Icahn School of Medicine at Mount Sinai, New York, NY, USA
Background
Definition of disease
Convulsive status epilepticus (CSE) is defined as ‘an acute epileptic condition characterized by continuous generalized convulsive seizures for at least 5 minutes, or by 2 seizures without full recovery of consciousness between seizures.’
Non‐convulsive status epilepticus (NCSE) is defined as ‘continuous or intermittent ictal discharges without the patient regaining consciousness, and no overt clinical signs of convulsive activity.’
Incidence/prevalence
Between 20 and 40/100 000 per year in the USA, with a first peak before 1 year of age and a second peak after 60 years of age.
About 31–43% of status epilepticus become refractory.
NCSE affects up to 10% of patients with altered mental status and 16% of confused elderly patients.
Etiology
Common etiologies include anoxic brain injury, antibody‐mediated disease (autoimmune or paraneoplastic), brain tumor, infection (meningitis, encephalitis, abscess, sepsis), drug or alcohol intoxication/withdrawal, low antiepileptic drug levels or change in antiepileptic drug regimen, metabolic disturbance, stroke, trauma, congenital malformation/remote brain injury, and idiopathic causes.
Pathology/pathogenesis
Status epilepticus occurs when there is either excessive excitation or ineffective inhibition of seizures. Increased excitation occurs as a result of increased glutamate or other excitatory amino acids. During status epilepticus, N‐methyl‐d‐aspartate (NMDA) receptors accumulate rapidly and increase glutaminergic excitation. Decreased inhibition results from decreased γ‐aminobutyric acid (GABA), and GABA‐A receptors change in number and sensitivity during status epilepticus. Other mechanisms, such as mitochondrial failure, inflammatory processes, and changes in gene expression, are also involved.
Predictive/risk factors
Risk factor
Odds ratio
Coma
7.7
History of epilepsy
2.7
Convulsive seizures during the current illness prior to monitoring
2.4
Prevention
Screening
EEGs should be performed in:
Patients who are critically ill and have alteration of consciousness without an alternative explanation.
Patients who had convulsive seizures and did not return to their baseline within 10–20 minutes after cessation of convulsive activity.
Patients with unexplained focal neurologic deficits, such as hemiparesis, aphasia, or visual field defect.
Patients with repetitive, involuntary movements.
A 30–60 minute EEG monitoring will miss all seizures in more than half of patients having non‐convulsive seizures.
Continuous monitoring is recommended for at least 24 hours for patients who are not comatose, and 48 hours for patients who are comatose or those with frequent periodic epileptiform discharges.
Diagnosis
A careful history should be taken to investigate the etiology of the status epilepticus.
Overt CSE is readily diagnosed by clinical presentation, and in this case, does not require continuous EEG.
NCSE cannot be diagnosed without an EEG. In critically ill patients with decreased level of consciousness, regardless of primary neurologic or medical condition, NCSE is common. Patients with a history of epilepsy, fluctuating level of consciousness, acute brain injury, and recent CSE are at most risk for NCSE.
ICU patients commonly have abnormal involuntary movements, which may not be epileptic in origin. Continuous EEG is indicated to correctly diagnose them in order to avoid unnecessary treatments.
Differential diagnosis
Differential diagnosis
Features
Persistent non‐convulsive seizures vs. prolonged postictal state, medication effects, or from underlying neurologic condition that caused the seizures
Persistent decreased consciousness after cessation of convulsive seizures
Seizures, tremor, clonus, or dyskinesia
Abnormal involuntary movements
Typical presentation
CSE is manifested by repetitive generalized tonic‐clonic seizures without return to baseline in between seizures. After convulsive seizures stop, the patient can still have electrographic status epilepticus with no apparent abnormal body movement. So if the patient does not show significant improvement in the level of consciousness within 10–20 minutes after the movement stops, the clinician should suspect ongoing NCSE and an EEG should be performed urgently.
Focal NCSE can present as very subtle changes, such as mild confusion, mouth or hand automatism, speech arrest, eye deviation, nystagmus, or subtle twitching.
Clinical diagnosis
History
History should include the onset of seizure or altered mental state, time course, past medical history including prior history of seizures or epilepsy, medications and recent medication changes, history of drug or alcohol abuse, etc.
It is important to get collateral history from the family or a person who knows the patient well.
Any function the brain is capable of generating can manifest as a symptom of NCSE, such as subtle behavioral or cognitive changes, autonomic disturbance, or motor/sensory disturbance.
Physical examination
In addition to typical general and neurologic examination, observe subtle signs such as:
Refractory status epilepticus is defined as recurrent seizure activity despite two appropriately selected and dosed antiepileptic drugs, including benzodiazepine.
Super‐refractory status epilepticus refers to status epilepticus that continues or recurs 24 hours or more after the initiation of anesthetic drugs.
