"One size does not fit all" - Barriers to and facilitators of physical activity in adolescents with epilepsy.

OBJECTIVE: To explore the barriers to physical activity and to identify the support needed to facilitate physical activity in adolescents with epilepsy (AWE). METHODS: AWE (aged 11-16 years) and their caregivers completed survey-based open questions regarding perceived barriers to, and facilitators of physical activity in young people with epilepsy. The responses were analysed using Thematic Analysis. RESULTS: Themes concerning barriers to physical activity included concerns about seizure safety, general anxiety and anxiety related to seizures, stigma/negative attitudes associated with having epilepsy, tiredness, and perceived lack of physical competence. Themes regarding the support needed to facilitate physical activity included better education amongst staff/coaches about epilepsy (e.g., seizure management/prevention, associated fatigue/tiredness), improvements in societal attitudes towards epilepsy, flexibility/tailoring of activities to the child's needs (e.g., need for breaks), and peer support for young people with epilepsy to encourage engagement in physical activity. CONCLUSIONS: There is a perception among AWE and caregivers, that significant barriers exist with regard to engaging in physical activity for young people with epilepsy. Barriers are related to concerns about seizure management but also wider safety and social issues. A number of facilitators were identified to promote physical activity engagement in AWE, including education for staff and caregivers, peer support, and tailoring activities to the adolescent's needs. There is a need to develop interventions to reduce barriers to physical activity in young people with epilepsy.

Mental health in secondary school-aged children with epilepsy and their primary caregivers: A case control study.

PURPOSE: To describe the prevalence and associated factors of mental health problems in secondary school-aged (11-16 years) children with epilepsy and their primary caregivers compared to a control group without epilepsy. METHODS: Children with epilepsy (n = 60), controls (n = 49), and caregivers (n = 60 epilepsy and n = 49 control group) completed a measure of the child's mental health (Strengths and Difficulties Questionnaire; SDQ). Primary caregivers in both groups completed a measure of their own mental health (Depression, Anxiety, and Stress Scale-21; DASS-21). Factors associated with child and caregiver mental health in the epilepsy group were explored using linear regression. RESULTS: There were no significant differences between the epilepsy and control group regarding age, gender, ethnicity and socioeconomic status. A higher proportion of children with epilepsy scored in the at-risk range on the SDQ indicating more mental health problems than the control group, as reported by the children (45% vs. 24 %) (p = 0.026) and caregivers (52% vs. 14 %) (p < 0.001). Primary caregivers of children with epilepsy had more symptoms of depression (p = 0.001), anxiety (p = 0.028) and stress (p = 0.019) than caregivers in the control group. Children with epilepsy with greater motor coordination problems had greater mental health difficulties. Children with epilepsy with more mental health difficulties had caregivers with more difficulties and caregivers of children with earlier onset of seizures had more mental health difficulties. CONCLUSIONS: Epilepsy confers a high risk for mental health problems in adolescents and their primary caregivers. There is a need to better understand the relationship between caregiver and child mental health difficulties in epilepsy.

Epileptogenic Tubers Are Associated with Increased Kurtosis of Susceptibility Values: A Combined Quantitative Susceptibility Mapping and Stereoelectroencephalography Pilot Study.

