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.

INTRODUCTION: Hypothalamic 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. METHODS: Patient records of all HH cases operated on since 2011 were reviewed to confirm history of presentation and clinical outcomes. RESULTS: Ten 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. CONCLUSIONS: IOMR 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.

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

BACKGROUND: Tonic-clonic convulsions and convulsive status epilepticus (currently defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical emergencies and require urgent and appropriate anticonvulsant treatment. International consensus is that an anticonvulsant drug should be administered for any tonic-clonic convulsion that has been continuing for at least five minutes. Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line drugs. This is an update of a Cochrane Review first published in 2002 and updated in 2008. OBJECTIVES: To evaluate the effectiveness and safety of anticonvulsant drugs used to treat any acute tonic-clonic convulsion of any duration, including established convulsive (tonic-clonic) status epilepticus in children who present to a hospital or emergency medical department. SEARCH METHODS: For the latest update we searched the Cochrane Epilepsy Group's Specialised Register (23 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 May 2017), MEDLINE (Ovid, 1946 to 23 May 2017), ClinicalTrials.gov (23 May 2017), and the WHO International Clinical Trials Registry Platform (ICTRP, 23 May 2017). SELECTION CRITERIA: Randomised and quasi-randomised trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information. MAIN RESULTS: The review includes 18 randomised trials involving 2199 participants, and a range of drug treatment options, doses and routes of administration (rectal, buccal, nasal, intramuscular and intravenous). The studies vary by design, setting and population, both in terms of their ages and also in their clinical situation. We have made many comparisons of drugs and of routes of administration of drugs in this review; our key findings are as follows:(1) This review provides only low- to very low-quality evidence comparing buccal midazolam with rectal diazepam for the treatment of acute tonic-clonic convulsions (risk ratio (RR) for seizure cessation 1.25, 95% confidence interval (CI) 1.13 to 1.38; 4 trials; 690 children). However, there is uncertainty about the effect and therefore insufficient evidence to support its use. There were no included studies which compare intranasal and buccal midazolam.(2) Buccal and intranasal anticonvulsants were shown to lead to similar rates of seizure cessation as intravenous anticonvulsants, e.g. intranasal lorazepam appears to be as effective as intravenous lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial; 141 children; high-quality evidence) and intranasal midazolam was equivalent to intravenous diazepam (RR 0.98, 95% CI 0.91 to 1.06; 2 trials; 122 children; moderate-quality evidence).(3) Intramuscular midazolam also showed a similar rate of seizure cessation to intravenous diazepam (RR 0.97, 95% CI 0.87 to 1.09; 2 trials; 105 children; low-quality evidence).(4) For intravenous routes of administration, lorazepam appears to be as effective as diazepam in stopping acute tonic clonic convulsions: RR 1.04, 95% CI 0.94 to 1.16; 3 trials; 414 children; low-quality evidence. Furthermore, we found no statistically significant or clinically important differences between intravenous midazolam and diazepam (RR for seizure cessation 1.08, 95% CI 0.97 to 1.21; 1 trial; 80 children; moderate-quality evidence) or intravenous midazolam and lorazepam (RR for seizure cessation 0.98, 95% CI 0.91 to 1.04; 1 trial; 80 children; moderate-quality evidence). In general, intravenously-administered anticonvulsants led to more rapid seizure cessation but this was usually compromised by the time taken to establish intravenous access.(5) There is limited evidence from a single trial to suggest that intranasal lorazepam may be more effective than intramuscular paraldehyde in stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 160 children; moderate-quality evidence).(6) Adverse side effects were observed and reported very infrequently in the included studies. Respiratory depression was the most common and most clinically relevant side effect and, where reported, the frequency of this adverse event was observed in 0% to up to 18% of children. None of the studies individually demonstrated any difference in the rates of respiratory depression between the different anticonvulsants or their different routes of administration; but when pooled, three studies (439 children) provided moderate-quality evidence that lorazepam was significantly associated with fewer occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to 0.93).Much of the evidence provided in this review is of mostly moderate to high quality. However, the quality of the evidence provided for some important outcomes is low to very low, particularly for comparisons of non-intravenous routes of drug administration. Low- to very low-quality evidence was provided where limited data and imprecise results were available for analysis, methodological inadequacies were present in some studies which may have introduced bias into the results, study settings were not applicable to wider clinical practice, and where inconsistency was present in some pooled analyses. AUTHORS' CONCLUSIONS: We have not identified any new high-quality evidence on the efficacy or safety of an anticonvulsant in stopping an acute tonic-clonic convulsion that would inform clinical practice. There appears to be a very low risk of adverse events, specifically respiratory depression. Intravenous lorazepam and diazepam appear to be associated with similar rates of seizure cessation and respiratory depression. Although intravenous lorazepam and intravenous diazepam lead to more rapid seizure cessation, the time taken to obtain intravenous access may undermine this effect. In the absence of intravenous access, buccal midazolam or rectal diazepam are therefore acceptable first-line anticonvulsants for the treatment of an acute tonic-clonic convulsion that has lasted at least five minutes. There is no evidence provided by this review to support the use of intranasal midazolam or lorazepam as alternatives to buccal midazolam or rectal diazepam.

