New England Medical Center Posterior

Circulation Registry
Louis R. Caplan, MD, Robert J. Wityk, MD, Thomas A. Glass, PhD, Jorge Tapia, MD, Ladislav Pazdera, MD,
Hui-Meng Chang, MD, Phillip Teal, MD, John F. Dashe, MD, Claudia J. Chaves, MD, Joan C. Breen, MD,
Kostas Vemmos, MD, Pierre Amarenco, MD, Barbara Tettenborn, MD, Megan Leary, MD, Conrad Estol, MD,
L. Dana Dewitt, MD, and Michael S. Pessin, MD

Among 407 New England Medical Center Posterior Circulation registry patients, 59% had strokes without transient
ischemic attacks (TIAs), 24% had TIAs then strokes, and 16% had only TIAs. Embolism was the commonest stroke
mechanism (40% of patients including 24% cardiac origin, 14% intraarterial, 2% cardiac and arterial sources). In 32%
large artery occlusive lesions caused hemodynamic brain ischemia. Infarcts most often included the distal posterior
circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes); the proximal (medulla and
posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Severe
occlusive lesions (>50% stenosis) involved more than one large artery in 148 patients; 134 had one artery site involved
unilaterally or bilaterally. The commonest occlusive sites were: extracranial vertebral artery (52 patients, 15 bilateral)
intracranial vertebral artery (40 patients, 12 bilateral), basilar artery (46 patients). Intraarterial embolism was the com-
monest mechanism of brain infarction in patients with vertebral artery occlusive disease. Thirty-day mortality was 3.6%.
Embolic mechanism, distal territory location, and basilar artery occlusive disease carried the poorest prognosis. The best
outcome was in patients who had multiple arterial occlusive sites; they had position-sensitive TIAs during months to
years.
Ann Neurol 2004;56:389 –398

Clinical information about management of patients at the New England Medical Center, we thoroughly
with posterior circulation ischemia has lagged behind evaluated all posterior circulation ischemia patients us-
that for anterior circulation ischemia.1–3 Posterior cir- ing brain imaging and vascular studies—at first angiog-
culation stroke often has been attributed to hemody- raphy, and later magnetic resonance angiography
namically significant vertebral (VA), basilar artery (MRA), extracranial and transcranial ultrasound—and
(BA), and penetrating artery disease, whereas anterior appropriate cardiac and hematological investigations.
circulation ischemia most often is attributed to embo- We collected the data in a prospective computerized
lism from the heart or extracranial internal carotid ar- registry. The 407 New England Medical Center Poste-
teries (ICAs) and penetrating artery disease.2,3 Patients rior Circulation Registry (NEMC-PCR) patients serve
with carotid territory ischemia usually have brain im- as the database for this and other reports.2–11,53
aging and cardiac and ICA evaluations, whereas pa-
tients with vertebrobasilar territory ischemia seldom
have extensive cardiac or vascular investigations. Be- Subjects and Methods
cause of these different clinical practices, much more is The NEMC-PCR had three major inclusion criteria (1) all
patients were examined by stroke specialists (L.R.C., M.S.P.,
known about anterior circulation than about posterior
or L.D.D.); 2) patients had posterior circulation transient
circulation disease. ischemic attacks (TIAs) or strokes within the prior 6 months;
Before the mid-1980s, posterior circulation brain 3) investigations must have been adequate. All clinical data
and vascular imaging required catheter angiography and neuroimages were reviewed by the senior clinicians, of-
and computed tomography (CT). Precise definition of ten in a conference where all were present. All 407 cases were
brain lesions was not possible during life before mag- re-reviewed at least twice to ensure that data entered and
netic resonance imaging (MRI). From 1988 to 1996, diagnoses were complete and accurate.

