Handbook of Neurosurgery 7th Ed

29. Stroke

AKA cerebral infarction. The term stroke is preferred to cerebrovascular accident (CVA), although “CVA” is used widely (sometimes as an abbreviation for stroke).

Also see Occlusive cerebro-vascular diseasepage 1144Intracerebral hemorrhage on page 1118, and SAH and aneurysms on page 1034 for those related topics.



(transient ischemic attack): transient neuronal dysfunction secondary to focal ischemia (of brain, spinal cord, or retina) without (permanent) acute infarction1*

10-15% of patients with TIA have a stroke within 3 months, 50% of which occur within 48 hours.


AKA cerebrovascular accident (sometimes called completed stroke). A permanent (i.e. irreversible) neurologic deficit caused by inadequate perfusion of a region of brain or brain stem

* obsolete operational definitions used an arbitrary 24 hour cutoff for duration of symptoms

29.1. Cerebrovascular hemodynamics


Table 29-1 shows typical CBF values and the corresponding neurophysiologic state. CBF < 20 is generally associated with ischemia and if prolonged will produce cell death2. However, this assumes normal metabolic rate and may be more applicable to global cerebral hypoperfusion3. There is a higher CBF threshold for loss of electrical excitability than that for cell death - this has lead to the concept of the ischemic penumbra - non-functioning cells that are still viable2.

CBF is related to blood pressure as shown in Eq 29-1,


where CPP = cerebral perfusion pressure (see page 866), CVR = cerebrovascular resistance (see below), and MAP = mean arterial pressure.

Cerebrovascular resistance (CVR) is affected by the PaCO2 such that there is a linear increase in CBF with increasing PaCO2 within the range of 20-80 mm Hg.

CVR is also affected by changes in CPP which produce changes in blood vessel tone via a myogenic mechanism. In the range of CPP = 50-150 mm Hg the CVR of normal brain tissue varies linearly to maintain an almost constant CBF. This phenomenon is called (cerebral) autoregulation, which is altered in pathologic states.

The cerebral metabolic rate of oxygen consumption (CMRO2) averages 3.0-3.8 ml/100 gm tissue/min. The ratio of CBF to CMRO2 (the coupling ratio4) in the quiescent brain is 14-18. With focal cortical activity, local CBF increases ≈ 30% while CMRO2 increases ≈ 5%5. CMRO2 can be manipulated to some degree (see page 1063).

Table 29-1 Correlates of CBF

CBF (ml per 100 gm tissue/min)


> 60 (approx)

hyperemia (CBF > tissue demand)


normal brain at rest


gray matter


white matter



EEG becomes flatline


physiologic paralysis


brainstem auditory evoked response (BAER) changes


alterations in cell membrane transport (cell death; stroke)


May be evaluated with xenon-enhanced CT, CTP (see page 128), TCD, SPECT, or MRI98-101. Response of CBF to a vasodilator challenge with 1000 mg of IV acetazolamide (ACZ) (Diamox®) is classified as100101:

Type I: normal baseline CBF with 30-60% increase following ACZ challenge

Type II: decreased baseline CBF with blunted response of < 10% increase or < 10 mL/100 g/min absolute increase after ACZ challenge

Type III: decreased baseline CBF with paradoxical decrease of regional CBF following ACZ challenge, suggesting a steal phenomenon in regions with maximally dilated vasculature at baseline

29.2. Strokes: general information


For a patient presenting to the E/R with the abrupt onset of a new focal cerebral deficit:

• 5% are seizure, tumor, or psychogenic

• 95% are vascular (i.e stroke):

image 85% ischemic infarct: early angiography has shown that arterial occlusion can be demonstrated in 80% of these, regardless of subtype6

• 41% unknown cause (may decrease with the use of early angiography)

• 21% lacune (small artery or arteriole cerebrovascular lesion)

• 16% cardiogenic embolus7

• 11% large artery cerebrovascular lesion

• 11% tandem arterial pathology

• atherosclerotic plaques in the aortic arch > 4 mm thick are a risk factor for recurrent strokes and other vascular events (MI, peripheral embolism, and death from vascular causes)8

image 15-30% hemorrhagicA:

• intracerebral hemorrhage (ICH): ≈11%. “Hypertensive” hemorrhage, amyloid angiopathy (see page 1122)…

• SAH: ≈ 7%. Aneurysmal, AVM-related


image venous infarction: a small proportion of strokes. Typically seen in dural sinus thrombosis (see page 1166)


A. intracerebral hemorrhage (ICH) should be suspected with smooth onset of symptoms over minutes to hours, presence of severe H/A, frequent vomiting, and when depression of level of consciousness is prominent (in contrast to ischemic infarct which typically has significant motor or sensory deficit with little or no impairment of consciousness except with massive or brainstem stroke); these features may be less prominent in lobar ICH. Also see Intracerebral hemorrhagepage 1118


29.2.1. Modifiable risk factors for stroke

1. hypertension: the most powerful & treatable risk factor. Both systolic & diastolic BP independently correlate with risk of stroke9

2. cigarette smoking: relative risk values of 1.5-2.210-12

3. blood lipids: lowering lipids may reduce the risk of some types of cerebrovascular disease. Current recommendations: treat if LDL > 70. Use of a statin drug is recommended

4. alcohol: heavy consumption is associated with increased risk of stroke, whereas moderate use may have no effect or may be slightly protective. The effects may be different for ischemic vs. hemorrhagic stroke13

5. antiplatelet therapy: reduces the risk of stroke and other vascular events in high-risk patients. The optimal dose is not known, the acceptable range for aspirin is 30-1300 mg/d, with a recommended initial dose of 325 mg/d14

29.2.2. Rationale for acute stroke treatment

In the complete absence of blood flow, neuronal death occurs within 2-3 minutes from exhaustion of energy stores. However, in most strokes, there is a salvageable penumbra (tissue at risk) that retains viability for a period of time through suboptimal perfusion from collaterals. Progression of local cerebral edema from the injury results in compromise of these collaterals and progression of ischemic penumbra to infarction if flow is not restored and maintained. Prevention of this secondary neuronal injury drives the treatment of stroke and has led to the creation of designated Primary Stroke Centers that offer appropriate and timely triage and treatment of all potential stroke patients.

Current standard of care requires the administration of IV tPA to all eligible patients. Documentation is necessary to justify deviation from this standard of care in the current medicolegal environment.

In centers with advanced capabilities (Comprehensive Stroke Centers), other treatment modalities are also offered.

29.2.3. Evaluation


• time last seen normal (stroke on awakening being increasingly evaluated by perfusion studies to ensure the presence of viable tissue)

• current deficit and clinical presentation

• NIH Stroke Scale score should be assessed and recorded (see page 1014)

• reasons for not administering IV tPA (if any) should be documented


Upon presentation with symptoms of a potential stroke, a noncontrast brain CT scan should be done immediately to rule-out hemorrhage (intraparenchymal or SAH), hematoma, early signs of ischemia, old infarcts or injuries, and other lesions (e.g. tumor).

CAT scan findings with ischemic stroke (“pale” infarcts)

NB: These principles do not apply to small lacunar infarcts, nor to hemorrhagic strokes.

NB: CT is normal in 8-69% of MCA strokes in the first 24 hours15.

Hyperacute (< 6 hours after stroke): Early signs of infarction involving large areas of the MCA territory correlate with poor outcome16. Early findings may include17:

1. hyperdense artery sign (see below): low sensitivity, but helpful if present

2. focal low attenuation within the gray matterA

3. loss of the gray-white interfaceA

4. attenuation of the lentiform nucleus

5. mass effectA

A. early: effacement of the cerebral sulci (often subtle)19

B. late: midline shift in large territory infarction

6. loss of the insular ribbon (hypodensity involving the insular region)

7. enhancement: occurs in only 33%. Stroke becomes isodense (called “masking” effect) or hyperdense with normal brain, and, rarely, may be the only indication of infarction19


A. these findings are probably due to increased water content resulting from the following: cellular edema arising from altered cell permeability which produces a shift of sodium and water from the extra-cellular to the intracellular compartment, which also increases the extracellular osmotic pressure causing transudation of water from capillaries into the interstitium18


24 hrs: Most strokes can be identified as a low density by this time.

