cerebral blood flow, its autoregulation and role of collaterals in ischemic stroke

1. CEREBRAL BLOOD FLOW, ITS
AUTOREGULATION , CLINICAL
RELEVANCE AND
ROLE OF COLLATERALS IN
ISCHEMIC STROKE
By-Varun Kumar Singh
18/12/2015

2. OVERVIEW
• CEREBRAL BLOOD SUPPLY(ARTERIAL AND VENOUS)
• AUTOREGULATION MECHANISM AND ITS CLINICAL
IMPORTANCE
• CEREBRAL COLLATERALS AND ITS SIGNIFICANCE IN
ACUTE ISCHEMIC STROKE

3. AORTIC ARCH
1.Innominate artery (IA) /
Brachiocephalic trunk
• Rt subclavian artery (SCA)- Right
vertebral artery
• Rt common carotid artery (CCA)
2.Left Common Carotid Artery (CCA)
3.Left Subclavian Artery (SCA)
• Left Vertebral Artery (VA)

4. Major Arteries
1.INTERNAL CAROTID-
-TWO IN NO.
• ARCH OF AORTA-
BRACHIOCEPHALIC-INTERNAL
+EXTERNAL CAROTID AT
SUPERIOR BORDER OF THYROID
CARTILAGE(C3-C4)
• ENTER THE BRAIN-CAROTID
CANAL
2. VERTEBRAL ARTERIES
-TWO IN NO.
• FROM 1st PART OF SUBCLAVIAN
ARTERY.
• TRAVERSE FROM C6 TO C1 –
FORAMAN MAGNUM
• UNITES TO FORM BASILAR
ARTERY AT THE LOWER BORDER
OF THE PONS

5. INTERNAL CAROTID ARTERY
• Four segments:
– Cervical (extracranial)
– Petrous (extracranial)
– Cavernous (intracranial)
– Cerebral /Supraclinoid (intracranial)
• Branches (proximal to distal)
– Meningohypophyseal trunk
– Ophthalmic artery (OA)
– Superior hypophyseal artery
– Posterior communicating artery (PComA)
– Anterior choroidal artery (AChA)
– Anterior cerebral artery (ACA)
– Middle cerebral artery (MCA) (continuation of the ICA)

6. Cervical segment
– From the bifurcation of CCA
– Enters the skull through carotid canal in
petrous part of temporal bone
– No branches
– Persistent embryonic vessels may give
rise to ECA – ICA anastomoses

7. PETROUS SEGMENT
-Extends from base of skull
to the petrous apex
-Ascending , Genu, Horizontal
-Enters cranial vault via
foramen lacerum.
-Branches :
Carotico tympanic A & A of pterygoid canal

8. CAVERNOUS SEGMENT
• S- shaped course in sinus
referred to as CAROTID SIPHON
• Passes through cavernous sinus
• In proximity to CN III, IV, V1, V2
and VI
• Ascending sympathetic fibres
surround artery
• Branches supply posterior lobe
of pituitary and adjacent
meninges
(Meningohypophyseal Artery)

9. SUPRACLINOID SEGMENT
• Begins after penetration of
dura
• Continues until bifurcation into
ACA & MCA

10. SUPRACLINOID SEGMENT
• Three Branches:
1.Ophthalmic A
2.Posterior Communicating A
3.Anterior Choroidal A

11. OPHTHALMIC ARTERY
 1st intradural branch of ICA
 Supplies globe, orbit, frontal and
ethmoidal sinuses, & frontal
scalp
 Central retinal A, Long & Short
posterior ciliary branches
 Branches of Ophthalmic A
anastamose with Maxillary A
branches - potential for collateral
flow in cases of proximal carotid
occlusion

12. POSTERIOR COMMUNICATING A
• Branches enters the base of brain between
infundibulum and optic tract
• Supply anteromedial thalamus and walls of
third ventricle

13. ANTERIOR CHOROIDAL A
• Branch of supraclinoid segment of ICA close to
its terminal bifurcation
• Passes backward along the optic tract and
around the cerebral peduncle as far as the
lateral geniculate body
• Enters the inferior horn of the lateral ventricle

14. ANTERIOR CHOROIDAL A
• Supplies the choroid plexus of lateral ventricle
• Branches to optic tract, hippocampus, tail of
caudate nucleus, medial and intermediate
portions of globus pallidus, posterior 2/3 of
internal capsule along with retro and
sublenticular part, middle third of cerebral
peduncle and outer part of lateral geniculate
body

