What is the work-up for refractory non-convulsive status epilepticus (NCSE)?

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Last updated: May 23, 2025 • View editorial policy

From the Guidelines

The workup for non-convulsive status epilepticus (NCSE) that is refractory to initial treatment should include continuous EEG monitoring, neuroimaging, and comprehensive laboratory testing, with treatment typically involving escalating to anesthetic agents such as midazolam, propofol, or pentobarbital, as recommended by the most recent guidelines 1. The management of refractory NCSE requires a multifaceted approach, including:

  • Continuous EEG monitoring to identify ongoing seizure activity and guide treatment
  • Neuroimaging, such as MRI of the brain with and without contrast, to identify structural lesions, inflammation, or other pathologies
  • Comprehensive laboratory testing, including complete blood count, comprehensive metabolic panel, toxicology screen, antiepileptic drug levels, inflammatory markers, and autoimmune panels
  • Lumbar puncture to analyze cerebrospinal fluid for infection, inflammation, or autoimmune processes Treatment should involve escalating to anesthetic agents, such as:
  • Midazolam, starting at 0.2 mg/kg bolus followed by 0.1-0.4 mg/kg/hr infusion
  • Propofol, 1-5 mg/kg/hr after loading dose
  • Pentobarbital, 5-15 mg/kg loading dose followed by 0.5-5 mg/kg/hr These medications should be titrated to achieve burst suppression on EEG for 24-48 hours before attempting to wean, as recommended by the Neurocritical Care Society’s Status Epilepticus Guideline Writing Committee 2. Concurrently, at least two non-sedating antiepileptic drugs should be maintained at therapeutic levels, and the underlying etiology must be addressed simultaneously, as refractory NCSE often results from structural lesions, autoimmune encephalitis, or metabolic derangements, as suggested by the international multidisciplinary consensus conference on multimodality monitoring in neurocritical care 3. This aggressive approach is necessary because prolonged NCSE can lead to neuronal injury, cognitive impairment, and increased mortality, with outcomes worsening as seizure duration increases.

From the FDA Drug Label

The treatment of status, however, requires far more than the administration of an anticonvulsant agent. It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required. Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected. Furthermore, patients who are susceptible to further seizure episodes should receive adequate maintenance antiepileptic therapy Propofol injectable emulsion was found to be effective in status epilepticus which was refractory to the standard anticonvulsant therapies.

The work-up for NCSE (Non-Convulsive Status Epilepticus) that is refractory involves:

  • Observation and management of all parameters critical to maintaining vital function
  • Identification and correction of any underlying metabolic or toxic derangement, such as: + Hypoglycemia + Hyponatremia
  • Administration of anticonvulsant agents, such as lorazepam or propofol
  • Consideration of maintenance antiepileptic therapy for patients susceptible to further seizure episodes
  • Consultation with a neurologist if the patient fails to respond to treatment 4, 5, 6

From the Research

NCSE Refractory Work-up

  • The treatment of refractory non-convulsive status epilepticus (NCSE) is less clear and requires additional study 7.
  • Refractory status epilepticus (RSE) usually requires anesthetic doses of anti-seizure medications 7.
  • If an auto-immune or paraneoplastic etiology is suspected or no etiology can be identified, early treatment with immuno-modulatory agents is now recommended by many experts 7.
  • The optimal treatment of refractory generalized convulsive status epilepticus (GCSE) has not been defined, but patients should be treated in an intensive care unit, as artificial ventilation and haemodynamic support are required 8.
  • Barbiturate anaesthetics, pentobarbital, and thiopental sodium are the most frequently used agents and are highly effective for refractory GCSE both in children and adults 8.
  • Midazolam and propofol are other options for the treatment of refractory GCSE, with midazolam being effective and well-tolerated in both adults and children 8, 9.
  • The treatment of established status epilepticus (ESE) is incompletely studied, and effective treatment is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists 10.
  • Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE, but there are no class 1 data to support pharmacologic recommendations of one agent over another 10.
  • New treatment options are urgently required for refractory status epilepticus, and randomized controlled trials or at least prospective observational studies based on strict protocols incorporating long-term outcome data are urgently required 11.

Treatment Strategies

  • Levetiracetam may be administered after failure of first-line and/or second-line agents in complex partial status epilepticus 11.
  • Lacosamide may be an interesting new adjunct, but reliable data are pending 11.
  • Propofol seems to be as efficient as barbiturates in the treatment of refractory generalized convulsive status epilepticus 11.
  • The use of midazolam in the treatment of refractory status epilepticus has been reported to be effective, well-tolerated, and fast-acting 9.

Key Considerations

  • Refractory status epilepticus is a major medical and neurologic emergency that requires immediate treatment to avoid significant morbidity and mortality 9.
  • The incidence of refractory status epilepticus is between 2000 and 6000 cases per year in the United States 9.
  • Continuous EEG monitoring is required during high-dose treatment and while therapy is gradually withdrawn 8.
  • Intravenous phenytoin/fosphenytoin or valproate should be continued during withdrawal of anaesthetic therapy to ensure an adequate baseline of antiepileptic medication 8.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatment of Convulsive Status Epilepticus.

Current treatment options in neurology, 2016

Research

Treatment of Established Status Epilepticus.

Journal of clinical medicine, 2016

Research

Treatment strategies for refractory status epilepticus.

Current opinion in critical care, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.