Cerebrovascular Diseases

Include some of the most common and devastating disorders:

 ischemic stroke,
 hemorrhagic stroke, and
 cerebrovascular anomalies such as ICA and AVMs.

-are a major cause of disability. The

incidence increases with age, and with a doubling in stroke deaths by 2030.
A stroke, or cerebrovascular accident, is defined by abrupt onset of a neurologic
deficit that is attributable to a focal vascular cause.
Thus, the definition of stroke is clinical, and laboratory studies including brain
imaging are used to support the diagnosis. Neurologic symptoms are manifest
within seconds because neurons lack glycogen, so energy failure is rapid.
When blood flow is quickly restored, brain tissue can recover fully and the
patient's symptoms are only transient. TIA improvement of
all neurologic signs and symptoms within 24 hours regardless of whether there
is imaging evidence of new permanent brain injury but stroke has occurred if
the neurologic signs and symptoms last for >24 hours.

Approach to the Patient with Cerebrovascular Disease

Rapid evaluation is essential for use of time-sensitive treatments such as
thrombolysis. However, patients often do not
seek medical assistance on their own because :

 they are rarely in pain

 they may lose the appreciation that something is wrong (anosognosia
Some indication:
 loss of sensory and/or motor function (hemiparesis);
 change in vision, gait, or ability to speak or understand; or
 if they experience a sudden, severe headache.
Common causes of sudden-onset neurologic symptoms that may mimic stroke,
including seizure, intracranial tumor, migraine, and metabolic encephalopathy.
Absence of convulsive activity occurred at the onset reasonably excludes seizure.
Tumors may present with acute neurologic symptoms due to hemorrhage, seizure,
or hydrocephalus. When migraine develops without
head pain (acephalgic migraine), the diagnosis may remain elusive.
Deficit tends to migrate slowly across a limb over minutes rather than seconds as
with stroke.

Classically, metabolic encephalopathies produce fluctuating mental status

without focal neurologic findings. However, in the setting of
prior stroke or brain injury, a patient with fever or sepsis may manifest
hemiparesis. The metabolic process serves to "unmask" a
prior deficit.

 Once the diagnosis of stroke is made, a brain imaging study is necessary

to determine if the cause of stroke is ischemia or hemorrhage

CT imaging of the brain is the standard imaging modality to detect the presence
or absence of intracranial hemorrhage . If the stroke is ischemic,
administration of rtPA or endovascular mechanical thrombectomy may be
beneficial in restoring cerebral perfusion
Medical management to reduce the risk of complications becomes the next
priority, followed by plans for secondary prevention.
Differential diagnosis

 Migraine
 Intracerebral hemorrhage
 Head trauma
 Brain tumor
 Todd's palsy (paresis, aphasia, neglect, etc. after a seizure)
 Functional deficit (conversion reaction)
 Systemic infection
 Toxic-metabolic disturbances
-hypoglycemia, acute renal failure, hepatic insufficiency, exogenous drug
intoxication.
Ischemic Stroke
Pathophysiology of Ischemic Stroke

 Acute occlusion of an intracranial vessel . The

magnitude of flow reduction is a function of collateral blood flow and this
depends on individual vascular anatomy, the site of occlusion, and likely
systemic blood pressure.

A decrease in cerebral blood flow to zero causes death of brain tissue within 4–10
minutes; values <16–18 mL/100 g tissue per minute cause infarction within an hour;
and values <20 mL/100 g tissue per minute cause ischemia without infarction unless
prolonged for several hours or days.
Tissue surrounding the core region of infarction is ischemic but reversibly
dysfunctional and is referred to as the ischemic penumbra.
Hence saving the ischemic penumbra is the goal of revascularization therapies .

Focal cerebral infarction occurs via two distinct pathways:

necrotic pathway due to energy failure of the cell; and

apoptotic pathway in which cells become programmed to die.

Ischemia produces necrosis by starving neurons of glucose and oxygen, which in

turn results in failure of mitochondria to produce ATP.
Without ATP, membrane ion pumps stop functioning and neurons depolarize,
allowing intracellular calcium to rise. Cellular depolarization also causes glutamate
release from synaptic terminals; excess extracellular glutamate produces
neurotoxicity by activating postsynaptic glutamate receptors that increase
neuronal calcium influx. Free radicals cause
catalytic destruction of membranes and likely damage other vital functions of cells.

Fever dramatically worsens brain injury during ischemia, as does hyperglycemia

[glucose >200 mg/dL)], so it is reasonable to suppress fever and prevent
hyperglycemia as much as possible.
Treatment of Acute Ischemic Stroke

 The first goal is to prevent or reverse brain injury.

 Attend to the patient's airway, breathing, circulation (ABC's), and treat
hypoglycemia or hyperglycemia if identified.

Perform an emergency head CT scan to differentiate between ischemic stroke and

hemorrhagic stroke; b/c there are no reliable clinical findings that conclusively
separate ischemia from hemorrhage, although a more depressed level of
consciousness, higher initial blood pressure, or worsening of symptoms after
onset favor hemorrhage, and a deficit that is maximal at onset, or remits,
suggests ischemia. Treatments fall within six categories:
1- Medical support
2- IV thrombolysis,
3 -Endovascular techniques,
4 -Antithrombotic treatment,
5 -Neuroprotection, and
6 -Rehabilitation.
Medical Support
The immediate goal is to optimize cerebral perfusion in the surrounding ischemic
penumbra. Attention is also directed toward
preventing the common complications:
-infections and DVT with pulmonary embolism. Subcutaneous
heparin (unfractionated and low-molecular weight) is safe and more effective and
can be used concomitantly.
Blood pressure should be lowered if there is malignant hypertension or concomitant
myocardial ischemia or if blood pressure is >185/110 mm Hg and thrombolytic
therapy is anticipated.

Fever should be treated with antipyretics and surface cooling.

Serum glucose should be monitored and kept at < 110 mg/dL using an insulin infusion
if necessary. Water restriction
and IV mannitol may be used to raise the serum osmolarity, but hypovolemia should
be avoided as this may contribute to hypotension and worsening infarction.

Even small amounts of cerebellar edema can acutely increase intracranial pressure
(ICP) or directly compress the brainstem. The resulting brainstem compression can
result in coma and respiratory arrest and require emergency surgical
decompression.