From the Cerebrovascular Disease sections of the New England Published online Aug 31, 2004, in Wiley InterScience
Medical Center and the Beth Israel Deaconess Medical Center, Bos- (www.interscience.wiley.com). DOI: 10.1002/ana.20204
ton, MA.
Address correspondence to Dr Caplan, Palmer 127, West Campus,
Received May 5, 2003, and in revised form Feb 6 and May 26,
Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Bos-
2004. Accepted for publication May 26, 2004
ton, MA 02215. E-mail: lcaplan@bidmc.harvard.edu
This article includes appendices available via the internet at http://
www.interscience.wiley.com/jpages/0364-5134/suppmat

© 2004 American Neurological Association 389

Published by Wiley-Liss, Inc., through Wiley Subscription Services
 We used standardized criteria to classify stroke mecha- Cardiac disease was common. Coronary artery dis-
nisms (see Appendix A). Brain lesions were categorized as ease was present in 143 patients (35%). Among 231
involving proximal, middle, and distal intracranial posterior registry patients who had thorough cardiac evaluations,
circulation territories (Fig 1). Brain imaging was performed
147 (64%) had cardiac abnormalities. We did not rou-
on all patients with more than 80% having MRI. Vascular
imaging also was performed for all patients, with 80% hav- tinely investigate the aorta as a potential donor embolic
ing contrast catheter angiography. A severe occlusive lesion source, so that aortic-source embolism is undoubtedly
was defined as greater than 50% stenosis of an intracranial underestimated (see Appendix B).
artery or of the extracranial vertebral artery. Echocardiogra-
phy and heart rhythm monitoring were performed when
clinically indicated.
Distribution of Infarcts
Results Territorial infarcts were present in 339 (83%) patients
and 8 others had signs localizable to one intracranial
Clinical Features
territory. Among 347 patients with localizable posterior
In the NEMC-PCR, there were 256 men (63%) and
151 women (37%) with an average age of 60.5 years circulation infarcts, the distribution of brain locations
(Appendix Figure 1). There were 343 (84%) white pa- is displayed in Figures 2 and 3. The distal territory was
tients; nonwhites included 39 (9.5%) Asian origin, 18 most often involved, either as an isolated infarct or in
(4%) black, and 7 (2%) Hispanic patients. Stroke combination with other territory infarcts (Appendix
without TIAs developed in 240 patients (59%); 4 pa- C). Among patients with more than one territory in-
tients (1%) had strokes followed by TIAs; 63 patients volved, the middle and distal (34 patients) and the
(16%) had only TIAs, whereas 98 (24%) had TIAs be- proximal and distal (31 patients) territories were in-
fore stroke. volved most often.

Fig 1. Anatomy of the vertebrobasilar circulation with proximal, middle, and distal brainstem territories. (From Chaves CJ, Caplan
LR, Chung CS, et al. Cerebellar infarcts in the New England Medical Center Posterior Circulation Stroke Registry. Neurology
1994;44:1385–1390).

