Timothy Martland

Social cognition in children with epilepsy in mainstream education

To establish whether deficits in social cognition are present in children with generalized or focal epilepsy in mainstream education, and whether any relation exists between social cognition, communication, and behaviour measures.

Effectiveness and tolerability of zonisamide in children with epilepsy: A retrospective review

PURPOSE To evaluate the effectiveness and tolerability of zonisamide in children with epilepsy. METHOD Retrospective case note review of young people (less than 19 years) with epilepsy from three UK tertiary centres who received treatment with zonisamide and were followed up for a minimum of 12 months. RESULTS Fifty-seven children were included, aged 1.5-18.5 (median, 12) years. Thirty-three (57.9%) patients had generalised epilepsy, 21 (36.8%) focal epilepsy, and three (5.3%) a mixed, generalised and focal, epilepsy. Fifty-six of the 57 patients had been refractory to at least three previous antiepileptic drugs. The maintenance dose of zonisamide was [range (median)] 0.7-14 (5)mg/kg/day. The median duration of treatment for all patients was 12 (range 0.25-35) months. After 2 months of treatment, 51 patients remained on zonisamide, 18 (35.3%) of whom demonstrated a > or =50% reduction in seizure frequency. At the end of the follow-up period, there was a loss of effect for some patients. Thirteen (25.5%) of the 51 patients continued to demonstrate a > or =50% reduction in seizure frequency whilst two who had become seizure-free started having seizures again. Six (11.8%) had <50% reduction, twenty-four (47%) had no change, and eight (15.7%) had increasing seizures. Twenty-five (43.9%) patients reported unwanted effects although this contributed to the withdrawal of zonisamide in only ten (17.6%) patients. CONCLUSIONS Zonisamide appeared to be a reasonably effective and generally well-tolerated antiepileptic drug in a heterogeneous group of 57 children with poorly controlled epilepsy and provides another treatment option for children with refractory seizures.

Admissions to paediatric intensive care units (PICU) with refractory convulsive status epilepticus (RCSE): A two-year multi-centre study.

AIMS To obtain national epidemiological data on the aetiology, management and outcome of refractory convulsive status epilepticus (RCSE) in children. METHODS Data on children admitted with RCSE between 01.01.2008 and 31.12.2009, to eight paediatric intensive care units (PICUs) were retrospectively collected using a standard proforma designed with and co-ordinated by PICANet. RESULTS Data were collected on 245 (male, 179) patients aged between <1 month and 16.5 years (median 2.8 years, IQR 1-7.43 years), of which: One hundred and fifty-one patients (male, 89) aged between <1 month and 16.5 years (median 2.3 years, IQR 1-7.17 years) met the study criteria for a diagnosis of RCSE. Causes included acute symptomatic (15.2%), remote symptomatic (29.0%), epilepsy-related (10.6%), progressive encephalopathy (10.6%) febrile seizures (18.2%); no cause was identified in 16.4%. First line treatments included lorazepam (118 patients, 78.1%), diazepam (72, 47.7%) and midazolam (37, 24.5%). Second-line treatments included phenytoin (125 patients, 82.8%) and phenobarbital (seven patients, 4.6%). Third-line treatments included a thiopentone bolus (99 patients, 65.6%), thiopentone infusion (20, 13.2%) midazolam infusion (56, 37.1%) phenobarbital (18, 11.9%), propofol (6, 4.0%) and clonazepam (2, 1.3%). Deviation from the national advanced paediatric life support (APLS) protocol was noted in approximately one quarter of all patients. Six patients died (4.0%). Seventeen patients (11.3%) developed a new neurological deficit on discharge from PICU, of which eight (5.3%) continued to show this deficit at a 30-day follow-up and 12 patients (7.9%) developed de novo epilepsy. CONCLUSIONS Thiopentone was the most commonly used 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.

Epilepsy with reversible bulbar dysfunction.

In patients with focal epilepsy, focal neurological dysfunction can occur due to status epilepticus and also as a post‐ictal phenomenon. Bulbar dysfunction as evident by drooling, dysarthria, swallowing difficulties, and palatal‐glossalpharyngeal weakness has been reported in conjunction with epilepsy. This is non‐progressive and is correlated in its severity with the frequency of seizures. Accompanying EEG discharges are often localized to rolandic areas that cortically represent oral movements and salivation. We report a 6‐year‐old male and a 6½‐year‐old female with progressive bulbar dysfunction resulting from epilepsy. Ictal EEGs in patient 1 did not confirm a diagnosis of epilepsy. With no evidence of a cortical or brainstem focus from EEG or MRI, it is very difficult to explain the mechanism of bulbar dysfunction. The complete restoration of bulbar function after treatment with antiepileptic drugs demonstrates the need to consider epilepsy in similar clinical situations.

