The capsular warning syndrome:
Pathogenesis and clinical features
G.A. Donnan, MD, FRACP; H.M. O’Malley, RN; L. Quang, Grad. Dip. Sci.; S. Hurley, PhD;
and P.F. Bladin, BSc, MD, FRACP

Article abstract-Transient ischemic attacks (TIAS)are not homogeneous and may consist of subsets with mechanisms as varied as their stroke counterparts. We describe a form of TIA in 50 patients where crescendo episodes of
ischemia were restricted to the region of the internal capsule, usually causing symptoms affecting face, arm, and leg.
These patients composed 4.5% of a consecutive series of patients admitted with TIAs over a 15-year period and 33% of
all TIAs classified as subcortical. We believe that the ischemia was most often due to hemodynamic phenomena in diseased, single, small penetrating vessels. When cerebral infarction developed, it was usually lacunar and involved a single penetrating vessel, although occasionally striatocapsular or anterior choroidal artery territory infarction occurred.
There was no evidence of artery-to-artery or heart-to-artery embolism. Resistance to various forms of therapy, including hemodiluting, anticoagulant, and thrombolytic agents, was common. Because of dramatic and easily recognizable
clinical presentation, apparent specific pathophysiologic mechanism, and the development of early capsular stroke in a
high proportion of cases (42%), we have termed this the “capsular warning syndrome.”
NEUROLOGY 1993;43:957-962

Transient i s c h e m i c a t t a c k s (TIAs) h a v e been
defined as brief, focal neurologic events of 24 hours’
duration, o r less. Only a limited classification of
TIAs into subtypes has occurred so far; most clinic i a n s recognize TIAs in the c a r o t i d and v e r t e brobasilar territories, but little further refinement
of classification exists. More importantly, it has
been difficult to relate the clinical features of TIA
t o p a t h o g e n e s i s . H o w e v e r , it is r e a s o n a b l e t o
assume that the pathogeneses of TIAs are as varied
as their stroke counterparts a n d m a y reflect similar mechanisms. We described earlier a particular
pattern of TIA consisting of repeated bursts of focal
neurologic events due to ischemia in t h e region of
the internal capsule.’-4 This form of TIA is relatively easy to recognize and is pathophysiologically distinct. In many instances, the patients were examined during the attack, thus improving the reliabili t y of o u r observations. T h e ischemia is probably
due t o i n situ s m a l l p e n e t r a t i n g vessel disease,
w i t h n o evidence t o s u g g e s t a r t e r y - t o - a r t e r y o r
h e a r t - t o - a r t e r y e m b o l i . We h a v e t e r m e d this
sequence the “capsular warning syndrome” because
of i t s dramatic clinical presentation and high probability of early capsular stroke. In this study, we
expand on o u r original observations in a series of
50 consecutive patients.

Methods. Patients with clinical features suggesting
transient cerebral ischemia in the region of the internal
capsule have been prospectively studied during Stroke
~~

Unit data collection from 1977 to 1991. For the present
study, all patients with TIA were also retrospectively
categorized into groups depending on the presumed site
of transient cerebral ischemia based on the following criteria:
1. Probably subcortical. Motor, sensory, or sensorimotor symptoms affecting face, arm, and leg simultaneously, with no cortical signs such as neglect, dyspraxia, or
dysphasia; involvement of face and arm or arm and leg
was accepted if also: (a)the patient was examined during
the event, (b) a fresh infarct was seen in subcortex appropriate to clinical findings, or (c) ischemia was in the left
hemisphere and patient spoke with no evidence of dysphasia (dysarthria may be present in cases where
ischemia affects either hemisphere).
2. Probably cortical. Typically, the presence of cortical
symptoms such as dysphasia, neglect, or dyspraxia with
or without hemiparesis involving face, arm, and leg, or:
( a ) brachiofacial weakness with or without sensory
involvement, (b) monoparesis with or without cortical
signs, (c) patient examined during the event and cortical
signs documented, or (d) amaurosis fugax occurred within the study period in the same vascular territory.
3. Probably uertebrobasilar. Evidence of brainstem
involvement by documentation of more than one of the
symptoms of diplopia, visual blurring bilaterally,
dysarthria, alternating hemiparesis, crossed hemisensory loss, vertigo, nausea, vomiting, or examination during
the event confirming these findings.
4. Retinal. Obscuration of vision in one eye, typically
vertically like a “blind” and sudden and complete with no
directional onset or with a more generalized blurring.
5. Uncertain. Hemiparesis involving arm and leg during which no cortical symptoms were documented or noted

