How to write the cause of death in a case of New-Onset Refractory Status Epilepticus (NORSE)?

How to Write Cause of Death in NORSE Cases

When documenting cause of death in New-Onset Refractory Status Epilepticus (NORSE), list the immediate physiological mechanism of death as the primary cause, with NORSE and its underlying etiology (if identified) as contributing conditions, following standard death certificate guidelines that prioritize the chain of events leading to death.

Understanding NORSE Mortality Context

NORSE carries significant mortality risk that must be accurately documented:

• Mortality rates range from 11-27% in most series, with pooled analysis showing 22% mortality (95% CI 17%-27%) 1
• The condition affects primarily school-age children and young adults, with devastating neurological outcomes in survivors 2
• Approximately 50% of cases remain cryptogenic despite exhaustive workup, while autoimmune encephalitis accounts for 36.2% of identified cases 1

Death Certificate Documentation Structure

Part I: Immediate Cause of Death Chain

Document the physiological mechanism that directly caused death, working backwards through the causal chain:

• Line (a) - Immediate cause: Specify the terminal event such as:

  • Cardiopulmonary arrest
  • Respiratory failure
  • Cerebral herniation
  • Multi-organ failure
  • Refractory hypotension 2, 3

• Line (b) - Due to (or as a consequence of): Super-refractory status epilepticus (if seizures persisted despite 24+ hours of anesthesia) 4

• Line (c) - Due to (or as a consequence of): New-Onset Refractory Status Epilepticus (NORSE) 2, 3

• Line (d) - Due to (or as a consequence of):

  • If etiology identified: Specify (e.g., "Autoimmune encephalitis with anti-NMDA receptor antibodies" or "Paraneoplastic encephalitis secondary to ovarian teratoma") 3, 1
  • If cryptogenic: "NORSE of unknown etiology" or "Cryptogenic NORSE" 1

Part II: Other Significant Conditions

List complications and comorbidities that contributed to death but were not part of the direct causal chain:

• Prolonged ICU stay complications (mean 33.4 days) 1
• Nosocomial infections (pneumonia, sepsis)
• Medication-related complications (anesthesia effects, immunosuppression complications) 4
• Seizure-related injuries
• Thromboembolic events 5

Specific Clinical Scenarios

When Autoimmune Etiology is Identified

Document the specific antibody or autoimmune syndrome:

• Line (d): "Anti-NMDA receptor encephalitis" or "Anti-LGI1 encephalitis" 5, 3
• This applies to the 36.2% of cases where autoimmune etiology is confirmed 1

When Etiology Remains Unknown (49.9% of cases)

• Use "Cryptogenic NORSE" or "NORSE of unknown etiology" on line (d) 1
• This accurately reflects that despite extensive workup including autoimmune panels, infectious studies, metabolic testing, neuroimaging, and genetic testing, no cause was identified 3, 4

When Death Occurs After Prolonged Course

For patients who die months after initial presentation:

• If death is from refractory epilepsy: Document "Refractory epilepsy secondary to NORSE" 1
• If death is from complications: List the immediate complication with NORSE as underlying cause 6

Critical Documentation Pitfalls to Avoid

Do not list NORSE alone as the cause of death - it is a clinical syndrome, not a terminal physiological event. Always specify the immediate mechanism (respiratory failure, cardiac arrest, etc.) 2, 3

Do not delay documentation waiting for final etiology - if the patient dies during acute phase before complete workup, document as "NORSE, etiology under investigation" or "Cryptogenic NORSE" 1

Do not omit the term "refractory" - this distinguishes NORSE from standard status epilepticus and reflects the severity requiring multiple antiseizure medications and anesthetic agents 4

Do not use vague terms like "seizure disorder" or "encephalitis" without specifying NORSE, as this fails to capture the specific clinical entity and its implications 2, 3

Additional Documentation Considerations

For FIRES Subcategory

When febrile illness preceded NORSE by 2 weeks to 24 hours:

• Specify "Febrile Infection-Related Epilepsy Syndrome (FIRES)" instead of NORSE 2, 4
• Document the preceding febrile illness in Part II 3

For Pediatric Cases with Specific Radiographic Findings

In young children (<5 years) with diffuse cerebral restricted diffusion (DCRD):

• Consider documenting the radiographic phenotype as it may represent a distinct entity 6
• Note: "NORSE with diffuse cerebral restricted diffusion" if this pattern was present 6

Treatment-Related Deaths

If death occurs from treatment complications (immunotherapy, anesthesia, ketogenic diet):

• List the complication as immediate cause
• Maintain NORSE in the causal chain as the underlying condition requiring treatment 4