Status Epilepticus is a condition resulting from failure of the mechanisms responsible for seizure termination or the initiation of mechanisms, which leads to abnormally prolonged seizures (time point, T1) that might have long-term consequences (time point T2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.

3. ◘ Epilepsy is a disease characterized by recurrent
unprovoked seizures.
◘ A seizure is defined as a transient occurrence of
signs and/or symptoms due to abnormal
excessive, synchronous neuronal discharges.
◘ The term transient is used as demarcated in time,
with a clear start and finish.

5. ◘ SE is the English translation of état de mal,
which was used in the 19th century in the
Salpêtriére.
◘ Armand Trousseau defined SE
- “In the SE, when the convulsive condition is
almost continuous, something special takes
place which requires an explanation”.
Armand Trousseau (1801 – 1867)

6. ◘ In 1970, the first ILAE defined SE as a
seizure persists for a sufficient length of time
or is repeated frequently enough to produce a
fixed and enduring condition. It was divided
into partial, generalized, or unilateral types.
◘ In 1980, the ILAE redefined SE as a seizure
that persists for a sufficient length of time or is
repeated frequently enough that recovery
between attacks does not occur. It was
classified to partial, generalized, and epilepsia
partialis continua.
Henri Gastaut (1915 – 1995)

7. ◘ In both 1970 and 1980 defined SE in 2 axes:
- The duration of a seizure which was not well
identified (“fixed and enduring” or “sufficient
length of time”)
- The semiology which was deficient and
described mainly the convulsive types
◘ Time oriented definitions described SE as a
prolonged seizure or a series of seizures during
which the patient has incomplete recovery of
consciousness.

8. ◘ Old studies based on animal experiments used 30
min as a specific time point to define SE as this is
the duration after which irreversible neuronal
damage take place.
◘ Human applications revealed that the prognosis of
SE worsens with prolongation of time and ≥5
min of continuous seizure or two or more
discrete seizures between which there is
incomplete recovery of consciousness are less
likely to stop spontaneously.

9. ◘ SE is a condition resulting from failure of the
mechanisms responsible for seizure
termination or the initiation of mechanisms,
which leads to abnormally prolonged seizures
(time point, T1) that might have long-term
consequences (time point T2), including
neuronal death, neuronal injury, and alteration
of neuronal networks, depending on the type
and duration of seizures.
Ingrid Scheffer (1958)

11. ◘ The median seizure durations are 70 – 130 seconds and seizures longer
than 10 min are more likely to continue as SE.

12. ◘ Calcium and sodium entry during the action
potential activates potassium efflux,
membrane hyperpolarization, and cessation of
firing.
◘ Potassium efflux results in membrane potential
depolarization exceeding the firing threshold
for sodium action potentials, sodium channels
inactivation, and neuronal firing cessation.
◘ ATP depletion resulting in cessation of
neuronal firing.

13. ◘ Seizures evolution and spread require amplification and synchronization among
neurons within susceptible networks which form recurrent excitatory collaterals
feedback loops and, returning excitatory synaptic activity to the neurons within
the seizure onset zone.
◘ Seizure activities stop through:
(1) Depletion of the synaptic neurotransmitter vesicles especially
glutamate with consecutive decrease in synaptic efficacy.
(2) Prolonged seizure discharge increase CO2 production resulting in
extracellular acidosis with consecutive decrease in NMDA receptor function
and loss of synaptic long-term potentiation.