390 Annals of Neurology Vol 56 No 3 September 2004

Cause of Stroke often caused middle territory infarcts and spread or
Table 1 records the frequency of the various stroke embolization to the distal territory. Some patients with
mechanisms, with all potential mechanisms listed as a ECVA occlusive disease had emboli to the ipsilateral
range of frequencies. Embolism was the commonest ICVA causing proximal territory ischemia, which then
stroke mechanism accounting for 40 to 54% of cases. embolized to recipient arteries in the distal territory.
Cardiac-origin embolism accounted for 24 to 33% of The distribution of large artery hemodynamic-
strokes, whereas artery-to-artery embolism accounted related infarcts was even, reflecting almost equal in-
for 14 to 18%. volvement of the ICVAs and the BA and frequent in-
Approximately half of the proximal territory infarcts volvement of multiple intracranial arteries.
are caused by cardiac origin and artery-to-artery emboli
arising from the extracranial vertebral arteries (ECVAs),
Vascular Occlusive Lesions
whereas the other half are explained by hypoperfusion
Table 2 lists occlusive lesions showing greater than
related to intracranial vertebral artery (ICVA) occlusive
50% stenosis. The most common occlusive lesions in-
disease.6 Middle territory infarcts are explained by oc-
volved the VAOs and ICVAs, often bilaterally. A strik-
clusive lesions of the BA or its branches. Most distal ter-
ing and unexpected finding was the prevalence of ex-
ritory infarcts are attributable to cardiogenic and artery-
tensive occlusive disease. Single arteries were involved
to-artery embolism (donor sites mainly the ECVAs and
in 134 patients; 148 patients had multiple occlusive
ICVAs), whereas most of the remainder are related to
lesions (84 patients had 2 lesions, 53 had 3, and 11
penetrating artery disease (Appendix Figure 2).
patients had 4 or more occlusive large artery lesions;
Cardiogenic embolism caused predominantly distal
Appendix D).
only or distal included infarcts; infarcts limited to or
including the proximal and middle territories were
much less common. Patients with posterior cerebral ar- EXTRACRANIAL VERTEBRAL ARTERY. Occlusive lesions
tery (PCA), superior cerebellar artery, and top-of-the were often present at or near the ECVA origins. VAO
BA infarcts had a very high likelihood of cardiac or stenosis (⬎50%) was found in 131 patients, bilateral in
artery-to-artery embolism. 29 (Appendix E). In six, the lesions were dissections
Artery-to-artery embolism caused more even distri- and the remainder were atherosclerotic. ECVA lesions
bution of infarction. ICVA occlusive disease caused in- cause infarction primarily because of artery-to-artery
farction locally (proximal territory) and embolizes to embolism.9,11 The commonest recipient sites were the
recipient distal territory arteries. BA occlusive disease ipsilateral ICVAs causing proximal territory infarcts

Fig 2. New England Medical Center Posterior Circulation Registry brain infarct locations.

Caplan et al: Posterior Circulation Registry 391

Fig 3. Distribution of brain infarcts based upon brainstem territory. (A) Proximal territory; (B) middle territory; (C) distal terri-
tory.

392 Annals of Neurology Vol 56 No 3 September 2004

Table 1. Stroke Mechanisms in the NEMC-PCR

Stroke Mechanism Single Most Likely Mechanism All Possible Mechanisms

Large artery (hemodynamic) 132 (32%) 132–141 (32–35%)

Embolism 162 (40%) 162–219 (40–54%)
Cardiac-origin 99 (24%) 99–134 (24–33%)
Artery-to-artery 55 (14%) 55–74 (14–18%)
Cardiac ⫹ artery-to-artery 8 (2%) 8–11 (2–3%)
Branch artery (BrA-P ⫹ BrA-C) 58 (14%) 58–68 (14–17%)
Migraine 13 (3%) 13–18 (3–4%)
Other 42 (10%) 42–55 (10–14%)
NEMC-PCR ⫽ New England Medical Center Posterior Circulation Registry; BrA-P ⫽ branch artery–penetrating; BrA-C ⫽ branch artery–
circumferential

