Detailed presentation based on the latest guidelines for the management of status epilepticus

1. Status Epilepticus
By
Dr. Basit Ali Khan
HO, MU-II, HFH

2. Patient : Shaheen
 A 27-year-old, female presented in ER with sudden regression of language for the past 2
days.
 The patient could follow verbal commands, but had lost the ability to talk.
 Rest of the neurological examination was unremarkable.
 At the age of 19, she had suffered from a left parietal lobe trauma that led to a intracranial
hematoma in the left parietal lobe for that she underwent a decompressive craniectomy.
 There was no known history of epileptic seizures in the patient or her family.
 CT revealed a lesion in the left parietal lobe.
Qiu, Ji-Qing et al. “Aphasic status epilepticus as the sole symptom of epilepsy: A case report and literature review.” Experimental and therapeutic medicine vol. 14,4 (2017): 3501-3506.
doi:10.3892/etm.2017.4979

3. What is your provisional diagnosis?

4. Epidemiology
 Overall incidence of SE is 9.9 to 41 per 100,000/year. [1]
 Mortality of status epilepticus is 16% to 26% and increases with age.
1 Sánchez S, Rincon F. Status Epilepticus: Epidemiology and Public Health Needs. J Clin Med. 2016 Aug 16;5(8):71. doi: 10.3390/jcm5080071. PMID: 27537921; PMCID: PMC4999791.

5. Definition
 Defined in 1993 by the American foundation of epilepsy as:
“More than 30 mins of continuous seizures activity
Or
two or more sequential seizures without full recovery of consciousness.” *
WHY 30 MINS?
* 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. PMID: 8340986.

6. What is the problem with
this definition?

7. Operational Definition
 Lowenstein et al. gave operational definition for the generalized convulsive
status epilepticus in adults and children older than 5 years:
“≥5 min of (1) continuous seizure or (2) two or more discrete seizures between
which there is incomplete recovery of consciousness” *
*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.

8. ILAE (International League Against Epilepsy)
Definition
 SE is a condition resulting either from the failure of the mechanisms
responsible for seizure termination or from the initiation of mechanisms which
lead to abnormally prolonged seizures (after time point t1).
 It is a condition that can have long‐term consequences (after time point t2)
T1= time at which the treatment should be started.
T2= determines how aggressive treatment is required to prevent long term
consequences.

9. Limited data

10. Grover, E.H., Nazzal, Y. & Hirsch, L.J. Treatment of Convulsive Status Epilepticus. Curr Treat Options Neurol 18, 11 (2016). https://doi.org/10.1007/s11940-016-0394-5
Pathophysiology

11. Loss of GABAergic drug efficacy over
time in SE
 Receptor trafficking may be responsible.
(internalization)
 A study showed in rat model of SE, A 10 fold
greater dose of Diazepam is needed to control
seizures lasting 45 mins compared to those
lasting 10 mins.
Jaideep Kapur and Robert L. Macdonald Journal of Neuroscience 1 October 1997, 17 (19) 7532-7540; DOI: https://doi.org/10.1523/JNEUROSCI.17-19-07532.1997

12. Classification*
AXES:
1. Semiology (Clinical presentation)
2. Etiology
3. EEG correlates
4. Age
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: 1515-1523. https://doi.org/10.1111/epi.13121

13. 1.Semiology A. With prominent motor
symptoms
Convulsive SE
Generalized
convulsive
Focal onset
evolving into
bilateral convulsive
SE
Unknown whether
focal or generalized
Myoclonic SE
With coma
Without
coma
Focal motor
Repeated focal motor seizures
(Jacksonian)
Epilepsia partialis continua
(EPC)
Adversive
status
Oculoclonic status
Ictal paresis (i.e., focal inhibitory SE
Tonic
status
Hyperkinetic

17. Without prominent motor symptoms (i.e., nonconvulsive
SE, NCSE)
NCSE with coma (including so-
called “subtle” SE) NCSE without coma
Generalized
Typical absence
status
Atypical absence
status
Myoclonic absence status
Focal
Without impairment of consciousness
(aura continua, with autonomic, sensory, visual, olfactory,
gustatory, emotional/psychic/experiential, or auditory
symptoms)
Aphasic status
With impaired
consciousness
Unknown whether focal or
generalized
1.Semiology

18. 2. Etiology
Known
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 PMEs, dementias)
SE in defined electroclinical syndromes
Unknown(cryptogenic)

