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Objective: Historically, epilepsy has been the most frequently presenting feature of tuberous sclerosis complex (TSC). Advances in TSC health care have occurred over the past decade; thus, we studied whether TSC epilepsy outcomes have changed. Method: A retrospective chart review was undertaken for all children with TSC in Queensland, Australia. Epilepsy outcome and TSC diagnosis data were extracted, and data were compared between children born before 2012 with those born in or after 2012. Results: In this retrospective cohort, TSC diagnosis in children born in or after 2012 is now predominantly antenatal (51%, p <.05). Most patients with epilepsy are now known to have TSC before they develop epilepsy. Despite earlier TSC diagnosis, the frequency of epilepsy (85%) has not changed (p =.92), but diagnosis trends toward an earlier age (median = 3 months for patients born in or after 2012 vs. 5.5 months for those born before 2012, p =.23). Most (95%) patients had focal seizures as their initial clinical seizure type; it was rare (5%) for epileptic spasms (ES) to be the initial seizure type. The frequency of ES was lower in patients born in or after 2012 (36% vs. 50%, p =.27). Infantile (<24 months) onset ES was not associated with worse epilepsy outcome. Late onset ES was seen in 14%, and these patients had a lower rate of epilepsy remission. Lennox–Gastaut syndrome was seen in 7%. Febrile/illness‐related status epilepticus occurred in 12% of patients, between 1 and 4 years of age. Despite many (78%) patients having multiple daily seizures at maximal seizure frequency, and 74% meeting criteria for treatment‐refractory epilepsy, most patients achieved epilepsy remission (66%), either with epilepsy surgery (47%) or with age (53%). At the time of inclusion in this study, only 21% of patients had uncontrolled frequent (daily to 3 monthly) seizures and 14% had uncontrolled infrequent (3 monthly to <2 yearly) seizures. Significance: This study provides updated information that informs the counseling of parents of newly diagnosed pediatric TSC patients. [ABSTRACT FROM AUTHOR]

Limited guidelines exist regarding osteoporosis prevention in the general population. Despite being a subject of controversy, the majority of research suggests that decreased vitamin D levels correlate with increased bone turnover, that is, an important risk factor for osteoporosis development. In most guidelines, daily vitamin D supplementation is recommended. In persons with epilepsy (PWE), the situation is more complex, as other factors can increase the chance of being vitamin D deficient. Currently, there are no internationally accepted guidelines regarding monitoring bone health in PWE. Our aim was to review the existing evidence in PWE on: (1) risk factors for vitamin D deficiency, (2) the identification of higher risk groups, and (3) the optimal ways to monitor bone health. Our narrative review shows that: (1) anti‐seizure medication (ASM) use, especially enzyme‐inducing ASM (EIASM) and valproic acid, is identified as an important risk factor for impaired bone health (e.g., increased risk for osteoporosis/fractures and/or vitamin D deficiency); (2) higher risk groups within the PWE population are present: intellectual or physical disability, institutionalized patients, puberty, early onset epilepsy and developmental epileptic encephalopathies, postmenopausal women, and use of multiple ASM/concomitant drugs (e.g. corticosteroids); and (3) a monitoring scheme can be suggested including laboratory tests, bone density measurements, managing of risk factors, and/or vitamin D supplementation. Overall, regular vitamin D measurement in PWE is a cost‐effective and practical method for monitoring vitamin D deficiency, whereas in high‐risk patients the combination of vitamin D measurement and bone densitometry is recommended. There is not enough evidence to advocate continuous vitamin D supplementation in all PWE. Children with epilepsy should receive the recommended daily intake of vitamin D for age and additional monitoring and supplementation if at higher risk of deficiency. There is a need for prospective trials exploring the potential benefit of vitamin D supplementation in PWE. [ABSTRACT FROM AUTHOR]