and the rostral BA causing distal territory infarcts (Ap- cholesterol, coronary artery disease, and smoked ciga-
pendix Figure 3). rettes (Appendix G).53 Nearly all had atherosclerotic
Only 13 patients had a hemodynamic mechanism of lesions. Most infarcts were in the middle intracranial
ischemia. Twelve of the 13 patients had severe bilateral territory in patients with lesions limited to the BA and
VA occlusive disease, 6 patients had severe bilateral when other arteries also were compromised. The distal
ECVA disease, and 6 had severe ICVA disease con- territory often was infarcted along with the middle ter-
tralateral to severe unilateral ECVA disease. TIAs were ritory indicating spread of disease to the rostral BA and
multiple and recurred during 1 week to several its distal branches or embolism to these branches (Ap-
months. Dizziness, often accompanied by veering to pendix Figure 5).
one side and gait ataxia, visual blurring, perioral pares-
thesias, and diplopia, were the commonest TIA symp- PENETRATING AND BRANCH ARTERY DISEASE. In this
toms. category, brain infarcts are limited to the distribution
of single branch penetrating arteries, clinical symptoms
INTRACRANIAL VERTEBRAL ARTERY DISEASE. Occlusive and signs are explained by involvement of this region,
lesions of greater than 50% stenosis were present in and vascular imaging shows no important compromise
132 patients, bilateral in 36 patients (Appendix F). of the parent artery feeding the involved branch. Using
Risk factors were particularly prevalent in patients with these strict criteria, we found that 14% of patients had
bilateral ICVA disease in whom 76% were hyperten- infarcts due to penetrating or branch artery disease. We
sive, 52% had elevated cholesterol, 36% had diabetes, cannot be sure that some patients did not have small
and 36% smoked cigarettes. Proximal territory infarcts emboli that blocked branches (Appendix Figure 6).
in patients with atherosclerotic ICVA disease most of-
ten were lateral medullary, whereas infarcts limited to POSTERIOR CEREBRAL ARTERY TERRITORY INFARCTS.
the PICA cerebellum most often were attributed to Most PCA territory infarcts were embolic. This finding
cardiac-origin embolism and artery-to-artery embolism corroborates prior reports.3,10 Most patients had car-
from the ECVAs (Appendix Figure 4). diac or ECVA, ICVA, or BA disease that was the likely
source of emboli to the PCA. All patients with somato-
BASILAR ARTERY DISEASE. Among 109 patients with sensory findings had lateral thalamic infarction or PCA
BA occlusive disease (⬎50% stenosis), 2 of 3 were hy- occlusion before the thalamogeniculate pedicle.5 Motor
pertensive, and approximately 1 of 3 had diabetes, high signs, usually slight and contralateral, were present in
29% and 25% had cognitive and/or behavioral abnor-
Table 2. Vascular Lesions with ⬎50% Luminal Stenosis malities.10 In only seven patients could we be confi-
dent that the PCA occlusive lesion represented in situ
Artery N atherostenosis rather than embolic occlusion. Four
PCA territory infarcts were migrainous.
Innominate 2
Subclavian 5
Vertebral artery origin 131 (29bilateral) Outcomes
Intracranial vertebral artery 132 (36bilateral) Patients with cardiac-origin embolism had more poor
Basilar artery 109 outcomes (death or severe disability) compared with
Posterior cerebral artery 38 (4 bilateral) patients with other stroke mechanisms. The relative
Posterior inferior cerebellar artery 14 risk of poor outcome in cardiogenic embolism patients
Anterior inferior cerebellar artery 2
Superior cerebellar artery 10 was 1.89 compared with artery-to-artery embolism (rel-
ative risk of 0.82). Patients with large artery hemody-