16. ANTERIOR CEREBRAL ARTERY
Three segments:
 A1 –Horizontal/Pre
communicating segment
 Medial lenticulostriate
branches
 A2-Vertical/Post
communicating segment
From its connection to
the AComA to its
bifurcation into the
pericallosal and
callosomarginal arteries
 Recurrent artery of
Heubner
 Orbitofrontal
 Frontopolar
 A3- distal ACA / cortical
branches
 Pericallosal
 Callosomarginal

17. ACA SUPPLY
• Medial and orbital surface of frontal lobe
• Medial surface of the parietal lobe as far as the
parietooccipital fissure
• Genu and Anterior 4/5th of the corpus callosum
• A longitudinal 2 cm wide strip of superior surface of
the frontal & parietal lobes next to the central
sulcus
• Anterior parts of Basal Ganglia & Anteroinferior
parts of Internal Capsule

18. ACA Supply

19. RECURRENT ARTERY OF HEUBNER
• Also called medial striate artery
• Give few branches to orbital cortex, passes
through anterior perforated space to join deep
branches of MCA
• Supplies lower part of head of caudate, lower part
of frontal pole of putamen, frontal pole of globus
pallidus, frontal half of anterior limb of internal
capsule, and anterior portions of external capsule
and lateral ventricle

20. Infarct in Heubner
artery territory

21. MIDDLE CEREBRAL ARTERY
Four segments:
• M1- horizontal /
sphenoidal segment:
The stem of MCA  5-15
lenticulostriate branches
• M2- insular segment:
Runs deep in sylvian fissure
and along insula ; Superior
& Inferior divisions
• M3- opercular segment:
Follows the curvature of
operculum and ends as
terminal branches of MCA
• M4- cortical branches:
Terminal segment as it
emerges from the sylvian
fissure

22. Middle cerebral Artery
M1- Horizontal segment
•Lateral Lenticulostriate
•Temporoparietal artery
•Frontobasal artery
M2- Insular segment
M3- Opercular segment
•Opercular segment branches
•Operculofrontal artery
M4- Cortical branches
•Lat Orbitofrontal
•Pre rolandic
•Rolandic
•Ant. parietal
•Post. parietal
•Angular
•Temporopolar
•Ant temporal
•Middle temporal
•Post. temporal

23. MCA SUPPLY
• Most of the convex surface of the brain, except
the frontal (ACA)and occipital(PCA) poles & the
superior rim of the convex surface(ACA)
• Lenticulostriate arteries (Artery of cerebral
hemorrhage) supply
-All of the putamen except for its anterior pole
-Upper part of head of caudate N and all of its
body
-Lateral part of globus pallidus
-Posterior part of anterior limb, genu and anterior
third of posterior limb

24. Posterior cerebral artery
P1Segment
(Precommunicating/mesencephalic)
short segment from the basilar tip to the
PComA
– Mesencephalic br. – Cr. Nv. Nuclei 3 - 6
– Thalamoperforating arteries -
diencephalon and midbrain
P2 or ambient segment
runs in the ambient cistern from the PComA
to the posterior aspect of the midbrain
– Thalamogeniculate br.
– Medial posterior choroidal arteries
– Lateral posterior choroidal arteries
P3 or quadrigeminal segment
runs within the quadrigeminal cistern behind
the brainstem
– Hippocampal artery
– Antetior, middle, and posterior
temporal arteries
– Parieto-occipital artery
– Calcarine artery
– Posterior pericallosal artery
P4 –DISTAL SEGMENT

25. POSTERIOR CEREBRAL ARTERY

26. PCA SUPPLY
-Uncus
-Medial and inferior surface of temporal lobe
(Temporal pole- MCA)
-Thalamus, midbrain
-Cuneus and splenium of corpus callosum
-Medial surface of occipital lobe including entire
visual cortex

29. VERTEBRAL ARTERY
• V1(EXTRAOSSEOUS):
Segmental cervical muscular
and spinal branches -
passing into spinal canal via
intervertebral foramina and
reinforce blood supply of
spine and vertebrate.
• V2 (FORAMINAL):
-In foramina transversaria of
C6-C2
-meningeal/muscular/spinal
branches

