Seizures, status epilepticus and the ictal-interictal continuum


6
Seizures, status epilepticus and the ictal-interictal continuum


6.1 Electrographic and Electroclinical seizures


Seizures are very common in the ICU, particularly in patients with acute or chronic brain injuries. The prevalence of seizures in those undergoing continuous EEG monitoring (generally for 24 hours or more) ranges from 8% in those without prior seizures and with no subtle signs of seizures to 48% after convulsive status epilepticus. Most studies of acute brain injury (including traumatic brain injury, intraparenchymal hemorrhage and subarachnoid hemorrhage) show a prevalence of seizures of 15–40%. It is clear from many studies now that the majority of seizures in the critically ill are nonconvulsive and can therefore only be diagnosed via EEG. Seizures appear to be an independent predictor of worse outcome in multiple populations, including worse long-term functional outcomes, cognition, hippocampal atrophy and later epilepsy.


Electrographic seizures (ESz) are defined by the ACNS critical care EEG terminology 2021, as either (Figure 6.1):



  1. epileptiform discharges1 averaging >2.5 Hz for ≥10 seconds (>25 discharges in 10 seconds), or
  2. any pattern with definite evolution (in either frequency, morphology, or location) and lasting ≥10 seconds.

Electroclinical seizures (ECSz) are defined as any EEG pattern with either (Figure 6.1):



  1. definite clinical correlate2 time-locked to the pattern (of any duration), or
  2. EEG and clinical improvement with a parenteral (typically IV) anti-seizure medication.

Seizures in the critically ill with encephalopathy tend to be of slower frequencies, last longer and have less clearly defined onset, evolution and offset than seizures in awake patients. Thus, they can be more difficult to recognize, both visually and via computer-based detection. In general, there must be clear evolution in frequency, morphology or location of an ongoing EEG pattern to be sure it represents seizure activity. However, in prolonged nonconvulsive seizures, the evolution can be subtle or even absent.


6.2 Status epilepticus


Status epilepticus in concept basically refers to ongoing and prolonged seizure activity. A strong misconception among clinicians is that all status epilepticus is the same. It must be stressed that just as seizures can be highly variable (e.g., absence vs. focal seizure with impaired awareness vs. generalized tonic-clonic), the states and patterns that meet criteria for status epilepticus are also highly variable. These varied presentations have significantly different associations with neuronal injury and therefore can vary greatly with regard to how aggressively/urgently they need to be treated. This diversity was reflected in the ILAE position statement on the definitions and classification of status epilepticus.


Electrographic status epilepticus (ESE) is defined by the ACNS as an ESz for ≥10 continuous minutes, or for a total duration of ≥20% of any 60-minute period of recording. Previously, it was common to require ESzs to occupy ≥30 minutes (or ≥50%) total duration of any 60-minute period of recording to qualify as ESE. The reduction to ≥20% is largely based on one large study that demonstrated that a seizure burden of >20% was associated with significantly increased chance of neurological decline in a cohort of critically ill children. A similar cutoff was identified in neonates with hypoxic ischemic encephalopathy. Multiple other studies in a variety of ages and conditions have shown a ‘dose-response’ effect, with greater seizure burden (either measured as peak burden in 1 hour or in 12 hours, or cumulative number of hours) resulting in worse outcomes, both short-term and long-term.


Electroclinical status epilepticus (ECSE) is defined as an ECSz for ≥10 continuous minutes, or for a total duration of ≥20% of any 60-minute period of recording. An ongoing seizure with prominent bilateral motor activity (and impaired awareness) only needs to be present for ≥5 continuous minutes to qualify as ECSE. This can also be referred to as ‘convulsive SE’, a subset of ‘SE with prominent motor activity’. In any other clinical situation, the minimum duration to qualify as SE is 10 minutes.


Some of the more common types of status epilepticus include:



  1. Convulsive (synonymous with ‘tonic-clonic’, a form of ‘SE with prominent motor activity’): with ‘episodes of excessive abnormal muscle contractions, usually bilateral, which may be sustained, or interrupted’. It is well established that convulsive SE represents a medical emergency, can cause irreparable neurological damage, and should be treated urgently. This is why convulsive activity only needs to be present for ≥5 minutes before meeting criteria for convulsive SE (as opposed to ≥10 minutes for any other type of SE).
  2. Nonconvulsive (NCSE, a form of ‘SE without prominent motor activity’): can equally represent a prolonged focal seizure in a patient that has a brain tumor, a continuous generalized pattern in a patient with primary generalized epilepsy that is mildly interactive but slightly confused, or a >2.5 Hz pattern of GPDs in a medically ill severely obtunded or comatose patient.
  3. Myoclonic SE: often seen in hypoxic ischemic encephalopathy and discussed further in Chapter 8: Post cardiac arrest EEG.
  4. Focal motor SE (a subtype of which is epilepsia partialis continua [EPC]): A patient in EPC represents a specific class of focal motor status where there is periodic jerking of one particular part of the body and fully retained awareness (focal aware motor status epilepticus). This can be associated with periodic discharges or no scalp EEG correlate (as with any focal aware seizure, lack of scalp EEG correlate is common). EPC can be present for weeks to months, even years on rare occasion, without progressing to any other type of seizure. The finding is often associated with a discrete structural abnormality/lesion resulting in a very limited circuit of re-entrant seizure activity.

In the ICU there are many patients where it is uncertain if the ongoing electrographic pattern is contributing to their clinical signs. These patients are classified in the category of ‘possible ECSE’. It should be noted that if it is certain that the electrographic pattern is causing clinical signs (irrespective of the pattern), this would qualify as ECSE. ‘Possible ECSE’ is defined as a RPP that qualifies for the ictal-interictal continuum (IIC) (i.e., it does not qualify as a ESz/ESE: further discussed and defined below) that is present for ≥10 continuous minutes, or for a total duration of ≥20% of any 60-minute period of recording, which shows EEG improvement with a parenteral anti-seizure medication BUT without clinical improvement. This remains largely in line with ‘possible NCSE’ as defined by the Salzburg criteria, commonly accepted criteria for electrographic SE that were largely incorporated into the ACNS terminology.


A specific population that can pose diagnostic challenge are patients with a known prior epileptic encephalopathy. In these patients the baseline EEG is often severely abnormal (at times meeting criteria for ESE). For these patients to qualify as having ECSE, the EEG pattern needs to represent either:



  1. an increase in prominence or frequency of epileptiform discharges compared with baseline with an observable decline in clinical state, or
  2. EEG and clinical improvement with a parenteral (typically IV) anti-seizure medication.

6.3 Ictal-interictal continuum (IIC)


The definitions of what constitutes seizures are mostly based on historical consensus. For example, there is little evidence that a 2.3-Hz pattern causes less neuronal injury than a 2.7-Hz pattern. Yet one is classified as an ESz (or ESE if persistent) and the other is not. There are many patterns (that do not qualify as ESz/ESE) that appear clinically worrisome, can cause subtle clinical signs, are associated with ictal physiology (e.g., increased blood flow and metabolism), and could contribute to additional neuronal injury, especially in the setting of acute brain injury. Thus, they are potentially ictal in some sense. These patterns fall on the ‘ictal-interictal continuum’, a synonym for ‘possible status epilepticus’. When patients with chronic epilepsy are monitored in the epilepsy monitoring unit (EMU) there is a clear distinction between ictal and interictal states (i.e., what is seizure, and what is not). There is also, for the most part, a crisp and immediate transition between these two states, with a clearly identifiable seizure onset, and offset. In critically ill patients the mechanisms of seizure generation, and perhaps more importantly the maintenance of seizure cessation, is often severely impaired. In these patients there is commonly a gradual waxing and waning between patterns, ranging from those that are fairly benign and those that are more epileptic, and at times ESz/ESE.


This phenomenon resulted in the term ictal-interictal continuum (IIC). The definition of the IIC is broad and deliberately inclusive, mostly to stimulate further studies into differentiating between patterns that are potentially injurious vs. those that are not. Patterns currently thought to qualify as the IIC, based on the ACNS definition in 2021, include (Figure 6.2):



  1. any PD or SW pattern that averages >1.0 Hz and ≤2.5 Hz over 10 s (>10 and ≤25 discharges in 10 s); or
  2. any PD or SW pattern that averages ≥0.5 Hz and ≤1.0 Hz over 10 s (≥5 and ≤10 discharges in 10 s), and has a plus modifier or fluctuation; or
  3. any lateralized RDA averaging >1 Hz for at least 10 s (at least 10 waves in 10 s) with a plus modifier or fluctuation

and



  1. does not qualify as an ESz or ESE.

