4. Cerebrovascular diseases (Stroke)

Question 1

Percentages of Stroke Types

Question 3

Stroke Definition

Answer 3

= Neurological deficit of acute onset,
with a focal or global functional alteration, that is of vascular, non-traumatic origin
with
- symptoms present for more than 24 h
- or that causes death within 24 hours

Question 4

Circle of Willis

Answer 4

4. 5.

Question 5

Arterial supply brain: 2 sources =

Answer 5

1. ICA
2. Vertebral Arteries

Question 6

Def + Function of Circle of Willis

Answer 6

= An anastomotic circuit of vessels

Functions:
- supplies majority of the Cerebrum
- allows equal flow to both hemispheres
- due to its anastomotic nature it allows to bypass a potential site of occlusion

Question 7

ICP values

Answer 7

• normal: 5 - 15 mmHg
  
  • raised: 20 – 25 mmHg
  • compensation phase: ICP > 25 mmHg

Question 8

CBF Formula

Answer 8

CBF = CPP / R
* CPP: Cerebral perfusion pressure = MAP - ICP
* R: Cerebral vascular Resistance

Question 9

What happens with the CBF in a pt with incr. BP?

Answer 9

!!

Question 10

What happens with the CBF in a pt with incr. ICP?

Answer 10

If the ICP is incr (i.e. > 20 mmHg), the CPP decreases, this means that the CBF would decrease; but the CBF can be maintained stable by II) Cerebral Selfregulation, d.h. in this case the Cerebral vascular Resistance (R) decreases (= vasodilation), which leads to an unchanged CBF

Question 11

Cerebral Hyperemia -> when could we have it?

Answer 11

Hyperemia means: incr. CBF
-> CBF is incr. when Cerebr. Perf. Pr. (CPP) increases due to incr. of MAP

There can be 2 possibilites:
1. MAP incr, but stays < 150 mmHg -> II) Cerebral selfregulation of CBF is happening = R increases by vasoconstriction of cerebral vasculature
=> CBF remains stable

2. MAP incr. to > 150 mmHg: increasing R cannot compensate anymore => CBF increases, we get Cerebral Hyperemia

Question 12

ICA branches contributing to the Circle of Willis

Answer 12

!!

Question 13

Infarction vs. Ischemic tissue

Answer 13

Tissue Ischemia = there is an inadequate blood supply to a tissue -> this means the tissue demand for O2 + Glucose does not match with the blood supply it receives
-> ischaemia can lead to cell dysfunction + damage

2. Infarction = irreversible tissue death due to prolonged complete ischemia (lack of blood flow)

After an acute ischemic event (such as a stroke), there is a central core area where tissue has already suffered infarction (cell death) due to lack of blood supply
But the surrounding tissue of this core area is still ischemic (receiving reduced blood flow), i.e. has not yet progressed to full infarction
-> If this ischemic tissue does not receive adequate blood supply quickly, it may also progress to infarction!

Question 14

Pathogenic mechanisms in Ischemic damage (nur overview)

Answer 14

1. Decr. energy production, bc there is impaired intrinsic excitability of cells leading to dysfunctional ion pumps (Na/K pump)
2. Release of inflammation mediators
3. Mitochondrial dysfunction -> insufficient energy production -> O2 radicals production
4. (old Hypothesis) NT-release imbalances leading to Ion imbalances: incr. release of Glutamate -> incr. permeability of Ion receptors -> ECFV changes in osmolality -> water inflow to compensate -> Edema

Question 15

Pathogenesis Ischemic stroke

Answer 15

Ischemia -> 4 main processes (s.o.) -> Cytotoxic Edema -> Apoptosis (intrinsic pw.) -> Ischemic damage progression (s.u.)

