Outcomes of Neonates with Hypoxic-Ischemic Encephalopathy Treated with Magnesium Sulfate: A Systematic Review with Meta-analysis.

OBJECTIVE: To assess magnesium sulfate (MgSO4) as a neuroprotective agent in hypoxic-ischemic encephalopathy. STUDY DESIGN: For this systematic review, PubMed, EMBASE, the Cochrane Library, EMCARE, and MedNar were searched in November 2022 for randomized controlled trials (RCTs). Meta-analysis was conducted using Stata 16.0 and RevMan 5.3. RESULTS: Twenty RCTs with a total sample size of 1485 were included, of which 16 were from settings where therapeutic hypothermia (TH) was not offered. Regarding MgSO4 in settings where TH was not offered, only 1 study evaluated composite outcome of death or disability at ≥18 months and reported such poor outcome in 8 of 14 control infants and 4 of 8 in the MgSO4 group. MgSO4 was not associated with mortality (RR, 0.86; 95% CI, 0.72-1.03; 13 RCTs) or hypotension (RR, 1.02; 95% CI, 0.88-1.18; 5 RCTs). Thirteen studies reported that MgSO4 improved in-hospital outcomes, such as reduced seizure burden and improved neurological status at discharge. MgSO4 reduced the risk of poor suck feeds (RR, 0.52; 95% CI, 0.40-0.68; 6RCTs) and abnormal electroencephalogram (RR, 0.64; 95% CI, 0.45-0.93; 5 RCTs). Certainty of evidence was moderate for mortality and low or very low for other outcomes. For studies with MgSO4 as an adjunct to TH, none reported on death or neurodevelopmental disability at ≥18 months. MgSO4 was not associated with mortality (RR, 0.65; 95% CI, 0.34-1.27; 3 RCTs) or hypotension (RR, 1.0; 95% CI, 0.71-1.40; 3 RCTs). CONCLUSIONS: Evidence around long-term outcomes of MgSO4 when used with or without TH was scant. MgSO4 therapy may improve in-hospital neurological outcomes without affecting mortality in settings where TH is not offered. Well-designed RCTs for neuroprotection are needed, especially in low-resource settings. TRIAL REGISTRATION: "Open Science Forum" (https://doi.org/10.17605/OSF.IO/FRM4D).

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

Discordant electroencephalogram epileptiform activity and hemispherectomy in children with refractory epilepsy and encephaloclastic lesions: a case series.

This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was in the neonatal period in three children, at 17 months in two, and at 5 years in one. Their ictal and interictal electroencephalogram (EEG) abnormalities showed paradoxical lateralization to the incorrect/'normal' hemisphere or showed bilateral abnormalities. After cautious discussion regarding the discordant electroclinical profile and implications for outcome, they proceeded to a functional hemispherectomy (between ages 4-11y) with good outcomes (at 1-10y follow-up). Their clinical details, EEG findings, electrocorticography, neuroimaging, and histology are reported. Possible surgical candidacy should be evaluated early in children with refractory epilepsy, even those with complex profiles and discordant data from the different investigations. Contralateral or bilateral EEG abnormalities should not preclude consideration of hemispherectomy in children with refractory epilepsy, hemiparesis, and uniclastic lesions.

Risk of Hospitalizations Following Gastrostomy in Children with Intellectual Disability.

OBJECTIVE: To examine the frequency of hospital admissions before and after gastrostomy insertion in children with severe intellectual disability. STUDY DESIGN: We conducted a retrospective cohort study using linked health administrative and disability data from Western Australia (WA) and New South Wales (NSW). Children born between 1983 and 2009 in WA and 2002 and 2010 in NSW who had a gastrostomy insertion performed (n = 673 [WA, n = 325; NSW, n = 348]) by the end of 2014 (WA) and 2015 (NSW) were included. Conditional Poisson regression models were used to evaluate the age-adjusted effect of gastrostomy insertion on acute hospitalizations for all-cause, acute lower respiratory tract infections (LRTI), and epilepsy admissions. RESULTS: The incidence of all-cause hospitalizations declined at 5 years after procedure (WA cohort 1983-2009: incidence rate ratio, 0.70 [95% CI, 0.60-0.80]; WA and NSW cohort 2002-2010: incidence rate ratio, 0.63 [95% CI, 0.45-0.86]). Admissions for acute LRTI increased in the WA cohort and remained similar in the combined cohort. Admissions for epilepsy decreased 4 years after gastrostomy in the WA cohort and were generally lower in the combined cohort. Fundoplication seemed to decrease the relative incidence of acute LRTI admissions in the combined cohort. CONCLUSIONS: Gastrostomy was associated with health benefits including reduced all-cause and epilepsy hospitalizations, but was not protective against acute LRTI. These decreases in hospitalizations may reflect improved delivery of nutrition and medications.