CSF: cell count, glucose, protein, Gram stain and culture (when an infectious or inflammatory etiology is suspected, the threshold for lumbar puncture should be low in patients with no history of epilepsy or seizures and no apparent CT head findings, and even in patients with epilepsy whose seizure frequency is usually low).
Brain and/or meningeal biopsy: in patients whose thorough evaluation is non‐diagnostic and if anyill‐defined lesion is present on MRI.
List of imaging techniques
CT head: indicated in all patients unless the history offers an obvious explanation for the status epilepticus.
Brain MRI: in patients whose etiology is not established after history, basic laboratory evaluation, lumbar puncture, and CT head.
Chest/abdomen/pelvis CT: in patients who are suspected to have autoimmune/paraneoplastic encephalitis.
Ovarian or testicular ultrasound: in patients who are suspected to have NMDA encephalitis.
Angiogram: in patients who are suspected to have vasculitis.
Potential pitfalls/common errors made regarding diagnosis of disease
Sometimes, patients who are having a cluster of non‐epileptic seizures are misdiagnosed as having convulsive status epilepticus and it can lead to iatrogenic complications.
Psychogenic status epilepticus should be suspected when:
Convulsions are prolonged without accompanying signs of sympathetic activation.
There is pelvic thrusting, eye closure, or asynchronous or side‐to‐side body or head movement.
There is minimal postictal confusion between or after convulsions.
There are bilateral convulsions with preserved consciousness.
Treatment
Diagnosis of status epilepticus, evaluation for the etiology, and management of status epilepticus should occur simultaneously. Patients who present with convulsive status epilepticus should receive treatment without delay. Patients who are suspected to have NCSE should have urgent continuous EEG monitoring.
Treatment rationale
First line therapy: the first line treatment of choice in CSE is a benzodiazepine. If IV access is established, use IV lorazepam. If IV access is not established, use IM, nasal, or buccal midazolam or rectal diazepam.
Second line therapy: even if the seizures stop after first line therapy, it is recommended to initiate second line therapy to prevent seizures from returning when the effect of the benzodiazepines wears off. The choice of second line therapy is guided by the patient’s etiology and comorbidities. Fosphenytoin is often recommended for this, but if the patient has idiopathic generalized epilepsy, valproic acid may be a better choice. Randomized controlled trials have shown that IV valproate is not inferior and may even be more effective than IV phenytoin.
Failure of second line therapy = refractory status epilepticus. For generalized CSE or NCSE with severe impairment of consciousness, if seizures continue after one first line and one second line drug, it is recommended to start anesthetic drugs to prevent acute systemic complications, with initial bolus or repeated boluses followed by continuous infusion. If the patient is awake or has mild alteration of consciousness, it is recommended postponing the use of anesthetic drugs and try more than one second line drugs. The NCS guidelines recommend at least 24–48 hours of electrographic seizure control before slowly withdrawing the drug, which is usually done over 24 hours.
Failure of anesthesic drugs = super‐refractory status epilepticus. When seizures do not stop or recur after withdrawal of anesthesic medications, therapeutic options include a second trial of the same anesthetic drug, switching to another anesthetic drug, or a combination of anesthetic drugs. Other therapies including immune therapies, ketogenic diet, hypothermia, neurosurgery, and electroconvulsive therapy could be considered.
When to hospitalize
Patients who present with status epilepticus should be hospitalized for proper evaluation and management.
Patients who have refractory CSE or who are suspected of having NCSE should be managed in an ICU that can provide continuous EEG.
Managing the hospitalized patient
The priority is always to ensure ABC (airway, breathing, circulation).
Check finger‐stick glucose, and, if low, give thiamine 100 mg IV once prior to dextrose.
Initiate first line therapy and consult neurology.
Table of treatment: anticonvulsant drugs for status epilepticus
Treatment
Loading dose/route
Maintenance dose
Mechanism of action
Adverse reactions
First line agents
Lorazepam
0.1 mg/kg up to 4 mg IV
n/a, repeat loading dose once if necessary
GABA agonist
Respiratory depression, sedation, hypotension
Midazolam
0.2 mg/kg up to 10 mg IM
n/a, repeat loading dose once if necessary
GABA agonist
Same as above
Diazepam
0.2 mg/kg up to 20 mg rectally or 0.1 mg/kg up to 10 mg IV
n/a, repeat loading dose once if necessary
GABA agonist
Same as above
Second line agents
Phenytoin
18–20 mg/kg IV up to 50 mg/min
5–7 mg/kg/day PO/IV divided every 8 hours
Sodium channel modulation
Cardiorespiratory depression, arrhythmia, hypotension, metabolic acidosis, infusion site injury
Fosphenytoin
18–20 phenytoin equivalents/kg IV up to 150 mg/min
5–7 phenytoin equivalents/kg/day IV, divided every 8 hours
