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Tuberous sclerosis complex (TSC) is one of the most commonly occurring and recognised neurocutaneous syndromes, with a prevalence of approximately 1 in 30 000 and a birth incidence of 1 in 10 000. It is a multi-system disorder affecting predominantly the CNS and skin. The underlying genetic defect and pathophysiology in TSC is unclear, but is thought to involve an impairment of normal cell migration resulting in dysplastic and dysfunctional organ systems.

Epilepsy in children is frequently misdiagnosed and inappropriately managed with major medical, social, and educational consequences. The advent of the newer anti-epileptic drugs has paradoxically, and in contrast to what was expected, contributed to a therapeutic confusion, which in certain instances, has perpetuated this unsatisfactory management. The purpose of this paper is to address some of the diagnostic and management issues and outline drug regimens for specific seizure types and epilepsy syndromes. Alternative and surgical therapies, and the treatment of neonatal and ‘febrile seizures’ and status epilepticus will not be discussed in detail, as these particular aspects fall outside the remit of this paper.

Aim Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives. Method Participants were identified prospectively from referrals to the Epilepsy Genetics Service in Glasgow and contacted via their referring clinicians. Questionnaires exploring the consequences of SCN1A genetic testing for each case were sent to carers and physicians. Results Of the 244 individuals contacted, 182 (75%) carried a SCN1A mutation. Carers of 187 (77%) patients responded (90 females, 97 males; mean age at referral 4y 10mo; interquartile range 9y 1mo). Of those participants whose children tested positive for a mutation, 87% reported that genetic testing was helpful, leading to treatment changes resulting in fewer seizures and improved access to therapies and respite care. Out of 187 physicians, 163 responded (87%), of whom 48% reported that a positive test facilitated diagnosis earlier than with clinical and electroencephalography data alone. It prevented additional investigations in 67% of patients, altered treatment approach in 69%, influenced medication choice in 74%, and, through medication change, improved seizure control in 42%. Interpretation In addition to confirming a clinical diagnosis, a positive SCN1A test result influenced treatment choice and assisted in accessing additional therapies, especially in the very young.

Objective To assess the effectiveness and safety of melatonin in treating severe sleep problems in children with neurodevelopmental disorders. Design 12 week double masked randomised placebo controlled phase III trial. Setting 19 hospitals across England and Wales. Participants 146 children aged 3 years to 15 years 8 months were randomised. They had a range of neurological and developmental disorders and a severe sleep problem that had not responded to a standardised sleep behaviour advice booklet provided to parents four to six weeks before randomisation. A sleep problem was defined as the child not falling asleep within one hour of lights out or having less than six hours’ continuous sleep. Interventions Immediate release melatonin or matching placebo capsules administered 45 minutes before the child’s bedtime for a period of 12 weeks. All children started with a 0.5 mg capsule, which was increased through 2 mg, 6 mg, and 12 mg depending on their response to treatment. Main outcome measures Total sleep time at night after 12 weeks adjusted for baseline recorded in sleep diaries completed by the parent. Secondary outcomes included sleep onset latency, assessments of child behaviour, family functioning, and adverse events. Sleep was measured with diaries and actigraphy. Results Melatonin increased total sleep time by 22.4 minutes (95% confidence interval 0.5 to 44.3 minutes) measured by sleep diaries (n=110) and 13.3 (−15.5 to 42.2) measured by actigraphy (n=59). Melatonin reduced sleep onset latency measured by sleep diaries (−37.5 minutes, −55.3 to −19.7 minutes) and actigraphy (−45.3 minutes, −68.8 to −21.9 minutes) and was most effective for children with the longest sleep latency (P=0.009). Melatonin was associated with earlier waking times than placebo (29.9 minutes, 13.6 to 46.3 minutes). Child behaviour and family functioning outcomes showed some improvement and favoured use of melatonin. Adverse events were mild and similar between the two groups. Conclusions Children gained little additional sleep on melatonin; though they fell asleep significantly faster, waking times became earlier. Child behaviour and family functioning outcomes did not significantly improve. Melatonin was tolerable over this three month period. Comparisons with slow release melatonin preparations or melatonin analogues are required. Trial registration ISRCT No 05534585.

