Critical incidents, nocturnal supervision, and caregiver knowledge on SUDEP in patients with Dravet syndrome: A prospective multicenter study in Germany.

OBJECTIVE: The aim was to investigate the monitoring, interventions, and occurrence of critical, potentially life-threatening incidents in patients with Dravet syndrome (DS) and caregivers' knowledge about sudden unexpected death in epilepsy (SUDEP). METHODS: This multicenter, cross-sectional study of patients with DS and their caregivers in Germany consisted of a questionnaire and prospective diary querying the disease characteristics and demographic data of patients and caregivers. RESULTS: Our analysis included 108 questionnaires and 82 diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 (SD ± 10.0 years) and primary caregivers were 92.6% (n = 100) female, with a mean age of 44.7 (SD ± 10.6 years). Monitoring devices were used regularly by 75.9% (n = 82) of caregivers, and most monitored daily/nightly. Frequently used devices were pulse oximeters (64.6%), baby monitors (64.6%), thermometers (24.1%), and Epi-Care (26.8%). Younger caregiver and patient age and history of status epilepticus were associated with increased use of monitoring, and 81% of monitor users reported having avoided a critical incident with nocturnal monitoring. The need for resuscitation due to cardiac or respiratory arrest was reported by 22 caregivers (20.4%), and most cases (72.7%) were associated with a seizure. Caregivers reported frequently performing interventions at night, including oropharyngeal suction, oxygenation, personal hygiene, and change of body position. Most caregivers were well informed about SUDEP (n = 102; 94%) and monitored for a lateral or supine body position; however, only 39.8% reported receiving resuscitation training, whereas 52.8% (n = 57) knew what to do in case the child's breathing or heart activity failed. SIGNIFICANCE: Critical incidents and the need for resuscitation are reported frequently by caregivers and may be related to high mortality and SUDEP rates in DS. Resuscitation training is welcomed by caregivers and should be continuously provided. Oxygen monitoring devices are frequently used and considered useful by caregivers.

Bilateral Foramina Parietalia Permagna - A Calvarial Defect Caused by Haploinsufficiency of the Msh Homeobox 2 Gene: A Case Report and Current Literature Review.

Foramina parietalia permagna (FPP) is a rare anatomical defect that affects the parietal bones of the human skull. FPP is characterized by symmetric perforations on either side of the skull, which are caused by insufficient ossification during embryogenesis. These openings are typically abnormally large and can range from a few millimeters to several centimeters in diameter. Enlarged foramina are often discovered incidentally during anatomical or radiological examinations and in most cases left untreated unless symptoms develop. Although this calvarial defect is usually asymptomatic, it may be accompanied by neurological or vascular conditions that can have clinical significance in certain cases. FPP is an inherited disorder and arises due to mutations in either Msh homeobox 2 (MSX2) or aristaless-like homeobox 4 (ALX4) genes. In almost all cases, one parent is affected. Clinical findings and diagnostic imaging typically contribute to determine the diagnosis.

Consultation Requests and Satisfaction with a Telehealth Network for Epilepsy: Longitudinal Analysis of the Epilepsy Network Hessen Evaluation.

Background: Telemedicine improves access to specialized medical expertise, as required for paroxysmal disorders. The Epilepsy Network Hessen Evaluation (ENHE) is a pilot cross-sectoral teleconsultation network connecting primary neurologists and pediatricians with epilepsy centers in Hessen, a federal German state. Methods: We prospectively and longitudinally evaluated telehealthcare in the ENHE. Participating physicians rated each consultation for satisfaction and impact on further management. The survey was administered at each consultation and 3 months later. Results: We analyzed 129 consultations involving 114 adult and pediatric patients. Their mean age was 34 years (standard deviation: 26, range: 0.1-91 years), 48% were female, and 34% were children and adolescents. The most common consultation requests were co-evaluation of an electroencephalogram (electroencephalogram [EEG]; 76%) and therapeutic (33%) and differential diagnosis (24%) concerns. Physicians transmitted one paraclinical examination on average (range: 1-4), predominantly EEG (85%), followed by magnetic resonance imaging (17%) and written records (9%). Response rates were 72% for the initial and 67% for the follow-up survey. Across respondents, 99% (n = 92) were satisfied with the ENHE. Overall, 80% of the consultations contributed to the diagnosis, and 90% were considered helpful for treatment, influencing it in 71% of cases. Seizure frequency had decreased more often (96%) than increased (4%) at 3 months. The initial diagnosis was confirmed in 78% of patients. Discussion: In this pilot teleconsultation network for paroxysmal disorders, diagnostic and therapeutic advice was perceived as helpful. Clinical outcomes were largely positive, suggesting tele-epileptology is viable for paroxysmal (seizure) disorders.

