Status Epilepticus Differential Diagnoses
- Author: Julie L Roth, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA more...
Recognition of status epilepticus (SE) may be easy or difficult. SE in the patient with sequential, generalized major motor convulsions is obvious; the patient with nonconvulsive or subtle SE presents a diagnostic dilemma.
Nonepileptic seizures (NES), formerly called psychogenic seizures, may at times be indistinguishable from generalized convulsive SE. The risk in such cases is that the physician may immediately assume that a neurologic emergency was present and embark on an aggressive course of pharmacotherapy, neglecting physical examination and historical information. A brief period of observation for atypical features (see Physical Examination) may lead to the conclusion that the patient has nonepileptic seizures and does not need anticonvulsant therapy.
In one study, unresponsiveness without movement was the most common presentation of psychogenic SE. Other reviews of psychogenic SE note other frequently seen presentations, including asynchronous extremity movement, forward pelvic thrusting, and geotropic eye movements (a physical finding that indicates the eyes deviating toward the ground in a nonphysiologic manner whether the head is turned left or right).
A retrospective study from one institution noted that patients with psychogenic nonepileptic SE were younger, had implanted port devices for intravenous medication administration, had lower creatine kinase levels, and received higher doses of benzodiazepines compared with patients with generalized convulsive SE epilepticus.
NES is associated with several behavioral characteristics that help distinguish it from a nonepileptic event. Motor activity during an NES often is punctuated by brief periods of rest, whereas epileptic convulsions are usually sustained without pause until the end of each individual seizure.
When seizure activity spreads during an epileptic seizure, it usually follows the organization of the homunculus. NES may fail to show this stereotypical and predictable evolution of behavior.
Behaviors such as pelvic thrusting, head turning from side to side, and bizarre vocalizations are usually not seen in epileptic seizures. The exception to this rule is seizure of frontal-lobe onset.
Although clinical features are usually helpful, the ultimate test to differentiate between epileptic seizures and NES is EEG.
Simple partial status epilepticus
Given the relative rarity of simple partial SE (SPSE), maintain a high degree of skepticism before considering this diagnosis. Other common processes (eg, vascular CNS insult) and other focal processes may mimic this rare entity; keep these well in mind, especially when tempted to apply increasingly risky treatment strategies. Invest more time in confirming the diagnosis and in deliberately observing the effect of each successive treatment.
The list of alternative diagnoses for SPSE is a subset of the list associated with complex partial SE (CPSE). These include the following:
Transient ischemia attack (TIA) and stroke
Migraine and its attendant neurologic phenomena (eg, sensory, visual)
Transient postictal phenomena analogous to Todd paresis
Ophthalmic disorders (eg, retinal detachment), which may mimic visual simple partial (occipital) SE
Peripheral neurologic syndromes and
Diagnosing SPSE is understandably easiest when it arises in a patient with an established history of focal epilepsy. Evolution of SPSE from or to a clinically overt complex partial or secondarily generalized seizure also permits accurate diagnosis.
Given that confirming SPSE on clinical grounds alone may be difficult, EEG validation can be especially important. However, the yield of EEG in detecting simple partial seizure activity is variable.
Complex partial status epilepticus
CPSE is associated with more differential diagnoses than SPSE because of its variable clinical manifestations and associated altered consciousness. In addition to TIA, stroke, and migraine, other key disturbances of CNS function that mimic CPSE include toxic or metabolic encephalopathy, delirium of diverse etiologies, and transient global amnesia.
Absence SE (persistent generalized 3-Hz spike-and-wave activity) may be clinically indistinguishable from CPSE. Prolonged postictal states may closely resemble, and are more common than, CPSE.
Psychiatric causes of decreased responsiveness resembling CPSE are familiar to many tertiary epilepsy referral centers. These include severe mood disorders, psychotic disorders, and related nonepileptic phenomena (ie, pseudo-CPSE).
Periodic lateralized epileptiform discharges (PLEDs) may occur with and without focal SE. In focal SE, PLEDs may represent an ictal correlate. This interpretation is supported by an overt clinical correlate (ie, focal twitching) or by improvement in the patient's findings on neurologic examination after PLED resolution, as may occur after treatment.
However, such clinical improvement may lag the disappearance of PLEDs by hours owing to residual postictal CNS dysfunction. Marked evolution of PLEDs, such as abrupt frequency or amplitude changes, may also signify an ictal correlate. Whether the absolute discharge frequency reliably differentiates interictal from ictal PLEDs remains controversial.
Single-photon emission computed tomography (SPECT) may assist in distinguishing ictal and interictal PLEDs in the setting of possible focal SE. In instances of PLEDs in focal SE, SPECT may show focal hyperperfusion.