14. (3) Glial uptake of peri-synaptic glutamate which point to the role of
astrocytes in seizure termination.
(4) Neurons within the seizure onset zone have different excitatory inter-connecting
collaterals resulting in non-simultaneous re-excitation and sequential loss of
synchrony which is a hallmark of seizure pathogenesis.
(5) Increased GABAergic synaptic inhibition mediated by local interneurons.
This action may be mediated through activation of endogenous neuromodulators
like endocannabinoids, adenosine, and neuropeptide Y

15. (1) Vagal nerve stimulation which activates brainstem nuclei including nucleus
solitaries and locus creuleus which have cortical inhibitory effect and could
abort the seizures.
(2) Activation of certain subcortical brain regions like substantia nigra pars
reticulata, subthalamic nucleus, deep layers of the superior colliculus, the
anterior thalamic nucleus and the deep cerebellar nuclei by the successive
seizure discharges causes decreasing excitatory feedback amplification,
increasing inhibitory tone diffusely, and regulating the synchrony between
cortical regions resulting in limitation of seizure spread.

17. ◘ Failure of the normal mechanisms that terminate seizures occur due to
dynamic changes in GABA and NMDA receptors during the prolonged
seizure activity termed receptor trafficking with the resultant
internalization into endocytic vesicles and subsequent degradation.

18. ◘ These changes results in gradual reduction of GABAA receptors at the
synaptic membrane with loss of endogenous GABAergic inhibition giving
rise to sustained epileptic activity.

19. ◘ Loss of post-synaptic GABAA receptors is a relevant pathophysiological
factor on the way to progressive pharmaco-resistance of drugs such as
benzodiazepines, barbiturates and propofol.

20. ◘ In contrast, during ongoing epileptic activity,
NMDA receptors are progressively
transported to the synaptic membrane,
resulting in increasing numbers of
excitatory NMDA receptors persynaptically.
◘ This process facilitates neuronal excitability
and consecutively sustained SE.

21. ◘ On the other hand, enhanced glutamate
receptors expression and elevations of
extracellular glutamate, contribute to
excitotoxic damage and may present a useful
target in the pharmacological management
of advanced stages of SE.
◘ Absence SE with 3-Hz spike-wave discharges
is induced by excessive inhibition. This form
of SE does not lead to the neuronal injury
seen with excessive excitation.

23. ◘ SE is a neurologic emergency with mortality
rate of 3% in children and 30% for adults.
Survivors may develop serious
consequences including changing epilepsy
characters to get refractory.
◘ > 50% of SE patients have no prior history of
epilepsy (de novo SE).

24. ◘ The annual incidence of GCSE and NCSE
range from 3.6 – 6.6 and 2.6 – 7.8 per 100
000 respectively.
◘ Mortality and morbidity rates of SE are
heavily influenced by the underlying
etiology, patients’ age and clinical seizure
form (higher in NCSE) as well as successful
therapeutic intervention.

26. ◘ SE is a symptom and not a disease etiology. So, its
classification cannot simply based on seizure semiology as
at least half of the patients do not have epilepsy or specific
epilepsy syndromes.
◘ Therefore, the axes used previously in seizure classification
need to be modified as acute neurologic disorders and the
long duration of status leads to significant variability in its
clinical presentation and prognosis.

27. ◘ The semiology of SE is highly dynamic and
could change over a short period of time
◘ The axis of semiology refers to the clinical
presentation of SE which is divided to:
(1) The presence or absence of prominent
motor symptoms.
(2) The degree of impaired consciousness
(qualitative or quantitative).

28. A.1 Convulsive SE (CSE)
A.1.a. Generalized CSE
A.1.b. Focal onset evolving into bilateral CSE
A.1.c. Unknown whether focal or generalized
A.2 Myoclonic SE (prominent myoclonic
jerks)
A.2.a. With coma
A.2.b. Without coma
A.3 Focal motor
A.3.a. Repeated focal motor seizures (Jacksonian)
A.3.b. Epilepsia partialis continua (EPC)
A.3.c. Adversive status
A.3.d. Oculoclonic status
A.3.e. Ictal paresis (i.e., focal inhibitory SE)
A.4 Tonic SE
A.5 Hyperkinetic SE
B.1 NCSE with coma ( subtle SE)
B.2 NCSE without coma
B.2.a. Generalized
B.2.a.a Typical absence status
B.2.a.b Atypical absence status
B.2.a.c Myoclonic absence status
B.2.b. Focal
B.2.b.a Without impairment of consciousness (aura
continua, with autonomic, sensory, visual,
olfactory, gustatory, emotional / psychic /
experiential, or auditory symptoms)
B.2.b.b Aphasic status
B.2.b.c With impaired consciousness
B.2.c Unknown whether focal or generalized
B.2.c.a Autonomic SE

