NEUROLOGICAL MANIFESTATION

OF COVID-19
ASHARI BAHAR
DIVISION OF NEUROINTERVENTION AND ENDOVASCULAR THERAPY
DEPARTMENT OF NEUROLOGY FACULTY OF MEDICINE HASANUDDIN UNIVERSITY
BRAIN CENTRE OF Dr. WAHIDIN SUDIROHUSODO HOSPITAL
MAKASSAR
 LAYOUT

Introduction 11 44 Clinical Manifestation

Potential mechanism 55 Stroke Pre Covid

VS Covid Period
underlying the 22
neurological
manifestation in covid 19 66 Management

Covid-19 Presenting Prevention

As Stroke 33 77
 INTRODUCTION

• Coronavirus Disease 2019 (Covid-19) has affected over 8.2 million

people and caused 445,000 deaths worldwide (June 17th 2020)

• In Indonesia Covid-19 has affected 40.400 people and caused

2.231 deaths (June 17th 2020)

• Although Covid-19 is primarily affecting respiratory tract, yet some

reports also revealed its neurological manifestation.
 BASIC PRINCIPLES

1. It is recommended to suspend non-emergency

neurointerventional surgeries, especially for the highly
suspected and confirmed patients during the epidemic period
2. Neurointerventional staff should participate in the training to
update their knowledge of the epidemic
3. Medical institution should inform patients without urgent
medical to postpone treatment through extensive publicity
and recommend them to consult health problems on the
online clinic
 POTENTIAL MECHANISM UNDERLYING THE
NEUROLOGICAL MANIFESTATION IN COVID-19

Direct Hematogenous Maladaptive

Invasion Inflammation

Neural Retrograde Invasion

Wang L, Shen Y, Li M, Chuang H, Ye Y, Zhao H, et al. Clinical manifestations and evidence of neurological involvement in
2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. J Neurol [Internet]. 2020 Jun 11.
Binding to Angiotensin-Converting Enzyme 2 (ACE2)
receptor Cell types that express
ACE2 receptors in the
central nervous system

Neuron

Microglia

Astrocytes

Olygodendrocytes
Neuropathogenesis and Neurologic
Manifestations of the Coronaviruses in the Age of
Coronavirus Disease 2019 A Review (Zubair Adeer
et al.)
Transsynaptic Viral Spread

A. Coronavirus (CoV) has been

shown to spread via the
transcribrial route from the
olfactory epithelium

B. CoV spread retrograde via

transsynaptic transfer using
an endocytosis or
exocytosis mechanism and
a fast axonal transport (FAT)
mechanism of vesicle
transport to move virus
along microtubules back to
neuronal cell bodies.

Neuropathogenesis and Neurologic Manifestations of

the Coronaviruses in the Age of Coronavirus Disease
2019 A Review (Zubair Adeer et al.)
 Spread across the Blood-Brain Barrier

Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019 A
Review (Zubair Adeer et al.)
MAJOR REPORTED NEUROLOGICAL ABNORMALITIES

Acute Ischemic Stroke

Intracerebral Hemorrhage

Cerebral Venous Sinus Thrombosis

Sheraton M, Deo N, Kashyap R, Surani S. A Review of Neurological Complications of COVID-19. Cureus [Internet]. 2020 May 18
[cited 2020 Jun 16];
Neurologic Manifestations of Hospitalized Patients
With Covid-19 in Wuhan, China (Mao Ling et al)

5 Ischemic Stroke, 1 Hemorrhagic Stroke

 COVID-19 PRESENTING AS STROKE
• Stroke teams should be wary and use appropriate personal protective
equipment in every suspected patient

• Some patients without typical symptoms of Covid-19

• Reports from New York suggest that numbers of emergent large vessel
occlusion (ELVO) strokes were significantly elevated, occurring in younger
patients without vascular risk factors

• Incidence : 2 - 6%
 Ischemic stroke

• Many patients had a stroke due to cardioembolism and large vessel

atherosclerosis

• Thrombotic events may occured because of inflammatory and

hypercoagulable mechanisms, including the presence of
antiphospholipid antibodies

• Mechanism not clear

 Case Report 1
73-year-old male with a past medical history of hypertension, dyslipidemia, and
carotid stenosis presented with fever, respiratory distress, and altered mental status

Patient 1
 Case Report 2
83-year-old female with a past medical history of hypertension, hyperlipidemia,
diabetes mellitus type 2 presented with fever, facial droop,slurred speech, and
reduced oral intake

