Status Epilepticus: Practical Guidelines in Management Ashalatha Radhakrishnan
INDEX
Page numbers followed by f refer to figure and t refer to table
A
Airway 1012
Antiepileptic drugs 2, 7, 28, 39, 40, 40t, 47, 65, 73, 105
B
Benzodiazepines 12, 25, 32, 33, 39, 47, 50, 104
Breathing 1012
Buccal midazolam 16
C
Calcium-channel blockers 69
Cerebrovascular accidents 8
Circulation 1012
Clobazam 3941, 45, 47
Clonazepam 35, 3941, 46, 47
Cluster seizures 8
Complex partial seizures 43
D
Desflurane 52
Diazepam 12, 13, 34, 39, 47
E
Electroconvulsive therapy 39, 68
Electroencephalography 25
role of 25
Emergency surgery 66
Encephalopathy syndrome, posterior reversible 68
Epilepsy 11, 18, 18f
syndrome, febrile-infection-related 58
Epileptiform discharges
generalized 105
lateralized 105
F
Fosphenytoin 35, 39, 73
G
Gamma-amino-butyric acid 58
Glasgow coma scale 7, 12
Glutamate decarboxylase 58
H
Hypothermia 67
I
Intensive care unit 7, 105
International League Against Epilepsy 1, 24, 32
Intramuscular midazolam 18
Intranasal midazolam, dosage of 16t
Intravenous methyl prednisolone 68
Isoflurane 52
K
Ketamine 52
Ketogenic diet 66
L
Lacosamide 3941, 44, 47
Levetiracetam 18, 3941, 43, 47, 50
Liver diseases 73
Lorazepam 18, 33, 39, 47
M
Magnesium 67
Midazolam 12, 14, 34, 39, 51
nasal spray 14, 15f
N
New-onset refractory status epilepticus 57, 64
N-methyl-D-aspartate receptor 58, 63
P
Periodic epileptiform discharges 80
Phenobarbitone 40, 73
Phenytoin 35, 47, 50, 104
Propofol 51, 52, 73
infusion syndrome 51
Pseudostatus epilepticus 25
Psychogenic nonepileptic seizures 25
Pyridoxine 68
R
Rectal diazepam 14
Renal diseases 74
Repetitive seizures, acute 8
Respiratory depression 12
Resuscitation, cardiopulmonary 17
S
Sodium valproate 3942, 47
Status epilepticus 1, 2f, 3, 7, 8, 12, 19, 23, 25, 25t, 28, 32, 39, 39t, 40t, 47, 50, 57, 72, 81, 83, 105
classification of 24t
convulsive 8, 23
duration of 23
evaluation of 29
general management of 26
management of 10, 33, 33f, 47, 56, 7274, 75
nonconvulsive 1, 3, 7, 24, 72, 80, 83, 104, 105
partial 84
poststroke 75
prehospital management of 7, 11, 11, 13t
refractory 11, 50, 52, 56, 57, 57t, 60, 63
severity score 56
stages of 9
super-refractory 56, 57, 57t, 63, 68
treatment 13t
trials 41t
T
Thiopentone 52
sodium 73
Tonic-clonic seizures, generalized 2, 43, 75
Topiramate 3941, 45
V
Voltage-gated potassium channel 58, 63
×
Chapter Notes

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Evolution of ‘Definitions’ of Status Epilepticus and Nonconvulsive Status EpilepticusChapter 1

Malcolm Jeyaraj K
 
HISTORY
The definition of status epilepticus (SE) has been remarked in literature in the early 1900s by Clark and Prout as a state in which seizures occur so frequently that ‘coma and exhaustion are continuous between seizures’.1 Kinnier Wilson, in his observation in 1940, observed that SE is the severest form of seizures in which ‘the postconvulsive sleep of one attack is cut short by development of the next’.2 The first International Classification of Seizures in 1964 by the International League Against Epilepsy (ILAE) defined SE as a situation in which ‘a seizure persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic condition’.3 In the 1981 revision of the same, the definition was minimally changed into a ‘seizure’ that ‘persists for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur (Fig. 1.1)’.4
In the aforementioned definitions, confusion existed regarding the exact time frame as to when a continuous seizure activity be termed as SE. Subsequently several studies have fixed varying time intervals in their studies on the duration of status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on SE re-defined SE as that lasting more than 30 minutes on the basis of estimates of the time needed to sustain neuronal injury from a prolonged seizure.5 Bleck et al. later defined SE as continuous or repeated seizures lasting more than 20 minutes.6 Subsequently, the Veteran Affairs Co-operative Trial on treatment of generalized convulsive SE used 10 minutes as the cut-off for inclusion criterion for SE.7
The practical difficulty in setting the time frame for duration of SE arises from our limited understanding of the basic pathophysiological mechanisms underlying SE and the variations in clinical phenotype. In this background, two definitions were proposed namely an ‘operational’ and a ‘mechanistic’ definition.8
 
