This is seminar slides for updates of status epilepticus ,Febrile seizures and seizure clusters.

1. Status Epilepticus
1
7/18/2022
Presenter : Dr Eliezer H. MD
Pediatrics and child health, R II
Moderator : Dr Solomon G. MD
Consultant pediatrician and Assistant professor of PCH
Eliezer H. MD

2. Status Epilepticus Eliezer H. MD
Outline
 Introduction
 Definition
 Epidemiology
 Classification & Etiology
 Pathophysiology
 Clinical features and complications
 Management
 Out come
 Febrile status epilepticus and Seizure clusters
2

3. Status Epilepticus Eliezer H. MD
Objectives
 Describe clinical presentation and classification
 Summarize the etiology
 Enable to make urgent, focused evaluation, act on
time and prevent complications
 Identify options of management
3

4. Status Epilepticus Eliezer H. MD
Introduction to Status epilepticus
4
 One of the most common medical neurologic emergency in childhood 1
 Not a disease entity but rather a symptom with a myriad of etiologies
 Any type of seizure may become prolonged (SE) 2
 Associated with mortality & neurodevelopmental sequelae
 Early managed much complications can be prevented
References
1. Kliegman, Robert. Nelson Textbook of Pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020
2. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice. Pp 559-566

5. Status Epilepticus Eliezer H. MD
Operational definition 1
 Considering the need for rapid evaluation and intervention in GCSE
 To avoid cardiovascular morbidity and refractory status,
 Accepted operational definition of GCSE :
• ≥5 minutes of continuous seizures, or
• ≥2 discrete seizures between which there is incomplete recovery of
consciousness
5
Definition
References
1. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. 1999 Jan;40(1):1202. doi:
10.1111/j.1528-1157.1999.tb02000.x. PMID: 9924914.

6. Status Epilepticus Eliezer H. MD
Cont’d …
6
SE is defined by the ILAE as:1
 A condition resulting either from
• Failure of the mechanisms responsible for seizure termination or
• Initiation of mechanisms that lead to abnormally prolonged seizures (after time
point t1); and
 A condition that can have long-term consequences (after time point t2),
• Including neuronal death, neuronal injury, and alteration of neuronal networks
References
1. Trinka, E . et al, 2015. A definition and classification of status epilepticus–Report of the ILAE Task Force on Classification of
Status Epilepticus. Epilepsia, 56(10), pp.1515-1523.

7. Status Epilepticus Eliezer H. MD
t1 and t2 …
7
 Only 28% arrive within 2 hours of presentation. 1
References
1. Abayneh, M., & Bacha, T. (2017). CLINICAL PRESENTATION, CAUSE, AND SHORT-TERM OUTCOME OF CHILDREN WITH STATUS EPILEPTICUS IN TIKUR
ANBESSA SPECIALIZED HOSPITAL ADDIS ABABA, ETHIOPIA: A 5-YEAR RETROSPECTIVE CROSS-SECTIONAL STUDY. Ethiopian Journal of Pediatrics and Child
Health, 12(1). Retrieved from https://ejpch.net/index.php/ejpch/article/view/96

8. Status Epilepticus Eliezer H. MD
Epidemiology
 Incidence of SE ranges between 10 and 60 per 100,000 population in various
studies.1
 Approximately 17 to 23 of 100,000 children experience SE every year 1
• The highest incidence in children < 1 year of age. If febrile SE is excluded,incidence
decreases by 25% to 40%.
 Generalized tonic-clonic seizure was the commonest type of seizure (74.8%). 2
• There was a previous history of seizure disorder in 34(38.2%) of the cases.
• Temperature greater than 38 oC was documented for 40 (44.9%) patients at presentation.
8
References
1. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566
2. Abayneh, M., & Bacha, T. (2017). CLINICAL PRESENTATION, CAUSE, AND SHORT-TERM OUTCOME OF CHILDREN WITH STATUS
EPILEPTICUS IN TIKUR ANBESSA SPECIALIZED HOSPITAL ADDIS ABABA, ETHIOPIA: A 5-YEAR RETROSPECTIVE CROSS-SECTIONAL STUDY.
Ethiopian Journal of Pediatrics and Child Health, 12(1). Retrieved from https://ejpch.net/index.php/ejpch/article/view/96