Question 16

Factors contributing to ischemic damage progression

Answer 16

1. Haematological factors: e.g. Polycythemia vera (+ RBCs -> + Resistance in vessels)
2. Temperature
3. Cerebral self-regulation (vasoconstriction to incr. CBF if MAP decr. or ICP incr.)
4. Onset velocity & Duration of occlusion: small thrombus that is travelling slowly can be destroyed by the brain itself -> transient s&s;
   bigger thrombus -> changes are permanent and the core area will become infarcted

Question 17

MRI of ischemic lesions

Answer 17

Following an acute ischemic event, there is an INFARCTED core area
-> it becomes ischemic if it doesn’t get any blood supply

Around the Infarcted Core area (=irreversibly damaged) there is the:
Penumbra = non-ischemic, viable tissue around the Ischemic core
-> the Penumbra can only be reduced by Thrombolysis, which thus prevents the extension of the Ischemic area;
otherwise there is a domino-effect and the infarcted area becomes bigger with time

Question 18

MRI of ischemic lesions: Reperfusion therapy goal

Answer 18

Managing the diffusion of the ischemic damage can limit the lesion to the infarcted core level only;
but if treatment is not done quickly enough, the entire Penumbra area can become infarcted too!

Question 19

Ischemic damage progression
- Mild/Moderate Ischemia

Answer 19

Insufficient O2 & Glucose supply = Inadequate energy suppy -> Failure of neuronal activity + Regional brain dysfunction

Question 20

Ischemic damage progression
- Severe Ischemia

Answer 20

Inadequate energy supply (lack of O2 + Glucose) -> Influx of water, Na+ and Cl- -> Cytotoxic Edema -> Influx of Ca2+ ->
-> Irreversible cellular injury -> Anaerobic metabolism
-> Accumulation of Lactic acid and H+ & Apoptosis => Advanced Ischemia

Question 21

Advanced ischemia

Answer 21

Loss of function causes accumulation of Glutamate + Aspartate -> binds to NMDA receptors -> influx of Water, Na+ and Ca2+
=> Destrcution of cell components, formation of ROS (react. oxyg. species), eicosanoids + leukotrienes

Question 22

Reperfusion injury

Answer 22

72% of the tissue damage observed after 2-5 h of Ischemia is caused by a Reperfusion injury

Reperfusion injury is caused by Post-ischemic Hyper-perfusion
-> re-establishing normal flow should improve ischemic damage, but if it is done too quickly in a vessel, that was preparing to closing completely, it causes Trauma that can induce:
- Inflammation
- BBB rupture
- Edema
- Haemorrhages

Question 23

TIA Def

Answer 23

Transient Ischemic Attack:
brief episode of Neurological dysfunction,
caused by focal Ischemia of the brain or retina
-> with clinical Symptoms, that last < 1 h (in most cases)
-> with no evidence of an Acute Infarction
TIA resolves within 24 h

Diagnosis: only clinical, i.e. looking at the symptoms! bc no acute infarction can be seen

Question 24

TIA types:

Answer 24

I. Carotid TIA
II. Vertebro-Basilar TIA

-> They cause 2 different clinical pictures *

Question 25

II. Vertebro-Basilar TIA manifestations

Answer 25

• Vertigo
• uni-/bilateral Motor + Sensory deficits
• Diplopia
• Campimetric deficits (VF deficits)
• bilat. Vision blurring
• Eyelid ptosis
• Gaze deviation

Question 26

Stroke risk after TIA

Answer 26

10-15% in the 3 months following the TIA;
most strokes occur in the 2 days following the TIA

Question 27

Territories supplied by ACA, PCA, MCA, Ant. Choroidal A.
-> Coronary view

Answer 27

vllt löschen ??

Question 28

Territories supplied by ACA, PCA, MCA, Ant. Choroidal a. - Superior view

Answer 28

vllt löschen ??

Question 29

What structures do the MCAs supply?

