Cerebral function monitoring in term or near term neonates at MDH : preliminary experience and proposal of a guideline

Introduction: Cerebral function monitoring (CFM) is a simplified EEG device that is used to monitor cerebral function at the cot-side. Various studies have shown its value in detecting neonatal encephalopathy and electrographic seizures, prognostication of neonatal cerebral insults, assessment of response to anticonvulsant therapy and in selecting encephalopathic infants for therapeutic hypothermia. This paper describes our preliminary experience with this monitoring device at Mater Dei Hospital, and a draft of a protocol for its clinical application. Methods: Fourteen recordings were performed on neurologically normal and abnormal term neonates. The quality of the records and their correlation with other imaging and standard EEG findings was assessed. A dataset including technical and clinical particulars of these cases was then compiled, analyzed and discussed. Results: Amplitude aEEG traces were recorded from a total of 14 patients, 4 of whom were normal term or near term infants, and 10 were infants with a neurological abnormality. All records were of satisfactory quality, and all showed very high impedance levels. Five out of 11 neurologically-abnormal patients had signs of seizure activity on CFM. A technical fault caused high impedance level in the first 2 traces. Annotations were generally lacking. Five out of 10 infants with CNS problems had clinical seizures of which 4 had electrographic seizures on CFM, 4 had electrographic seizures on formal EEG, and 3 had abnormal MRI findings. Conclusion: Our local experience has confirmed the usefulness of CFM monitoring in the setting of a neonatal intensive care unit. Despite some initial problems with high impedance levels and electrode attachment, the tracings obtained were reproducible and of good quality. Almost half of the neurologically-abnormal neonates showed signs of seizure activity on CFM with good correlation with clinical and standard EEG. The timely diagnosis enabled the clinicians to confirm seizure activity, initiate anticonvulsant therapy and monitor the response. Staff training is vital in order to improve utilisation of CFM in neonatal practice.peer-reviewe

Video-EEG long term monitoring as a new service at Mater Dei Hospital

Introduction: Video-EEG long-term monitoring (LTM) was introduced into Mater Dei Hospital (MDH) in May 2012. The audit aims to evaluate LTM in terms of diagnostic outcomes and impact on patient management. Methods: Analysis was carried out after retrospective review of 30 inpatients who underwent LTM at MDH between May 2012 and May 2014. 31 LTM sessions were performed. Referrals were made by 3 consultant neurologists. LTM and medical records were compared to evaluate whether LTM determined a change in diagnosis and how this affected management outcomes. Results: Patient ages ranged from 3 months to 73 years (35.5% paediatric cases) (16 male , 15 female studies). The most common indication was for uncontrolled seizures (54.8%), followed by suspected non-epileptic seizures (NES) (29%). The average hospital stay was 2 days for paediatric patients and 5 for adult cases. Major monitoring interruptions were recorded in 5 paediatric and 1 adult case. Comparing pre- with post-LTM diagnosis showed that the investigation changed or identified a new diagnosis in 38.7%, confirmed the diagnosis in 29%, and was inconclusive in 32.3% (inconclusive in 45.5% of paediatric cohort and 25% of adult cohort). It led to medication optimisation in 38.7% and neuropsychiatry referrals in 22.6%. The remaining were unchanged, not followed up or referred for other tests. None were referred for surgery. Conclusion: LTM is an important tool which influenced patient management through changes in medication or referrals in 64.5% of cases. Continuous evaluation of the techniques used and resources available is recommended to increase the yield of conclusive LTM studies.peer-reviewe

Using antiepileptic drugs in children : recent developments and recommendations

Epilepsy is one of the most common neurological disorders, with approximately 45 per 100,000 children developing new-onset epilepsy every year. Children are a vulnerable population with unique health needs and a correct diagnosis and thus correct treatment of epilepsy in children, particularly a diagnosis of early onset epilepsy, is important in order to ensure better quality of life, neurodevelopmental outcomes, cognition, education, improved level of function and future employment. Therapy with antiepileptic drugs (AEDs) aims to minimize the frequency of epileptic seizures with minimal side effects. The first generation AEDs (such as phenytoin, carbamazepine and valproic acid) are still widely used, although they are associated with serious side effects and pharmacokinetic problems (narrow therapeutic indices, nonlinear kinetics, and drug-drug interactions due to enzyme inhibition and enzyme induction properties). The novel AEDs (such as lamotrigine, levetiracetam, rufinamide, and zonisamide) have expanded the treatment options of epilepsy, however they are also associated with severe pharmacokinetic shortcomings, especially for paediatric populations. This educational article will discuss how the correct use of these drugs can lead to improved quality of life measures. This paper also provides an overview of ongoing research on the use of population pharmacokinetics in addressing the challenges paediatric populations offer to drug and dose individualisation.peer-reviewe