Perampanel as precision therapy in rare genetic epilepsies.

OBJECTIVE: Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g., SCN1A), overactive excitatory neurons (e.g., SCN2A, SCN8A), and variants in glutamate receptors (e.g., GRIN2A) hold special interest. We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy. METHODS: This multicenter project was based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel were collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified. RESULTS: A total of 137 patients with 79 different etiologies, aged 2 months to 61 years (mean = 15.48 ± 9.9 years), were enrolled. The mean dosage was 6.45 ± 2.47 mg, and treatment period was 2.0 ± 1.78 years (1.5 months-8 years). Sixty-two patients (44.9%) were treated for >2 years. Ninety-eight patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61% ± 34.36%. Sixty patients (43.5%) sustained >75% reduction in seizure frequency, including 38 (27.5%) with >90% reduction in seizure frequency. The following genes showed high treatment efficacy: SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, and NEU1. Eleven of 17 (64.7%) patients with Dravet syndrome due to an SCN1A pathogenic variant were responders to perampanel treatment; 35.3% of them had >90% seizure reduction. Other etiologies remarkable for >90% reduction in seizures were GNAO1 and PIGA. Fourteen patients had a continuous spike and wave during sleep electroencephalographic pattern, and in six subjects perampanel reduced epileptiform activity. SIGNIFICANCE: Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1, and POLG, suggesting a targeted effect related to glutamate transmission.

No role for electroencephalogram in the initial work-up of pediatric acute lymphoblastic leukemia.

PURPOSE: The purpose of this study was to verify whether there is a prognostic benefit of electroencephalogram (EEG) performed during initial work-up of children with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: In this retrospective monocenter study, we analyzed the value of electroencephalogram (EEG) performed during initial work-up of children with newly diagnosed acute lymphoblastic leukemia (ALL). All pediatric patients were included in this study who were diagnosed with de novo ALL in our institution between January 1, 2005, and December 31, 2018, and in whom an EEG was performed for initial work-up within 30 days of diagnosis of ALL. EEG findings were associated with the occurrence and the etiology of neurologic complications occurring during intensive chemotherapy. RESULTS: Out of 242 children, EEG revealed pathological findings in 6 patients. Two of them developed a seizure at a later time point due to adverse effects of chemotherapy, whereas 4 children had an uneventful clinical course. In contrast, 18 patients with normal initial EEG findings developed seizures during therapy for different reasons. CONCLUSION: We conclude that routine EEG does not predict seizure susceptibility in children with newly diagnosed ALL and is unnecessary in the initial work-up as EEG investigation in young and often sick children requires sleep deprivation and/or sedation, and our data demonstrate no benefit in predicting neurological complications.

Use of Health-Related Apps and Telehealth in Adults with Epilepsy in Germany: A Multicenter Cohort Study.

Background: Telehealth can improve the treatment of chronic disorders, such as epilepsy. Telehealth prevalence and use increased during the coronavirus disease 2019 (COVID-19) pandemic. However, familiarity with and use of telehealth and health-related mobile applications (apps) by persons with epilepsy remain unknown. Methods: We investigated telehealth use, demographics, and clinical variables within the multicenter Epi2020 cross-sectional study. Between October and December 2020, adults with epilepsy completed a validated questionnaire, including individual questions regarding knowledge and use of apps and telehealth. Results: Of 476 included individuals (58.2% women; mean age 40.2 ± 15.4 years), 41.6% reported using health-related apps. Health apps were used more frequently (pedometer 32.1%, exercise app 17.6%) than medical apps (health insurance 15.1%, menstrual apps 12.2%) or apps designed for epilepsy (medication reminders 10.3%, seizure calendars 4.6%). Few used seizure detectors (i.e., apps as medical devices 1.9%) or mobile health devices (fitness bracelet 11.3%). A majority (60.9%) had heard the term telehealth, 78.6% of whom had a positive view. However, only 28.6% had a concrete idea of telehealth, and only 16.6% reported personal experience with telehealth. A majority (55%) would attend a teleconsultation follow-up, and 41.2% would in a medical emergency. Data privacy and availability were considered equally important by 50.8%, 21.8% considered data privacy more important, and 20.2% considered data availability more important. Current health-related app use was independently associated with younger age (p = 0.003), higher education (p < 0.001), and subjective COVID-19-related challenges (p = 0.002). Persistent seizure occurrence (vs. seizure freedom ≥12 months) did not affect willingness to use teleconsultations on multivariable logistic regression analysis. Conclusions: Despite positive telehealth views, few persons with epilepsy in Germany are familiar with specific apps or services. Socioeconomic factors influence telehealth use more than baseline epilepsy characteristics. Telehealth education and services should target socioeconomically disadvantaged individuals to reduce the digital care gap. German Clinical Trials Register (DRKS00022024; Universal Trial Number: U1111-1252-5331).