BACKGROUND AND PURPOSE: Prior studies have found an association between calcification and the epileptogenicity of tubers in tuberous sclerosis complex. Quantitative susceptibility mapping is a novel tool sensitive to magnetic susceptibility alterations due to tissue calcification. We assessed the utility of quantitative susceptibility mapping in identifying putative epileptogenic tubers in tuberous sclerosis complex using stereoelectroencephalography data as ground truth. MATERIALS AND METHODS: We studied patients with tuberous sclerosis complex undergoing stereoelectroencephalography at a single center who had multiecho gradient-echo sequences available. Quantitative susceptibility mapping and R2* values were extracted for all tubers on the basis of manually drawn 3D ROIs using T1- and T2-FLAIR sequences. Characteristics of quantitative susceptibility mapping and R2* distributions from implanted tubers were compared using binary logistic generalized estimating equation models designed to identify ictal (involved in seizure onset) and interictal (persistent interictal epileptiform activity) tubers. These models were then applied to the unimplanted tubers to identify potential ictal and interictal tubers that were not sampled by stereoelectroencephalography. RESULTS: A total of 146 tubers were identified in 10 patients, 76 of which were sampled using stereoelectroencephalography. Increased kurtosis of the tuber quantitative susceptibility mapping values was associated with epileptogenicity (P = .04 for the ictal group and P = .005 for the interictal group) by the generalized estimating equation model. Both groups had poor sensitivity (35.0% and 44.1%, respectively) but high specificity (94.6% and 78.6%, respectively). CONCLUSIONS: Our finding of increased kurtosis of quantitative susceptibility mapping values (heavy-tailed distribution) was highly specific, suggesting that it may be a useful biomarker to identify putative epileptogenic tubers in tuberous sclerosis complex. This finding motivates the investigation of underlying tuber mineralization and other properties driving kurtosis changes in quantitative susceptibility mapping values.

The effect of the classical and medium chain triglyceride ketogenic diet on vitamin and mineral levels.

BACKGROUND: The risk of nutritional deficiency in children on restrictive dietary treatments and a lack of ketogenic diet (KD)-specific UK supplements raises concerns about micronutrient status. Vitamin A, E, zinc, selenium and magnesium levels were therefore examined in children with intractable epilepsy treated with the KD. METHODS: Plasma vitamins A and E, zinc, selenium and magnesium levels were measured at baseline and after 3, 6 and 12months on the classical (n=46) or medium chain triglyceride (MCT) (n=45) KD in children aged 2-16years, as part of a randomised trial, and pairwise comparisons with baseline were performed. RESULTS: Data were available from 91 children. From baseline to 12months, mean plasma vitamin A decreased from 1.41µmol L(-1) to 1.13µmol L(-1) in the classical group (P<0.001) but increased from 1.52µmol L(-1) to 1.81µmol L(-1) in the MCT group (P<0.001). Mean plasma vitamin E increased from 22.7µmol L(-1) to 33.2µmol L(-1) in the classical group (P<0.001) and from 22.3 µmol L(-1) to 23.3µmol L(-1) in the MCT group (P<0.05). No significant change in plasma zinc was seen at 12months, although mean plasma selenium decreased from 0.95µmol L(-1) to 0.88µmol L(-1) in the group as a whole (P<0.05). Mean plasma magnesium decreased from 0.87mmol L(-1) to 0.83mmol L(-1) in the group as a whole (P<0.001); when subdivided by KD type, this was limited to the classical group. CONCLUSIONS: Changes in plasma vitamins A and E and the decline in magnesium status after 12months of KD treatment suggest that micronutrient status may be suboptimal in this group and that available formulations for KD supplementation may need reviewing.

A role for sleep disruption in cognitive impairment in children with epilepsy.

Early-onset epilepsy is associated with a poor cognitive outcome, with the cumulative burden of both ictal and interictal epileptiform discharges likely to contribute significantly. Memory consolidation has been shown to occur during sleep in healthy children, with an associated electroencephalographic signature. This may be disrupted in children with epilepsy, who exhibit a high incidence of sleep disorders, whether directly related to their seizures or as a comorbidity. Conversely, seizure semiology may be influenced by sleep. In this review we present clinical and experimental evidence that suggests that the disruption of sleep architecture by epileptiform discharges may be an important factor contributing to cognitive impairment in children with epilepsy.

Dietary Management of Children With Super-Refractory Status Epilepticus: A Systematic Review and Experience in a Single UK Tertiary Centre.