Intravenous Thrombolysis
IV rtPA (0.9 mg/kg to a 90-mg max; 10% as a bolus, then the remainder over 60
minutes) in patients with ischemic stroke within 3 hours of onset.
Thus, despite an increased incidence of symptomatic intracerebral hemorrhage,
treatment with IV rtPA within 3 hours of the onset of ischemic stroke improved
clinical outcome.
The time of stroke onset is defined as the time the patient's symptoms began or
the time the patient was last seen as normal.
Patients who awaken with stroke have the onset defined as when they went to bed.
Indication

 Clinical diagnosis of stroke

  Onset of symptoms to time of drug administration within 3h
 CT scan showing no hemorrhage or edema of >1/3 of the
 MCA territory
 Age greater than 18 years
 Consent by patient or surrogate

Contraindication

 Sustained BP >185/110 mm Hg despite treatment

 Platelets <100,000; HCT <25%; glucose <50 or >400 mg/dL
 Use of heparin within 48 h and prolonged PTT, or elevated INR
 Rapidly improving symptoms
 Prior stroke or head injury within 3 months; prior intracranial hemorrhage
 Major surgery in preceding 14 days
 Minor stroke symptoms
 Gastrointestinal bleeding in preceding 21 days
 Recent myocardial infarction
 Coma or stupor

Administer 0.9 mg/kg IV (maximum 90 mg) IV as 10% of total dose by bolus,

followed by remainder of total dose over 1 h

Frequent cuff blood pressure monitoring No other

antithrombotic treatment for 24 h For decline in
neurologic status or uncontrolled blood pressure, stop infusion, give
cryoprecipitate, and reimage brain emergently
Avoid urethral catheterization for 2 h
Endovascular Techniques
Occlusions in large vessels [middle cerebral artery (MCA), internal carotid artery,
and the basilar artery] generally involve a large clot volume and often fail to open
with IV rtPA alone. Intraarterial pro urokinase for acute MCA occlusions up to the
sixth hour following onset of stroke. Endovascular
mechanical thrombectomy has recently shown promise as an alternative or
adjunctive treatment of acute stroke.
Antithrombotic Treatment

Recommendations on Chronic Use of Antithrombotics for Various Cardiac

Conditions
Condition Recommendation
Nonvalvular atrial fibrillation Calculate CHADS2a score
Aspirin or no antithrombotic
CHADS2 score 0
Aspirin or VKA
CHADS2 score 1
VKA
CHADS2 score >1

CHADS2 score calculated as follows: 1 point for age >75 years, 1 point for
hypertension, 1 point for congestive heart failure, 1 point for diabetes, and 2
points for stroke or TIA; sum of points is the total CHADS2 score.
Dose of aspirin is 50–325 mg/d

Platelet Inhibition Aspirin

is the only antiplatelet agent that has been proven effective for the acute
treatment of ischemic stroke - use of aspirin within 48 hours of
stroke onset reduce both stroke recurrence risk and mortality minimally.
Anticoagulation
Use of SC unfractionated heparin has no additional benefit over aspirin and
increased bleeding rates. Neuroprotection
Neuroprotection is the concept of providing a treatment that prolongs the brain's
tolerance to ischemia. Drugs that block the excitatory
amino acid pathways have been shown to protect neurons and glia in animals.
Hypothermia is a powerful neuroprotective treatment in patients with cardiac
arrest.

Rehabilitation
Proper rehabilitation of the stroke patient includes early physical, occupational,
and speech therapy. It is directed toward educating
the patient and family about the patient's neurologic deficit, preventing the
complications of immobility :

 pneumonia, DVT and pulmonary embolism, pressure sores of the skin, and
muscle contractures, and

Providing encouragement and instruction in overcoming the deficit.

Etiology of Ischemic Stroke

Initial management of AIS often does not depend on the etiology, but establishing
a cause is essential in reducing the risk of recurrence.

Particular focus should be on atrial fibrillation and carotid atherosclerosis, as

these etiologies have proven secondary prevention strategies.
The clinical presentation and examination findings often establish the cause of
stroke or narrow the possibilities to a few.
Nevertheless, nearly 30% of strokes remain unexplained despite extensive
evaluation.

Pathophysiology of ischemic stroke

The three major mechanisms that underlie ischemic stroke:

 Occlusion of an intracranial vessel by an embolus

 In situ thrombosis of an intracranial vessel
  Hypoperfusion caused by stenosis of a major extracranial or intracranial
vessel, often producing "watershed" ischemia

Causes of Ischemic Stroke

 Common Causes
Thrombosis
Embolic occlusion
Cardioembolic
Valvular lesions
 Paradoxical embolus
Atrial septal aneurysm

Uncommon Causes   

Hypercoagulable disorders
Venous sinus thrombosis
Fibromuscular dysplasia
Vasculitis
Meningitis (syphilis, tuberculosis, fungal, bacterial, zoster)
Cardiogenic
Subarachnoid hemorrhage vasospasm
Drugs: cocaine, amphetamine
Moyamoya disease
Eclampsia

Clinical examination Carotid

auscultation for bruits, blood pressure, and pressure comparison between arms,
the heart (dysrhythmia, murmurs), extremities (peripheral emboli), and retina
[effects of hypertension and cholesterol emboli].
A complete neurologic examination is performed to localize the site of stroke.
A CXR;ECG;U/A, CBC, ESR, serum electrolytes, BUN, creatinine, blood sugar,
serologic test for syphilis, serum lipid profile, PT, and PTT are often useful and
should be considered in all patients.
An ECG may demonstrate arrhythmias or reveal evidence of recent myocardial
infarction (MI).

Cardioembolic Stroke
Responsible for 20% of all ischemic strokes. Embolism of
thrombotic material forming on the atrial or ventricular wall or the left heart
valves ,then detach and embolize into the arterial circulation.
The thrombus may fragment or lyse quickly, producing only a TIA.
Alternatively, the arterial occlusion may last longer, producing stroke.

Embolic strokes tend to be sudden in onset, with maximum neurologic deficit

at once. With reperfusion following
more prolonged ischemia, petechial hemorrhage can occur within the ischemic
territory.

Emboli from the heart most often lodge in the MCA, the PCA, or one of their
branches; infrequently, the ACA territory is involved.