OPERATIONAL DEFINITION
The initial operational definition had been proposed by Lowenstein in the year 1999 and reads as follows ‘generalized convulsive SE in adults and older children (>5 years old) refers to: (a) 5 minutes of a continuous seizure, or (b) two or more discrete seizures between which there is incomplete recovery of consciousness’.
The rationale behind this definition is based on the following observations. The first among them is based on the work done by Meldrum et al. who had established that seizures lasting more than 82 minutes in unanesthetized baboons could cause irreversible brain injury.92
zoom view
Figure 1.1: Evolution of definitions of status epilepticus
Other, clinical studies have also established a relation between seizure duration and mortality. Secondly, generalized tonic-clonic seizures (GTCS) in adults last rarely more than 5 minutes. Studies by Gastaut and Theodore have shown that the duration of GTCS lasts between a few seconds and 4 minutes in the former, and 16–108 seconds in the latter.10,11 However, the biologic differences between seizures that last a few minutes and more than 5 minutes, are not clear. Lastly, and perhaps the most important consideration, is that GTCS that last beyond the typical duration should be promptly treated with antiepileptic drugs (AEDs) to induce cessation of seizures and thereby reduce systemic complications. Further, the assessment and management of the patient becomes much easier when seizures are promptly stopped.
The ILAE Task Force on Classification of SE has proposed a definition of SE that includes all types and takes into consideration the pathophysiology of SE, clinical treatment end points, as well as it aids the conduct of clinical and epidemiologic studies.123
The definition is conceptual with two operational dimensions: the first is based on the length of seizures and at which point the seizure should be regarded as an abnormally prolonged seizure. The second point is the time beyond which the ongoing seizure activity leads to long-term consequences. On the practical side, the time point 1 (t1) indicates the time at which treatment should be initiated. The time point 2 (t2) indicates the time at which treatment should be aggressively implemented to prevent long-term consequences. The time domain could vary between different types of SE as detailed (Table 1.1).12
 
MECHANISTIC DEFINITION
Generalized convulsive SE refers to a condition in which there is a failure of the normal factors that serve to terminate a typical GTCS. This definition is an ideal one that can be considered a basic research definition because our knowledge of the mechanisms governing cessation remains incomplete. If the factors responsible for termination are clearly understood, then this definition would supplant the operational definition.8
 
NONCONVULSIVE STATUS EPILEPTICUS
‘Nonconvulsive status epilepticus (NCSE) is a term used to denote a range of conditions in which electrographic (EEG) seizure activity is prolonged and results in nonconvulsive clinical symptoms’.13 This definition was proposed by delegates in the Epilepsy Research Foundation Workshop on NCSE in Oxford in March 2004.13 The clinical features are as much variable as are the anatomical, pathophysiological and etiological factors. The duration of the electrographic activity required to identify an NCSE was arbitrarily fixed at 30 minutes as an operational time limit for epidemiological purposes. There are also a lot of boundary conditions which need to be identified 4as the electrographic activity noted may not be the cause for the ongoing electrical activity.13 The electrographic activity could take several forms, which clearly denote NCSE and could be equivocal otherwise.13
Table 1.1   Operational dimensions with t1, indicating the time that emergency treatment of SE should be started, and t2, indicating the time at which long-term consequences may be expected12
Type of SE
Operational dimension 1
Time (t1), when a seizure is likely to be prolonged leading to continuous seizure activity
Operational dimension 2
Time (t2), when a seizure may cause long-term consequences (including neuronal injury, neuronal death, alteration of neuronal networks and functional deficits)
Tonic-clonic SE
5 minutes
30 minutes
Focal SE with impaired consciousness
10 minutes
>60 minutes
Absence status epilepticus
10–15 minutes2
Unknown
Evidence for the time frame is currently limited and future data may lead to modifications
Abbreviation: SE, status epilepticus
 