Neuronal ceroid lipofuscinosis type 2: an Australian case series.

AIM: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative disorder presenting in children aged 2-4 years with seizures and loss of motor and language skills, followed by blindness and death in late childhood. Initial presenting features are similar to a range of common epilepsies. We aim to highlight typical clinical and radiological features that may prompt diagnosis of CLN2 disease in early disease stages. METHODS: We present a series of 13 Australian patients with CLN2 disease, describing clinical features, disease evolution, neuroimaging, electroencephalogram, biochemical and genetic results. Expert neuroradiological magnetic resonance imaging (MRI) analysis was retrospectively performed on 10 cases. RESULTS: Twelve patients presented with seizures, with initial seizures being focal (n = 4), generalised tonic-clonic (n = 3), absence (n = 3) and febrile (n = 2). Eleven patients (85%) had a language delay before the onset of seizures. Cerebellar or cerebral atrophy was noted in all patients on centralised MRI review, with abnormalities of the brain-stem, ventricles, corpus callosum and hippocampi. CONCLUSIONS: Early language delay with the onset of seizures at 2-4 years of age is the hallmark of CLN2 disease. MRI findings of early subtle atrophy in the cerebellum or posterior cortical regions should hasten testing for CLN2 disease to enable early initiation of enzyme replacement therapy.

Epidemiology of gastrostomy insertion for children and adolescents with intellectual disability.

The largest group of recipients of pediatric gastrostomy have neurological impairment with intellectual disability (ID). This study investigated trends in first gastrostomy insertion according to markers of disadvantage and ID etiology. Linked administrative and health data collected over a 32-year study period (1983-2014) for children with ID born between 1983 and 2009 in Western Australia were examined. The annual incidence rate change over calendar year was calculated for all children and according to socioeconomic status, geographical remoteness, and Aboriginality. The most likely causes of ID were identified using available diagnosis codes in the linked data set. Of 11,729 children with ID, 325 (2.8%) received a first gastrostomy within the study period. The incidence rate was highest in the 0-2 age group and there was an increasing incidence trend with calendar time for each age group under 6 years of age. This rate change was greatest in children from the lowest socioeconomic status quintile, who lived in regional/remote areas or who were Aboriginal. The two largest identified groups of ID were genetically caused syndromes (15.1%) and neonatal encephalopathy (14.8%).Conclusion: Gastrostomy is increasingly used in multiple neurological conditions associated with ID, with no apparent accessibility barriers in terms of socioeconomic status, remoteness, or Aboriginality. What is Known: • The use of gastrostomy insertion in pediatrics is increasing and the most common recipients during childhood have neurological impairment, most of whom also have intellectual disability (ID). What is New: • Nearly 3% of children with ID had gastrostomy insertion performed, with the highest incidence in children under 3 years of age. • Gastrostomy use across different social groups was equitable in the Australian setting.

Paediatric new-onset seizure clinic in Australia: Experience and lessons learnt.

AIM: A new-onset seizure clinic (NOSC) was established at our hospital in 2011, with the aim to provide accurate diagnosis and appropriate management to children with new-onset seizures or seizure mimics. METHODS: We report on the data analysis of the first 200 children seen in NOSC. A paediatric neurologist or paediatric/neurology trainee under supervision of a neurologist reviewed all the children. A detailed history and clinical examination were undertaken. Electroencephalogram (EEGs) were undertaken prior to clinic review in most emergency departments. Children were classified as 'epilepsy positive' (EP+) or 'epilepsy negative' (EP-) after the first consultation. RESULTS: Of 200 patients, 109 were classified as EP+: generalised epilepsy in 57 of 109, focal in 36, childhood seizure susceptibility syndrome in 26 and epileptic encephalopathy in 5. EEG was available in 192: in 117, it was abnormal - 23 with background abnormalities and 109 with epileptiform activity. Of the 109 patients, 80 were commenced on anti-epileptic drugs (AEDs): 12 were able to come off medication after seizure-free period, 61 were controlled on AEDs and 7 were refractory. Children were followed up for 12-48 months. None of the children had diagnosis revised on follow-up. CONCLUSIONS: This is the first Australian study to report on a large cohort of children from a NOSC. An EEG and a paediatric neurologist assessment is a good combination to enable diagnostic accuracy: In the first 200 patients seen, there were no revisions of the initial diagnosis on follow-up.