Preparing an interdisciplinary guidance for the management of generalised paediatric status epilepticus

BACKGROUND: A guidance was created to assist family doctors in managing generalized paediatric status epilepticus (GPSE) at Primary HealthCare (PHC) clinics.AIM: The article aims to discuss the process by which the GPSE guidance was prepared.OBJECTIVES: The authors intend to provide information on how the literature review was carried out, what clinical threshold was decided as appropriate for the administration of rescue medication, and what treatments may be used in PHC.METHOD: An initial search and guidance draft was forwarded to a Joint Working Group (JWG) composed of professionals working at PHC and Mater Dei Hospital (MDH). The names of benzodiazepines and their formulations available at PHC clinics were forwarded to the JWG by the clinical Chairperson of Primary HealthCare. A Pubmed search was carried out for the terms “status epilepticus,” “children”, and “prehospital”, filtering for free full text publications, humans, English language, and dating from 1999 to 2019, yielding seventeen results in the English language. Eight were relevant. A second Pubmed search for “diazepam use in paediatric seizures” and “midazolam use in paediatric seizures” yielded fifty-five results, filtering for English and dating from 2010-2019. Two were relevant. Several guidelines and literature were directly referenced. The literature review process and results were summarised and modified into a flowchart.RESULTS: An interdisciplinary approach was used to decide how GPSE should be treated. Consensus was agreed that if a seizure lasts more than five minutes, benzodiazepines midazolam and diazepam available at PHC clinics, may be used. Intramuscular, intranasal, buccal, or rectal routes are preferred per the child’s weight; and time the duration of seizure activity.CONCLUSION: GPSE may terminate during the first five minutes of ictal activity. Midazolam and diazepam may be administered by different methods if seizures persist, depending on the clinical scenario.peer-reviewe

Genetic landscape of ALS in Malta based on a quinquennial analysis

Genetic risk for amyotrophic lateral sclerosis (ALS) is highly elevated in genetic isolates, like the island population of Malta in the south of Europe, providing a unique opportunity to investigate the genetics of this disease. Here we characterize the clinical phenotype and genetic profile of the largest series of Maltese ALS patients to date identified throughout a 5-year window. Cases and controls underwent neuromuscular assessment and analysis of rare variants in ALS causative or risk genes following whole genome sequencing. Potentially damaging variants or repeat expansions were identified in more than 45% of all patients. The most commonly affected genes were ALS2, DAO, SETX and SPG11, an infrequent cause of ALS in Europeans. We also confirmed a significant association between ATXN1 intermediate repeats and increased disease risk. Damaging variants in major ALS genes C9orf72, SOD1, TARDBP and FUS were however either absent or rare in Maltese ALS patients. Overall, our study underscores a population that is an outlier within Europe and one that represents a high percentage of genetically explained cases.peer-reviewe

International consensus recommendations on the diagnostic work-up for malformations of cortical development

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk

International consensus recommendations on the diagnostic work-up for malformations of cortical development

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. In this Consensus Statement, the international MCD network Neuro-MIG provides recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs. Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management. In this article, the international MCD network Neuro-MIG provides consensus recommendations to aid both expert and non-expert clinicians in the diagnostic work-up of MCDs with the aim of improving patient management worldwide. We reviewed the literature on clinical presentation, aetiology and diagnostic approaches for the main MCD subtypes and collected data on current practices and recommendations from clinicians and diagnostic laboratories within Neuro-MIG. We reached consensus by 42 professionals from 20 countries, using expert discussions and a Delphi consensus process. We present a diagnostic workflow that can be applied to any individual with MCD and a comprehensive list of MCD-related genes with their associated phenotypes. The workflow is designed to maximize the diagnostic yield and increase the number of patients receiving personalized care and counselling on prognosis and recurrence risk

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.

Aicardi-Goutières syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level. The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid. Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe