Order publications from the NINDS Catalog. A prescription for at least one selected ASM. Sachdeo RC, Glauser TA, Ritter F, et al. Incidence, reported in 2 studies, was estimated at approximately 1.9 per 100,000 people in both studies [42, 45]. Camfield P, Camfield C. Long-term prognosis for symptomatic (secondarily) generalized epilepsies: a population-based study. nformation is available from the following organizations: 301-459-3700 or 800-332-1000; 866-748-8008 Spanish. During the development of the protocol (Prospero: CRD42022333410), it was anticipated that the studies identified in this SLR would be diverse with regard to study design, definition of LGS (especially as there is no specific ICD-9 or 10 code for LGS in some regions and diagnosis can be challenging), size of the populations, the ages of the patients and the length of the follow-up period, and therefore the synthesis of the data was planned to be narrative in nature, without any statistical analyses/comparisons (e.g meta-analyses). Dealing with defectives Foster Kennedy and William Lennox on eugenics. Stockl K, Funk S, Reaven N, et al. [46] reported LGS patients may be inadequately treated; the majority, but importantly not all probable LGS patients had 1 claim for an ASM (62.682.3% across age cohorts), while clobazam and rufinamide, both specifically licensed for LGS in the US, were infrequently used, especially in the older cohorts (17.5% for clobazam and 7.4% for rufinamide in patients 5 years, 5.5% for both ASMs in the 20-year cohort and <1.0% of patients in the 60-year cohort). Expert opinion on the management of LennoxGastaut syndrome: treatment algorithms and practical considerations. In: Etext on Health Technology Assessment (HTA) Information Resources [Internet]. Various treatments have been shown to have some degree of efficacy. The methods were latterly reported in more detail by Vekeman et al (2019), showing that an LGS classifier that used input variables including the number of distinct ASMs received, epilepsy-related outpatient/inpatient visits, electroencephalogram procedures and claims for delayed development, showed high sensitivity and specificity in identifying LGS patients [65]. Gallop K, Wild D, Verdian L, et al. Lennox-Gastaut syndrome is a severe form of epilepsy. Another limitation is that LGS is likely to be underdiagnosed/ misdiagnosed, especially in adults [11, 14], and therefore many aspects of the burden of illness may have been underestimated. Pnd34 economic burden of probable LennoxGastaut syndrome, probable Dravet syndrome, and other refractory epilepsies for united states medicaid health plans. Death is often related to accidents. Other smaller retrospective, observational studies reporting on the epidemiology of LGS included patients who had been diagnosed based on standard diagnostic/ILAE criteria [39, 4245, 48], while the HRQoL studies generally recruited caregivers and/or patients through support groups, patient associations, clinicians and/or websites [5862]. Like all epilepsy curative surgeries, seizures may recur in the years following surgery, but surgery allows the child to have better brain development during the seizure free period. Rosso M, Chu D, Santoro JD. Roughly half have ongoing behavioral problems. Trevathan et al (1997) reported the lifetime prevalence of LGS at the age 10 years to be 26 per 100,000 people (0.26 per 1000 people) [44]. [1], The peak age of onset of seizures is typically between 3 and 5 years of age. Philadelphia, PA 19104, Know My Rights About Surprise Medical Bills, Epilepsy Neurogenetics Initiative (ENGIN), Buerger Center for Advanced Pediatric Care, Tonic (stiffening) seizures, especially in sleep, Generalized tonic-clonic seizures (also called grand mal seizures). Three studies used quantitative methods (one assessed caregiver HRQoL using the SF-36 and the HADS (Hospital Anxiety and Depression Scale), while two studies used a VAS (visual analog scale). A comparison of results of empirical studies of supplementary search techniques and recommendations in review methodology handbooks: a methodological review. [10][11] They occur most frequently during non-REM sleep (90%). Trevathan E, Murphy CC, Yeargin-Allsopp M. Prevalence and descriptive epidemiology of LennoxGastaut syndrome among Atlanta children. [39], Zonisamide showed promise in an overview of controlled and uncontrolled trials conducted in Japan. LGS occurs secondary to many different causes including injury, brain malformations, infections, and genetic factors. LGS accounts for 3% to 4% of all children with epilepsy. Gastaut H, Roger J, Soulayrol R, et al. Publications identified via the bibliographic database searches were managed and screened in Covidence, which is an online tool that helps to facilitate the systematic review process [34]. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease. Regular medical care is needed to adjust treatment to changing seizure patterns. Although not always present at the onset of seizures, most people living with Lennox-Gastaut syndrome experience some degree of impaired intellectual functioning or information processing, along with developmental delays and behavioral disturbances. New York: Raven Press, 1980: 14954, Choi MH, Yang JO, Min JS, Lee JJ, Jun SY1, Lee YJ, Yoon JY, Jeon SJ, Byeon I, Kang JW, Kim NS (2019) A novel X-linked variant of IQSEC2 is associated with Lennox-Gastaut syndrome and mild intellectual disability in three generations of a Korean Family. Secondary LGS occurs when an identifiable underlying pathology is responsible. Studies showed that the HRQoL of patients and caregivers was adversely affected, although only a few studies were identified. In addition, economic evaluations (e.g cost-effectiveness, cost-utility and budget impact models) reporting on specific interventions without any original data on e.g HRQoL (e.g utilities) and healthcare resource utilization were excluded, however the reference lists were searched for publications containing original data. Lennox-Gastaut syndrome is a condition that almost always starts before age 10, with a diagnosis most likely to happen between ages 3 and 5. Heiskala H. Community-based study of LennoxGastaut syndrome. Studies by Auvin et al. [7] The mainstay symptoms are seizures that are frequent occurring daily and difficult to treat with antiseizure medications. Slow spike waves may occur during seizure or between seizures, or may occur in absence of any observable clinical changes which helps distinguish pattern from extended 3-Hz spike-wave discharges. Gallop et al. Data were extracted into tables in MS Word by one reviewer, which was checked for accuracy by a second independent reviewer. In a quarter to a third of cases, no cause can be identified. LGS is reviewed in this topic. Lennox-Gastaut syndrome is a severe condition characterized by recurrent seizures (epilepsy) that begin early in life. Yagi K. Evolution of LennoxGastaut syndrome: a long-term longitudinal study. In the study by Reaven et al. [61] and Radu et al. Lennox Gastaut Syndrome Foundation International league against epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE task force on nosology and definitions. Rantala H, Putkonen T. Occurrence, outcome, and prognostic factors of infantile spasms and LennoxGastaut syndrome. Grau J, Zllner JP, Schubert-Bast S, et al. ASM, anti-seizure medication; DS, Dravet syndrome; ED, emergency department; LGS, LennoxGastaut syndrome; PPPY, per person per year; OP, outpatient; TSC, tuberous sclerosis complex. LennoxGastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. 1 ASM claim and medical claims with 1 diagnosis code for LGS or refractory epilepsy or 1 claim for clobazam or rufinamide. Furthermore, Murray reported in 1993 that parents had to deal with a lot of uncertainty around diagnosis, etiology, seizure activity, treatment and prognosis, which caused feelings of guilt and stress in some parents [60]. Initially, primary screening was performed by reviewing the title and abstract and articles were excluded if they were clearly not relevant according to the PICOS eligibility criteria (e.g if the article was about a different condition and clearly not about patients with LGS etc). Markand ON. The KD was administered to 19 patients, five patients maintained a seizure free state during the KD but only one patient was . Without a precise definition of LGS and a lack of consistency in using recent and specific diagnostic codes for LGS, there was considerable heterogeneity between studies on how LGS was defined. The electronic database searches initially identified 868 articles, of which 595 were screened after the removal of duplicates. LGS is associated with a substantial burden of illness, with seizure events associated with higher costs and worse HRQoL. All authors read and approved the final manuscript. Epilepsy surgery program in a resource-limited setting in Vietnam: a multicentered collaborative model. In addition, Chin et al (2021) reported that in patients with confirmed LGS the mean number of ASMs was 6.7 (SD 3.4) during the 812 years follow-up period, with only 3.7% being prescribed only one ASM during this period, while the mean number of ASMs per year was 1.06 during 201013 and 1.12 during 201417 [40]; this suggests that patients had to switch to different ASMs many times over the course of the study period. [32] Two studies on LGS patients series who underwent curative surgery in Korea[33] and China,[34] showed very good results, up to seizure freedom for 80% of these patients below 5 years old, and 40% above 5 years old. About 10% to 30% of children with LGS have a prior history of earlier onset epilepsy syndromes, such as West syndrome or Ohtahara syndrome. Pia-Garza JE, Chung S, Montouris GD, et al. [citation needed], Nonconvulsive status epilepticus occurs in about 50% of patients. No limits were applied (e.g regarding publication dates or language), except for conference abstracts that were limited to the previous 3 years. Mean annual direct costs per person varied from $24,048 to $80,545 across studies, and home-based care and inpatient care were significant cost drivers. In addition, while the literature was searched in major electronic databases, we may still have missed