate development of autoimmune epilepsy ConclusionsFIRDA, EDB and delta range slowing with refractory seizures suggest AE. Epileptiform abnormalities, status epilepticus and seronegativity predict autoimmune epilepsy.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients

BackgroundRecognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses.MethodsA prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome.ResultsThis study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869.ConclusionWe established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

2200 Association between gait speed deterioration and EEG abnormalities

Abstract Introduction Physical and cognitive decline at an older age is preceded by changes that accumulate over time until they become clinically evident difficulties. These changes, frequently overlooked by patients and health professionals, may respond better than fully established conditions to strategies designed to prevent disabilities and dependence in later life. The objective of this study was twofold: to provide further support for the need to screen for early functional changes in older adults and to look for an early association between decline in mobility and cognition. Methods A cross-sectional cohort study was conducted on 95 active functionally independent community-dwelling older adults in Havana, Cuba. We measured their gait speed at the usual pace and their cognitive status using the MMSE. A value of 0.8 m/s was used as the cut-off point to decide whether they presented a decline in gait speed. A quantitative analysis of their EEG at rest was also performed to look for an associated subclinical decline in brain function. Results Results show that 70% of the sample had a gait speed deterioration (i.e. lower than 0.8 m/s), of which 80% also had an abnormal EEG frequency composition for their age. While there was no statistically significant difference in the MMSE score between participants with a gait speed above and below the selected cut-off, individuals with MMSE scores below 25 also had a gait speed&amp;lt;0.8 m/s and an abnormal EEG frequency composition. Conclusions Our results provide further evidence of early decline in older adults – even if still independent and active - and point to the need for clinical pathways that incorporate screening and early intervention targeted at early deterioration to prolong the years of functional life in older age.

Early automated classification of neonatal hypoxic-ischemic encephalopathy − An aid to the decision to use therapeutic hypothermia

ObjectiveThe study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. MethodsEEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. ResultsThe selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. ConclusionsThe combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. SignificanceThe proposed model has potential as a bedside clinical decision support tool for TH.

Assessment of the diagnostic utility of the electroencephalogram in pediatric emergencies

IntroductionWe analyze the diagnostic utility of urgent EEG (electroencephalogram) performed in children under 16 years of age in our center. Material and methodsDescriptive, retrospective, observational study of consecutive patients from 0 to 16 years of age, who underwent an urgent EEG for any reason, from January to December 2022. ResultsOf the 388 patients, 70 were children: 37 (52.85%) women, and 33 (47.14%) men. Average age: 6.27 ± 4.809. Of the 70 patients, 6 (8.57%) had previous epilepsy. Reasons for consultation: 17 febrile seizures, 10 first focal seizures, 10 first TCG seizures, 6 paroxysmal episodes, 6 absences, 3 myoclonus of extremities, 3 syncope, 2 SE, 2 visual alterations, 2 low level of consciousness, 2 cyanosis, 2 suspected meningitis or encephalitis, 1 choking, 1 atypical headache, 1 chorea, 1 presyncope, 1 language delay. Of the 70 patients, 47 had a normal EEG (67.14%). Of the 47 patients with a normal EEG, 10 were diagnosed with epilepsy, and 3 of them began receiving antiepileptic treatment upon discharge. None of the patients with suspected syncope or paroxysmal disorder (17 patients, 24.28%) had EEG abnormalities. Of the 17 patients with atypical febrile seizures, 3 had EEG abnormalities. ConclusionsA third of the EEG records performed in the Emergency Department showed alterations, probably due to the time taken. Almost half of the patients with suspected epilepsy or EE showed EEG abnormalities, which confirmed the diagnosis in these cases and encouraged the clinician to start drug treatment. No case with a high suspicion of epilepsy was dismissed due to the normality of the EEG recording in our series. No patient diagnosed with syncope or paroxysmal disorder had EEG abnormalities. Nearly a quarter of patients with atypical febrile seizures showed EEG abnormalities. We barely register cases of status epilepticus, probably due to the degree of complexity of our center.

Clinical cases series and pathogenesis of Lamb-Shaffer syndrome in China

BackgroundLamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF.MethodsThis study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF.ResultsThree of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein.ConclusionsThrough a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.

Grading objective diagnostic components in paroxysmal events: One-year follow-up at a tertiary epilepsy center.

