The burden of illness in Lennox–Gastaut syndrome: a systematic literature review

Strzelczyk, Adam; Zuberi, Sameer M.; Striano, Pasquale; Rosenow, Felix; Schubert‐Bast, Susanne

doi:10.1186/s13023-023-02626-4

Cited by 22 publications

(9 citation statements)

References 87 publications

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“…Overall, SE and the sudden unexpected death in epilepsy (SUDEP) are the leading seizure-related causes of death in patients with epilepsy and DEEs such as DS [ 34 , 35 ] and LGS [ 36 ]. A recent pooled analysis of phase III clinical trials and long-term open-label observational studies showed a reduction of all-cause (including SE-related) and SUDEP mortality rates in DS patients treated with FFA [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review

Strzelczyk,

Becker,

Tako

et al. 2024

Neurol. Res. Pract.

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Background Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE. Methods A case of an adult patient with Lennox–Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search. Results Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases. Conclusions Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations. Key points We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine. Refractory SE resolved after 4–7 days on fenfluramine. Swift fenfluramine up-titration was well-tolerated during SE treatment. Treatment-emergent adverse events on fenfluramine were not observed. Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox–Gastaut syndromes.

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Section: Discussionmentioning

confidence: 99%

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review

Strzelczyk,

Becker,

Tako

et al. 2024

Neurol. Res. Pract.

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“…The manifestation of this condition includes heightened respiratory effort, observable inward chest or sternum movement known as retractions, and cyanosis, characterized by a bluish tint in the skin or mucous membranes. These symptoms serve as indicators of inadequate oxygen supply [ 4 ]. Although not a primary clinical manifestation, it is crucial to acknowledge the possible life-threatening implications of respiratory failure in individuals with epileptic encephalopathies.…”

Section: Reviewmentioning

confidence: 99%

“…LGS represents another archetypal epileptic encephalopathy characterized by multiple seizure types, including tonic, atonic, and atypical absence seizures. LGS typically manifests between the ages of one and eight and is often refractory to conventional antiepileptic drugs (AEDs) [ 4 ]. Cognitive decline and behavioral disturbances are hallmarks of the syndrome, leading to significant impairments in daily functioning.…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between epilepsy and respiratory function is bidirectional and complex. Seizures can directly impact respiration, leading to alterations in breathing patterns, apneas, or oxygen desaturation [ 4 ]. Conversely, respiratory dysfunction, such as chronic hypoventilation, can influence seizure susceptibility and exacerbate the severity of seizures [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…LGS typically manifests between the ages of one and eight and is often refractory to conventional antiepileptic drugs (AEDs) [4]. Cognitive decline and behavioral disturbances are hallmarks of the syndrome, leading to significant impairments in daily functioning.…”

Section: Introductionmentioning

confidence: 99%

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Respiratory Dysfunction in Epileptic Encephalopathies: Insights and Challenges

Khan,

Dev,

Kumari

et al. 2023

Cureus

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Epileptic encephalopathies constitute a group of severe epileptic disorders characterized by intractable seizures and cognitive regression. Beyond the hallmark neurological manifestations, these disorders frequently exhibit associated respiratory dysfunction, which is increasingly recognized as a critical aspect of their pathophysiology. Respiratory abnormalities in epileptic encephalopathies encompass a spectrum of manifestations, ranging from subtle alterations in breathing patterns to life-threatening events such as apneas and hypoventilation. These respiratory disturbances often occur during seizures, the interictal period, or even persist chronically, leading to significant morbidity and mortality. We explore the varied clinical presentations and their implications on patient outcomes, emphasizing the need for heightened awareness among clinicians. This review unravels the intricate mechanisms linking epilepsy and respiratory dysfunction. GABAergic and glutamatergic imbalances, alterations in central respiratory centers, and abnormal autonomic control are among the key factors contributing to respiratory disturbances in these patients. We elucidate the neurobiological intricacies that underlie these processes and their relevance to therapeutic interventions. Accurate diagnosis of respiratory dysfunction in epileptic encephalopathies is often hindered by its diverse clinical phenotypes and the absence of routine screening protocols. We scrutinize the diagnostic hurdles, highlighting the necessity of comprehensive respiratory assessments in managing these patients. Timely recognition of respiratory issues may guide treatment decisions and mitigate complications. Management of respiratory dysfunction in epileptic encephalopathies is complex and necessitates a multidisciplinary approach. We explore various therapeutic modalities, including antiepileptic drugs (AEDs), ventilatory support, and novel interventions like neuromodulation techniques. The review emphasizes the individualized nature of treatment strategies tailored to each patient's specific needs. In conclusion, this narrative review offers a comprehensive overview of respiratory dysfunction in epileptic encephalopathies, shedding light on its clinical importance, underlying mechanisms, diagnostic challenges, and therapeutic considerations. By addressing these insights and challenges, we hope to inspire further research and innovation to enhance the care and outcomes of patients with epileptic encephalopathies.

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Dravet syndrome: A systematic literature review of the illness burden

Strzelczyk,

Lagae,

Wilmshurst

et al. 2023

Epilepsia Open

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ObjectiveWe performed a systematic literature review and narrative synthesis according to a pre‐registered protocol (Prospero: CRD42022376561) to identify the evidence associated with the burden of illness in Dravet syndrome (DS), a developmental and epileptic encephalopathy characterised by drug‐resistant epilepsy with neurocognitive and neurobehavioural impairment.MethodsWe searched MEDLINE, Embase and APA PsychInfo, Cochrane's database of systematic reviews, and Epistemonikos from inception to June 2022. Non‐interventional studies reporting on epidemiology (incidence, prevalence and mortality), patient and caregiver health‐related quality of life (HRQoL), direct and indirect costs and healthcare resource utilisation were eligible. Two reviewers independently carried out the screening. Pre‐specified data were extracted and a narrative synthesis was conducted.ResultsOverall, 49 studies met the inclusion criteria. The incidence varied from 1:15,400–1:40,900, and the prevalence varied from 1.5 per 100,000 to 6.5 per 100,000. Mortality was reported in 3.7–20.8% of DS patients, most commonly due to sudden unexpected death in epilepsy and status epilepticus. Patient HRQoL, assessed by caregivers, was lower than in non‐DS epilepsy patients; mean scores (0 [worst] to 100/1 [best]) were 62.1 for the Kiddy KINDL/ Kid‐KINDL, 46.5–54.7 for the PedsQL and 0.42 for the EQ‐5D‐5L. Caregivers, especially mothers, were severely affected, with impacts on their time, energy, sleep, career, and finances, while siblings were also affected. Symptoms of depression were reported in 47% to 70% of caregivers. Mean total direct costs were high across all studies, ranging from $11,048 to $77,914 per patient per year (PPPY), with inpatient admissions being a key cost driver across most studies. Mean costs related to lost productivity were only reported in three publications, ranging from approximately $19,000 to $20,000 PPPY ($17,596 for mothers versus $1,564 for fathers). High seizure burden was associated with higher resource utilisation, costs and poorer HRQoL.SignificanceThe burden of DS on patients, caregivers, the healthcare system and society is profound, reflecting the severe nature of the syndrome. Future studies will be able to assess the impact that newly approved therapies have on reducing the burden of DS.

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The burden of illness in Lennox–Gastaut syndrome: a systematic literature review

Cited by 22 publications

References 87 publications

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox–Gastaut syndrome and literature review

Respiratory Dysfunction in Epileptic Encephalopathies: Insights and Challenges

Dravet syndrome: A systematic literature review of the illness burden

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