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OBJECTIVE Arterial ischemic stroke (AIS) is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood AIS have been completed. We aimed to investigate the outcome of childhood AIS 12 months after the event in a population-based cohort. METHODS Children aged 29 days to

BACKGROUND: Infantile spasms constitute a severe form of epileptic encephalopathy. In the International Collaborative Infantile Spasms Study (ICISS), we showed that combining vigabatrin with hormonal therapy was more effective than hormonal therapy alone at stopping spasms between days 14 and 42 of treatment. In this planned follow-up, we aimed to assess whether combination therapy was associated with improved developmental and epilepsy outcomes at 18 months of age.METHODS: In ICISS, a multicentre, open-label, randomised controlled trial, infants were enrolled from 102 hospitals (three in Australia, 11 in Germany, two in New Zealand, three in Switzerland, and 83 in the UK). Eligible infants had a clinical diagnosis of infantile spasms and a hypsarrhythmic (or similar) electroencephalogram (EEG) no more than 7 days before enrolment. Participants were randomly assigned (1:1) by a secure website to receive hormonal therapy with vigabatrin or hormonal therapy alone. If parents consented, there was an additional randomisation (1:1) of type of hormonal therapy used (prednisolone or tetracosactide depot). Block randomisation was stratified for hormonal treatment and risk of developmental impairment. Parents and clinicians were not masked to therapy, but investigators assessing epilepsy and developmental outcomes at 18 months were masked to treatment allocation. Minimum doses were oral prednisolone 10 mg four times a day or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days with or without oral vigabatrin 100 mg/kg per day. The primary outcome at 18 months was development as assessed by the Vineland Adaptive Behaviour Scales (VABS) composite score. Secondary outcomes were the presence or absence of epileptic seizures or infantile spasms in the previous 28 days, as recorded by parents and carers, and the use of any anti-epileptic treatment (including ketogenic diet) in the previous 28 days. Analysis was by intention to treat. The trial is registered with the ISRCTN registry, number 54363174, and EudraCT, number 2006-000788-27.FINDINGS: Between March 7, 2007, and May 22, 2014, 766 infants were screened and, of those, 377 were randomly assigned to hormonal therapy with vigabatrin (n=186) or hormonal therapy alone (n=191). 362 infants were assessed for developmental and epilepsy outcomes at 18 months, 181 in each treatment group. Mean VABS scores did not differ significantly between the combination therapy group and the hormonal therapy alone group (73·9 [SE 1·3] vs 72·7 [1·4], difference -1·2 [95% CI -4·9 to 2·6], p=0·55). Presence of epilepsy at the assessment at age 18 months was similar in both treatment groups (54 [30·0%] of 180 infants who received combination therapy vs 52 [29·2%] of 178 who received hormonal therapy alone; difference 0·8% [95% CI -8·8 to 10·4], p=0·90). Presence of spasms was also similar in both treatment groups (27 [15·0%] of 180 infants on combination therapy vs 28 [15·7%] of 178 on hormonal therapy alone; difference 0·7% [95% CI -6·9 to 8·3], p=0·85). At the 18-month assessment, 158 (44·1%) of 358 infants were on some form of anti-epileptic treatment. Initial control of spasms between days 14 and 42 of treatment was associated with higher mean VABS scores at 18 months (79·1 [SE 1·2] vs 63·2 [1·1], difference 15·9 [95% CI 12·4 to 19·5], pINTERPRETATION: Combination therapy did not result in improved developmental or epilepsy outcomes at 18 months. However, early clinical response to treatment was associated with improved developmental and epilepsy outcomes at 18 months. Longer lead-time to treatment was associated with poorer outcomes. Rapid diagnosis and effective treatment of infantile spasms could therefore improve outcomes.FUNDING: The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

