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Objective Cannabidiol is efficacious as an adjunctive treatment in children with epilepsy associated with Dravet and Lennox-Gastaut syndromes. As cannabidiol is currently co-prescribed with other antiseizure medications (ASMs), a literature review was undertaken to review the evidence of interactions between cannabis-based medicinal products and other ASMs. Methods A search of Cochrane, Pubmed and Embase from January 2015 to April 2020 was performed. All original research papers investigating interactions between cannabidiol and ASMs were included. Bibliographies of review articles were searched to identify further papers. Adverse events and side effects were excluded. Results Thirty studies (eighteen observational cohort studies, two randomised-control trials, three case reports/series, three animal studies, two briefing reports, an analysis of cohort data and a clinical trial simulation) were identified. Pharmacokinetic interactions were identified between CBD and clobazam, rufinamide, zonisamide, stiripentol, sirolimus/everolimus, eslicarbazepine, brivaracetam, potassium bromide, tiagabine and gabapentin. Pharmacodynamic interactions were identified for clobazam, valproate and levetiracetam. There is further contention regarding whether pharmacokinetic interactions are present with topiramate, oxcarbazepine, lacosamide, phenobarbital and pregabalin. An animal study identified that the brain concentration of ASMs may alter while the serum concentration remains the same. Conclusions The studies to date suggest a number of possible interactions between CBD and ASMs. Possible mechanisms include alterations in metabolism through cytochrome p450. The existing literature is limited for some ASMs, with studies having relatively small cohorts. As increasing numbers of patients use cannabidiol, clinicians need to monitor closely for interactions clinically and with blood levels when needed.

Introduction Taking valproate during pregnancy can cause serious birth defects, 1 out of 10 children will have physical defects and 3 to 4 out of 10 will have early developmental problems potentially leading to significant learning disabilities. In April 2018 the Medicines and Healthcare products Regulatory Agency (MHRA) released guidelines stating, ‘Valproate must no longer be prescribed to Women or girls of childbearing potential unless they are on the Pregnancy Prevention Programme (PPP)’. Childbearing potential is defined as a premenopausal female capable of becoming pregnant. Hospital specialists are required to review females on valproate to establish childbearing potential and only continue if other treatments are ineffective and pregnancy is excluded by means of a serum pregnancy test. PPP should be started if valproate is to be continued ensuring there is understanding of the risks to an unborn child and an Annual Risk Acknowledgement form (ARAF) is completed. Aim Identify all female paediatric patients taking valproate under the care of a paediatrician in a district general hospital in November 2018 to assess compliance with PPP. Method 163 female paediatric patients identified via clinic lists of 5 consultants seeing Epilepsy and neurology patients. Results 12 (7.4%) were taking Valproate (mean age 10; range 4 to 16). 5 out of the 12 (41.7%) had a signed ARAF. 1 GP and 1 pharmacist had alerted hospital specialists of 2 of the 12 (16.7%) patients. There was no documentation regarding contraception. 2 patients without an ARAF (16.7%) were in the process of being weaned off valproate following the MHRA guidance. Conclusion Following departmental presentation in February 2019, 2 further female patients were weaned off valproate and consultants have been made aware of PPP and familiarised with the ARAF. Concerns were raised by specialists regarding the ethics of contraception in young females that may lack capacity to consent. On the 29th March 2019 A Guidance Document on Valproate Use in Women and Girls of Childbearing Years was released. It provides practical information, guidance and sources of further support to clinicians managing patients on Valproate. Valproate is now under strict regulation and use is expected to be in line with the modified ARAF and updated guidance.

Objective Cannabidiol is efficacious as an adjunctive treatment in children with epilepsy associated with Dravet and Lennox-Gastaut syndromes. As its role is currently adjunctive, we reviewed the interactions of cannabidiol with other antiseizure medications (ASMs). Methods A search of Cochrane, Pubmed and Embase databases from January 2015 to April 2020 was performed. All original research papers discussing interactions between cannabidiol and ASMs were included. Bibliographies of review articles were searched to identify further papers. Adverse events and side effects were excluded. Results Cannabidiol interacts with ASMs through both pharmacokinetic and pharmacodynamic mechanisms. Thirty studies were identified (eighteen observational cohort studies, two randomised-control trials, three case reports/series, three animal studies, two briefing reports, an analysis of cohort data and a clinical trial simulation). There is potential for pharmacokinetic interactions between CBD and brivaracetam, clobazam, eslicarbazepine, lacosamide, gabapentin, oxcarbazepine, phenobarbital, potassium bromide, pregabalin, rufinamide, sirolimus/everolimus, stiripentol, tiagabine, topiramate and zonisamide. Pharmacodynamic interactions were identified for clobazam, valproate and levetiracetam. An animal study identified that the brain concentration of ASMs may be altered while the serum concentration remains the same. Conclusion Pharmacokinetic and pharmacodynamic interactions exist between cannabidiol and ASMs. The cytochrome p450 system in particular has been implicated in pharmacokinetic interactions, although not exclusively. The existing literature is limited for some ASMs by studies having relatively small cohorts. As increasing numbers of patients use cannabidiol, specialists need to monitor closely for interactions clinically and with blood levels when required.