9. Status Epilepticus Eliezer H. MD
Risk factors for status epilepticus
Independent risk factors Genetic syndromes Genetic risk factors Others in symptomatic
epileptic
History of prior Status
epilepticus
Known epileptic
Dravet syndrome Concordance rate highest in
monozygotic twin
Focal background EEG
abnormality
Focal seizure with secondary
generalization
Young age < 1 year at onset Generalized epilepsy with
Febrile seizure plus
[GEFS+],
Nature of the genetic factor
is not yet settle
Occurrence of Status
epilepticus as first seizure
Symptomatic etiology Angelman syndrome Generalized abnormality on
neuroimaging
Patient with partial seizure that
occur in cluster
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References
1.. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022
[1]

10. Status Epilepticus Eliezer H. MD
Classification…
 A new diagnostic classification system of SE is proposed, which will provide a
framework for
• Clinical diagnosis,
• Investigation, and
• Therapeutic approaches for each patient.
 There are four axes 1
• Semiology(symptoms and signs);
• Etiology;
• Electroencephalography (EEG) correlates; and
• Age.
10
Reference
1. Trinka, E., et al, 2015. A definition and classification of status epilepticus–Report of the ILAE Task Force on Classification of Status
Epilepticus. Epilepsia, 56(10), pp.1515-1523.

11. Status Epilepticus Eliezer H. MD
Cont’d …
11
Reference
1. Trinka, E., et al, 2015. A definition and classification of status epilepticus–Report of the ILAE Task Force on Classification of Status
Epilepticus. Epilepsia, 56(10), pp.1515-1523.

12. Status Epilepticus Eliezer H. MD
Etiology
 Known (i.e., symptomatic)
• Acute (e.g., stroke, intoxication, malaria, encephalitis, etc.)
• Remote (e.g., posttraumatic, postencephalitic, poststroke, etc.)
• Progressive (e.g., brain tumor, Lafora’s disease and other progressive myoclonic
epilepsies )
• SE in defined electroclinical syndromes
 Unknown (i.e., cryptogenic)
12
Reference
1. Trinka, E., et al, 2015. A definition and classification of status epilepticus–Report of the ILAE Task Force on Classification of Status
Epilepticus. Epilepsia, 56(10), pp.1515-1523.

13. Status Epilepticus Eliezer H. MD
Cont’d …
13
Most common etiology is febrile/infectious followed by other acute
symptomatic causes 1
Reference
1. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566
Acute symptomatic Remote (Chronic process)
Acute CNS infection (meningitis ,encephalitis
,abscess )
Congenital brain malformations : Lissencephaly or
schizencephaly
Vascular event: ischemic stroke, intracerebral
hemorrhage, subarachnoid hemorrhage
Cerebral dysgenesis
cerebral sinus thrombosis Perinatal hypoxic ischemic encephalopathy
Head trauma with or without epidural or subdural
hematoma
Remote CNS pathology ( Stroke, Abscess, TBI,
Cortical dysplasia)
Hypertensive encephalopathy CNS tumors
Metabolic disorders (hypoglycemia,
hyperglycemia, hyponatremia, hypocalcemia,
hypomagnesemia …
Progressive neurodegenerative disorder
Toxins ,AED overdose and noncompliance Idiopathic/Cryptogenic

14. Status Epilepticus Eliezer H. MD
Pathophysiology …
 On a neurochemical level seizure are sustained by excess excitation and reduced
inhibition
• Failure of the normal mechanisms that limit the spread and recurrence of isolated seizures.
 Role of neurotransmitters
• Excitatory : Glutamate ,aspartate and acetylcholine
• Inhibitory : GABA main inhibitor in the brain, calcium ion-dependent potassium ion current and
blockage of N-methyl-d-aspartate (NMDA) channels by magnesium.
14
[2]
Reference
1. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566

15. Status Epilepticus Eliezer H. MD
Cont’d …
Disturbance of the NMDA channels appears to be an important mechanism of
neuronal injury in SE. 1
 When neurons are depolarized, calcium enters the cell through NMDA channels
and causes injury or death.
15
Reference
1. Swaiman, K.F. and Ferriero, D.M.et al, 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566
2. www.google .com, status epilepticus neurobiology image 2013

16. Status Epilepticus Eliezer H. MD
Complications of status epilepticus
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Complications
of status
epilepticus
Medical : Hypoxemia, aspiration pneumonia and leukocytosis
 Cardiac arrythmia and acidemia
 Glycemic and hemodynamic disturbance
 Raised intracranial pressure
Neurologic : progression to chronic epilepsy
Recurrent status epilepticus
And it could be immediate or delayed
[1],[2]
 13% has CSF pleocytosis not caused by meningitis or encephalitis
 High fever can result in brain damage in rare instances of febrile status epilepticus 1
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022
2. Sutter R, Dittrich T, Et al. Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review. Crit Care Med. 2018 Jan;46(1):138-145.