~

~~

~

~

From the Department of Neurology, Austin Hospital, Melbourne, Australia.
Received May 1, 1992. Accepted for publication in final form September 4, 1992.
Address correspondence and reprint requests to Dr. Geoffrey A. Donnan, Department of Neurology, Austin Hospital, Heidelberg, Vic. 3084, Melbourne,
Australia.

May 1993 NEUROLOGY 43 957

by the patient. This involved mainly cases of ischemia in
the right hemisphere or cases of left-hemisphere ischemia
where the patient did not speak (right handed) or the
nature of the speech disturbance was unclear.
Patients were recognized a s having t h e capsular
warning syndrome if the region of ischemia was classified as being subcortical and if repetitive neurologic
events occurred a t presentation. The time frame during
which these events occurred was usually quite brief
(most often within 72 hours), but for the purposes of this
study those in whom three or more events occurred within 24 hours were identified to provide a benchmark for
study entry. Hypertension was defined as two readings of
diastolic blood pressure >95 mm Hg after the cerebral
event had settled and antihypertensive treatment was
then needed, or antihypertensive treatment was already
being taken prior to admission. CTs were performed
within 48 hours of admission and in most cases repeated
between days 7 and 14 if the initial scan was negative.
Carotid angiography was performed in patients where
minimal or no clinical deficit was present and where
information gained was likely to contribute to clinical
management. Treatment was not systematized in any
way, and selection of treatment type was based on the
individual preference of the managing neurologist.

Results. During the period of study from 1977 t o
1992, 4,950 patients were a d m i t t e d t o the Stroke
Unit and 1,093 (22%)w e r e classified as h a v i n g
TIAs. One h u n d r e d fifty-three (14%)of the TIAs
were classified as probably subcortical, 429 (39%)as
probably cortical, 114 (10%)as p r o b a b l y v e r t e brobasilar, and 124 (11%)as retinal; in 273 (25%)
patients t h e location of ischemia w a s u n c e r t a i n .
Fifty-seven of these had features consistent with the
capsular warning syndrome, and 50 (33%of patients
with subcortical TIAs and 4.5%of all TIAs) of these
had three or more events within 24 hours. Of the 50
patients, 31 were m e n and 19 were women; m e a n
age was 63 years (range, 26 to 84). Twenty-seven of
the patients (54%)with capsular warning syndrome
were examined during the event, thus increasing
the precision of clinical localization of the ischemic
event to the region of the internal capsule.
Representative case reports. Patient 1. A 52-year-old,
right-handed chauffeur with a history of untreated hypertension developed sudden onset of left face, arm, and leg
weakness while driving on July 4, 1977. A dull, generalized headache had preceded the onset of symptoms.
Complete recovery occurred in approximately 5 minutes,
but two more episodes quickly followed lasting 45 minutes
and 30 minutes. He drove to the emergency department
where examination was normal. An intravenous dextran
plasma expander was commenced and he was admitted to
a general medical ward. Another episode occurred the next
day. Blood pressure was 160/90, pulse regular, and he was
started on a diuretic. Four-vessel arteriography was normal. A further episode occurred 3 days later, four episodes
the day after, and an unknown number on the following
day, with complete recovery between each event. A psychiatrist was consulted, who felt that these might have been
functional. On July 11, 1977, further events occurred during continuous EEG monitoring. After forward head flexion the patient stated, “I can feel it coming on,” and over
the next 30 seconds he developed a dense pure motor
958 NEUROLOGY 43 May 1993