This study was undertaken to develop a model and perform a preliminary internal validation study of the Scale for Objective Diagnostic Components of Paroxysmal Events (STAMP). We developed STAMP, which builds on the International League Against Epilepsy task force scale for functional seizures with additional categories for epileptic seizures and syncope. We included 200 consecutive referrals to a Dutch tertiary epilepsy center to evaluate seizurelike events. We recorded demographic and clinical data and collected the clinical evaluation at referral and after 3, 6, 9, and 12 months of follow-up. We ascertained the STAMP at each time point and evaluated factors predicting an improvement in STAMP grade during follow-up. Of the 200 referrals at baseline, 131 were classified as having epileptic seizures, 17 as functional seizures, and three as syncope, and 49 were unclassifiable. STAMP grade at baseline was 4 (absent) in 56 individuals, 3 (circumstantial) in 78, 2 (clinically established) in six, and 1 (documented) in 11. Over time, 62 cases STAMP grades improved, and 23 remained unclassifiable. A refinement of STAMP grade during follow-up was due to successful event recordings in 34 people (30 video-electroencephalographic [EEG] recordings, four tilt table testing), home videos or clinician-witnessed events in 13, and identification of interictal EEG or magnetic resonance imaging abnormalities in seven. An improved STAMP grade after 12 months of follow-up was significantly more likely in those with higher event frequency, unclassifiable events, longer event duration, and a shorter time since the first event and less likely in those with a history suggestive of seizures. This epilepsy service evaluation underscores the crucial role of event recording in improving diagnostic certainty. STAMP may be used to monitor diagnostic performance over time but requires further validation.

Visual Electroencephalography Assessment in the Diagnosis and Prognosis of Cognitive Disorders.

Electroencephalography (EEG) is a noninvasive diagnostic tool that can be of diagnostic value in patients with cognitive disorders. In recent years, increasing emphasis has been on quantitative EEG analysis, which is not easily accessible in clinical practice. The aim of this study was to assess the diagnostic and prognostic value of visual EEG assessment to distinguish different causes of cognitive disorders. Patients with cognitive disorders from a specialized memory clinic cohort underwent routine workup including EEG, neuropsychological testing and brain imaging. Electroencephalography parameters including posterior dominant rhythm, background activity, and response to photic stimulation (intermittent photic stimulation) were visually scored. Final diagnosis was made by an expert panel. A total of 501 patients were included and underwent full diagnostic workup. One hundred eighty-three patients had dementia (111 Alzheimer disease, 30 vascular dementia, 15 frontotemporal dementia, and 9 dementia with Lewy bodies), 66 patients were classified as mild cognitive impairment, and in 176, no neurologic diagnosis was made. Electroencephalography was abnormal in 60% to 90% of patients with mild cognitive impairment and dementia, most profoundly in dementia with Lewy bodies and Alzheimer disease, while frontotemporal dementia had normal EEG relatively often. Only 30% of those without neurologic diagnosis had EEG abnormalities, mainly a diminished intermittent photic stimulation response. Odds ratio of conversion to dementia was 6.1 [1.5-24.7] for patients with mild cognitive impairment with abnormal background activity, compared with those with normal EEG. Visual EEG assessment has diagnostic and prognostic value in clinical practice to distinguish patients with memory complaints without underlying neurologic disorder from patients with mild cognitive impairment or dementia.

Psychotic attack during the clinical course of megalencephalic leukoencephalopathy with subcortical cysts: a case report.

Van der Knaap disease or megalencephalic leukoencephalopathy with subcortical cysts (MLC), is a slowly progressive neurodegenerative disease with macrocephaly. We present a case of MLC with a confirmed homozygous MLC1 mutation who presented with a psychotic attack at a very young age. An 11-year-old girl was admitted to the emergency room with delusions, hallucinations, and irritability. She was diagnosed with MLC at 18 months old. Her psychotic symptoms were improved with the administration of risperidone treatment added to her valproic acid treatment for EEG abnormality. In this case study we reported the first episode of a psychotic attack during the clinical course of MLC. This case indicates the possibility that MLC influences the onset of the psychotic attack. Further investigation with more patients is needed to identify the relationship.