17. Status Epilepticus Eliezer H. MD
Risk factors for recurrence
 Remote symptomatic etiology
 Abnormal electroencephalogram like
Focal background EEG abnormalities
 Seizure during sleep
 History of prior febrile seizures
 Focal post-ictal deficits
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 Neurologically abnormal children.
 Partial seizures with secondary
generalization
 Occurrence of SE as the first seizure
 History of prior SE
 Young age (one year or less) at onset
Reference
1. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566

18. Status Epilepticus Eliezer H. MD
Initial studies
 Start with the RBS 1,2
 Sodium, calcium, magnesium, complete blood count,
 Serum antiepileptic drug (AED) levels
 Arterial blood gases and pH
 EEG
 Neuroimaging : MRI and CT
18
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022
2. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566

19. Status Epilepticus Eliezer H. MD
Rapid recognition and focused evaluation
History: 1
 Prehospital administration of benzodiazepines and any other antiseizure medications
 Patient history of epilepsy, current medications, including prior or current use of antiseizure
medications
 Precipitating factors prior to seizure (e.g, febrile illness, possible toxic exposure, trauma,
change in antiseizure medications)
 For patients with prior SE, history of treatment response
 Other active medical diagnoses, especially those associated with hypoglycemia,
hyponatremia, or hypocalcemia
 Allergies to any medications
19
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

20. Status Epilepticus Eliezer H. MD
URGENT FOCUSED EVALUATION …
Physical examination : 1
 In patients with SE, the initial physical examination is limited.
 In addition to assessing :Vital signs, airway, breathing, and Circulation,
 Clinician should identify:
• Signs of head trauma (e.g. swelling, ecchymosis, or lacerations)
• Signs of sepsis or meningitis (e.g., fever, poor perfusion, or rash [e.g., petechiae,
erythroderma, or cellulitis])
• Seizure characteristics (e.g., focal or generalized)
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Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

21. Status Epilepticus Eliezer H. MD
Management …
Immediate supportive care : 1
• Prolonged seizures cause brain damage independently from the underlying etiology.
 Main goals of management :
• Establish and maintain adequate airway, breathing, and circulation
• Identify and treat hypoglycemia
• Stop the seizure and thereby prevent brain injury
• Identify and treat life-threatening causes of SE
 All patients with GCSE should have continuous monitoring [1]
21
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

22. Status Epilepticus Eliezer H. MD
Airway and breathing …
Important airway interventions in children with SE include : 1
 Open the airway and maintain it through positioning, jaw thrust and/or airway adjunct
 Suction secretions and administer 100%
 Pt with any one of the following should undergo RSI and MV
• Unprotected or unmaintainable airway
• Apnea or inadequate ventilation or Hypoxemia
• SE lasting 30 minutes
22
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

23. Status Epilepticus Eliezer H. MD
Circulation and Vascular access
 Establish venous access 1
• Sampling of blood and administration of medications and fluids.
• Alternative routes e.g. rectal, intramuscular, buccal, or intranasal) should be used if IV
administration is not possible within the first five minutes;
• An intraosseous (IO) line should be placed if IV access is further delayed.
 Hemodynamic support not commonly required
• In the Presence of low BP with SE consider systemic illness, traumatic hemorrhage or infection
23
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

24. Status Epilepticus Eliezer H. MD
EMERGENCYANTISEIZURE TREATMENT
 Clinically obvious CSE should be treated immediately with a benzodiazepine, with
out waiting for EEG or other studies 1
 The ideal AED for the treatment of SE should have the following properties:2
• Rapid onset of action with wide spectrum of activity
• Intravenous preparation and ease of administration
• Minimal redistribution from the CNS
• Short elimination half-life
• Wide therapeutic safety margin
24
References
1. Katzung, B.G., 2018. Basic and clinical pharmacology. Mc Graw Hill.
2. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?