30. VERTEBRAL ARTERY
• V3 (EXTRASPINAL): Posterior meningeal
artery
• V4(INTRADURAL):
– Anterior and posterior spinal arteries(Two anterior
spinal A join to supply lower medulla,
cervicomedullary junction and upper spinal cord)
– Perforating branches to medulla
– PICA: Arises from distal Vertebral Artery, supply
medulla and cerebellum

31. BASILAR ARTERY
• Forms at pontomedullary junction from two
vertebral artery
• Ends at the upper border of pons
• Major 5 branches
1.The pontine arteries
2. The labyrinthine
3. The anterior inferior cerebellar artery
4. The superior cerebellar artery
5.The posterior cerebral

32. BASILAR ARTERY
1.The pontine arteries
2. The labyrinthine
-the internal ear.
- often arises as a branch of the anterior
inferior cerebellar artery.
3. The anterior inferior cerebellar artery
-the anterior and inferior parts of the
cerebellum
- A few branches pass to the pons and
the upper part of the medulla
oblongata.
4. The superior cerebellar artery
-arises close to the termination of the
basilar artery
-supply superior surface of the
cerebellum, pons, the pineal gland,
and the superior medullary velum.
5.The posterior cerebral

33. • Medulla-Vertebral
Pons – Basilar
Midbrain- Basilar and proximal Posterior
cerebral Artery
• Two vertebral artery are rarely the same size.
Left is most often dominant; Right can be
smaller or completely atretic
• SCP-SCA, ICP-PICA, MCP-AICA and SCA

34. CIRCLE OF WILLIS
-In the interpeduncular
fossa at the base of
the brain.
-It is formed by the
anastomosis
between the two
internal carotid
arteries and the two
vertebral arteries

35. VARIATIONS IN THE CIRCLE OF WILLIS

37. Anteroinferior part-
medial lenticulostriate
arteries
Superior part of head
and body of caudate
nucleus, lentiform
nucleus- Lateral
lenticulostriate
arteries
Thalamus and tail of
caudate- by
thalamogeniculate and
posterior choroidal
artery

38. VENOUS DRAINAGE OF THE BRAIN
The characteristic features of venous drainage of the brain
are:
• The venous return in the brain does not follow the
arterial pattern
• The veins of the brain are extremely thin-walled due to
absence of muscular tissue in their walls
• The veins of the brain possess no valves
• The veins of the brain run mainly in the subarachnoid
space
• The cerebral veins, generally enter obliquely into the
dural venous sinuses against the flow of blood in the
sinuses to avoid their possible collapse following an
increased intracranial pressure as they are thin walled

39. SINUSES OF THE DURA MATER
.
(1) Postero-superior at the upper and back part of the skull.
1 Superior Sagittal (Convex or attached margin of falx cerebri)
2 Straight sinus
3 Inferior Sagittal (free or inferior margin of falx cerebri)
4 Two Transverse.
5 Occipital
(2) Antero-inferior at the base of the skull.
1 Two Cavernous
2 Two Superior Petrosal
3 Two Intercavernous
4 Two Inferior Petrosal
5 Two sphenoparietal

40. VENOUS DRAINAGE OF BRAIN
• Anterior cerebral vein + Deep middle cerebral Vein
+ Striate veins = Basal Vein of Rosenthal
• Thalamostriate vein + Choroidal vein = Internal
cerebral vein
• Internal cerebral vein + Basal Vein of Rosenthal =
Great vein of Galen
• Great vein of Galen + ISS = Straight sinus

42. • Superior cerebral vein drain to SSS
• SSS + straight sinus + Occipital sinus = Transverse
sinus(Attached margin of tentorium cerebelli)
• Inferior cerebral vein drain to superficial middle
cerebral vein terminates to cavernous sinus
• SSS connects to superficial middle cerebral vein by
Troland’s vein AND Transverse sinus to superficial
middle cerebral vein by vein of Labbe’
• Cavernous sinus (drain to transverse and IJV via
superior and inferior petrosal sinus.
VENOUS DRAINAGE OF BRAIN

43. VENOUS DRAINAGE OF BRAIN

44. CEREBRAL BLOOD FLOW
AUTOREGULATION
• Neurons produce energy (ATP) almost entirely by
oxidative metabolism of substrates including
glucose and ketone bodies, with very limited
capacity for anaerobic metabolism.
• Without oxygen, energy-dependent processes cease
leading to irreversible cellular injury if blood flow is
not re-established rapidly (4 to 10 minutes under
most circumstances)