The most significant causes of cardioembolic stroke in most of the world are
nonrheumatic atrial fibrillation, MI, prosthetic valves, rheumatic heart
disease, and ischemic cardiomyopathy Nonrheumatic atrial fibrillation is the most
common cause of cerebral embolism overall.
Patients with atrial fibrillation have an average annual risk of stroke of 5%.
Rheumatic heart disease usually causes ischemic stroke when there is prominent
mitral stenosis or atrial fibrillation. Paradoxical embolization occurs when venous
thrombi migrate to the arterial circulation, usually via a patent foramen ovale or
atrial septal defect. Bacterial
endocarditis can cause valvular vegetations that can give rise to septic emboli.
The appearance of multifocal symptoms and signs in a patient with stroke
makes bacterial endocarditis more likely.

Artery-to-Artery Embolic Stroke

Thrombus formation on atherosclerotic plaques may embolize to intracranial
arteries. Appears to be the
dominant vascular mechanism causing brain ischemia.
Carotid bifurcation atherosclerosis is the most common source of artery-to-
artery embolus, and specific treatments have proven efficacy in reducing risk .

Carotid Atherosclerosis
Occurs most frequently within the common carotid bifurcation and proximal
internal carotid artery. Male gender,
older age, smoking, hypertension, diabetes, and hypercholesterolemia are risk
factors for carotid disease, as they are for stroke in general.
Carotid atherosclerosis produces an estimated 10% of ischemic stroke.

Risk Factors for Stroke

Hypertension
Atrial fibrillation
Diabetes
Smoking
Hyperlipidemia
Asymptomatic carotid stenosis
Symptomatic carotid stenosis (70–99%)

Symptomatic carotid stenosis (50–69%)

Symptomatic carotid disease implies that the patient has experienced a stroke
or TIA within the vascular distribution of the artery, and it is associated with
a greater risk of subsequent stroke than asymptomatic stenosis .

Other Causes of Artery-to-Artery Embolic Stroke

Intracranial atherosclerosis produces stroke either by an embolic mechanism or by
in situ thrombosis of a diseased vessel.
Recurrent stroke risk is 15% per year, similar to symptomatic untreated carotid
atherosclerosis. Dissection of the
internal carotid or vertebral arteries is a common source of embolic stroke in
young (age <60 years) patients.
The dissection is usually painful and precedes the stroke by several hours or
days.
Intracranial dissections may produce SAH because the adventitia of intracranial
vessels is thin and pseudoaneurysms may form, requiring urgent treatment to
prevent rerupture. The cause of dissection is usually unknown and recurrence is
rare.

Small-Vessel Stroke
Lacunar stroke denotes occlusion of such a small penetrating artery.
Small-vessel strokes account for 20% of all strokes. Pathophysiology
Small-vessel penetrate the deep gray and white matter of the cerebrum or
brainstem. Thrombosis of these vessels
causes small infarcts that are referred to as lacunes.

Hypertension and age are the principal risk factors.

Occlusion of a single penetrating artery gives rise to a discrete area of infarct.

Note that these vessels are too small to be visualized on CT angiography.
Clinical Manifestations
The most common lacunar syndromes are:

 Pure motor hemiparesis from an infarct in the posterior limb of the internal
capsule or basis pontis; the face, arm, and leg are almost always involved
 Pure sensory stroke from an infarct in the ventral thalamus;
 Ataxic hemiparesis from an infarct in the ventral pons or internal capsule
 Dysarthria and a clumsy hand or arm due to infarction in the ventral pons or
in the genu of the internal capsule.

Secondary prevention of lacunar stroke involves risk factor modification,

specifically reduction in blood pressure

Less Common Causes of Stroke

Hypercoagulable disorders primarily cause increased risk of venous thrombosis and
therefore may cause venous sinus thrombosis.
Protein S deficiency and homocysteinemia may cause arterial thromboses as well.
Venous sinus thrombosis occurs as a complication of oral contraceptive use,
pregnancy and the postpartum period, inflammatory bowel disease, intracranial
infections (meningitis), and dehydration.

Patients present with headache and may also have focal neurologic signs
(especially paraparesis) and seizures. Often, CT imaging is normal
unless an intracranial venous hemorrhage has occurred, but readily visualized using
MR- or CT-venography or x-ray angiography.
Intravenous heparin, regardless of the presence of intracranial hemorrhage, has
been shown to reduce morbidity and mortality, and the long-term outcome is
generally good.

Sickle cell anemia is a common cause of stroke in children. Treatment with

aggressive exchange transfusion dramatically reduces risk of stroke.

In cases where inflammation is confirmed, aggressive immunosuppression with

glucocorticoids, and often cyclophosphamide, is usually necessary to prevent
progression; a diligent investigation for infectious causes such as tuberculosis is
essential prior to therapy

Moyamoya disease is a poorly understood occlusive disease involving large

intracranial arteries, especially the distal internal carotid artery and the stem of
the MCA and ACA. Vascular inflammation is absent.

Reversible posterior leukoencephalopathy can occur in head injury, seizure,

migraine, sympathomimetic drug use, eclampsia, and the postpartum period.
The pathophysiology is uncertain but likely involves widespread cerebral segmental
vasoconstriction and cerebral edema. Patients complain of headache and
manifest fluctuating neurologic symptoms and signs, especially visual symptoms .
Transient Ischemic Attacks
TIAs are episodes of stroke symptoms that last only briefly; the standard
definition of duration is <24 hours, but most TIAs last <1 hour.
The causes of TIA are similar to the causes of ischemic stroke. With a TIA, the
occluded blood vessel reopens and neurologic function is restored.
However, infarcts of the brain do occur in 15–50% of TIAs even though neurologic
signs and symptoms are absent. The risk of stroke after a TIA
is 10–15% in the first 3 months, with most events occurring in the first 2
days. This risk can be directly estimated using the well
validated ABCD2 method.
Therefore, urgent evaluation and treatment are justified

Risk of Stroke Following Tia: The Abcd2 Score

Clinical Factor Score
A: Age gretear than 60 years 1
B: SBP >140 mm Hg or DBP >90 mm Hg 1
C: Clinical symptoms  
    Unilateral weakness 2
    Speech disturbance without 1
weakness
D: Duration  
    >60 minutes 2
    10–59 minutes 1
D: Diabetes (oral medications or insulin) 1
Total Score Sum Each Category
ABCD2 Score Total 3-Month Rate of Stroke (%)
 
0 0
1 2
2 3
3 3
4 8
5 12
6 17
7 22
Treatment
General Principles
Identification and control of modifiable risk factors is the best strategy to reduce
the burden of stroke Atherosclerosis Risk Factors
Older age, family history of thrombotic stroke, diabetes mellitus,
hypertension, tobacco smoking, abnormal blood cholesterol, and other factors
are either proven or probable risk factors for ischemic stroke, largely by their link
to atherosclerosis.