19. Main Etiology
1. Cerebrovascular diseases
2. CNS infections (meningitis/encephalitis/TB)
3. Neurodegenerative diseases (e.g. Alzheimer's disease, Frontotemporal dementia)
4. Intracranial tumors
5. Head trauma
6. Intoxication (e.g. Drugs/ alcohol)
7. Withdrawal of or low levels of antiepileptic drugs

20. Main Etiology
8. Metabolic disturbances (e.g., electrolyte imbalances, glucose imbalance, organ failure,
acidosis, renal failure, hepatic encephalopathy, radiation encephalopathy, etc.)
9. Autoimmune disorders (e.g. Multiple sclerosis)
10. Chromosomal aberrations and genetic anomalies (e.g Ring chromosome 20 ,Ring
chromosome 17, Down syndrome (trisomy 21))
11. Metabolic disorders (e.g. Wilson disease, Alexander disease)

21. 3. EEG correlates
1) Location: generalized (including bilateral synchronous patterns), lateralized,
bilateral independent, multifocal.
2) Name of the pattern: Periodic discharges, rhythmic delta activity or
spike‐and‐wave/sharp‐and‐wave plus subtypes.
3) Morphology: sharpness, number of phases (e.g., triphasic morphology),
absolute and relative amplitude, polarity.
4) Time‐related features: prevalence, frequency, duration, daily pattern duration
and index, onset (sudden vs. gradual), and dynamics (evolving, fluctuating, or
static).
5) Modulation: stimulus‐induced vs. spontaneous.
6) Effect of intervention (medication) on EEG.

22. 4. Age
1. Neonatal (0 to 30 days).
2. Infancy (1 month to 2 years).
3. Childhood (> 2 to 12 years).
4. Adolescence and adulthood (> 12 to 59 years).
5. Elderly (≥ 60 years)

23. Diagnosis
 The diagnostic studies should be done once the patient is stabilized and
appropriate rx for SE is initiated.
 The diagnosis of convulsive status epilepticus is straightforward.
 As status epilepticus continues, the tonic phase shortens as the clonic
movements disperse and ultimately disappear, sometimes with ongoing
non-convulsive seizure activity. This is referred to as subtle status
epilepticus

24. EEG
 To exclude subtle SE, an EEG should be obtained if the pt has not returned to
his/her baseline within 10 to 20 mins of cessation of tonic-clonic activity.
 Critically ill patients who are comatose without an alternate explanation
require at least a routine EEG to rule out non-convulsive status epilepticus.
 The diagnosis of both focal and generalized non-convulsive status epilepticus
requires clinical suspicion, EEG confirmation, and both clinical and
electrographic improvements following a trial of a fast-acting AED.

25. Labs/Imaging
 LABS
 Serum electrolytes, S.ca, S.mg
 Glucose
 RFT,LFT ,ABG
 Toxicological screening when suspected
 If the patient is known to be taking an antiepileptic drug a laboratory assay for
drug levels.

26. Labs/Imaging
 Lumber Puncture
 CNS infection.
 Imaging
 A head CT scan should be considered for all GCSE patients once they
have been stabilized.

27. Indications for Continuous EEG (CEEG)
Monitoring in ICU *
A. CEEG is recommended to identify non-convulsive seizures and non-convulsive status
epilepticus in critically ill patients with:
1. Persistently abnormal mental status following generalized convulsive status epilepticus
(GCSE) or other clinically-evident seizures.
2. Acute supra-tentorial brain injury with altered mental status e.g.
1. subarachnoid hemorrhage (SAH)/intracerebral hemorrhage (ICH),
2. Encephalitis,
3. Acute ischemic stroke,
4. Moderate to severe traumatic brain injury
*Herman, Susan T et al. “Consensus statement on continuous EEG in critically ill adults and children, part I: indications.” Journal of clinical neurophysiology : official publication of the American
Electroencephalographic Society vol. 32,2 (2015): 87-95. doi:10.1097/WNP.0000000000000166

28. Indications for Continuous EEG (CEEG)
Monitoring in ICU
3. Fluctuating mental status or unexplained alteration of mental status without known
acute brain injury
4. Requirement for pharmacological paralysis (e.g. therapeutic hypothermia protocols,
extracorporeal membrane oxygenation (ECMO)) and risk for seizures.
B. Assessment of Efficacy of Therapy for Seizures and Status Epilepticus
C. Identification of Cerebral Ischemia

29. cEEG Treatment Endpoints for SE
1. Cessation of non-convulsive seizures
2. Diffuse beta activity
3. Burst suppression 8–20 s intervals
4. Complete suppression of EEG
Brophy, G.M., Bell, R., Claassen, J. et al. Guidelines for the Evaluation and Management of Status Epilepticus. Neurocrit Care 17, 3–23 (2012). https://doi.org/10.1007/s12028-012-
9695-z

30. SHAHEEN
 Labs + LP = unremarkable

31. What is your diagnosis?

32. Management of
Status Epilepticus

33. Goals of Management
 To Maintain vital functions
 To stop seizures & prevent recurrence
 To identify the cause & precipitating factors and treat
 To identify post ictal sequalae - cerebral or systemic and treat

34. Hrs

35. Stabilization Phase
(0-5 mins.)
1. Stabilize patient (airway, breathing, circulation, disability - neurologic exam)
2. Time seizure from its onset, monitor vital signs
3. Assess sats, give oxygen via nasal cannula/mask, consider intubation if respiratory
assistance needed
4. Collect finger stick blood glucose. If glucose < 60 mg/dl then:
50 ml D50W IV or 100ml 25% DW
And/or
100 mg thiamine IV
(in case of suspected alcohol abuse or impaired nutrition)
Interventionsforemergencydepartment,in-patient
setting,orprehospitalsetting.

36. Stabilization Phase
(0-5 mins.)
5. Maintain IV line and collect samples for serum electrolytes, RFT and LFT,
calcium and Mg, hematology (cbc + coagulation screen), toxicology screen, (if
appropriate) anticonvulsant drug levels.
6. Initiate ECG monitoring
Interventionsforemergencydepartment,in-patient
setting,orprehospitalsetting.

37. Initial Therapy Phase
(5-20 Minutes)
A benzodiazepine is the initial therapy of choice
Choose one of the following 3 equivalent first line options with dosing and frequency:
• Intramuscular midazolam DORMICUM (10 mg for > 40 kg, 5 mg for 13-40 kg, single
dose)
OR
• Intravenous lorazepam (0.1 mg/kg/dose, max: 4 mg/dose, may repeat dose once)
OR
• Intravenous diazepam (0.15-0.2 mg/kg/dose, max: 10 mg/dose, may repeat dose
once)

38. Initial Therapy Phase
(5-20 Minutes)
If none of the 3 options above are available, choose one of the following:
• Intravenous phenobarbital (15 mg/kg/dose, single dose, Level A)
OR
• Rectal diazepam (0.2-0.5 mg/kg, max: 20 mg/dose, single dose, Level B)
OR
• Intranasal midazolam (Level B), buccal midazolam (Level B)

39. Second Therapy Phase
20-40 Minutes
There is no evidence based preferred second therapy of choice
Choose one of the following second line options and give as a single dose
• Intravenous fosphenytoin (20 mg PE/kg, max: 1500 mg PE/dose, single dose, Level U)
OR
• Intravenous valproic acid (40 mg/kg, max: 3000 mg/dose, single dose, Level B)
OR
• Intravenous levetiracetam (60 mg/kg, max: 4500 mg/dose, single dose, Level U)

40. Second Therapy Phase
20-40 Minutes
If none of the options above are available, choose one of the following (if not given
already)
• Intravenous phenobarbital (15 mg/kg, single dose, Level B)

41. Third Therapy Phase
(40-60 Minutes)
There is no clear evidence to guide therapy in this phase
Choices include:
Repeat second line therapy
Or
Anesthetic doses of either thiopental, midazolam, pentobarbital, or propofol
(all with continuous EEG monitoring)

42. Refractory Status Epilepticus
 Persistent seizure after first line (benzodiazepines) and second line therapy
(Anti-epileptic drugs)
 Refractory status epilepticus develops in about 23% to 43% of SE patients
 Therapeutic options: Midazolam infusion, ketamine or another second line
anti-epileptic medication not already used or anesthetics [third-line therapy]
The longer convulsive SE continues, the less convulsive it
appears clinically, and continuous EEG monitoring should be
started as soon as feasible.

43. Super-Refractory status epilepticus
 Super-refractory status epilepticus is a status epilepticus that continues
for ≥24 hours despite anesthetic treatment, or recurs on an attempted
wean of the anesthetic regimen

44. Treatmentoptionsforsuper-
refractorySE
Shorvon, S. and M. Ferlisi. “The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol.” Brain : a journal of
neurology 134 Pt 10 (2011): 2802-18 .

