SMALL VESSEL DISEASE

RELATED IN COVID-19
 INTRODUCTION
• endothelium provides the crucial interface between the blood compartment and tissues, and
displays a series of remarkable properties that normally maintain homeostasis

• This tightly regulated palette of functions includes control of haemostasis, fibrinolysis,

vasomotion, inflammation, oxidative stress, vascular permeability, and structure

• SARS-CoV-2, the aetiological agent of COVID-19, produces protean manifestations ranging from
head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the
lungs, heart, brain, kidney, and vasculature

• The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture

of this raging infection, and also provides a framework for a rational treatment strategy at a time
 INTRODUCTION
• Cerebral small vessel disease (CSVD) is composed of several diseases affecting the
small arteries, arterioles, venules, and capillaries of the brain

• refers to several pathological processes and etiologies

• Neuroimaging features of CSVD include recent small subcortical infarcts, lacunes, white
matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy

• The main clinical manifestations of CSVD include stroke, cognitive decline, dementia,
psychiatric disorders, abnormal gait, and urinary incontinence

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018

Das et al. Neurological Insights of COVID-19 Pandemic.2020
Baig et al. Evidence of COVID19. ACS chem Neuosci.2020
ibby et al. COVID 19 is the end of endothelial Disease.2020
 Paybast et al. CoVID-19 And CNS Complication.2020
Enciso Et al. Time of Stroke Onset In Corona Virus Disease. Elsevier 2020
Abou – Ismail et al. Thrombosis resc. 2020
Ellul et al. Neurological Complication of COVID-19. Elsevier.2020
PATOPHYSIOLOGY

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018
Patophysiology Of Hypercoagulable State In
COVID-19
• Zhang et al ( 2020 ) : comparing cohort of 94 patient with
SARSCoV2 with control found that values of D Dimer, fibrin /
fibrinogen-degradation products and fibrinogen significantly
higher among patients with COVID-19

• Zhang also found antiphospolipid antiboies ( anticardiolipin

immunoglobulin A & immunoglobulin G may play role in both
arterial and venous infarcts

• Wang et al ( 2020 ) : observed positive correlation between degree

of D-Dimer elevation and the incidence of deep venous thrombosis
with the severity of disease ( possibly related to overwhelming
endothelial cell activation )

• More studies are needed to clarify the direct relationship of the

SARSCoV2 and thromboembolic disease

Abou – Ismail et al. Thrombosis resc. 2020

Libby et al. COVID 19 is the end of endothelial Disease.2020
The “ STORM ” signaling in COVID – 19

Bradykinin in, Cytokine out ?

The “Old” Storm
Cytokine Storm

Libby et al. COVID 19 is the end of endothelial Disease.2020

The “New” Storm
Bradykinin Storm

Roche et al. A Hypothezised Role For Dysregulated Bradykinin Signaling In Covid-19 Respiratory Complication. 2020
Garvin et al. A Mechanic Model And Therapeutic Intervention For Covid -19. 2020
CYTOKINE STORM COAGULATION DUE TO SARSCoV-2
INFECTON

Jorge Henrique Paiter Nascimento et al. COVID-19 and Hypercoagulable State : A New therapeutic Perspective. Arq Bras Cardiol.2020.114(5):829-833
BRADYKININ STORM COAGULATION HYPOTHESIS DUE
TO SARSCoV-2 INFECTON

Hoffman et al. Bradykinin : Inflamatory Product Of The Coagulation System. Springer.2016

Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med 2020
Abou – Ismail et al. Thrombosis resc. 2020
LOCATION

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018

PATOPHYSIOLOGY CSVD TO
COGNITIVE DYSFUNCTION

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018

PATOPHYSIOLOGY CSVD TO
AMYLOID ANGIOPATHY

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018

IMAGING

Li et al. Cerebral Small Vessel Disease. Cell Transplant.2018

THROMBOEMBOLIC RISK ASSESMENT, MONITORING AND ANTITHROMBOTIC
STATEGIES IN COVID-19 PATIENTS

Antonio Coppola et al. COVID-19, Thromboembolic and Thromboprophylaxis : Learning Lesson From The Bedside Awating Evidence. Blood Transfus 2020;18:226-9
Bridwell et al. Neurologic Complication Of COVID-19. Elsevier.2020
NOVEL THERAPY FOR HUMAN CORONAVIRUS
Memantine
MEMANTINE

• Memantine is a medication used to treat moderate-

to-severe Alzheimer disease

• Memantine was first synthesized and patented by

Eli Lilly and Company in 1968 as an anti-diabetic
agent

• In the US, some CNS activities were discovered

at Children Hospital Of Boston  in 1990, and
Children's licensed patents covering uses of
memantine outside the field of ophthalmology
to Neurobiological Technologies (NTI) in 1995
Brison et al. Novel Treatment Wit Neuroprotective And Antiviral Proprties Againt=st a Neuroinvasive Human Respiratory Virus. 2020