29. ◘ The diagnosis of NCSE is based on changes in
behavior and/or mental processes from
baseline associated with continuous
epileptiform discharges in the EEG.
◘ Absence status with persistent 3-Hz spike-
wave discharges.
◘ Complex partial SE (CPSE) represents the most
frequent type of NCSE and the second cause
of all forms of SE.
◘ Subtle status epilepticus (SSE).

30. ◘ Subtle SE is a form of NCSE that develops due to non-
treated or insufficiently treated GCSE as a result of
exhaustion of the motor phenomena.
◘ Subtle SE occur in 14 – 20% of GCSE and should be
suspected if consciousness is not improved or
fluctuating ≥ 20 min or the mental status remains
abnormal 30 - 60 min after cessation of GCSE.
◘ Subtle SE is also suspected if the patient has
automatism, facial twitches or ocular movement
abnormalities e.g. hippus, sustained deviation or
nystagmus.

31. A) Known (i.e., symptomatic)
A.1- Acute (e.g., stroke, intoxication,
malaria, encephalitis, etc.)
A.2- Remote (e.g., posttraumatic, post-
encephalitic, poststroke, etc.)
A.3- Progressive (e.g., brain tumor,
Lafora’s disease and other PMEs,
dementias)
A.4- SE in defined electroclinical
syndromes
B) Unknown (i.e., cryptogenic)
Currently indeterminate conditions
(boundary syndromes)
A) Epileptic encephalopathies
B) Coma with non evolving epileptiform
EEG pattern
C) Behavioral disturbance (e.g., psychosis)
in patients with epilepsy
D) Acute confusional states, (e.g., delirium)
with epileptiform EEG patterns

32. ◘ The EEG will affect choice and aggressiveness of
treatment, prognosis, and clinical approaches,
so an EEG should be sought where possible.
◘ The EEG pattern of SE could repeatedly change
over a short period of time and some forms of
SE may only be reliably diagnosed by EEG
◘ Advances in EEG techniques with the use of
automated rejection modes had increased the
utility of EEG in ICU settings and allow better
delineation of dynamic changes in EEG
patterns.

33. 1 Location: generalized (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 or spontaneous.
6 Effect of intervention (medication) on EEG.

35. (1) SE occurring in neonatal and
infantile-onset epilepsy syndromes
Tonic status (e.g., in Ohtahara syndrome or
West syndrome)
Myoclonic status in Dravet syndrome
Focal status
Febrile SE
(2) SE occurring mainly in childhood and
adolescence
Autonomic SE in early-onset benign childhood
occipital epilepsy (Panayiotopoulos
syndrome)
NCSE in specific childhood epilepsy syndromes
and etiologies (e.g., Ring chromosome 20
and other karyotype abnormalities,
Angelman syndrome, epilepsy with
myoclonic-atonic seizures, other childhood
myoclonic encephalopathies;
Tonic status in Lennox-Gastaut syndrome
Myoclonic status in progressive myoclonus
epilepsies
Electrical status epilepticus in slow wave sleep
(ESES)
Aphasic status in Landau-Kleffner syndrome
(3) SE occurring mainly in adolescence
and adulthood
Myoclonic status in juvenile myoclonic epilepsy
Absence status in juvenile absence epilepsy
Myoclonic status in Down syndrome
(4) SE occurring mainly in the elderly
Myoclonic status in Alzheimer’s disease
Nonconvulsive status epilepticus in Creutzfeldt-
Jakob disease
De novo (or relapsing) absence status of later life

