SEIZURE ASSOCIATED

WITH
CORONA VIRUS
INFECTION

Meiti Frida
PERDOSSI Cabang Padang
OUTLINES
•Introduction
1

2
•Mechanism of corona virus infection on the nervous system damage

•Neurologic manifestation of patient with covid-19

3

• COVID-19 presenting with seizure

4

• EEG abnormalities in acutely ill patients with COVID-19

5

• Conclusion
6
 • Severe acute respiratory syndrome corona virus 2
(SARS-CoV-2) emerged first in Wuhan, China 2019
• Spread rapidly worldwide as pandemic
• WHO : Corona Virus Disease 2019 (COVID-19) in
INTRODUCTI February 2020
• The neurologic manifestation of the disease are not
ON well known
• Retrospective report  effect of CNS from several
centres
• In Wuhan China : 4.5 – 5% patients with COVID-19
disease also CVD, acute symptomatic seizure,
skeletal muscle symptoms.
 MECHANISM OF CORONA VIRUS
INFECTION
ON THE NERVOUS SYSTEM DAMAGE

Direct infection injury Angiotensin –

• Blood circulation pathway Hypoxia injury Others
converting enzyme
• Neuronal pathway Immune Injury

Yeshun Wu, et al. Brain, Behavior, and Immunity 87 (2020) 18–2

 MECHANISM OF CORONA VIRUS
INFECTION
ON THE NERVOUS SYSTEM DAMAGE

Yeshun Wu, et al. Brain, Behavior, and Immunity 87 (2020) 18–2

 Mechanisms of
COVID 19 infections
and neurological
damage

Yeshun Wu, et al. Brain, Behavior, and Immunity 87 (2020) 18–2

 Blood Circulation Pathway
• JE : A typical virus entering the CNS through
the blood circulation
• Multiplies in the vascular cells of the skin area
 into blood to reproduce mononuclear
macrophage
• Release into blood  increase permeability
BBB through the produced cytokine  enter
the brain  viral encephalitis
• Rare evidence in CoV1, SARS CoV2
Neuronal Pathway
• Viruses can migrate by infecting sensory or
motor nerve ending
• Anterograde or retrograde neuronal transport
example olfactory neuron transport
• Unique anatomical organization of olfactory
nerve and the olfactory bulb in nasal cavity
and fore brain  channel between nasal
epithelium and CNS
• CoV can enter brain through olfactory in the
early stage ( 7 days )  inflammation and
demyelinating reaction
Yeshun Wu, et al. Brain, Behavior, and Immunity 87 (2020) 18–2
 Hypoxia injury Angiotensin Converting enzyme
• Virus proliferation is lung tissue cells • ACE2 : cardio cerebral protection factor
• Diffuse alveolar and interstitial inflammatory exudation, • Existing in variety of organs, including nervous system, skeletal
edema, formation of transparent membrane. muscle
• Role in regulating BP and anti atherosclerotic mechanisms
• Alveolar gas exchange disorder
• Important target for CoV
• Hypoxia in CNS
• Binding to ACE2 receptor  elevated BP  risk of cerebral
• Increasing anaerobic metabolism in the mitochondria of hemorrhage
brain cells • SARS-CoV-2 spike protein interact with ACE2  capillary
• Accumulation of acid  cerebral vasodilation, swelling endothelium  damage BBB - CNS  attacking vascular
brain and interstitial edema, obstruction of CBF and even system
headache ( due to ischemia and congestion )
• Hypoxia continues  cerebral edema and ecerebral
circulation worsen  intracranial hypertension
 Brain function deteriorates  drowsiness, bulbar
conjunctival edema  coma
 Hypoxia  acute CVD ( acute ischemic stroke )

Yeshun Wu, et al. Brain, Behavior, and Immunity 87 (2020) 18–2

 Mechanisms of
nervous system
infections and
neurologic
repercussion caused
by SARS-CoV-2

Hilal Abboud, World Neurosurg. (2020) 140:49-53.

NEUROLOGIC MANIFESTATIONS OF COVID 19

Coronaviruses can cause multiple systemic infection

Several studies  COVID-19 have typical clinical manifestation : fever, cough,

diarrhea and fatigue, characteristic laboratory finding and lung CT abnormality.