Local glucose metabolism is unaltered in reversible splenial lesion syndrome.

BACKGROUND AND PURPOSE: Transient splenial oedema, also known as reversible splenial lesion syndrome (RESLES), is a rare magnetic resonance imaging (MRI) finding that presents as a round or ovoid focal oedema in the posterior corpus callosum, and is associated with a wide range of clinical conditions. The aetiology of RESLES is not fully clear. We aimed to investigate conflicting pathophysiological hypotheses by measuring local glucose metabolism in patients with RESLES. METHODS: We retrospectively analysed patients with RESLES after reductions in antiseizure medications during in-hospital video electroencephalography monitoring. We measured local glucose uptake using positron emission tomography/computed tomography and compared matched cohorts of patients with and without MRI evidence of RESLES using nonparametric tests. RESULTS: Local glucose metabolism in the splenium of seven patients with RESLES was not significantly different from the glucose metabolism of the seven patients in the matched cohort. This was true using both regular and normalized standardized glucose uptake value calculation methods (p = 0.902 and p = 0.535, respectively). CONCLUSION: We found no evidence of local glucose hypometabolism in RESLES, which supports previous pathophysiological considerations that suggest that RESLES is an intercellular, intramyelinic oedema rather than a typical intracellular cytotoxic oedema, which is not reversible.

Epidemiology, healthcare resource use, and mortality in patients with probable Dravet syndrome: A population-based study on German health insurance data.

OBJECTIVE: Ten-year retrospective study to assess burden of illness in patients with probable Dravet syndrome (DS) identified from German healthcare data. METHODS: In the absence of an International Classification of Diseases code, patients with probable DS were identified using a selection algorithm considering diagnoses and drug prescriptions. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, annual hospitalization rate (AHR) and length of stay (LOS), medication use, and mortality. RESULTS: In the final study year, 64 patients with probable DS (mean [range] age: 33.2 [3-82] years; male: 48%) were identified. Prevalence: 4.7 per 100,000 people. During the study, 160 patients with probable DS were identified and followed up for 1,261 patient-years. Mean cost of healthcare was €11,048 per patient-year (PPY), mostly attributable to inpatient care (47%), medication (26%), and services and devices (19%). Annual healthcare costs were significantly greater for those with prescribed rescue medication (15% of patient-years) vs. without (€16,123 vs. €10,125 PPY, p < 0.001). Mean (standard deviation [SD]) AHR and LOS were 1.1 (1.7) and 17.5 (33.5) days PPY. AHR was significantly greater in patients with prescribed rescue medication vs. without (1.6 [2.0] vs. 1.0 [1.6] PPY, p < 0.001). Mean (SD) number of antiseizure medications prescribed was 2.6 (1.2) PPY and 5.0 (2.5) over the entire observable time for each patient. Mortality rate was significantly higher for probable DS vs. matched controls (11.88% [19 events] vs. 1.19% [172 events], p < 0.001). CONCLUSION: Probable DS is associated with substantial healthcare costs in Germany.

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.

OBJECTIVE: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy. METHODS: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management. RESULTS: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%). SIGNIFICANCE: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.

Long-term efficacy, tolerability, and retention of brivaracetam in epilepsy treatment: A longitudinal multicenter study with up to 5 years of follow-up.

