WHAT IS SRSE?

Super-refractory status epilepticus (SRSE): A life-threatening neurologic emergency1,2

Super-refractory status epilepticus (SRSE) is a form of status epilepticus (SE) in which unremitting seizures do not respond to treatment.1,2

SRSE is a complex neurological crisis

When SE progresses, a patient may develop SRSE in three ways1,2:

physical

Patient with refractory status epilepticus (RSE) and receiving intravenous (IV) general anesthetics has breakthrough seizure activity that cannot be controlled with 3rd-line treatments

physical

Patient with RSE cannot be weaned off intravenous (IV) general anesthetics without return of SE

physical

Patient with RSE is removed from IV general anesthesia but SE returns within 24 hours and requires 3rd-line agents

FOLLOW THE CLINICAL PROGRESSION TO SRSE arrow

Status epilepticus may present as convulsive or nonconvulsive3,4

SE can manifest as convulsive and/or nonconvulsive status epilepticus (NCSE), in which seizure activity is electrographically present but absent of tonic-clonic activity associated with generalized convulsive status epilepticus (GCSE).3,4

NCSE has been found in 8% to 34% of neurological intensive care unit (ICU) patients in comatose states4,6 and may also occur after convulsive seizures end.6,7 Because uncontrolled seizures progress over time causing neuronal damage and death10-12, it is imperative to detect and treat NCSE as early as possible to avoid further brain injury.3,8

DIAGNOSE AND MONITOR SRSE WITH CONTINUOUS EEG arrow

Clinical complexity of SRSE poses challenges for practitioners

Clinical Challenges of SRSE

  • Evidence-based SRSE treatment guidelines are limited2
  • There are currently no FDA-approved treatments for SRSE8
  • In each case, identifying the underlying cause of SRSE may prove exceptionally difficult.2

Challenges in Community Settings

  • Hospitals may not have convenient access to cEEG equipment or specialists trained in interpreting results
  • Community practitioners may be unaware of or unable to easily contact local SRSE experts for consultation or centers with specialized care to allow patient transfer, if necessary

SEE UNDERLYING SRSE CAUSES arrow

Refractory seizures puts patients at risk13,14

Mortality and morbidity are high in SRSE patients.1,2,14,15 As seizure activity continues and progresses beyond SE, functional outcomes worsen.10 Excitotoxicity accompanying and perpetuating status epilepticus may contribute to neuronal damage and cell death.10-12

Estimated SRSE Clinical Outcomes

~30%
recovery with
neurologic deficits13
~18%-35%
return to baseline13,14
~35%-40%
mortality13,14

~65%-70% of patients with RSE or SRSE will die or be left with neurological deficits13,14

ESTIMATED FINANCIAL
OUTCOMES of SRSE

In a recent study using 2012 data from the Premier Hospital Database covering hospital discharges in the US*15:

Hospital
$51,24715
SRSE
SRSE mean hospitalization cost
$18,96316
Ischemic
stroke
Mean cost of SRSE
hospitalization was estimated at
$51,247,15 (compared to $18,963
for ischemic stroke in the US
in 200816)
Mean length of hospital stay Mean hospital length
of stay (LOS) was
16.5 days15
1 in 4 SRSE patients
  • 1 in 4 patients
spend ≥20 days in the hospital15
  • Mean length of days in the ICU
Mean LOS in ICU was
9.3 days15
32%
of SRSE patients
were hospitalized
10-19 days15

VIEW MECHANISM OF SRSE arrow

*The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure-related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.g., benzodiazepines, antiepileptic drugs [AEDs], and ventilator use). Secondary analyses were conducted using more restricted algorithms for SRSE. The study was sponsored by Sage Therapeutics, Inc.15

What Is the Incidence of
SRSE in the United states?

Estimates of the prevalence of SRSE may vary country to country based on differences in the rate of occurrence of underlying conditions and differences in accurate diagnosis rates and reporting. Based on a recent study using 2012 data from the Premier Hospital Database covering hospital discharges in the US,* it is estimated that there are ~25,000 to 41,000 cases of SRSE in the US each year.15 The estimated incidence rate in the study was approximately 11-13/100,000 annually.15

*The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure-related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.g., benzodiazepines, antiepileptic drugs [AEDs], and ventilator use). Secondary analyses were conducted using more restricted algorithms for SRSE. The study was sponsored by Sage Therapeutics, Inc.15

References:

  1. Hocker S, Tatum WO, LaRoche S, Freeman WD. Refractory and super-refractory status epilepticus – an update. Curr Neurol Neurosci Rep. 2014;14(6):452.
  2. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011;134(10):2802-2818.
  3. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-23.
  4. Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology. 2000;54:340-345.
  5. Jordan KG. Continuous EEG and evoked potential monitoring in the neuroscience intensive care unit. J Clin Neurophysiol. 1993;10:445-475.
  6. DeLorenzo RJ, Waterhouse EJ, Towne AR. Persistent nonconvulsive status epilepticus after control of convulsive status epilepticus. Epilepsia. 1998;38:833-840.
  7. Claassen J, Mayer SA, Kowalski RG, Emerson RG, Hirsch LJ. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology. 2004;62(10):1743-1748.
  8. Al-Mufti F, Claassen J. Neurocritical care: status epilepticus review. Crit Care Clin. 2014;30(4):751-764.
  9. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998;338:970-976.
  10. Scholtes FB, Renier WO, Meinardi H. Generalized convulsive status epilepticus: causes, therapy, and outcome in 346 patients. Epilepsia. 1994;35(5):1104-1112.
  11. Payne T, Bleck TP. Status epilepticus. Crit Care Clin. 1997;13(1):17-38.
  12. Meldrum B. Excitotoxicity and epileptic brain damage. Epilepsy Res. 1991;10:55-61.
  13. Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012;135(Pt 8):2314-2328.
  14. Delaj L, Novy J, Ryvlin P, Marchi NA, Rossetti AO. Refractory and super-refractory status epilepticus in adults: a 9-year cohort study. Acta Neurol Scand. 2017;135(1):92-99.
  15. Beg JM, Anderson TD, Francis K, et al. Burden of illness for super-refractory status epilepticus patients. J Med Econ. 2017;20(1):45-53.
  16. Wang G, Zhang Z, Ayala C, Dunet DO, Fang J, George MG. Costs of hospitalization for stroke patients aged 18-64 years in the United States. J Stroke Cerebrovasc Dis. 2014;23(5):861-868.