Treatment of Epileptic Encephalopathies: Current State of the Art

Abstract

Childhood epileptic encephalopathies are age-dependent disorders of the brain whose hallmarks include loss of neurologic function over time, abnormal electroencephalographic findings, and seizures. Ictal and interictal electrographic activity are conjointly thought to be at the root of the often devastating neuropsychological deterioration, which is specific to the maturing brain. The goals of treatment are not only to control seizures, but also to prevent or reverse neurologic loss of function. In general, time is of the essence in diagnosis, and experienced specialists should promptly design a treatment plan. Hormonal and immune therapies are at the forefront of treatment in many cases, with traditional antiepileptic drugs and surgery (when an identifiable lesion is present) playing a limited role. However, gold standard evidence for treatment of epileptic encephalopathies remains limited. Ongoing clinical and basic research may lead to better understanding of these catastrophic conditions and to better and more effective therapies.

Seizures and memory impairment induced by patient‐derived anti‐N‐methyl‐D‐aspartate receptor antibodies in mice are attenuated by anakinra, an interleukin‐1 receptor antagonist

“…We cannot determine from our data whether the improved memory is a consequence of the reduced seizure burden or an anti‐inflammatory effect of anakinra itself. The effects of persistent ictal and interictal activity are well documented in patients with epilepsy along with the improvement in cognition upon seizure control achieved with surgery or conventional antiseizure medications 50,51 . IL‐1 blockade with anakinra was also effective to reduce cognitive impairment in other acute seizure models and in a mouse model of traumatic brain injury 52,53 .…”

Scalp EEG high frequency oscillations as a biomarker of treatment response in epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS)

“…Hormonal therapy including ACTH or steroid is considered as disease-modifying agent in epileptic encephalopathy [9], and hormonal therapies may exert different effects on HFOs than conventional antiseizure medications. Also, fast ripples (> 250 Hz) may be a more specific biomarker of epileptogenesis than ripple (80-250 Hz), [22][23][24][25][26][27][28], and interictal fast ripples can be detected with scalp EEG in children [35].…”

“…[2,3] Classically, ESES is defined as a SWI that exceeds 85% of non-REM sleep [3], yet other studies have used different cut-off rates. [4][5][6][7] Anti-seizure medications including valproate, levetiracetam, benzodiazepines, and steroids have been used to treat epileptic encephalopathy with ESES and other related syndrome including Landau Kleffner syndrome, but the current evidence supports the use of steroids as the most effective therapy [8][9][10][11]. SWI has been used to evaluate the efficacy of treatment, yet it does not always reflect seizure and cognitive outcome [4,7,12].…”

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies

“…Early and accurate diagnosis is crucial for effective management [ 5 , 6 ], which is especially important given the compelling data in other DEEs that early treatment is associated with improved outcomes [ 7 ]. However, early diagnosis is significantly hampered by a number of challenges including a lack of agreed-upon clinical criteria and assessment measures, absence of specific biological markers and the diverse and evolving manifestations of the syndrome, which may have overlapping clinical features with other DEEs (Fig.…”