Cerebrovascular Disease

Brain arteries
The circle of Willis
 The brain
• 1.3 kg ≈ 2% body weight
• Accounts for 18-20% of blood and oxygen consumption of
the body

• Cerebral blood flow (CBF)

= 55 ml/100g tissue / min
= 972 l/ day
Depends on:
- mean arterial pressure
- resistance to the flow (size of cerebral arteries)
- blood viscosity
 Cerebral autoregulation
Adapt CBF to fluctuation of systemic blood pressure
Mechanisms: metabolic (pH, CO2), neural (sympathetic,
parasympathetic)
 Stroke
• Sudden neurological deficit caused by
impairment in perfusion to the brain

– Clinical manifestations are direct consequences

of the territory of the vessels involved

– Ishemic S = occlusion of the vessel

– Hemorrhagic S = rupture of the vessel
Leading causes of death,
All ages, 2004

1. Ischemic heart disease

7.2 million deaths
12.2 % of all deaths

2. Cerebrovascular diseases
5.7 million deaths
9.7 % of all deaths
 Estimated prevalence of
moderate to severe disability

Stroke

World all ages 12.6 million

High income countries

0–59 years 1.4 million
>60 years 2.2 million

Low-middle income countries

0–59 years 4.0 million
>60 years 4.9 million

44 % of all with moderate to

severe disability are <60 years
 INCIDENCE: all types of stroke
Incidenta primului AVC, orice tip, pe grupe de
varsta si sex, in Europa

45

40

35

30
in rates per 1000

25

20

15

10

0
55-59 60-64 65-69 70-74 75-79 80-84 85-89 90+
Age ranges
Males Females

6 statistici, ambulatori si institutionalizati

Incidenta medie 65 - 84: 8.72 / 1 000 ambe sexe

Incidenta medie 75 + : 17.31 / 1 000 ambe sexe
Ischemic stroke
 Types of ischemic impairment

• Permanent = stroke
- duration over 3 h
- positive imaging (CT, MRI)
- disability / death
• Transitory = Transient Ischemic Attack
- duration less 3 h
- negative imaging
- total recovery
 Classification
TOAST (Trial of Organon in Acute Stroke)

• Large artery atherosclerosis

• Cardioembolism
• Small artery disease
• Other determined etiologies
• Undetermined etiology
 Types of stroke (CT, RMN)

stroke

15% Hemorrhagic
. Intraparenchimatos
. Subarahnoidian
85%

Ischemic

20% 25% 20% 30% 5%

Large vessels dis Small vessel occlusion Cardio-aortic rare
- Hypertension embolism cryptogenetic
- Diabetes
. AF
- Dyslipidemia . Abn thrombosis
. Valvulopaties
- Smoke . Diissections
. Coronary heart dis . vasculitis
- age . Heart failure
. Migraine/Vasospasm
. drugs
. others
 Mechanisms
• Atherosclerosis - thrombosis
– Outside brain: aortic arch
– Brain vessel:
• Large vessel: in situ
thrombosis, artery-to-artery
embolism, hemodinamic
• Small vessel: lipohyalinosis, in
situ thrombosis

• Cardioembolism
Pathophisiology of Cerebral Ischemia

J. Astrup, L. Symon, N.M. Branston, N.A. Lassen 1977;

L. Symon, N.A. Lassen, J. Astrup, N.M. Branston 1977;
J. Astrup, B.K. Siesjo, L. Symon 1981
 Propagation of Ischemic Damage

Flow Disturbance
Breakdown of Energy Metabolism
ATP -Depletion

Membrane- Depolarization
GABA -
Glutamate Na+ - Influx
Adenosine -
SD – like 2. Geneexpression
Glycine + Depolarization 3. Cytoskeleton

1. Ca 2+ -Influx

Cell Damage
Evolution of Injury in Acute Cerebral Ischemia

1000 direct:
O2 depletion
energy failure
terminal depolarisation
ion homeostasis failure
extent of damage

100 :
secondary
excitotoxicity
SD-like depolarisation delayed
disturbance of ion homeostasis vasogenic
edema
inflammation
apoptosis
10

min hours days weeks

Reperfusion is the first and most important strategy!

CBF Thresholds for Preservation
of Function and Structure
 Diagnosis
• Sudden onset
• Focal deficit: motor, sensitiv, vizual,
language
• High BP
• +/- headache
 Clinical presentation
Large vessel occlusion
• ACA: contralateral lower
limb paresis
• MCA: CL facio-brachial
paresis, cl hypoestesia, cl
hemianopia, aphasia
• PCA: cl hemianopia
• VA: vestibular + cerebellar
sy
• BA: altern sy + coma
Small vessel occlusion:
lacunar stroke
• Ataxic hemiparesis
• Hemihypoestesia
• Facial palsy / facio-brachial
• !! Complete remission in 3-
7 days
 Investigations
• CT / MRI
• Ultrasound – vascular and heart
• Lab: lipids, inflammation, glycemia,
coagulation
CT: hypodensity
Angiography + MRI
Cardioembolic stroke
Microangiopathy
Ultrasound
 Complications
Specific
• Hemorrhagic
transformation General
• Brain edema • Pulmonary infections
(aspiration, prolonged
– Cytogenic: interruption
Na/K pump – immobilisation)
increased intracellular • Skin lesions – sepsis
osmolarity + water
• Deep venous
– Vasogenic: disruption
thrombosis - PE
of the blood-brain
barrier (BBB)
• Brain swallowing,
herniation
Treatment
 Primary Prevention
Treatment of the risk factors:
• Hypertension
• dyslipidemia
• diabetes
• Cardiac diseases

• No smoke, alcohol, drugs

 Treatment in the acute phase
Reperfusion:

• IV, IA thrombolytic therapy -> r-TPA

(tissue plasminogen activator) (Alteplase)

• Endovascular therapies
– Thrombectomy
– Stenting
 Treatment in the acute phase
• Brain edema: Manitol 20%
• Avoid hypertemia, hyperglycemia,
• Maintain BP < 210/130 mmHg !!!
• Complications:
– Brain edema (Herniation) -> surgical
decompression
– PVT: LWM heparines
 Recurrence
20 AVC recurent

IM sau eveniment cardiac fatal

Pacienţi cu evenimente (%)

15
(n=655)

10

0
30 zile 1 an 5 ani
Momentul monitorizării
IM = infarct miocardic.

Adapted from Dhamoon MS et al. Presented at the 57th Annual Meeting of the American Academy of Neurology;
Miami Beach, FL. April 9-16, 2005. S38.005.
 Secondary prevention
Pharmacological interventions:
– antithrombotics:
• aspirin: 150-300 mg/d first week
• Antiplatelets: aspirin, clopidogrel, dipiridamol + aspirin –
atherothrombotic strokes
• Anticoagulants: only cardioembolice strokes, after 1-14 days
– Antivit K: dicumarinic
– Non-antivit k: only non valvular AF

– Risk factors: IEC/ sartans, statins

Non-pharmacological
– surgery: endarterectomy
– Endovascular: stent