Incidence: Overall incidence of SE is 7-41/100,000.

• Bimodal distribution with peaks in children < 1 yo and adults > 60 yo. Population-based studies vary widely depending on classification, duration, and definition used for SE.

  • • In a study restricted to generalized convulsive SE, incidence was reported to be 6.8/100,000.

Mortality: Depends on age, underlying etiology, and duration.

• In the Veterans Affairs cooperative study, 30 d mortality for patients with overt generalized convulsive SE was 27%.

• Two clinical scoring systems have been devised to attempt to predict mortality from SE: Further validation is required before these scores are universally adopted for clinical use.

  • • STESS is based on level of consciousness, seizure type, patient age, and seizure history. 

    • EMSE incorporates age, etiology, comorbidities, and EEG characteristics. 

Terminology: 

I. Seizures

• manifest due to a brief disruption in normal brain activity, caused by rhythmic electrical discharges

II. Convulsive Seizures

• classically seen with rhythmic jerking of extremities 

• typically generalized tonic / clonic or tonic-clonic activity with mental status impairment

• May have focal neurological deficits in the post ictal period (e.g., Todd’s paralysis) 

III. Nonconvulsive Seizures 

• The vast majority of seizures and SE in the intensive care unit (ICU) are not associated with convulsive activity and are hence nonconvulsive in nature. 

• Nonconvulsive seizures does not mean complete absence of motor activity however, as these seizures are frequently associated with subtle motor findings. 

Clinical Manifestations of nonconvulsive seizures:

• Coma, altered consciousness, or altered sensorium​

• Catatonia​

• Behavior changes and psychotic symptoms (e.g. delusions, paranoia, hallucinations)​

• Subtle motor signs (e.g. automatisms, cyclonic jerks, myoclonus, eye twitching, eye deviation)​

• Speech disorders (e.g. verbal perseveration, aphasia, speech arrest, disorganized speech)​

• Autonomic dysfunction

IV. Status Epilepticus (SE) 

• SE is clinical or electrographic seizure activity lasting > 5 min or recurrent seizure activity without fully returning to neurologic baseline between seizures.

• Pathophysiology of SE is not completely understood but involves an imbalance of neurotransmitters with excess excitation and reduced inhibition. 

  • • Glutamate acts as the principal excitatory neurotransmitter while GABA serves as the main inhibitory neurotransmitter in the CNS

V: Non-Convulsive Status Epilepticus (NCSE)

• Electrographic seizure activity without clear clinical convulsive activity

• Two Distinct clinical phenotypes are seen

1. 1. 1.  ‘‘wandering confused’’ or “twilight status”  patient presenting to the emergency department with a relatively good prognosis  or chronic epileptic syndromes or, ​

      2.  The acutely ill patient with severely impaired mental status, with or without subtle motor movements (e.g., rhythmic muscle twitches or tonic eye deviation that often occurs in the setting of acute brain injury) 

VI: Refractory Status Epilepticus (RSE)  

• Patients who do not respond to standard treatment for status epilepticus 

• Have continued electrographic or clinical seizures despite adequate doses of initial benzodiazepine therapy + at least 1 anti-seizure  anti-seizure medication (ASM) 

VII: Super-refractory Status Epilepticus (SRSE)

• RSE that continues or recurs 24hrs after the onset of anesthetic therapy (ie burst suppression / seizure suppression) or recurs with weaning of anesthetic agents 

VIII: New-onset Refractory Status Epilepticus (NORSE)

• The cause of NORSE s is eventually found in about  50% of cases (usually autoimmune or paraneoplastic encephalitis), the other 50% of cases often do not have an identifiable etiology and often are termed “cryptogenic” NORSE or NORSE of unknown etiology

• A online resource for more information on NORSE, including a workup and treatment algorithm can be found here www.norseinstitute.org/definitions 

• commonly encountered etiologies of status epilepticus in the Neuro ICU include acute symptomatic epilepsy (related to underlying structural brain injury), remote symptomatic epilepsy (due to a prior history of injury such as stroke several years prior), and low anti-seizure medication levels in patients with known epilepsy.

• In elderly patients (> 70yo), prior stroke is the leading cause of status epilepticus 

Initial evaluation recommended for all patients:

• ABCs

• Fingerstick glucose – treat with D50 or insulin as appropriate

• Non-contrast CT head (appropriate for most cases)

• Neuroimaging should be obtained in patients who do not return to normal level of consciousness, have new focal neurologic findings, or have new onset SE without an otherwise identifiable cause. Only obtain imaging once patient is stable and discuess with attending / fellow.

• Laboratory tests: blood glucose, CBC, CMP, magnesium, phosphorus, AED levels

• cEEG monitoring or routine EEG (unless patient quickly returns to baseline)

Dependent on clinical presentation:

• Brain MRI w/ and w/o contrast

• LP: cell count, protein, glucose, gram stain and bacterial culture, viral PCRs (ie HSV1/HSV2), autoimmune workup

• Comprehensive toxicology panel (alcohol level, urine drug screen)

• Other laboratory tests: ABG, LFTs, ammonia, lactic acid, infectious work-up (UA, UCx, Bcx, CXR), coagulation studies, urine HCG

Evaluation of  NORSE / cryptogenic SE: 

• A diagnostic checklist for the work-up of NORSE can be found at http://www.norseinstitute.org/definitions

• CT chest/abdomen/pelvis

• Testicular and ovarian ultrasound (evaluate for teratoma)

• CSF studies: cytology, flow cytometry, viral PCRs, other microbiologic serologies/meningoencephalitis panels, autoimmune/paraneoplastic panels

• Serum studies: meningoencephalitis panels, other microbiologic serologies, rheumatologic antibodies/work-up, paraneoplastic/autoimmune panels, genetic testing (mitochondrial disorders such as POLG1)

• Heavy metals

• Porphyrins

• conventional angiogram (vasculitides)

Emergent (1st Line) Therapy

• Benzodiazepine for abortive therapy if clinical seizure > 5 min

• Then more benzodiazepines

• Then more benzodiazepines

  • Ok you get the point, maximize as they have the best chance at seizure cessation

Urgent Control (2nd Line) Therapy 

• The most common urgent control therapies are:

  • • • Valproic Acid

      • Levetiracetam 

      • Fosphenytoin 

• Levetiracetam and valproic acid are favored more in the NSICU given their predictable pharmacokinetics and relatively minimal cross-drug reactivities
  
  

Treatment Options for Refractory Status

• Treatment approaches vary considerably as there is no agreed upon universal guidelines for management of RSE and SRSE

• Patient / clinical / time course / EEG characteristics dictate AED direction

• Addition of 2nd, 3rd, 4th anti-seizure medications commonly encountered in addition to burst suppression 

  • • Commonly encountered treatment approaches: 

      • • Valproic Acid gtt 

        • Topiramate (high dose)

        • Phenobarbital 

        • Clobazam 

The addition and anti-seizure medications should be discussed with attending / fellow prior to presumptive therapy

• Anesthetic choices for RSE treatment

  • • Midazolam

    • Propofol 

    • Ketamine

    • Others: Pentobarbital, Thiopental (no longer available in US) 

Other Considerations in Super Refractory Cases

• Surgical 

• Ketogenic diet

• Stimulation (VNS, ECT, TMS) 

• Immunotherapy 

• Hypothermia (controversial)