Apart from focal SE, PLEDs often represent an interictal finding associated with acute structural CNS lesions (eg, infarct, tumor, infection) or a chronic CNS lesion with a new, superimposed systemic disturbance. In this setting, PLEDs are still associated with seizures in 70-80% of cases. Both focal SE and PLEDs arise from similar clinical contexts, and both imply an increased risk of future seizures and epilepsy.
Epilepsy partialis continua
For epilepsy partialis continua (EPC), with its associated semirhythmic, repetitive muscle twitching, the differential diagnosis is a bit different from that of SPSE and CPSE. Other entities to consider include nonepileptic myoclonus, such as those of basal ganglia, brainstem, or spinal origin. The coexistence of other overt complex partial and secondarily generalized seizures and epileptiform changes in the EEG help make this distinction.
A finding of bilateral or multifocal myoclonic process argues against focal epilepsy. Multifocal myoclonus is frequently encountered in very ill, hospitalized patients, often after systemic hypoxemia, though it is occasionally related to medications or metabolic derangements.
Other movement disorders (eg, choreiform disorders, hemiballismus, tic disorders, opsoclonus-myoclonus syndrome) might theoretically be mistaken for EPC. Careful evaluation of the movements, EEG, and accompanying history may assist in differentiation. Finally, a psychogenic process may emulate EPC in rare cases.
Hyperosmolar Hyperglycemic Nonketotic Coma
Hypocalcemia in Emergency Medicine
Neuroleptic Malignant Syndrome
LÃ¼ders HO, Rona S, Rosenow F, et al. A semiological classification of status epilepticus. Epileptic Disord. 2005 Jun. 7(2):149-50. [Medline].
Brenner RP. EEG in convulsive and nonconvulsive status epilepticus. J Clin Neurophysiol. 2004 Sep-Oct. 21(5):319-31. [Medline].
Kaplan PW. The EEG of status epilepticus. J Clin Neurophysiol. 2006 Jun. 23(3):221-9. [Medline].
D'Giano CH, Del C Garcia M, Pomata H, Rabinowicz AL. Treatment of refractory partial status epilepticus with multiple subpial transection: case report. Seizure. 2001 Jul. 10(5):382-5. [Medline].
Ma X, Liporace J, O'Connor MJ, Sperling MR. Neurosurgical treatment of medically intractable status epilepticus. Epilepsy Res. 2001 Jul. 46(1):33-8. [Medline].
Duane DC, Ng YT, Rekate HL, et al. Treatment of refractory status epilepticus with hemispherectomy. Epilepsia. 2004 Aug. 45(8):1001-4. [Medline].
Winston KR, Levisohn P, Miller BR, Freeman J. Vagal nerve stimulation for status epilepticus. Pediatr Neurosurg. 2001 Apr. 34(4):190-2. [Medline].
Proceedings and abstracts of the First London Colloquium on Status Epilepticus, University College London, April 12-15, 2007. Epilepsia. 2007. 48 Suppl 8:1-109. [Medline].
Shorvon SD, Trinka E, Walker MC. The proceedings of the First London Colloquium on Status Epilepticus--University College London, April 12-15, 2007. Introduction. Epilepsia. 2007. 48 Suppl 8:1-3. [Medline].
Kälviäinen R. Status epilepticus treatment guidelines. Epilepsia. 2007. 48 Suppl 8:99-102. [Medline].
Wilson JV, Reynolds EH. Texts and documents. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. Med Hist. 1990 Apr. 34(2):185-98. [Medline].
Wolf P, Trinka E, Bauer G. Absence status epilepticus: the first documented case?. Epilepsia. 2007. 48 Suppl 8:4-5. [Medline].
Epilepsy Foundation of America. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA. 1993 Aug 18. 270(7):854-9. [Medline].
Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. 1999 Jan. 40(1):120-2. [Medline].
Lowenstein DH, Cloyd J. Out-of-hospital treatment of status epilepticus and prolonged seizures. Epilepsia. 2007. 48 Suppl 8:96-8. [Medline].
Geier S, Bancaud J, Bonis A, Enjelvin M. [Tele-E.E.G. recordings of three epileptic attacks classified as episodes of PM status (author's transl)]. Rev Electroencephalogr Neurophysiol Clin. 1977 Apr-Jun. 7(2):201-2. [Medline].
Ellis JM, Lee SI. Acute prolonged confusion in later life as an ictal state. Epilepsia. 1978 Apr. 19(2):119-28. [Medline].
Niedermeyer E, Fineyre F, Riley T, Uematsu S. Absence status (petit mal status) with focal characteristics. Arch Neurol. 1979 Jul. 36(7):417-21. [Medline].
Celesia GG. Modern concepts of status epilepticus. JAMA. 1976 Apr 12. 235(15):1571-4. [Medline].