45. REGULATION OF CEREBRAL BLOOD FLOW
Cerebral blood flow (CBF) is dependent on a number
of factors that can broadly be divided into:
a. those affecting cerebral perfusion pressure
b. those affecting the radius of cerebral blood vessels

46. • CBF = 50ml/100g/min (ranging from
20ml/100g/min in white matter to 70ml/100g/min
in grey matter)
• Adult brain weighs 1400g or 2% of the total body
weight.
• But CBF is 700ml/min or 15% of the resting cardiac
output

47. 1) CEREBRAL PERFUSION PRESSURE
• Perfusion of the brain is dependent on the
pressure gradient between the arteries and the
veins and this is termed the cerebral perfusion
pressure (CPP)
• This is the difference between the mean arterial
blood pressure (MAP) and the mean cerebral
venous pressure
CPP = MAP – ICP

48. • MAP can be estimated as equal to:
diastolic blood pressure + 1/3 pulse
pressure, usually around 90mmHg
• ICP is much lower and is normally less
than 13mmHg.

49. • An increase in CPP is usually the result of an
increase in MAP, the contribution made by
reducing ICP is minimal, apart from in pathological
states when ICP is very high
• In a normal brain, despite the potential for
changes in MAP (sleep, exercise etc.), CBF remains
constant over a wide range of CPPs.
This is achieved by a process called autoregulation

50. 2) THE RADIUS OF CEREBRAL BLOOD
VESSELS
This is regulated by four primary factors:
1. Cerebral metabolism
2. Carbon dioxide and oxygen
3. Autoregulation
4. Other factors

51. CEREBRAL METABOLISM
• Local or global increases in metabolic demand are
met rapidly by an increase in CBF and substrate
delivery and vice versa
• These changes are controlled by several vasoactive
metabolic mediators including hydrogen ions,
potassium, CO2, adenosine, glycolytic and
phospholipid metabolites and NO

52. CARBON DIOXIDE AND OXYGEN
• At normotension, the relationship between partial
pressure of carbon dioxide in arterial blood (PaCO2)
and CBF is almost linear and at a PaCO2 80mmHg CBF is
approximately doubled.
• No further increase in flow is possible at this point as
the arterioles are maximally dilated.
• Conversely at 20mmHg flow is almost halved and again
cannot fall further as the arterioles are maximally
vasoconstricted

53. • Arteriolar tone has an important influence on
how PaCO2 affects CBF.
• Moderate hypotension impairs the response of
the cerebral circulation to changes in PaCO2,
and severe hypotension abolishes it altogether
• Oxygen has little effect on the radius of blood
vessels at partial pressures used clinically

54. • Blood flow increases once PaO2 drops below
50mmHg.
• Hypoxia acts directly on cerebral tissue to promote
the release of adenosine, and in some cases
prostanoids that contribute significantly to
cerebral vasodilatation.
• Hypoxia also acts directly on cerebrovascular
smooth muscle to produce hyperpolarisation and
reduce calcium uptake, both mechanisms
enhancing vasodilatation.

55. • In adults under normal circumstances (ICP
<10mmHg), CPP and MAP are very similar and
CBF remains constant with a CPP of 60-160mmHg
• The higher the ICP the more CPP deviates from
MAP.
• Autoregulation is thought to be a myogenic
mechanism, whereby vascular smooth muscle
constricts in response to an increase in wall
tension and to relax to a decrease in wall tension
AUTOREGULATION

56. • At the lower limit of autoregulation, cerebral
vasodilation is maximal, and below this level the
vessels collapse and CBF falls passively with falls in
MAP.
• At the upper limit, vasoconstriction is maximal and
beyond this the elevated intraluminal pressure
may force the vessels to dilate, leading to an
increase in CBF and damage to the blood-brain-
barrier.

57. OTHER FACTORS
• Blood viscosity: As viscosity falls, CBF increases.
However, there will also be a reduction in oxygen-
carrying capacity of the blood
• Temperature: CMRO2 decreases by 7% for each
1°C fall in body temperature and is paralleled by a
similar reduction in CBF.
• Drugs: Cerebral metabolism can be manipulated
(reduced) and consequently CBF ,cerebral blood
volume and ICP is reduced.