Figure 1. CT of a 52-year-old man (pt 1) with repetitive
episodes of left hemiplegia that culminated in lacunar
stroke 1 1 days later. Scan shows a right internal-capsule
lacune.
hemiplegia of the left face, arm, and leg. His speech was
slurred, there was no visual or sensory neglect or eye deviation, and he was able to recognize objects placed in his
left hand. Left toe was extensor. The hemiplegia lasted for
approximately 10 minutes, during which the EEG was
normal. Recovery occurred over 30 seconds. The next day,
a slight left facial paresis and extensor left plantar
response were noted; 3 days later he developed a left pure
motor hemiparesis (215 face, 215 arm, and 315 leg). A head
CT was normal. He returned to work in October 1977 in a
clerical capacity. CT was performed a year later and
showed a lacune in the posterior limb of the capsule in the
right paraventricular region (figure 1).He later developed
ischemic heart disease and hypercholesterolemia but had
no further neurologic events. He suffered a presumed cardiac death at a railway station in 1983.

Patient 2. A 56-year-old, right-handed woman with a
history of untreated hypertension was seated a t her
kitchen table a t 9:30 AM on October 20, 1983, when she
noted the sudden onset of weakness and numbness of her
right face, arm, and leg. She slipped to the floor and lay
there for some time before crawling to the telephone. Her
speech was slurred but there was no malapropriation of
words. Seventy-five minutes later, a rapid resolution
occurred over seconds. At 11:30 AM t h e symptoms
returned, but this time they only lasted for 45 minutes. A
15-minute episode occurred a t 12:30 PM. A t 1:30 PM,
while in the emergency department lying on a couch, she
again developed a dense right hemiplegia involving face,
arm, and leg. She was dysarthric, and a complete motor
and sensory loss involving right face, arm, and leg was
present; reflexes were symmetric, but right plantar was
extensor. Sensory signs cleared over the next hour but
the hemiplegia remained. No visual or sensory inattention was present. General examination revealed no cardiac abnormalities and no cervical bruits. Blood pressure
was 2401130, pulse 82 beats per minute and regular.
Hypertension was treated with a n oral beta blocker.

-

10
9.
8 .

Frequency

5 *

3

4

5

6

7

8

9

1 0 1 1 1 2 1 3

Event number

Figure 3. Frequency of neurologic events among 50 cases
of the capsular warning syndrome.

Table. The distribution of motor and sensory
symptoms in 50 cases of the capsular warning
syndrome
Symptoms

Figure 2. CT of a 56-year-old woman (pt 2) who presented
with repetitive episodes of right hemiparesis and
developed a capsular stroke. Scan shows an infarct
involving more than one penetrator in the territory of the
left anterior choroidal artery.

EEG, hematologic study, and liver and renal functions
were all normal. CT showed an infarct involving more
than one penetrating vessel in the territory of the left
anterior choroidal artery (figure 2). She later was noted
to be acromegalic, and a pituitary tumor was removed
transphenoidally on November 17, 1983. Postoperatively,
she became dysphasic for about 18 hours. Carotid
angiography revealed a 30% stenosis of the left internal
carotid artery, and subsequent endarterectomy revealed
a calcific plaque extending up the anteromedial wall for 2
cm. Some pits within the plaque were seen but no evidence of hemorrhage or ulceration was present. Modest
gains ensued over the next 2 years, but functional weakness persisted. No further neurologic events occurred.
Patient 3. A 75-year-old widow awoke a t 4:OO AM and
found that she was unable to get out of bed because of
inability to move her left side. Her speech was slurred.
After about 15 minutes the weakness suddenly resolved.
She got up and went to the kitchen where again leftsided weakness developed, this time including her face,
which resolved in 10 minutes. Two more brief episodes
(minutes) occurred prior to her arrival at the hospital
that morning. History included coronary artery bypass
grafting, and a t the time of coronary angiography a left
carotid stenosis (uncertain degree) was noted. There was
no history of hypertension, and she was a nonsmoker. A
left cervical bruit was heard a t the angle of the jaw, and
blood pressure was 160/90 with pulse 70 beats per
minute and regular. Neurologic examination was normal,
but when she was stood to examine her gait a t about
midday she again developed weakness involving her left
arm (2/5) and leg (2/5) over a period of seconds. No sensory change was experienced, reflexes were symmetric, but
left plantar was extensor. There was no visual or sensory
neglect. Intravenous plasma expander was commenced.
Blood pressure was 180/90 during this event. She had

