Basics
Description
- Status epilepticus (SE) is defined as continuous seizure activity >30 minutes or recurrent seizures in 30 minutes without return to baseline. In practice, an operational definition of convulsive seizures >5 minutes is treated as presumed SE.
- SE presents in several forms:
- Generalized SE: continuous or repeated generalized convulsion(s) with persistent loss of consciousness and neurologic function
- Nonconvulsive SE, myoclonic SE, or absence SE: persistent encephalopathy, often with variable subtle motor signs such as myoclonus or nystagmus
- Repeated partial seizures with alteration of consciousness (focal SE) or preserved consciousness (epilepsia partialis continua)
- Systemic complications of SE:
- Hyperthermia, rhabdomyolysis
- Tachycardia, hypertension early ¢ † ’ hypotension late
- Hypoxia, hypercapnia, aspiration pneumonia
- Impaired cerebral autoregulation
- Rare: cardiac arrhythmias, neurogenic pulmonary edema, bone fractures
Alert
- Neuromuscular blockers used in intubation may obscure ongoing seizures. EEG monitoring is mandatory for all patients who have had any pharmacologic paralysis during SE.
- Continued encephalopathy after convulsions have ended may indicate continued electrographic seizures (nonconvulsive SE).
- Nonepileptic seizures can be mistaken for SE. EEG establishes the diagnosis.
Epidemiology
- Incidence in pediatric patients is 17 " “23/100,000. In children <1 year old, incidence is 135 " “156/100,000.
- ¢ ˆ ¼40 " “70% of children have no history of seizures.
Risk Factors
- Known epilepsy
- Remote or acute central nervous system insult
- History of previous SE
- Low anticonvulsant drug levels
- Younger age
General Prevention
- Adherence to the anticonvulsant medication regimen and clinical follow-up in patients with epilepsy
- Refrain from rapid changes in anticonvulsants unless urgently needed.
- Prompt treatment of convulsive seizures
Pathophysiology
SE may be related to acute or chronic factors or frequently of unknown etiology. ‚
- Common acute factors:
- Fever
- Infectious meningoencephalitis
- Metabolic: electrolyte abnormalities, hypoglycemia
- Intoxications
- Trauma or hemorrhage
- Ischemic stroke, hypoxic " “ischemic injury
- Medications: low anticonvulsant drug levels or abrupt withdrawal of anticonvulsants, inappropriate anticonvulsants (e.g., absence SE with phenytoin or carbamazepine use in generalized epilepsy)
- Subacute or chronic factors:
- Epilepsy of any cause
- Brain tumors
- Brain malformations (e.g., lissencephaly, polymicrogyria, hemimegalencephaly, neurocutaneous syndromes " ”tuberous sclerosis complex, Sturge-Weber syndrome)
- Other structural brain abnormalities such as strokes hypoxic " “ischemic encephalopathy (HIE), or periventricular leukomalacia (PVL)
- Genetic epilepsies: Dravet syndrome (febrile SE), Angelman syndrome (myoclonic SE), progressive myoclonic epilepsy syndromes
- Inflammatory disorders (e.g., Rasmussen encephalitis, N-methyl-D-aspartate [NMDA] receptor antibody syndrome)
Diagnosis
History
- Ask about prior seizures, treatment with antiepileptic drugs (AEDs), and other neurologic abnormality, including previous neurologic workup such as MRI brain or EEG.
- Ask specifically about precipitating factors: fever, preceding illness, head trauma, change in antiepileptic medication, and family history of seizures
Physical Exam
- Vital signs: fever, respiratory rate/O2 sats (adequacy of air exchange and abnormal breathing patterns), heart rate, BP (hypertension suggests intracranial hypertension)
- Signs of head trauma: retinal hemorrhages, excess bruising, bone fractures, evidence of intracranial hypertension such as bulging fontanelle
- Meningismus signals CNS infection, intracranial hemorrhage, or spine trauma. May be absent in young infants with meningitis
- Signs of systemic infection: fever (also potentiates seizure activity), petechiae, rash, mucosal lesions, lymphadenopathy
- Skin examination: Check for evidence of neurocutaneous disorders (e.g., cafe au lait spots, ash leaf spots, shagreen patches).
- Observe clinical presentation, specifically focal features or asymmetry.
- Postictal exam: Transient neurologic abnormalities (e.g., pupillary asymmetries, eye deviation, focal motor weakness [Todd paresis], aphasia) may not correlate with the underlying structural lesion. After seizure has stopped, a neurologic examination should be performed, with attention to mental status, focal weakness, tone, or sensation.