Stroke is a major cause of mortality in children. Conditions that mimic stroke also cause severe morbidity and require prompt diagnosis and treatment. We have investigated the time to diagnosis in a cohort of children with stroke.A population-based cohort of children with stroke was prospectively identified in the south of England. Case notes, electronic hospital admission databases and radiology records were reviewed. Timing of symptom onset, presentation to hospital, first neuroimaging, first diagnostic neuroimaging and presenting clinical features were recorded.Ninety-six children with an arterial ischaemic stroke (AIS) and 43 with a haemorrhagic stroke (HS) were identified. The median time from symptom onset to diagnostic neuroimaging was 24.3 h in AIS and 2.9 h in HS. The initial imaging modality was CT in 68% of cases of AIS. CT was diagnostic of AIS in 66% of cases. MRI was diagnostic in 100%. If initial neuroimaging was non-diagnostic in AIS, then median time to diagnosis was 44 h. CT was diagnostic in 95% of HS cases. Presentation outside normal working hours resulted in delayed neuroimaging in AIS (13 vs 3 h, p=0.032). Diffuse neurological signs or a Glasgow Coma Scale9 resulted in more expeditious neuroimaging in both HS and AIS.The diagnosis of AIS in children is delayed at every stage of the pathway but most profoundly when the first neuroimaging is CT scanning, which is non-diagnostic. MRI should be the initial imaging modality of choice in any suspected case of childhood AIS.

Isolated paediatric neurosarcoidosis (IPN) is exceptionally rare and only seven cases have been reported so far in the literature. We report the clinical and radiological profile of a 7 year-old boy with epilepsia partialis continua (EPC) who was initially thought to have Acute Disseminated Encephalomyelitis (ADEM), but was subsequently found to have isolated neurosarcoidosis. Additionally, we performed a literature search on Medline and Embase and secondary sources of data such as reference list of articles reviewed. Whilst cranial neuropathy is the commonest presenting feature in adults with neurosarcoidosis, paediatric patients are more likely to present with seizures. Diagnosis presents a clinical challenge as a result of its protean manifestations. Due to its rarity, there remains a lack of evidence base to inform the best choice of treatment for these children. Our patient was successfully treated with a combination of various immunomodulants.

Objective:To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease.Methods:We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques.Results:Patients first presented in early childhood (median age of presentation 10 months, range 0–48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16.Conclusions:Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia.

Alice is referred by her general practitioner (GP) for a paediatric neurology opinion with a history of episodes of her legs giving way. The referral letter from her GP mentions that when Alice is picked up when she has one of these episodes, she cannot control her legs, which move abnormally. Alice is seen by the registrar. Her parents' say that these episodes are occurring at a frequency of one every month, and they describe non-rhythmic jerky movements involving her legs lasting approximately 20 min. She falls and cannot walk or stand when these happen. Recovery occurs without intervention. She has experienced a total of five episodes, and they all occurred in the evening following exertion. Her consciousness is not impaired during these events, and between the episodes Alice is well. The prenatal and perinatal history are normal, and her development is in keeping with her chronological age. An interesting aspect of Alice's family history is the fact that her father had experienced similar episodes when he was 8 years old, and they had lasted until he was 13. He described episodic paroxysmal movements involving both his upper and lower limbs, and he recalled needing to sit down when these episodes occurred. He had been given the diagnosis of Sydenham's chorea by his GP. Alice's head circumference and neurological examination are normal. The paediatric registrar discusses Alice with the neurology consultant, and given the history of Alice's father having similar episodes in childhood, they consider the possibility of a familial movement disorder such as a ‘Benign hereditary chorea.’ Since Alice is clinically well, the decision is made not to investigate further at that point but to keep her under review. The neurologist suggests a video recording of the event should it happen again. ### Comment Chorea is characterised by frequent, random, unpredictable …

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a treatable condition resulting from impaired glucose transport into the brain. The classical presentation is with infantile-onset epilepsy and severe developmental delay. Non-classical phenotypes with movement disorders and early-onset absence epilepsy are increasingly recognized and the clinical spectrum is expanding. The hallmark is hypoglycorrhachia (cerebrospinal fluid [CSF] glucose

Epilepsy is not a single condition but a group of disorders with differing diagnostic criteria, management pathways and outcomes. In recent years our understanding and knowledge of the childhood epilepsies has improved. An evidence-based approach may help us provide the best treatment for our patients although randomised trials remain limited. The National Institute for Clinical Excellence guidelines, introduced in 2004, have provided a benchmark for the diagnosis and management of the epilepsies and are due for review in 2009. In this paper, we review the current definitions and guidelines and suggest a practical approach to treatment decisions in children with epilepsy.