Caplan et al: Posterior Circulation Registry 393

namic and those with penetrating artery disease had with anterior circulation ischemia collected at NEMC
relatively low risk of poor outcome (0.59 and 0.58 rel- during the same time, we found there were more car-
ative risks, respectively).4 Patients with infarcts limited diogenic emboli (38 vs 24%) and fewer large artery
to the proximal territory had better outcomes than pa- occlusive lesions (9 vs 32%) in anterior circulation pa-
tients with infarcts limited to other territories.4 tients, but the frequency of intraarterial embolism and
The frequency of poor outcome (mortality or severe penetrating artery lesions were similar. Comparison
disability at 30 days after hospital discharge) was higher with other stroke registries is given in Table 3 (Appen-
among patients with BA disease than with ECVA and dix H).
ICVA disease. Thirty percent had poor outcomes yield- Differences in stroke mechanisms are explainable
ing a relative risk of poor outcome of 3.64 (95% con- considering anatomical and blood flow differences. Ap-
fidence interval [CI], 1.9 –7.0).4 The worst outcomes proximately two fifths of brain blood flow goes into
occurred among patients with embolism to the BA; each ICA and only one fifth into the vertebrobasilar
58% of these had major deficits. Patients with disease arteries.12 By chance alone, one fifth of cardiac-origin
limited to the ECVA had better outcomes than those emboli should go to the posterior circulation. The pos-
with ICVA and BA disease.4 They had a relative risk of terior circulation consists of relatively more brainstem
0.62 compared with all patients with poor outcomes and thalamic tissue supplied by penetrating arteries
(death or severe disability). compared with the anterior circulation. Relatively more
Mortality was highest among patients who had em- lacunes and branch territory infarcts are expected in
bolism to the distal territory arising from the ICVA; the posterior circulation. The data from the NEMC-
one fourth of these patients died. The mortality and PCR and other registries show that the frequencies of
morbidity in all other groups was low. At hospital dis- stroke mechanisms are more alike than dissimilar. His-
charge, one fourth of the patients had moderate or se- torical differences are explained by the phenomenon of
vere disability but one half had no disability. At self-fullfilling prophecy. Vertebrobasilar angiography
follow-up examinations 3 years or more after discharge, was considered dangerous and was performed only in
37% had no disability and 89% had no or only slight patients with severe brainstem signs. The nonstudy of
disability.7 Most surprising was the good outcomes in posterior circulation cases led to continuation of early
patients with bilateral ICVA disease. These patients diagnostic biases, whereas at the same time patients
with the most severe occlusive disease had the best out- with carotid territory ischemia were more thoroughly
comes, indicating the durability of collateral circula- investigated.
tion. At follow-up examination greater than 3 years af-
ter discharge, 33 of 41 patients with severe bilateral Concurrent Cardiac Disease
ICVA disease were still alive, among whom 32% had Cardiac and aortic lesions are well recognized and ac-
no disability and 76% had no or slight disability.8 cepted sources of embolism to anterior circulation in-
tracranial arteries. Coronary artery and ICA disease of-
Discussion ten coexist. Mortality in anterior circulation stroke
Stroke Mechanisms: Do Posterior and Anterior patients is often cardiac. However, it has not been cus-
Circulation Ischemia Patients Differ? tomary to examine the heart and aorta in vertebrobasi-
Modern investigations show that most anterior circula- lar disease patients.2,3 The NEMC-PCR confirms a
tion infarcts are attributable to embolism from the significant frequency of cardiac-origin embolism, poor
heart, aorta, and proximal arteries. Comparing outcome associated with cardiogenic embolism, and a
NEMC-PCR data with that from prospective patients relatively high occurrence rate of coexistent coronary

Table 3. Stroke Mechanisms in Registries That Compared Posterior and Anterior Circulations

NEMC P NEMC A LSR BSR ASR TOAST TOAST

Registry circ circ LSR Pcirc A circ BSR P circ A circ ASR P circ A circ P circ A circ

Years 1988–1996 1987–1995 1982–1987 1987–1994 1992–1997

N 407 516 233 609 251 710 259 568 180 1044
C emb 24% 38% 16% 19% 30% 41% 23% 45% 17% 21.5%
LA sten 32% 9% 16% 28% 15.5% 15% 16% 9.5% 14% 19%
LA no sten 14% 15% 26% 15% 19% 13%
Penetrating 14% 18% 16% 8% 7% 4% 23% 20% 24% 24%
artery
P circ ⫽ posterior circulation; A circ ⫽ anterior circulation; C Emb ⫽ cardioembolic; LA ⫽ large artery; Sten ⫽ stenosis; NEMC ⫽ New
England Medical Center; LSR ⫽ Lausanne Stroke Registry47; BSR ⫽ Besancon Stroke Registry48,49; ASR ⫽ Athens Stroke registry50;
TOAST ⫽ Trial of ORG 10172 in Acute Stroke Treatment.51,52