58. Clinical implications
• Hyperventilation reduces the PaCO2 and causes
vasoconstriction of the cerebral vessels and therefore
reduces cerebral blood volume and ICP in patients with
raised intracranial pressure, for example after traumatic
brain injury.
• However if PaCO2 is reduced too much, it may reduce
CBF to the point of causing or worsening cerebral
ischaemia
• PaCO2 is therefore best maintained at level of 35-
40mmHg to prevent raising ICP. This reactivity may be
lost in areas of the brain that are injured.

59. Clinical implications
• Pressure autoregulation can be impaired in many
pathological conditions including patients with a
brain tumour, subarachnoid haemorrhage, stroke,
or head injury.
• The reduction in CMRO2 with decrease in
temperature is the factor that allows patients to
withstand prolonged periods of reduced CBF
without ischemic damage for example during
cardiopulmonary bypass (Hypothermia helps to
reduce excitatory neurotransmitter release,
important to central nervous system protection)

60. Clinical implications
• Infusions of the barbiturate thiopentone are used
to reduce cerebral metabolic rate and so
decrease high ICP after head injury
• Anaesthetic drugs (volatile agents) cause a
reduction in the tension of cerebral vascular
smooth muscle resulting in vasodilatation and an
increase in CBF(minimal with isoflurane)

61. •Arterial insufficiency due to thromboembolism,
hemodynamic compromise, or a combination of
these factors may lead to the recruitment of
collaterals
•The arterial anatomy of the collateral circulation
includes extracranial sources of cerebral blood
flow and intracranial routes of ancillary perfusion
COLLATERALS IN CEREBRAL CIRCULATION

62. • It is commonly divided into primary or
secondary collateral pathways
• Primary collaterals include the arterial
segments of the circle of Willis,
whereas,
the ophthalmic artery and leptomeningeal
vessels constitute secondary collaterals

63. • Interhemispheric blood flow across the anterior
communicating artery and reversal of flow in the
proximal anterior cerebral artery provide
collateral support in the anterior portion of the
circle of Willis
• Additional interhemispheric collaterals include
the proximal posterior cerebral arteries at the
posterior aspect of the circle of Willis.
• The posterior communicating arteries may supply
collateral blood flow in either direction between
the anterior and posterior circulations

64. • Anatomic studies note absence of the anterior
communicating artery in 1% of subjects, absence
or hypoplasia of the proximal anterior cerebral
artery in 10%, and absence or hypoplasia of either
posterior communicating artery in 30%
• The number and size of these anastomotic vessels
are greatest between anterior and middle
cerebral arteries, with smaller and fewer
connections between middle and posterior
cerebral arteries and even less prominent
terminal anastomoses between posterior and
anterior cerebral arteries.

65. • Distal branches of the major cerebellar arteries
similarly provide collateral links across the vertebral
and basilar segments of the posterior circulation
• Leptomeningeal and dural arteriolar anastomoses
with cortical vessels further enhance the collateral
circulation.
• Other collateral routes less commonly encountered in
acute stroke are tectal plexus joining supratentorial
branches of the posterior cerebral artery with
infratentorial branches of the superior cerebellar
artery
And the orbital plexus linking the ophthalmic artery
with facial, middle meningeal, maxillary, and
ethmoidal arteries

66. Extracranial arterial collateral circulation. Anastomoses from the facial (a), maxillary (b), and
middle meningeal (c) arteries to the ophthalmic artery and dural arteriolar anastomoses from
the middle meningeal artery (d) and occipital artery through the mastoid foramen (e) and
parietal foramen (f)

67. Intracranial arterial collateral circulation in lateral (A) and frontal (B) views. Posterior
communicating artery (a); leptomeningeal anastomoses between anterior and middle cerebral
arteries (b) and between posterior and middle cerebral arteries (c); tectal plexus between
posterior cerebral and superior cerebellar arteries (d); anastomoses of distal cerebellar
arteries (e); and anterior communicating artery (f)

68. • Moyamoya syndrome represents the ultimate
example of excessive collateralization over a
chronic time course, recruiting a wide range of
leptomeningeal and deep parenchymal vessels

69. VENOUS COLLATERALS
• Venous collaterals augment drainage of
cerebral blood flow when principal routes are
occluded or venous hypertension ensues
• The anatomy of venous collateral circulation
is highly variable, allowing diversion of blood
through numerous routes when exiting the
brain

70. Venous collateral circulation. Pterygoid plexus (a), deep middle cerebral vein (b), inferior
petrosal sinus and basilar plexus (c), superior petrosal sinus (d), anastomotic vein of Trolard (e),
anastomotic vein of Labbé (f), condyloid emissary vein (g), mastoid emissary vein (h), parietal
emissary vein (i), and occipital emissary vein (j).