OBJECTIVE: This study was undertaken to evaluate the long-term efficacy, retention, and tolerability of add-on brivaracetam (BRV) in clinical practice. METHODS: A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021. RESULTS: Long-term data for 262 patients (mean age = 40 years, range = 5-81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost-to-follow-up), including 10.9% reported as seizure-free. The retention rate for the entire study period was 50.8%, and at last follow-up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25-400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short-term responses, but no investigated parameters correlated with positive long-term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons. SIGNIFICANCE: BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short-term response and retention predictors, we could not identify significant predictors for long-term outcomes.

Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany.

OBJECTIVE: Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP). METHODS: We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add-on therapy with oral FFA gradually titrated to a target dose between .13 and .7 mg/kg/day. RESULTS: Overall, 78 patients with DS (median age = 8.0 years, range = 2.1-46.0; 53% female, median concomitant antiseizure medications [ASMs] = 3) were treated with FFA for a median duration of 255.5 days (range = 31-572). Responder rates (a ≥50% reduction; n = 78) and seizure-freedom rates at 3 months were 68% and 14% for total seizures, respectively, and 67% and 23% for generalized tonic-clonic seizures. Responder rates were consistent at 6 and 12 months (n = 66 and n = 43, respectively). Median seizure days per month significantly decreased from 10.0 (range = .5-30) to 3.0 (range = 0-30) in the 3-month period before and after FFA treatment (p < .001). Significantly fewer patients reported at least one episode of status epilepticus (28% vs. 14% patients before and after FFA initiation, p = .005). During FFA treatment, 35 (45%) patients were able to discontinue a concomitant ASM. At the last follow-up date, 66 (85%) patients remained on treatment with FFA. The most common adverse events were somnolence (36%), decreased appetite (22%), and ataxia (8%). Forty-eight (62%) patients were reported as having a meaningful global clinical improvement. SIGNIFICANCE: In a large cohort of patients, FFA demonstrated efficacy across a range of outcomes including clinically significant reductions in convulsive seizures, and was well tolerated, providing valuable information for real-world practice.

Epidemiology, healthcare resource use, and mortality in patients with probable Lennox-Gastaut syndrome: A population-based study on German health insurance data.

OBJECTIVE: This retrospective study examined patients with probable Lennox-Gastaut syndrome (LGS) identified from German healthcare data. METHODS: This 10-year study (2007-2016) assessed healthcare insurance claims information from the Vilua Healthcare research database. A selection algorithm considering diagnoses and drug prescriptions identified patients with probable LGS. To increase the sensitivity of the identification algorithm, two populations were defined: all patients with probable LGS (broadly defined) and only those with a documented epilepsy diagnosis before 6 years of age (narrowly defined). This specific criterion was used as LGS typically has a peak seizure onset between age 3 and 5 years. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, hospitalization rate and length of stay (LOS), medication use, and mortality. RESULTS: In the final year of the study, 545 patients with broadly defined probable LGS (mean [range] age: 31.4 [2-89] years; male: 53%) were identified. Using the narrowly defined probable LGS definition, the number of patients was reduced to 102 (mean [range] age: 7.4 [2-14] years; male: 52%). Prevalence of broadly defined and narrowly defined probable LGS was 39.2 and 6.5 per 100,000 people. During the 10-year study, 208 patients with narrowly defined probable LGS were identified and followed up for 1379 patient-years. The mean annual cost of healthcare was €22,787 per patient-year (PPY); greatest costs were attributable to inpatient care (33%), home nursing care (13%), and medication (10%). Mean annual healthcare costs were significantly greater for those with prescribed rescue medication (45% of patient-years) versus those without (€33,872 vs. €13,785 PPY, p < 0.001). Mean (standard deviation [SD]) annual hospitalization rate was 1.6 (2.0) PPY with mean (SD) annual LOS of 22.7 (46.0) days. Annual hospitalization rate was significantly greater in those who were prescribed rescue medication versus those who were not (2.2 [2.3] vs. 1.1 [1.6] PPY, p < 0.001). The mean (SD) number of different medications prescribed was 11.3 (7.3) PPY and 33.8 (17.0) over the entire observable time per patient (OET); antiepileptic drugs only accounted for 2.1 (1.1) of the medications prescribed PPY and 3.8 (2.0) OET. Over the 10-year study period, mortality in patients with narrowly defined probable LGS was significantly higher than the matched control population (six events [2.88%] vs. oneevent [0.01%], p < 0.001). CONCLUSION: Annual healthcare costs incurred by patients with probable LGS in Germany were substantial, and mostly attributable to inpatient care, home nursing care, and medication. Patients prescribed with rescue medication incurred significantly greater costs than those who were not. Patients with narrowly defined probable LGS had a higher mortality rate versus control populations.

