Question 21

A 23-year-old female is admitted to your ICU following her first presentation with seizures. A collateral history suggested that she had been acting unusually for the previous few days before she was seen to collapse with a tonic-clonic seizure. She continued to fit during transfer to hospital.

On arrival to the Emergency Department she was given further doses of midazolam IV and loaded with levetiracetam IV. After 20 minutes she continued to have sporadic seizure activity with a best GCS of 6 and was intubated using propofol and rocuronium.

a) List six possible causes for her presentation. (30% marks)

On admission to ICU she is on a propofol infusion at 20 mg/hr, minimal ventilatory support and is haemodynamically stable. She continues to have intermittent seizures .

b) Briefly outline your specific management with respect to the seizures. (70% marks)

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College answer

Acute structural brain injury (stroke, HI, SAH) 
Infection (encephalitis, meningitis, abscess) 
Tumour (CNS, Paraneoplastic syndromes / autoantibodies to remote tumours) 
Withdrawal (Alcohol, barbiturates, BDZ) 
Metabolic (hypoglycaemia, HE, uraemia, hyponat, hypergly/Ca/Mg) 
Drug OD 
Autoimmune encephalitis 
Or any acceptable cause – PRES, CNS vasculitis etc. 
Look for and treat underlying cause of refractory status epilepticus (RSE) 
Principles of treatment for RSE 
•    Look for and treat underlying cause 
History including travel, examination, CT, LP, BSL, U&E, metabolic screen, drug screen, auto-immune screen, beta-HCG, paraneoplastic markers, MRI 
•    Additional agents (one to three or more) to prevent emergence seizures, e.g. Phenytoin, Fosphenytoin, Levetiraetam, Valporate, Phenobarbitone BDZ – clonazepam / diazepam / lorazepam 
•    General Anaesthesia with EEG monitoring  
Propofol / thiopentone / inhalational anaesthetics 
•    EEG to burst suppression OR seizure suppression only (controversial) 
•    No guidelines for duration of therapy - initially 24 to 48 hours (controversial) 
•    If emergence seizures develop treat for longer or deeper or both (controversial) 
•    Try to avoid rapid switches or changes in agent dosing (as per conventional seizure Mx) 
•    Avoid NMBs unless continuous EEG monitoring 
•    Avoid hyperthermia and consider hypothermia 
Additional Examiners' Comments: 
Almost all the candidates were able to answer the first part. Although all the candidates wrote something about the management of the case, it tended to be limited and largely disorganised. There was a lot of generic information not related to the "specific management with respect to the seizures", e.g. „FAST HUG‟ that did not score the candidate any marks. 




The most common causes of status epilepticus are failure to take one’s own epilepsy tablets.  For the weird causes, there is a good article which lists a massive spectrum of toxins, genetic diseases, rare autoimmune conditions and what have you.

  • Vascular causes:
    • Stroke
    • Decreased cerebral blood flow: ischaemic encephalopathy
    • Increased cerebral blood flow: hypertensive encephalopathy
    • Eclampsia
    • Intracranial haemorrhage
  • Infectious causes:
    • Encephalitis
    • Meningitis
    • Brain abscess
  • Neoplastic lesions:
    • Space-occupying tumour
  • Drug-induced status epilepticus
    • Cocaine
    • Methamphetamine
    • Phenothiazines
    • Tricyclics
    • Isoniazid
  • Drug withdrawal
    • Alcohol
    • Benzodiazepines
  • Idiopathic neurological causes:
    • By this, I mean poorly controlled epilepsy. It is possible to be fully compliant with your medications and still find them totally ineffective. Non-convulsive status could account for the unusual behaviour seen in the "previous few days".
  • Congenital causes:
    • congenital disorder of metabolism
    • structural; congenital abnormality, such as cerebral palsy.
  • Autoimmune causes:
    • Cerebral vasculitis
    • Limbic (NMDA receptor antibody) encephalitis - the presentation of this is pretty classical; the patient has a prodrome of weird behaviour, progressively becoming more confused and ultimately presenting with stupor, coma or relentless seizures. Classically, it is also very difficult to control and these are the people that end up on fourth and fifth line therapies to manage their first-ever episode of epileptic activity.
  • Traumatic causes
    • penetrating head injury
    • neurosurgery
  • Endocrine and metabolic causes
    • hyponatremia
    • hypokalemia
    • hypomagnesemia
    • hypocalcemia
    • an extremely low or extremely high BSL
    • uremic encephalopathy
    • hepatic encephalopathy


Management of status epilepticus is discussed in greater detail elsewhere. To borrow from that chapter, here is a list of specific therapies for status epilepticus:

First line agents

  • Benzodiazepines: boluses every 2-5 minutes
  • Phenytoin: 20mg/kg loading dose
    • Phenytoin on its own is useless. Or rather, it is inferior to benzodiazepines as a solitary agent. Always, both must be used simultaneously.

Second line agents

  • Midazolam infusion
  • Phenytoin (well, rather, the American study recommends fosphenytoin)
  • Phenobarbital and levetiracetam are also in this second line of attack

Third line agents: for refractory status epilepticus

  • Propofol infusion, or midazolam infusion, or thiopentone infusion.
  • At this stage, continuous EEG monitoring becomes mandatory
    • It does not matter which "general anaesthetic agent" you start an infusion of in refractory status epilepticus. However, one would be well advised to mention in their CICM fellowship answer that the patient has been intubated a long time ago, and that continuous EEG monitoring is now in progress.
  • The role of traditional antiepileptic drugs is also exhausted at this stage, as there will probably be no benefit from adding them into a situation where a constantly observed burst suppression is already achieved by high dose anaesthetic infusion.

Fourth line agents: for these, there is little evidence.

Fifth line therapies: for these, the evidence borders on the veterinarian


Oh's Intensive Care manual:

Chapter 49   (pp. 549) Disorders  of  consciousness  by Balasubramanian  Venkatesh

Chapter   50   (pp. 560) Status  epilepticus  by Helen  I  Opdam

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Johnson, Nicholas, et al. "Anti-NMDA receptor encephalitis causing prolonged nonconvulsive status epilepticus." Neurology 75.16 (2010): 1480-1482.

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Treiman, David M., et al. "A comparison of four treatments for generalized convulsive status epilepticus." New England Journal of Medicine 339.12 (1998): 792-798.

Meierkord, Hartmut, and Martin Holtkamp. "Non-convulsive status epilepticus in adults: clinical forms and treatment." The Lancet Neurology 6.4 (2007): 329-339.

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Storchheim, Frederic. "Status epilepticus treated by magnesium sulphate, injected intravenously." Journal of the American Medical Association 101.17 (1933): 1313-1314.

Kluger, G., et al. "Pyridoxine-dependent epilepsy: normal outcome in a patient with late diagnosis after prolonged status epilepticus causing cortical blindness." Neuropediatrics 39.5 (2008): 276-279.

Mirsattari, Seyed M., Michael D. Sharpe, and G. Bryan Young. "Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane." Archives of neurology 61.8 (2004): 1254-1259.

Hamani, Clement, et al. "Deep brain stimulation of the anterior nucleus of the thalamus: effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus." Epilepsy research 78.2 (2008): 117-123.

Cervenka, Mackenzie C., et al. "The ketogenic diet for medically and surgically refractory status epilepticus in the neurocritical care unit." Neurocritical care15.3 (2011): 519-524.

Corry, Jesse J., et al. "Hypothermia for refractory status epilepticus."Neurocritical care 9.2 (2008): 189-197.