Ketogenic diet therapies (KDT) are high-fat, low carbohydrate diets used as an effective treatment option for drug-resistant epilepsy. There is limited research on the efficacy of KDT for super-refractory status epilepticus (SRSE). We systematically review evidence for use of KDT in children with SRSE and present a single UK tertiary centre's experience. Thirty one articles were included, of which 24 were "medium" or "low" quality. One hundred and forty seven children with SRSE started KDT, of which 141 (96%) achieved ketosis. KDT was started mean 5.3 days (range 1-420) after status epilepticus (SE) started. SRSE resolved in 85/141 (60%) children after mean 6.3 days (range 0-19) post SE onset, but it is unclear whether further treatments were initiated post-KDT. 13/141 (9%) children died. Response to KDT was more likely when initiated earlier (p = 0.03) and in females (p = 0.01). Adverse side effects were reported in 48/141 (34%), mostly gastrointestinal; potentially serious adverse effects occurred in ≤4%. Eight children with SRSE, all diagnosed with febrile infection-related epilepsy syndrome, were treated with KDT at Great Ormond Street Hospital for Children. KDT was initiated enterally at mean day 13.6+/- 5.1 of admission. Seven of 8 (88%) children reported adverse side effects, which were potentially serious in 4/8 (50%), including metabolic acidosis, hypoglycaemia and raised amylase. SE ceased in 6/8 (75%) children after mean 25+/- 9.4 days post onset, but other treatments were often started concomitantly and all children started other treatments post-KDT. Two of 8 (25%) children died during admission and another died post-admission. Four of the remaining 5 children continue to have drug-resistant seizures, one of whom remains on KDT; seizure burden was unknown for one child. Our findings indicate that KDT is possible and safe in children with SRSE. Cessation of SRSE may occur in almost two-thirds of children initiated with KDT, but a causal effect is difficult to determine due to concomitant treatments, treatments started post-KDT and the variable length of time post-KDT onset when SRSE cessation occurs. Given that serious adverse side effects seem rare and response rates are (cautiously) favorable, KDT should be considered as an early treatment option in this group.

The impact of COVID-19 on epilepsy care: Perspectives from UK healthcare workers.

The COVID-19 pandemic has created an immense pressure on healthcare providers, resulting in a shift to remote consultations and the redeployment of healthcare workers (HCWs). We present survey data from the United Kingdom (UK) HCWs to outline how changes in healthcare provision impact clinicians' wellbeing and ability to provide adequate care. We designed an online survey to gather the experiences of HCWs providing care to people with epilepsy. We received seventy-nine responses from UK-based HCWs, of whom 43% reported an impact on their mental health. Changes to service delivery have resulted in 71% of clinicians performing > 75% of their consultations remotely. Diagnosing and treating epilepsy has changed, with a fifth of respondents being significantly less confident in diagnosing epilepsy. Ultimately, these results show that COVID-19 has had an overall negative impact on HCWs and their ability to provide epilepsy care. These results must be considered when reorganizing health services to ensure optimal outcomes for people with epilepsy.

Efficacy of dietary treatments for epilepsy.

The ketogenic diet (KD) is a high fat, restricted carbohydrate regime that has been used as a treatment for seizures since the 1920s, when it was designed to induce a similar metabolic response to fasting. A modification of this early classical version of the KD was introduced in the 1970s using medium chain triglycerides as an alternative fat source. More recently, two alternative, less-restrictive dietary treatments have been developed: the modified Atkins diet and the low glycaemic index diet. There are many case reports and observational studies reporting successful use of the KD, and a growing number of studies reporting similar success with the modified Atkins protocol. A recent randomised controlled trial has shown a significant benefit of the KD compared to no change in treatment. The use of these dietary therapies in the UK is supported by literature evidence, although often is limited by a lack of resources; increasing awareness and knowledge is fundamental to ensure availability for those individuals with intractable epilepsy who may benefit from them.

Transovarial transmission of Japanese encephalitis virus by mosquitoes.

Female Aedes albopictus and Aedes togoi mosquitoes infected with Japanese encephalitis virus either by intrathoracic inoculation or by ingestion of a virus-sucrose-erythrocyte mixture transmitted the virus to a small percentage of their F1 progeny. Adult F1 female Aedes albopictus thus infected transmitted the virus in turn to newly hatched chickens by feeding on them.

An investigation of the expression of G1-phase cell cycle proteins in focal cortical dysplasia type IIB.