Answer 29

-> Lateral Cortex regiions:
o Frontal lobe (lat-inf. part):
 Primary Motor Cortex: upper body (face, arm, hand)
 Broca’s area = Motor speech area of Broca (in dominant hemisphere -> left side)

o Parietal lobe - inferior part:
 Primary Sensory Cortex: upper body → face, arm, hand

o Temporal lobe - lat-superior part:
- Auditory Cortex
- Wernicke’s area (present on dominant side = left)

Central branches:
o Basal Ganglia: Putamen, N. caudatus, Lentiform nucleus
o Hippocampus

Question 30

PCA Stroke syndrome

Question 31

Post. Cerebral As (PCAs) supply the:

Answer 31

• Occipital lobe
• postero-med. Temporal lobe
• Midbrain (part of Brainstem)
• Thalamus
• Choroid plexus
• part of the Lateral + 3rd Ventricle

Question 32

ICA branches

Answer 32

1. Sup. Pituitary A.
2. Ophtalmic A.
3. Ant. Choroid A.
4. Post. Communicating A.

Terminal branches:
5. MCA
6. Ant. Cerebral A.

Question 33

ICA occlusion - Manifestations

Answer 33

Occlusion of the ICA -> Carotid TIA (or Ischemic Stroke)

5 manifestations:
IPSI-lat. to occluded ICA
o Monocular blindness (by occlusion of the Ophtalmic A.)
o Gaze deviates to the side of the occluded ICA

CONTRA-lat. to occluded ICA:
o Motor + Sensory deficits

If the ICA of the dominant Hemisphere is occluded (in most ps. left):
o Aphasia

If the ICA of the non-dominant Hemisphere is occluded (for most ps. right side):
o Hemi-inattention = Hemispatial Neglect of the left side

Question 34

Dominant & Non-dominant Hemispheres

Answer 34

Dominant
- in most ppl it is the left Hemisphere
- it is responsible for language + logic skills

Non-dominant
- in most ppl. the right Hemisphere
- responsible for attention

Question 35

If a pt has Hemispatial Neglect, a Thrombus is likely occluding

Answer 35

… the right ICA
(the right Hemisphere is the non-dominant Hemisphere in most people)

Question 36

If a pt has gaze deviation to the right side + right monocular VL, there is probably

Answer 36

an occlusion of the ipsilateral (i.e. right) ICA
If it lasts < 1h it is a TIA,
if it lasts > 24h it is an Ischemic stroke

Question 37

Cortical vascular Territories - overview

Answer 37

ACA
MCA
PCA

Question 38

What is the usual level of cerebral blood flow?

Answer 38

55ml/100mg/min

Question 39

TIA vs. Ischemic Stroke

Answer 39

TIA:
- lasts usually only 1 hour, resolves within max. 24 h
- no evidence of acute Infarction on imaging

Ischemic Stroke:
- not transient
- acute Infarction is present -> irreversible damage to brain tisue

Question 40

Ischemic strokes - Frequency of involved Artery in %

Answer 40

70% MCA

Question 41

Ischemic stroke: Thrombotic vs. Embolic

Answer 41

Thrombotic -> progressive occlusion and subsequent collapse of one vessel

Embolic -> Emboli travel to brain from anywhere in the body (most likely from DVT) and reach different part of the brain
-> on diffusion weighted MRI we see multiple infarcted areas!

Question 42

Gerstmann’s syndrome

Answer 42

Occurs in stroke affecting the Parietal Lobe of the dominant hemisphere (-> due to prbls w. MCA, andere??)

4 S&S:
o Agraphia
o Acalculia
o Digital Agnosia
o L-R Confusion

Question 43

Stroke Types %

Answer 43

85% Ischemic

15% Hemorrhagic
-> 10% Intracerebral H.
-> 5% Subdural H.

Question 44

CBF Regulation

Answer 44

Cerebral Selfregulation
= intrinsic ability of cerebral vessels to maintain CBF constant even during CPP fluctuations
Mechanism: occurs by changes of the cerebral vascular resistance = by vasodilation / vasoconstriction of the cerebral arterioles
When does it work? for MAP btw. 50 - 150 mmHg