1-2 wks: Strokes are sharply demarcated.

3 wks: Stroke approaches CSF density.

In 5-10% there may be a short window (at around day 7-10) where the stroke becomes isodense, called “fogging effect”. IV contrast will usually demonstrate these.

Mass effect: common between day 1 to 25. Then atrophy is usually seen by ≈ 5 wks (2 wks at the earliest). Serial CT scans have shown that midline shift increases after ischemic stroke and reaches a maximum 2-4 days after the insult.

Calcifications: only ≈ 1-2% of strokes calcify (in adults, it is probably a much smaller fraction than this; and in peds it is a higher percentage than this). Therefore, in an adult, calcifications almost rule-out a stroke (consider AVM, low grade tumor…).

Hyperdense artery sign: The cerebral vessel (usually the MCA) appears as a high density on unenhanced CT, indicating intraarterial clot (thrombus or embolus)20. Seen in 12% of 50 patients scanned within 24 hrs of stroke, and in 34% of 23 very early CTs done to R/O hemorrhage. Sensitivity for MCA occlusion is low, but specificity is high (although it may also be seen with carotid dissection, or (usually bilaterally) with calcific atherosclerosis or high hematocrit20). Does not have independent prognostic significance21.

Enhancement: CT enhancement with IV contrast in stroke:

1. many enhance by day 6, most by day 10, some will enhance up to 5 wks

2. rule of 2’s: 2% enhance at 2 days, 2% enhance at 2 mos

3. gyral enhancement: AKA called “ribbon” enhancement. Common. Usually seen by 1 week (grey matter enhances > white). DDx includes inflammatory infiltrating lesions such as lymphoma, neurosarcoidosis… (due to breakdown of BBB)

4. rule of thumb: there should not be enhancement at the same time there is mass effect


CTA (see page 128) is useful for assessing the location and extent of vascular occlusion in acute ischemic stroke22, and may identify the bleeding source in subarachnoid hemorrhage. Findings can direct treatment towards endovascular options when a proximal or significant large vessel occlusion is seen (see page 1018).


Theoretically identifies salvageable penumbra as a region of mismatch between CBF and CBV. Assumption: the infarcted core (with no salvageable tissue) has decreased CBF within a region of decreased CBV (CBF/CBV match). A mismatched area (decreased CBV without a decrease in CBF) represents potentially salvageable penumbra23. Implication: thrombolytics and interventional treatment modalities without mismatch will likely increase morbidity and mortality without clinical benefit.


With newer, faster acquisition times, and with gradient echo sequences that are highly sensitive to hemorrhage, MRI is increasingly being utilized in the hyperacute setting and is at times replacing CT as the initial evaluation. More sensitive than CT (especially DWI-MRI (see page 132) - and particularly in the 1st 24 hrs after stroke), and especially with brainstem or cerebellar infarction. More contraindications than CT (see page 130).

Contrast MRI: not often used. 4 enhancement patterns24:

1. intravascular enhancement: occurs in ≈ 75% of 1-3 day-old cortical infarcts, and is probably due to sluggish flow and vasodilatation (thus, it is not seen with complete occlusion). May indicate areas of brain at risk of infarction

2. meningeal enhancement: especially involving the dura. Seen in 35% of cortical strokes 1-3 days old (not seen in deep cerebral or brainstem strokes). No angiographic nor CT equivalent

3. transitional enhancement: above two types of enhancement coexist with early evidence of BBB breakdown; usually seen on days 3-6

4. parenchymal enhancement: classically appears as a cortical or subcortical gyral ribbon enhancement. May not be apparent for the first 1-2 days, and gradually approaches 100% by 1 week. Enhancement may eliminate “fogging effect” (as on CT) which may obscure some strokes at ≈ 2 weeks on unenhanced T2WI


Similar to CT perfusion (see page 132), areas of matched DWI and PWI abnormality are thought to represent infarcted tissue. PWI abnormalities that do not have a DWI correlate are thought to represent potentially salvageable penumbra25.



1. early stroke in carotid distribution + history of amaurosis fugax or bruit or retinal emboli, etc. suggesting increasing carotid stenosis, thrombogenic ulcerated plaque, or carotid dissection

2. if diagnosis still questionable (e.g. aneurysm, vasculitis)

3. with rapid recovery, suggesting carotid TIA in face of increasing stenosis

4. AVOID angio if unstable or if severe disabling neuro deficit


1. cutoff sign: vessel ends abruptly at the point of obstruction

2. string sign: narrow strand of contrast in a vessel with high grade stenosis

3. “luxury perfusion”: reactive hyperemia is a recognized response of cerebral tissue to injury (trauma, infarction, epileptogenic focus…). Luxury perfusion is blood flow in excess of demand due to abolition of CBF autoregulation due to acidosis26. On angiography it shows up as accelerated circulation adjacent to the infarct with a stain or blush and early venous drainage


Administer in order shown. Record initial performance only (do not go back).

Higher NIHSS scores correlate with more proximal vascular lesions (larger vessel occlusion causes more widespread deficit).


A Revised 1/24/91. Based on Cincinnati stroke scale27. Contact the Public Health Service, National Institutes of Health, National Institute of Neurologic Disorders and Stroke, Bethesda, Maryland, U.S.A. for copies of a grading form (which has more details on some aspects of grading) and for training information28


1a. Level of consciousness (LOC)

0 alert; keenly responsive

1 not alert, but arousable by minor stimulation to obey, answer or respond

2 not alert, requires repeated stimulation to attend, or is obtunded and requires strong painful stimulation to make movements (not stereotyped)

3 comatose: responds only with reflex motor (posturing) or autonomic effects, or totally unresponsive, flaccid and areflexic

1b. Level of consciousness questions

Patient is asked the month and their age.

0 answers both questions correctly: must be correct (no credit for being close)

1 answers one question correctly, or cannot answer because of: ET tube, orotracheal trauma, severe dysarthria, language barrier, or any other problem not secondary to aphasia.

2 answers neither question correctly, or is: aphasic, stuporous, or does not comprehend the questions

1c. Level of consciousness commands

Patient is asked to open and close the eyes, and then to grip and release the non-paretic hand. Substitute another 1-step command if both hands cannot be used. Credit is given for an unequivocal attempt even if it cannot be completed due to weakness. If there is no response to commands, demonstrate (pantomime) the task. Record only first attempt.

0 performs both tasks correctly

1 performs one task correctly

2 performs neither task correctly

2. Best gaze

Test only horizontal eye movement. Use motion to attract attention of aphasic patients.

0 normal

1 partial gaze palsy (gaze abnormal in one or both eyes, but forced deviation or total gaze paresis are not present) or patient has an isolated cranial nerve III, IV or VI paresis

2 forced deviation or total gaze paresis not overcome by oculocephalic (Doll’s eyes) maneuver (do not do caloric testing)

3. Visual

Visual fields (upper and lower quadrants) are tested by confrontation. May be scored as normal if patient looks at side of finger movement. Use ocular threat where consciousness or comprehension limits testing. Then test with double sided simultaneous stimulation (DSSS).

0 no visual loss

1 partial hemianopia (clear cut asymmetry), or extinction to DSSS

2 complete hemianopia

3 bilateral hemianopia (blind, including cortical blindness)

4. Facial palsy

Ask patient (or pantomime) to show their teeth, or raise eyebrows and close eyes. Use painful stimulus and grade grimace response in poorly responsive or non-comprehending patients.

