Absence Status Epilepticus

Absence status epilepticus is prolonged or repeated absence seizures lasting 30 minutes or longer, with continuous or fluctuating generalised spike-and-wave on EEG and clouding of consciousness. It is a form of nonconvulsive status epilepticus and usually responds to intravenous benzodiazepines.

It occurs in about 3 to 8% of patients with genetic generalised epilepsy and in some with de novo late onset disease. It is more common in adolescents and adults than in young children.

Types. Typical absence status in genetic generalised epilepsy; atypical absence status in developmental encephalopathies such as Lennox-Gastaut syndrome; and de novo absence status of late onset, often triggered by drug or alcohol withdrawal, psychotropic drugs or metabolic disturbance.

Triggers. Sleep deprivation, withdrawal of a benzodiazepine or antiseizure drug, tramadol and other drugs that lower the seizure threshold, hyperventilation and stress.

Pathophysiology.

Failure of thalamocortical inhibitory control, with persistent T-type calcium channel oscillation, sustains generalised spike wave discharge.

Withdrawal of GABAergic drugs or the use of sodium channel blockers and GABA-enhancing drugs such as tiagabine can aggravate the thalamocortical rhythm.

• Fluctuating confusion lasting from 30 minutes to days, with slowed responses, mutism or dysarthria, and some retained function.
• Subtle eyelid flutter, facial or hand myoclonus and automatisms.
• Preserved ability to do simple tasks, giving a dreamlike or stuporous state.
• Occasional recurrent generalised tonic clonic seizure at the end of the episode.

Red flags.

• Persistent confusion in a patient with known generalised epilepsy.
• Sudden onset of confusion after drug withdrawal in an older adult.
• Failure to respond to an intravenous benzodiazepine.

• Urgent EEG: continuous or nearly continuous generalised 2.5 to 4 Hz spike-and-wave, with clinical and EEG improvement after intravenous benzodiazepine.
• Bedside glucose, electrolytes, renal and liver function, toxicology and drug levels.
• CT or MRI when a structural, vascular or infective cause is suspected.
• Review of recent drug changes and withdrawal.

Differential diagnosis. Focal impaired awareness status epilepticus, delirium, metabolic encephalopathy, psychiatric illness, intoxication, transient global amnesia and stroke.

• Lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes if the EEG shows continuing spike wave. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; no renal adjustment; use only when needed in pregnancy.
• Sodium valproate if benzodiazepines fail or to prevent relapse: 40 mg/kg intravenously (maximum 3000 mg) over 10 minutes, then oral continuation. Monitor liver function, ammonia, platelets and pancreatitis. Avoid in liver disease, mitochondrial disease and urea cycle disorders; contraindicated in girls and women of childbearing potential unless no alternative works and a pregnancy prevention programme is in place.
• Levetiracetam 60 mg/kg intravenously (maximum 4500 mg) over 10 minutes as an alternative. Monitor mood, behaviour and renal function. Reduce dose when creatinine clearance is under 50 mL/min; acceptable in pregnancy.
• Avoid phenytoin, carbamazepine, tiagabine, vigabatrin and gabapentin, which can aggravate absence seizures.
• De novo late onset absence status: treat the precipitant (restart the withdrawn benzodiazepine or antiseizure drug, correct electrolytes, stop the offending drug) and usually give a short course of an antiseizure drug.
• Genetic generalised epilepsy: review long term treatment, with valproate, lamotrigine, levetiracetam or ethosuximide chosen by sex and syndrome.

Monitoring. Repeat EEG to confirm resolution; clinical review in 1 to 2 weeks; monitor drug levels where relevant.

Referral and escalation. Epilepsy specialist for diagnosis and treatment change; intensive care for refractory status or respiratory depression.

Special groups. Older adults: assess for drug and withdrawal causes and cognitive impairment. Women of childbearing potential: avoid valproate unless required.