Unanticipated improvement in seizure control in drug-resistant epilepsy- real world observations

Abstract

To determine the clinical features and anti-seizure medication (ASM) strategies associated with an unanticipated substantial improvement in seizure control in patients with drug-resistant epilepsy (DRE). Methods: This retrospective analysis of patients attending a tertiary care epilepsy clinic between 2008 and 2017 identified all patients with active DRE (at least 1 seizure per month for 6 months, despite treatment with 2 different ASMs). All treatment interventions were recorded from when DRE was first identified to the end of the study. The primary end points were seizure freedom or meaningful reduction in seizure frequency (greater than 75 %) sustained for at least 12 months after a treatment intervention. Results: Three hundred and twenty-two patients were included in the analysis. Overall, 10 % became seizure free following ASM adjustment and an additional 10 % had a greater than 75 % improvement in seizure control (median follow-up, 4 years). An ASM introduction was ten times more likely than an ASM dose increase to improve seizure control. Combined focal and generalized epilepsy, intellectual disability and prior treatment with more than 5 ASMs were more frequently observed in those with continued pharmacoresistance. ASM responders were more likely to have primary generalized epilepsy. Rational polytherapy (combining ASMs with different mechanisms of action) was almost ubiquitous amongst ASMs responders (95 % taking at least 2 drugs with different mechanistic targets). Of the ASM additions that heralded improved seizure control, 85 % were maintained at submaximal doses. Conclusions: This retrospective analysis of a large number of 'real-world' patients provides evidence to persist with ASM trials in DRE. Early rotation of ASMs if a clinical response is not observed at a substantial dose and rational ASM polytherapy may yield better clinical outcomes in patients with DRE, although a prospective study would need to be conducted to validate these findings.

High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial)

“…Participants will be randomized between SRT and standard of care at a ratio of 1:1. We expect that 50% of the patients in the SRT group will reach RAEC I–III after 2-year follow-up compared to at best 15% in the standard of care group [ 17 , 18 ]. Sample size calculation is based on a two-sided Z -test for proportions with pooled variance and continuity correction.…”

High precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION-trial).

“…Comparison to current standard treatment Comparison to Anti-Seizure Medication (ASM): According to the Dutch Epilepsy guidelines from the Dutch Neurology Society (NVN) the standard of care treatment for patients with focal epilepsy is ASM. In patients with drug-resistant epilepsy 10 % become seizure free following ASM adjustment and an additional 10 % have a greater than 75 % improvement in seizure control after a median follow-up of 4 years [19]. Comparison to neuromodulation: VNS and DBS are both palliative treatment alternatives when patients are not eligible for open surgery.…”

Brain Injury and Neuroinflammation of the Gut-Brain Axis in Subjects with Cerebral Palsy

“…The specific activation of GABA receptors induces the opening of chloride channels in the neuron membrane, amplifying the influx of this anion into the cell, which results in decreased excitability and the spread of excitatory impulses. Among the effects observed for these drugs are described the reduction of salivary flow, the vomiting reflex and the relaxation of skeletal muscles [33].…”

“…Voltage-dependent Na + is one of the principal channels responsible for the rapid depolarization of the widely and disorganized presence and neuronal membrane in the epileptic processes [34]. These channels represent the important site of connection for several antiepileptic drugs such as hydantoin, carbamazepine, valproic acid, lamotrigine, among others [33].…”

“…For example, the presynaptic Ca + 2 entry is associated with the liberation of these neurotransmitters and to their postsynaptic entry with sustained neuron depolarization. Blocking the Ca + 2 channels can produce several effects on the neuronal functioning: (a) blocking Type T channels (associated to absence crisis treatment); (b) blocking type L channels (associated with partial crisis treatment); (c) blocking Ca + 2 channels can prevent the liberation of excitatory neurotransmitters such as glutamate and (d) blocking these channels reduces the concentration of Ca + 2 ions in the neuronal cytoplasm, reducing the possibility of excitotoxic cellular damage [33].…”