ADDITIONAL SLIDE

CARDIOVASCULAR

Atika Rahmadini

February 27th, 2024

Soeharso, SMF Neurologi, FKKMK UGM

 Content
01 Definition of Seizure in ICH

02 Epidemiology of Seizure in ICH

03 Workup for Patient with Hemorrhage stroke

04 Seizures Pathomechanism in ICH

05 Seizure treatment in ICH

06 CAVE Score

07 101 LEVETIRACETAM

08 Seizure Effect in ICH

09 Tools

10 Terminology
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 01 Definition of Seizure in ICH

International League Against Epilepsy

• Seizure is a transient occurrence of signs and/or symptoms due to
abnormal excessive or synchronous neuronal activity in the brain

American Clinical Neurophysiology Society

• epileptiform discharges averaging >2.5 Hz for ≥10 s (>25 discharges
in 10 s) or any pattern with definite evolution and lasting ≥10 s

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 02 EPIDEMIOLOGY SEIZURE IN
ICH
subclinical seizures (diagnosed
Global prevalence of by continuous EEG) in ICH
intracerebral hemorrhage in reaches 30%
2019 was 20.7 million true incidence is still unknown
because of the difficulty of
detecting nonconvulsive seizures
Seizures reported in about 10%
of patients with ICH and about Currently, the American Clinical
50% of patients with lobar Neurophysiology Society recommends
hemorrhage. continuous EEG monitoring in acute
supratentorial brain injury with altered
Seizures typically occur at the onset mental status.
of bleeding or within the first 24
hours
However, continuous EEG remains
underused in stroke and neurointensive
care units, potentially because of logistical
and financial issues
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 03
Workup for Patient with Hemorrhage Stroke

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 04 Seizures in ICH
Delayed seizure
POST STROKE EPILEPSY

unprovoked seizure
Intracerebral
hemorrhage
ACUTE
Recurrent
SYMPTOMATIC
Seizure
SEIZURE

≤ 7 days > 7 days

Early seizure Late seizure
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 Pathomechanism
Early Seizure in Intracerebral Hemorrhage
destruction of erythrocyte
Intracerebral hemorrhage (hemoglobin)

vascular injury
inflammatory processes heme globin
(iron)
extravasation of blood into the brain parenchyma

induced macrophages produce hemosiderin

drives calcium- (iron complex storage)
dependent glutamate release
glutamate into the
release extracellular space
neuronal cell excessive hemosiderin
injury (iron complex storage)

Continuous potent oxidant

depolarization SEIZURE neurons have high
intracellular
concentrations of
glutamate
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 Pathomechanism
Post Stroke Epilepsy in Intracerebral Hemorrhage
Intracerebral hemorrhage scarring

vascular injury
inflammatory processes
gliosis
extravasation of blood into the brain parenchyma

the area will be easily

excitated

unprovoked
SEIZURE
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 05 Seizure Treatment in Intracerebral Hemorrhage

The morbidity is defined as LOS >14

days or discharge to somewhere other
than home or a rehabilitation facility

Source :
AHA ASA Guideline 2022
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 PNPK STROKE 2019 : When seizures happen

Give diazepam bolus IV slowly 5–20mg then continued by giving phenytoin

loading dose 15–20 mg/kg bolus with max rate 50 mg/min

If seizure remains happen, then need to be treated in the ICU.

Levetiracetam is also used for status epilepticus. If this drug is given in the
first 4 days at a dose of 3000 mg/day, the response rate increases to 43%.

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 PNPK STROKE 2019 :
Seizure as Complication

Carbamazepin and sodium phenytoin is the first choice of focal

seizure
• Carbamazepine is given with a target plasma level of 20-50γmol/L. Carbamazepine
can cause hyponatremia.
• Phenytoin can be given at a dose of 15-20 mg/kg BW/day orally or i.v. Initial dose
100 mg orally or IV 3 times/day. Maintenance dose 300-400 mg orally/day in divided
doses. The recommended dose of phenytoin sodium is until the serum level reaches
14-23 ug/mL. Administration can be stopped after 1 month of seizure-free.

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 06 CAVE SCORE
Score for Predicting Late Seizures After Intracerebral Hemorrhage

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 07 101 LEVETIRACETAM

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 LEVETIRACETAM
a newer generation antiepileptic drug

Levetiracetam produces its effects

by modulating neurotransmitter
release via binding to synapse
vesicle protein 2A (SV2A) and by
inhibiting N-type Ca2+ channels

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 LEVETIRACETAM as Seizure Therapy in
Intracerebral Hemmorrhage
LEVETIRACETAM

modulating
neurotransmitter release
via binding to synapse
vesicle protein 2A (SV2A)
and by inhibiting N-type
Ca2+ channels

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 Why choose
Levetiracetam
Earlier studies suggested that
prophylactic antiseizure drugs such as
phenytoin were associated with
worse outcomes in patients with
ICH.
One small randomized trial evaluated
the use of prophylactic valproic acid
and suggested no difference in
mortality or long-term seizure control
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Naidech AM, Garg RK, Liebling S,
Levasseur K, Macken MP, Schuele SU,
Batjer HH. Anticonvulsant use and
outcomes after intracerebral hemorrhage.
Stroke. 2009;40:3810–3815. doi:
10.1161/STROKEAHA.109.559948
Messe SR, Sansing LH, Cucchiara BL, Herman ST,
Lyden PD, Kasner SE;
CHANT Investigators. Prophylactic antiepileptic
drug use is associated
with poor outcome following ICH. Neurocrit Care.
2009;11:38–44. doi:
10.1007/s12028-009-9207-y
Gilad R, Boaz M, Dabby R, Sadeh M,
Lampl Y. Are post intracerebral hemorrhage
seizures prevented by anti-epileptic
treatment? Epilepsy Res.
2011;95:227–231. doi:
10.1016/j.eplepsyres.2011.04.002
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 LEVETIRACETAM and Cognitive Function

Conclusions
This exploratory study suggests that levetiracetam might improve executive function in specific
populations. However, the diversity in study populations and potential publication bias warrant
caution (Concurrently, levetiracetam was associated with more frequent somnolence than a placebo)

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 Effects of Levetiracetam with
Anxiety and Depression
LEV can increase the risk of behavioral and mood
problems such as depression and anxiety
The rate of behavioral and mood problems because of
levetiracetam have been reported in a range from 0.3% to 13.5%

LEVETIRACETAM Decreased antioxidant activities

zinc glutathion

augmented oxidative stress activities play role of

pathophysiology mood problems

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 In contrast, others studies showed a protection effect of
levetiracetam against oxidative stress in animal models

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 08 Seizure effect in Intracerebral Hemorrhage
Vespa PM, O'Phelan K, Shah Met al. Acute
seizures after intracerebral hemorrhage: a
factor in progressive midline shift and
outcome. Neurology 2003; 60: 1441–
1446.

Several studies
reported an Szaflarski JP, Rackley AY, Kleindorfer DOet
al. Incidence of seizures in the acute phase of
stroke: a population-based

increase of 30- study. Epilepsia 2008; 49: 974–981

day mortality rate Arboix A, Garcia-Eroles L, Massons JBet

al. Predictive factors of early seizures after
acute cerebrovascular
disease. Stroke 1997; 28: 1590–1594.

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 09 TOOLS

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 National Institutes of Health Stroke Scale
(NIHSS)

to quantify
stroke severity

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 modified Rankin Scale (mRS)

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 Hospital Anxiety and
Depression Scale

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 Stroke Impact Scale

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 Common Terminology
Criteria for Adverse Event

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 10 TERMINOLOGY

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THANK YOU