6.4 Rapid EEG


For the most part, the primary goal of cEEG is to detect seizures as quickly as possible, and have this information fed back to clinicians to allow prompt treatment in order to improve outcomes. Although many centers have a dedicated service in order to do this, there are often delays in setting up the EEG, which requires technical training, and reviewer feedback to clinicians. To avoid these delays, there have been systems/devices (caps, belts, headbands, etc.) developed that allow for the rapid application (within a few minutes) of EEG with minimal training that allows instant review by clinicians and/or has automated interpretation. There is even the feature to ‘sonify’ the EEG (i.e., convert the EEG waves into sound waves) so clinicians can learn to distinguish the constant hum of a non-epileptiform record, versus a louder, more irregular and sometimes crescendo pattern of seizures or status epilepticus, which requires little to no knowledge of the EEG to interpret. Through these means detection of seizures and feedback to clinicians can often occur markedly faster (minutes rather than hours or longer) compared to conventional cEEG. The limited montages of several of these devices do have a mildly reduced sensitivity and specificity compared to traditional full montage; however, rapid EEG is becoming an important supplement to conventional cEEG in many centers for the benefits described, and an important new option for centers without capability for rapid EEGs (especially off-hours) or continuous EEG monitoring.


Figure list



EEGs throughout this atlas have been shown with the following standard recording filters unless otherwise specified: LFF 1 Hz, HFF 70 Hz, notch filter off.


Suggested reading



  1. Beniczky S, Hirsch LJ, Kaplan PW, et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia. 2013; 54 Suppl 6:28–29.
  2. 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 Apr; 22(2):79–91.
  3. 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.
  4. 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.
  5. DeLorenzo RJ, Waterhouse EJ, Towne AR, et al: Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia 1998; 39(8):833–840.
  6. De Marchis GM, Pugin D, Meyers E, et al. Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome. Neurology. 2016; 86(3):253–260.
  7. Drislane FW, Blum AS, Schomer DL. Focal status epilepticus: clinical features and significance of different EEG patterns. Epilepsia. 1999 Sep; 40(9):1254–1260.
  8. Granner MA, Lee SI. Nonconvulsive status epilepticus: EEG analysis in a large series. Epilepsia. 1994 Jan-Feb;35(1):42–47.
  9. Hirsch LJ, Fong MWK, Leitinger M, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2021 Version. J Clin Neurophysiol. 2021; 38(1):1–29.
  10. Jette N, Claassen J, Emerson RG, Hirsch LJ. Frequency and predictors of nonconvulsive seizures during continuous electroencephalographic monitoring in critically ill children. Arch Neurol. 2006; 63(12):1750–1755.
  11. Kamousi B, Grant AM, Bachelder B, Yi J, Hajinoroozi M, Woo R. Comparing the quality of signals recorded with a rapid response EEG and conventional clinical EEG systems. Clin Neurophysiol Pract. 2019; 4:69–75.
  12. Leitinger M, Trinka E, Gardella E, et al. Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus: a retrospective study. Lancet Neurol. 2016; 15(10):1054–1062.
  13. McKay JH, Feyissa AM, Sener U, et al. Time Is Brain: The use of EEG electrode caps to rapidly diagnose nonconvulsive status epilepticus. J Clin Neurophysiol. 2019; 36(6):460–466.
  14. Nei M, Lee J-M, Shanker VL, Sperling MR. The EEG and prognosis in status epilepticus. Epilepsia. 1999; 40(2):157–163.
  15. Payne ET, Zhao XY, Frndova H, et al. Seizure burden is independently associated with short term outcome in critically ill children. Brain. 2014; 137(Pt 5):1429–1438.
  16. Privitera M, Hoffman M, Moore JL, Jester D: EEG detection of nontonic-clonic status epilepticus in patients with altered consciousness. Epilepsy Res 1994; 18(2):155–166.
  17. Sivaraju A, Gilmore EJ. Understanding and managing the ictal-interictal continuum in neurocritical care. Current Treatment Options in Neurology. 2016; 18(2)8.
  18. Struck AF, Westover MB, Hall LT, Deck GM, Cole AJ, Rosenthal ES. Metabolic correlates of the ictal-interictal continuum: FDG-PET during continuous EEG. Neurocrit Care. 2016; 24(3):324–331.
  19. Swingle N, Vuppala A, Datta P, et al. Limited-montage EEG as a tool for the detection of nonconvulsive seizures. J Clin Neurophysiol. 2020.
  20. Towne AR, Waterhouse EJ, Boggs JG, et al: Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000; 54(2):340–345.
  21. Treiman DM, Walton NY, Kendrick C. A progressive sequence of electroencephalographic changes during generalized convulsive status epilepticus. Epilepsy Res. 1990; 5(1):49–60.
  22. Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015; 56(10):1515–1523.
  23. Vespa PM, Nuwer MR, Nenov V, et al: Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J Neurosurg 1999; 91(5):750–760.
  24. Vespa PM, O’Phelan K, Shah M, et al: Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome. Neurology 2003; 60(9):1441–1446.
  25. Vespa PM, McArthur DL, Xu Y, et al. Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy. Neurology. 2010; 75(9):792–798.
  26. Vespa P, Tubi M, Claassen J, et al. Metabolic crisis occurs with seizures and periodic discharges after brain trauma. Ann Neurol. 2016; 79(4):579–590.
  27. Vespa PM, Olson DM, John S, et al. Evaluating the clinical impact of rapid response electroencephalography: The DECIDE multicenter prospective observational clinical study. Crit Care Med. 2020; 48(9):1249–1257.
  28. Westover MB, Gururangan K, Markert MS, et al. Diagnostic value of electroencephalography with ten electrodes in critically ill patients. Neurocrit Care. 2020; 33(2):479–490.
  29. Witsch J, Frey HP, Schmidt JM, et al. Electroencephalographic periodic discharges and frequency-dependent brain tissue hypoxia in acute brain injury. JAMA Neurol. 2017; 74(3):301–309.
  30. Young GB, Jordan KG, Doig GS: An assessment of nonconvulsive seizures in the intensive care unit using continuous EEG monitoring: an investigation of variables associated with mortality. Neurology 1996; 47(1):83–89.
  31. Zafar SF, Subramaniam T, Osman G, Herlopian A, Struck AF. Electrographic seizures and ictal–interictal continuum (IIC) patterns in critically ill patients. Epilepsy & Behavior. 2020; 106:107037.
  32. Zafar SF, Rosenthal ES, Jing J, et al. Automated annotation of epileptiform burden and its association with outcomes. Ann Neurol. 2021; 90(2):300–311.