Treiman DM. Generalized convulsive, nonconvulsive, and focal status epilepticus. In: Feldman E, ed. Current Diagnosis in Neurology. St. Louis: Mosby-Year Book. 1994:11-8.
Lennox W, Lennow MA. Epilepsy and Related Disorders. Boston, MA: Little Brown;. 1960.
Cascino GD. Nonconvulsive status epilepticus in adults and children. Epilepsia. 1993. 34 Suppl 1:S21-8. [Medline].
Shorvon S. The outcome of tonic-clonic status epilepticus. Curr Opin Neurol. 1994 Apr. 7(2):93-5. [Medline].
White PT, Grant P, Mosier J, Craig A. Changes in cerebral dynamics associated with seizures. Neurology. 1961 Apr. 11(4)Pt 1:354-61. [Medline].
Aminoff MJ, Simon RP. Status epilepticus. Causes, clinical features and consequences in 98 patients. Am J Med. 1980 Nov. 69(5):657-66. [Medline].
Meldrum BS, Horton RW. Physiology of status epilepticus in primates. Arch Neurol. 1973 Jan. 28(1):1-9. [Medline].
Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci. 2005 Aug 24. 25(34):7724-33. [Medline].
Sloviter RS, Zappone CA, Bumanglag AV, Norwood BA, Kudrimoti H. On the relevance of prolonged convulsive status epilepticus in animals to the etiology and neurobiology of human temporal lobe epilepsy. Epilepsia. 2007. 48 Suppl 8:6-10. [Medline].
Goodkin HP, Sun C, Yeh JL, Mangan PS, Kapur J. GABA(A) receptor internalization during seizures. Epilepsia. 2007. 48 Suppl 5:109-13. [Medline].
Holmes GL. Influence of brain development on status epilepticus. Epilepsia. 2007. 48 Suppl 8:19-20. [Medline].
DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG. Epidemiology of status epilepticus. J Clin Neurophysiol. 1995 Jul. 12(4):316-25. [Medline].
Shinnar S, Pellock JM, Moshe SL, et al. In whom does status epilepticus occur: age-related differences in children. Epilepsia. 1997 Aug. 38(8):907-14. [Medline].
DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology. 1996 Apr. 46(4):1029-35. [Medline].
Shorvon S. Definition, classification and frequency of status epilepticus. In: Shorvon S, ed. Epilepticus: Its Clinical Features and Treatment in Children and Adults. Cambridge: Cambridge University Press; 1994. 21-33.
Waterhouse EJ, DeLorenzo RJ. Status epilepticus in older patients: epidemiology and treatment options. Drugs Aging. 2001. 18(2):133-42. [Medline].
Drislane FW, Blum AS, Lopez MR, Gautam S, Schomer DL. Duration of refractory status epilepticus and outcome: Loss of prognostic utility after several hours. Epilepsia. 2009 Jan 19. [Medline].
Rossetti AO, Oddo M, Liaudet L, Kaplan PW. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology. 2009 Feb 24. 72(8):744-9. [Medline].
Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998 Sep 17. 339(12):792-8. [Medline].
Thomas P. How urgent is the treatment of nonconvulsive status epilepticus?. Epilepsia. 2007. 48 Suppl 8:44-5. [Medline].
Aicardi J, Chevrie JJ. Convulsive status epilepticus in infants and children. A study of 239 cases. Epilepsia. 1970 Jun. 11(2):187-97. [Medline].
Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med. 1998 Apr 2. 338(14):970-6. [Medline].
Hauser WA. Status epilepticus: epidemiologic considerations. Neurology. 1990 May. 40(5 Suppl 2):9-13. [Medline].
Boggs JG, Marmarou A, Agnew JP, et al. Hemodynamic monitoring prior to and at the time of death in status epilepticus. Epilepsy Res. 1998 Aug. 31(3):199-209. [Medline].
Krumholz A, Sung GY, Fisher RS, Barry E, Bergey GK, Grattan LM. Complex partial status epilepticus accompanied by serious morbidity and mortality. Neurology. 1995 Aug. 45(8):1499-504. [Medline].
Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res. 1990 Jan-Feb. 5(1):49-60. [Medline].
Treiman DM, Meyers PD, Walton NY. DVA Status Epilepticus Cooperative Study Group. Duration of generalized convulsive status epilepticus: relationship to clinical symptomatology and response to treatment. Epilepsia. 1992. 33(Suppl 3):66.
Treiman DM. Electroclinical features of status epilepticus. J Clin Neurophysiol. 1995 Jul. 12(4):343-62. [Medline].
Bien CG, Elger CE. Epilepsia partialis continua: semiology and differential diagnoses. Epileptic Disord. 2008 Mar. 10(1):3-7. [Medline].
Leis AA, Ross MA, Summers AK. Psychogenic seizures: ictal characteristics and diagnostic pitfalls. Neurology. 1992 Jan. 42(1):95-9. [Medline].