0 normal symmetrical movement

1 minor paralysis (flattened nasolabial fold, asymmetry on smiling)

2 partial paralysis (total or near total paralysis of lower face)

3 complete paralysis of one or both sides (absent facial movement in upper and lower face)

5. Motor Arm (5a = left, 5b = right)

Instruct patient to hold the arms outstretched, palms down (at 90° if sitting, or 45° if supine). If consciousness or comprehension impaired, cue patient by actively lifting arms into position while verbally instructing patient to maintain position.

0 no drift (holds arm at 90° or 45° for full 10 seconds)

1 drift (holds limbs at 90° or 45° position, but drifts before full 10 seconds but does not hit bed or other support)

2 some effort against gravity (cannot get to or hold initial position, drifts down to bed)

3 no effort against gravity, limb falls

4 no movement 9 amputation or joint fusion: explain

6. Motor leg (6a = left, 6b = right)

While supine, instruct patient to maintain the non-paretic leg at 30°. If consciousness or comprehension impaired, cue patient by actively lifting leg into position while verbally instructing patient to maintain position. Then repeat in paretic leg.

0 no drift (holds leg at 30° full 5 seconds)

1 drift (leg falls before 5 seconds, but does not hit bed)

2 some effort against gravity (leg falls to bed by 5 seconds)

3 no effort against gravity (leg falls to bed immediately)

4 no movement 9 amputation or joint fusion: explain

7. Limb ataxia

(Looking for unilateral cerebellar lesion). Finger-nose-finger and heel-knee-shin tests are performed on both sides. Ataxia is scored only if clearly out of proportion to weakness. Ataxia is absent in the patient who cannot comprehend or is paralyzed.

0 absent

1 present in one limb

2 present in two limbs

9 amputation or joint fusion: explain

8. Sensory

Test with pin. When consciousness or comprehension impaired, score sensation normal unless deficit clearly recognized (e.g. clear-cut asymmetry of grimace or withdrawal). Only hemisensory losses attributed to stroke are counted as abnormal.

0 normal, no sensory loss

1 mild to moderate sensory loss (pin-prick dull or less sharp on the affected side, or loss of superficial pain to pinprick but patient aware of being touched)

2 severe to total (patient unaware of being touched in the face, arm and leg)

9. Best language

In addition to judging comprehension of commands in the preceding neurologic exam, the patient is asked to describe a standard picture, to name common items, and to read and interpret the standard text in the box below. The intubated patient should be asked to write.

You know how.

Down to earth.

I got home from work.

Near the table in the dining room.

They heard him speak on the radio last night.

0 normal, no aphasia

1 mild to moderate aphasia (some loss of fluency, word finding errors, naming errors, paraphasias and/or impairment of communication by either comprehension or expression disability)

2 severe aphasia (great need for inference, questioning and guessing by listener; limited range of information can be exchanged)

3 mute or global aphasia (no usable speech or auditory comprehension) or patient in coma (item 1a = 3)

10. Dysarthria

Patient may be graded based on information already gleaned during evaluation. If patient is thought to be normal, have them read (or repeat) the standard text shown in this box.








0 normal speech

1 mild to moderate (slurs some words, can be understood with some difficulty)

2 severe (unintelligible slurred speech in the absence of, or out of proportion to any dysphasia, or is mute/anarthric)

9 intubated or other physical barrier

11. Extinction and inattention (formerly neglect)

Sufficient information to identify neglect may already be gleaned during evaluation. If the patient has severe visual loss preventing visual DSSS, and the cutaneous stimuli are normal, the score is normal. Scored as abnormal only if present.

0 normal, no sensory loss

1 visual, tactile, auditory, spatial or personal inattention or extinction to DSSS in one of the sensory modalities

2 profound hemi-inattention or hemi-inattention to more than one modality. Does not recognize own hand or orients to only one side of space.

A. Distal motor function (not part of NIHSS) (a = left arm, b = right)

Patients hand is held up at the forearm by the examiner, and is asked to extend the fingers as much as possible. If patient cannot do so, the examiner does it for them. Do not repeat the command.

0 normal (no finger flexion after 5 seconds)

1 at least some extension after 5 seconds (any finger movement is scored)

2 no voluntary extension after 5 seconds

29.2.4. Management of TIA or stroke

Treatment options timeline



1. within 4.5 hours of onset of symptoms:

A. patients may be candidates for IV tPA (see page 1017)

B. failures to respond to IV tPA who are in good clinical grade (NIHSS > 8-10, see page 1014) may be candidates for

1. intraarterial tPA (IA tPA) or

2. mechanical embolectomy/clot disruption

2. 4.5-6 hours after onset:

A. intraarterial tPA (IA tPA) or

B. mechanical embolectomy/clot disruption

3. 6-8 hours, check perfusion with CTP or MRI-DWI before mechanical embolectomy (studied up to 8 hours after onset).  Embolectomy contraindicated if stroke > 1/3 of MCA distribution (risk of ICH with reperfusion)

These times are more applicable to anterior circulation strokes. Posterior circulation occlusions may be treated more aggressively, e.g. IA tPA has been used up to 12 hrs.


Plasminogen activators catalyze the conversion of plasminogen to the fibrinolytic compound plasmin. The primary agent used is alteplase (recombinant tissue plasminogen activator (rtPA, or just tPA)) (Activase®) which is FDA approved for the IV treatment of acute ischemic stroke (see below).



A randomized double-blind NINDS study of 624 patients with an ischemic stroke having a clearly defined time of onset and a CT scan prior to drug administration, found improved neurologic outcome at 3 months in patients who received alteplase (these patients were 30% more likely to have minimal or no disability)29 which persisted at 6 and 12 mos30 in all subgroups of ischemic stroke. The recurrent stroke rate in control and tPA patients was similar (5%). In contrast, statistical benefit at 90 days could not be confirmed in the second European Cooperative Acute Stroke Study (ECASS II)31.

Early data indicated tPA had to be given ≤ 3 hrs after the onset of symptoms, however, this window was extended to 4.5 hours after the ECASS-III32 looked at 821 stroke patients randomized between placebo or tPA in the 3- to 4.5-hour time-window. Compared to placebo, tPA-treated patients experienced a 7.2% absolute increase in the rate of excellent recovery at 90-day follow-up (P=0.04). Although tPA therapy was associated with an increased rate of symptomatic intracerebral hemorrhage (7.9% for tPA versus 3.5% for placebo, P<0.001), it was not associated with an increased rate of death (7.7% for tPA versus 8.4% for placebo, P=0.68). For every 100 acute ischemic stroke patients given tPA in accordance with the NINDS protocols, 32 will benefit and 3 will be harmed33.

Guidelines for the administration of IV tPA

Also see http://www.stroke-site.org (The Brain Attack Coalition - NINDS).


1. age ≥ 18 years (although use in childhood stroke is increasing34)

2. time last seen normal < 3 hrs prior (ECASS III extends window to 4.5 hours in selectA patients35)

3. “wake-up” stroke (seen in 25% of ischemic stroke patients) may also be safe to treat in select circumstances36


A. ECASS III did not include: patients ≥ 80 years of age, patients with baseline NIHSS scores > 25 (see page 1014), and prior stroke in diabetics. These patients are not excluded from treatment with IV tPA in the 0-3-hour window by the regulatory authorities in the United States and Canada.


Contraindications: (see http://www.stroke-site.org and reference29)

1. intracerebral hemorrhage (ICH): on admitting CT, or history of prior ICH

2. clinical presentation of SAH (even with negative CT)

3. known intracranial aneurysm or AVM

4. active internal bleeding

5. known bleeding diathesis, including but not limited to:

A. patients on anticoagulants, or those who received heparin in past 48 hrs

B. platelet count < 100,000/mm3

6. serious head trauma, serious stroke, or intracranial surgery within past 3 months

7. SBP > 185 mm Hg, or DBP > 110 mm Hg that cannot be controlled despite use of nicardipine infusion or IV labetalol


1. seizure witnessed at the time of onset of stroke symptoms

2. major surgery within the last 14 days

3. arterial puncture at non-compressible site within past 7 days

4. recent lumbar puncture

5. rapidly improving or minor symptoms

6. blood glucose > 400 mg/dL or < 50 mg/dL

7. history of GI or urinary tract hemorrhage within past 21 days

8. post myocardial infarction pericarditis

Treatment protocol: Also, see Contraindicationspage 1017.

