Status epilepticus - Emerging treatments

Topiramate

Topiramate blocks voltage-gated sodium channels, enhances gamma-aminobutyric acid (GABA) transmission, blocks AMPA receptors of glutamate, and inhibits carbonic anhydrase. Reported effective in aborting SE in some patients when other medications failed.[62][63]

Intranasal diazepam

Diazepam nasal spray is approved by the Food and Drug Administration (FDA) for the treatment of acute repetitive seizures. In a small retrospective study of stroke patients presenting with SE, intranasal diazepam compared favorably with the intravenous formulation.[64] Intranasal administration of diazepam may be a practical alternative to the conventional administration of acute medication in SE, especially in patients with no intravenous access.

Allopregnanolone analogs

Ganaxolone and brexanolone are synthetic analogs of allopregnanolone, an endogenous neurosteroid that modulates the brain neurotransmitter GABA. In preclinical trials, intravenous ganaxolone yielded positive results in benzodiazepine-resistant SE.[65] The FDA has granted orphan drug designation to both drugs for the treatment of SE. While open-label phase 2 trials of ganaxolone and brexanolone have been promising, phase 3 trials have not met primary end points in refractory SE (RSE) and super-RSE.[66][67]

Ketamine

The FDA has granted orphan drug designation to ketamine for the treatment of SE. One retrospective study of 68 patients (mean age 53 years +/-18 years) found that seizure burden decreased by at least 50% within 24 hours of starting ketamine in 81% of patients with complete seizure cessation in 63% of patients. Ketamine also resulted in decreased vasopressor requirement without increased intracranial pressure.[68] Ketamine appears most effective if given early in the course of SE.[69]

Ketogenic diet

High-fat, low-carbohydrate diets (administered via gastric tube) that induce nutritional ketosis have been used for prolonged SE, with reports of 70% to 90% of patients emerging from SE after treatment with a ketogenic diet and other therapies.[70][71][72] The ketogenic diet is contraindicated in patients on propofol (a general anesthetic) due to an increased risk of propofol infusion syndrome.

Brivaracetam

Brivaracetam is an analog of the anticonvulsant levetiracetam that displays high and selective affinity for synaptic vesicle glycoprotein 2A (SV2A) and is believed to reduce neuronal excitability by modulating synaptic transmission.[73] Oral brivaracetam has demonstrated efficacy for the adjunctive treatment of adults with focal seizures in randomized, controlled clinical trials in the outpatient setting.[74][75][76][77] One retrospective observational study showed intravenous brivaracetam (n=56) to be effective in 32 (57%) of patients with SE.[78] Time to seizures resolution appears shorter when brivaracetam is administered in the early phases of SE.[78] Brivaracetam may be a valid alternative for the treatment of SE after the failure of first-line therapy, although it is not currently approved for this indication.[79]