Postoperative outcomes and surgical ratio at a newly established epilepsy center: The first 100 procedures.

PURPOSE: To describe the patients' characteristics, surgical ratio, and outcomes following epilepsy surgery at the newly established Epilepsy Center Frankfurt Rhine-Main. METHODS: We retrospectively studied the first 100 consecutive patients, including adult (n = 77) and pediatric (n = 23) patients, with drug-resistant epilepsy who underwent resective or ablative surgical procedures at a single, newly established epilepsy center. Patient characteristics, seizure and neuropsychological outcomes, histopathology, complications, and surgical ratio were analyzed. RESULTS: The mean patient age was 28.8 years (children 10.6 years, adults 34.2 years). The mean epilepsy duration was 11.9 years (children 3.9 years, adults 14.3 years), and the mean follow-up was 1.5 years. At the most recent visit, 64% of patients remained completely seizure free [Engel IA]. The rates of perioperative complications and unexpected new neurological deficits were 5%, each. The proportion of patients showing deficits in one or more cognitive domains increased six months after surgery and decreased to presurgical proportions after two years. Symptoms of depression were significantly decreased and quality of life was significantly increased after surgery. The surgical ratio was 25.3%. CONCLUSION: Similar postsurgical outcomes were achieved at a newly established epilepsy center compared with long-standing epilepsy centers. The lower time to surgery may reflect a general decrease in time to surgery over the last decade or the improved accessibility of a new epilepsy center in a previously underserved area. The surgical ratio was not lower than reported for established centers.

Expectations and knowledge of cannabidiol therapy for childhood epilepsy - A German caregiver survey.

BACKGROUND: Cannabidiol (CBD) has gained popularity among parents of children with epilepsy, even before evidence of efficacy and safety was available. The aim of our survey was to gain information about parental attitude to CBD, as well as expectations and knowledge of CBD for treatment of their child's epilepsy. METHODS: A survey using an open-access online questionnaire for parents or caregivers of children with epilepsy within German-speaking countries from March to June 2019 was used. RESULTS: Of 378 complete questionnaires (mean age of children: 11.1 (standard deviation [SD] 7.4) years), 28% (n = 106) reported previous or current CBD treatment over a mean time of 17.31 months (SD: 19.74), whereas 72% had no personal experience with CBD. Treatment was proposed by parents and not by physicians in 83% of cases and was mainly carried out with prescription-only products (71%, n = 67). Nevertheless, 29% used unregulated, artisanal products. Of all parents with previous experience, n = 77 (73%) reported that they expected CBD to be more efficient than the common antiseizure drugs (ASDs) at the beginning. Forty-five percent reported that their expectations were not met during therapy. Consistently, lack of seizure reduction was the most common reason to discontinue CBD (12/26). Of those responders without CBD experience, 93% would consider CBD for their child. However, the self-reported level of information was considered to be poor or very poor regarding efficacy (76%, n = 177), tolerance (83%, n = 191), interaction with other medication (91%, n = 211), and potential long-term effects (87%, n = 212). CONCLUSIONS: There is a huge interest in CBD but includes potentially unrealistic expectations of its efficacy and tolerance combined with a low level of information. Neuropediatricians should address parents of children with epilepsy regarding potential motivation and expectations of CBD. In addition, parental education, especially on interactions and potential side effects, is strongly recommended.

Advantages of methohexital over amobarbital in determining hemispheric language and memory lateralization in the Wada test - A retrospective study.

OBJECTIVE: Due to supply shortage, amobarbital, the traditional anesthetic agent in Wada testing, was replaced by methohexital in many epilepsy centers. This study aimed to compare the two barbiturates to identify possible advantages or disadvantages of methohexital as compared to amobarbital with regard to the adequacy of language and memory testing during the Wada test. METHODS: Data from 75 patients with temporal lobe epilepsy who underwent bilateral Wada tests using either amobarbital (n = 53) or methohexital (n = 22) as part of presurgical work-up were analyzed retrospectively. The two subgroups were compared regarding hemispheric language and memory lateralization results and Wada testing characteristics, and the adequacy of language and memory testing was assessed. RESULTS: We observed shorter durations of motor-, speech-, and EEG recovery after each injection in patients receiving methohexital compared to amobarbital. In addition, significantly more items could be presented during effective hemispheric inactivation in the methohexital group. Moreover, significant correlations of Wada memory scores with standard neuropsychological memory test scores could be found in the methohexital group. SIGNIFICANCE: Our findings confirm that methohexital is not only equally suitable for Wada testing but has several advantages over amobarbital. Wada testing can be performed more efficiently and under more constant hemispheric inactivation using methohexital. Furthermore, the adequacy of language and memory testing during the Wada test might be affected by the anesthetic agent used.