Difficulties in initiating and maintaining sleep are common in children with neurodevelopmental disorders. Melatonin is unlicensed in children yet widely prescribed for sleep problems. To determine whether or not immediate-release melatonin is beneficial compared with placebo in improving total duration of night-time sleep in children with neurodevelopmental problems. Randomised, double-blind, placebo-controlled, parallel study. Hospitals throughout England and Wales recruited patients referred by community paediatricians and other clinical colleagues. Children with neurodevelopmental problems aged from 3 years to 15 years 8 months who did not fall asleep within 1 hour of lights out or who had < 6 hours of continuous sleep. Before randomisation, patients meeting eligibility criteria entered a 4- to 6-week behaviour therapy period in which a behaviour therapy advice booklet was provided. Sleep was measured using sleep diaries and actigraphy. After this period the sleep diaries were reviewed to determine if the sleep problem fulfilled the eligibility criteria. Eligible participants were randomised and followed for 12 weeks. Melatonin or placebo capsules in doses of 0.5 mg, 2 mg, 6 mg and 12 mg for a period of 12 weeks. The starting dose was 0.5 mg and the dose could be escalated through 2 mg and 6 mg to 12 mg during the first 4 weeks, at the end of which the child was maintained on that dose. The primary outcome was total night-time sleep time (TST) calculated using sleep diaries at 12 weeks compared with baseline. Secondary outcome measures included TST calculated using actigraphy data, sleep-onset latency (SOL) (time taken to fall asleep), sleep efficiency, Composite Sleep Disturbance Index score, global measure of child's sleep quality, Aberrant Behaviour Checklist, Family Impact Module of the Pediatric Quality of Life Inventory (PedsQL™), the Epworth Sleepiness Scale, number and severity of seizures and adverse events. Salivary melatonin concentrations and association of genetic variants with abnormal melatonin production were also investigated. A total of 275 children were screened to enter the trial; 263 (96%) children were registered and completed the 4- to 6-week behaviour therapy period and 146 (56%) children were randomised, of whom 110 (75%) contributed data for the primary outcome. The difference in TST time between the melatonin and placebo groups adjusted for baseline was 22.43 minutes [95% confidence interval (CI) 0.52 to 44.34 minutes; p = 0.04] measured using sleep diaries. A reduction in SOL, adjusted for baseline, was seen for melatonin compared with placebo when measured by sleep diaries (-37.49 minutes, 95% CI -55.27 to -19.71 minutes; p < 0.0001) and actigraphy (-45.34 minutes, 95% CI -68.75 to -21.93 minutes; p = 0.0003). There were no significant differences between the two groups in terms of the reporting of adverse events. The results of other secondary outcomes favoured melatonin but were not statistically significant. On average, the children treated with melatonin slept 23 minutes longer than those in the placebo group; however, the upper limit of the confidence interval was less than 1 hour, the minimum clinically worthwhile difference specified at the outset of the trial. Melatonin is effective in reducing SOL in children with neurodevelopmental delay by a mean of 45 minutes; a value of 30 minutes was specified a priori to be clinically important. Future studies should be conducted over longer periods and directly compare different formulations of melatonin with conventional hypnotic and sedative medications. It would also be important to study groups of children with specific neurological disorders. Current Controlled Trials ISRCTN05534585. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 40. See the HTA programme website for further project information.