25. Status Epilepticus Eliezer H. MD
Time line with stabilization phase of mgt …
25
Reference
1. AES Clinical Practice Guideline Development Manual, 2020 Ed. Chicago, IL: American Epilepsy Society. 2020

26. Status Epilepticus Eliezer H. MD
Initial therapy phase …
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Reference
1. AES Clinical Practice Guideline Development Manual, 2020 Ed. Chicago, IL: American Epilepsy Society. 2020

27. Status Epilepticus Eliezer H. MD
Second therapy phase …
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Reference
1. AES Clinical Practice Guideline Development Manual, 2020 Ed. Chicago, IL: American Epilepsy Society. 2020

28. Status Epilepticus Eliezer H. MD
Third therapy phase …
28
Reference
1. AES Clinical Practice Guideline Development Manual, 2020 Ed. Chicago, IL: American Epilepsy Society. 2020

29. Status Epilepticus Eliezer H. MD
First therapy: Benzodiazepines
29
Summarized algorithm approach to
antiseizure treatment for CSE in children and
adolescents. 2022 UPTODATE

30. Status Epilepticus Eliezer H. MD
First therapy … BDZ
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31. Status Epilepticus Eliezer H. MD
First line therapy pharmacologic features …
Lorazepam Diazepam Midazolam
Max effect can be as long as two min High lipid solubility with max effect
10 to 20 sec
Rapidly cross BBB
Very effective less than one minute
Effective duration of action 4-6hrs Duration of effect 20min With short half-life
Half life in newborns may reach
40hrs,children 10hrs,adults 13hrs
CSF concentration reach one-half of
their max value in three min
IV/IO/IN/Rectal IV/IO/PO/Rectal IV/IM/po/buccal/Rectal
31
 Treatment with lorazepam did not result in improved efficacy or safety
compared with diazepam. 1
 Lorazepam more sedative, no secondary outcome difference 1
Reference
1. James M Chamberlin MD et al; Lorazepam vs Diazepam for Pediatric Status epilepticus a RCT ,JAMA. 2014;311(16):1652-1660.
doi:10.1001/jama.2014.2625
2. Katzung, B.G., 2018. Basic and clinical pharmacology. Mc Graw Hill.

32. Status Epilepticus Eliezer H. MD
Second therapy: Antiseizure medications
 Seizures continue for 10 minutes after at least two injections of lorazepam or
diazepam, a second therapy.
 Phenytoin, valproate, and levetiracetam are safe and equally efficacious following
lorazepam in GCSE.1
• The choice of AEDs could be individualized based on co-morbidities.
• SE could be controlled in 92% of patients with AEDs only and anesthetics were not required in them.
32
Reference
1. Mundlamuri RC, Sinha S, Subbakrishna DK, et al. Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of
combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam--Pilot study. Epilepsy Res. 2015 Aug;114:52-8. doi:
10.1016/j.eplepsyres.2015.04.013. Epub 2015 May 1. PMID: 26088885.

33. Status Epilepticus Eliezer H. MD
Factors influencing choice of agent…
 Knowledge of the patient's previous response to antiseizure medications
 Current medication use may guide the approach to management
 History of trauma levetiracetam and fosphenitoin drug of choice
• Phenobarbital and Valproate less useful
 Antiseizure medication adherence
 Change in antiseizure medications, nonprescription and illicit drugs
 Paradoxical effects of antiseizure medications
33
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

34. Status Epilepticus Eliezer H. MD
Antiseizures worsening seizure …
 Carbamazepine, phenytoin, and lamotrigine worsen myoclonic seizures.
 Carbamazepine and phenytoin may worsen focal seizures with impairment of
consciousness and increase generalized tonic-clonic seizures.
 Carbamazepine is known to precipitate drop attacks, often with atypical absence
seizures.
 Carbamazepine and lamotrigine may worsen seizures in patients with Dravet syndrome.
 Even benzodiazepines can rarely worsen seizures and precipitate tonic SE, particularly
in children with Lennox-Gastaut syndrome
34
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

35. Status Epilepticus Eliezer H. MD
Second therapy … agent of choice
35
Fosphenytoin Phenytoin
Prodrug of phenytoin Active drug
Faster rate of infusion (water soluble) Slower rate of infusion (mixed in propylene
glycol)
Does not precipitate Can precipitate in IV solutions
Fewer cardiovascular side effects Can cause cardiac arrythmias or hypotension
Fewer tissue side effects : perineal paresthesia
and pruritus
Extravasation or purple glove syndrome
leading to tissue necrosis
Both less effective for seizure due to toxins or drugs e.g. lidocaine ,cocaine
,amphetamine, lindane or theophylline
In such cases alternatives Levetiracetam, Phenobarbital or valproate should
be used.
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022

