Explore the vast range of titles available.

ABSTRACT BACKGROUND: Open surgery effectively treats mesial temporal lobe epilepsy, but carries the risk of neurocognitive deficits, which may be reduced with minimally invasive alternatives. OBJECTIVE: To describe technical and clinical outcomes of stereotactic laser amygdalohippocampotomy with real-time magnetic resonance thermal imaging guidance. METHODS: With patients under general anesthesia and using standard stereotactic methods, 13 adult patients with intractable mesial temporal lobe epilepsy (with and without mesial temporal sclerosis [MTS]) prospectively underwent insertion of a saline-cooled fiberoptic laser applicator in amygdalohippocampal structures from an occipital trajectory. Computer-controlled laser ablation was performed during continuous magnetic resonance thermal imaging followed by confirmatory contrast-enhanced anatomic imaging and volumetric reconstruction. Clinical outcomes were determined from seizure diaries. RESULTS: A mean 60% volume of the amygdalohippocampal complex was ablated in 13 patients (9 with MTS) undergoing 15 procedures. Median hospitalization was 1 day. With follow-up ranging from 5 to 26 months (median, 14 months), 77% (10/13) of patients achieved meaningful seizure reduction, of whom 54% (7/13) were free of disabling seizures. Of patients with preoperative MTS, 67% (6/9) achieved seizure freedom. All recurrences were observed before 6 months. Variances in ablation volume and length did not account for individual clinical outcomes. Although no complications of laser therapy itself were observed, 1 significant complication, a visual field defect, resulted from deviated insertion of a stereotactic aligning rod, which was corrected before ablation. CONCLUSION: Real-time magnetic resonance-guided stereotactic laser amygdalohippocampotomy is a technically novel, safe, and effective alternative to open surgery. Further evaluation with larger cohorts over time is warranted.

Exome sequencing has found an excess of de novo mutations in the ∼4,000 most intolerant genes in patients with two classical epileptic encephalopathies (infantile spasms and Lennox–Gastaut syndrome); among them are multiple de novo mutations in GABRB3 and ALG13 . Epilepsy-linked mutations revealed An extensive exome sequencing study of patients with two 'classical' epileptic encephalopathies — infantile spasms and Lennox-Gastaut syndrome — has found an excess of de novo mutations in the approximately 4,000 genes that are the most intolerant to functional genetic variation in the human population. Among them are de novo mutations in GABRB3 and ALG13 , both showing statistical evidence of an association with epileptic encephalopathy. As in autism spectrum disorders, these de novo mutations are enriched in genes regulated by fragile X protein. Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown 1 . Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms ( n = 149) and Lennox–Gastaut syndrome ( n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population ( P = 2.9 × 10 −3 ). Among these are GABRB3 , with de novo mutations in four patients, and ALG13 , with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10 −10 and P = 7.8 × 10 −12 , respectively. Other genes with de novo mutations in this cohort include CACNA1A , CHD2 , FLNA , GABRA1 , GRIN1 , GRIN2B , HNRNPU , IQSEC2 , MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein ( P  < 10 −8 ), as has been reported previously for autism spectrum disorders 2 .

BackgroundCerebral palsy is a heterogeneous group of neurodevelopmental brain disorders resulting in motor and posture impairments often associated with cognitive, sensorial, and behavioural disturbances. Hypoxic–ischaemic injury, long considered the most frequent causative factor, accounts for fewer than 10% of cases, whereas a growing body of evidence suggests that diverse genetic abnormalities likely play a major role.Methods and resultsThis report describes an autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1, one of the four subunits of the adaptor protein complex-4 (AP-4), identified by chromosomal microarray analysis.ConclusionThese findings, along with previous reports of human and mouse mutations in other members of the complex, indicate that disruption of any one of the four subunits of AP-4 causes dysfunction of the entire complex, leading to a distinct ‘AP-4 deficiency syndrome’.