Sixty percent of the epilepsies start in childhood, and most of the clinically significant and often life-changing aspects of the disease occur at this time. Childhood epilepsy is frequently a complex disorder, demanding integrated medical, educational and community services. Its treatment encompasses acute and disability medicine. The many types or syndromes of childhood epilepsy present both diagnostic and management challenges. Although many children with epilepsy will be referred to specialist units, the majority will initially present to paediatricians and paediatric neurologists. This book provides a practical, problem-oriented manual to help clinicians with diagnosis, evaluation and management. This book addresses epilepsy as an evolving disorder from presentation, through active disease and finally to either spontaneous remission or a chronic lifelong condition. Structured on the child's age at presentation, Childhood Epilepsy offers a practical overview for paediatricians, paediatric neurologists and primary care practitioners who treat children with epilepsy in their daily practice.

Phenytoin is used to treat acute tonic-clonic seizures in children who have not responded to a benzodiazepine. In the UK, the loading dose of phenytoin is 18 mg/kg. There is limited evidence on whether this loading dose will achieve the desired levels in paediatric patients. Intravenous loading doses of phenytoin were retrospectively and prospectively audited over 19 months. Doses were normalised for weight and compared with the serum phenytoin concentrations. Errors in dose calculations and adverse events were recorded. Serum phenytoin concentrations were measured on 31 occasions in 27 children (24 retrospective and 10 prospective) between 60 and 180 (median, 153) min after completion of the loading dose. Serum phenytoin concentrations were within the therapeutic range (10-20 μg/ml) on 24 occasions. No errors in dose calculations or adverse effects were identified. A phenytoin loading dose of 18 mg/kg gave serum concentrations within the recommended therapeutic range in most children.

Five unrelated patients are described with the clinical and electrical features of eyelid myoclonia with absences (EMA). In this syndrome brief, typical absences occur with rapid eyelid myoclonia associated with retropulsive movements of the eyeballs and occasionally of the head. The seizures are of shorter duration than in childhood absence epilepsy, and are accompanied by less profound impairment of consciousness. The electroencephalogram demonstrates high amplitude discharges consisting of spikes, multiple spikes and slow waves at a fluctuating frequency of 3-5 Hz and following eye closure, which disappear in darkness. Photosensitivity is also seen. Onset is in early childhood and EMA appears to persist into adult life. Treatment is sodium valproate in combination with either ethosuximide or a benzodiazepine. On the basis of the clinical features, EEG findings, and the response to treatment and prognosis, it is suggested that EMA be classified as a specific epilepsy syndrome.

Aims Pneumococcal vaccination (PnV) was introduced into the UK immunisation schedule in 2006. This paper reviews presentation, diagnosis, management and outcomes of children with pneumococcal meningitis from a tertiary children’s hospital before and following the introduction of the PnV. The study evaluated differences in outcome between patients in the hospital’s catchment area (internal) and those transferred from another hospital (external). Method Retrospective case note audit of patients admitted with a diagnosis of pneumococcal meningitis. The audit covered six years before and following the introduction of PnV. Results Sixty two case notes were audited, 37 in the pre-PnV and 25 in the post PnV group. Forty-four patients (71%) were internal and 18 were transferred in from another hospital (external). Mean age was 2.2 years (median 11 months, range The mean time from presentation to diagnosis was twice as long in the post-vaccination (0.72 days), compared to the pre-vaccination group (0.33 days). 5 patients died, 4 (80%) in the pre-vaccination group. The average number of neurological sequelae in survivors was just over 1 in the pre-vaccination and under 0.5 in the post-vaccination group (i.e. for every two patients in this group one would be expected to have neurological sequelae). All of the patients who died were internal. There was an average of one neurological sequelae per patient in the external group. Conclusion There were fewer patients in the post-PnV group, mortality was less and on average fewer patients had neurological sequelae in this group. This may reflect a reduced population of pathogenic serotypes following vaccination. Time to diagnosis was longer on average in the post-PnV group, which could suggest that as pneumococcal meningitis has become less common it takes longer to make the diagnosis, the small number of patients (62) precludes definitive conclusion. Management and duration of admission were similar. Internally-derived patients were less likely to die but slightly more likely to have neurological sequelae. These findings require confirmation with a nationally-conducted audit.