Evolving Trends of Gastrostomy Insertion Within a Pediatric Population.

OBJECTIVE: Gastrostomy insertion in pediatrics is usually used in children with complex needs and severe disability. The accessibility and acceptance of the procedure is increasing but population-based occurrence data are lacking and there is limited understanding of its use in clinical subgroups. METHODS: This birth cohort study investigated the trends in first gastrostomy insertion among a pediatric population born between 1983 and 2009 in Western Australia using linked administrative and health data collected over a 32-year period (1983-2014). Indications were identified using diagnosis codes from linked hospitalization data and grouped according to a refined classification system. Age and birth cohort patterns of first gastrostomy use, over calendar year and age respectively, were described. RESULTS: Of the 690,688 children born between 1983 and 2009, 466 underwent a gastrostomy insertion. Overall, the prevalence was approximately 7 cases per 10,000 births. New gastrostomy insertions were increasingly performed in children during the preschool years over calendar years and in successive birth cohorts. Children with a neurological disorder constituted the largest group receiving gastrostomy (n = 372; 79.8) including 325 (87.4%) with comorbid intellectual disability. CONCLUSIONS: New gastrostomy insertion among children who require long-term enteral feeding support increased over the study period. The procedure is most often performed in the context of severe neurological disability, including intellectual disability, and offers families potential for long-term home-based management of feeding difficulties.

Lacosamide as adjunctive therapy in treatment-resistant epilepsy in childhood.

AIMS: Lacosamide (LCM) is a novel anti-epileptic drug (AED) that enhances the slow inactivation of voltage-gated sodium channels. Its efficacy as adjunctive therapy for focal seizures is confirmed in adult placebo controlled trials with >50% reduction in seizure frequency in up to 50% patients. There is paucity of data on its efficacy and tolerance in treatment-resistant epilepsy in childhood (TREC). This study aims to assess efficacy and tolerance of LCM as adjunct therapy in TREC. METHODS: Audit of medical records and seizure diaries in children with TREC on LCM. A response (RR) was defined as ≥50% reduction in seizure frequency. RESULTS: Forty children (age range: 2-19 years) with TREC received LCM as add-on therapy. All had abnormal electroencephalograms, and 36 had abnormal neuroimaging. All children failed >2 AED trials, nine had trialled the ketogenic diet, five had failed the vagal nerve stimulator and 11 had failed resective epilepsy surgery. Median dose and duration of LCM therapy were 5.7 mg/kg/day and 10.5 months, respectively. RR was seen in 20% with persistence of RR in 8/36, 8/30 and 8/26 children on LCM at 3-, 6- and 9-month follow-up. Two children became seizure free. Retention on LCM was 65% at 9 months. LCM was well tolerated with minor side effects in seven children; no child discontinued LCM because of side effects. CONCLUSION: LCM is a well-tolerated AED with RR in 20%: in 5%, it resulted in seizure freedom. LCM may be useful even in TREC when seizures have not responded to intervention with multiple modalities.

Genotyping of Orientia tsutsugamushi circulating in and around Vellore (South India) using TSA 56 gene.