Epicenter in Wuhan report characteristic neurological manifestation of SARS-CoV-2

infection in 78 of 219 patients with laboratory-confirmed diagnosis of COVID-19

Ling Mao, et al. JAMA neurol 2020; 77(6) 683-690

Neurologic
manifestatio
ns

Sheraton M, Deo N, Kashyap R, et al. (May 18, 2020) A Review of Neurological Complications of COVID-19. Cureus 12(5):
Seizure and Acute Symptomatic Seizure
•sudden attack ( as of disease ), the physical manifestation
Seizure (convulsion, sensory disturbance or loss of consciousness)
resulting from abnormal electrical discharge in the brain

Acute •a clinical seizure occurring at the time of systemic insult or

close temporal association with documented brain insult
Symptomatic occurring one week of anoxic encephalopathy or
intracranial surgery  provoked seizure
Seizure
 Epilepsy

A disease of the brain by any of the following conditions :

1. At least two unprovoked seizure ( or reflex seizure) occurring > 24 hour
apart
2. One unprovoked seizure ( or reflex ) and a probability of further seizures
similar to the general recurrence risk ( at least 60% ) after two unprovoked
seizure, occurring over the next 10 years.
3. Diagnosis of epileptic syndrome
 CLASSIFICA
TION OF THE
EPILEPSIES

Scheffer, Ingrid E. et al. “ILAE Classification Of The Epilepsies: Position Paper Of The ILAE Commission For Classification And Terminology”. Epilepsia (2017)
 • Seizures and status epilepticus have not appropriate in the past 5
month onset of COVID - 19 pandemic.
• Seizures in COVID-19 patients have been documented by Moriguchi et
al.
• Mao L, Wang M, Chen S : retrospective study in Wuhan China
CNS manifestation in 25% of the COVID-19 patients
Seizures in - Headache 13%
- Dizziness 17%
COVID-19 - Impaired consciousness 8%
- Acute CVD 3%
- Ataxia 0,5%
- Sezure 0,5%
• Moriguchi T, Harit N, et al : reported meningitis / encephalitis
associated with SRAS-CoV2 accompanied with seizures
• Rollo E, et al : Primary presentation was a focal status epilepticus
Mechanisms of seizures associated with
COVID-19

Ali A Assadi. Seizure: European Journal of Epilepsy 79 (2020) 49–52

 • EEG is one of the main tools used in evaluation of patients
with seizure and epilepsy.
EEG • EEG on adult patient with suspicion of COVID-19 epileptic
form discharge 40,9% with frontal sharp waves as the
Abnormalitie predominant pattern.

s in Acutely
Ill Patients
with COVID-
19
Rhythmic discharges noted in the
right frontocentral/vertex region
corresponding to clonic movements
of the left arm (color figure online)
 Management of Seizures

• Seizures can present from convulsive activity, twitching, lethargy, change in

mental status ( NCSE )
• Start treatment urgently, especially in clinical seizure or status epilepticus
• Determine cause of seizure and manage the cause (hypoxia, fever,
metabolic derangement )
• Start antiseizure medication ( ASM ) to abort prolonged seizures
• Pay attention to drug factors ( onset of action, drug interaction ), adverse
event, patient factors ( age, respiratory, renal, hepatic, cardiac factor )
 Several Managements in Seizure Patient
With COVID-19
1.A single seizure less than 5 minutes
• No need for rescue treatment with benzodiazepine (careful use in severe respiratory
failure)
• Critical ill patient  drug with IV formulation is preferable (e.g Levetiracetam IV)
• Special attention :
• Respiratory/cardiac adverse effects : Phenytoin, phenobarbital , lacosamide 
should be prescribed cautiously
• Hepatic problems  do not use Lacosamide
• ECMO ( Extra corporal membrane oxygenation ) in severe pneumonia  impact the
pharmacokinetic of highly protein bound drug ( phenytoin and valproic acid)
• Levetiracetam and Brivaracetam are effective and safe for treatment
 Several Managements in Seizure Patient
With COVID-19

2. More than one seizures or status epilepticus (convulsive or non convulsive )

• Principals of serial seizures and status epilepticus management should be initiated
• Rescue treatment with ASM should be started
• Investigation of the underlying cause of seizure
• New onset seizure  considered as acute symptomatic sizures
• If necessary, continue the ASM for about 6 weeks and tapper and discontinue the drug
rapidly in 1 – 2 weeks
 • COVID-19 can cause neurological manifestation such
as the onset of seizures and altered mental status.
• There are multiple mechanism of CNS involvement
including retrograde movement from the olfactory
nerve  to CNS via circulating lymphocytes or entry
Conclusions via permeable BBB.
• Patient affected by COVID-19 develop seizures as a
consequence of hypoxia, metabolic dearrangement,
oxygen failure or cerebral damage.
• Patient with COVID-19 develops a clinical or
subclinical seizures or status epilepticus  start
treatment urgently.