Epilepsies are a diverse group of disorders which differ regarding prognosis for seizure control and associated comorbidities. Accurate classification is critical to choose the highest yield investigations and best therapeutic options and to provide the most accurate prognoses regarding the expected degree of seizure control, possible remission, and risk of associated comorbidities to patients and their families. This article reviews the recent updates in epilepsy classification to illustrate how accurate classification impacts care for persons with epilepsy. The authors discuss the ILAE 2017 Classification of the Epilepsies along with the modification of the classification for neonatal seizures and epilepsies. They also discuss the ILAE position papers on Epilepsy syndromes in neonates and infants and children of variable age and the Idiopathic Generalized Epilepsies. Accurate epilepsy classification allows selection of the highest yield investigations, choice of optimal therapies, and accurate prognostication of seizures (likelihood of response to antiseizure treatments and likelihood of remission with age), as well as comorbidities (likelihood, type, and severity). As we move into the era of disease modifying therapy, early accurate identification of underlying causes with timely introduction of specific treatments will be crucial to lessen the severity of epilepsy, with improved seizure control and attenuation of associated comorbidities. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome. Methods: This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2–18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6‐week baseline period were randomized to placebo, fenfluramine.2 mg/kg/day, or fenfluramine.7 mg/kg/day (1:1:1 ratio) administered orally (maximum dose = 26 mg/day). Doses were titrated over 2 weeks and maintained for an additional 12 weeks. The primary endpoint was a comparison of the monthly convulsive seizure frequency (MCSF) during baseline and during the combined titration–maintenance period in patients given fenfluramine.7 mg/kg/day versus patients given placebo. Results: A total of 169 patients were screened, and 143 were randomized to treatment. Mean age was 9.3 ± 4.7 years (±SD), 51% were male, and median baseline MCSF in the three groups ranged 12.7–18.0 per 28 days. Patients treated with fenfluramine.7 mg/kg/day demonstrated a 64.8% (95% confidence interval = 51.8%–74.2%) greater reduction in MCSF compared with placebo (p <.0001). Following fenfluramine.7 mg/kg/day, 72.9% of patients had a ≥50% reduction in MCSF compared with 6.3% in the placebo group (p <.0001). The median longest seizure‐free interval was 30 days in the fenfluramine.7 mg/kg/day group compared with 10 days in the placebo group (p <.0001). The most common adverse events (>15% in any group) were decreased appetite, somnolence, pyrexia, and decreased blood glucose. All occurred in higher frequency in fenfluramine groups than placebo. No evidence of valvular heart disease or pulmonary artery hypertension was detected. Significance: The results of this third phase 3 clinical trial provide further evidence of the magnitude and durability of the antiseizure response of fenfluramine in children with Dravet syndrome. [ABSTRACT FROM AUTHOR]

Objective: Antiseizure medications (ASMs) remain the mainstay of epilepsy treatment. These ASMs have mainly been tested in trials in adults with epilepsy, which subsequently led to market authorization (MA). For treatment of – especially young – children with epilepsy, several ASMs do not have a MA and guidelines are lacking, subsequently leading to "off‐label" use of ASMs. Even though "off‐label" ASM prescriptions for children could lead to more adverse events, it can be clinically appropriate and rational if the benefits outweigh the risks. This could be the case if "on‐label" ASM, in mono‐ or polytherapy, fails to achieve adequate seizure control. Methods: The Medical Therapies Task Force of the International League Against Epilepsy (ILAE) Commission for Pediatrics performed a survey to study the current treatment practices in six classic, early life epilepsy scenarios. Our aim was not only to study first‐ and second‐line treatment preferences but also to illustrate the use of "off‐label" drugs in childhood epilepsies. Results: Our results reveal that several ASMs (e.g. topiramate, oxcarbazepine, benzodiazepines) are prescribed "off‐label" in distinct scenarios of young children with epilepsy. In addition, recent scientific guidelines were not always adopted by several survey respondents, suggesting a potential knowledge gap. Significance: We report the relatively common use of "off‐label" prescriptions that underlines the need for targeted and appropriately designed clinical trials, including younger patients, which will also result in the ability to generate evidence‐based guidelines. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording. Methods: Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video‐EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification. Results: Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients. Significance: This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to evaluate the long‐term safety and effectiveness of fenfluramine in patients with Lennox–Gastaut syndrome (LGS). Methods: Eligible patients with LGS who completed a 14‐week phase 3 randomized clinical trial enrolled in an open‐label extension (OLE; NCT03355209). All patients were initially started on.2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3‐month intervals. The protocol‐specified treatment duration was 12 months, but COVID‐19‐related delays resulted in 142 patients completing their final visit after 12 months. Results: As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2–4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was −28.6% over the entire OLE (n = 241) and −50.5% at Month 15 (n = 142, p <.0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was −45.9% (n = 192, p =.0038). Generalized tonic–clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p <.0001, n = 106) and 35.8% (p <.0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%–44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%–41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment‐emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed. Significance: Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long‐term. Fenfluramine may provide an important long‐term treatment option for LGS. [ABSTRACT FROM AUTHOR]