Effectiveness and tolerability of Perampanel in children, adolescents and young adults with refractory epilepsy: A UK national multicentre study

PURPOSE Perampanel is one of the latest antiepileptic drugs (AEDs) approved for the treatment of focal and generalised epilepsy in individuals with epilepsy aged 12 years and older. There is sparse data on the use of Perampanel in children under 12. We conducted a study amongst paediatric neurologists in the United Kingdom to investigate its effectiveness and tolerability as an adjunctive therapy in children of all ages with refractory epilepsy. METHODS Data was collected via an online questionnaire sent to paediatric neurologists in the UK. Data gathered, prospective in 62 (64.5%) and retrospective in 34 (35.5%) patients, included changes in seizure frequency from baseline and unwanted effects at 3, 6 and 12 months follow-up. Only patients with a minimum follow-up of six months were included. RESULTS Ninety six patients (48 females) with refractory epilepsy from 11 of 29 tertiary centres were included. Median [IQR] (range) age was 14 years 11 months [12 years, 16 years 6 months] (11 months-24 years 5 months). Seventy three (76%) had focal epilepsy, sixteen (17%) generalised, and seven (7%) patients both generalised and focal epilepsy. The responder rate, ≥50% seizure reduction from baseline, was 19% for all seizure types at both 6 and 12 months, 19% and 24% for focal seizures, and 25% and 7% for generalised seizures at these time points respectively. The retention rate was 42% at 12 months. Treatment was discontinued due to unwanted effects in 29 (36.7%) of the 79 patients with follow-up data available up to 12 months: 30% due to challenging behaviour, 14% dizziness, and 7.6% somnolence. CONCLUSION Perampanel was fairly effective in a heterogeneous group of 96 children and adolescents with very refractory epilepsy. The rate of adverse events leading to discontinuation was considerable in this group.

Best clinical and research practice in pediatric neurology.

Many children with epilepsy experience it as part of a broader disability. The cause is often a developmental, genetic, or early acquired abnormality associated with learning difficulties and impairments in other systems. In addition, it has become increasingly recognized in recent years that even children with so-called idiopathic generalized epilepsies may have specific language or cognitive impairments. The combination of seizures and these factors can form a significant barrier to the child and family in social and emotional terms as well. A childs brain must mature and learn new skills; and a large proportion of childhood epilepsies directly impact on this. The degree of control of the epilepsy can affect cognitive progress; but for many children the underlying cause of the impairment is the significant factor. For all children, access to appropriate clinical, educational, and social services for assessment and therapy is paramount. Specific initiatives in the North West of the United Kingdom are attempting to address service and organizational issues. Current research projects are investigating the impairments children with epilepsy have in addition to having seizures.

Correction to: Open resection of hypothalamic hamartomas for intractable epilepsy revisited, using intraoperative MRI

The authors apologize to have sent a final manuscript draft omitting “Athanasius Chawira” from the list of authors. The correct list of authors is given in this article.The original article has been corrected.

Open resection of hypothalamic hamartomas for intractable epilepsy revisited, using intraoperative MRI

IntroductionHypothalamic hamartomas (HHs) are rare non-neoplastic lesions which cause drug-resistant epilepsy with associated behavioural, psychiatric and endocrine issues. With the development of new minimally invasive techniques for the treatment of HH, there is a need to reappraise the effectiveness and safety of each approach. We review the outcomes of HH patients treated surgically, utilizing intraoperative magnetic resonance imaging (IOMRI), by a team of Alder Hey NHS Foundation Trust tumour and epilepsy neurosurgeons since 2011.MethodsPatient records of all HH cases operated on since 2011 were reviewed to confirm history of presentation and clinical outcomes.ResultsTen patients have undergone surgery for HH under the dual care of Alder Hey tumour and epilepsy neurosurgeons during this period. Eight cases had a midline transcallosal, interforniceal approach with the remaining 2 having a transcallosal, transforaminal approach. All patients had an IOMRI scan, with 40% needing further tumour resection post-IOMRI. Forty percent had a total resection, 3 patients had near-total resection and 3 patients had subtotal resection (~ 30% tumour residual on post-operative MRI). No new neurological complications developed post-operatively. Hypothalamic axis derangements were seen in 3 cases, including 1 diabetes insipidus with hypocortisolaemia, 1 hypodipsia and 1 transient hyperphagia. Eighty percent are seizure free; the remaining two patients have had significant improvements in seizure frequency.ConclusionsIOMR was used to tailor the ideal tumour resection volume safely based on anatomy of the lesion, which combined with the open transcallosal, interforniceal route performed by surgeons experienced in the approach resulted in excellent, safe and effective seizure control.