Rx alteplase (Activase®): initiate < 4.5 hrs from onset of deficit. NINDS protocol: 0.09 mg/kg IV bolus over 1 min, followed by 0.81 mg/kg constant infusion over 60 minutes (up to a maximum of 90 mg total, including the bolus)29.

HTN is aggressively controlled.

Anticoagulants and antiplatelet drugs are held for 24 hrs after treatment. If there is an indication for anticoagulation, obtain a non-contrast CT 24 hours prior to starting anticoagulation since there is a risk of subclinical intracerebral hemorrhage.

ICH following IV tPA

There is an increased risk of symptomatic intracerebral hemorrhage (ICH) with the use of tPA (NINDS study: 6.4% vs. 0.6% with placebo; ECASS II: 8.8% vs. 3.4%). In spite of this, the NINDS study found that mortality in the tPA group was similar to controls at 3 mos (17% vs. 21%). The following factors were associated with an increased risk of symptomatic ICH (with only a 57% efficiency rate of predicting ICH): severity of NIHSS score, or pretreatment CT showing brain edema or mass effect. In one study, ICH did not influence outcome except in the rare instance when a massive hematoma occurred37. Outcomes were still better in the treated group, and the conclusion is that these patients are still reasonable candidates for tPA38. Since then, multicenter analyses have demonstrated that size of infarction and elevated blood sugar are independent risk factors for symptomatic ICH39.

Management of post-tPA ICH:

1. discontinue tPA infusion of and obtain STAT head CT

2. send labs: PT, aPTT, platelet count, fibrinogen, and type & cross

3. prepare to administer 6-8 units cryoprecipitate containing Factor VIII

4. prepare to administer 6-8 units of platelets

5. if emergent EVD placement or other interventional procedure is needed, consider the use of recombinant Factor VIIa (40-80mg/kg) immediately beforehand (NB: this is only a temporizing measure and cryoprecipitate needs to still be given)


Intraarterial tPA

May be employed up to 6 hours after stroke onset for patients ineligible for the IV protocol above (e.g. after the 4.5 hour window), as long as there is not a contraindication for tPA. For statistics with IA-tPA/stenting with total carotid occlusions, see page 1157.


MERCI retriever: Acronym: Mechanical Embolus Removal in Cerebral Ischemia. Nitinol corkscrew-shaped wire passed through angio catheter to pull out thrombus. An alternative for opening intracranial vessels for patients ineligible for intravenous tPA.

Use of the MERCI device within 8 hours of the onset of stroke symptoms in patients ineligible for intravenous tPA resulted in recanalization in 48% (68/141) (nonrandomized, multicenter prospective trial40). Clinically significant procedural complications occurred in 7.1% (10 of 141). Symptomatic intracerebral hemorrhage occurred in 7.8% (11 of 141). Good neurological outcomes (modified Rankin score 2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% vs. 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% vs. 54%).

Penumbra system: An aspiration catheter to remove thrombus with a separator wire used to macerate the clot and maintain catheter patency.

• 81.6% rate of revascularization (TIMI 2 or 3 flow) vs. 48.2% historical controls.

• 3.2% procedural serious adverse events vs. 7.1% historical control

• ICH: symptomatic ICH in 11.2%; asymptomatic ICH in 16.8%

• improvement ≥ 4 point in NIHSS at discharge in 57.8%

• modified Rankin Score (mRS) < 2 at 90 days achieved by 25% of patients

Balloon angioplasty and stenting: Stenting likely works by buttressing the clot. High efficacy reported in failure of other options.

EKOS ultrasound catheter: Combines clot softening using a distal catheter ultrasound transducer with infusion of a thrombolytic agent through the catheter.


These guidelines are for TIA or stroke, but not SAH (for this, see page 1040) nor intracerebral hemorrhage (ICH) (see page 1126)41. The following guidelines for initial management should be maintained 48 hrs after last neuro deterioration.

1. frequent VS with crani checks (q 1 hr x 12 hrs, then q 2 hrs)

2. activity: bed rest

3. labs:

A. routine: CBC + platelet count, electrolytes, PT/PTT, U/A, EKG, CXR, ABG

B. “special” (when appropriate): RPR (to rule-out neurosyphilis), ESR (to rule-out giant cell arteritis), hepatic profile, cardiac profile

C. at 24 hrs: CBC, platelet count, cardiac profile, lipid profile, EKG

4. O2 at 2 L per NC; repeat ABG on 2 L O2

5. monitor cardiac rhythm x 24 hrs (literature quotes 5-10% prevalence of EKG changes, and 2-3% acute MIs in patients with stroke)

6. diet: NPO

7. nursing care

A. indwelling Foley (urinary) catheter if consciousness impaired or if unable to use urinal or bedpan; intermittent catheterization q 4-6 hrs PRN no void if Foley not used

B. accurate I’s & O’s; notify M.D. for urine output < 20 cc/hr x 2 hrs by Foley, or < 160 cc in 8 hrs if no Foley

8. IV fluids: NS or 1/2 NS at 75-125 cc/hr for most patients (to eliminate dehydration if present)

A. avoid glucose: hyperglycemia may extend ischemic zone (penumbra)42. Although hyperglycemia may be a stress response and may not be neurotoxic43, recommendations are to strive for normoglycemia44

B. avoid overhydration in cases of ICH, CHF, or SBP > 180. It had been suggested that an optimal Hct for compromise between O2 delivery and decreased viscosity was ≈ 33% and that fluid management should strive for this, however the early promise of this theory has not been borne out

9. treat CHF and arrhythmias (check CXR & EKG). MI or myocardial ischemia may present with neuro deficit, these patients should be admitted to CCU

10. avoid diuretics unless volume overloaded

11. blood pressure (BP) management:

A. for patients presenting with HTN: management must take baseline BP into account: see Hypertension in stroke patients below for management

B. for patients presenting with hypotension (SBP < 110 or DBP < 70):

1. unless contraindicated (viz.: ICH, cerebellar infarct, or decreased cardiac output) give 250 cc NS over 1 hr, then 500 cc over 4 hrs, then 500 cc over 8 hrs

2. if fluid ineffective or contraindicated: consider pressors

12. medications

A. ASA 325 mg PO q d (unless hemorrhagic stroke proven or suspected)

B. stool softener

13. see following sections for discussion of anticoagulation (page 1020), steroids (page 1020), and mannitol (page 1020)


HTN may actually be needed to maintain CBF in the face of elevated ICP, and it usually resolves spontaneously. Therefore treat HTN cautiously and slowly to avoid rapid reduction and overshooting the target. Avoid treating mild HTN. Indications to treat HTN emergently include:

1. acute LV failure (rare)

2. acute aortic dissection (rare)

3. acute hypertensive renal failure (rare)

4. neurologic complications of HTN

A. hypertensive encephalopathy

B. converting a massive pale (ischemic) infarct into a hemorrhagic infarct

C. patients with ICH (some HTN is needed to maintain CBF, see Initial management of ICHpage 1126)

Hypertension treatment algorithm (modified41)

Recommended lower limits for treatment endpoints are shown in Table 29-2.