No. of patients

Motor
Face/Arm/Leg
Face/Arm
M L e g

16
1
5

Sensory
Face/Arm/Leg
FaceIArm
A r d g

1
0
1

Sensoryhlotor
FaceIAdLeg
FaceIArm
M h g

14

2
9

DysarthriaMotorISens. Arm

1

Total

50

recovered except for mild left leg weakness the next day
Right carotid angiography was normal a s was CT.
During the same night she again developed dysarthria
and left-sided weakness. By morning she was unable to
move her left arm or leg and had a profound left facial
weakness with dysarthria. There were no sensory or cortical signs. CT performed 10 days later showed a right
striatocapsular infarct516(films since destroyed). EEG
showed increased slow activity over the right hemisphere, and neuropsychological examination did show
some visuospatial difficulties. She made a gradual recovery over the next few months.

C l i n i c a l features. The definition of this group
specifies at least three clinical e v e n t s within 24
hours, and the number of events ranged from three
to 13 (figure 3). Characteristically, the onset tended
t o occur over seconds; several patients described a
feeling of the weakness “coming on” rather than presenting abruptly (see patient 1). Pure motor hemiparesis was the most common presenting symptom
(table), although the onset w a s often accompanied
by sensory symptoms that usually cleared quickly
before the motor symptoms resolved.
May 1993 NEUROLOGY 43 959

14 1

12
10
8

Frequency

6
4

2

0

Figure 4. Duration of neurologic events among 50 cases of
the capsular warning syndrome.

The mean duration of events was quite brief at
6.1 minutes (figure 4) and ranged from 2 minutes
to 4 hours. The episodes were usually clustered
within a relatively narrow time frame, for example,
five episodes within 3 h o u r s i n one p a t i e n t ,
although the range of the completion of the burst of
clinical events was from 1 hour to several bursts
over 5 days. The maximum documented number of
events was 13, and this occurred over a 4-day period. However, often the events were so frequent and
close together that the exact count was lost by both
physician and patient. The presentation was so
spectacular in two patients with such sudden and
complete resolution, that prior t o neurologic consultation the symptoms were considered to be hysterical in nature. Headache was not a feature of the
presentation, although a small number complained
of mild cranial ache of a nonspecific nature.
Risk factors. Forty-two patients (84%)had either
preexisting hypertension or hypertension was diagnosed upon admission. Nineteen (38%) were current smokers, nine had a history of hyperlipidemia,
five were diabetic, 10 had a history of myocardial
infarction, one had valvular heart disease, and one
patient had atrial fibrillation.
CT. All patients had CTs at the time of initial
assessment. Twenty-five showed ipsilateral small
deep infarcts, and the remaining scans were normal. Seven patients had relevant infarcts on CT
but no fixed neurologic deficit. In 18 of 21 patients
with subsequent stroke either during inpatient
stay or prior t o admission, the side of the infarct
was confirmed as being in the clinically relevant
internal capsule. In 15 of the 18 patients with relevant infarcts, the infarct was in the territory of a
single small penetrating vessel (eg, patient l),in
two patients striatocapsular infarction was seen
(eg, patient 2), and in another, infarction in the territory of the anterior choroidal artery (patient 3).
Angiography I ultrasonography. Twenty-seven
patients underwent angiographic study, and six
had duplex ultrasound scanning of internal carotid
arteries. In 30, the study was normal or minimal
change was demonstrated at the origin of the ipsilateral internal carotid artery. Three patients had
significant change (50% stenosis in one and 20%
960 NEUROLOGY 43 May 1993

