DeCure for Developmental and epileptic encephalopathy, 5

The term developmental and epileptic encephalopathy (DEE) describes a group of conditions in which cognitive function is affected by both seizure activity and the underlying neurobiological process. Many DEEs are linked to gene variants, with onset typically in early childhood. A 2021 review notes that while seizure control alone does not improve neurocognition in DEE, some precision therapies may offer benefit. The same review distinguishes DEE from developmental encephalopathy (DE), where epileptiform activity has minimal effect on function, and from epileptic encephalopathy (EE), where cognition is directly impaired by seizures and can often return to near normal with aggressive treatment. The authors state that patients with DE are unlikely to gain from aggressive antiseizure medication, while those with EE will gain.

A 2023 study from a reference centre in Northeast Brazil reports that, as of August 2022, 105 genes had been associated with DEE according to OMIM. A 2022 case report describes an 8-year-old male with EIEE-50, an autosomal recessive DEE caused by CAD mutations, who presented with global developmental delay and regression, refractory epilepsy, and anaemia. After diagnosis, uridine treatment was used and the authors describe encouraging results, though they provide no quantitative outcomes such as seizure frequency or developmental scores.

A 2021 retrospective study of eight paediatric patients (≤14 years) with epileptic encephalopathy or refractory focal epilepsy treated with brivaracetam found that all patients achieved at least a 50% reduction in seizure frequency. Of these, 37.5% became seizure-free, 25% had a ≥75% reduction, and 37.5% had a ≥50% reduction. The maximum effect was seen at 2 mg/kg/day, and the effect was not dose-dependent. All patients with epilepsy onset after 12 months and epilepsy duration of six years or less became seizure-free. Focal seizures responded better than epileptic encephalopathy, but a positive effect was noted in patients with encephalopathy related to status epilepticus during sleep. No relevant side-effects were reported.

A 2023 systematic review of ketamine for neonatal refractory status epilepticus identified eight cases (seven published plus one novel case). Seizures typically began in the first 24 hours of life and were resistant to a mean of five antiseizure medications. Ketamine appeared safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for four of the five surviving children; three of those five were seizure-free at 1–17 months. The authors note that neonatal brain is more susceptible to seizures due to increased excitation, providing a rationale for ketamine use, but call for further studies and clinical trials on larger populations. A 1990 case report describes cat-scratch encephalopathy in a five-year-old with status epilepticus and lymphadenitis; seizures were refractory to usual anticonvulsant therapy, but all neurologic symptoms resolved within nine months without sequelae. A 2020 case report describes metronidazole-induced encephalopathy in a 5-month-old infant presenting with nonconvulsive status epilepticus.