Risk of stroke is much greater in those with prior stroke or TIA. Many cardiac
conditions predispose to stroke, including atrial fibrillation and recent MI.
Hypertension is the most significant of the risk factors; in general, all
hypertension should be treated. Statin drugs reduce
the risk of stroke even in patients without elevated LDL or low HDL(atorvastatin,
80 mg/d). Tobacco smoking should be discouraged in
all patients. Tight
control of blood sugar in patients with type II diabetes lowers stroke risk MI and
death of any cause

Antiplatelet Agents
Can prevent atherothrombotic events, including TIA and stroke, by inhibiting the
formation of intraarterial platelet aggregates. Aspirin is the most widely studied
antiplatelet agent. Aspirin in low doses given once daily inhibits the
production of thromboxane A2 in platelets without substantially inhibiting
prostacyclin formation.
However, it causes epigastric discomfort, gastric ulceration, and gastrointestinal
hemorrhage, which may be asymptomatic or life threatening.
50–325 mg/d of aspirin is generally recommended for stroke prevention.
Ticlopidine and clopidogrel block the adenosine diphosphate (ADP) receptor on
platelets and thus prevent the cascade resulting in activation of the glycop rotein
IIb/IIIa receptor that leads to fibrinogen binding to the platelet and consequent
platelet aggregation. Ticlopidine is
more effective than aspirin; however, it has the disadvantage of causing diarrhea,
skin rash, and, in rare instances, neutropenia and TTP.
Anticoagulation Therapy and Embolic Stroke
In patients with chronic nonrheumatic atrial fibrillation prevents cerebral
embolism and is safe. For primary prevention
and for patients who have experienced stroke or TIA, anticoagulation with a VKA
reduces the risk by about 67%, which clearly outweighs the 1–3% risk per year of a
major bleeding complication.

The decision to use anticoagulation for primary prevention is based primarily on

risk factors. The history of a TIA or
stroke tips the balance in favor of anticoagulation regardless of other risk
factors. Because of the high annual stroke risk in untreated
rheumatic heart disease with atrial fibrillation.
These patients generally should receive long-term anticoagulation.
Anticoagulation also reduces the risk of embolism in acute MI. VKAs are
recommended long-term if atrial fibrillation persists. Treatment of Carotid
Atherosclerosis Can be removed
surgically (endarterectomy) or mitigated with endovascular stenting with or
without balloon angioplasty. Surgical Therapy
Symptomatic carotid stenosis A patient's
risk of stroke and possible benefit from surgery are related to the presence of
retinal versus hemispheric symptoms, degree of arterial stenosis, extent of
associated medical conditions institutional surgical morbidity and mortality, timing
of surgery relative to symptoms, and other factors.
Endarterectomy is most beneficial when performed within 2 weeks of symptom
onset. In addition, benefit is
more pronounced in patients >75 years, and men appear to benefit more than
women.

Medical therapy for reduction of atherosclerosis risk factors, including

cholesterol-lowering agents and antiplatelet medications, is generally recommended
for patients with asymptomatic carotid stenosis.
Endovascular Therapy
Balloon angioplasty coupled with stenting is being used to open stenotic carotid
arteries and maintain their patency. Bypass Surgery
Ineffective for atherosclerotic stenoses that are inaccessible to conventional
carotid endarterectomy.

Stroke Syndromes
A careful history and neurologic examination can often localize the region of brain
dysfunction. For example, if a patient
develops language loss and a right homonymous hemianopia, a search for causes
of left middle cerebral emboli should be performed.
Stroke syndromes are divided into:

 Large-vessel stroke within the anterior circulation,

 Large-vessel stroke within the posterior circulation, and
 Small-vessel disease of either vascular bed.
Territories of the major cerebral vessels that branch from the internal carotid

arteries

The branches and distribution of the middle cerebral artery and the principal
regions of cerebral localization.
Signs and Symptoms and Structures involved

 Paralysis of the contralateral face, arm, and leg; sensory impairment over
the same area.
  Motor aphasia: Motor speech area of the dominant hemisphere

 Central aphasia, word deafness, anomia, jargon speech, sensory agraphia,

acalculia, alexia, finger agnosia, right-left confusion.
Central, suprasylvian speech area and parietooccipital cortex of the
dominant hemisphere

 Conduction aphasia: Central speech area (parietal operculum)

 Anosognosia, unilateral neglect, agnosia for the left half of external space,
dressing "apraxia," constructional "apraxia," distortion of visual coordinates,
inaccurate localization in the half field, impaired ability to judge distance,
upside-down reading, visual illusions:
Nondominant parietal lobe lesion, occasionally to a dominant one

 Homonymous hemianopia:
Optic radiation deep to second temporal convolution

 Paralysis of conjugate gaze to the opposite side:

Frontal contraversive eye field or projecting fibers

Branches and distribution of the anterior cerebral artery and the principal regions
of cerebral localization.
Signs and Symptoms and Structures involved

 Paralysis of opposite foot and leg:

Motor leg area

 A lesser degree of paresis of opposite arm:

Arm area of cortex or fibers descending to corona radiate

 Cortical sensory loss over toes, foot, and leg:

Sensory area for foot and leg

 Urinary incontinence:
Sensorimotor area in paracentral lobule

 Contralateral grasp reflex, sucking reflex, gegenhalten (paratonic rigidity):

Medial surface of the posterior frontal lobe; likely supplemental motor
area
  Abulia (akinetic mutism), slowness, delay, intermittent interruption, lack of
spontaneity, whispering, reflex distraction to sights and sounds:
Uncertain localization—probably cingulate gyrus and medial inferior
portion of frontal, parietal, and temporal lobes

 Impairment of gait and stance (gait apraxia):

