Status epilepticus · Grey Matter

Status epilepticus is a seizure that does not stop by itself, or seizures that follow one another without recovery in between, and it is the emergency of epilepsy: the longer it lasts, the harder it is to stop and the more likely it is to leave damage.

Status epilepticus. Status epilepticus is a seizure that does not stop by itself, or seizures that follow one another without recovery in between, and it is the emergency of epilepsy: the longer it lasts, the harder it is to stop and the more likely it is to leave damage.

The definition is built on two times. The first (t1) is when the mechanisms that normally end a seizure have failed and treatment should start; the second (t2) is when lasting consequences, including neuronal death, become likely. For a convulsive tonic-clonic seizure the international definition of 2015 puts t1 at 5 minutes and t2 at 30 minutes; for a focal seizure with impaired awareness they are about 10 and 60 minutes. Most seizures end within two minutes, so one still going at five is unlikely to stop on its own.

It is treated in stages. A benzodiazepine comes first, given as early as possible; a second-line antiseizure drug follows if the seizure continues; refractory status is managed in intensive care with anaesthetic drugs.

Inhibition erodes while it lasts. During prolonged seizures, GABA-A receptors are pulled from the synapse into the cell, so a drug that boosts them has fewer targets; this is a leading explanation of why benzodiazepines work less well the later they are given.

Most cases are provoked. Stroke, bleeding, infection, metabolic disturbances, drug toxicity and stopping antiseizure medication are common causes; only about a quarter of people with status have epilepsy.

Nonconvulsive status, a long seizure without convulsions, is easily missed and is recognised only on the EEG, often in confused patients in hospital.

A seizure is self-limiting until it is not, and time is the variable that changes the treatment.

The brain's own brakes and the drugs that help them both weaken as a seizure continues.

Questions: Does a long seizure burn the brain with its electricity? The currents of a seizure are those of ordinary firing neurons and do not heat or burn the tissue. When damage happens, it is metabolic and chemical. Neurons driven to fire for many minutes release glutamate continuously, calcium floods in through NMDA and other receptors, and the calcium switches on enzymes that break down membranes, the cytoskeleton and DNA, a process called excitotoxicity. Energy demand outruns supply, mitochondria are strained, free radicals accumulate and cells swell. This is why status epilepticus has a time point, about 30 minutes for convulsive seizures, after which neuronal death becomes likely, while a brief seizure usually leaves no detectable damage. Why are benzodiazepines the first treatment for status epilepticus, and why do they work less the later they are given? Benzodiazepines act within minutes by making GABA-A receptors open more often, strengthening the inhibition that a seizure has overwhelmed, which is why guidelines put them first. During a prolonged seizure, however, synaptic GABA-A receptors are pulled into the cell, so there are fewer targets for the drug to act on. In animal models this internalisation tracks the loss of benzodiazepine effect, which is the main explanation for why delay matters and why second-line drugs act on other mechanisms. Why is a convulsive seizure that lasts more than five minutes treated as an emergency? Most tonic-clonic seizures stop within about two minutes, so one still running at five shows that the mechanisms that normally end a seizure have failed and it is unlikely to stop by itself. The international definition of 2015 sets that point, t1, at five minutes for convulsive status epilepticus, and a second point, t2, at 30 minutes, after which lasting consequences such as neuronal death become likely. Treatment starts at t1 because seizures become harder to stop the longer they run.