394 Annals of Neurology Vol 56 No 3 September 2004

artery disease and myocardial infarction. Cardiac and promised. When one ICVA was narrowed or occluded
aortic evaluation is just as important in posterior cir- by atherosclerosis, the contralateral VA was often hyp-
culation disease as it is in the anterior circulation. oplastic or narrowed extracranially or intracranially,
and the BA was also often severely compromised.
Posterior Circulation Territories and
Stroke Mechanisms Subclavian and Innominate Artery Disease Rarely
Dividing the posterior circulation into vascular supply Caused Posterior Circulation Infarcts
territories helps predict stroke mechanisms, arterial le- In 1961, Reivich and colleagues20 and Fisher21 de-
sions, and outcomes.2– 4 In the NEMC-PCR, distal ter- scribed the “subclavian steal syndrome.” Physicians
ritory lesions were most common. Lateral medullary were alerted and patients with the syndrome often had
infarction (proximal territory) is most often caused by subclavian artery surgery. Subsequent studies showed
atherosclerotic ICVA disease. Pontine infarction (mid- that most patients with subclavian artery disease are
dle territory) is most often related to BA or penetrating asymptomatic, even those with subclavian steal shown
artery disease. Isolated thalamic infarcts (distal terri- by ultrasound or vascular imaging.22,23 Two NEMC-
tory) are most often attributable to penetrating artery PCR patients had innominate artery stenosis and five
disease, whereas distal territory infarcts that include the had subclavian artery disease, but only one patient with
thalamus and PCA supplied regions are mostly caused isolated subclavian artery disease had posterior circula-
by cardiac origin and intraarterial embolism. tion ischemia attributable to the extracranial lesion.
Subclavian artery disease is an important marker of
Risk Factors atherosclerosis but a rare cause of posterior circulation
Hypertension was a prevalent risk factor being noted in infarction.
61% of patients. Diabetes mellitus was slightly more
common in patients with intracranial compared with The Importance of Extracranial Vertebral Artery
extracranial disease, whereas coronary and peripheral Disease as a Cause of Posterior Circulation Infarction
vascular disease more often were associated with ex- Fisher and colleagues concluded from their autopsy
tracranial disease. Prior studies showed that extracranial study that atherosclerosis affected neck and intracranial
ICA lesions are highly associated with white race, male posterior circulation arteries equally although extracra-
sex, hypertension, smoking, and coronary and periph- nial lesions were seldom symptomatic.24 They noted
eral artery occlusive disease.13–16 Studies of populations that proximal ECVA atherosclerotic lesions occasion-
of white and black patients confirmed that this pattern ally became ulcerated, and that three of their patients
was also true for VAO occlusive disease.17 NEMC- may have had artery-to-artery emboli arising from the
PCR patients with occlusive VAO disease were most ECVA. Fisher commented on the usual benignity of
often white and male and had risk factors similar to ECVA disease.25 The benignity of atherosclerotic VAO
ICA disease patients. Hypertension was more common lesions was attributed to (1) the capacity to develop
in patients with only ECVA disease compared with collateral reconstitution of the ECVAs; (2) the usual
those with intracranial disease. ICA and VAO occlusive presence of two viable arteries that join together in-
disease often coexist.18 Intracranial occlusive lesions are tracranially, so that if one became compromised, the
most common in blacks, individuals of Asian origin, contralateral artery could compensate adequately; and
and women.14,17,19 The NEMC-PCR includes more (3) the slow development of luminal compromise by
Asian patients, predominantly Chinese, than the Har- atherosclerotic plaques allowing time for collateral de-
vard and Lausanne Registries, and the Stroke Data velopment.
Bank (Appendix I). Artery-to-artery embolism from a VAO donor source
was also reported in small series of patients.26 –28 A key
Frequency of Various Vascular Lesions observation was reported by Pelouze who showed that
Necropsy studies of posterior circulation vascular le- a VAO specimen removed from a patient with repeated
sions differ for the patients studied and the focus of posterior circulation TIAs contained a typical ulcerated
interest. In the NEMC-PCR, the VAs were the com- plaque, similar to plaques found within ICA surgical
monest vessels involved and the ECVAs and ICVAs specimens.29 Caplan and colleagues reported 10 pa-
were involved with about the same frequency. When tients who had artery-to-artery embolism arising from
only single vascular regions were involved, the VAO occlusive VAO lesions; the commonest recipient site
was more often severely stenotic or occluded than other was the ICVA causing PICA cerebellar infarcts.30
vascular regions. BA disease was also very common. In the NEMC-PCR, VAO atherosclerosis was very
The most important and surprising finding was the fre- common. Infarcts in patients with VAO disease were
quency of multiple vascular involvement. Often ex- mostly attributable to artery-to-artery embolism arising
tracranial and intracranial arteries were narrowed. In from the ECVA. Extracranial aneurysms31 and dissec-
many patients, multiple intracranial arteries were com- tions9,32 are other potential sources of artery-to-artery