Frontal cortex near leg motor area

 Dyspraxia of left limbs, tactile aphasia in left limbs:

Corpus callosum

The branches and distribution of the posterior cerebral artery and the principal
anatomic structures shown.
Signs and Symptoms and Structures involved

I. Medial medullary syndrome (occlusion of vertebral artery or of branch of

vertebral or lower basilar artery)
On side of lesion
Paralysis with atrophy of one-half half the tongue:
Ipsilateral twelfth nerve
 On side opposite lesion
Paralysis of arm and leg, sparing face; impaired tactile and proprioceptive
sense over one-half the body:
Contralateral pyramidal tract and medial lemniscus

J. Lateral medullary syndrome (occlusion of any of vertebral, posterior

inferior cerebellar, superior, middle, or inferior lateral medullary arteries)
On side of lesion
Pain, numbness, impaired sensation over one-half the face:
Descending tract and nucleus fifth nerve
Ataxia of limbs, falling to side of lesion:
Uncertain—restiform body, cerebellar hemisphere, cerebellar fibers,
spinocerebellar tract (?)
Nystagmus, diplopia, oscillopsia, vertigo, nausea, vomiting:
Vestibular nucleus
Horner's syndrome (miosis, ptosis, decreased sweating):
Descending sympathetic tract
Dysphagia, hoarseness, paralysis of palate, paralysis of vocal cord,
diminished gag reflex: Issuing fibers ninth and tenth nerves
Loss of taste:
Nucleus and tractus solitaries
Numbness of ipsilateral arm, trunk, or leg:
Cuneate and gracile nuclei
Weakness of lower face:
Genuflected upper motor neuron fibers to ipsilateral facial nucleus

On side opposite lesion

Impaired pain and thermal sense over half the body, sometimes face:
Spinothalamic tract

 Paralysis or weakness of all extremities, plus all bulbar musculature:

Corticobulbar and corticospinal tracts bilaterally

Regions involved in medial and lateral inferior pontine stroke syndromes.

I. Medial inferior pontine syndrome (occlusion of paramedian branch of basilar

artery)
On side of lesion
Paralysis of conjugate gaze to side of lesion (preservation of convergence):
 Center for conjugate lateral gaze
Nystagmus: Vestibular nucleus
Ataxia of limbs and gait: Likely middle cerebellar peduncle
Diplopia on lateral gaze: Abducens nerve

On side opposite lesion

Paralysis of face, arm, and leg:
Corticobulbar and corticospinal tract in lower pons
Impaired tactile and proprioceptive sense over one-half of the body:
Medial lemniscus

J. Lateral inferior pontine syndrome (occlusion of anterior inferior cerebellar

artery)
On side of lesion
Horizontal and vertical nystagmus, vertigo, nausea, vomiting, oscillopsia:
Vestibular nerve or nucleus
Facial paralysis: Seventh nerve
Paralysis of conjugate gaze to side of lesion:
Center for conjugate lateral gaze
Deafness, tinnitus:
Auditory nerve or cochlear nucleus
Ataxia:
Middle cerebellar peduncle and cerebellar hemisphere
Impaired sensation over face:
Descending tract and nucleus fifth nerve

On side opposite lesion

Impaired pain and thermal sense over one-half the body (may include face):
Spinothalamic tract

Regions involved in medial and lateral midpontine stroke syndromes.

I. Medial midpontine syndrome (paramedian branch of midbasilar artery)

On side of lesion
Ataxia of limbs and gait (more prominent in bilateral involvement):
Pontine nuclei
On side opposite lesion
Paralysis of face, arm, and leg:
Corticobulbar and corticospinal tract
 Variable impaired touch and proprioception when lesion extends posteriorly:
Medial lemniscus

J. Lateral midpontine syndrome (short circumferential artery)

On side of lesion
Ataxia of limbs:
Middle cerebellar peduncle
Paralysis of muscles of mastication:
Motor fibers or nucleus of fifth nerve
Impaired sensation over side of face:
Sensory fibers or nucleus of fifth nerve

On side opposite lesion

Impaired pain and thermal sense on limbs and trunk:
Spinothalamic tract

Regions involved in medial and lateral superior pontine stroke syndromes.

I. Medial superior pontine syndrome (paramedian branches of upper basilar

artery)

On side of lesion
Cerebellar ataxia (probably):
Superior and/or middle cerebellar peduncle
Internuclear ophthalmoplegia:
Medial longitudinal fasciculus
Myoclonic syndrome, palate, pharynx, vocal cords, respiratory apparatus, face,
oculomotor apparatus, etc.:
Localization uncertain—central tegmental bundle, dentate projection, inferior
olivary nucleus
 On side opposite lesion
Paralysis of face, arm, and leg:
Corticobulbar and corticospinal tract
Rarely touch, vibration, and position are affected:
Medial lemniscus

J. Lateral superior pontine syndrome (syndrome of superior cerebellar artery)

On side of lesion
Ataxia of limbs and gait, falling to side of lesion:
Middle and superior cerebellar peduncles, superior surface of
cerebellum, dentate nucleus
Dizziness, nausea, vomiting; horizontal nystagmus:
Vestibular nucleus
Paresis of conjugate gaze (ipsilateral):
Pontine contralateral gaze
Skew deviation: Uncertain
Miosis, ptosis, decreased sweating over face (Horner's syndrome):
Descending sympathetic fibers
Tremor: Localization unclear—Dentate nucleus, superior cerebellar peduncle

On side opposite lesion

Impaired pain and thermal sense on face, limbs, and trunk:
Spinothalamic tract
Impaired touch, vibration, and position sense, more in leg than arm (there is
a tendency to incongruity of pain and touch deficits):
Medial lemniscus (lateral portion)

Regions involved in medial and lateral midbrain stroke syndromes.