36. (1) Fever & systemic infection 35.7%.
(2) Medication change 19.8%.
(3) Metabolic 8.2%.
(4) Congenital 7.0%.
(5) Anoxia 5.3%.
(6) CNS infection 4.8%.
(7) Trauma 3.5%.
(8) Cerebrovascular 3.3 %.
(9) Drug related 2.4%.
(10) Tumor 0.7%.
(11) Unknown 9.3%.
(1) AED non-compliance 26%.
(2) Alcohol related 24%.
(3) Drug toxicity 10% e.g. cephalosporins,
penicillin, ciprofloxacin, theophylline
(4) CNS infection 8%.
(5) CNS tumors 6%.
(6) Head trauma 5%.
(8) Stroke 4%.
(9) Metabolic abnormalities 4% e.g. hyper
or hypoglycemia, electrolyte
abnormalities, sepsis and uremia.
(10) Cardiac arrest 4%
(11) Idiopathic 10%.

38. (1) Excitotoxicity.
(2) Increased neuronal
metabolic demand.
(3) Mass effect.
(4) Changes in blood flow.
(1) Pulmonary edema.
(2) High output cardiac failure.
(3) Cardiac arrhythmias.
(4) Aspiration pneumonia.
(5) Fever.
(6) Hypoxia.
(7) Electrolyte imbalance.
(8) Acute tubular necrosis.
(9) Rhabdomyolosis.

39. (1) Acute medical or neurological
disorders.
(2) Severe mental impairment.
(4) Extremes of age.
(3) Longer GCSE duration:
◘ < 10 hours has 10% death rate.
◘ > 20 hours has up to 85% deaths.

41. 1. ABC (airway, breathing, circulation).
2. Identify the time of seizure onset.
3. Consider intubation if respiratory assistance is
needed.
4. Initiate ECG monitoring.
5. Collect finger stick blood glucose. If glucose < 60
mg/dl then Adults: 100 mg thiamine IV then 50
ml dextrose 50% (children ≥ 2 years: 2 ml/kg
dextrose 25%) and children < 2 years: 4 ml/kg
dextrose 12.5%).

42. ◘ EMS personnel should provide prehospital
notification to improve the readiness of the
hospital team.
◘ IV access and collect electrolytes, hematology,
toxicology screen, anticonvulsant drug levels.
◘ Fever, hypoxia and hypotension should be treated
as they aggravate seizures and brain damage.
◘ Brain imaging should be obtained as soon as the
patient is stable.
◘ Avoid drugs that lower seizure threshold.

43. ◘ Choose one of the following 3 equivalents:
(1) IM midazolam (dormicum); 10 mg for > 40 kg, 5 mg
for 13-40 kg, single dose (Level A) OR,
(2) IV lorazepam; 0.1 mg/kg/dose, max: 4 mg/dose,
(Level A) OR,
(3) IV diazepam; 0.15-0.2 mg/kg/dose, max: 10 mg/dose,
(Level A).
◘ Lorazepam or diazepam could be repeated once if the
seizure continued or repeated within 10 min.

44. ◘ If none of the 3 options above are
available, choose one of the following:
(1) IV phenobarbital (15 mg/kg/dose, single dose,
Level A) OR,
(2) Rectal diazepam (0.2-0.5 mg/kg, max: 20
mg/dose, single dose, Level B) OR,
(3) Intranasal midazolam (Level B) OR,
(4) Buccal midazolam (Level B).

45. ◘ Hypoventilation in 10–17% of patients.
◘ Hypotension in 26–34%.
◘ Cardiac arrhythmias in 2–7%.
◘ These side effects were more frequent in
subtle SE.
◘ The initial therapy could be started out-of-
hospital without significant increase in the
rate of side effects.