Caplan et al: Posterior Circulation Registry 395

emboli. Only two patients who most likely had artery- good outcome from emboli to the “top-of-the basilar”
to-artery emboli arising from the proximal ECVA also likely relates to passage of small emboli.
had potential cardiac embolic sources. Hypoperfusion
related to VAO occlusive lesions was usually transient Multiple Intracranial Large Artery Compromise
causing brief spells of dizziness, veering, visual blurring, This report documents the frequent coexistence of
and ataxia. Attacks were self-limited probably reflecting multiple arterial constrictive lesions, most often involv-
reconstitution of the ECVA distal to the occlusion. ing the ICVAs bilaterally, often with accompanying BA
and ECVA stenosis. TIAs dominated the clinical find-
ings. Few had severe strokes despite months or years of
Intracranial Vertebral Artery Disease
TIAs. The most frequent TIA components were dizzi-
There is general agreement that severe ICVA and BA
ness, faintness, visual blurring, and ataxia. Ischemic at-
occlusive lesions are not benign and frequently cause
tacks were usually multiple and brief and often were
strokes. The closer an artery is to the brain, the more
precipitated by rising from a supine or seated position,
likely that occlusion will lead to brain infarction. Few
prolonged standing, defecating, and new or increased
reports concern patients selected because they had
antihypertensive treatment. Despite severe vascular oc-
ICVA disease discovered by vascular imaging. In the
clusive disease, these patients had surprisingly good
NEMC-PCR, only one fifth of patients with severe
outcomes. Adequate collateral circulation developed
ICVA occlusive disease had infarcts limited to the
and stabilized. Patients with multiple occlusive vascular
proximal intracranial posterior circulation territory.
lesions might have been the basis of early reports of
Occlusive ICVA lesions predominantly involved the
“vertebrobasilar insufficiency” in patients in whom vas-
most distal portion of the artery, at or near the
cular lesions were not studied.36,37
ICVA-BA junction beyond the PICA and medullary
branches, explaining sparing of the proximal territory.
Penetrating Artery Disease
Emboli arising from the ECVA was a more common
The pathology within penetrating arteries consists of
cause of proximal territory infarction than intrinsic
lipohyalinotic disruption of the arterial lumen38 or ath-
ICVA disease. More common were emboli arising from
eromatous branch disease in which plaques within par-
the ICVA causing distal territory infarction. The com-
ent arteries obstruct the orifice of penetrating branch-
monest group of patients with ICVA disease, account-
es.39,40 Ischemia due to penetrating artery disease is
ing for more than half, had extensive atherosclerosis in
important to differentiate from large artery disease be-
multiple intracranial arteries. These patients with severe
cause causes, prognoses, and treatments are different.
multifocal disease most often had benign courses char-
In the NEMC-PCR, as in other reports, most branch
acterized by multiple TIAs but few serious strokes.
territory infarcts were located in the pons (middle in-
tracranial territory) and the thalamus (distal intracra-
Basilar Artery Disease nial territory). Paramedian pontine infarcts causing
BA occlusive disease has been considered a highly mor- pure motor hemiparesis or ataxic hemiparesis and lat-
tal condition since publication of the necropsy findings eral thalamic infarcts causing contralateral hemisensory
of Kubik and Adams.33 BA disease was associated with symptoms occasionally accompanied by contralateral
the poorest outcome among all NEMC-PCR vascular limb ataxia and extrapyramidal abnormalities were the
occlusive lesions, but outcomes were better than prior commonest syndromes. Occasional patients had mid-
reports. The case mix of our patients with BA disease brain41 or medullary42 branch territory infarcts.
likely included more patients with less severe ischemia
that in other reports. We evaluated more patients with Outcomes according to Mechanism and Location
minor posterior circulation ischemia using noninvasive NEMC-PCR 30-day mortality was very low, 3.6%4;
vascular and brain imaging than was possible in the 21% of patients died or had major disability. Nearly
past. Undoubtedly, this led to discovery of BA disease four fifths of patients had no or little disability. Verte-
in patients who would likely not have had catheter an- brobasilar territory disease has an undeserved reputa-
giography in the past so that BA disease would have tion for causing high rates of morbidity and mortality.
been missed. Prior series were biased toward including mostly pa-
Patients with BA disease mostly had infarcts involv- tients with severe neurological signs and did not in-
ing the paramedian pontine base sometimes extending clude the broad spectrum of posterior circulation isch-
into the paramedian tegmentum.53 These infarcts are emia patients. The NEMC-PCR may contain a referral
in the territory of the large median penetrators; flow in bias. Patients entering other hospitals in coma or with
these penetrators is most compromised by BA thrombi severe disabling deficits might not have been referred
and stenotic plaques. The distal BA is occasionally the to NEMC. The NEMC Stroke Center was well known
site of intrinsic atherosclerotic narrowing but more of- for interest in caring for patients with vertebrobasilar
ten distal occlusions are embolic.34,35 The relatively territory strokes, so that the case mix might be differ-