1. If DBP > 140 (malignant hypertension): ≈ 20-30% reduction is desirable. Cardene infusion or IV labetalol are agents of choice; arterial-line monitor recommended; sympatholytics (e.g. trimethaphan) contraindicated (they reduce CBF)

2. SBP > 230 or DBP 120-140 x 20 mins: labetalol (unless contraindicated, see page 20): start at 10 mg slow IVP over 2 mins, then double q 10 min (20, 40, 80, then 160 mg slow IVP) until controlled or total of 300 mg given. Maintenance: effective dose (from above) q 6-8 hrs PRN SBP > 180 or DBP > 110

3. SBP 180-230 or DBP 105-120: defer emergency treatment unless there is evidence of LV failure or if readings persist x 60 mins

A. oral labetalol (unless contraindicated - see page 20) dosed as follows:

1. for SBP > 210 or DBP > 110: 300 mg PO BID

2. for SBP 180-210 or DBP 100-110: 200 mg PO BID

B. if labetalol contraindicated:

nifedipine start with 10 mg PO/SL, if still HTN after 1 hr, give 20 mg; then follow with 10-20 mg PO or SL q 6 hrs

C. if monotherapy fails, or labetalol contraindicated, try either:

• hydralazine (Apresoline®) 10 mg slow IVP q 6 hrs (SIDE EFFECTS: tachycardia, use with caution in ASHD)


• captopril (Capoten®) 6.25 mg, 12.5 mg or 25 mg PO q 8 hrs

4. SBP < 180 or DBP < 105: antihypertensive therapy usually not indicated

Table 29-2 Guidelines for lower limits of treatment endpoints for HTN in strokes


No prior history of HTN

Prior history of HTN

do not lower SBP below

160-170 mm Hg

180-185 mm Hg

do not lower DBP below

95-105 mm Hg

105-110 mm Hg


Heparin: A prospective trial45 administering continuous IV infusion of unfractionated heparin titrated to keep APTT 1.5-2.5 x control found no significant improvement in outcome46. The recurrent stroke rate in the 7 days following a stroke was only 0.6-2.2% per week4547. Effectiveness is unproven in strokes and TIAs except with cardiogenic brain embolism (see Cardiogenic brain embolismpage 1022). Anticoagulation may also be hazardous48, however the complication rate has not been assessed prospectively (small, nonrandomized studies have found symptomatic ICH in 1-8%, and other bleeding complications in 3-12%45). Conversion rate of pale → hemorrhagic stroke is 2-5% (dog studies suggest the risk is increased only when HTN not well controlled). Conclusion: the risk of heparin therapy for acute focal cerebral ischemia exceeds any proven benefit45, and is not justified in most cases (especially when used just to placate the frustrated clinician)4950. The American Heart Association has recommended: “Until more data are available, the use of heparin remains a matter of preference of the treating physician”45. A small but significant reduction in recurrent stroke has been shown with ASA.

Warfarin: High-intensity warfarin therapy has proven helpful for the antiphospholipid antibody syndrome (APLAS) (see page 1025).

For the rare indication for anticoagulation therapy:

1. first, R/O hemorrhage by CT before beginning therapy

2. ASA 325 mg PO q d in all patients with non-hemorrhagic stroke where anticoagulants or surgery not indicated

3. anticoagulants (heparin/warfarin):

A. indications (rare)

1. probably effective for cardiogenic emboli (see Cardiogenic brain embolism below)

2. shown ineffective for stroke in evolution (neuro deficit that begins, recurs, fluctuates, or worsens while patient in hospital), crescendo TIAA or completed stroke

3. unproven, but generally used for carotid dissection

B. contraindicated with large cardiac embolism, large stroke (risk of hemorrhagic conversion), pepticulcer disease that has bled in past 6 mos, uncontrolled severe HTN

C. start IV heparin and simultaneous warfarin (Coumadin®) (maintain heparin during first ≈ 3 days of warfarin because of initial hypercoagulability, see Anticoagulationpage 36 for target APTT and INR)

D. stop warfarin after 6 months (benefits decline, risks rise)


A. in 74 patients with recent TIAs, elevating PTT 1.5-2.5 x normal with heparin did not reduce recurrent TIAs nor strokes. Bleeding occurred in 9 (12.2%). Additional risk: hemorrhage from heparin induced thrombocytopenia51




1. steroid responsive vasculitis, e.g. giant cell arteritis (temporal arteritis)

2. cerebellar infarct/bleed with mass effect


1. indicated for cerebellar infarct/bleed, prior to surgery, or if mass effect

2. contraindicated in hypotension

3. initial dose: 50 to 100 gm IV over 20 minutes


Possible indications:

1. herniation from subdural hematoma

2. suboccipital craniectomy for progressive neurologic deterioration due to brainstem compression from cerebellar hemorrhage/infarction (see below)

3. decompressive craniectomy for malignant MCA territory stroke (see below)

4. carotid endarterectomy for high grade carotid stenosis ipsilateral to fluctuating neuro deficit (see Emergency carotid endarterectomypage 1156)


Relatively rare (seen on only 0.6% of all CTs obtained for any reason52). Cerebellar infarcts may be classified as involving the PICA distribution (cerebellar tonsil and/or inferior vermis), superior cerebellar artery distribution (superior hemisphere or superior vermis), or other indeterminate patterns53. 80% of patients developing signs of brainstem compression will die, usually within hours to days.

Early findings

In most cases the onset is sudden, without premonitory symptoms54. The first 12 hrs after onset were characterized by lack of progression. Early findings are due to the intrinsic cerebellar lesion (ischemic infarction or hemorrhage):

1. symptoms

A. dizziness or vertigo

B. nausea/vomiting

C. loss of balance, often with a fall and inability to get up

D. headache (infrequent in one series54)

2. signs

A. truncal and appendicular ataxia

B. nystagmus

C. dysarthria

Later findings

Patients with cerebellar infarction may subsequently develop increased pressure within the posterior fossa (due to cerebellar edema or mass effect from clot), with brainstem compression (particularly posterior pons). Clinical findings generally increase between 12-96 hrs following onset.

Surgical indications

Surgical decompression (see below) should probably be done as soon as any of the following signs developA if there is no response to medical therapy55. Findings proceed in the approximate following sequence if there is no intervention:

1. abducens (VI) nerve palsy

2. loss of ipsilateral gaze (compression of VI nucleus and lateral gaze center)

3. peripheral facial nerve paresis (compression of facial colliculus)

4. confusion and somnolence (may be partly due to developing hydrocephalus)

5. Babinski sign

6. hemiparesis

7. lethargy

8. small but reactive pupils

9. coma

10. posturing→ flaccidity

11. ataxic respirations


A. it is important to recognize a lateral medullary syndrome (LMS) (see page 1028) which may often accompany a cerebellar infarct. With LMS, the signs are usually present from the onset (dysphagia, dysarthria, Horner’s syndrome, ipsilateral facial numbness, crossed sensory loss…), and are not accompanied by a change in sensorium. There is no place for surgical decompression in LMS since it represents primary brainstem ischemia and not compression


Imaging studies

CT scan: may be normal very early in these patients. There may be subtle findings of a tight posterior fossa: compression or obliteration of basal cisterns or 4th ventricle.

MRI: (including DWI) more sensitive for ischemia, especially in the posterior fossa.

Suboccipital craniectomy for cerebellar infarction

Unlike the situation with supra tentorial masses causing herniation, there are several reports of patients in deep coma from direct brainstem compression who were operated upon quickly who made useful recovery55-57. Guidelines for patients with cerebellar hemorrhage appear on page 1130.

The operation of choice is a suboccipital decompression to include enlargement of the foramen magnum. The dura is then opened and the infarcted cerebellar tissue usually exudes “like toothpaste” and is easily aspirated. Avoid using ventricular drainage alone as this may cause upward cerebellar herniation (see page 285) and does not relieve the direct brainstem compression. Malignant middle cerebral artery territory infarction

A distinct syndrome that occurs in up to 10% of stroke patients5859, which carries a mortality of up to 80% (mostly due to severe postischemic cerebral edema → increased ICP → herniation)59.