36. Status Epilepticus Eliezer H. MD
Cont’d…
36
 Phenobarbital is safe and effective second line drug 1
 Levetiracetam is not superior to phenytoin but equivalent 2, 3
 AED levetiracetam, fosphenytoin, and valproate each led to seizure cessation and
improved alertness by 60’ in approximately half the patients, and the three drugs were
associated with similar incidences of adverse events”. 4
 Valproate, levetiracetam and phenobarbital can all be used as first line therapy . 5
 The evidence does not support the first-line use of phenytoin 5
Reference
1. Burman RJ, Ackermann S, et al. A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line Management for Pediatric Convulsive Status Epilepticus in a
Resource-Limited Setting. Front Neurol. 2019;10:506. Published 2019 May 15. doi:10.3389/fneur.2019.00506
2. Dalziel SR, et al; PREDICT research network. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label,
multicentre, randomised controlled trial. Lancet. 2019 May 25;393(10186):2135-2145. doi: 10.1016/S0140-6736(19)30722-6. Epub 2019 Apr 17. PMID: 31005386.
3. Lyttle MD, Rainford NEA et al; Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI) collaborative. Levetiracetam versus phenytoin for second-line treatment
of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019 May 25;393(10186):2125-2134. doi: 10.1016/S0140-6736(19)30724-X.
Epub 2019 Apr 17. PMID: 31005385; PMCID: PMC6551349.
4. Kapur J, Elm J, Chamberlain JM, et al; NETT and PECARN Investigators. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov
28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795. PMID: 31774955; PMCID: PMC7098487.
5. Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published
studies. British epilepsy association . 2014 Mar;23(3):167-74. Doi: 10.1016/j.seizure.2013.12.007. Epub 2013 Dec 25. PMID: 24433665.

37. Status Epilepticus Eliezer H. MD
Phenytoin vs phenobarbital pharmacology
37
Phenytoin Phenobarbital
Mechanism Promotes N+ efflux or decrease influx in motor
cortex
At GABA receptor in the polysynaptic
midbrain reticular formation
Onset IV/PO 1 week (PO), 2-24hr (PO with loading),0.5-1hr IV 5 min IV, 3-12 hrs. po with loading neonate
[26]
Peak plasma time
Therapeutic Conc.
1.5-3 hrs. immediate release
4-12 hrs. extended release
10 to 20 mcg/mL
8-12 hrs
10-40mcg/ml may require 3-4 weeks to
achieve therapeutic level
Protein bound 95% adult ,85% infant ,80% neonate 20-45%
Metabolized Hepatic P450 enzyme CYP2C9 Hepatic oxidative hydroxylation
Enzyme induced CYP3A4 CYP1A2,CYP2B6,CYP2c19,CYP2c9/10,CYP3A4
Half life/excretion 22 hrs. (PO), 10-15 hrs. (IV)/urine 50-140hrs /urine
Reference
1. Burman RJ, et al. A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line Management for Pediatric Convulsive Status
Epilepticus in a Resource-Limited Setting. Front Neurol. 2019;10:506. Published 2019 May 15. doi:10.3389/fneur.2019.00506
2. www.Medscape.com online drug reference
1,2

38. Status Epilepticus Eliezer H. MD
Refractory and Super-Refractory SE…
Refractory SE: When it has not been controlled with appropriate doses of benzodiazepines
and 1 or 2 doses of nonbenzodiazepine antiseizure drugs.1,2
• continuous infusions of antiseizure drugs or anesthetic therapies are often recommended.
The most commonly used continuous infusions are midazolam, pentobarbital, and, less
commonly in the pediatric setting, propofol.
Super-Refractory SE: SE that continues for 24 hours or more after the onset of anesthesia,
including those cases in which the SE recurs on the reduction or withdrawal of anesthesia.
• several therapeutic approaches should be tried sequentially 2
38
Reference
1. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022
2. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566

39. Status Epilepticus Eliezer H. MD
Treatment Alternatives for Refractory and Super-Refractory SE
39
[1]
Reference
1. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice pp 559-566

40. Status Epilepticus Eliezer H. MD
Outcome …
 Overall mortality low in pediatric patients, highest risk in young children 1
 Death rarely occurs during the acute episode of SE
 Most deaths occur 13–30 days after onset of the SE episode
 Refractory SE represent a special population at particularly high risk for mortality and
morbidity
 All deaths occur in acute symptomatic SE 2
 HIV infection was found to be statically associated with poor outcome 2
40
Reference
1. Swaiman, K.F. et al., 2017. Swaiman's Pediatric Neurology: Principles and Practice. Pp 559-566
2. Abayneh, M., & Bacha, T. (2017). CLINICAL PRESENTATION, CAUSE, AND SHORT-TERM OUTCOME OF CHILDREN WITH STATUS EPILEPTICUS IN
TIKUR ANBESSA SPECIALIZED HOSPITAL ADDIS ABABA, ETHIOPIA: A 5-YEAR RETROSPECTIVE CROSS-SECTIONAL STUDY. Ethiopian Journal of
Pediatrics and Child Health, 12(1). Retrieved from https://ejpch.net/index.php/ejpch/article/view/96