I. Medial midbrain syndrome (paramedian branches of upper basilar and

proximal posterior cerebral arteries)
On side of lesion
Eye "down and out" secondary to unopposed action of fourth and sixth
cranial nerves, with dilated and unresponsive pupil:
Third nerve fibers
On side opposite lesion
 Paralysis of face, arm, and leg:
Corticobulbar and corticospinal tract descending in crus cerebri

J. Lateral midbrain syndrome (syndrome of small penetrating arteries arising

from posterior cerebral artery)
On side of lesion
Eye "down and out" secondary to unopposed action of fourth and sixth
cranial nerves, with dilated and unresponsive pupil:
Third nerve fibers and/or third nerve nucleus

On side opposite lesion

Hemiataxia, hyperkinesias, tremor:
Red nucleus, dentatorubrothalamic pathway

Stroke Within the Anterior Circulation

The internal carotid artery and its branches. Can be
occluded by intrinsic disease of the vessel (e.g., atherosclerosis) or by embolic
occlusion. Occlusion of each major
intracranial vessel has distinct clinical manifestations.
Middle Cerebral Artery
Most often due to an embolus rather than intracranial atherothrombosis.
Collateral formation via leptomeningeal vessels often prevents MCA stenosis from
becoming symptomatic. The cortical
branches of the MCA supply the lateral surface of the hemisphere.
The proximal MCA (M1 segment) gives rise to penetrating branches that supply the
putamen, outer globus pallidus, posterior limb of the internal capsule, the adjacent
corona radiata, and most of the caudate nucleus . Also
supply the inferior parietal and temporal cortex, and frontal and superior parietal
cortex.
If the entire MCA is occluded and the distal collaterals are limited, the clinical
findings are contralateral hemiplegia, hemianesthesia, homonymous hemianopia, and
a day or two of gaze preference to the ipsilateral side .
Dysarthria is common because of facial weakness.

When the dominant hemisphere is involved, global aphasia is present also, and when
the nondominant hemisphere is affected, anosognosia, constructional apraxia, and
neglect are found. Partial syndromes
may also be due to emboli that enter the proximal MCA without complete occlusion,
occlude distal MCA branches, or fragment and move distally.
A combination of sensory disturbance, motor weakness, and nonfluent aphasia
suggests that an embolus has occluded the proximal superior division and infarcted
large portions of the frontal and parietal cortices . If a fluent (Wernicke's)
aphasia occurs without weakness, the inferior division of the MCA supplying
the posterior part (temporal cortex) of the dominant hemisphere is probably
involved. Jargon speech and an inability to comprehend
written and spoken language are prominent features, often accompanied by a
contralateral, homonymous superior quadrantanopia. Hemineglect or spatial
agnosia without weakness indicates that the inferior division of the MCA in
the nondominant hemisphere is involved.

Stroke within the internal capsule produces pure motor stroke or sensory-motor
stroke contralateral to the lesion. Ischemia within the
genu of the internal capsule causes primarily facial weakness followed by arm then
leg weakness as the ischemia moves posterior within the capsule.

Lacunar infarction affecting the globus pallidus and putamen often has few clinical
signs, but parkinsonism and hemiballismus have been reported.

Anterior Cerebral Artery

The A1 segment gives rise to several deep penetrating branches that supply the
anterior limb of the internal capsule, the anterior perforate substance, amygdala,
anterior hypothalamus, and the inferior part of the head of the caudate nucleus.
Occlusion of the proximal ACA is usually well tolerated because of collateral flow.
Occlusion of a single A2 segment results in the contralateral symptoms.
Anterior Choroidal Artery
Supplies the posterior limb of the internal capsule and the white matter
posterolateral to it. Contralateral
hemiplegia, hemianesthesia (hypesthesia), and homonymous hemianopia.
Internal Carotid Artery
When the origins of both the ACA and MCA are occluded at the top of the carotid
artery, abulia or stupor occurs with hemiplegia, hemianesthesia, and aphasia or
anosognosia. In addition to supplying the ipsilateral brain, the
internal carotid artery perfuses the optic nerve and retina via the ophthalmic
artery. In 25% of
symptomatic internal carotid disease, recurrent transient monocular blindness
(amaurosis fugax) warns of the lesion.

Stroke Within the Posterior Circulation

Composed of the paired vertebral arteries, the basilar artery, and the paired
posterior cerebral arteries. The vertebral arteries join
to form the basilar artery at the pontomedullary junction .
The basilar artery divides into two posterior cerebral arteries in the
interpeduncular fossa. These major
arteries give rise to long and short circumferential branches and to smaller deep
penetrating branches that supply the cerebellum, medulla, pons, midbrain,
subthalamus, thalamus, hippocampus, and medial temporal and occipital lobes.
Occlusion of each vessel produces its own distinctive syndrome. Posterior Cerebral
Artery
PCA syndromes usually result from atheroma formation or emboli that lodge at the
top of the basilar artery. Two clinical syndromes are
commonly observed with occlusion of the PCA:

 P1 syndrome: midbrain, subthalamic, and thalamic signs

 P2 syndrome: cortical temporal and occipital lobe signs.
 P1 Syndromes
A third nerve palsy with contralateral ataxia (Claude's syndrome) or with
contralateral hemiplegia (Weber's syndrome) may result.

Paresis of upward gaze and drowsiness, and often abulia. Coma, unreactive pupils,
bilateral pyramidal signs, and decerebrate rigidity.

P2 Syndromes
Causes infarction of the medial temporal and occipital lobes. Contralateral
homonymous hemianopia with macula sparing is the usual manifestation.
Occasionally, only the upper quadrant of visual field is involved. May cause an acute
disturbance in memory, particularly if it occurs in the dominant hemisphere.
The defect usually clears because memory has bilateral representation .
Bilateral infarction in the distal PCAs produces cortical blindness (blindness with
preserved pupillary light reaction). The patient is often
unaware of the blindness or may even deny it (Anton's syndrome).

Embolic occlusion of the top of the basilar artery can produce any or all of the
central or peripheral territory symptoms. The hallmark is the sudden
onset of bilateral signs, including ptosis, pupillary asymmetry or lack of reaction to
light, and somnolence.

Vertebral and Posterior Inferior Cerebellar Arteries

PICA in its proximal segment supplies the lateral medulla and, in its distal
branches, the inferior surface of the cerebellum. Atherothrombotic lesions have
a predilection for V1 and V4 segments of the vertebral artery .
Low-flow TIAs may occur, consisting of syncope, vertigo, and alternating
hemiplegia. Stenosis proximal to
the origin of the PICA can threaten the lateral medulla and posterior inferior
surface of the cerebellum. Embolic occlusion or thrombosis of a V4 segment
causes ischemia of the lateral medulla.
The constellation of vertigo, numbness of the ipsilateral face and contralateral
limbs, diplopia, hoarseness, dysarthria, dysphagia, and ipsilateral Horner's
syndrome - lateral medullary syndrome. Hemiparesis is not a feature of
vertebral artery occlusion, however, quadriparesis may result from occlusion of
the anterior spinal artery. Cerebellar
infarction with edema can lead to sudden respiratory arrest due to raised ICP in
the posterior fossa. Drowsiness, Babinski signs, dysarthria, and bifacial weakness
may be absent, or present only briefly, before respiratory arrest ensues.