396 Annals of Neurology Vol 56 No 3 September 2004

ent from that in the community. We cannot determine 7. Muller-Kuppers M, Graf KJ, Pessin MS, et al. Intracranial ver-
whether treatment in the NEMC-PCR was responsible tebral artery disease in the New England Medical Center Pos-
terior Circulation Registry. Eur Neurol 1997;37:146 –156.
for the relatively good outcomes.
8. Shin H-K, Yoo K-M, Chang H-M, Caplan LR. Bilateral intra-
In the NEMC-PCR, cardioembolic stroke mecha- cranial vertebral artery disease in the New England Medical
nism increased the risk of poor outcome. Embolic Center Posterior Circulation Registry. Arch Neurol 1999;56:
mechanism conveyed similar higher risks in other stud- 1353–1358.
ies. Petty and colleagues reported Mayo Clinic data 9. Wityk RJ, Chang H-M, Rosengart A, et al. Proximal extracra-
that showed the following figures for mortality and se- nial vertebral artery disease in the New England Medical Center
Posterior Circulation Registry. Arch Neurol 1998;55:470 – 478.
vere disability (Rankin 4 and 5) at 90 days after stroke: 10. Yamamoto Y, Georgiadis AI, Chang H-M, Caplan LR. Poste-
cardioembolism 56.8%, atherosclerosis with stenosis rior cerebral artery territory infarcts in the New England Med-
32.4%, lacunar stroke 4.2% , and IUC 35.8%.43 ical Center Posterior Circulation Registry. Arch Neurol 1999;
In the NEMC-PCR, patients with distal intracranial 56:824 – 832.
territory ischemia had more poor outcomes compared 11. Caplan LR, Amarenco P, Rosengart A, et al. Embolism from
vertebral artery origin disease. Neurology 1992;42:1505–1512.
with patients with other territory lesions. Patients with
12. Boyajian RA, Schwend RB, Wolfe MM, et al. Measurement of
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398 Annals of Neurology Vol 56 No 3 September 2004