46. ◘ Choose one of the following options
(1) IV 18 mg/kg phenytoin (50 mg/min) or
fosphenytoin (100 mg/min) to a maximum of
1500 mg OR,
(2) IV 40 mg/kg valproic acid (3 – 6 mg/kg/min)
to a maximum 3000 mg/dose OR,
(3) IV 60 mg/kg LEVETIRACETAM (maximum
4500 mg/dose). The drug was effective in
seizure termination in up to 90% of cases
with negligible side effects.

47. ◘ If none of the previous options are available,
give IV 15 mg/kg phenobarbital in a single
dose (100 mg/min) (if not given in initial
therapy).
◘ Initial and second line therapies are effective
in stoppage of GCSE in 60% of cases.
◘ IV lacosamide has been tries as a future
treatment of SE with good results but till
now both levetiracetam and lacosamide are
not licensed for the treatment of SE.

48. ◘ Refractory SE (RSE) is the sector of SE
which does not respond to first and
second lines of anticonvulsants
(benzodiazepines and phenytoin) which
represents 35–45% of SE patients.
◘ Super refractory SE (SRSE) is defined
as SE that continues 24 h or more after the
onset of anesthesia, including those cases
in which the SE recurs on the reduction or
withdrawal of anesthesia.

49. ◘ There is no clear evidence to guide therapy in
this phase including repetition of the second
line therapy or anesthetic doses of either
thiopental, midazolam, pentobarbital, or
propofol.
◘ The rationale for treating refractory SE with
anaesthetizing anticonvulsants is to prevent
both neurological and systemic complications
which are more common in GCSE.

50. ◘ However the situation is different for NCSE
because the risks of anesthesia (e.g. arterial
hypotension, gastroparesis and
immunosuppression) may be greater than the
risks of ongoing non-convulsive status.
◘ Anesthetics should be used under continuous EEG
monitoring if initial therapy of GCSE has not
controlled SE within 1–2 hours.
◘ The therapeutic decision may be also influenced
by the age of the patient, comorbidity and
prognostic issues.

51. ◘ General anesthesia are recommended for RSE
to the depth which produces a burst
suppression pattern or an isoelectric EEG.
◘ Propofol IV bolus of 2 mg/kg; repeated
if necessary followed by continuous infusion
of 5 - 10 mg/kg/hour initially; reduced to a
dose sufficient to maintain burst suppression
pattern on EEG (usually 1 – 3 mg/kg/hour).

52. ◘ Thiopental IV bolus of 100 - 250 mg given
over 20 seconds; with further 50 mg boluses every 2
– 3 min until seizure is controlled followed by
continuous IV infusion in a dose of 3 – 7
mg/kg/hour to maintain EEG burst suppression.
◘ Midazolam IV bolus of 0.1 – 0.3 mg/kg at a
rate not exceeding 4 mg/min initially followed by
continuous IV infusion at a dose of 0.05 – 0.4
mg/kg/hour. Burst suppression is extremely difficult
in midazolam use. So, midazolam treatment is
judged on the basis of seizure cessation.

53. ◘ When seizure has been controlled with 12
hours burst suppression, the drug dosage
should be slowly reduced over a further 12
hour.
◘ If seizure recur, the general anesthetic agent
should be given again for a further 12 hour
and then withdrawal attempted again.
◘ This cycle may be needed to be repeated
until seizure control is achieved.

54. ◘ There is no evidence based guidelines for management of refractory CPSE are
present but only good practice points which give a lower level of evidences.
◘ As a general rule, more prolongation of T1 and T2 than GCSE is allowed which
permits less aggressive measures including avoidance of anesthetic agents due to
higher complication rates than the seizures themselves.
◘ IV Phenobarbital in an initial bolus of 20 mg/kg at an infusion rate of 50
mg/min.
◘ IV Valproic acid in a bolus of 25–45 mg/kg infused at rates of up to 6
mg/kg/min.
◘ IV Levetiracetam in a bolus of 1000–4000 mg over a period of 15 min.