From Request To Result: The Clinical Significance of EEG in a Tertiary Hospital in Turkey

Objective: This study aimed to assess the clinical and demographic profiles of patients undergoing electroencephalography (EEG) over one year, evaluate EEG's impact on patient management, and ascertain the appropriateness of EEG requests. Methods: A retrospective analysis was conducted in the neurophysiology department at XXX University Faculty of Medicine over 12 months from October 2022 to October 2023. The study included the EEG request to the neurophysiology department; pediatrics and the cases that had artifacts or technical issues were excluded. Age, gender, imaging characteristics, EEG findings, and the reasons for EEG requests were recorded. The contribution of EEG to patient management was analyzed. Results: The study included 1217 patients with a mean age of 34.4±16.5 years, ranging from 18 to 90 years. Of these, 656 were female and 561 male. A history of epilepsy was reported in 821 patients. Neurology outpatient clinics, inpatient wards, and intensive care units requested the majority of EEGs. Epilepsy, presyncope/syncope, and psychogenic non-epileptic seizures (PNES) were the top reasons for EEG requests. Among the newly diagnosed epilepsy patients, 13 showed abnormal EEG results. The study identified MRI abnormalities in 202 patients, with a 27% concordance between EEG and MRI findings. EEG significantly influenced patient management in 577 cases (46.5%), demonstrating its crucial role in clinical decision-making. Conclusion: EEG's diagnostic value, particularly in epilepsy and complex neurological conditions, remains unique. Advocating suiting EEG requests and increasing physician knowledge of seizures can optimize patient care and resource use.

Safety and efficacy of deoxycytidine/deoxythymidine combination therapy in POLG-related disorders: 6-month interim results of an open-label, single arm, phase 2 trial

DNA polymerase gamma (POLG)-related disorders are a group of rare neurodegenerative mitochondrial diseases caused by pathogenic variants in POLG, the gene encoding POLG. Patients may experience a range of signs and symptoms, including seizures, vision loss, myopathy, neuropathy, developmental impairment or regression, and liver failure. The diseases follow a progressive, degenerative course, with most affected individuals dying within 3 months-12 years of diagnosis. At present, there are no effective treatments for POLG-related disorders. In this study we report the interim 6-month data from a long term open-label, single arm phase 2 trial, in which we assessed the safety and efficacy of combination therapy with deoxycytidine and deoxythymidine (dC/dT) in children with POLG-related disorders. dC/dT was given enterally in powder form, dissolved in water. The primary outcome measures included Newcastle Mitochondrial Disease Scale (NMDS) score, serum growth differentiation factor 15 (GDF-15; a biomarker of mitochondrial dysfunction), electroencephalography (EEG), seizure diary, and blood and urine tests to assess end organ and mitochondrial function. Secondary outcome measures included recording of all adverse events to evaluate the safety of the intervention. The trial is registered with ClinicalTrials.gov, NCT04802707 (https://clinicaltrials.gov/ct2/show/NCT04802707). Data were collected from 14 October, 2021 to 13 December,2023. We present 6-month interim data from the first ten people with POLG-related disorders enrolled in the trial, six with Alpers-Huttenlocher syndrome, two with ataxia-neuropathy spectrum, and two who do not fit into a classical POLG-related phenotype. During the 6 months of treatment, NMDS score improved from a mean of 27.3at baseline to 20.7at 6 months (estimated difference 6.0; 95% CI 2.5-∞). GDF-15 values remained stable or decreased in all patients; the mean decreased from 1031pg/ml to 729pg/ml (estimated difference 200; 95% CI 12-∞). 8/10 patients had abnormal baseline EEG; improvement in EEG was seen in 5 of these 8. There were no significant changes in other blood and urine testing. Regarding adverse events, two patients experienced diarrhea that spontaneously resolved. dC/dT is a promising treatment option for people with POLG-related disorders. Further research is needed to assess the long-term safety and efficacy in POLG-related disorders, as well as safety and efficacy in other mitochondrial DNA depletion disorders. This study was primarily funded by the Liam Foundation, with additional funding from the Savoy Foundation, Grand Défi Pierre Lavoie Foundation, and Fonds de Recherche du Québec - Santé.

