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  • Epilepsy in childhood

Modern therapy management is more than just seizure control

    • Market & Medicine
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    • Pediatrics
    • Pharmacology and toxicology
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  • 3 minute read

Lennox-Gastaut syndrome and Dravet syndrome are rare and severe developmental and epileptic encephalopathies with onset in infancy or early childhood. In addition to the seizures, comorbidities often occur, which represent a considerable physical, financial, social and psychological burden for both the patients and their caregivers. Therefore, modern therapy management should not focus solely on seizure control.

Epilepsy can manifest itself in different ways in childhood. Dravet syndrome (DS) occurs in infancy and is characterized by infection-associated focal and generalized seizures. Status epilepticus is common, which means that inpatient emergency treatment is often indicated, reported Prof. Dr. Regina Trollmann, Erlangen (Germany). Over time, developmental disorders and comorbidities can occur. A correlation of seizure frequency and severity with comorbidities and quality of life was found. Lennox-Gastaut syndrome (LGS) usually manifests itself between the ages of three and five and is characterized by severe epileptic encephalopathy (DEE). 90% of seizures are refractory, significantly increasing the risk of morbidity and mortality. Comorbidities often include behavioral disorders such as hyperactivity, aggression and autistic traits, sleep cycle disorders and restricted mobility. Developmental and epileptic encephalopathies are associated with a high frequency of clinical seizures and interictal seizure patterns – and often with pharmacoresistance. According to the expert, pharmacoresistance in children with epilepsy is 28-36%.

Cannabidiol ready-to-use medicine at a glance
Epidyolex® is used as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in combination with clobazam in patients aged 2 years and older.
The flexible and gradual dosage can be tailored to the patient’s needs.
Improvement in seizure-related goals has been demonstrated in LGS and DS patients across a wide range of seizure types and age groups.
An improvement in non-seizure-related goals such as cognition, behavior and communication was also observed.
The finished product is characterized by its long-lasting and good tolerability.

Effective treatment with cannabidiol

A significant reduction in seizure frequency in both DS and LGS has been demonstrated in several clinical studies for cannabidiol (CBD), the non-psychoactive component of cannabis. However, preclinical data also suggest anti-inflammatory and antioxidant effects on various neuroglial structures as well as effects on behavior. An open extension study also showed that there was a 48-71% reduction in falls within 156 weeks of treatment with cannabidiol. Current real-world data now show that modern treatment management can do more than generate effective seizure control. The BEhavior, COgnition, and More with Epidiolex® (BECOME) was a 20-minute online cross-sectional survey developed with extensive input from caregivers, healthcare professionals, and epilepsy researchers, based on questions from validated measures and previously published caregiver reports. US-based caregivers of people with LGS or DS who had been treated with CBD (Epidiolex®, 100 mg/mL oral solution) for ≥3 months were asked to compare the last month with the period before CBD treatment and rate their impression of changes using symmetrical Likert scales. A total of 498 caregivers (97% parents) of patients with LGS (80%) or DS (20%) completed the survey. The patients took a median CBD dose of 14 mg/kg/d and an average of four anti-seizure medications at the same time. A large proportion of respondents reported improvements on at least one question in all seizure-free domains: Alertness, cognition and executive function (85%); emotional function (82%); language and communication (79% for nonverbal and 74% for verbal patients); activities of daily living (51%); sleep (51%); and physical function (46%). Respondents reported improvements in seizure-related domains, including overall seizure frequency (85%), overall seizure severity (76%), seizure-free days per week for ≥1 seizure type (67%), and seizure freedom in the last month (16%). The majority of respondents who reported a reduction in seizure frequency also reported improvements in seizure-free areas (5-80%). However, improvements in seizure-free ranges (18-56%) were also reported by patients in whom the seizure frequency had either not changed or had worsened. 93% of respondents stated that they wanted to continue CBD treatment. The reasons for this were both the lower seizure burden and the improvement in non-seizure-related comorbidities, the expert summarized.

Source: Press conference “Beyond Seizures – Insights into the therapy of difficult-to-treat, rare forms of epilepsy in children and adults”, 16.05.2024. Jazz Pharmaceuticals.

Further reading:

  • Berg AT, Dixon-Salazar T, Meskis MA, et al.: Caregiver-reported outcomes with real-world use of cannabidiol in Lennox-Gastaut syndrome and Dravet syndrome from the BECOME survey. Epilepsy Research 2024; 200: 107280.
  • Rosenberg EC, Chamberland S, Bazelot M et al. Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity. Neuron 2023; 111(8): 1282–1300.e8.
  • Patel AD, Mazurkiewicz-Bełdzińska M, Chin RF et al. Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial. Epilepsia 2021; 62(9): 2228–2239.
  • EPIDYOLEX® Information for healthcare professionals, current status. swissmedicinfo.ch.

InFo NEUROLOGIE & PSYCHIATRIE 2024; 22(3): 31

Autoren
  • Leoni Burggraf
Publikation
  • InFo NEUROLOGIE & PSYCHIATRIE
Related Topics
  • Epilepsy
  • Lennox-Gastaut syndrome
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