Gait unsteadiness, headache, dizziness, nausea, and vomiting may be the only early
symptoms and signs and should arouse suspicion of this impending complication.

Headache, neck stiffness, and unilateral dysmetria favor stroke.

Basilar Artery
Supply the base of the pons and superior cerebellum. Atheromatous lesions can
occur anywhere along the basilar trunk but are most frequent in the proximal
basilar and distal vertebral segments.
The picture of complete basilar occlusion is easy to recognize as a constellation of
bilateral long tract signs (sensory and motor) with signs of cranial nerve and
cerebellar dysfunction. A "locked-in" state of
preserved consciousness with quadriplegia and cranial nerve signs suggests
complete pontine and lower midbrain infarction.
The therapeutic goal is to identify impending basilar occlusion before devastating
infarction occurs. A
series of TIAs and a slowly progressive, fluctuating stroke are extremely
significant. Many neurologists
treat with heparin to prevent clot propagation.

Occlusion of the superior cerebellar artery results in severe ipsilateral cerebellar

ataxia, nausea and vomiting, dysarthria, and contralateral loss of pain and
temperature sensation over the extremities, body, and face .
Occlusion of the anterior inferior cerebellar artery produces Ipsilateral deafness,
facial weakness, vertigo, nausea and vomiting, nystagmus, tinnitus, cerebellar
ataxia, Horner's syndrome, and paresis of conjugate lateral gaze; and contralateral
loss of pain and temperature sensation.

Imaging Studies

CT Scans
Identify or exclude hemorrhage as the cause of stroke, and they identify
extraparenchymal hemorrhages, neoplasms, abscesses, and other conditions.
The infarct may not be seen reliably for 24–48 hours. CT may fail
to show small ischemic strokes in the posterior fossa because of bone artifact;
small infarcts on the cortical surface may also be missed.
After an IV bolus of contrast, deficits in brain perfusion produced by vascular
occlusion can be demonstrated and used to predict the region of infarcted brain
and the brain at risk of further infarction.
Because of its speed and wide availability, noncontrast head CT is the imaging
modality of choice in patients with acute stroke.

MRI
Documents the extent and location of infarction in all areas of the brain, including
the posterior fossa and cortical surface. MR angiography is highly
sensitive for stenosis of extracranial internal carotid arteries and of large
intracranial vessels. MRI is less sensitive for acute blood products
than CT and is more expensive and time consuming and less readily available.
However, MRI is useful outside the acute period by more clearly defining the
extent of tissue injury and discriminating new from old regions of brain infarction.
It is also more likely to identify new infarction, which is a strong predictor of
subsequent stroke.
 Cerebral Angiography
Gold standard for identifying and quantifying atherosclerotic stenoses of the
cerebral arteries and for identifying and characterizing other pathologies.
Ultrasound Techniques
Doppler ultrasound assessment of flow velocity ("duplex" ultrasound).

Intracranial Hemorrhage
Classified by their location and the underlying vascular pathology.
Bleeding into subdural and epidural spaces is principally produced by trauma .
SAHs are produced by trauma and rupture of intracranial aneurysms.
Intraparenchymal and intraventricular hemorrhage will be considered here.

Diagnosis
Intracranial hemorrhage is often discovered on noncontrast CT imaging of the
brain during the acute evaluation of stroke. The location of the
hemorrhage narrows the differential diagnosis to a few entities.

Causes of Intracranial Hemorrhage

Cause Location Comments
Head trauma Intraparenchymal: Coup and contrecoup injury
frontal lobes, anterior during brain deceleration
temporal lobes; subarachnoid
Hypertensive Putamen, globus pallidus, Chronic hypertension
hemorrhage thalamus, cerebellar produces hemorrhage from
hemisphere, pons small (100 microm) vessels
in these regions
Transformation of Basal ganglion, subcortical Occurs in 1–6% of
prior ischemic regions, lobar ischemic strokes with
infarction predilection for large
 hemispheric infarctions
Arteriovenous Lobar, intraventricular, Risk is 2–4% per year for
malformation subarachnoid bleeding
Aneurysm Subarachnoid, Mycotic and nonmycotic
intraparenchymal, rarely forms of aneurysms
subdural

Emergency Management
Close attention should be paid to airway management. Until more
results are available it is recommended to keep mean arterial pressure (MAP) <130
mm Hg, unless an increase in ICP is suspected.
Keep the cerebral perfusion pressure (MAP-ICP) above 60 mm Hg.
Blood pressure should be lowered with nonvasodilating IV drugs such as nicardipine,
labetalol, or esmolol. Treat for elevated ICP, with tracheal
intubation and hyperventilation, mannitol administration, and elevation of the
head of the bed while surgical consultation is obtained .

Intraparenchymal Hemorrhage
ICH is the most common type of intracranial hemorrhage. It
accounts for 10% of all strokes and is associated with a 50% case fatality rate .
Hypertension, trauma, and cerebral amyloid angiopathy cause the majority of
these hemorrhages. Advanced age and heavy alcohol
consumption increase the risk, and cocaine and methamphetamine use is one of the
most important causes in the young.

Hypertensive Intraparenchymal Hemorrhage Usually

results from spontaneous rupture of a small penetrating artery deep in the brain .
The most common sites are the basal ganglia (esp,putamen), thalamus,
cerebellum, and pons. The hemorrhage may be
small or a large clot may form and compress adjacent tissue, causing herniation and
death. Most hypertensive intraparenchymal hemorrhages develop over
30–90 minutes, whereas those associated with anticoagulant therapy may evolve
for as long as 24–48 hours.