Jagoda A, Richey-Klein V, Riggio S. Psychogenic status epilepticus. J Emerg Med. 1995 Jan-Feb. 13(1):31-5. [Medline].
Holtkamp M, Othman J, Buchheim K, Meierkord H. Diagnosis of psychogenic nonepileptic status epilepticus in the emergency setting. Neurology. 2006 Jun 13. 66(11):1727-9. [Medline].
Kutluay E, Beattie J, Passaro EA, Edwards JC, Minecan D, Milling C, et al. Diagnostic and localizing value of ictal SPECT in patients with nonconvulsive status epilepticus. Epilepsy Behav. 2005 Mar. 6(2):212-7. [Medline].
Assal F, Papazyan JP, Slosman DO, Jallon P, Goerres GW. SPECT in periodic lateralized epileptiform discharges (PLEDs): a form of partial status epilepticus?. Seizure. 2001 Jun. 10(4):260-5. [Medline].
Karlov VA. Complex partial status epilepticus. Epilepsia. 2007 Sep. 48(9):1815. [Medline].
DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia. 1998 Aug. 39(8):833-40. [Medline].
Szabo K, Poepel A, Pohlmann-Eden B, Hirsch J, Back T, Sedlaczek O, et al. Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus. Brain. 2005 Jun. 128:1369-76. [Medline].
[Guideline] Glauser, T. et al. Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Currents. Jan/Feb 2016. 16(1):48-61. [Full Text].
Rossetti AO. Which anesthetic should be used in the treatment of refractory status epilepticus?. Epilepsia. 2007. 48 Suppl 8:52-5. [Medline].
Arif H, Hirsch LJ. Treatment of status epilepticus. Semin Neurol. 2008 Jul. 28(3):342-54. [Medline].
Parviainen I, Uusaro A, Kalviainen R, et al. Propofol in the treatment of refractory status epilepticus. Intensive Care Med. 2006 Jul. 32(7):1075-9. [Medline].
Iyer VN, Hoel R, Rabinstein AA. Propofol infusion syndrome in patients with refractory status epilepticus: an 11-year clinical experience. Crit Care Med. 2009 Dec. 37(12):3024-30. [Medline].
Synowiec AS, Singh DS, Yenugadhati V, Valeriano JP, Schramke CJ, Kelly KM. Ketamine use in the treatment of refractory status epilepticus. Epilepsy Res. 2013 Jan 28. [Medline].
Blumkin L, Lerman-Sagie T, Houri T, Gilad E, Nissenkorn A, Ginsberg M, et al. Pediatric refractory partial status epilepticus responsive to topiramate. J Child Neurol. 2005 Mar. 20(3):239-41. [Medline].
Prasad M, Krishnan PR, Sequeira R, Al-Roomi K. Anticonvulsant therapy for status epilepticus. Cochrane Database Syst Rev. 2014 Sep 10. 9:CD003723. [Medline].
Misra UK, Kalita J, Patel R. Sodium valproate vs phenytoin in status epilepticus: a pilot study. Neurology. 2006 Jul 25. 67(2):340-2. [Medline].
Limdi NA, Shimpi AV, Faught E, Gomez CR, Burneo JG. Efficacy of rapid IV administration of valproic acid for status epilepticus. Neurology. 2005 Jan 25. 64(2):353-5. [Medline].
Rossetti AO, Bromfield EB. Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes. Eur Neurol. 2005. 54(1):34-8. [Medline].
Patel NC, Landan IR, Levin J, Szaflarski J, Wilner AN. The use of levetiracetam in refractory status epilepticus. Seizure. 2006 Apr. 15(3):137-41. [Medline].
Bialer M. Clinical pharmacology of parenteral use of antiepileptic drugs. Epilepsia. 2007. 48 Suppl 8:46-8. [Medline].
Aggarwal P, Wali JP. Lidocaine in refractory status epilepticus: a forgotten drug in the emergency department. Am J Emerg Med. 1993 May. 11(3):243-4. [Medline].
Koubeissi MZ, Mayor CL, Estephan B, Rashid S, Azar NJ. Efficacy and safety of intravenous lacosamide in refractory nonconvulsive status epilepticus. Acta Neurol Scand. 2011 Feb. 123(2):142-6. [Medline].
Costello DJ, Simon MV, Eskandar EN, Frosch MP, Henninger HL, Chiappa KH, et al. Efficacy of surgical treatment of de novo, adult-onset, cryptogenic, refractory focal status epilepticus. Arch Neurol. 2006 Jun. 63(6):895-901. [Medline].
McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005 Jul 16-22. 366(9481):205-10. [Medline].
de Haan GJ, van der Geest P, Doelman G, Bertram E, Edelbroek P. A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia. 2010 Mar. 51(3):478-82. [Medline].