First clinical experience with the new noninvasive transfontanelle ICP monitoring device in management of children with premature IVH.

We previously introduced a novel noninvasive technique of intracranial pressure (ICP) monitoring in children with open fontanelles. Within this study, we describe the first clinical implementation and results of this new technique in management of children with hydrocephalus caused by intraventricular hemorrhage (IVH). In neonates with posthemorrhagic hydrocephalus (PHH), an Ommaya reservoir was implanted for initial treatment of hydrocephalus. The ICP obtained noninvasively with our new device was measured before and after CSF removal and correlated to cranial ultra-sonographies. Six children with a mean age of 27.3 weeks and mean weight of 1082.3 g suffering from PHH were included in this study. We performed an overall of 30 aspirations due to ventricular enlargement. Before CSF removal, the mean ICP was 15.3 mmHg and after removal of CSF the mean ICP measured noninvasively decreased to 3.4 mmHg, p = 0.0001. The anterior horn width (AHW), which reflects early expansion of the ventricles, was before and after CSF removal 15.1 mm and 5.5 mm, respectively, p < 0.0006. There was a strong correlation between noninvasively measured ICP values and sonographically obtained AHW, r = 0.81. Ultimately, all children underwent ventriculoperitoneal shunt procedures. This is the first study providing proof for a noninvasively ICP-based approach for management of posthemorrhagic hydrocephalus in newborn children.

Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population-based study on German health insurance data.

OBJECTIVE: Status epilepticus (SE) is an important medical emergency condition with particularly unfavorable outcome in refractory and superrefractory SE (SRSE). The economic impact of SE and especially of SRSE in the pediatric population remains unclear. We aimed to determine the burden of illness of SE in a pediatric patient population. METHODS: Insurance records for patients aged 0-18 years admitted between 2008 and 2015 were selected from a nationwide insurance research database utilizing International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes for SE (G41), epilepsy (G40), or febrile convulsions (R56). Patients were further classified based on admission to the intensive care unit and use of mechanical ventilation. RESULTS: The algorithm identified 11 693 seizure-related admissions and classified 4% as SE. Of these cases, 282 (60.4%) were classified by the algorithm as nonrefractory SE (NRSE), 125 (26.8%) as refractory SE (RSE), and 60 (12.8%) as SRSE. The crude SE incidence was 17.6/100 000, with NRSE being 11.4/100 000, RSE 3.9/100 000, and SRSE 2.3/100 000. SRSE incidence peaked in the 0- to 1-year-old age subgroup accounting for 48.3% of all pediatric SRSE admissions. The median length of stay (LOS) for all SE cases was 7 days, with median 44.5 days in SRSE, 5 days in NRSE, and 12 days in RSE. Mean admission costs for total SE were €15 880, with a mean expense for SRSE of €75 358, for NRSE of €4119, and for RSE of €13 864. The mean LOS for non-SE epilepsy admissions was 3 days, with mean costs of €2697 for epilepsy and €1614 for febrile convulsion admissions. There were no deaths in non-SE and NRSE admissions, whereas the overall mortality for SE was 3%, with 5.6% in RSE and 11.7% in SRSE. SIGNIFICANCE: Although cases classified as SE represented 4% of the seizure-associated admissions, they accounted for 22% of the overall costs. These costs were disproportionately represented by SRSE cases, which accounted for 62% of all SE-associated costs.

A multicenter, matched case-control analysis comparing burden-of-illness in Dravet syndrome to refractory epilepsy and seizure remission in patients and caregivers in Germany.