Patient 2
Case Report 3
Case Report 4
Case Report 5
Case Report 6
 Probable Mechanism
Inflammatory

Binding to
Angiotensin- Hypercoagulable
Converting Enzyme 2 State
(ACE2) receptor

The ability of a
Neurotropism
pathogen to invadeof Hypoxemia
SARS-CoV-2
and survive in the
nervous system

RAS system
Disturbance
 Intracerebral Hemorrhage

• Most patients treated with anticoagulant (because of DVT/PE or

prophylactic purpose)
• Commonly : located in lobar territories
• None of the patients have an underlying vascular abnormality on
intracranial CT-A examination
• No haemorrhagic transformation of infarcts

The delay between time of COVID-19 symptom onset and

time of ICH diagnosis had a median of 32 days
 Case Report 1

Intracerebral haemorrhage and COVID-19: Clinical characteristics from a case series (Benger et al.)
Case Report 2
Cerebral Venous Thrombosis (CVT)

Particularly for SARS-CoV2, it

can lead to
hypercoagulability state,
CVT
CVT Caused
Caused by
by viral
viral manifesting as an increase of
infection
infection is
is D-dimer, lactate
dehydrogenase (LDH) and
uncommon
uncommon prolonged coagulation times
is associated with more
severe disease and increase
risk of CVT.
 Case Report

• A 29-year-old right-handed woman with no known

medical history presented with new onset
generalized tonic-clonic seizures with post-ictal
confusion.
• She later reported that prior to admission, she had
over a week of cough, low grade fever, mild shortness
of breath and a mild headache.
 Cont’ Case Report

Non-contrast head CT
demonstrating left
temporoparietal hemorrhagic
venous infarct with edema and
mass effect causing 5 mm
rightwardshift, red arrow
pointing to increased attenuation
and venous thrombosis indistal
left transverse and sigmoid sinus

Klein DE, Libman R, Kirsch C, Arora R. Cerebral venous thrombosis: A typical presentation of COVID-
19 in the young. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104989.
 Cont’ Case Report

3T DWI MRI, yellow arrow

pointing to hyperintense DWI
signal of evolving left
temporoparietal hemorrhagic
infarct, with mass effect and
effacement of the left lateral
and third ventricle with 5 mm
rightward shift.

Klein DE, Libman R, Kirsch C, Arora R. Cerebral venous thrombosis: A typical presentation of COVID-
19 in the young. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104989.
 Cont’ Case Report

2D time of flight MR venography with

red arrows denoting absence of flow
in the left transverse and sigmoid
sinus and left internal jugular vein
secondary to venous thrombosis.
Light blue arrows denoting normal
flow related signal in the right
transvers and sigmoid sinus
extending to a patent right internal
jugular vein.

Klein DE, Libman R, Kirsch C, Arora R. Cerebral venous thrombosis: A typical presentation of COVID-
19 in the young. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104989.
 STROKE PRE-COVID 19 vs COVID-19 PERIOD

Falling stroke rates during COVID-19 pandemic at a

comprehensive stroke center: Cover title: Falling stroke rates during COVID-19 (Siegler et al.)
 STROKE PRE-COVID 19 vs COVID-19 PERIOD

Falling stroke rates during COVID-19 pandemic at a

comprehensive stroke center: Cover title: Falling stroke rates during COVID-19 (Siegler et al.)
 MANAGEMENT
Protection

Qureshi AI, Abd-Allah F, Alsenani F, Aytac E, Borhani-Haghighi A, Ciccone A, et al. Management of acute ischemic stroke in patients
with COVID-19 infection: Report of an international panel. Int J Stroke. 2020 May 3;174749302092323.
MANAGEMENT

Baracchini C, Pieroni A, Viaro F, Cianci V,

Cattelan AM, Tiberio I, et al. Acute
stroke management pathway during
Coronavirus-19 pandemic. Neurol Sci Off
J Ital Neurol Soc Ital Soc Clin
Neurophysiol. 2020 May;41(5):1003–5.
MANAGEMENT

Baracchini C, Pieroni A, Viaro F, Cianci V,

Cattelan AM, Tiberio I, et al. Acute stroke
management pathway during
Coronavirus-19 pandemic. Neurol Sci Off J
Ital Neurol Soc Ital Soc Clin Neurophysiol.
2020 May;41(5):1003–5.
STRATIFIED PRECAUTIONS FOR MEDICAL STAFF DURING COVID-19
EPIDEMIC