*Reference defining the terms used in this atlas.

Schematic illustration of electrographic and electroclinical seizures.

Figure 6.1. Electrographic and electroclinical seizures. Electrographic seizures (ESz) are defined as either: 1. epileptiform discharges averaging >2.5 Hz for ≥10 s (>25 discharges in 10 s) (panel A), or 2. any pattern with definite evolution and lasting ≥10 s. Electrographic status epilepticus (ESE) is defined as an electrographic seizure for >10 continuous minutes or for a total duration of >20% of any 60-minute period of recording.


Electroclinical seizure (ECSz) is defined as any EEG pattern with either: 1. definite clinical correlate time-locked to the pattern (of any duration, including subtle clinical correlate as long as it is time-locked to the pattern) (panel B), or 2. EEG and clinical improvement with a parenteral (typically IV) anti-seizure medication. The EEG pattern during an ‘electroclinical seizure’ does not necessarily need to qualify as an ‘electrographic seizure’. For example, if static 1-Hz PDs have a clinical correlate, this would not qualify as an electrographic seizure, but would qualify as an electroclinical seizure (as shown in panel B). Many seizures would however qualify for both ‘electrographic’ and ‘electroclinical’ seizures, and these should be reported under both terms. Electroclinical status epilepticus (ECSE) is defined as an electroclinical seizure for >10 continuous minutes or for a total duration of >20% of any 60-minute period of recording. An ongoing seizure with bilateral tonic-clonic (BTC) motor activity only needs to be present for >5 continuous minutes to qualify as ECSE. This is also referred to as ‘convulsive SE’, a subset of ‘SE with prominent motor activity’. In any other clinical situation, the minimum duration to qualify as SE is >10 minutes. ‘Possible ECSE’ is an RPP that qualifies for the IIC that is present for ≥10 continuous minutes or for a total duration of >20% of any 60-minute period of recording, which shows EEG improvement with a parenteral anti-seizure medication BUT without clinical improvement. This remains largely in line with ‘possible NCSE’ as defined by the Salzburg criteria.


Reproduced from Hirsch LJ, Fong MWK, Leitinger M, et al. American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2021 Version. J Clin Neurophysiol. 2021;38(1):1–29, with permission.

Schematic illustration of ictal-interictal continuum (IIC).

Figure 6.2. Ictal-interictal continuum (IIC).

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

May 12, 2023 | Posted by in Uncategorized | Comments Off on Seizures, status epilepticus and the ictal-interictal continuum

Full access? Get Clinical Tree

Get Clinical Tree app for offline access