Episodic dyscontrol syndrome (EDS) or intermittent explosive disorder (IED) is a clearly identified category in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). It affects children and adults. Children are often considered to have epilepsy or a mental health problem. The episodes comprise of recurrent attacks of uncontrollable rage, usually after minimal provocation, and may last up to an hour. Following an episode, children are frequently exhausted, may sleep and will usually have no recall. These features often raise the possibility of epilepsy, and children may be referred for an electroencephalogram (EEG). An abnormal EEG may subsequently lead to a diagnosis of epilepsy and the prescription of an anticonvulsant. Five patients with EDS are described, all referred to a single neurology clinic with a possible diagnosis of epilepsy, one of whom was being treated with an anticonvulsant. Four had an EEG, which was normal in two patients and showed "abnormalities" in two, leading to an incorrect diagnosis of temporal lobe epilepsy in one patient. All five children responded to psychological (behavioural) intervention. Recognition of the clinical features of IED/EDS should preclude the need for EEG and other investigations in these patients and prompt referral to psychological services.

Epilepsy is frequently diagnosed incorrectly through a failure to obtain an adequate history and placing inappropriate emphasis on the electroencephalogram (EEG). We describe four children with common, nonepileptic events who were diagnosed initially as having epilepsy.

The aim of this review is to describe the properties and uses of the more recently available anticonvulsant agents. The goal of epilepsy treatment is to achieve total seizure freedom with no side effects. Despite the appropriate use of anticonvulsants approximately 25% of children will continue to experience seizures. The development of new anticonvulsants is therefore imperative. Since the late 1980s there have been a number of new anticonvulsant agents with various modes of action and differing applications in clinical practice. Although this potentially increases the therapeutic options available to clinicians, the increased choice of drugs may also lead to irrational polypharmacy and some agents are recognised to increase seizures in certain epilepsy syndromes. Epilepsy is a common problem in childhood with an annual incidence of 60/100 000 children.1 The goal of epilepsy treatment is to achieve complete seizure freedom without any adverse side effects. When considering all the childhood epilepsies, approximately 25–30% of children will continue to experience seizures that are resistant to all currently available antiepileptic drugs. The term “antiepileptic” is somewhat of a misnomer because all that the current antiepileptic therapies are able to achieve—with the exception of epilepsy surgery—is to prevent seizures in someone who has epilepsy. Most but not all of these drugs are effective against tonic-clonic convulsions, which is why antiepileptic drugs may also be called “anticonvulsants”. The antiepileptic drugs that are currently available have no effect on the underlying cause of the seizures. Given the current limitations of therapy, it remains important to try and identify new drugs which are not only effective in preventing seizures and are safe, but which may also be able to act directly on the underlying cause of the epilepsy, or at least modify the pathogenesis of the seizures. Modern epilepsy treatment began in 1857 with the introduction …