Social cognition in children with epilepsy in mainstream education.

AIM: 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. METHOD: In a cross-sectional study, children with an epilepsy-only diagnoses in mainstream education (n=20 with generalized epilepsy; eight males, 12 females; mean age 11y 6mo, SD 2y 6mo; and n=27 with focal epilepsy; 12 males, 15 females; mean age 11y 8mo, SD 2y 2mo) and comparison participants (n=57; 28 males, 29 females; mean age 11y 2mo, SD 2y 4mo) were administered the Strange Stories task and the Mind in the Eyes task, as well as an IQ assessment. Parents completed the Children's Communication Checklist-2 and the Child Behavior Checklist (CBCL). RESULTS: Both groups of children with epilepsy performed more poorly than control children on the Mental Stories component of the Strange Stories task, F(2,101)=3.2, p<0.001. Performance on Mental Stories was related to pragmatic communication, but only in the generalized epilepsy group (r=0.51, p=0.03, 95% CI=0.2-0.8). There were no differences between epilepsy groups or control participants in the Mind in the Eyes task, F(2,101)=0.4, p=0.4. INTERPRETATION: Children with 'epilepsy only' are at risk of deficits in social cognition and may require appropriate support.

Effect of reducing the recording time of standard EEGs on the detection of EEG-abnormalities in the management of the epilepsies of childhood.

PURPOSE: The ILAE recommends baseline recordings of 30 min to detect abnormalities supporting a clinical diagnosis of epilepsy in children. A shorter recording time may be better tolerated by children and be more resource-efficient. Our aim was to determine how many abnormalities supporting a diagnosis of epilepsy would be missed by reducing the recording time of paediatric standard electroencephalograms (EEGs) from 20 to 15 min. METHODS: We evaluated standard EEGs of 300 patients aged 2 months to 17 years referred consecutively with confirmed or suspected epilepsy. EEGs were recorded for 20 min on digital media. A digital copy of each EEG was truncated to give consecutive sequences of 10 min (sequence "A") and 5 min duration (sequences "B" and "C" respectively). A panel of EEG raters blinded to the children's' details other than age identified these sequences as "normal" or "abnormal" if they contained spike waves, discrete sharp waves or notched slow waves in the respective EEG period. RESULTS: EEGs of 297 children were analysed (three were omitted for technical reasons). 109 out of 297 EEGs (37%) had specific abnormalities supportive of a diagnosis of an epilepsy. 17 of these EEGs showed the abnormality in EEG sequences "B" or "C" and 7 (95% CI: 1.9-12.2) out of these demonstrated the abnormality in sequence "C" only. 105 out of 297 EEGs had non-specific findings. CONCLUSION: We conclude that reducing the recording time of standard EEGs to 15 min may miss abnormalities in 2.36% [95% CI: 0.63-4.09%] overall and 6.42% [95% CI: 2.2-11.8%] of those with an abnormality supportive of an epilepsy to explain the reported symptoms. This result should inform any future discussions on seeking resource-efficiencies.

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.

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 child's 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.

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

BACKGROUND: Tonic-clonic (grand mal) convulsions and convulsive status epilepticus (currently defined as a grand mal convulsion lasting at least 30 minutes) are medical emergencies and demand urgent and appropriate anticonvulsant treatment. Benzodiazepines (midazolam, diazepam, lorazepam), phenobarbitone, phenytoin and paraldehyde may all be regarded as drugs of first choice. This is an update of a Cochrane review first published in 2002 and previously updated in 2005. OBJECTIVES: To review the evidence comparing the efficacy and safety of midazolam, diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status epilepticus in children treated in hospital. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's Specialized Register (1st July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), and MEDLINE (1966 to July 2007). SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. We contacted study authors for additional information. MAIN RESULTS: Four trials involving 383 participants were included.(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions, 19/27 (70%) versus 22/34 (65%), RR 1.09 (95% CI 0.77 to 1.54), has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam, 6/6 versus 6/19 (31%), RR 3.17 (95% CI 1.63 to 6.14)(2) Buccal midazolam controlled seizures in 61/109 (56%) compared with 30/110 (27%) of rectal diazepam treated episodes with acute tonic-clonic convulsions, RR 2.05 ( 95% CI 1.45 to 2.91)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile convulsions, 23/26 (88%) versus 24/26 (92%), RR 0.96 (95% CI 0.8 to 1.14)(4) There is moderate evidence that intranasal lorazepam is more effective than intramuscular paraldehyde for acute tonic-clonic convulsions and patients treated with intranasal lorazepam are significantly less likely to require further anticonvulsants to control continuing seizures, 8/80 (10%) versus 21/80 (26%), RR 0.58 (95% CI 0.42 to 0.79). AUTHORS' CONCLUSIONS: The conclusions of this update have changed to suggest that intravenous lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions. Where intravenous access is unavailable there is evidence from one trial that buccal midazolam is the treatment of choice.

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 6 1/2-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.