41. Status Epilepticus Eliezer H. MD
Outcome …
 The outcome depends upon the 1,2
• Underlying cause
• Duration of the seizure
• Age of the child
 Mortality 3,4
• From respiratory, cardiovascular, or metabolic complications of SE.
• 3% and 9%
• The underlying etiology is the main predictor of mortality.
41
References
1 Abayneh, M., & Bacha, T. (2017). CLINICAL PRESENTATION, CAUSE, AND SHORT-TERM OUTCOME OF CHILDREN WITH STATUS EPILEPTICUS IN TIKUR ANBESSA SPECIALIZED
HOSPITAL ADDIS ABABA, ETHIOPIA: A 5-YEAR RETROSPECTIVE CROSS-SECTIONAL STUDY. Ethiopian Journal of Pediatrics and Child Health, 12(1). Retrieved from
https://ejpch.net/index.php/ejpch/article/view/96
2 Raspall-Chaure, M., Chin, R.F., Neville, B.G., et al., 2006. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol. 5, 769–779
3. Kliegman, Robert. Nelson Textbook of Pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020
4. Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice. Pp 559-566

42. Status Epilepticus Eliezer H. MD
Febrile status epilepticus
 FSE was defined as seizures lasting 30 minutes or longer; the definition was
updated in 2015 to include continuous seizures lasting five minutes or longer 1
 Febrile status epilepticus (FSE) accounts : 2
• 5% of FS but 25% of all childhood SE and
• >70% of SE in the second year of life.
 Strongly associated with Temporal lobe epilepsy 3
 Rarely stops spontaneously
 Acute hippocampal injury following febrile status epilepticus 4
42
Reference
1. https://www.uptodate.com/contents/clinical-features-and-evaluation-of-febrile-seizures?
2. Shinnar S, Pellock JM, Moshe SL, et al. In whom does status epilepticus occur: age-related differences in children. Epilepsia. 1997;38:907–914.
3. Shinnar S. Febrile seizures and mesial temporal sclerosis. Epilepsy Currents. 2003;3:115–118.
4. Lewis DV, Barboriak DP, MacFall JR, et al. Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI evidence and unanswered questions.
Prog Brain Res. 2002;135:263–278.

43. Status Epilepticus Eliezer H. MD
Cont’d …
 FSE does not include episodes of SE in children with fever due to meningitis 1
 Four factors in the prospective cohort study increased the recurrence risk 2 :
• Young age at onset
• History of febrile seizures in a first-degree relative
• Low degree of fever while in the emergency department
• Brief duration between the onset of fever and the initial seizure
43
References
1. https://www.uptodate.com/contents/clinical-features-and-evaluation-of-febrile-seizures?2022
2. Berg, A.T., Shinnar, S., Shapiro, E.D., et al., 1995. Risk factors for a first febrile seizure: a matched case control study. Epilepsia 36, 33

44. Status Epilepticus Eliezer H. MD
Treatment
 IV diazepam or lorazepam if not rectal diazepam, midazolam spray at time of
occurrence 1
 Antipyretic treatment does not affect the recurrence rate 2
 Long term antiepileptic drug is rarely indicated 3
 Role of preventive therapy : Prophylactic AED can decrease the risk of recurrent
febrile seizures 4
44
Reference
1. Swaiman, K.F. et al., 2017. Swaiman's Pediatric Neurology: Principles and Practice. Pp 559-566
2. Rosenbloom, E., Finkelstein, Y et al (2013). Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized
controlled trials and meta-analysis. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 17(6),
585–588. https://doi.org/10.1016/j.ejpn.2013.04.008
3. Subcommittee on Febrile Seizures; American Academy of Pediatrics, 2011. Clinical practice guideline: febrile seizures: guideline for the neurodiagnostic
evaluation of the child with a simple febrile seizure. Pediatrics. 127, 389–394
4. Offringa, M., Newton, R., Nevitt, S. J., & Vraka, K. (2021). Prophylactic drug management for febrile seizures in children. The Cochrane database of
systematic reviews, 6(6), CD003031. https://doi.org/10.1002/14651858.CD003031.pub4