Patients usually present with findings of severe hemispheric stroke (hemiplegia, forced eye and head deviation) often with CT findings of major infarct within the first 12 hours. Most develop drowsiness shortly after admission. There is progressive deterioration during the first 2 days, and subsequent transtentorial herniation usually within 2-4 days of stroke. Fatalities are often associated with: severe drowsiness, dense hemiplegia, age > 45-50 yrs60, early parenchymal hypodensity involving > 50% of the MCA distribution on CT scan61, midline shift > 8-10 mm, early sulci effacement and hyperdense artery sign60 (see page 1013) in MCA.

Neurosurgeons may become involved in caring for these patients because aggressive therapies in these patients may reduce morbidity and mortality. Options include:

1. conventional measures to control ICP (with or without ICP monitor): mortality is still high, and elevated ICP is not a common cause of initial deterioration

2. hemicraniectomy (decompressive craniectomy): see below

3.  to date, the following treatments have not improved outcome: agents to lyse clot, hyperventilation, mannitol, or barbiturate coma

Hemicraniectomy for malignant MCA territory infarction

May reduce mortality to as low as 32% in nondominant hemisphere strokes62 (37% in all comers63) with surprising reduction of hemiplegia, and in dominant hemisphere strokes, with only mild-moderate aphasia (better results occur with early surgery, especially if surgery is performed before any changes associated with herniation occur). Meta-analysis64 of 3 randomized controlled trials found that hemicraniectomy within 48 hours after stroke onset resulted in decreased mortality and increased the number of patients with a favorable functional outcome.

Indications: No firm indications. Guidelines:

1. age < 70 years

2. more strongly considered in nondominant hemisphere (usually right)

3. clinical & CT evidence of acute, complete ICA or MCA infarcts and direct signs of impending or complete severe hemispheric brain swelling (severe post-admission neurologic deterioration is the usual event that triggers surgical intervention)

Technique: see page 165.

29.2.5. Cardiogenic brain embolism

About one stroke in six is cardioembolic. Emboli may be composed of fibrin-rich thrombi (e.g. mural thrombi due to segmental myocardial hypokinesis following MI or ventricular aneurysm), platelets (e.g. nonbacterial thrombotic endocarditis), calcified material (e.g. in aortic stenosis), or tumor particles (e.g. atrial myxoma).

Following acute myocardial infarction (AMI): 2.5% of patients will have a stroke within 1-2 weeks of an AMI (the period when most emboli occur). The risk is higher with anterior wall MI (≈ 6%) vs. inferior wall MI (≈ 1%).

Atrial fibrillation (A-fib): Nonrheumatic patients with a-fib have a 3-5 fold increased risk of stroke65, with a 4.5% rate of stroke per year without treatment66. The incidence of a-fib in the U.S. is 2.2 million. About 75% of strokes in patients with A-fib are due to left atrial thrombi67. Independent risk factors for stroke in patients with A-fib are: advanced age, prior embolism (stroke or TIA), HTN, DM, and echocardiographic evidence of left atrial enlargement or left ventricular dysfunction65.

The CHADS2 scoring system for patients with a-fib has been widely validated68 and is shown in Table 29-3. The points are totalled and risk assessment is shown in Table 29-4. For patients with a CHADS2 score ≥ 2, warfarin therapy was significantly protective for out-of-hospital death or hospitalization for stroke, MI or hemorrhage (CI = 0.61-0.91)69.

Prosthetic heart valves: Patients with mechanical prosthetic heart valves on long-term anticoagulation have an embolism rate of 3%/year for mitral and 1.5%/year for aortic valves. With bioprosthetic heart valves and no anticoagulation the risk is 2-4%/year.

Paradoxical embolism: Paradoxical embolism can occur with a patent foramen ovale which is present in 10-18% of the general population, but in up to 56% of young adults with unexplained stroke70.

Endocarditis: Blood cultures and TEE help evaluate.

Table 29-3 CHADS2 scoring items



CHF (any history)


HTN (prior history)


Age > 75 yrs


Diabetes mellitus


Secondary prevention: in patients with prior ischemic stroke or TIA; most also include systemic embolic events


Table 29-4 Risk based on CHADS2 score

CHADS 2 score

Annual stroke risk (%/year)
















No specific neurologic features can distinguish these patients. The diagnosis is suggested in imaging studies showing multiple intracranial ischemic strokes in different arterial distributions, the differential diagnosis includes: vasculitis, intracranial atherosclerosis (focal plaques, more common in Asian populations that consume Western diets), and intravascular lymphomatosis.

The diagnosis of cardiogenic brain embolism (CBE) as a cause of a stroke relies on demonstrating a potential cardiac source, the absence of cerebrovascular disease, and non-lacunar stroke.

Large areas of hemorrhagic transformation within an ischemic infarct may be more indicative of CBE due to thrombolysis of the clot and reperfusion of infarcted brain with subsequent hemorrhagic conversion. Hemorrhagic transformation most often occurs within 48 hrs of a CBE stroke, and is more common with larger strokes.


Most centers rely on echocardiography (without transesophageal ability). Using restricted criteria (i.e. excluding mitral valve prolapse), about 10% of patients with ischemic stroke will have potential cardiac source detected by echo, and most of these patients have other manifestations of cardiac disease. In stroke patients without clinical heart disease, only 1.5% will have a positive echo; the yield is higher in younger patients without cerebrovascular disease71.

EKG may detect atrial fibrillation which may be seen in 6-24% of ischemic strokes, and may be associated with a 5-fold increased risk of stroke (see below).


CBE is essentially the only condition for which anticoagulation has been shown to significantly reduce the rate of further strokes.

One must balance the risk of recurrent emboli (12% of patients with a cardioembolic stroke will have a second embolic stroke within 2 weeks) against that of converting a pale infarct into a hemorrhagic one. No study has shown a clear benefit of early anticoagulation.

Recommendations for anticoagulation:

1. if anticoagulation is to be used, it should not be instituted within the first 48 hrs of a probable CBE stroke

2. CT should be obtained after 48 hrs following a CBE stroke and before starting anticoagulation (to R/O hemorrhage)

3. anticoagulation should not be used in the face of large infarcts

4. start heparin and warfarin simultaneously. Continue heparin for 3 days into warfarin therapy (see Anticoagulationpage 36)

5. optimal range of oral anticoagulation to minimize subsequent embolism and/or hemorrhage has not been determined, but pending further data, an INR of 2-3 appears satisfactory

6. patients with asymptomatic A-fib have 66-86% reduction in stroke risk with warfarin (Coumadin®)6572. ASA is only about half as effective, but may be sufficient for those without associated risk factors (listed on page 1022)65

29.3. Stroke in young adults

Only 3% of ischemic strokes occur in patients < 40 yrs age73. Over 10% of ischemic strokes occur in patients ≤ 55 yrs74. Incidence: 10 per 100,000 persons age 35-44 yrs7573 per 100,000 for age < 55 yrs74.


The differential diagnosis is lengthy73, with trauma being the most common cause of strokes (22%) in patients under 45 yrs76. Most of the rest are covered by the small number of etiologies listed below (excludes: trauma, post-op stroke, SAH, and intracerebral hemorrhage).