Isolated Psychiatric Symptoms in Children With Anti-N-Methyl-d Aspartate Receptor Encephalitis

BackgroundIsolated psychiatric symptoms can be the initial symptom of pediatric anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis (pNMDARE). Here we report on the prevalence of isolated psychiatric symptoms in pNMDARE. We also assess whether initial neurodiagnostic tests (brain magnetic resonance imaging [MRI], electroencephalography [EEG], and/or cerebrospinal fluid [CSF] white blood cell count) are abnormal in children with isolated psychiatric symptoms and pNMDARE. MethodsThis multicenter retrospective cohort study from CONNECT (Conquering Neuroinflammation and Epilepsies Consortium) from 14 institutions included children under age 18 years who were diagnosed with pNMDARE. Descriptive statistics using means, medians, and comparisons for continuous versus discrete data was performed. ResultsOf 249 children included, 12 (5%) had only psychiatric symptoms without other typical clinical features of autoimmune encephalitis at presentation. All but one (11 of 12 = 92%) had at least one abnormal finding on initial ancillary testing: eight of 12 (67%) had an abnormal EEG, six of 12 (50%) had an abnormal MRI, and five of 12 (42%) demonstrated CSF pleocytosis. The single patient with a normal MRI, EEG, and CSF profile had low positive CSF NMDA antibody (titer of 1:1), and symptoms improved without immunotherapy. ConclusionsIsolated first-episode psychiatric symptoms in pNMDARE are uncommon, and the majority of children will exhibit additional neurodiagnostic abnormalities. Delaying immunotherapy in a child with isolated psychiatric symptoms and normal neurodiagnostic testing may be warranted while awaiting confirmatory antibody testing.

Postoperative EEG abnormalities in relation to neurodevelopmental outcomes after pediatric cardiac surgery.

We had reported that postoperative EEG background including sleep-wake cycle (SWC) and discharge (seizures, spikes/sharp waves) abnormalities were significantly correlated with adverse early outcomes in children after cardiac surgery. We aimed to analyze the relations between these EEG abnormalities and neurodevelopmental outcomes at about2 years after cardiac surgery. We enrolled 121 patients undergoing cardiac surgery at 3.3 months (0.03 ~ 28 months). EEG abnormalities described above during the first postoperative 48 h were evaluated. Griffiths Mental Development Scales-Chinese was used to evaluate the quotients of overall development and 5 subscales of the child's locomotor, language, personal-social, eye-hand coordination and performance skills at 16 ~ 31 months of age. EEG background abnormalities occurred in 59/121 (48.8%) patients and 33 (55.9%) unrecovered to normal by 48 h. Abnormal SWC occurred in 15 (12.4%) patients and 7 (5.8%) unrecovered to normal by 48 h. EEG seizures occurred in 11 (9.1%) patients with frontal lobe seizures in 4. Spikes/sharp waves occurred in 100 (82.6%). EEG background abnormalities, number of spikes/sharp waves and frontal lobe seizures were significantly associated with neurodevelopmental impairment at about 1 ~ 2 year after surgery (Ps ≤ 0.05). Most parameters of EEG abnormalities were significantly associated with neurodevelopmental impairment after cardiac surgery. Neurodevelopmental impairment in children with congenital heart disease remain poorly understood. Previous studies had reported that either EEG seizures or background abnormalities were associated with worse neurodevelopmental outcomes. Our present study showed that all the EEG background and discharge abnormalities including EEG background, seizures and spikes/sharp waves in the early postoperative period were significantly associated with neurodevelopmental impairment at about 1 ~ 2 years after cardiac surgery. Comprehensive evaluation of early postoperative EEG may provide further insights about postoperative brain injury, its relation with neurodevelopmental impairment, and guide to improve clinical management.

Prediction of Cerebral Palsy and Other Motor Developmental Trajectories in High-Risk Neonate Using the Rapid Neurodevelopmental Assessment (RNDA)