PURPOSE: The immunodominant TSA 56 gene of Orientia tsutsugamushi, (scrub typhus agent) has four variable regions (VD-I to VD-IV) making it useful for genotyping. This study was undertaken to determine Orientia tsutsugamushi genotypes circulating in and around Vellore using complete and partial TSA 56 gene. METHODS: Of the 162 patients positive by 47 â€‹kDa qPCR, on 21 samples PCR to amplify the complete TSA 56 gene (≈1605 bp: Long protocol) and the partial gene sequence using the Horinouchi (≈650bp) and the Furuya (≈480 bp) protocol was performed. Sanger and Nanopore sequencing was performed to obtain sequence data for assigning genotype. For 13 amplicons partial and complete gene data was obtained. RESULTS: Phylogenetic analysis of the complete gene (Long protocol) which includes VD-I to VD-IV region and partial gene (Horinouchi) which amplifies the VD-I to VD-III regions showed identical genotypes. Twelve belonged to TA763 genotype and one belongs to Karp genotype. The Furuya sequence (in silico) correctly identified the Karp genotype and 10 of the TA763 genotypes. Two TA763 genotypes (identified by complete and 650 bp partial gene analysis) were misidentified by Furuya sequence analysis as Karp genotype. CONCLUSIONS: Analysis of the 13 complete 56 â€‹kDa gene sequences suggests that TA763 is the commonest genotype in Vellore. Sanger sequencing of the 650 bp fragment gives similar results. However, these results need to be validated by larger prospective multi-centric studies.

Tolerability and Effectiveness of Cathodal Transcranial Direct Current Stimulation in Children with Refractory Epilepsy: A Case Series.

There are limited treatment options for drug-resistant epilepsy (DRE) in children. We performed a pilot study to investigate the tolerability and effectiveness of cathodal transcranial direct current stimulation (tDCS) in DRE. Twelve children with DRE of varied etiology underwent three to four daily sessions of cathodal tDCS. The seizure frequency at 2 weeks before and after tDCS was obtained from seizure diaries; clinic reviews at 3 and 6 months assessed any longer-term benefits or adverse effects. The spike wave index (SWI) was analyzed in the EEGs done immediately before and after tDCS on the first and last day of tDCS. One child remained seizure free for a year after tDCS. One child had reduced frequency of ICU admissions for status epilepticus for 2 weeks, likely due to reduced severity of seizures. In four children, an improvement in alertness and mood was reported for 2-4 weeks after tDCS. There was no benefit following tDCS in the other children. There were no unexpected or serious adverse effects in any child. Benefit was seen in two children, and the reasons for the lack of benefit in the other children need further study. It is likely that tDCS stimulus parameters will need to be tailored for different epilepsy syndromes and etiologies.

Is sleep captured during a standard daytime EEG sufficient to diagnose Electrical Status Epilepticus in Sleep.

Electrical Status epilepticus of sleep (SES) is an EEG pattern where there is significant activation of epileptiform activity in NREM sleep. A spike wave index (SWI) of > 80-85% is often labelled as typical SES. We aimed to explore if sleep during a standard daytime-EEG, as compared an overnight-EEG, was adequate to diagnose ESES. Ten children with daytime and overnight studies suggestive of SES were audited. SWI and Spike Wave Density (SWD) were calculated for 5-minute epochs of wake in the daytime and overnight study, as well daytime-EEG sleep and first and last NREM cycle in the overnight-EEG. SWI in daytime NREM was not significantly different from SWI in the first sleep cycle of the overnight study. SWI in the last sleep cycle was significantly lower than the first sleep cycle in the overnight-EEG. SWD was significantly higher in the first sleep cycle in the overnight-EEG than the daytime sleep and the last NREM cycle. SES may be diagnosed in NREM sleep from a daytime-EEG study. Larger studies are needed to explore the significance of the disparity between SWI and SWD in the first and last NREM cycles in the overnight study.

Effects of bumetanide on neonatal seizures: A systematic review of animal and human studies.