OBJECTIVES To compare clinicians' choice of one of the standard epilepsy drug treatments (carbamazepine or valproate) versus appropriate comparator new drugs. DESIGN A clinical trial comprising two arms, one comparing new drugs in carbamazepine and the other with valproate. SETTING A multicentre study recruiting patients with epilepsy from hospital outpatient clinics. PARTICIPANTS Patients with an adequately documented history of two or more clinically definite unprovoked epileptic seizures within the last year for whom treatment with a single antiepileptic drug represented the best therapeutic option. INTERVENTIONS Arm A was carbamazepine (CBZ) versus gabapentin (GBP) versus lamotrigine (LTG) versus oxcarbazepine (OXC) versus topiramate (TPM). Arm B valproate (VPS) versus LTG versus TPM. MAIN OUTCOME MEASURES Time to treatment failure (withdrawal of the randomised drug for reasons of unacceptable adverse events or inadequate seizure control or a combination of the two) and time to achieve a 12-month remission of seizures. Time from randomisation to first seizure, 24-month remission of seizures, incidence of clinically important adverse events, quality of life (QoL) outcomes and health economic outcomes were also considered. RESULTS Arm A recruited 1721 patients (88% with symptomatic or cryptogenic partial epilepsy and 10% with unclassified epilepsy). Arm B recruited 716 patients (63% with idiopathic generalised epilepsy and 25% with unclassified epilepsy). In Arm A LTG had the lowest incidence of treatment failure and was statistically superior to all drugs for this outcome with the exception of OXC. Some 12% and 8% fewer patients experienced treatment failure on LTG than CBZ, the standard drug, at 1 and 2 years after randomisation, respectively. The superiority of LTG over CBZ was due to its better tolerability but there is satisfactory evidence indicating that LTG is not clinically inferior to CBZ for measures of its efficacy. No consistent differences in QoL outcomes were found between treatment groups. Health economic analysis supported LTG being preferred to CBZ for both cost per seizure avoided and cost per quality-adjusted life-year gained. In Arm B for time to treatment failure, VPS, the standard drug, was preferred to both TPM and LTG, as it was the drug least likely to be associated with treatment failure for inadequate seizure control and was the preferred drug for time to achieving a 12-month remission. QoL assessments did not show any between-treatment differences. The health economic assessment supported the conclusion that VPS should remain the drug of first choice for idiopathic generalised or unclassified epilepsy, although there is a suggestion that TPM is a cost-effective alternative to VPS. CONCLUSIONS The evidence suggests that LTG may be a clinical and cost-effective alternative to the existing standard drug treatment, CBZ, for patients diagnosed as having partial seizures. For patients with idiopathic generalised epilepsy or difficult to classify epilepsy, VPS remains the clinically most effective drug, although TPM may be a cost-effective alternative for some patients. Three new antiepileptic drugs have recently been licensed in the UK for the treatment of epilepsy (levetiracetam, zonisamide and pregabalin), therefore these drugs should be compared in a similarly designed trial.

Summary Background Carbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes. Methods SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. Findings For time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0·78 [95% CI 0·63–0·97]), gabapentin (0·65 [0·52–0·80]), and topiramate (0·64 [0·52–0·79]), and had a non-significant advantage compared with oxcarbazepine (1·15 [0·86–1·54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0·75 [0·63–0·90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0·91 [0·77–1·09]), topiramate (0·86 [0·72–1·03]), and oxcarbazepine (0·92 [0·73–1·18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (−8 to 7) and 5 (−3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine. Interpretation Lamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.

Summary Background Valproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify. Methods SANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748. Findings For time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1·57 [95% CI 1·19–2·08]), but there was no significant difference between valproate and lamotrigine (1·25 [0·94–1·68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1·55 [1·07–2·24] and topiramate (1·89 [1·32–2·70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0·76 [0·62–0·94]), and for the subgroup with an idiopathic generalised epilepsy 0·68 (0·53–0·89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy. Interpretation Valproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

Few suitable instruments exist for use with people, especially children, with both epilepsy and learning disabilities. One such measure is the Epilepsy and Learning Disabilities Quality of Life scale (ELDQOL), which has recently undergone revision following feedback from relevant users. This article reports on the final psychometric testing phase of this scale. ELDQOL consists of 70 items covering seizure severity, seizure-related injuries, antiepileptic drug side effects, behavior, mood, physical, cognitive, and social functioning, parental concern, communication, overall quality of life, and overall health. Revalidation involved a qualitative phase, to ascertain users’ opinions on the wording, coverage, and layout of the questionnaire, and a quantitative phase, to examine internal consistency, test–retest reliability, and validity. There is very good evidence of the reliability and validity of the final version of ELDQOL, making it a promising instrument for assessing quality of life in children/young adults with epilepsy and learning disabilities.

The aim of this review is to discuss some of the neurological diseases that present mainly in the adolescent period. The article focuses on the usual presentation and course of the more common, and some uncommon, epilepsies, neuromuscular disorders, neurodegenerative disorders, inflammatory disorders of the central nervous system and some other, miscellaneous conditions. The article ends with a very brief and general discussion about management issues in this age group.