Background: Cerebral Palsy (CP) is a prevalent motor disability affecting children globally, emphasizing the need for early identification and intervention. The Rapid Neurodevelopmental Assessment (RNDA) offers a comprehensive approach to predict CP and other motor developmental trajectories in high-risk neonates. Objective: This longitudinal cohort study aims to evaluate the effectiveness of RNDA in predicting CP and motor developmental trajectories. Method: Seventy term neonates from Dhaka Shishu (Children) Hospital were included, with neurodevelopmental assessments conducted using RNDA. Assessments were performed at 3 months and 6-9 months, with CP evaluation at 12 months using clinical examinations. Results: Prolonged labor (44.3%) and delayed cry after birth (31.4%) were common among the study patients (n=70), with varying modes of delivery including normal vaginal delivery (50.0%), vaginal delivery with complications (12.9%), and lower uterine cesarean section (37.1%). Muscle tone, primitive reflexes, gross and fine motor skills, epilepsy, and microcephaly were evaluated across visits to identify impending CP. Significant associations were found between hypertonicity, primitive reflex impairment, gross motor impairment, and fine motor impairment with impending CP across visits, particularly in the 3rd visit (p&lt;0.05). Sensitivity, specificity, accuracy, and predictive values varied across parameters and visits, with fine motor skills and gross motor skills showing the highest sensitivity in the 3rd visit (86.4% and 100.0%, respectively). Additionally, abnormal EEG, USG of the brain, and MRI findings were significantly associated with impending CP, with USG of the brain demonstrating the highest sensitivity (93.3%) and MRI showing the highest specificity (70.0%). Conclusion: RNDA emerges as a valuable tool for early prediction of CP and motor developmental trajectories in high-risk neonates. Early identification through RNDA facilitates timely interventions, optimizing long-term neurodevelopmental outcomes.

Brain age revisited: Investigating the state vs. trait hypotheses of EEG-derived brain-age dynamics with deep learning

Abstract The brain’s biological age has been considered as a promising candidate for a neurologically significant biomarker. However, recent results based on longitudinal magnetic resonance imaging (MRI) data have raised questions on its interpretation. A central question is whether an increased biological age of the brain is indicative of brain pathology and if changes in brain age correlate with diagnosed pathology (state hypothesis). Alternatively, could the discrepancy in brain age be a stable characteristic unique to each individual (trait hypothesis)? To address this question, we present a comprehensive study on brain aging based on clinical Electroencephalography (EEG), which is complementary to previous MRI-based investigations. We apply a state-of-the-art temporal convolutional network (TCN) to the task of age regression. We train on recordings of the Temple University Hospital EEG Corpus (TUEG) explicitly labeled as non-pathological and evaluate on recordings of subjects with non-pathological as well as pathological recordings, both with examinations at a single point in time TUH Abnormal EEG Corpus (TUAB) and repeated examinations over time. Therefore, we created four novel subsets of TUEG that include subjects with multiple recordings: repeated non-pathological (RNP): all labeled non-pathological; repeated pathological (RP): all labeled pathological; transition non-patholoigical pathological (TNPP): at least one recording labeled non-pathological followed by at least one recording labeled pathological; and transition pathological non-pathological (TPNP): similar to TNPP but with opposing transition (first pathological and then non-pathological). The results show that our TCN reaches state-of-the-art performance in age decoding on non-pathological subjects of TUAB with a mean absolute error of 6.6 years and an R2 score of 0.73. Our extensive analyses demonstrate that the model underestimates the age of non-pathological and pathological subjects, the latter significantly (-1 and -5 years, paired t-test, p = 0.18 and p = 6.6e−3). Furthermore, there exist significant differences in average brain age gap between non-pathological and pathological subjects both with single examinations (TUAB) and repeated examinations (RNP vs. RP) (-4 and -7.48 years, permutation test, p = 1.63e−2 and p = 1e−5). We find mixed results regarding the significance of pathology classification based on the brain age gap biomarker. While it is indicative of pathological EEG in datasets TUAB and RNP versus RP (61.12% and 60.80% BACC, permutation test, p = 1.32e−3 and p = 1e−5), it is not indicative in TNPP and TPNP (44.74% and 47.79% BACC, permutation test, p = 0.086 and p = 0.483). Additionally, all of these classification scores are clearly inferior to the ones obtained from direct EEG pathology classification at 86% BACC and higher. Furthermore, we could not find evidence that a change of EEG pathology status within subjects relates to a significant change in brain age gap in datasets TNPP and TPNP (0.46 and 1.35 years, permutation test, p = 0.825 and p = 0.43; and Wilcoxon-Mann-Whitney and Brunner-Munzel test, p = 0.13). Our findings, thus, support the trait rather than the state hypothesis for brain age estimates derived from EEG. In summary, our findings indicate that the neural underpinnings of brain age changes are likely more multifaceted than previously thought, and that taking this into account will benefit the interpretation of empirically observed brain age dynamics.

Dysregulated Apoptosis and Autophagy in Childhood Epilepsy: Correlation to Clinical and Pharmacological Patterns.