OBJECTIVE: To compare direct and indirect costs and quality of life (QoL) of pediatric and adult patients with Dravet syndrome (DS), with drug-resistant epilepsy (DRE) and in seizure remission (SR), and their caregivers, in Germany. METHODS: Questionnaire responses from 93 DS patients and their caregivers were matched by age and gender with responses from 93 DRE and 93 SR patients collected in independent studies, and were compared across main components of QoL, direct costs (patient visits, medication use, care level, medical equipment, and ancillary treatments), and indirect costs (quitting job, reduced working hours, missed days). RESULTS: Mean total direct costs were highest for DS patients (€4864 [median €3564] vs €3049 [median €1506] for DRE [excluding outliers], P = 0.01; and €1007 [median €311], P < 0.001 for SR). Total lost productivity over 3 months was highest among caregivers of pediatric DS (€4757, median €2841), compared with those of DRE (€1541, P < 0.001; median €0) and SR patients (€891, P < 0.001; median €0). The proportions of caregivers in employment were similar across groups (62% DS, 63% DRE, and 63% SR) but DS caregivers were more likely to experience changes to their working situation, such as quitting their job (40% DS vs 16% DRE and 9% SR, P < 0.001 in both comparisons). KINDL scores were significantly lower for DS patients (62 vs 74 and 72, P < 0.001 in both comparisons), and lower than for the average German population (77). Pediatric caregiver EQ-5D scores across all cohorts were comparable with population norms, but more DS caregivers experienced moderate to severe depressive symptoms (24% vs 11% and 5%). Mean Beck Depression Inventory (BDI-II) score was significantly higher in DS caregivers than either of the other groups (P < 0.001). SIGNIFICANCE: This first comparative study of Dravet syndrome to difficult-to-treat epilepsy and to epilepsy patients in seizure remission emphasizes the excess burden of DS in components of QoL and direct costs. The caregivers of DS patients have a greater impairment of their working lives (indirect costs) and increased depression symptoms.

The role of mTOR inhibitors in preventing epileptogenesis in patients with TSC: Current evidence and future perspectives.

Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Mutations in the TSC1 or TSC2 genes lead to the dysregulation of the mechanistic target of rapamycin (mTOR) pathway. This mTOR pathway hyperactivation is associated with several processes resulting in epileptic conditions. The occurrence of seizures and their treatment outcomes seem to play a crucial role in cognitive and behavioral developments in patients with TSC. Mechanistic target of rapamycin inhibitors have been proven to be effective in epilepsy treatment in individuals with TSC. Specifically, because of their disease-modifying mechanism of action, they have the capability to prevent epileptogenesis in patients with TSC. This article will provide an overview of the current evidence of and delineate future perspectives for mTOR inhibitors and their role in preventing epileptogenesis.

Invasive EEG-electrodes in presurgical evaluation of epilepsies: Systematic analysis of implantation-, video-EEG-monitoring- and explantation-related complications, and review of literature.

INTRODUCTION: Stereoelectroencephalography (sEEG) is a diagnostic procedure for patients with refractory focal epilepsies that is performed to localize and define the epileptogenic zone. In contrast to grid electrodes, sEEG electrodes are implanted using minimal invasive operation techniques without large craniotomies. Previous studies provided good evidence that sEEG implantation is a safe and effective procedure; however, complications in asymptomatic patients after explantation may be underreported. The aim of this analysis was to systematically analyze clinical and imaging data following implantation and explantation. RESULTS: We analyzed 18 consecutive patients (mean age: 30.5 years, range: 12-46; 61% female) undergoing invasive presurgical video-EEG monitoring via sEEG electrodes (n = 167 implanted electrodes) over a period of 2.5 years with robot-assisted implantation. There were no neurological deficits reported after implantation or explantation in any of the enrolled patients. Postimplantation imaging showed a minimal subclinical subarachnoid hemorrhage in one patient and further workup revealed a previously unknown factor VII deficiency. No injuries or status epilepticus occurred during video-EEG monitoring. In one patient, a seizure-related asymptomatic cross break of two fixation screws was found and led to revision surgery. Unspecific symptoms like headaches or low-grade fever were present in 10 of 18 (56%) patients during the first days of video-EEG monitoring and were transient. Postexplantation imaging showed asymptomatic and small bleedings close to four electrodes (2.8%). CONCLUSION: Overall, sEEG is a safe and well-tolerated procedure. Systematic imaging after implantation and explantation helps to identify clinically silent complications of sEEG. In the literature, complication rates of up to 4.4% in sEEG and in 49.9% of subdural EEG are reported; however, systematic imaging after explantation was not performed throughout the studies, which may have led to underreporting of associated complications.