He Y, et al. Neurointervent Surg 2020;12:658-663

FLOW CHART SUGGESTING STRATEGY TO MINIMIZE EXFOSURE
FROM COVID-19 INFECTION

Qureshi AI et al. International Journal of Stroke. April 2020

PROPOSED WORKFLOW OF HIPER ACUTE STROKE CARE IN ERA OF
COVID-19 INFECTION PANDEMIC

Qureshi AI et al. International Journal of Stroke. April 2020

 PREVENTION

Control the source of infection

Use personal protective measures to reduce the risk of

transmission
Protect vulnerable groups ( elderly and individuals with
cerebrovascular diseases)

Good personal protection and hygiene

Maintain good living habits

 INFECTION PREVENTION AND CONTROL STRATEGIES FOR
EMERGENCY STROKE PATIENT

• Medical treatment process for emergency patients

1. A standard screening procedure should be performed for all emergency
patients before their admission.
2. It is recommended that the confirmed patients without urgent medical
needs should be transferred to the fever clinic first.
3. Patients with subarachnoid hemorrhage should be strictly identified in
accordance with the above procedures, as fever is a common symptom
for this condition.
4. Use currently available guidelines and recommendations for identification
and management of large vessel occlusion whenever possible.
 INFECTION PREVENTION AND CONTROL STRATEGIES FOR
EMERGENCY STROKE PATIENT

• Strategies of self-protection for medical staff

1. Neurointerventionalists involved in emergency work
should implement the first-level precautions and
immediately increase the level of precaution once the
suspected case is admitted.
2. The consultation room should be fixed to ensure that
there is no crossover with the infected patients during
diagnosis and treatment.
 Reference

1. Klein DE, Libman R, Kirsch C, Arora R. Cerebral venous thrombosis: A typical presentation of COVID-19 in the young. J Stroke Cerebrovasc Dis. 2020
Aug;29(8):104989.
2. Wang L, Shen Y, Li M, Chuang H, Ye Y, Zhao H, et al. Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a
systematic review and meta-analysis. J Neurol [Internet]. 2020 Jun 11 [cited 2020 Jun 16]; Available from: http://link.springer.com/10.1007/s00415-020-09974-2
3. Sheraton M, Deo N, Kashyap R, Surani S. A Review of Neurological Complications of COVID-19. Cureus [Internet]. 2020 May 18 [cited 2020 Jun 16]; Available from:
https://www.cureus.com/articles/32076-a-review-of-neurological-complications-of-covid-19
4. Qureshi AI, Abd-Allah F, Alsenani F, Aytac E, Borhani-Haghighi A, Ciccone A, et al. Management of acute ischemic stroke in patients with COVID-19 infection: Report
of an international panel. Int J Stroke. 2020 May 3;174749302092323.
5. Khosravani H, Rajendram P, Notario L, Chapman MG, Menon BK. Protected Code Stroke. Stroke. 2020 Jun;51(6):1891–5.
6. Baracchini C, Pieroni A, Viaro F, Cianci V, Cattelan AM, Tiberio I, et al. Acute stroke management pathway during Coronavirus-19 pandemic. Neurol Sci Off J Ital
Neurol Soc Ital Soc Clin Neurophysiol. 2020 May;41(5):1003–5.
7. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol.
2020 Jun 1;77(6):683.
8. Siegler JE, Heslin ME, Thau L, Smith A, Jovin TG. Falling stroke rates during COVID-19 pandemic at a comprehensive stroke center: Cover title: Falling stroke rates
during COVID-19. J Stroke Cerebrovasc Dis. 2020 Aug;29(8):104953.
9. Avula A, Nalleballe K, Narula N, Sapozhnikov S, Dandu V, Toom S, et al. COVID-19 presenting as stroke. Brain Behav Immun [Internet]. 2020 Apr [cited 2020 Jun 16];
Available from: https://linkinghub.elsevier.com/retrieve/pii/S0889159120306851
10. Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of
Coronavirus Disease 2019. JAMA Neurol [Internet]. 2020 May 29 [cited 2020 Jun 16]; Available from:
https://jamanetwork.com/journals/jamaneurology/fullarticle/2766766
11. Alexandre J, Cracowski J-L, Richard V, Bouhanick B. Renin-angiotensin-aldosterone system and COVID-19 infection. Ann Endocrinol. 2020 Jun;81(2–3):63–7.
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Jun [cited 2020 Jun 16]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0889159120310977
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