Variants in the FIG4 gene, which encodes a phosphatidylinositol-3,5-bisphosphatase lead to obstruction of endocytic trafficking, causing accumulation of enlarged vesicles in murine peripheral neurons and fibroblasts. Bi-allelic pathogenic variants in FIG4 are associated with neurological disorders including Charcot-Marie-Tooth disease type-4J (CMT4J) and Yunis-Varon syndrome (YVS). We present four probands from three unrelated families, all homozygous for a recurrent FIG4 missense variant c.506A>C p.(Tyr169Ser), with a novel phenotype involving features of both CMT4J and YVS. Three presented with infant-onset dystonia and one with hypotonia. All have depressed lower limb reflexes and distal muscle weakness, two have nerve conduction studies (NCS) consistent with severe sensorimotor demyelinating peripheral neuropathy and one had NCS showing patchy intermediate/mildly reduced motor conduction velocities. All have cognitive impairment and three have swallowing difficulties. MRI showed cerebellar atrophy and bilateral T2 hyperintense medullary swellings in all patients. These children represent a novel clinicoradiological phenotype and suggest that phenotypes associated with FIG4 missense variants do not neatly fall into previously described diagnoses but can present with variable features. Analysis of this gene should be considered in patients with central and peripheral neurological signs and medullary radiological changes, providing earlier diagnosis and informing reproductive choices.

Drug-resistant epilepsy (DRE) occurs in 20%–30% of children with epilepsy with significant impact on their quality of life. Management of this group of children has greatly improved in the recent years with streamlining of epilepsy surgery services and associated quaternary multimodal evaluation. This article provides a review of DRE in children and management based on recent evidence and published opinion. We have also presented an algorithmic approach to the child with possible DRE.

There has been a long-held belief that outcomes for babies born at moderate and late preterm gestations do not differ substantially from those of infants born at full term. This has recently been challenged by studies highlighting an increased risk of adverse neonatal outcomes, and of poorer cognitive, behavioural and educational outcomes in this population. Data about the effects of birth at moderate and late preterm gestations on later health outcomes are limited, but emerging evidence suggests that ongoing physical health may also be worse in those born just a few weeks before full term. This review summarises the available evidence, considers the factors influencing health outcomes and discusses the implications for the planning and provision of children's health care services.

Aim: This study explored inter-rater reliability, discriminative, construct and predictive validity of the Neurobehavioral Assessment of the Preterm Infant (NAPI) in a gestational-age-based cohort. Methods: The NAPI was conducted at 35 weeks post-menstrual age for 170 infants born

Nerve injuries after thoracic and cardiovascular surgery have been reported but generally concern the brachial plexus, phrenic nerve, recurrent laryngeal, and facial nerve. Common peroneal nerve injury (CPNI) following cardiopulmonary bypass has been reported in adults (4); however bilateral injury is extremely uncommon. Age, low body weight, co-morbidities such as peripheral arteriosclerotic disease, diabetes mellitus, and arrhythmias were associated with CPNI following cardiothoracic surgery in adults. Common peroneal nerve injury (CPNI) following cardiopulmonary by-pass has been reported in adults; however, bilateral injury is extremely uncommon. The superficial course of CPN makes it vulnerable to traction or compression. We report a 5-year-old girl manifesting with bilateral CPNI following prolonged cardiopulmonary by-pass. To the best of our knowledge, she is the first pediatric patient presenting with bilateral CPNI following cardiothoracic surgery and cardiopulmonary by-pass.

Children and adolescents treated with antiepileptic drugs are known to have problems with bone metabolism, bone mineral density loss, and 2–3 times the fracture risk of healthy controls. We reviewed the literature regarding bone mineral density in children with epilepsy and vitamin D therapy in children treated with anti-epileptic drugs. Studies of bone mineral density markers in children with epilepsy have mostly found little significant difference in bone mineral density markers in children with epilepsy. They have been limited by small sample size and many of the studies have not corrected for confounding factors such as comorbidities, mobility, nutrition, and obesity. Studies of vitamin D therapy in children with epilepsy have shown little evidence of effect and have been similarly limited by lack of stratification with regard to confounding factors. There is a need for larger studies, using clinically significant outcomes such as fractures, including at risk populations such as symptomatic generalised epilepsy, impaired mobility, and polytherapy. At the present time in the absence of good evidence to the contrary, there remains concern that children with epilepsy are at risk of poor bone health and that vitamin D therapy may be beneficial. As low-dose vitamin D supplementation (400 IU per day) is now recommended for healthy children and it is biologically feasible that children with epilepsy may be at higher risk of clinically significant deficiency, it is important that neurologists ensure that low-dose vitamin D supplementation should be prescribed and compliance followed up in children with epilepsy.

Cerebral cavernous malformations (CCMs) are vascular malformations causing seizures and cerebral hemorrhages. We report a 20-month old male with multiple CCMs associated with Krev interaction trapped 1 (KRIT1) c.845 + 1 G > C heterozygous transversion mutation. This case demonstrates the importance of molecular genetic analysis in cases of multiple CCM.