Diagnostic Tests & Interpretation
Lab
Initial: ‚
- STAT glucose, electrolytes, calcium, magnesium, and arterial blood gas
- Anticonvulsant levels if indicated
- CBC, liver function tests
- Toxicology screen, urinalysis
imaging
Neuroimaging, CT, or MRI: indicated for SE, especially with partial-onset seizures (including aura), focally abnormal EEG, focal neurologic signs, or history of head trauma. MRI is the preferred neuroimaging test, but CT may be more appropriate for urgent imaging or if the patient is medically unstable. ‚
Diagnostic Procedures/Other
- EEG: recommended to determine continued electrographic seizures and to identify focal versus generalized abnormalities. Urgent EEG recommended in patients with persistent SE or encephalopathy and in those with concern for nonconvulsive SE and nonepileptic SE.
- Lumbar puncture (LP): indicated to evaluate CNS infection in cases with suspected meningitis of encephalitis. Contraindications include intracranial hypertension known or suspected from exam or CT scan, cerebral mass lesion, and obstructive hydrocephalus. Lumbar puncture may be deferred if suspicion of CNS infection is low, that is, patient is afebrile, and an alternate etiology is present
Differential Diagnosis
- Nonepileptic SE: clinically suspected with eye closure; asynchronous, thrashing limb movements; pelvic thrusting, fluctuating responsiveness, head side to side movements, purposeful resistance to passive movement; and normal concurrent EEG. Induction of a seizure by suggestion further supports this diagnosis.
- Movement disorders (including dystonia, chorea, and very frequent tics) can be mistaken for persistent seizure activity.
- Postanoxic myoclonus: status after prolonged cardiopulmonary arrest. These movements are usually nonrhythmic and segmental but can appear rhythmic at times. EEG is recommended for diagnosis.
Treatment
Initial Stabilization
- ABCs (stabilization of airway, supporting respiration, maintaining BP, and gaining intravascular access)
- Assess for hypoxia, hemodynamics, hyperthermia, hypoglycemia, hyponatremia.
- BP, EKG, and respiratory function should be monitored.
- Airway control may be maintained by head positioning, and oral airway placement and oxygen supplementation provided via nasal cannula, mask, or bag " “valve " “mask ventilation. If the need for respiratory assistance persists, endotracheal intubation may be required.
- For hypoglycemia: 2 " “4 mL/kg of D25
- Rectal acetaminophen and a cooling blanket for fever
Medication
Anticonvulsant administration should be initiated when continuous seizure activity persists for >5 minutes. The most important modifiable treatment parameter is timing to treatment, and sooner treatment provides better seizure control. ‚
Alert
- 1st line: benzodiazepines
- Lorazepam 0.05 " “0.1 mg/kg IV (max 5 mg over 1 " “4 minutes)
- If no IV: diazepam 0.2 " “0.5 mg/kg/dose PR (max 20 mg/dose) or nasal or buccal midazolam
- 2nd line
- Fosphenytoin 20 mg PE/kg IV
- If fosphenytoin unavailable: phenytoin 20 mg/kg IV
- 3rd line
- Phenobarbital 20 mg/kg IV; can give additional 10 mg/kg if needed
- Alternatives: valproic acid 20 " “40 mg/kg over 5 " “10 minutes, levetiracetam, or others
- 4th line: refractory SE
- Midazolam or pentobarbital continuous infusion to seizure control or burst suppression
- Alternatives: propofol (beware of propofol infusion syndrome with prolonged use), inhalational anesthetics
General Measures
- Attempt to establish IV access, but do not waste time on IV access. Consider IM midazolam, IN midazolam, or IO access or rectal diazepam immediately. The most important modifiable treatment parameter is timing to treatment.
- Consider bedside EEG monitoring in any patient who needs more than the listed second line treatment.
Ongoing Care
Patient Monitoring
- Cardiorespiratory monitoring, level of care as appropriate for clinical status
- Monitor hydration and creatine kinase (CK) levels in case of convulsive SE.
- Consider need for continued video-EEG monitoring and medication titration.
Patient Education
- Need for long-term anticonvulsant drug therapy after SE depends on the etiology, patient 's age, and circumstances in which SE occurred.
- Chronic anticonvulsant therapy is indicated when SE is caused by structural brain lesions and in other patients with a clear predisposition toward seizures.
- Chronic anticonvulsant therapy is generally not needed in children who have SE from transient metabolic disturbances (e.g., hyponatremia, intoxication, fever).
- Educate family members regarding first aid for seizures. Discuss potential risks of seizure recurrence even if the child is taking an anticonvulsant drug. Review risks of climbing, swimming, bathing, and head protection for wheeled toys (bikes, skateboards, scooters).
- Provide caregivers with rectal diazepam with instructions for its use for seizure ≥ 5 minutes in duration.
- For patients with known epilepsy, counsel families regarding importance of medication compliance.