G103(P) Children’s epilepsy surgery service in England: Audit of activity and outcome

Objective To examine trends in epilepsy-related surgical procedures (ERSPs), excluding vagal nerve stimulator procedures, in children performed at the four CESS centres in England since inception of the service in November 2012. To analyse outcome and follow-up data at one year, identify potential treatment gaps in different geographical areas, raise awareness about surgery as an option for medically refractory epilepsies, and reflect on challenges encountered since the inception of the CESS. Methods Epilepsy-related surgical activity for the first 20 months of CESS service (Nov 2012–June 2014- first period) was compared with a more recent 18 months (April 2014–Sep 2015- second period). Data was collected from the four CESS centres with regard to referrals, case evaluation, surgical procedures and outcome. The number of referrals to CESS for the commissioning year 2014–15 was compared to the expected number based on an epidemiological cohort.1 Adverse surgical outcomes were measured using the GOSH adverse surgical grading score. Results There were 183 ERSPs in the first period compared to 271 in the second period representing time-adjusted increase in activity of 61%. In 2014–15 commissioning year, 387 children were referred to the 4 CESS centres for consideration of epilepsy surgery (excludes VNS referrals), representing between 30–50% of expected numbers based on the previous epidemiological cohort.1 There is considerable variation in referral rates from different areas in England. Twelve months following surgery, 95 (58%) of children were Engel Class I (seizure-free) with 141 (87%) Engel Class I-III. Best outcomes were achieved with temporal lobe surgery with 77% seizure-free at 1 year. There were no mortalities but there were two unexpected surgery-related morbidities in this group. Conclusion There has been a major change in the children’s epilepsy surgery landscape in England since the inception of CESS, with a significant year-by-year increase in ERSPs during the study period. Outcomes by Engel classification remain equivalent to published international outcomes. The mortality rate has been zero with low surgical morbidity. Reference Berg et al. Frequency, prognosis and surgical treatment of structural abnormalities with MRI in childhood epilepsy. Brain 2009;132:2785–97

Misleading data in Shastin et al.’s paper

Dear Editor: We write to comment on a paper by Shastin and colleagues recently published online by your journal. It is entitled BMonitoring the changing pattern of delivery of paediatric epilepsy surgery in England—an audit of a regional service and examination of national trends^ [1]. The topic is currently of considerable interest, but unfortunately, we note a number of inaccuracies in the data relating to epilepsy surgery in children since the Children’s Epilepsy Surgery Service (CESS) for England was commissioned in November 2012. Shastin et al.’s paper reports on a national audit compiled by the British Paediatric Neurosurgical Group (BPNG), which records numbers and types of procedures performed on children up to the age of 16 years in centres in England, Scotland, Wales and Southern Ireland. The BPNG data suggest that there has been a drop in paediatric epilepsy surgery numbers in the four CESS centres: in 2012, the total number of operations in these centres reported by the BPNGwas 115, and in 2013, it was 104. The CESS is responsible for children in England and is gathering data prospectively through a national database with the aim of matching similar databases, such as that established in Sweden [2]. Since November 2012, the four centres making up the CESS have gathered and presented data both to NHS England and, latterly, to the British Paediatric Neurology Association (BPNA) in January of 2015. The abstract of the BPNA presentation has been published [3] and describes referrals to the CESS service and procedures performed for the first full financial year April 2013 toMarch 2014. During that time, there was a total of 445 referrals, resulting in 278 full evaluations and 138 surgical procedures (50 lobectomies, 24 lesionectomies, 28 hemidisconnections, 21 invasive EEGs, 9 disconnections and 6 corpus callosotomies). This compares with 112 paediatric surgery operations documented in a UK study in 2010–2011 [4], the last full year prior to initiation of the CESS process. In addition, the CESS data for the first 6 months of 2013 were presented, and when compared to the first 6 months of 2014, they demonstrate clear evidence of growth with 202 vs 271 referrals and 62 vs 93 surgeries (excluding operations related to vagal nerve stimulation). Shastin et al. [1] concluded from the BPNG data quoted in their paper that a trend of increasing numbers in the years prior to the CESS had been reversed since its inception. In contrast, the data prospectively collected by the CESS centres show that for the CESS, this conclusion is incorrect. The progressive increase in the years prior to the initiation of the CESS process can be mainly accounted for by the increase in surgeries at Great Ormond Street Hospital. The CESS process is designed to bring the expertise and experience of all four CESS centres up to the best international standards, increasing the numbers of surgeries to levels estimated using the results of a prospective epidemiological study [5]. Shastin et al. [1] state, Boutcomes from Leeds are comparable to those published elsewhere. Other UK units are encouraged to publish outcomes to facilitate patient, commissioner and provider decision making^. However, they report their single-centre experience of 43 cases over an 8-year period, an average of just 5 cases per year. They have based their analyses on small numbers obtained via a retrospective note-based review. It is misleading for them to suggest that the comparison of their outcome data * Christopher Verity christopher.verity@addenbrookes.nhs.uk; cm.verity@btinternet.com