8.1 Overview and Definitions

Status epilepticus (SE) is a neurologic emergency. This chapter will address the evaluation and management of a seizing patient.

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  Seizures may be focal (starting in one part of the brain) or generalized (starting in the whole brain at once)

  
  
  
  
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    Focal seizures may impair consciousness or may occur without impaired consciousness

    
    
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    Generalized seizures will always cause impaired consciousness

  
  
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  Seizures may consist of tonic (stiffening) and clonic (rhythmic jerking) phases, but may also consist of staring, nonresponsiveness, and automatisms (unconscious movements)

There are two types of SE: convulsive SE (CSE) and nonconvulsive SE (NCSE)

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  Clinical presentation:

  
  
  
  
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    CSE: Rhythmic jerking of the extremities, impairment in mental status, and may have postictal focal neurologic deficits ¹

    
    
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    NCSE: Subtle and variable semiology (may have positive or negative symptoms) ^{1 , 2}

  
  
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  SE definitions were applied generally to CSE and NCSE in the past (refer to the points below). But now the definition of NCSE is evolving as continuous EEG monitoring has become more readily available and we can learn more about it (see below in NCSE section for definitions).

  
  
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  SE is defined by the Neurocritical Care Society Status Epilepticus guidelines as:

  
  
  
  
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    Continuous clinical and/or electrographic seizure activity of 5 minutes or more ¹

    
    
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    Recurrent seizure activity without a return to baseline between seizures ¹

  
  
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  Epidemiology:

  
  
  
  
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    50,000 to 150,000 SE cases per year are reported in the United States ³

    
    
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    Up to 30% mortality in adults ³

  
  
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  Pathophysiology

  
  
  
  
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    SE occurs due to the failure of mechanisms that terminate seizures or initiation of mechanisms that lead to prolonged seizures ⁴

    
    
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    There is a decrease in inhibitory receptors and an increase in excitatory receptors ^{5 , 6}

    
    
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    Key timepoints as per the ILAE Task Force on Classification of Status Epilepticus ⁴ :

    
    
    
    
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      t ₁: when seizures are likely to be prolonged and become continuous

      
      
      
      
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        Tonic-clonic: 5 minutes

        
        
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        Focal SE with impaired consciousness: 10 minutes

        
        
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        Absence: 10 to 15 minutes

      
      
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      t ₂: when seizures can cause long-term consequences

      
      
      
      
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        Tonic-clonic: 30 minutes

        
        
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        Focal SE with impaired consciousness: >60 minutes

        
        
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        Absence: unknown

8.2 Convulsive Status Epilepticus Management

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  Two main CSE treatment guidelines

  
  
  
  
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    Neurocritical Care Society ¹

    
    
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    American Epilepsy Society ³

    
    
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    See Fig. 8‑1 for timeline and medication doses ³

  
  
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  Initial SE management (the below management is based on the NCS and AES guidelines in addition to our local institutional practice) ^{1 , 2 , 3}

  
  
  
  
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    Evaluate and secure adequate airway, breathing, and circulation (ABCs)

    
    
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    Obtain intravenous (IV) access

    
    
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    Check finger-stick glucose

    
    
    
    
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      If glucose <60 mg/dL, give thiamine 100 mg IV ×1, then 50 mg D50 IV

    
    
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    Monitor SpO2, blood pressure, heart rate, and rhythm as vital signs may become unstable

    
    
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    Treat hyperthermia

    
    
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    Obtain labs: CBC, CMP, ABG, PT, INR, aPTT, Ca²⁺, Mg²⁺, PO4^{– 2}, troponin, HCG, ammonia (if appropriate)

    
    
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    Check toxicology screen

    
    
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    Check antiepileptic drug (AED) levels (if appropriate)

    
    
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    Obtain computed tomography (CT) of the head to evaluate for structural lesion if no history of seizures

    
    
    
    
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      May consider magnetic resonance imaging (MRI) of brain with and without contrast after seizures are controlled

    
    
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    Consider lumbar puncture and/or antibiotics if there is clinical suspicion of infection

    
    
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    Begin continuous electroencephalography (cEEG) if appropriate; considering the indications outlined by the consensus statement by American Clinical Neurophysiology Society (ACNS) ²

    
    
    
    
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      Electroencephalography (EEG) is required for the diagnosis of nonconvulsive seizures and NCSE

      
      
      
      
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        CSE may transition to NCSE; cEEG should be used in patients who do not return to baseline despite therapy

      
      
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      EEG is required for the assessment of efficacy of continuous IV therapy in SE

      
      
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      cEEG should be continued until patient is seizure free for at least 24 hours