Clinical Manifestations
ICHs almost always occur while the patient is awake and sometimes when stressed.
Presents as the abrupt onset of focal neurologic deficit. Seizures are uncommon.
The focal deficit typically worsens steadily over 30–90 minutes and is associated
with a diminishing level of consciousness and signs of increased ICP such as
headache and vomiting. The putamen is the most common site
for hypertensive hemorrhage, and the adjacent internal capsule is usually damaged.
Contralateral hemiparesis is therefore the sentinel sign. When mild, the
face sags on one side over 5–30 minutes, speech becomes slurred, the arm and leg
gradually weaken, and the eyes deviate away from the side of the hemiparesis. The
paralysis may worsen until the affected limbs become flaccid or extend rigidly.
When hemorrhages are large, drowsiness gives way to stupor as signs of upper
brainstem compression appear. Coma ensues, accompanied by
deep, irregular, or intermittent respiration, a dilated and fixed ipsilateral pupil,
and decerebrate rigidity.

Hematoma involving the left putamen in a patient with rapidly progressive

onset of right hemiparesis.
Thalamic hemorrhages also produce a contralateral hemiplegia or hemiparesis from
pressure on. Thalamic hemorrhages
cause several typical ocular disturbances by virtue of extension inferiorly into the
upper midbrain.
These include deviation of the eyes downward and inward so that they appear to be
looking at the nose, unequal pupils with absence of light reaction, skew deviation.
In pontine hemorrhages, deep coma with quadriplegia usually occurs over a few
minutes. There is often prominent
decerebrate rigidity and "pinpoint" (1 mm) pupils that react to light.
Hyperpnea, severe hypertension, and hyperhidrosis are common.
Death often occurs within a few hours, but small hemorrhages are compatible with
survival.
Cerebellar hemorrhages usually develop over several hours and are
characterized by occipital headache, repeated vomiting, and ataxia of gait .
Dizziness or vertigo may be prominent. There is often
paresis of conjugate lateral gaze toward the side of the hemorrhage, forced
deviation of the eyes to the opposite side, or an ipsilateral sixth nerve palsy.

Other Causes of Intracerebral Hemorrhage

Cerebral amyloid angiopathy. It
accounts for some intracranial hemorrhages associated with IV thrombolysis given
for MI. Definitively diagnosed by pathologic
demonstration of Congo red staining of amyloid in cerebral vessels.
Currently, there is no specific therapy, although antiplatelet and anticoagulating
agents are typically avoided. Cocaine and
methamphetamine are frequent causes of stroke in young (age <45 years)
patients. ICH, ischemic stroke, and SAH are
all associated with stimulant use.
Cocaine enhances sympathetic activity causing acute, sometimes severe,
hypertension, and this may lead to hemorrhage.

Head injury often causes intracranial bleeding. The

common sites are intracerebral (especially temporal and inferior frontal lobes) and
into the subarachnoid, subdural, and epidural spaces.
Trauma must be considered in any patient with an unexplained acute neurologic
deficit (hemiparesis, stupor, or confusion), particularly if the deficit occurred in
the context of a fall.

Hemorrhage into a brain tumor may be the first manifestation of neoplasm.

Choriocarcinoma, malignant melanoma, renal cell carcinoma, and bronchogenic
carcinoma are among the most common metastatic tumors associated with ICH .
Hypertensive encephalopathy is a complication of malignant hypertension.
In this acute syndrome, severe hypertension is associated with headache,
nausea, vomiting, convulsions, confusion, stupor, and coma.

Laboratory and Imaging Evaluation

Blood chemistries and hematologic studies. Platelet count and
PT/PTT. CT imaging reliably
detects acute focal hemorrhages. MRI.
Lumbar puncture should be avoided as it may induce cerebral herniation.
Treatment of Intracerebral Hemorrhage
Acute Management
When ICH is associated with thrombocytopenia (platelet count <50,000/L),
transfusion of fresh platelets is indicated.

Although a score of 6 is possible with the scale, no patient was observed to

present with this combination of findings, and it is considered highly likely to be
fatal.

Prognosis and Clinical Outcomes in Intracerebral Hemorrhage

Clinical or Imaging Point Score
Factor
Age 
<80 years 0
80 years 1
Hematoma Volume 
<30 cc 0
30 cc 1
Intraventricular Hemorrhage Present 
No 0
Yes 1
Infratentorial Origin of Hemorrhage 
No 0
Yes 1
Glasgow Coma Scale Score 
13–15 0
5–12 1
3–4 2
Total Score Sum of each category above
ICH Score Total  Observed Mortality at 30 Walk Independently at 12
days (%)  months (%) 
0 0 70
1 13 60
2 26 33
3 72 3
4 97 8
5 100 None

Most cerebellar hematomas >3 cm in diameter will require surgical evacuation.

Patients with hematomas between 1 and 3 cm require careful observation for signs
of impaired consciousness and precipitous respiratory failure.
Glucocorticoids are not helpful for the edema from intracerebral hematoma.

Prevention
Hypertension is the leading cause of primary ICH. Prevention is
aimed at reducing hypertension, eliminating excessive alcohol use, and discontinuing
use of illicit drugs.

Vascular Anomalies
Can be divided into congenital vascular malformations and acquired vascular lesions.
Congenital Vascular Malformations
True AVMs), venous anomalies, and capillary telangiectasias are lesions that usually
remain clinically silent through life.

True AVMs are congenital shunts between the arterial and venous systems that
may present as headache, seizures, and intracranial hemorrhage.
AVMs occur in all parts of the cerebral hemispheres, brainstem, and spinal cord,
but the largest ones are most frequently in the posterior half of the hemispheres.

Bleeding, headache, or seizures are most common between the ages of 10 and
30, occasionally as late as the fifties. AVMs are more frequent in men,
and rare familial cases have been described.
Headache (without bleeding) may be hemicranial and throbbing, like migraine, or
diffuse. Focal seizures, with or without
generalization, occur in 30% of cases.
One half of AVMs become evident as ICHs. In
most, the hemorrhage is mainly intraparenchymal with extension into the
subarachnoid space in some cases. The risk of rerupture is 2–4%
per year and is particularly high in the first few weeks.
Hemorrhages may be massive, leading to death, or may be as small as 1 cm in
diameter, leading to minor focal symptoms or no deficit.
MRI is better than CT for diagnosis. Surgical
treatment of symptomatic AVMs. Paradoxically, smaller
lesions seem to have a higher hemorrhage rate.

Miesso(MD)