Balloon cells (BCs) are the pathologic hallmark of focal cortical dysplasia type IIB, a common cause of pharmacoresistent epilepsy. Expression of markers of cell immaturity and of the proliferation marker minichromosome maintenance protein 2 (mcm2) have been previously shown in BCs, suggesting that these cells might represent a pool of less-differentiated cells licensed for replication. An alternative explanation is that these cells are the remnants of early cortical plate cells that have failed to differentiate or to be eliminated during development and are arrested in the cell cycle, a hypothesis that this study aims to explore. Using immunohistochemical methods and semiquantitative analysis in 19 cases of focal cortical dysplasia (ages 1-81 years), we studied the expression of cell cycle proteins important either in regulating progression through the G1 phase or inducing cell arrest and promoting premature senescence. Only a small fraction of BCs expressed geminin, suggesting that few BCs enter the S phase or complete the cell cycle. Variable expression of nonphosphorylated retinoblastoma protein (Rb), cdk4, and p53 was noted in BCs. Cyclin E, D1, cdk2, phosphorylated Rb (795 and 807/811), and checkpoint 2 expression levels were low in BCs. These findings suggest early rather than late G1 arrest. Cell senescence could be induced by an undefined cerebral insult during development or alternatively represent a physiologic replicative senescence. These findings also suggest that dysregulation of cell cycle pathways may occur in focal cortical dysplasia, which opens further areas for exploration as potential new treatment avenues.

Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement.

Rasmussen encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patients.

Definition and diagnostic criteria of sleep-related hypermotor epilepsy.

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis.

1H magnetic resonance spectroscopy in the investigation of intractable epilepsy.

We have been using proton magnetic resonance spectroscopy (1H MRS) in the investigation of adults and children with intractable epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the epilepsy patients as a group show significant reductions in the NAA signal and in the NAA/Cho+Cr ratio, with increases in the Cho and Cr signals. The reduction in NAA is interpreted in terms of neuronal loss or damage, while the increase in Cr and Cho signals may be a reflection of reactive astrocytosis.

Functional magnetic resonance imaging of focal seizures.

Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. We aimed to establish whether this noninvasive technique could also map the cortical activation that occurs during focal seizures. In order to do this, we used a conventional 1.5-tesla clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. We acquired FLASH images (TE = 60 msec) every 10 seconds over intervals of 10 minutes and derived activation images by subtracting baseline images from images obtained during clinical seizures. Functional MRI revealed sequential activation associated with specific gyri within the left hemisphere with each of five consecutive clinical seizures, and also during a period that was not associated with a detectable clinical seizure. The activated regions included gyri that were structurally abnormal. We concluded that functional MRI can provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure.

Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy.

We used proton magnetic resonance spectroscopy (1H MRS) for the assessment of focal brain pathology in 22 right-handed children with a diagnosis of intractable temporal lobe epilepsy, and we related this pathology to cognitive dysfunction. Cognitive assessment was based on measurements of verbal IQ, performance IQ, and the Paired Associate Learning subtest of the Wechsler Memory Scale. Five of the 22 children showed no abnormalities of the temporal lobes on 1H MRS, seven showed unilateral pathology, and 10 showed bilateral abnormalities. We found that left-sided pathology is associated with a loss of verbal cognitive functions, whereas right-sided pathology is associated with a loss of nonverbal functions. These findings are consistent with the pattern of lateralization of brain function that has been observed in adults.

Quantitative magnetic resonance characterization of mesial temporal sclerosis in childhood.

OBJECTIVE: To investigate whether quantitative MR techniques can be used to distinguish between mesial temporal sclerosis in patients with a history of prolonged febrile convulsion and in patients without such a history. METHODS: Quantitative hippocampal T2 relaxometry, hippocampal volumetry, and single voxel (1)H-MRS data were acquired from 16 children who subsequently underwent temporal lobe resections for intractable temporal lobe epilepsy and histologically were shown to have sclerosis of the horn of Ammon. Eight children had a history of prolonged febrile convulsion in early childhood and eight children had other or no associations. RESULTS: Patients with a history of prolonged febrile convulsion had smaller hippocampi (p = 0.02) and prolonged T2 relaxation time (p = 0.03) ipsilateral to the seizure focus when compared with patients without such a history. There was also more side-to-side asymmetry of T2 relaxation time (p = 0.004) and hippocampal volume (p = 0.02) in the patients with a history of prolonged febrile convulsion than in those with other or no associations. No differences between the groups were identified using (1)H-MRS. CONCLUSIONS: These data support the view that there are at least two types of mesial temporal sclerosis. There may be several pathogenetic pathways from initial insult to later mesial temporal sclerosis, and these pathways are, at least in part, dependent on the initial insult.