45. New‐Onset Refractory Status Epilepticus
(NORSE)
 A clinical presentation, not a specific diagnosis, in a patient without active
epilepsy or other preexisting relevant neurological disorder, with new onset of
refractory status epilepticus without a clear acute or active structural, toxic, or
metabolic cause. This includes patients with viral or autoimmune causes.
 If no cause is found after extensive evaluation, this is considered “cryptogenic
NORSE”

46. Febrile Infection‐Related Epilepsy
Syndrome (FIRES)
 A subcategory of NORSE that requires a prior febrile infection, with fever
starting between 2 weeks and 24 hours prior to onset of refractory SE, with
or without fever at onset of SE.

47. Drugs in Status Epilepticus
Drug Loading/initial
dose
Administration
notes
Adverse Effect
Diazepam 0.15-0.2
mg/kg/dose, max:
10 mg/dose
5 mg/min IV push Hypotension
CNS depression
Intramuscular
midazolam
DORMICUM
(10 mg for > 40 kg,
5 mg for 13-40 kg,
single dose)
Hypotension
CNS depression
Intravenous
levetiracetam
LERACE
60 mg/kg,
max: 4500
mg/dose
May infuse over
15–30 min
Irritability,
behavioral changes

48. Drugs in Status Epilepticus
Drug Loading/initial
dose
Administration
notes
Adverse Effect
Phenytoin 15-20mg/kg/dose Max infusion rate
50 mg/min
Arrhythmia CNS
depression
Hypotension
Purple glove
syndrome
Intravenous
Valproic acid
EPIVAL
40 mg/kg, max:
3000 mg/dose
Max infusion rate 6
mg/kg/min
Hyper-ammonemia
Thrombocytopenia
Lacosamide
LACOLEP
200–400 mg IV May infuse over
15–30 min
Bradycardia
Dizziness

49. Drugs in Status Epilepticus
Do not use phenytoin/fosphenytoin in status epilepticus in patients who are known to
be taking these medications prior to arrival (increased risk of cardiovascular side
effects) or have suspected seizure due to toxicity (increased risk of Na blockade effects
leading to cardiovascular collapse)

50. How Shaheen was managed?
 She was treated with 10 mg diazepam IV over 2 min,
 which was repeated 10 min later.
 EEG demonstrated a rapid reversal of the aphasic disorder.
 She was discharged on oral AED.

51. Complications
 Cerebral:
 Increased ICP
 Cerebral edema
 Cognitive dysfunction
 Cerebral atrophy

52. SystemicComplications

53. Prognosis
 Various factors predict prognosis of status epilepticus, including:
age, duration of seizures, coma, and etiology.
Lower Mortality/ good
prognosis
High mortality / poor
prognosis
Low AED levels Metabolic disorders,
cerebrovascular disease, and,
particularly, anoxia.
Children Elders/adults

54. Prognostic Scores
 Status Epilepticus Severity Score (STESS)
 Epidemiology-based mortality score in status epilepticus (EMSE)

55. Covid-19 and Status
Epilepticus

56. Covid-19 and Status Epilepticus
 An 81-year-old man presented in ED with fever, dyspnea, and dry cough
for 7 days
 Past medical history showed mild hypertension.
 Covid-19 PCR came positive.
 Given symptomatic rx and symptoms relieved after 14 days.
 Two consecutive Covid PCR = -ve
 On day 16, patient became drowsy with Glasgow coma scale (GCS) of 5.
 Frequent jerky myoclonic contractions of the abdomen and the right
lower limb appeared.

57. Covid-19 and Status Epilepticus
 Laboratory tests excluded a wide range of encephalopathy causes.

58. Covid-19 and Status Epilepticus
 Pt. was managed on the line of NORSE.
 MRI showed multiple hyper intense areas in bilateral parietal cortex, left
temporal cortex.
 CSF examination showed pleocytosis.
 PCR for covid, HSV, EBV, VZV, CMV was negative
 A diagnosis of Possible autoimmune encephalitis was made according to Graus
Criteria.
 Pt started on Steriods and IVIG, Seizures on EEG stopped and clinical improved.
 However, pt died of nosocomial pneumonia and sepsis.

59. Take Home Message
 Status epilepticus is both a medical and neurologic emergency
with significant potential morbidity and mortality.
 Management is aimed at:
1. Stabilization and avoidance of secondary injury,
2. Rapid control of seizures,
3. Rapid identification and treatment of the etiology.

60. THANK YOU!