56. ◘ EEG stages of GCSE:
(1) Discrete seizures with interictal slowing.
(2) Waxing and waning of ictal discharges.
(3) Continuous ictal discharges.
(4) Continuous ictal discharges punctuated by flat
periods.
(5) Periodic epileptiform discharges (PEDS) on a
flat background (burst suppression).
(6) Iso-potentiality.

57. ◘ Consist of generalized fast activity or poly-spikes that build-up to increase
in amplitude then decrease in frequency over time due to neuronal
exhaustion.

58. ◘ A 72 year woman presented after cardiac arrest and completion of a
hypothermia protocol and rewarming, she began to have whole body
jerking movements and an EEG showed generalized poly-spike discharges.

59. ◘ Sequential small doses of midazolam
(1mg/dose) or diazepam infusion are
administered while the patient is
monitored and connected to an cEEG.
◘ The test must be stopped if there are
respiratory or CVS depression or
maximum dose is reached.
◘ Positive test if resolution of potential
ictal EEG pattern and improvement of
clinical status occur.

60. ◘ For absence SE a small IV dose of lorazepam or diazepam will terminate the
event.

61. ◘ There is currently no generally
accepted duration of electroclinical
alterations incorporated in the
diagnostic criteria of NCSE.
◘ Repetitive generalized or focal
spikes, polys-pike, sharp waves,
spike-and-wave or sharp and slow
wave complexes at >2.5 Hz.

62. ◘ Discharges <2.5 Hz but with EEG and clinical improvement after benzodiazepines
◘ Discharges <2.5 Hz with focal ictal phenomena (facial twitching, gaze deviation,
nystagmus, limb myoclonus).
◘ Rhythmic waves (theta-delta) at > 0.5 Hz with incrementing onset, evolution in
pattern or location, or decrementing termination and post-periodic epileptic
discharge background slowing and attenuation that respond to treatment with
IV BZDs

63. ◘ Frequent or continuous generalized
spike-wave discharges, which show
an increase in profusion or
frequency when compared to
baseline EEG with observable
change in clinical state
◘ Improvement of clinical or EEG
features with IV benzodiazepines

64. ◘ The dose of the anesthetic AEDs could be only adjusted by the appearance
of burst suppression.
◘ Allows the diagnosis of subclinical break through discharge in subtle GCSE.

65. ◘ The term burst-suppression refers to a cycling of marked depression of
cerebral activity alternating with bursts of cerebral activity of variable
amplitude, duration, and waveform.

66. ◘ > 50% of the record consists of suppression, alternating with 0.5–30 sec
bursts.
◘ Burst suppression is associated with lower metabolic expenditure of the
brain protecting against intense neuronal damage.

67. ◘ The bursts may be composed of multiphasic delta components, admixtures
of various frequencies, or epileptiform activity such as spikes or sharp
waves, often with admixed slow components.

68. ◘ Burst-suppression results from suppression of cortical activity via GABA-
ergic mechanisms with breakthrough EEG activity due to intact
glutaminergic transmission.

69. ◘ Periodic patterns are debated whether represent ictal or inter-ictal discharges:
- PLEDs / Lateralized Periodic Discharges (LPDs).
- BiPEDs / Bilateral independent Periodic Discharges (BiPDs).
- GPEDs / Generalized periodic discharges (GPDs).
◘ Slow (< 2.5Hz) spike and wave activity.
◘ Stimulus induced rhythmic, periodic, or ictal discharges (SIRPIDs).
◘ Rhythmic high amplitude delta activity.
◘ Alternating patterns of rhythmic activity without clear evolution in the context of
acute cerebral damage

71. ◘ SE management is an art and its bad
management has major consequences
with higher morbidity and mortality
rates including rendering epilepsy to be
intractable.
◘ Refractory and super-refractory SE are
dynamic emergency states needing
continuous updating of the
management protocols to deal with any
changes in the patient’s state.