Since its introduction in the early 1960s, circulatory arrest has been widely used in centers with expertise in infant open-heart surgery 1 – 3 . A great advantage of this technique is the absence of perfusion cannulas and blood in the operative field. The use of circulatory arrest is based on the premise that there is a “safe” duration of total circulatory arrest that has an inverse relation to body temperature 4 ; the organ with the shortest safe circulatory-arrest time is the brain. Conflicting reports of transient cerebral dysfunction and late neurologic and developmental adverse effects after circulatory arrest have generated considerable . . .

Deep hypothermia with total circulatory arrest is a method of support for vital organs that is often used during the repair of complex congenital heart abnormalities in infants. The maximal duration of circulatory arrest that will not result in impairment of the central nervous system is uncertain. 1 , 2 Few data are available on the developmental and neurologic sequelae of the most important alternative support strategy, continuous low-flow cardiopulmonary bypass. 3 In 1988 we began a randomized clinical trial to compare the incidence of brain injury in children with D-transposition of the great arteries undergoing an arterial-switch operation after assignment to a . . .

Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7–3·2, p=9·1 × 10−8; familial non-acquired focal epilepsy 3·6, 2·7–4·9, p=1·1 × 10−17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10−8) that were lower than expected from a random sampling of genes. We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK.

Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy using an implantable neuromodulatory device. The device is approved for refractory focal epilepsy in patients 12 years or older but also has been shown to be effective in generalized epilepsies and pediatric populations. It consists of a pulse generator inserted in the superficial left chest with electrodes attached to the left vagus nerve. The stimulus is delivered automatically at regular intervals and can also be triggered with a voluntary magnet swipe. It is proposed, but not proven, that the mild electrical impulses disrupt activity of thalamocortical connections and prevent seizure propagation. The stimulation settings can be changed in order to increase effectiveness or reduce side effects. Most of the common side effects can be attenuated or eliminated with setting adjustment.

Nodding syndrome is an unexplained illness characterised by head-bobbing spells. The clinical and epidemiological features are incompletely described, and the explanation for the nodding and the underlying cause of nodding syndrome are unknown. We aimed to describe the clinical and neurological diagnostic features of this illness. In December, 2009, we did a multifaceted investigation to assess epidemiological and clinical illness features in 13 parishes in Kitgum District, Uganda. We defined a case as a previously healthy child aged 5–15 years with reported nodding and at least one other neurological deficit. Children from a systematic sample of a case-control investigation were enrolled in a clinical case series which included history, physical assessment, and neurological examinations; a subset had electroencephalography (EEG), electromyography, brain MRI, CSF analysis, or a combination of these analyses. We reassessed the available children 8 months later. We enrolled 23 children (median age 12 years, range 7–15 years) in the case-series investigation, all of whom reported at least daily head nodding. 14 children had reported seizures. Seven (30%) children had gross cognitive impairment, and children with nodding did worse on cognitive tasks than did age-matched controls, with significantly lower scores on tests of short-term recall and attention, semantic fluency and fund of knowledge, and motor praxis. We obtained CSF samples from 16 children, all of which had normal glucose and protein concentrations. EEG of 12 children with nodding syndrome showed disorganised, slow background (n=10), and interictal generalised 2·5–3·0 Hz spike and slow waves (n=10). Two children had nodding episodes during EEG, which showed generalised electrodecrement and paraspinal electromyography dropout consistent with atonic seizures. MRI in four of five children showed generalised cerebral and cerebellar atrophy. Reassessment of 12 children found that six worsened in their clinical condition between the first evaluation and the follow-up evaluation interval, as indicated by more frequent head nodding or seizure episodes, and none had cessation or decrease in frequency of these episodes. Nodding syndrome is an epidemic epilepsy associated with encephalopathy, with head nodding caused by atonic seizures. The natural history, cause, and management of the disorder remain to be determined. Division of Global Disease Detection and Emergency Response, US Centers for Disease Control and Prevention.