45. Status Epilepticus Eliezer H. MD
Seizure clusters
 There is no consensus in terms of definition
 Two commonly stated definitions 1 clinical and statistical
 If seizures occur within 8 h it is more likely that they arise from a concordant focus and
thus not actually “independent”.2
 Based on these findings, many studies defined seizure clusters as 3 or more seizure in
24 h (interictal period of 8 h or less)
 A threefold or fourfold increase in seizure frequency within a 3-day period has been
considered as seizure clustering
45
Reference
1. Haut S.R. Shinnar S. Moshe S.L. Seizure clustering: risks and outcomes. Epilepsia. 2005; 46: 146-149
2. Haut S.R.Seizure clustering. Epilepsy Behav. 2006; 8: 50-55

46. Status Epilepticus Eliezer H. MD
Cont’d …
 Prevalence depends on the definition
 Most significant risk factor is having intractable epilepsy 1
• Extratemporal epilepsy especially frontal lobe epilepsy,
• Multifocal epilepsy, symptomatic generalized epilepsy, remote history of CNS infection, and
focal cortical dysplasia.
• History of seizure clusters and status epilepticus, head trauma,
• Earlier age of seizure onset, and high seizure frequency in the first 12 months after the onset
of epilepsy (one weekly seizure or more)
 Treatment : benzodiazepine rescue medications cornerstone 1
• Diazepam and midazolam
• One study concluded that no efficacy difference of levetiracetam vs phenytoin IV for SE and ARE. 1
46
Reference
1. Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment. Epilepsia. 1996; 37:
S74-S80

47. Status Epilepticus Eliezer H. MD
Reference
1. Kliegman, Robert. Nelson Textbook of Pediatrics. Edition 21. Philadelphia, PA: Elsevier, 2020
2. Ashwal, S., Gropman, A.L., Schor, N.F., Finkel, R.S., Swaiman, K.F. and Ferriero, D.M., 2017. Swaiman's Pediatric Neurology: Principles and Practice. Pp 559-566
3. https://www.uptodate.com/contents/management-of-convulsive-status-epilepticus-in-children?2022
4. Abayneh, M., & Bacha, T. (2017). CLINICAL PRESENTATION, CAUSE, AND SHORT-TERM OUTCOME OF CHILDREN WITH STATUS EPILEPTICUS IN TIKUR
ANBESSA SPECIALIZED HOSPITAL ADDIS ABABA, ETHIOPIA: A 5-YEAR RETROSPECTIVE CROSS-SECTIONAL STUDY. Ethiopian Journal of Pediatrics and Child
Health, 12(1). Retrieved from https://ejpch.net/index.php/ejpch/article/view/96
5. Trinka, E., Cock, H., Hesdorffer, D., Rossetti, A.O., Scheffer, I.E., Shinnar, S., Shorvon, S. and Lowenstein, D.H., 2015. A definition and classification of status epilepticus–
Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia, 56(10), pp.1515-1523.
6. AES Clinical Practice Guideline Development Manual, 2020 Ed. Chicago, IL: American Epilepsy Society. 2020
7. JAMA. 2014;311(16):1652-1660. doi:10.1001/jama.2014.2625
8.. Mundlamuri RC, Sinha S, Subbakrishna DK, Prathyusha PV, Nagappa M, Bindu PS, Taly AB, Umamaheswara Rao GS, Satishchandra P. Management of generalised
convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or
levetiracetam--Pilot study. Epilepsy Res. 2015 Aug;114:52-8. doi: 10.1016/j.eplepsyres.2015.04.013. Epub 2015 May 1. PMID: 26088885.
9. Katzung, B.G., 2018. Basic and clinical pharmacology. Mc Graw Hill.
10. Sutter R, Dittrich T, Semmlack S, Rüegg S, Marsch S, Kaplan PW. Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review. Crit Care Med.
2018 Jan;46(1):138-145.
11. https://emottawablog.com/2020/07/the-status-on-status-management-of-status-epilepticus
12. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia. 1999 Jan;40(1):120-2. doi: 10.1111/j.1528-1157.1999.tb02000.x.
PMID: 9924914.
13. Burman RJ, Ackermann S, Shapson-Coe A, Ndondo A, Buys H, Wilmshurst JM. A Comparison of Parenteral Phenobarbital vs. Parenteral Phenytoin as Second-Line
Management for Pediatric Convulsive Status Epilepticus in a Resource-Limited Setting. Front Neurol. 2019;10:506. Published 2019 May 15. doi:10.3389/fneur.2019.00506
14. Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, Francis KL, Sharpe C, Harvey AS, Davidson A, Craig S, Phillips N, George S, Rao A, Cheng N, Zhang M,
Kochar A, Brabyn C, Oakley E, Babl FE; PREDICT research network. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children
(ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019 May 25;393(10186):2135-2145. doi: 10.1016/S0140-6736(19)30722-6. Epub 2019 Apr 17.
PMID: 31005386.
15. Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, Woolfall K, Roper L, Noblet J, Lee ED, Potter S, Tate P, Iyer A, Evans V, Appleton RE;
Paediatric Emergency Research in the United Kingdom & Ireland (PERUKI) collaborative. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive
status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019 May 25;393(10186):2125-2134. doi: 10.1016/S0140-6736(19)30724-X. Epub 2019 Apr
17. PMID: 31005385; PMCID: PMC6551349.
47