some studies from other databases or from the grey literature. The reasons for exclusion at secondary screening were clearly documented according to the PICOS criteria. [12] They present often as tonic eyelid opening with some changes in breathing coupled with pupillary dilation, urinary incontinence, increased heart rate, and flushing can occur. [citation needed], The disease pathophysiology is mostly unknown, but some evidence implicates cortical hyperexcitability occurring at critical periods of brain development. B Adapted from Auvin et al (2021) [61]. However, the few studies that are available on DS caregivers and TSC patients or caregivers have shown that indirect costs are relevant [72, 7476], with a particular impact on mothers having to reduce their working hours or stop working completely [72, 74, 77]. J Clin Neurophysiol . Common seizure types include: There may be periods of frequent seizures mixed with relatively seizure-free periods. Direct and indirect costs and cost-driving factors of Tuberous sclerosis complex in children, adolescents, and caregivers: a multicenter cohort study. Lennox gastaut syndrome (LGS) presents with multiple seizures typestonic, atonic, atypical absenceand intellectual disability. In addition, 58% of parents experienced anxiety according to the HADS. Brown ML, Lipscomb J, Snyder C. The burden of illness of cancer: economic cost and quality of life. Clinical trials are studies that allow us to learn more about disorders and improve care. Doose syndrome has more myoclonic seizures and LGS has more tonic seizures. Prevalence of childhood epilepsy in Estonia. The burden of illness studies relies heavily on how the disease is defined. Use and cost comparison of clobazam to other antiepileptic drugs for treatment of LennoxGastaut syndrome. The situation in low and middle income countries is especially complex and many aspects of the burden of illness, especially mortality, costs, and resources are likely to be very different from high income countries. Reaven NL, Funk SE, Lyons PD, et al. Healthcare resource utilization and direct costs were substantial across all studies. Studies in this SLR have reported that seizure events are associated with higher resource and costs, and lower patient HRQoL. Some of these cases once thought to be of unknown cause may have definitive etiology by modern genetic testing. AS, SZ, PS, FR and SSB wrote the paper, discussed the results, and contributed to the final manuscript. * Costs were converted from Euros to US dollars on 21st June 2022 (exchange rate 1.00 Euro =1.06 US Dollars [xe.com]). The U.S. Food and Drug Administration (FDA) approved cannabidiol (Epidolex, derived from marijuana) for the treatment of seizures associated with Lennox-Gastaut syndrome in individuals ages 2 and older. National Library of Medicine [53], 22% (2329 of 10,618) of LGS patients with a medically-treated seizure event across insurance types had an injury. Gibson PA. LennoxGastaut syndrome: impact on the caregivers and families of patients. Varadkar S. Cannabidiol for drop seizures in LennoxGastaut syndrome. Children with LGS have seizures often, and they have several different kinds of seizures. Advunces in epileptology: The Xth Epilepsy Global, regional, and national burden of neurological disorders, 19902016: a systematic analysis for the Global Burden of Disease Study 2016. Definition and natural history of LennoxGastaut syndrome. The LGS cohort required a diagnosis code for LGS or all of the following: oooooo1 diagnosis code for refractory epilepsy. Wijnen B, Armstrong N, Ramaekers B, et al. Furthermore, many of the studies, especially regarding costs and resources, were conducted in the USA, with limited evidence in Europe, and no evidence from other parts of the world despite not having any language restrictions. No study reporting the indirect costs of patients with LGS or their caregivers was identified, although one paper reported that a large proportion of caregivers of patients with LGS struggled to access the available medical expense subsidies in Japan [57] (Table (Table22). Summaries of the costs across the different studies were provided inthe narrative synthesis in US dollars ($) using a simple conversion from Euros () to US dollars at an exchange rate of 1.00 Euro =$1.06 (xe.com on 21st June 2022). A Total direct costs in LGS patients (blue) versus control patients (grey), patients with other epilepsies (lilac), and in LGS patients with seizure events vs without seizure events and LGS patients in years where patients were prescribed with rescue medication vs years where patients were not prescribed rescue medication (blue) B resource utilization and costs in LGS patients vs controls; C resource utilization and costs in LGS patients with seizure events vs without seizure events. AS and SSB developed the idea for this study and conceived the paper. Asadi-Pooya AA, Farazdaghi M. Age at onset in patients with LennoxGastaut syndrome: correlations with clinical manifestations. Murray J. Coping with the uncertainty of uncontrolled epilepsy. [citation needed], Findings that strongly suggest LGS include consistent slow spike-wave (< 3 hertz [Hz]) on awake EEG. [8][9], The seizures are most commonly tonic seizures. Systematic review management platform [Available from: Hoy D, Brooks P, Woolf A, et al. The risk of bias was low or moderate in most studies. A double-blind, randomized trial of topiramate in LennoxGastaut syndrome. 