Arterial ischemic stroke (AIS) is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood AIS have been completed. We aimed to investigate the outcome of childhood AIS 12 months after the event in a population-based cohort.Children aged 29 days to 16 years with radiologically confirmed AIS occurring over a 1-year period residing in southern England (population = 5.99 million children) were eligible for inclusion. Outcome was assessed during a home visit using the Pediatric Stroke Outcome Measure (PSOM). Parental impressions of recovery were assessed using the Pediatric Stroke Recurrence and Recovery Questionnaire. PSOM score was estimated via telephone interview or clinician interview whenever home visit was not possible.Ninety-six children with AIS were identified. Two children were lost to follow-up. Nine of 94 (10%) children died before the 12-month follow-up. One child had an AIS recurrence. PSOM scores were available for 78 of 85 living children at follow-up. Thirty-nine of 78 (50%) had a good outcome (total PSOM score 1), and 39 of 78 (50%) had a poor outcome. Seizures at onset of AIS were associated with a poor outcome (odds ratio = 3.5, 95% confidence interval = 1.16-10.6). Twenty-eight of 73 (38%) children were judged by their carers to have fully recovered. Ten of 84 (12%) children had recurrent seizures, and 17 of 84 (20%) reported recurrent headaches.AIS carries a significant risk of mortality and long-term neurological deficit. However, the rates of mortality, recurrence, and neurological impairment were markedly lower in this study than previously published figures in the United Kingdom. Ann Neurol 2016;79:784-793.

Patients and methods. In this retrospective study, 36 children referred to paediatric neurology and neurosurgery during April 1995-June 1998 with a diagnosis of subdural haematoma (SDH) were studied. Nine were accidental secondary to witnessed trauma and 4 were iatrogenic. Non-accidental head injury (NAHI) was suspected in the remaining 23 children. Results. After a full clinical, radiological and social assessment, NAHI was diagnosed in 14, lateral sinus thrombosis in 1, 2 were accepted as accidental and 6 remained unexplained. In the NAHI group (n=14), 12 were between 4 and 16 weeks of age, 12 (85%) had retinal haemorrhages and skeletal surveys showed evidence of additional injury in 8. Computerised tomography (CT) brain scans showed bilateral SDH in 11, and 6 had inter-hemispheric bleeding along with loss of grey-white differentiation. Eleven had magnetic resonance imaging (MRI), which yielded additional information in 7. Seven required intensive care, and 2 died. Twelve had surgical aspiration. In the group with no satisfactory explanation for SDH (n=6); 5 had neonatal problems, all except 1 were older than 5 months of age and not as ill with bilateral, old SDH. All but 1 had skeletal surveys, which were normal, and eye examination showed no retinal haemorrhages. A social services enquiry was non-contributory. Conclusions. SDH is frequently traumatic whether accidental or non-accidental. SDH due to NAHI tends to present before 4 months of age with an inconsistent history; the patients are more seriously ill and have other findings, such as fractures and retinal haemorrhages. A small subgroup of patients was identified who had isolated, old SDH and in whom full investigation remained inconclusive. A consistent, comprehensive approach needs to be maintained in all cases with the essential backup of detailed neuro-imaging including MRI.

Brown-Vialetto-Van Laere syndrome (BVVLS) is a genetic condition caused by a mutation in the C20orf54 gene, which also codes for an intestinal riboflavin transporter. We report the case of a female who presented at 22 months with acute-onset stridor and generalized muscle weakness, in whom a genetic diagnosis of BVVLS was made, and whose symptoms improved on therapy with high-dose riboflavin. She had previously been developing normally and was able to walk at 11 months, then developed progressive muscle weakness at 22 months, and within 2 weeks was unable to sit without support. She also demonstrated stridor and paradoxical breathing indicating diaphragmatic weakness, and required continuous non-invasive ventilation (NIV) through a tracheostomy. After treatment with riboflavin she was able to walk unaided, and her Gross Motor Functional Classification level improved from level IV to level I, having fully regained the motor function she showed before symptom onset. There were no longer signs of diaphragmatic paralysis while on NIV, and she was able to tolerate 10-minute periods off NIV before paradoxical breathing again became apparent. We therefore recommend that in all cases suspected to be in the BVVLS or Fazio-Londe spectrum, early treatment with high-dose riboflavin must be considered.