1. atherosclerosis: 20% (all 18 patients in one series had either ID-DM, or were males > 35 yrs with ≥ 1 risk factors (see below), most had TIAs earlier)

2. embolism with recognized source: 20%

A. cardiac origin is the most common (see Cardiogenic brain embolism above), most have previously known cardiac disease:

1. rheumatic heart disease

2. prosthetic valve

3. endocarditis

4. mitral valve prolapse (MVP): present in 5-10% of young adults, in 20-40% of young adults with stroke (although one series found MVP in only 2% of stroke in young adults75)

5. A-fib

6. left-atrial myxoma

B. fat embolism syndrome: neurologic manifestation is usually global neurologic dysfunction

C. paradoxical embolism: ASD, pulmonary AVM including Osler-Weber-Rendu syndrome, patent foramen ovale (see Cardiogenic brain embolism above)

D. amniotic fluid embolism: may occur typically in the post-partum period

3. vasculopathy: 10%

A. inflammatory

1. Takayasu’s

2. infective: TB, syphilis, ophthalmic zoster

3. amphetamine abuse

4. herpes zoster ophthalmicus (HZO): usually presents with delayed contralateral hemiplegia with a mean of ≈ 8 weeks following HZO77

5. mucormycosis: a nasal and orbital fungal infection primarily in diabetics and immunocompromised patients that causes an arteritis which may thrombose the orbital veins and ICA or ACA. Produces proptosis, ocular palsy, and hemiplegia (see page 836)

6. associated with systemic disease

a. SLE (lupus) (also see below under Coagulopathy)

b. arteritis (especially periarteritis nodosa, see page 77): when confined to CNS is usually multifocal and progressive, but may mimic stroke early

c. multiple sclerosis (MS)

d. cancer

e. rheumatoid arthritis

B. non-inflammatory

1. fibromuscular dysplasia: see page 79

2. carotid or vertebral artery dissections (including posttraumatic)

3. moyamoya disease: see page 1170

4. homocystinuria: a genetic defect in methionine metabolism that produces intimal thickening and fibrosis in almost all vessels with associated thromboembolic events (arterial and venous, including dural venous sinuses). Estimated risk of stroke is 10-16%. Patients have a Marfan syndrome-like physical appearance, malar blotches, mental retardation, and elevated levels of urinary homocysteine

5. pseudoxanthoma elasticum

4. coagulopathy: 10%. The following are associated with hypercoagulable states

A. SLE: lupus anticoagulant → prolonged PTT incompletely corrects with 50/50 mix. Collagen vascular disease only rarely presents initially with stroke

B. polycythemia or thrombocytosis

C. sickle cell disease

D. TTP (thrombotic thrombocytopenic purpura)

E. antithrombin III deficiency (controversial - not seen in large series of young adults with stroke)

F. protein C or protein S deficiency (familial): protein C attenuates hemostatic reactions, homozygous deficiency is fatal in the neonatal period. Heterozygous deficiency is associated with thrombotic strokes. A rare complication during initial therapy with warfarin is a drop in protein C before other coagulation factors resulting in a hypercoagulable state

G. antiphospholipid-antibody syndrome (APLAS)7879: causes venous and/or arterial thrombosis. The two best known antiphospholipid-antibodies are anticardiolipin antibodies (ACLA), and lupus anticoagulant (LAC). Once they become symptomatic, treatment is high-intensity warfarin therapy to an INR ≥ 380. There is a dramatic increase in thrombotic events after discontinuing warfarin. Aspirin is useless

H. following use of the drug 3,4-methylenedioxymethamphetamine (MDMA, known on the street as ecstasy)81, possibly independent of the hypercoagulable state that occurs with hyperthermia when insufficient fluids are consumed in conjunction with use of the drug

5. peripartum: 5% (usually within 2 wks of parturition)

6. miscellaneous causes: 35%

A. uncertain etiology

B. oral contraceptives (BCP): associated with ninefold increased risk for stroke, many with prior migraine history

C. venous thrombosis (including dural sinus thrombosis): incidence may be increased with use of BCP

D. migraine 82: widely accepted, but difficult to assess objectively (incidence of stroke in these patients may be same as general population). Rare. Usually occurs in women, with a benign long-term course; recurs in < 3%. Possible mechanisms include: vasospasm, platelet dysfunction and arteriopathy83. strokes often occur during a migrainous attack84 or shortly thereafter

E. cocaine abuse85: stroke may result from vasoconstriction, or from HTN in the presence of aneurysms or AVMs (frank vasculitis occurs86 but is rare with cocaine, unlike amphetamines); strokes with alkaloidal cocaine (“crack”) are ≈ equally divided between ischemic and hemorrhagic

F. posterior reversible encephalopathy syndrome (PRES)see page 73


In a retrospective “neighborhood control” study of 201 Australian patients aged 15-55 (mean = 45.5) with first-time strokes, the following risk factors were identified74:

1. diabetes: odds ratio = 12

2. HTN: odds ratio = 6.8

3. current cigarette smoking: odds ratio = 2.5

4. long-term heavy alcohol consumption: odds ratio = 15 (heavy alcohol ingestion within 24 hrs preceding the stroke was not a risk factor)


1. history & physical exam directed at uncovering systemic disease (see above) and modifiable risk factors (see above)

2. cardiology work-up including EKG and echocardiogram

3. bloodwork (include as appropriate):

A. routine: electrolytes, CBC, platelet count and/or function, ESR (elevation may suggest SLE, arteritis, atrial myxoma… but a normal ESR does not rule-out vasculitis), PT/PTT, VDRL (should be obtained in all young adults with stroke), fasting lipid profile

B. for unexplained stroke: ANA, antithrombin III, protein C, protein S, homocysteine, factor V Leiden, PPD, sickle-cell screen, toxicology screen (blood and urine, to R/O drugs such as cocaine), SPEP, lupus anticoagulant, serum amino acid, tissue plasminogen-activator and - inhibitor

4. miscellaneous tests: U/A, CXR, CSF exam when indicated

5. cerebral angiography: not always necessary for patients with obvious systemic disease or strong evidence for cardiac embolism; may occasionally diagnose cerebral embolism if performed within 48 hrs of ictus

29.4. Lacunar strokes

Small infarcts in deep noncortical cerebrum or brain-stem (see Table 29-5) resulting from occlusion of penetrating branches of cerebral arteries. Size of infarcts ranges from 3-20 mm (CT detects larger ones; better sensitivity in white matter).

Small (3-7 mm) lacunes may be due to lipohyalinosis (vasculopathy due to HTN) of arteries < 200 microns (may also be cause of many ICHs); this vasculopathy is indicative of small vessel disease, unlikely to be prevented by carotid endarterectomy.

Clinically, diagnosis virtually excluded by: aphasia, apractagnosia, sensorimotor stroke, monoplegia, homonymous hemianopsia (HH), severe isolated memory impairment, stupor, coma, LOC, or seizures.

L’etat lacunaire: multiple lacunes → chronic progressive neuro decline with one or more episodes of hemiparesis; results in invalidism, dysarthria, small-step gait (marche á petits pas), imbalance, incontinence, pseudobulbar signs, dementia. Many signs and symptoms are possibly due to NPH (unrecognized originally).

Table 29-5 Typical locations for lacunar strokes (in descending frequency)

• putamen

• caudate

• thalamus

• pons

• internal capsule (IC)

• convolutional white matter


Major syndromes (see reference87 for others):

1. pure sensory stroke or TIA: (the most common lacunar manifestation) usually isolated unilateral numbness of face, arm, and leg. Only 10% of TIA go on to stroke. Lacune in sensory (posteroventral) thalamus → CT detection is poor. Dejerine-Roussy = rare thalamic pain syndrome that may develop late

2. pure motor hemiparesis (PMH): (2nd most common lacunar manifestation) pure unilateral motor deficit of face, arm and leg without sensory deficit, HH, etc.. Lacune in posterior limb of IC, or in lower basis pontis where corticospinal (CS) tracts coalesce, or rarely in mid-cerebral peduncle

3. ataxic hemiparesis: contralateral PMH + cerebellar ataxia of affected limbs (if they can move). Lacune in basis pontis at junction of upper third and lower two thirds → dysarthria, nystagmus and unidirectional toppling possible. Differential severity in face, arm and leg possible because CS fibers dispersed by nuclei pontis (unlike compact pyramids and peduncle)

A. variant: dysarthria-clumsy hand syndrome: lesion in same location or genu of IC. May be mimicked by a cortical infarct, but latter will have numb lips

4. PMH sparing the face: lacune in medullary pyramid; at onset, there may be vertigo and nystagmus (approaching lateral medullary syndrome)