71. • Primary collaterals provide immediate
diversion of cerebral blood flow to ischemic
regions through existing anastomoses
• Secondary collaterals such as leptomeningeal
anastomoses may be anatomically present,
although enhanced capacity of these
alternative routes for cerebral blood flow
likely requires time to develop.

72. • Specific pathophysiological factors leading to
the development of collaterals are uncertain,
diminished blood pressure in downstream
vessels is considered a critical variable
• Focal cerebral ischemia, a critical variable may
lead to the secretion of angiogenic peptides
with some potential for collateral formation

73. Factors determining functionality and
patency of LMCs
• The incipient development of collaterals does not
guarantee their persistence
• The efficacy of LMCs also depends upon age,
duration of ischemia, and associated
comorbidities.
• Hypertension may impair collateral
development in the setting of carotid
occlusion and therefore increase stroke risk.

74. • Chronic hypoperfusion due to arterial flow
restrictions such as extracranial carotid or
intracranial steno-occlusive disease promotes
collateral development
• Hemodynamic fluctuations may influence the
endurance of collaterals, possibly threatening
cerebral blood flow.
• Similarly, distal fragmentation of a thrombus
within the parent vessel may occlude distal
branches supplying retrograde collateral flow
from cortical arteries.

75. • The collateral circulation is also a critical
determinant of Cerebral Perfusion Pressure in
acute cerebral ischemia
• The hemodynamic effects of the collateral
circulation may be important in maintaining
perfusion to penumbral regions

76. • Deep parenchymal collaterals within the striatum
may be less effective, allowing undissolved
thrombus to be retained for longer periods of
time
• These factors may be involved in the
development of large subcortical infarcts with
cortical sparing of the basal ganglia in middle cerebral
artery occlusion and limited thalamic infarction in
posterior cerebral artery occlusion

77. Diagnostic Evaluation
• Numerous techniques, including xenon-
enhanced CT, SPECT, PET, CT perfusion, and
MR perfusion, assess cerebral blood flow and
thereby infer the status of collaterals
• CONVENTIONAL ANGIOGRAPHY remains the
gold standard for collateral flow evaluation,
given its high spatial resolution and the
possibility of dynamic evaluation

78. Collateral bloodflow distal to an occlusion of the middle cerebral artery manifest as vascular
enhancement (A, arrow) and FLAIR vascular hyperintensity (B, arrow)

79. Left ICA injection early (A) and late arterial phase.The left MCA is occluded. There is no filling of
the vascular territory. Leptomeningeal collaterals (arrows) are now filling the MCA territory. The
respective supply territories of the vessels are marked

80. Leptomeningeal collaterals (LMCs) also known as
pial collaterals, are small arterial connections
joining the terminal cortical branches of major
(middle, anterior and posterior) cerebral arteries
along the surface of the brain
• It remains dormant under normal conditions
when blood flow from all major cerebral arteries
is not impeded, but are recruited when one
major artery is either chronically or acutely
occluded.

81. • Their existence was first documented by Heubner in
1874. While trying to delineate the arterial territories
in cadaveric brains, he observed that the injected
product diffused in other arterial territories in the
absence of Willis circle connections
• The presence of LMCs has also been associated with
better outcomes, reduced infarct size, and faster
recanalization
Ringelstein EB, Biniek R, Weiller C et al. Type and extent of
hemispheric brain infarctions and clinical outcome in early and delayed
middle cerebral artery recanalization. Neurology. 1992;42:289-298

82. • In PROACT II trial investigators analysed pial
collateral formation on angiography and
categorized them as full, partial,or none and
found that presence of good collaterals influences
NIHSS score at initial presentation and infarct
volume on 24-hour CT scan in patients with MCA
occlusion
Roberts HC, Dillon WP, Furlan AJ et al. Computed
tomographic findings in patients undergoing intra-arterial
thrombolysis for acute ischemic stroke due to middle
cerebral artery occlusion: Results from the PROACT II trial.
Stroke. 2002;33:1557-1565