BACKGROUND: Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures. METHODS: A systematic review of animal and human studies was conducted to evaluate the efficacy and safety of bumetanide for neonatal seizures. PubMed, Embase, CINAHL and Cochrane databases were searched in March 2023. RESULTS: 26 animal (rat or mice) studies describing 38 experiments (28 in-vivo and ten in-vitro) and two human studies (one RCT and one open-label dose-finding) were included. The study designs, methods to induce seizures, bumetanide dose, and outcome measures were heterogeneous, with only 4/38 experiments being in animal hypoxia/ischaemia models. Among 38 animal experiments, bumetanide was reported to have antiseizure effects in 21, pro-seizure in six and ineffective in 11. The two human studies (n = 57) did not show the benefits of bumetanide as an add-on agent to phenobarbital in their primary analyses, but one study reported benefit on post-hoc analysis. Overall, hearing impairment was detected in 5/37 surviving infants in the bumetanide group vs. 0/13 in controls. Four of the five infants with hearing impairment had received aminoglycosides concurrently. Other adverse effects reported were diuresis, mild-to-moderate dehydration, hypotension, and electrolyte disturbances. The studies did not report on long-term neurodevelopment. The certainty of the evidence was very low. CONCLUSION: Animal data suggest that bumetanide has inconsistent effects as an antiseizure medication in neonates. Data from human studies are scarce and raise some concerns regarding ototoxicity when given with aminoglycosides. Well conducted studies in animal models of hypoxic-ischaemic encephalopathy are urgently needed. Future RCTs, if conducted in human neonates, should have an adequate sample size, assess neurodevelopment, minimize using aminoglycosides, be transparent about the potential ototoxicity in the parent information sheet, conduct early hearing tests and have trial-stopping rules that include hearing impairment as an outcome.

Continuous electroencephalography in the intensive care unit: A critical review and position statement from an Australian and New Zealand perspective.

Objectives: This article aims to critically review the literature on continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU) from an Australian and New Zealand perspective and provide recommendations for clinicians. Design and review methods: A taskforce of adult and paediatric neurologists, selected by the Epilepsy Society of Australia, reviewed the literature on cEEG for seizure detection in critically ill neonates, children, and adults in the ICU. The literature on routine EEG and cEEG for other indications was not reviewed. Following an evaluation of the evidence and discussion of controversial issues, consensus was reached, and a document that highlighted important clinical, practical, and economic considerations regarding cEEG in Australia and New Zealand was drafted. Results: This review represents a summary of the literature and consensus opinion regarding the use of cEEG in the ICU for detection of seizures, highlighting gaps in evidence, practical problems with implementation, funding shortfalls, and areas for future research. Conclusion: While cEEG detects electrographic seizures in a significant proportion of at-risk neonates, children, and adults in the ICU, conferring poorer neurological outcomes and guiding treatment in many settings, the health economic benefits of treating such seizures remain to be proven. Presently, cEEG in Australian and New Zealand ICUs is a largely unfunded clinical resource that is subsequently reserved for the highest-impact patient groups. Wider adoption of cEEG requires further research into impact on functional and health economic outcomes, education and training of the neurology and ICU teams involved, and securement of the necessary resources and funding to support the service.

Access to Pediatric Neurology Training and Services Worldwide: A Survey by the International Child Neurology Association.

Pediatric neurology is the medical subspecialty responsible for diagnosing and managing diseases and disorders of the nervous system in childhood and adolescence. In many, but not all, regions of the world, the discipline of pediatric neurology is recognized as a specialty or subspecialty of either neurology or pediatrics. Significant knowledge and competencies in this area are necessary to be effective in clinical practice. The need for this is driven by the high burden of disease from neurologic conditions in children and the effect on their families. As the first part of a multistaged project under the auspices of the International Child Neurology Association, in collaboration with key stakeholders, a survey was undertaken to establish which countries have practicing child neurologists. For those countries that have child neurologists, the survey established the number of practitioners and which countries have access to in-country child neurology training. Responses were obtained from 177 countries. Worldwide, there is a median of 0.07 and mean of 0.39 child neurologists per 100,000 population. The greatest deficits in child neurology specialists and access to training were evident in countries which fell under the World Bank rating of low-income country status (range of 0-0.008 child neurologists per 100,000 population). Seventy-three percent of low-income countries lack access to child neurologists: The majority are in the African and South-East Asia regions. For the population of 1.37 billion in the continent of Africa, there were 324 child neurologists, equating to a median of 0.01 per 100,000 population in comparison with a median of 0.59 child neurologists per 100,000 across high-income countries. Ninety-four countries had capacity to support in-country pediatric neurology training. Worldwide, there are inadequate numbers of child neurologists and a great need for increased training capacity.

BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.

BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).

CARFS7: A guide and proforma for reading a preterm neonate's EEG.