stenosis in two). One patient had high-grade stenosis of the ipsilateral middle cerebral artery.
Treatment. During the clinical episodes, plasma
expanders ( 10% dextrose in 500 ml over 1 hour and
then 500 ml over 6 hours in each 24 hours for the
next 72 hours) were used in 25 patients, but the
episodes continued. In eight of these, subsequent
stroke occurred (eg, patient 1). Three patients were
given intravenous heparin, one of whom developed
a stroke. Thirty-six patients were commenced on
aspirin and were taking this medication on discharge. Four patients were discharged on warfarin.
Carotid endarterectomy was performed in three
patients, but in no patient was active ulceration
with or without clot formation found.
Early prognosis. Twenty-one patients (42%) had
either developed a fixed deficit by the time they
arrived at the emergency department or went on to
develop stroke during their inpatient stay (mean
inpatient stay was 17 days; range, 3 to 54 days). Of
those patients with fixed deficit, 15 had pure motor
hemiparesis, one dysarthria and clumsy hand syndrome, and five sensorimotor stroke7; two patients
developed striatocapsular infarction and had a
hemiparesis with predominant arm weakness and
cortical signs typical of this s y n d r ~ m e ,and
~ . ~ one
had a pure motor hemiparesis with infarction in the
territory of the anterior choroidal artery (patient 2).

Discussion. We have outlined the clinical features
and pathogenesis of the capsular warning syndrome, a distinct form of TIA that may be clinically
located t o the region of the internal capsule and
which leads to early capsular infarction in a high
proportion of cases (42%).This expands upon our
earlier descriptions of this ~ o n d i t i o n land
- ~ other
studies of subcortical TI AS.^,^ While the majority of
the infarcts that developed following the burst of
clinical events were lacunar, this was not invariably so. Two patients developed striatocapsular
i n f a r c t i ~ n ,and
~ ? ~one developed infarction in the
region of the anterior choroidal artery territory.
While internal capsular infarction w a s the only
finding in those patients who developed permanent
deficits, it is possible that in some cases of the capsular warning syndrome the area of ischemia may
involve the pyramidal tracts below the capsule,
perhaps in the area of single penetrators from the
basilar artery. With the more widespread use of
MRI, the frequency with which this occurs may be
more clearly established. The pattern of frequent
clinical events suggesting incipient vessel occlusion
in other vascular territories has not yet been clearly defined.
The repetitive nature of clinical events leading
up to capsular infarction has been noted earlier by
both MarielO and Fisher and Curry.ll Marie stated,
“The multiplicity of episodes, with variable interval
between them, is an essential characteristic of lacunar degeneration. Of my 50 cases, 32 had two or
more previous episodes.” Fisher and Curry noted,
“In our experience, a burst of frequent hemiplegic

spells suggested the pure motor syndrome arising
more likely in the capsule than in the pons.” Similar
premonitory events were noted by Helgason et all2
in their series of patients with anterior choroidal
a r t e r y t e r r i t o r y infarction. Rothrock e t all3
described 47 patients with crescendo TIAs, nine of
whom had repetitive symptoms suggesting the capsular warning syndrome. In our experience, the
onset is not instantaneous, as in patient 2. More
often, the patient could feel “the weakness coming
on over a period of seconds,” and its resolution was
over a period of seconds or minutes.
The mechanism whereby such stereotypically
repeated events occur within such a brief period of
time is unclear. In general, it has been hypothesized t h a t clinical patterns of this type have a
hemodynamic basis. This is supported by the observation t h a t incipient occlusion of the internal
carotid artery may be accompanied by repetitive
events, although usually with associated cortical
signs.14 In two of the cases of lacunar infarction
reported by Waterson et
a hemodynamic basis
was postulated based on the finding of ipsilateral
internal carotid occlusion and the position of the
small infarcts in the borderzone between deep and
superficial penetrating arteries. These cases were
not preceded by the capsular warning syndrome.
We have not found any examples of ipsilateral
severe carotid occlusive disease in this condition.
Our own anecdotal experience would suggest that
embolic artery-to-artery phenomena cause events
more widely separated in time, and there was little
angiographic evidence to support an embolic mechanism in our patients. Another possible mechanism
would be artery-to-artery microemboli within the
penetrating vessels themselves, but for much the
same reasons cited above concerning the temporal
behavior of emboli in general, this seems less likely. Similarly, cardiac embolism seems unlikely in
view of the lack of cardiac abnormalities. The
brevity of duration of TIAs has been positively correlated with the degree of carotid artery stenosis in
two studies,16J7perhaps supporting the view that
hemodynamic events are of shorter duration than
embolic events from the heart allowed by more
open carotid systems. Could these events relate to
vasospasm? Friberg and 01sen18 recently ascribed
cerebrovascular instability, as documented by
intra-arterial xenon-133 cerebral blood flow studies, to vasospasm in several patients with TIA and
stroke, although perhaps on tenuous grounds given
that vasospasm was not demonstrated angiographically. Vasospasm of retinal vessels occurs during
episodes of amaurosis fugax when not in a migrainous settinglg and repetitive clinical events occasionally occur in hemiplegic migraine. In spite of this
indirect supporting evidence for this mechanism,
we feel that hemodynamic factors secondary t o
structural arterial change such as atheroma or
lipohyalinosis is the most likely mechanism in the
majority of our cases.
Given that hemodynamic phenomena within a