83. • Christoforidis et al22(2005) reviewed 65 patients
retrospectively who underwent thrombolysis for
acute ischemic stroke and reported that LMC
formation before thrombolytic treatment
predicted infarct volume and clinical outcome
independent of other predictive factors
Christoforidis GA, Mohammad Y, Kehagias D et al.
Angiographic assessment of pial collaterals as a prognostic
indicator following intra-arterial thrombolysis for acute
ischemic stroke. AJNR Am J Neuroradiol. 2005;26:1789-1797

84. • The presence of collateral sparing of penumbral
region may also because of enhanced blood flow
and retrograde collateral filling which allow
thrombolytic access to distal aspects of the clot
Caplan LR, Hennerici M. Impaired clearance of emboli
(washout) is an important link between hypoperfusion,
embolism, and ischemic stroke. Arch Neurol. 1998;55:1475–
1482

85. • The presence of leptomeningeal collaterals is also
predictive of improved long-term clinical
outcome in patients treated with and without
thrombolysis for middle cerebral artery occlusion
• In chronic ischemic conditions, such as
moyamoya syndrome and steno-occlusive carotid
disease, adequacy of collaterals may be used to
guide therapy

86. • The presence of collaterals on conventional
angiography has been associated with a
lower risk of hemispheric stroke and
transient cerebral ischemia in patients with
carotid stenosis
Henderson RD et al for the North American Symptomatic
Carotid Endarterectomy Trial (NASCET) Group.
Angiographically defined collateral circulation and risk of
stroke in patients with severe carotid artery stenosis. Stroke.
2000;31:128–132

87. • Hypertension may impair collateral development in the
setting of carotid occlusion and therefore increase stroke risk
• Several papers have found that the pre-morbid use of statins
is associated with better collateral flow in patients with
acute ischemic stroke
Hedera P et al. Stroke risk factors and development of collateral
flow in carotid occlusive disease. Acta Neurol Scand. 1998;98:182–
186
Lee M.J. et al. Role of statin in atrial fibrillation-related stroke: an
angiographic study for collateral flow. Cerebrovascular diseases
(Basel, Switzerland) 2014; 37:77-84.
Sargento-Freitas J et al. Preferential effect of premorbid statins
on atherothrombotic strokes through collateral circulation
enhancement. European neurology2012; 68:171-176

88. • Additionally, hemodynamic factors like arterial
blood pressure, central venous pressure,
intracranial pressure and distal micro-emboli can
alter the functionality of the collateral flow
Liebeskind D.S. Collateral therapeutics for cerebral ischemia. Expert
review of neurotherapeutics 2004; 4:255-265.

89. Two separate pathological processes have
been identified after an arterial occlusion
1)Arteriogenesisis(development of functional collateral
flow from pre-existing arterial anastomoses)
• This process starts immediately after the arterial
occlusion
• Opening of the anastomoses induced by mechanical
forces and involves endothelial cell activation,
infiltration of inflammatory cells and subsequent
inflammatory response leading to structural remodeling
and increased diameter
2. Angiogenesisis
• A much slower process that involves the proliferation of
endothelial cells and formation of new vessel

90. Temporal profile of development of
LMCs in acute ischemic stroke
• Yamashita et al 29 (1996) used Xenon enhanced CT rCBF
measurement with acetazolamide challenge in patients
with ICA stenosis and demonstrated that LMCs develop to
some extent immediately after occlusion and continue to
develop for some time
• The presence of secondary collateral pathways is
usually a marker of impaired cerebral hemodynamics.
• Secondary collateral pathways that require time to
develop are presumed to be recruited once primary
collaterals at the circle of Willis are inadequate

91. By understanding the role of LMA in acute stroke,
two avenues of research are opened.
• First, evaluation of collateral flow in the acute
setting can improve the clinical results of
revascularization treatments by helping identify
patients who benefit best and possibly extending
the currently accepted time window
• Second, a new generation of stroke treatments
can be developed, with the aim to improve
collateral flow.

93. Next seminar
Proteinopathies in movement disorder
By Dr. Robin Bansal
15/01/2016