A. variant: thalamic dementia: central region of one thalamus + adjacent subthalamus → abulia, memory impairment + partial Horner’s (miosis + anhidrosis)

5. mesencephalothalamic syndrome: “top o’ the basilar syndrome”. Usually caused by embolus. Infarct typically butterfly shaped & bilateral involving rostral brainstem and cerebral hemisphere regions fed by the distal basilar artery. Clinical: III palsy, Parinaud’s syndrome & abulia, may have amnesia, hallucinations and somnolence, usually without significant motor dysfunction

6. Weber’s syndrome: Cr. N. III palsy with contralateral PMH (no sensory loss). Usually due to occlusion of interpeduncular branches of basilar artery → central midbrain infarction, disrupting cerebral peduncle and issuing fibers of III. May also be due to aneurysm of basilar bifurcation or BA-SCA junction

7. PMH with crossed VI palsy: lacune in paramedian inferior pons

8. cerebellar ataxia with crossed III palsy (Claude syndrome): lacune in dentatorubral tract (superior cerebellar peduncle)

9. hemiballism: classically, infarct or hemorrhage in subthalamic semilunar nucleus of Luys

10. lateral medullary syndrome: see below

11. locked-in syndrome: bilateral PMH from infarct at IC, pons, pyramid or (rarely) cerebral peduncles

29.5. Collateral circulation


The effects of ICA stenosis/occlusion may be ameliorated by collateral blood flow. Potential alternate routes for blood to reach brain tissue include:

1. flow through the circle of Willis

A. from contralateral ICA through anterior communicating a.

B. from forward flow through the ipsilateral posterior communicating a.

2. retrograde flow through ophthalmic a. parasitizing blood from both ECAs via:

A. facial a. → angular a. → dorsal nasal a. & medial palpebral a.

B. maxillary a.

1. middle meningeal a. → lacrimal a.

2. vidian a. (a. of the pterygoid canal)

C. transverse facial a. → lateral palpebral a.

D. superficial temporal a. → supraorbital a.

3. proximal maxillary a. → anterior tympanic a. → caroticotympanic branch of ICA

4. cortical-cortical anastomoses

5. dural-leptomeningeal anastomoses


Available collaterals depend on the site of occlusion.

Basilar artery occlusion. Collateral flow via:

1. posterior communicating aa.

2. anastomoses between SCA and PICA

Proximal vertebral artery (VA) occlusion. Collateral flow via:

1. ECA → occipital a. → muscular branches of VA → VA

2. thyrocervical trunk → ascending cervical a. → direct connection or spinal radicular aa. → VA

3. contralateral VA and/or ascending cervical a. via spinal radicular branches and anterior spinal artery

29.6. “Occlusion” syndromes

See Figure 5-15page 96 for the distribution territories of the major cerebral arteries. Organized by vascular territoriesA

1. internal carotid artery: risk and extent of stroke is influenced by suddenness of occlusion, location of occlusion, and collateral circulation (see above)

A. statistics:

1. acute ICA occlusion (all comers): 26-49% risk of stroke88 (not all of these strokes are severe)

2. annual stroke risk in 1261 patients with symptomatic ICA occlusion: 7% overall, 5.9% ipsilateral to the occlusion (mean follow-up = 45.5 mos) (12 prospective studies89)

3. stroke risk is less when one includes asymptomatic ICA occlusions

4. in patients presenting with ICA territory stroke or TIA, complete ICA occlusion is found in 10-15%90

B. worst-case scenario of total ICA occlusion with no a-comm or p-comm flow and no collateral rescue: stroke in ACA and MCA territories

2. middle cerebral artery*


3. anterior cerebral artery: {CL} weakness of LE > UE

4. posterior cerebral artery

A. unilateral occipital lobe infarction → homonymous hemianopsia with macular sparing (visual cortex of the macula receives dual blood supply from MCA and PCA)

B. Balint syndrome

C. cortical blindness (Anton syndrome)

D. Weber syndrome

E. alexia without agraphia

F. thalamic pain syndrome (Dejerine-Roussy syndrome)

5. artery of Percheron (see page 104): bilateral thalamic and mesencephalic infarctions91

6. vertebral artery

A. medial medullary syndrome (Dejerine syndrome)

B. lateral medullary syndrome (Wallenberg syndrome): see below

7. basilar artery

8. AICA: lateral pontine syndrome (Marie-Foix syndrome)

9. PICA: sometimes lateral medullary (Wallenberg) syndrome: see below

10. SCA: infarction of superior cerebellar vermis and superior cerebellum

11. anterior spinal artery

12. recurrent medial striate artery (of Heubner): expressive aphasia + mild hemiparesis (UE > LE, proximal muscles weaker than distal)

13. anterior choroidal artery (AChA) syndrome: the complete triad consists of {CL} hemiplegia, hemihypesthesia and homonymous hemianopsia (mnemonic: 3 H’s), however, incomplete forms are more common92. Occlusion is usually due to small vessel disease and CT or MRI usually shows infarct in posterior limb of IC (just above temporal horn of lateral vent)93 and white matter posterior and lateral to it. Occlusion is usually tolerated fairly well, and ligation of this artery was actually utilized in treatment of Parkinsonism sometimes without ill effect94 (p 540) (see Surgical treatment of Parkinson’s diseasepage 532) but internal capsule infarct occurred in ≈ 15%.


A. to indicate lateralization of findings, {CL} = contralateral, {IL} = ipsilateral



AKA Wallenberg’s syndrome, AKA PICA syndrome. Classically attributed to PICA occlusion, but in 80-85% of cases the vertebral artery is also involved95. No cases have been reported arising from brainstem hemorrhage. Onset is usually acute. The findings are listed in Table 29-6 (NB: absence of pyramidal tract findings, and no change in sensorium).

image The location of the lesion and medullary structures are shown in Figure 29-1. This is essentially the only location where a lesion will produce sensory loss on one side of the face (ipsilateral to the lesion) and contralateral sensory loss in the body. All in the absence of pyramidal tract findings (i.e. overt weakness).

Table 29-6 Findings in lateral medullary syndrome94 (p 547)


Responsible lesion

• vertigo, N/V, nystagmus, diplopia, oscillopsia

vestibular nuclei & connections

• hiccups



Responsible lesion

• facial pain, paresthesias, & impaired sensation

descending tract and nucleus V over half of face

• ataxia of limbs

(restiform body?)

• Horner’s syndrome

descending sympathetic tract

• dysphagia, diminished gag, hoarseness

exiting fibers of IX & X

• numbness of arm, trunk, or leg

cuneate & gracile nuclei


Responsible lesion

• impaired pain & temp sense over half of body

spinothalamic tract


Figure 29-1 Typical lesion in lateral medullary syndrome (indicated as shaded area)

These patients sometimes develop severe cerebellar swelling that responds to neurosurgical decompression (the tissue aspirates easily) (see page 1022).

In a patient presenting with LMS, one needs to rule-out vertebral dissection (see page 1163) since this would be treated with heparin. MRI including fat-suppressed T1WI and MRA would detect dissection in most cases.

Prognosis: 12% of 43 patients died during the acute phase from respiratory and cardiovascular complications and 2 new posterior-fossa strokes occurred96. Recurrent vertebrobasilar territory stroke rate was 1.9% per year96.

29.7. Miscellaneous stroke


An ischemic infarction in a territory located at the periphery of two bordering arterial distributions due to a disturbance in flow in one or both of the arteries.


AKA emotionalism or emotional lability97. Usually consists of uncontrollable fits of crying or laughter in response to minor events. Generally without emotional content. Described with a variety of lesions in the cortex, diencephalon, and brainstem, but usually involving systems controlling motor function (pyramidal or extrapyramidal fibers) and an interruption of a control system purportedly located at the base of the brainstem. May respond to SSRI therapy (e.g. paroxetine)92.

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