10.1111/epi.17241. [14] In up to one-third of cases no cause can be found. The clinical, economic, and humanistic burden of Dravet syndromea systematic literature review. The impact of seizure frequency on quality of life in patients with LennoxGastaut syndrome or Dravet syndrome. Of concern though is the apparent lack of other therapies in development for patients with LGS at present. Short-term ketogenic diet might be associated with nonsignificant decreases in frequency of parent-reported seizures in children with LGS. Epileptic syndromes in infancy, childhood, and adolescence. Lagae L, Brambilla I, Mingorance A, et al. These studies have suggested that fewer seizures and additional seizure-free days are associated with better patient HRQoL, with seizure-free days having the greatest consequence on HRQoL (Fig4B). Three studies used qualitative methods (one for both patient and caregiver HRQoL, and two for caregiver HRQoL); the quality of the qualitative studies was assessed to be grade I (highest methodological and reporting quality) in one study and grade III (limitations in methodological and reporting quality) in 2 studies (Additional file 2: Table S4). No, I did not find the content I was looking for, Yes, I did find the content I was looking for, Please rate how easy it was to navigate the NINDS website. Likewise, using the IBM MarketScan commercial database, the mean number of distinct ASMs was 3.4, 2.6, and 2.1, respectively, representing 72.6%, 70.8%, and 65.8% of the pharmacy costs [55]. The mortality rate is 5%. We searched MEDLINE, Embase and APA PsychInfo (all via OVID), Cochranes database of systematic reviews (CDSR, Wiley), and Epistemonikos. Lennox-Gastaut syndrome treatment will generally include physical therapy, occupational therapy and speech therapy. The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. [. We found only a few studies evaluating the HRQoL in patients and caregivers. There are no studies using only one medication. For information about participating in clinical research visit, . The drug contains only small amount of the psychoactive elementin marijuana and does not induce euphoria associated with the drug. The seizures can cause sudden falling often leading to injury. [58] identified only one study of sufficient quality regarding caregivers of patients with LGS (also identified hererin) [38]. Genetic causes likely account for a majority of unexplained LGS. Affected individuals have multiple types of seizures, a particular pattern of brain activity (called slow spike-and-wave) measured by a test called an electroencephalogram (EEG), and impaired mental abilities. Cannabidiol with clobazam for treating seizures associated with LennoxGastaut syndrome 2019 [Available from: World Health Organization. Page MJ, McKenzie JE, Bossuyt PM, et al. Multiple types of drug-resistant seizures, including tonic, atonic, and atypical absences, with onset generally before the age of 8 years (peak age of onset between 3 and 5 years). International League Against Epilepsy Proposal for revised classification of epilepsies and epileptic syndromes. William Gordon Lennox (18841960). Lennox-Gastaut syndrome can be very difficult to treat. Molinier L, Bauvin E, Combescure C, et al. The Epilepsy Neurogenetics Initiative (ENGIN) at Childrens Hospital of Philadelphia (CHOP) integrates genetic testing into the diagnosis and treatment of children with difficult-to-treat or unexplained epilepsies, genetic epilepsy syndromes and other genetic neurodevelopmental disorders. Exploring the relationships between composite scores of disease severity, seizure-freedom and quality of life in Dravet syndrome. Of the 68 patients, 26 (38.2%) were treated solely with AEDs and six became seizure-free. [citation needed]. Similarly, Pia-Garza et al. The risk of bias in the studies reporting on costs and/or resources was assessed to be low in 6 studies [40, 46, 47, 51, 53, 54] and moderate in 3 studies, which were conference abstracts that provided limited information [52, 55, 56] (Additional file 2: Table S3). A summary of the eligibility criteria for this review according to population, intervention, comparator, outcomes and study design (PICOS) is presented in Table Table1.1. Children and adults with Lennox-Gastaut syndrome are at an increased risk of premature mortality, often from sudden unexpected death in epilepsy (SUDEP), injury, seizures, or as a consequence of the underlying brain disorder. Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement. We performed a systematic literature review according to the PRISMA guidelines to identify, synthesize and appraise the burden of illness in LGS (including probable LGS). Radu X, Damera V, Martin M, et al. Accessibility bEconomic evaluations reporting on specific interventions without any original data on e.g HRQoL (utilities) and healthcare resource utilisation will be excluded, however, the reference lists will be searched to ensure all relevant studies are captured in this SLR. Publication types Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. For information about participating in clinical research visit NIH Clinical Research Trials and You. The mortality ratios for children with Lennox-Gastaut syndrome and infantile spasms were 13.92 and 11.91, respectively. [40] estimated the mortality rates to be 6.12 deaths per 1000 person-years for confirmed LGS and 4.17 deaths per 1000 person-years for probable LGS over a follow-up period of 1796 and 1679 patient-years, substantially higher than the mortality rates for the general population and the epilepsy population (0.6 per 1000 person-years in England in 2018 [49], and 0.9 per 1000 person-years in the UK [50], respectively). Results. Home health= home-based nursing, personal care, and residential habilitation services. The main limitations have been discussed above, including the challenges around identifying the LGS population and the paucity of studies, especially on caregiver HRQoL and indirect costs. The direct cost of seizure events in severe childhood-onset epilepsies: a retrospective claims-based analysis. Strzelczyk A, Schubert-Bast S. Expanding the treatment landscape for LennoxGastaut syndrome: current and future strategies. HHS Vulnerability Disclosure, Help In vitro and in vivo studies, preclinical studies, review articles, SLRs, editorials, and case studies were not eligible, however the reference lists of reviews and SLRs were searched to ensure all relevant studies were captured. (17%) achieved late-life terminal seizure-freedom of at least two years before death, which occurred at a median age of 68 years with a . There are now seven anti-seizure medications (ASMs) specifically indicated in patients with LGS in the US [15]clobazam, felbamate, lamotrigine, topiramate, rufinamide, cannabidiol and fenfluramine, with efficacy demonstrated in clinical trials for seizures associated with drops in LGS patients (Fig1A) [1723]. For example, Reaven et al. [14], According to a 1997 community-based retrospective study in the Helsinki metropolitan area and the province of Uusimaa, the annual incidence of LennoxGastaut was 2 in 100,000 (0.002%) from 1975 to 1985. Increased risk of death among children with LennoxGastaut syndrome and infantile spasms. Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey. [6] Signs and symptoms [citation needed], Certain diagnoses must be ruled out before diagnosing LGS. Using the SF-36v2, a widely used generic instrument to measure health status, the parents mental health summary score (a composite of social functioning, vitality and mental health) was found to be below average (45 for LGS parents vs. 50 for US general population). The appearance of multiple types of seizures in early childhood, particularly a combination of tonic, atonic and atypical absence seizures, is a key diagnostic indicator of Lennox-Gastaut syndrome. Lennox-Gastaut syndrome (LGS) is a severe epileptic and developmental encephalopathy that is associated with a high rate of morbidity and mortality. 1Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital and Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528 Frankfurt am Main, Germany, 2LOEWE Center for Personalized and Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany, 3Paediatric Neurosciences Research Group, Royal Hospital for Children, School of Health and Wellbeing, University of Glasgow, Glasgow, UK, 4IRCCS G. Medication may be combined with the other treatments to optimize seizure control. More research is needed, especially in evaluating indirect costs and caregiver burden, where there is a notable lack of studies. The Doose syndromes is less likely to have cognitive disabilities. Royle P, Bain L, Waugh N. Systematic reviews of epidemiology in diabetes: finding the evidence. Across the studies, inpatient care and home-based care were significant cost drivers, whereas pharmacy costs, particularly for ASMs, generally represented a smaller share of all healthcare costs (Fig4A, Additional file 2: Table S1) [46, 47, 5155]. When Lennox-Gastaut syndrome is suspected, additional tests may be done to confirm a diagnosis, including: Many genes have been identified that are associated with Lennox-Gastaut syndrome, and in almost all cases the mutation in the child with LGS has occurred spontaneously (de novo) and was not inherited from either parent. Methodological considerations in cost of prostate cancer studies: a systematic review. They initially last only a few seconds and are activated by sleep. They can help connect patients with new and upcoming treatment options. In a study describing the nature of acute hospitalizations in LGS patients, 4658% were considered epilepsy-related across health plans (Commercial and Medicaid) compared to 6370% for DS, 26% for TSC, and 3751% for other DEEs; 67% were pneumonia-related, and approximately 2% were injury-related [56].
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