Dominant mutations in the skeletal muscle ryanodine receptor (RYR1) gene are well-recognized causes of both malignant hyperthermia susceptibility (MHS) and central core disease (CCD). More recently, recessive RYR1 mutations have been described in few congenital myopathy patients with variable pathology, including multi-minicores. Although a clinical overlap between patients with dominant and recessive RYR1 mutations exists, in most cases with recessive mutations the pattern of muscle weakness is remarkably different from that observed in dominant CCD. In order to characterize the spectrum of congenital myopathies associated with RYR1 mutations, we have investigated a cohort of 44 patients from 28 families with clinical and/or histopathological features suggestive of RYR1 involvement. We have identified 25 RYR1 mutations, 9 of them novel, including 12 dominant and 13 recessive mutations. With only one exception, dominant mutations were associated with a CCD phenotype, prominent cores and predominantly occurred in the RYR1 C-terminal exons 101 and 102. In contrast, the 13 recessive RYR1 mutations were distributed evenly along the entire RYR1 gene and were associated with a wide range of clinico-pathological phenotypes. Protein expression studies in nine cases suggested a correlation between specific mutations, RyR1 protein levels and resulting phenotype: in particular, whilst patients with dominant or recessive mutations associated with typical CCD phenotypes appeared to have normal RyR1 expression, individuals with more generalized weakness, multi-minicores and external ophthalmoplegia had a pronounced depletion of the RyR1 protein. The phenomenon of protein depletion was observed in some patients compound heterozygous for recessive mutations at the genomic level and silenced another allele in skeletal muscle, providing additional information on the mechanism of disease in these patients. Our data represent the most extensive study of RYR1-related myopathies and indicate complex genotype-phenotype correlations associated with mutations differentially affecting assembly and function of the RyR1 calcium release channel.

Simultaneous video (closed circuit television [CCTV]) and EEG recordings are important in the differentiation of epileptic and non-epileptic paroxysmal episodes and in the classification of epilepsy syndromes. An additional benefit from the observation of the child on CCTV is the possible identification of specific clinical, including genetic, conditions. This three-year prospective study of 2780 consecutive children undergoing routine EEG investigations identified 17 conditions that had not previously been diagnosed by the clinicians who had requested the EEG.

Decreased arterial carbon dioxide tension (PaCO2) results in decreased cerebral blood flow, which is associated with diminished cerebral electrical activity. In such a situation, cerebral fractional oxygen extraction (CFOE) would be expected to increase to preserve cerebral oxygen delivery. This study aimed to determine whether changes in blood gases in infants less than 30 wk' gestation were associated with changes in background electroencephalograms (EEG) and CFOE. Thirty-two very low birth weight infants were studied daily for the first three days after birth. Digital EEG recordings were performed for 75 min each day. CFOE, mean blood pressure and arterial blood gases were measured midway through each recording. EEG was analysed by (a) spectral analysis and (b) manual calculation of interburst interval. Blood pressure, pH and PaCO2 did not have any effect on the EEG. On day one, only PaCO2 showed a relationship with the relative power of the delta frequency band (0.5-3.5 Hz) and the interburst interval. The relative power of the delta band remained within normal limits when PaCO2 was between 24 and 55 mmHg on day one. There was a negative association between PaCO2 and CFOE. The associations between PaCO2 and EEG measurements were strongest on day one, weaker on day two, and absent on day three. The slowing of EEG and increased CFOE at lower levels of PaCO2 are likely to be due to decreased cerebral oxygen delivery induced by hypocarbia. When PaCO2 was higher, there was suppression of the EEG.