EEG Criteria for NCSE
  • Frequent or continuous focal electrographic seizures, with ictal patterns that wax and wane with change in amplitude, frequency and/or spatial distribution.
  • Frequent or continuous generalized spike wave discharges in patients without a prior history of epileptic encephalopathy or epilepsy syndrome.
  • Frequent or continuous generalized spike wave discharges, which shows significant changes in intensity or frequency (usually a faster frequency) when compared to baseline EEG, in patients with an epileptic encephalopathy/syndrome.
  • Periodic lateralized epileptiform discharges (PLEDs) or bilateral periodic lateralized epileptiform discharges (BIPLEDs) occurring in patients in coma in the aftermath of a generalized tonic-clonic SE (subtle SE).
EEG patterns which are less easy to interpret include:
  • Frequent or continuous EEG abnormalities (spikes, sharp waves, rhythmic slow activity, PLEDs, BIPLEDs, generalized periodic discharges [GPEDs], triphasic waves) in patients whose EEG showed no previous similar abnormalities, in the context of acute cerebral damage (e.g. anoxic brain damage, infection, trauma).
  • Frequent or continuous generalized EEG abnormalities in patients with epileptic encephalopathies in whom similar interictal EEG patterns are seen, but in whom clinical symptoms are suggestive of NCSE.
 
BEDSIDE APPLICATION OF THE DEFINITION
In India and developing countries, and even in many provinces of developed nations as well, patients with SE may reach the next available hospital much beyond the t1 time limit for convulsive SE. Hence, the treatment protocol for SE should be initiated the moment they arrive at the emergency with persistent seizures. However, as regards to absence status and focal SE, identification of the above conditions may be difficult clinically at a primary care level and would need electrophysiological studies and specialist advice to identify the same. This does make timely management an issue at a primary care level.
 
CONCLUSION
The proposed definitions do have a number of benefits in that they give us a time frame to guide us regarding the start of specific treatment. The early initiation of therapy thereby would lead to fewer complications. The generalized tonic-clonic convulsions that extend beyond 5 minutes have been proposed to be a distinct entity but the pathophysiological basis for the same is not yet distinctly proved. As regards dyscognitive status (complex partial SE) and absence status, further studies are needed to enlighten on the long-term consequences of prolonged seizures. The recently proposed definitions would serve as realistic definitions for the purpose of clinical studies on SE. However, at a practical level, to strictly apply time limits would have its own difficulties.5
Test Yourself
  1. In the first classification of seizures by ILAE in 1964, how was status epilepticus (SE) defined?
    In 1964, ILAE defined SE as a situation in which ‘a seizure persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic condition’.
  1. How did Lowenstein, in 1999, proposed an initial operational definition of SE?
    Lowenstein's initial operational definition is as follows: ‘Generalized convulsive SE in adults and older children (>5 years old) refers to (a) 5 minutes of a continuous seizure, or (b) two or more discrete seizures between which there is incomplete recovery of consciousness’.
  1. In the proposed definition of SE by ILAE Task Force in 2015, what do time point 1 (t1) and time point 2 (t2) indicate?
    The time point 1 (t1) indicates the time at which treatment should be initiated. The time point 2 (t2) indicates the time at which treatment should be aggressively implemented to prevent long-term consequences.
  1. In case of tonic-clonic SE, what is the duration of the time point 1 (t1) and time point 2 (t2) to prevent long-term consequences?
    In case of tonic-clonic SE, time point 1 (t1) is 5 minutes and time point 2 (t2) is 30 minutes to prevent long-term consequences.
  1. What was the definition proposed by Epilepsy Research Foundation Workshop on NCSE in Oxford in March 2004?
    Nonconvulsive status epilepticus (NCSE) is a term used to denote a range of conditions in which electrographic seizure activity is prolonged and results in nonconvulsive clinical symptoms.
  1. For epidemiological purposes, what was the duration of the electrographic activity required to identify an NCSE?
    30 minutes.
Courtesy
Dr Hemanga Dhing
Senior Resident
Department of Neurology
SCTIMST, Kerala, India
REFERENCES
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  1. Wilson S. Williams and Wilkins.  Neurology. Baltimore, 1940.
  1. Commission on Terminology of the International League Against Epilepsy. A proposed international classification of epileptic seizures. Epilepsia. 1964;5:297–306.
  1. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1981;22:489–501.
  1. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA. 1993;270:854–9.
  1. Bleck T. Convulsive disorders: Status epilepticus. Clin Neuropharmacol. 1991;14:I91–8.
  1. 6 Treiman D, Meyera P, Walton N, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998;339:792–8.
  1. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. 1999;40:120–2.
  1. Meldrum B, Brierley J. Prolonged epileptic seizures in primates: ischemic cell change and its relation to ictal physiological events. Arch Neurol. 1973;28:10–7.
  1. Gastaut H. Clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1970;11:102–13.
  1. Theodore W, Porter R, Albert P, et al. The secondarily generalized tonic-clonic seizure: a videotape analysis. Neurology. 1994;44:1403–7.
  1. A definition and classification of status epilepticus-Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56:1515–23.
  1. Nonconvulsive status epilepticus: Epilepsy Research Foundation Workshop Reports. Epileptic Disord. 2005;7:253–96.