  
  
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  Initial medical therapy

  
  
  
  
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    Benzodiazepines ^{1 , 3} should be administered in parallel with the initial management steps listed above

    
    
    
    
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      IV Lorazepam 2 to 4 mg at a time for up to 0.1 mg/kg total dose

      
      
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      IM Midazolam (especially in prehospital ⁸ setting) 10 mg ×1 (if the patient weighs more than 40 kg)

      
      
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      IV Diazepam 0.15 to 0.2 mg/kg/dose for up to 10 mg/dose

  
  
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  Second medical therapy

  
  
  
  
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    Administered if benzodiazepines fail, but often concurrently ordered

    
    
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    No definitive evidence for a preferred AED ³

    
    
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    AED options include:

    
    
    
    
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      IV Fosphenytoin/Phenytoin (20 PE/kg or 20 mg/kg load, max 1,500 mg/dose)

      
      
      
      
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        Fosphenytoin may be administered more rapidly than phenytoin and does not have risk of purple glove syndrome

        
        
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        Patients must be monitored on telemetry, given risk of cardiac arrhythmias

        
        
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        Post-load phenytoin level 2 hours after administration, goal 15 to 20 μg/mL

      
      
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      IV Valproic Acid (40 mg/kg load, max 3,000 mg/dose)

      
      
      
      
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        May cause hepatotoxicity, hyperammonemia, and thrombocytopenia

        
        
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        Post-load level 1 hour after administration, target level 70 to 100 μg/mL

      
      
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      IV Levetiracetam (60 mg/kg load, max 4,500 mg/dose)

      
      
      
      
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        Renal clearance; dose must be adjusted for creatinine clearance

      
      
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      IV Phenobarbital (if the above options are not available, 15 mg/kg load)

      
      
      
      
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        May cause hypotension, metabolic acidosis, and respiratory depression

      
      
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      While more research needs to be done lacosamide is commonly used in the clinical setting for the treatment of SE. As it is more recent it is not part of the guidelines. IV lacosamide is typically given as a 300 or 400 mg load.

      
      
      
      
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        A systematic review of the available evidence showed most clinicians using anywhere from 200 to 400 mg. ¹⁰

        
        
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        However, another study showed that weight-adjusted dosing showed better efficacy when a loading dose of >5.3 mg/kg was used (for the average 60-70 kg person this would equate to 300-400 mg). ¹¹

        
        
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        May cause PR prolongation and AV block. Hypotension and arrhythmias have also been occasionally reported.

    
    
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    Individual patient scenario may play a role in the choice of AED ¹

    
    
    
    
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      Consider patient comorbidities and potential side effects of AEDs noted above

    
    
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    In patients with known epilepsy and on an AED, it is reasonable to give an IV bolus of that AED if IV formulation is available ¹

  
  
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  The Established Status Epilepticus Treatment Trial (ESETT) ^{12 , 13}

  
  
  
  
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    No statistically significant difference was seen in terms of efficacy and safety outcome between the three drugs (fosphenytoin, valproic acid, and levetiracetam) for the treatment of benzodiazepine-refractory SE

8.3 Nonconvulsive Status Epilepticus (NCSE)

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  Variable definitions in the past with the below listed points:

  
  
  
  
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    Nonconvulsive status lasting more than30 minutes or recurrent over 30 minutes without return to normal consciousness ²

    
    
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    Continuous nonconvulsive seizure lasting more than 5 minutes NOT continuous and recurrent ¹

    
    
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    Electrographic seizures seen on more than 50% of an EEG epoch ²

  
  
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  There are upcoming new definitions for nonconvulsive status epilepticus based on the American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2021 version

  
  
  
  
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    This document is currently in “public comment format” after which the revision and publication process will occur; see the public comment link. ²⁶

    
    
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    Based on this upcoming publication:

    
    
    
    
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      The definition should change here from NCS ≥ than 30 minutes to electrographic seizure for ≥ 10 continuous minutes

      
      
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      The required seizure burden to diagnose NCSE will also decrease from 50% to 20% or more of a 60-minute epoch

  
  
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  Must be monitored on EEG ²

  
  
  
  
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    EEG recording less than 1 hour only identifies 45 to 58% of patients who eventually have seizures

    
    
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    Recording for at least 24 hours is recommended

  
  
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  Often occurs after CSE

  
  
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  Worse prognosis, ⁷ especially if no history of seizures ¹⁴

  
  
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  Treatment typically extrapolated from the guidelines for the treatment of CSE and practice is variable

  
  
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  Determining and treating the underlying etiology is important