Summary Background Rectal diazepam and buccal midazolam are used for emergency treatment of acute febrile and afebrile (epileptic) seizures in children. We aimed to compare the safety and efficacy of these drugs. Methods A multicentre, randomised controlled trial was undertaken to compare buccal midazolam with rectal diazepam for emergency-room treatment of children aged 6 months and older presenting to hospital with active seizures and without intravenous access. The dose varied according to age from 2·5 to 10 mg. The primary endpoint was therapeutic success: cessation of seizures within 10 min and for at least 1 hour, without respiratory depression requiring intervention. Analysis was per protocol. Findings Consent was obtained for 219 separate episodes involving 177 patients, who had a median age of 3 years (IQR 1–5) at initial episode. Therapeutic success was 56% (61 of 109) for buccal midazolam and 27% (30 of 110) for rectal diazepam (percentage difference 29%, 95% CI 16–41). Analysing only initial episodes revealed a similar result. The rate of respiratory depression did not differ between groups. When centre, age, known diagnosis of epilepsy, use of antiepileptic drugs, prior treatment, and length of seizure before treatment were adjusted for with logistic regression, buccal midazolam was more effective than rectal diazepam. Interpretation Buccal midazolam was more effective than rectal diazepam for children presenting to hospital with acute seizures and was not associated with an increased incidence of respiratory depression.

Continuous EEG monitoring has not been used widely in neonatal intensive care, especially in the care of extremely premature infants, probably in part because of a lack of a reliable quantitative method. The purpose of this study was to quantify the EEG of the very premature infants just after birth by using spectral analysis and to describe the characteristics of the spectral signal when infants were clinically stable. Digital EEG recordings were performed on 53 infants who were < or =30 wk gestation for 75 min each day during the first 4 d after birth. Artefact was rejected manually after visual inspection of trace. The EEG was analyzed by manual measurement of interburst interval and automatically by spectral analysis using Fast Fourier Transformation. Spectral analysis generated the normal ranges of the relative power of the delta (0.5-3.5 Hz), theta (4-7.5 Hz), alpha (8-12.5 Hz), and beta (13-30 Hz) frequency bands, spectral edge frequency, and symmetry. The median (range) relative power of the delta band increased significantly from 68% (62-76%) on day 1 to 81% (72-89%) on day 4 (p=0.001). The interburst intervals became progressively shorter between days 1 [14s (10-25)] and 3 [8s (6-12)]; there were no significant differences between days 3 and 4. The relative power of the delta band seemed to be the most useful and repeatable spectral measurement for continuous long-term monitoring. However, automatic artefact rejection software needs to be developed before continuous quantitative EEG monitoring can be used in the neonatal intensive care environment.

Aims To obtain epidemiological data on the prevalence, aetiology, management and outcome of refractory convulsive status epilepticus (RCSE). Methods Data on children admitted with RCSE to eight paediatric intensive care units (PICUs) were collected retrospectively using a standard proforma designed and co-ordinated by PICAnet. Data were collected between 31/12/2007 and 31/12/2009. Results Data were collected on 245 (male, 179) patients aged Thirty nine patients received treatment (midazolam > diazepam) at home and 73 received treatment from paramedics (diazepam > midazolam). In the Emergency Department (ED), 219 patients (89%) received at least one benzodiazepine dose, 197 (80.4%) received phenytoin and 23 (9.3%) received phenobarbital. Subsequent anticonvulsants in ED included thiopentone (105 patients, 42.9%), midazolam (15, 6.12%) and midazolam and propofol (4, 1.63%). In ED the APLS guidelines were followed precisely in 90 patients (36.7%); 88 patients (35.9%) received an inappropriate dose of benzodiazepine (above guideline dose in 62, below guideline dose in 26). Thirty seven patients (15.1%) received anticonvulsants in the wrong sequence. The mean duration of admission to PICU was 3.7 days (range 1–45, median 2). The mean length of days ventilated (on PICU) was 3.2 days ventilated (range 1–31, median 2). Nine patients died (3.7%). Twenty seven patients (11%) demonstrated a new neurological deficit on discharge from PICU, of whom 10 (4% of the entire cohort) continued to show this deficit at 30 days. Conclusions Approximately one third of the patients admitted to PICU with RCSE had been treated in the ED appropriately using the APLS algorithm. Thiopentone was the most commonly used first-choice anticonvulsant to treat RCSE on admission to PICU. Mortality was low and approximately 1 in 25 showed a new neurological deficit at the 30-day follow-up.