We aimed to assess the serum levels of caspase-3 as a marker of apoptosis and microtubule-associated protein 1A/1B-light chain 3 (MAP1-LC3) as an autophagy marker in epileptic children with various clinical and pharmacological types. This case-control study was carried out on 90 participants (50 pediatric patients with epilepsy and 40 healthy matched children), the patients were categorized into three groups: Group (A): 25 pharmacosensitive epilepsy, Group (B): 25 pharmacoresistant epilepsy, and Group (C): 40 (age, sex, and body mass index) matched healthy children selected as controls. Serum caspase-3 and MAP1-LC3 were measured in all study groups, using commercially available ELISA kits. Serum caspase-3 was significantly higher among epileptic children, especially in the pharmacoresistant group, cases managed with multiple antiepileptic drugs, and cases with abnormal EEG findings. Conversely, circulating MAP1-LC3 levels showed a significant reduction in epilepsy cases, particularly in pharmacoresistant cases, in cases treated with multiple antiepileptic drugs, and in cases with abnormal EEG data. A significant negative correlation between serum caspase-3 and MAP1-LC3 was found among epileptic children (r = -0.369, p = 0.0083). Serum caspase-3 was a more valid biomarker in helping diagnose childhood epilepsy, while serum MAP1-LC3 was more valid in predicting pharmacoresistant type. The study reveals that serum caspase-3 levels were significantly elevated, particularly in pharmacoresistant cases and those managed with multiple drugs. Conversely, MAP1-LC3 levels were significantly reduced in epilepsy cases, suggesting potential involvement of altered apoptosis and autophagy in childhood epilepsy.

The Effect of Therapeutic Hypothermia on Serum Carboxy-Terminal Hydrolase L1 and Amplitude EEG Changes in Hypoxic-Ischemic Neonates

Abstract Background Hypoxia-ischemic encephalopathy (HIE) is one of the most important complications of the newborn period. It is the result of depriving nerve tissue of oxygen and glucose, which may be the result of either hypoxia or ischemia. Objective To assess effect of therapeutic hypothermia (TH) on EEG changes and Carboxy-terminal hydrolase L1level in neonatal HIE at Al-Zahraa university and El Haram hospitals. Patients and Methods This was a prospective comparative study that was conducted at the NICU unit Al ZahraaUniversity and El Haram hospitals for a period from (May 2020 till June 2022). This study included 50 full term newborns (37 to 40 weeks of gestational age) with clinical and laboratory evidence of HIE II–III, They were divided into two groups: Group 1: 25 HIE neonates who were treated with therapeutic hypothermia and group 2: 25 HIE neonates who weren’t received therapeutic hypothermia. Newborns with congenital anomalies, intracranial lesion, epileptic seizure, spinal cord injury or cardiac arrest were excluded from the study. We record EEG changes during 72 hrs by an electroencephalogram with a bioelectric amplifier (Deltamed, Bourgogne), (Philips) Screen. Blood samples were analyzed for UCH-L1 levels by (SEG945Mi). The neonates involved in cooling group were placed over a cooling blanket (Blanketrol III), for 72 hours. Results The results showed there was statistically significant relation between high UCH-L1 level and higher grades of the Sarnat score and primitive reflexes of both the cooling group and non cooling group. The results also showed that there were lower levels of UCH-L1 in cooling group compared to non cooling group of the studied neonates Also there was significant negative correlation found between UCH-L1 level and PH, and HCO3 values. This study showed that there was statistically significant relation found between UCH-L1 level and EEG recording on the 3rd day of both the studied groups. This study showed that (84%) of the non cooling group had EEG abnormalities compared to (68%) of the cooling group. Among both groups of the studied neonates, 76% had EEG abnormalities in form of (34%) had suppression EEG, (16%) were occipito-temporal, (20%) fronto-temporal and (6%) centro-parital. Regarding the site of EEG abnormality (18%) were right sided, (24%) were left sided. The study showed that 72% of cooling group were discharged compared to 48% of non cooling group. Conclusion From our study we concluded significant improvement in EEG records in ischemic neonates who were treated with therapeutic hypothermia. UCH- L1 is a good early neuronal injury biomarker for detecting severity of HIE P value &amp;lt; 0.001 and is a good predictor of hypoxia with specificity 92% and ppv 86.7% and NPV 65.7%. Therapeutic hypothermia has been noted to reduce severe disability among survivors.