48. Status Epilepticus Eliezer H. MD
Reference
16. Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN
Investigators. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795. PMID:
31774955; PMCID: PMC7098487.
17. Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published
studies. Seizure. 2014 Mar;23(3):167-74. Doi: 10.1016/j.seizure.2013.12.007. Epub 2013 Dec 25. PMID: 24433665.
18. Raspall-Chaure, M., Chin, R.F., Neville, B.G., et al., 2006. Outcome of paediatric convulsive status epilepticus: a systematic review. Lancet Neurol. 5, 769–779
19. Shinnar S, Pellock JM, Moshe SL, Maytal J, O’Dell C, Driscoll SM, Alemany M, Newstein D, DeLorenzo RJ. In whom does status epilepticus occur: age-related differences in
children. Epilepsia. 1997;38:907–914.
20. Shinnar S. Febrile seizures and mesial temporal sclerosis. Epilepsy Currents. 2003;3:115–118.
21. Lewis DV, Barboriak DP, MacFall JR, Provenzale JM, Mitchell TV, VanLandingham KE. Do prolonged febrile seizures produce medial temporal sclerosis? Hypotheses, MRI
evidence and unanswered questions. Prog Brain Res. 2002;135:263–278.
22. Haut S.R. Shinnar S. Moshe S.L. Seizure clustering: risks and outcomes. Epilepsia. 2005; 46: 146-149
23. Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment. Epilepsia. 1996; 37: S74-S80
24. Haut S.R.Seizure clustering. Epilepsy Behav. 2006; 8: 50-55
25. Seinfeld S, Shinnar S, Sun S, Hesdorffer DC, Deng X, Shinnar RC, O'Hara K, Nordli DR Jr, Frank LM, Gallentine W, Moshé SL, Pellock JM; FEBSTAT study team. Emergency
management of febrile status epilepticus: results of the FEBSTAT study. Epilepsia. 2014 Mar;55(3):388-95. doi: 10.1111/epi.12526. Epub 2014 Feb 6. PMID: 24502379; PMCID:
PMC3959260.
26. Turhan, A. H., Atici, A., Okuyaz, C., & Uysal, S. (2010). Single enteral loading dose of phenobarbital for achieving its therapeutic serum levels in neonates. Croatian medical
journal, 51(3), 215–218. https://doi.org/10.3325/cmj.2010.51.215
27. Berg, A. T., Shinnar, S., Darefsky, A. S., Holford, T. R., Shapiro, E. D., Salomon, M. E., Crain, E. F., & Hauser, A. W. (1997). Predictors of recurrent febrile seizures.
A prospective cohort study. Archives of pediatrics & adolescent medicine, 151(4), 371–378. https://doi.org/10.1001/archpedi.1997.02170410045006
28. Rosenbloom, E., Finkelstein, Y., Adams-Webber, T., & Kozer, E. (2013). Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review
of randomized controlled trials and meta-analysis. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology
Society, 17(6), 585–588. https://doi.org/10.1016/j.ejpn.2013.04.008
29. Offringa, M., Newton, R., Nevitt, S. J., & Vraka, K. (2021). Prophylactic drug management for febrile seizures in children. The Cochrane database of systematic
reviews, 6(6), CD003031. https://doi.org/10.1002/14651858.CD003031.pub4
30. www.google .com, status epilepticus neurobiology image 2013
48

49. Status Epilepticus Eliezer H. MD
7/18/2022
49
Thank you.