Resuscitation of pulmonary contusion: hypertonic saline is not beneficial.

We postulated that hypertonic solutions could minimize the accumulation of lung water and subsequent respiratory derangements that occur after pulmonary contusion. Anesthetized pigs underwent contusion of the right chest at baseline and then were hemorrhaged (30 cc/kg) over 20 min. They were resuscitated with either 7.5% NaCl (4 cc/kg) or .9% saline (90 cc/kg) for 20 min and observed for 4 h. Gravimetric lung weights and spiral computed tomography scans were used to quantitate lung water. The hemodynamic response to contusion and hemorrhage was similar in both resuscitation groups. Arterial oxygen tension was not significantly altered by the method of resuscitation and remained close to baseline values for the entirety of the experiment. Static compliance measurements were significantly decreased from baseline in both groups following pulmonary contusion. There were no differences in wet to dry lung weights or computed tomography scan injury volume between groups. We conclude that small volume hypertonic saline resuscitation does not reduce the magnitude of lung injury or provide substantial physiologic benefit over isotonic solutions following pulmonary contusion.

Toxoplasmosis in man and animals in South Kalimantan (Borneo), Indonesia.

Sera from 1,050 persons, 69 cats, 18 goats, 23 bovines, 2 monkeys, and 1 dog from 7 villages in South Kalimantan were tested for indirect hemagglutination Toxoplasma gondii antibodies. A seroepidemiologic study with the methylene blue dye test was conducted 1 year later at one village among 25 families and their cats. Toxoplasma antibody prevalence in man in different villages varied from 9.7% to 51.0%. Forty-one percent of the cats and 61% of the goats also had positive titers. None of the bovines was positive. The epidemiologic study indicated that, in spite of the presence of many infected cats in the village, goat meat was a significant source of Toxoplasma infection for man in this population.

Nonresolution of an amebic liver abscess after parasitologic cure.

A 43-year-old Filipino male was admitted to a Manila hospital with a 1 month history of epigastric pain and fever, and was found to have a palpable epigastric mass. Computerized tomography revealed a large hepatic abscess which serologically was shown to be amebic. Chemotherapy resulted in clinical cure and an initial reduction in size of the liver abscess. However, resolution of the abscess cavity did not occur, and on closed needle aspiration, 80 cc of characteristic amebic pus was recovered. Parasitological cure without complete repair of the abscess cavity itself raises questions concerning the potential danger of clinically silent residua and the role of therapeutic aspiration in the management of amebic liver abscesses.

Counterimmunoelectrophoresis in the detection of antibodies to Schistosoma japonicum.

Counterimmunoelectrophoresis (CIE) was used to detect antibodies to Schistosoma japonicum soluble egg antigen in 118 sera from people living in a schistosomiasis endemic area in the Philippines. The sera were also tested for antibodies by the circumoval precipitin test (COPT); 53% were found positive by CIE and 48% positive by COPT. No significant differences were found between the tests (P = 0.18 by McNemar's test). Cross-reactions with sera from patients with intestinal capillariasis and monkeys with experimental angiostrongyliasis were not found and no false reactions were detected with sera from "normal" controls. The CIE test as used in the present studies was found to be comparable to the COPT in sensitivity and specificity as related to cross-reactivity with sera from nematode infections such as intestinal capillariasis and angiostrongyliasis. Results are usually available quickly with nearly 70% of any reactions occurring within 1 h. The test should be of value in seroepidemiologic surveys in schistosomiasis-endemic areas.