Regulation Mechanisms:
1. Collateral circle: Circle of Willis

2. Endothelial selfregulation:
   ECs release chemical mediators which act on SMCs and thereby lead to a change of their tone:
   o vasodilators: NO, Thromboxane, Prostaglandins
   o vasoconstricors: ET-1
   Pathological conditions leading to Endothelial dysfunction can cause Stroke: in this case there is e.g. reduced availability of NO + incr. release of ET-1 → endothelial compensation is not possible (normally the Endothelium would react to incr/decr CPP by adjusting R) → decr. CBF → Ischemia
3. Metabolic regulation:
   Synaptic activity → incr. blood levels of O2, CO2, Metabolic waste products → CBF needs to increase too, to meet the new requirements → Astrocytes release ions + chemical mediators on the SMCs of the Endothelium, inducing vasodilation
4. Neurogenic regulation:
   Extrinsic: by the Sympathetic NeSy = Symp. Neurons in the Trigeminal, Superior cervical, Sphenopalatine ganglion release NTs (Epi + NE) & Neuromodulators (e.g. NO) ⇒ induce vasodilation

Intrinsic: by Astrocytes, Interneurons

Question 45

MCA Ischemic stroke - Manifestations

Answer 45

= 9

1. Motor deficits (paresis or plegia) & Sensory deficits (contralateral to occlusion side)

👀
2. Gaze deviation to ipsilat. side (eyes “flee” from hemiplegic limb)
3. Monocular blindness (ipsilat.)
4. Homonymous Hemianopia / Homonymous inferior Quadrantopia (most frequent)
= VF loss of same halves of VF in each eye → e.g. both right sides of VF are lost in both eyes

Dominant Hemisphere (= left) affected:
5. Aphasia
6. Gerstmann’s syndrome (Parietal lobe):
- Agraphia
- Acalculia
- Digital Agnosia (in both dom + non-dom lesions)
- Left-Right confusion

Non-dominant Hemisphere (= right) affected:
7. Hemispatial Neglect / Hemi-Inattention = Pt not aware of contralat. side of the space
8. Constructional Apraxia = inability to copy drawings or 3D constructions
9. Digital Agnosia

Question 46

Penetrating Arteries

Answer 46

= small arteries, that supply the deep structures of the brain
-> they originate from:
- Large CoW-Arteries
- MCAs
- Basilar A.

if the Penetrating As. get occluded we have a Lacunar Stroke

Question 47

Lacunar Stroke

Answer 47

= small infarct (2-15 mm diam) of the deep brain structures,
caused by an (atherosclerotic thromboembolic) occlusion of the Penetrating As*

= 25% of all Ischemic strokes (thereby most common type of ischemic stroke)
-> caused by Atherosclerotic Thromboembolisms (causes 45% of all Ischemic strokes)

S&S:
- pure Motor stroke (Hemiparesis)
- Ataxic hemiparesis
- Dysarthria
- pure Sensory stroke

Question 48

What is the most common Type of ischemic stroke

Answer 48

Lacunar Stroke (= stroke caused by occlusion of small Penetrating As)
=> make up for 25% of all Ischemic strokes

(Lacunar Strokes belong to the group of Ischemic strokes caused by Atherosclerotic Thromboembolism, which cause 45% of all Ischemic Strokes)

Question 49

ACA Stroke Syndrome

Answer 49

< 5% of all Ischemic strokes (i.e. rare)

o Motor & Sensory impairments in the contralat. lower limb
o Urinary incontinence
o Left limb Apraxia (Parietal lobe)
o Behavioral changes: Apathy, Abulia
o Alterations in Thermoregulation + Sleep-wake rhythm (rare)

Question 50

Anterior Cerebral As (ACAs) supply the..

Answer 50

ACAs supply the Medial parts of the Cerebral hemispheres:
o Medial + Superior parts of Frontal lobe
o Anterior part of Parietal lobe
o Corpus callosum

Question 51

Basilar A. - branches

Answer 51

1. PCAs
2. Superior Cerebellar A.
3. Pontine As
4. Ant. inferior Cerebellar A.
   
   5. Internal Auditory A.

Question 52

Pt. with gaze deviating to the side that is not plegic has likely

Answer 52

-> typical Hemispheric Ischemic Stroke (e.g. ICA): Gaze deviates to the side of the lesion

(vs. Brainstem stroke: here gaze deviation is to the side that is contralateral to the lesion)