The paper by Chu et al 1 presents retrospective case note review data on a large number of patients with brain tumours. The authors used a large-scale number crunching exercise to show brain tumour diagnosis can be delayed and that these children often present with non-specific symptoms making diagnosis more difficult. The data for this study is relatively old as cohorts examined were between 1989 and 1997 to 2006. The patients had symptoms up to 2 years before diagnosis and presented to primary and secondary care with increasing frequency until the diagnosis was reached. What is to be done? The tabloid press regularly complains that UK doctors are slow to see patients and slow to do diagnostic tests. In the UK the general practitioner (GP) has traditionally been a gatekeeper, trying to prevent the unnecessary overinvestigation of patients. Most GPs and paediatricians recognise that resources are limited but are themselves usually very concerned when a diagnosis is missed. Subtle symptoms in preschool children are particularly difficult. Headache is a very common symptom at all ages, with up to 20% of children complaining of this symptom at some time.2 Trying to decide who should be referred for a scan can be a challenge. History and examination remains the cornerstone of diagnosis in medicine including paediatrics, but with non-specific symptoms and limited signs, or examination proving difficult, a …

Background: Epidemiological data are vital to quantify the scale of disease and can provide insights into aetiological factors. Objective: To describe the epidemiology of childhood stroke in southern England. Methods: Children (>28 days to Results: 153 cases of stroke were identified (96 cases of AIS, 14 cases of CSVT and 43 cases of HS). The incidence for overall stroke was 2.56 per 100,000 person years (95% CI 2.15 - 2.96). The age distribution is shown in Figure 1. There was no difference between males and females in the risk of ischemic (AIS and CSVT) stroke (RR=1.06, p=0.75), HS (RR=1.46, p=0.22) or overall stroke (RR=1.16, p=0.36). Compared to Whites the relative risk of ischaemic stroke was higher for Asians (RR=2.35, p=0.001) and Blacks (RR=2.52, p=0.003). There was no increased risk of HS for Asians (RR=0.84, p=0.77) or Blacks (RR=1.39, p=0.58). Conclusions: The incidence of childhood stroke found by this study is higher than previously found in the UK. This is the first study to show disparities in the risk of childhood stroke between ethnic groups in Europe. Although an increased risk for males is commonly reported a number of recent population based studies have found no gender disparity.

Worldwide, epilepsy is one of the most common neurological disorders. Prevalence data on the burden of epilepsy suggests considerable variation across the globe,1 with the highest prevalence in developing countries. While this heterogeneity is multifactorial, there is no denying that diagnostic difficulties in epilepsy have long been recognised globally. The paper from Wilhelmine et al 2 would suggest that the cumulative and annual incidence of epilepsy in children is declining. The change observed over just a decade is striking. The authors suggest a number of explanations, including greater accuracy in diagnosis and changes in population risk factors. This paper should give cause for reflection on the advances that have been made in the diagnosis and management of epilepsy in recent years. Epilepsy in children and adults has attracted a lot of attention in the past two decades. Sudden unexpected death in epilepsy (SUDEP) became an …

Brown-Vialetto-Van Laere syndrome (BVVLS) is a genetic condition caused by a mutation in the C20orf54 gene, which also codes for an intestinal riboflavin transporter. We report the case of a female who presented at 22 months with acute-onset stridor and generalized muscle weakness, in whom a genetic diagnosis of BVVLS was made, and whose symptoms improved on therapy with high-dose riboflavin. She had previously been developing normally and was able to walk at 11 months, then developed progressive muscle weakness at 22 months, and within 2 weeks was unable to sit without support. She also demonstrated stridor and paradoxical breathing indicating diaphragmatic weakness, and required continuous non-invasive ventilation (NIV) through a tracheostomy. After treatment with riboflavin she was able to walk unaided, and her Gross Motor Functional Classification level improved from level IV to level I, having fully regained the motor function she showed before symptom onset. There were no longer signs of diaphragmatic paralysis while on NIV, and she was able to tolerate 10-minute periods off NIV before paradoxical breathing again became apparent. We therefore recommend that in all cases suspected to be in the BVVLS or Fazio-Londe spectrum, early treatment with high-dose riboflavin must be considered.

To study the aetiology and outcome of previously well children admitted to a paediatric intensive care unit (PICU) over a 5.5-year period (January 2004–June 2009) with coma (Glasgow Coma Score