Many neurodevelopmental disorders adversely affect sleep; children often have difficulty in falling asleep, wake up more often during the night, and sleep less than their typically developing peers. ‘Sleep problems’ were found in 53% of over 300 children with autism, compared with 44% of 63 children with delayed development, and 32% of 163 children with normal (typical) development.1 Sleep problems arise from complex interactions between biological, psychological, social, family and cultural factors. Circadian sleep rhythm disorders (CSRD) may be acute but are more often chronic, and frequently result in associated health problems. CSRDs usually exacerbate any pre-existing learning and behavioural difficulties, and may affect the entire family's whole health and well-being and impair their ability to continue in employment or further education. There is considerable pressure for both parents and paediatricians to try and improve a child's disturbed sleep. Management options include behavioural, or pharmacological, or both. Behavioural interventions are probably undervalued, but may be difficult to implement, and may take weeks or months to show any benefit. Conventional medications including hypnotics and sedatives are frequently associated with unacceptable day-time sedation that may adversely affect the child's quality of life. The past 20 years have witnessed the introduction of melatonin which continues to be increasingly prescribed to many children both with and without neurodevelopmental disorders and using a wide range of doses. To many, it is the ubiquitous safe solution to any ‘sleep problem’. The popularity of melatonin reflects the …

The practical value or usefulness of any investigation is dependent upon the clinical information provided and subsequent interpretation; this is particularly important in the investigation and classification of the epilepsies. For two months the histories from clinicians and EEG technicians were prospectively evaluated from 255 consecutive patients. The histories were interpreted by a single paediatric neurologist who was blinded to their origin. The histories were reported as "adequate' or "inadequate', and "diagnostic' or "non-diagnostic' (of epilepsy). Overall 92% and 40% of technicians' and 41% and 13% of clinicians' histories were considered to have been "adequate' and "diagnostic', respectively. These results have implications for the electro-clinical interpretation of the EEG.

Sleep disturbances in children with neurodevelopmental disabilities are common and frequently difficult to treat with conventional pharmacological and behavioural methods. Melatonin is a pineal hormone known to be important in the regulation of the circadian rhythm, including the sleep-wake cycle. This systematic review of available evidence from randomized clinical trials assesses whether melatonin plays a beneficial role in these children and, in particular, its effect on total sleep time, time to sleep onset (sleep latency), and number of awakenings. We also looked at a parental view of the effect. Randomized clinical trials were identified where oral melatonin was compared with a placebo in children with any type of neurodevelopmental disability and associated sleep disturbance. Only three studies, reporting a total of 35 children, fulfilled the criteria for inclusion. The two studies that reported time to sleep onset showed a significant decrease (p

Levetiracetam is a new anti-epileptic drug that is currently not licensed for use in children. Studies in adults suggest that it may be a useful adjunctive treatment both in partial onset and generalised epilepsy. A retrospective case notes review of 26 children age 10 years and under with refractory epilepsy was undertaken to evaluate the efficacy and safety of the drug. The drug appeared to be most effective in children with partial onset seizures and least effective in those with myoclonic seizures. Sixty-one percent of patients showed a good response to levetiracetam with at least a 50% reduction in seizure frequency with two of these 26 children with previously refractory epilepsy becoming seizure-free. Levetiracetam was also found to be well-tolerated with very few reported side-effects.

The article by Karltorp et al (1) raised important issues about congenital cytomegalovirus (CMV) infection. We have recently diagnosed the oldest case reported in the literature of isolated late-onset sensorineural hearing loss (SNHL) due to congenital CMV. A previously well, 14-year-old boy developed acute right-sided deafness, confirmed to be SNHL on audiological assessment. ©2012 The Author(s)/Acta Paediatrica ©2012 Foundation Acta Paediatrica. Language: en