OBJECTIVES: The important role of the EEG in preterm and term babies in investigating brain function and seizures, predicting outcomes, evaluating therapeutic interventions and decision-making is being increasingly acknowledged. Development of the brain in the last trimester of pregnancy results in rapid changes in the EEG patterns in this period. Acquiring and interpreting the EEG of a preterm baby can be challenging. The aim of this study was to develop a proforma titled CARFS7 (Continuity, Amplitude, Reactivity, Frequency, Synchrony, Symmetry, Sleep, Sharps, Shapes, Size and Seizures) to enable neurologists to read EEGs of premature babies with greater confidence, ease and accuracy and produce a report more easily repeatable and homogenous among operators. METHODS: The CARFS7proforma was developed based on a literature review and the personal experience of the authors. The parameters of the EEG evaluated and scored in the proforma are Continuity, Amplitude, Reactivity/Variability, Frequency, Synchrony, Symmetry, Sleep, Sharps, Shapes/Patterns, Size and Seizures. We also assessed the interrater reliability of the proposed scoring system incorporated in the proforma. RESULTS: CARFS7 proforma incorporates a number of parameters that help evaluate the preterm EEG. The interrater reliability of the proposed scoring system in the CARFS7proforma was high. CONCLUSIONS: CARFS7 is a user friendly proforma for reading EEGs in the preterm infant. Interrater reliability using Cohen's k shows high agreement between two child neurologists who independently rated the EEGs of 25 premature babies using this proforma. CARFS7 has the potential to provide, accurate, reproducible and valuable information on brain function in the preterm infant in clinical practice.

Why do neonates receive antiseizure medications?

BACKGROUND: Continuous conventional video-electroencephalography (cVEEG), the gold standard, is not routinely available for monitoring neonatal seizures in Australia. Therefore, seizures are monitored with clinical observation and amplitude-integrated electroencephalography (aEEG), which may result in under- or over-treatment with antiseizure medications (ASMs). We aimed to investigate ASM usage and its relation to the "cVEEG-confirmed seizures" (cVEEG seizures) in the at-risk infants admitted to a tertiary referral neonatal intensive care unit (NICU). METHODS: The study was a part of a diagnostic study comparing cVEEG with aEEG for the detection of neonatal seizures. Thirty-six infants ≥35 weeks gestational age and at risk of seizures and admitted to NICU were recruited after informed parental consent. The infants were monitored and treated with ASMs based on clinical observation and aEEG findings. A simultaneous cVEEG, not available for clinical decision making, was recorded for 24-h and interpreted at a later date. Data regarding ASM usage and seizure burden on cVEEG were collected. Spearman's Rho coefficient was used to assess the correlation between the number of doses of ASMs administered and seizure burden on cVEEG. RESULTS: cVEEG recordings of 35 infants were available for analysis. The gestational age of the infants ranged from 36 to 42 weeks, and the most common diagnosis was hypoxic-ischemic encephalopathy. Twelve infants received ASMs during the 24-h study period, of which five (42%) did not have cVEEG seizures. Maximum cVEEG seizure burden was 8.3 h, and maximum number of ASMs used was three. The correlation between the number of doses of ASMs administered in an infant and the seizure burden on cVEEG was low (Spearman's Rho: 0.44; p = .148). CONCLUSION: Treatment of neonatal seizures based on clinical observation and aEEG, without cVEEG, results in unnecessary or inadequate exposure to ASMs for many infants.

Epilepsy surgery in PCDH 19 related developmental and epileptic encephalopathy: A case report.

We report a female child with PCDH19 related developmental and epileptic encephalopathy with drug-resistant seizures, cognitive and language impairment, autism spectrum disorder and sleep dysfunction. Her seizures, which started at 10 months of age, were resistant to multiple anti-seizure medications. Developmental stagnation followed by regression occurred after the onset of recurrent seizures. Her ictal EEGS suggested left temporal lobe origin for her recorded seizures. MRI upon expert re-review showed a subtle abnormality in the left temporal lobe. In view of the severe nature and frequency of her seizures, a left temporal lobectomy was undertaken at the age of 2 years and 3 months. Though her seizure outcome was Engel class 3, her seizure frequency and severity were significantly reduced. She has been seizure-free for 10 months at her last outpatient assessment when she was 4 years and 8 months of age (2 years and 5 months after epilepsy surgery). However she recently had an admission for COVID19 infection, with a breakthrough cluster of seizures. Her developmental trajectory changed, though she is making good progress with her cognitive and language skills.