Various disorders result from genetically determined abnormalities of enzymes, the metabolic consequences of which affect the development or functioning of the nervous system. The range of metabolic disturbances is wide, as is the resultant range of clinical syndromes. Although most occur in children, some can present in adult life, and increasing numbers of affected children survive into adult life. In some, specific treatments are possible or are being developed. The last 20 years has seen a considerable expansion in our understanding of the genetic and metabolic basis for many neurological conditions. Particular clinical presentations of neurometabolic disorders include ataxias, movement disorders, childhood epilepsies, or peripheral neuropathy. Detailed coverage of the entire range of inherited metabolic diseases of the nervous system is available in other texts (Brett 1997; Scriver et al. 2001; Menkes et al. 2005).Treatment is possible for some metabolic diseases. For instance, the devastating neurological effects of phenylketonuria have been recognized for many years. Neonatal screening for this disorder and dietary modification in the developed world has removed phenylketonuria from the list of important causes of serious neurological disability in children. This success has led to new challenges in the management of the adult with phenylketonuria and unexpected and devastating effect of the disorder on the unborn child of an untreated Phenylketonuria mother. More recently Biotinidase deficiency has been recognized as an important and easily treatable cause of serious neurological disease usually presenting with early onset drug resistant seizures. This and some other neurometabolic diseases can be identified on neonatal blood screening although a full range of screening is not yet routine in the United Kingdom. More disorders are likely to be picked up at an earlier asymptomatic stage as the sophistication of screening tests increases (Wilcken et al. 2003; Bodamer et al. 2007).Although individual metabolic disorders are rare, collectively such disorders are relatively common. In reality most clinicians will see an individual condition only rarely in a career. Furthermore, patients with certain rare conditions are often concentrated in specialist referral centres, further reducing the exposure of general and paediatric neurologists to these disorders. A recent study into progressive intellectual and neurological deterioration, PIND, gives some information about the relative frequency and distribution of some childhood neurodegenerative diseases in the United Kingdom (Verity et al. 2000; Devereux et al. 2004). Although primarily designed to identify any childhood cases of variant Creutzfeldt- Jakob disease, the study also provided much information about the distribution of neurometabolic disease in children in the United Kingdom. The commonest five causes of progressive intellectual and neurological deterioration over 5 years were Sanfilippo syndrome, 41 cases, adrenoleukodystrophy, 32 cases, late infantile neuronal ceroid lipofuschinosis, 32 cases, mitochondrial cytopathy, 30 cases, and Rett syndrome, 29 cases. Notably, geographical foci of these disorders were also found and correlate with high rate of consanguinity in some local populations.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a treatable condition resulting from impaired glucose transport into the brain. The classical presentation is with infantile-onset epilepsy and severe developmental delay. Non-classical phenotypes with movement disorders and early-onset absence epilepsy are increasingly recognized and the clinical spectrum is expanding. The hallmark is hypoglycorrhachia (cerebrospinal fluid [CSF] glucose2.2 mmol/l) in the presence of normoglycaemia with a CSF/blood glucose ratio of less than 0.4. GLUT1DS is due to a mutation in the solute carrier family 2, member 1 gene (SLC2A1). We present five individuals (four males, one female), all of whom had a mild phenotype, highlighting the importance of considering this diagnosis in unexplained neurological disorders associated with mild learning difficulties, subtle motor delay, early-onset absence epilepsy, fluctuating gait disorders, and/or dystonia. The mean age at diagnosis was 8 years 8 months. This paper also shows phenotypical parallels between GLUT1DS and paroxysmal exertion-induced dyskinesia.

Approximately 10% of children with epilepsy have absence epilepsy syndromes.1 The diagnosis is confirmed by recording events during a standard EEG recording synchronised with video.2 However, non-epileptic absence-like behaviour is common in children, and although there may be clinical pointers to non-epileptic behaviours, an EEG is often requested.3 To describe the EEG (synchronised with video) results in children …

Synchronous video and EEG recording is carried out when there is a desire to correlate the clinical behaviour of a child with their EEG activity;1 this is known as video-telemetry (VT). After a death during paediatric VT in 2010, the British Paediatric Epilepsy Group (BPEG), a subgroup of the British Paediatric Neurology Association (BPNA) surveyed members about their current practice for VT monitoring. A Medline search revealed few previous publications on this topic.1,–,3 Following a preliminary paper survey, we used the online system ‘Survey Monkey’4 to ask all BPNA BPEG members to complete a simple questionnaire. Nine of 16 units replied, giving a response rate of 56%. The indications described for VT were

To look at the outcome of the routine video EEG (vEEG) wake and sleep records on children referred following a single unprovoked afebrile seizure. We examined all the vEEGs that were undertaken in a regional paediatric neurophysiology department in Oxford, following a single unprovoked seizure over a 1-year period (2008–2009), several years after National Institute for Health and Clinical Excellence (NICE)1 guidelines for the management of …