Non-convulsive Status Epilepticus: Pearls and Pitfalls
Author: Brit Long, MD, CAPT (EM Resident Physician at SAUSHEC; USAF) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021)
It’s a crazy night in the ED, and you are about four hours into your shift. You have just received a new patient with chief complaint of altered mental status coming in via EMS. The EMS crew reports they were called by family for a 52 year-old male who was confused and then became unresponsive. Initial vitals were BP 144/82, HR 89, Sat 99% on room air, RR 18, T 37 degrees Celsius, and D-stick 114. Rhythm strip was normal. EMS established two peripheral IVs and transferred him to your ED.
Upon your evaluation, the vitals are unchanged. The patient is lying on the gurney unresponsive to any stimuli including pain with eyes deviated to the left. His extremities are still, with no motions. Initial repeat D-stick is 102, and you order CBC, renal function panel, LFT, lactate, VBG, ECG, UA, and head CT. With his low GCS, you draw up intubation medications and your trusty videoscope to intubate. While you ready your equipment, you quickly go through your differential. What could you be missing beyond the standard AEIOU TIPS (alcohol / acidosis, electrolyte / endocrine, infection, opiates / overdose, uremia, trauma / toxin, insulin, poisoning / psychosis, seizures / stroke / sepsis / syncope)?
Non-convulsive status epilepticus (NCSE) is commonly defined as persistent change (over thirty minutes) in behavior and mental processes from baseline with continuous EEG changes without motor signs (1). This is obviously difficult to diagnose in the ED, where we hardly ever have access to EEG. Unfortunately the diagnosis is often delayed over 24 hours!
Classification: There are two main types of NCSE: absence SE (primary generalized), and complex partial (secondary generalized) (2).
Epidemiology: NCSE occurs in approximately 50% of patients with coma or convulsive status epilepticus. Even more concerning, it occurs in anywhere from 8% to 37% of general ICU populations (3-4).
Risk Factors: A large percentage of NCSE patients are critically ill or already admitted to the ICU. In the ED, patients at risk for NCSE are those patients in coma, patients presenting with seizures, age less than one year, history of epilepsy or brain injury, recent neurosurgical procedure, and sepsis (5-6). Studies have demonstrated that 1/2 to 2/3 of patients in NCSE have a prior history of seizures. Many of these cases are patients with subarachnoid hemorrhage or hemorrhagic stroke whose mental status suddenly declines and they become unresponsive, so always consider NCSE in patients with prior nervous system pathology who suddenly decline (3, 5-8).
Features: There are two primary symptom complexes in patients with NCSE: positive vs. negative. Positive symptoms are often subtle, and thus overlooked (9). These symptoms include rhythmic twitching of one or more muscle groups, eye deviation, or rhythmic eye jerking. Negative symptoms include aphasia, mutism, amnesia, catatonia, and decreased responsiveness. Unfortunately, close to 75% of patients with NCSE have no discernible clinical finding other than decreased responsiveness (3-4, 10)!
Differential: As NCSE presents with a broad range of symptoms and signs, there is a large differential including encephalopathy, trauma, TIA, hypoglycemia, intoxication, and metabolic disease. Perhaps the most important and most common misdiagnosis is postictal state, so in that patient who stops seizing after treatment but has not returned to baseline, be suspicious of NCSE (3-4).
Diagnosis: The diagnosis requires an EEG, since clinical signs are non-specific (3-10). The EEG findings are often complex, so needless to say, if you are concerned about NCSE, talk with your neurologist. EEGs are usually not obtainable in the ED. Keys to consideration of NCSE include abrupt onset of altered or fluctuating mental status with subtle clinical signs such as eye fluttering or automatisms. If you discuss the patient with the neurology team, they can help guide diagnosis and your management. Some sources advocate a trial of anti-epileptic medication if the EEG is uncertain (11).
Investigations: As the differential is large, you’ll want to be excluding the life threats and looking for the common other diagnoses. Obtaining blood glucose, CBC, LFTs, renal function panel, head CT, and ECG is vital. A lumbar puncture should also be considered to evaluate for infection (1, 3-4). You do not want to miss the hypoglycemic, hyperkalemic, or head bleed patient! Once you rule out the common disorders, at this point talk to neurology about EEG and consider giving benzodiazepines.
Management: The first goal is to find and treat the life threats. Ensuring airway, breathing, circulation, IV access, O2, and monitor as a safety net are key. If a cause is found, treat it. If NCSE is considered, start with lorazepam 0.1mg/kg IV or diazepam 0.2mg/kg IV. Most studies recommend loading another anti-epileptic at the same time as the benzo. Fosphenytoin or valproate are two good options. If the patient is not responsive, it’s time to take control of the airway. Propofol is a great anti-epileptic and should be used for induction. Another option is midazolam (1, 3-4, 6-8). After you have taken control of the airway, work on reversing fever, hypoxia, hypoglycemia, electrolyte derangements, or infections. These factors all lower seizure threshold.
Complications: NCSE is associated with poor prognosis (8, 12). Studies have shown that surrogate markers of neuron damage such as enolase are elevated (13). Mortality is close to 50 percent, and most do not return to their primary functional status. Risk factors for worse outcomes include acute brain disease, longer seizure duration, and severe mental status impairment (1, 8, 12).
Major Points: NCSE is often overlooked. If a seizure patient is postictal for a long period of time, consider NCSE. If other parts of the differential have been excluded, consider NCSE. Get neurology involved early. Start with benzos early, and take the airway if necessary. Prognosis is poor, and the longer the patient seizes, the worse the outcome ultimately.
References // Further Reading:
- Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3.
- Shorvon S. What is nonconvulsive status epilepticus, and what are its subtypes? Epilepsia 2007; 48 Suppl 8:35.
- Shah AM, Vashi A, Jagoda A. Review article: Convulsive and non-convulsive status epilepticus: an emergency medicine perspective. Emerg Med Ausralas. 2009 Oct; 21 (5): 352066.
- Meierkord H, Holtkamp M. Nonconvulsive status epilepticus in adults: clinical forms and treatment. Lancet Neurol. 2007 Apr;6(4):329-39.
- Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG. J Neurol Neurosurg Psychiatry 2003; 74:189.
- DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 1998; 39:833.
- Abend NS, Dlugos DJ. Nonconvulsive status epilepticus in a pediatric intensive care unit. Pediatr Neurol 2007; 37:165.
- Kaplan PW. The clinical features, diagnosis, and prognosis of nonconvulsive status epilepticus. Neurologist 2005; 11:348.
- Foreman B, Hirsch LJ. Epilepsy emergencies: diagnosis and management. Neurol Clin 2012; 30:11.
- Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004; 62:1743.
- Chong DJ, Hirsch LJ. Which EEG patterns warrant treatment in the critically ill? Reviewing the evidence for treatment of periodic epileptiform discharges and related patterns. J Clin Neurophysiol 2005; 22:79.
- Mayer SA, Claassen J, Lokin J, et al. Refractory status epilepticus: frequency, risk factors, and impact on outcome. Arch Neurol 2002; 59:205.
- Correale J, Rabinowicz AL, Heck CN, et al. Status epilepticus increases CSF levels of neuron-specific enolase and alters the blood-brain barrier. Neurology 1998; 50:1388.