Prognosis
The morbidity and mortality of SE reflect etiology and are lower in children than in adults. Recent mortality estimates in children range from 1 to 3%, with risk of new neurologic sequelae estimated at 15% and subsequent epilepsy at 30%. Refractory SE, however, has a morbidity estimated at 32% and a mortality of 17%. Factors associated with outcome include duration of SE, patient age, and underlying cause. ‚
Additional Reading
- Appleton ‚ R, Macleod ‚ S, Martland ‚ T. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children. Cochrane Database Syst Rev. 2008;(3):CD001905. ‚ [View Abstract]
- Chin ‚ RF, Neville ‚ BG, Peckham ‚ C, et al. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol. 2008;7(8):696 " “703. ‚ [View Abstract]
- Hirsch ‚ LJ, Gaspard ‚ N. Status epilepticus. Continuum (Minneap Minn). 2013;19(3):767 " “794. ‚ [View Abstract]
- Loddenkemper ‚ T, Goodkin ‚ HP. Treatment of pediatric status epilepticus. Curr Treat Options Neurol. 2011;13(6):560 " “573. ‚ [View Abstract]
- Ostrowsky ‚ K, Arzimanoglou ‚ A. Outcome and prognosis of status epilepticus in children. Semin Pediatr Neurol. 2010;17(3):195 " “200. ‚ [View Abstract]
- Riviello ‚ JJ Jr., Ashwal ‚ S, Hirtz ‚ D, et al. Practice parameter: diagnostic assessment of the child with status epilepticus (an evidence-based review). Neurology. 2006;67(9):1542 " “1550. ‚ [View Abstract]
- Singh ‚ RK, Stephens ‚ S, Berl ‚ MM, et al. Prospective study of new-onset seizures presenting as status epilepticus in childhood. Neurology. 2010;74(8):636. ‚ [View Abstract]
- Trinka ‚ E, H ƒ ¶fler ‚ J, Zerbs ‚ A. Causes of status epilepticus. Epilepsia. 2012;53(Suppl 4):127 " “138. ‚ [View Abstract]
Codes
ICD09
- 345.3 Grand mal status
- 345.10 Generalized convulsive epilepsy, without mention of intractable epilepsy
- 345.00 Generalized nonconvulsive epilepsy, without mention of intractable epilepsy
- 345.80 Other forms of epilepsy and recurrent seizures, without mention of intractable epilepsy
ICD10
- G40.901 Epilepsy, unsp, not intractable, with status epilepticus
- G40.401 Oth generalized epilepsy, not intractable, w stat epi
- G40.411 Oth generalized epilepsy, intractable, w status epilepticus
- G40.801 Other epilepsy, not intractable, with status epilepticus
- G40.211 Local-rel symptc epi w cmplx partial seiz, ntrct, w stat epi
- G40.111 Local-rel symptc epi w simple part seiz, ntrct, w stat epi
- G40.311 Generalized idiopathic epilepsy, intractable, w stat epi
- G40.011 Local-rel idio epi w seiz of loc onset, ntrct, w stat epi
- G40.811 Lennox-Gastaut syndrome, not intractable, w stat epi
- G40.201 Local-rel symptc epi w cmplx prt seiz, not ntrct, w stat epi
- G40.501 Epileptic seiz rel to extrn causes, not ntrct, w stat epi
- G40.101 Local-rel symptc epi w simp part seiz, not ntrct, w stat epi
- G40.911 Epilepsy, unspecified, intractable, with status epilepticus
- G40.301 Gen idiopathic epilepsy, not intractable, w stat epi
SNOMED
- 230456007 Status epilepticus (disorder)
- 13973009 grand mal status (disorder)
- 442512002 Nonconvulsive status epilepticus (disorder)
- 230459000 Non-convulsive simple partial status epilepticus (disorder)
- 434211000124108 Grand mal status epilepticus, non-refractory (disorder)
- 434501000124107 Complex partial status epilepticus, refractory (disorder)
- 434201000124105 Grand mal status epilepticus, refractory (disorder)
- 434511000124105 Complex partial status epilepticus, non-refractory (disorder)
FAQ
- Q: Does SE cause brain injury?
- A: Research suggests that neuronal loss may occur with prolonged SE. This illness represents a neurologic emergency. Other determinants of outcome are hypoxic brain injury due to hypoventilation during a seizure and brain injury because of an identifiable underlying cause of SE such as encephalitis. Outcome in children with idiopathic SE without hypoxia is usually very good. Outcome of SE due to other brain injury (e.g., hypoxia, encephalitis, trauma) depends on the severity of the inciting process.
- Q: How safe is administration of rectal diazepam for clusters of seizures?
- A: Studies suggest that when dosing guidelines are followed, this agent is safe and effective in terminating clusters of seizures, obviating a trip to the emergency room. Respiratory depression is very rare but can occur.
- Q: How likely is SE to recur?
- A: It is estimated at 17% in the 1st year and predominantly in children with other neurologic conditions.