single penetrating vessel appears to be the most
likely mechanism of ischemia, how does this relate
to the underlying pathology? The earlier studies of
Fisher20-22
have shown that lacunar infarcts may be
caused by in situ disease of small penetrating vessels. This may include lipohyalinosis secondary to
the effects of hypertension, atheroma within the
penetrating vessel, or atheroma associated with a
larger parent vessel. This latter change may be
present in cases of middle cerebral artery stenosis,
as found in two of our patients. It appears most
likely that high-grade stenoses of penetrating vessels due to any of these pathologies may create the
hemodynamic environment for the clinical expression of the capsular warning syndrome.
In spite of various treatment modalities, including anticoagulants, plasma expanders, or aspirin, it
is uncertain as to whether these alter the natural
history of the syndrome. Anecdotal reports of failed
medical therapy (heparin) in progressing lacunar
stroke suggest that this form of cerebral infarction
may be therapeutically resistant,23 although the
complete recovery between episodes in cases of the
capsular warning syndrome may suggest a slightly
different situation than in progressing stroke per
se. Because of the repetitive nature of the events
and the relatively high incidence of subsequent
ischemic stroke, this form of TIA may be ideal to
formally test various therapies since relatively
small sample sizes would be required.

References
1. Donnan GA. A study of l a c u n a r infarction syndromes.
Melbourne, Australia: Melbourne University, 1980. Thesis.
2. Donnan GA, Tress BM, Bladin PF. A prospective study of
l a c u n a r i n f a r c t i o n u s i n g computerized tomography.
Neurology 1982;32:49-56.
3. Donnan GA, Bladin PF. The capsular warning syndrome:
repetitive hemiplegic events preceding capsular stroke
[abstract]. Stroke 1987;18:296.
4. Donnan GA, Bladin PF. Not all TIAs a r e equal [letter].
Neurology 1988;38:1659.
5. Bladin PF, Berkovic SF. Striatocapsular infarction: large
infarcts in the lenticulostriate arterial territory. Neurology
1984;34:1423-1430.
6 . Donnan GA, Bladin PF, Berkovic SF, Longley WA, Saling
MM. The stroke syndrome of striatocapsular infarction.
Brain 1991;114:51-70.
7. Fisher CM. Lacunar infarcts: a review. Cerebrovasc Dis
1991;1:311-320.
8. Hankey GJ, Warlow CP. Lacunar t r a n s i e n t ischaemic
attacks: a clinically useful concept? Lancet 1991;337:335338.
9. Kappelle L J , van Latum J C , Koudstaal PJ, van Gijn J .
Transient ischaemic a t t a c k s a n d small-vessel disease.
Lancet 1991;337:339-341.
10. Marie P. Des foyers lacunaires de desintegration. Rev Med
1901;21:281-289.
11. Fisher CM, Curry HB. Pure motor hemiplegia of vascular
origin. Arch Neurol 1965;13:30-44.
12. Helgason C, Wilbur A, Weiss A, Redmond KJ, Kingsbury
NA. Acute pseudobulbar mutism due to discrete bilateral
capsular infarction in the territory of the anterior choroidal
artery. Brain 1988;111:507-524.
13. Rothrock JF, Lyden PD, Yee J, Wiederholt WC. ‘Crescendo’
transient ischemic attacks: clinical and angiographic correlations. Neurology 1988;38:198-201.
14. Fisher CM. Occlusion of t h e internal carotid artery. Arch
May 1993 NEUROLOGY 43 961

Neural 1951;65:346-377.
15. Waterson JA. Brown MM. Butler P, Swash M. Small deep
cerebral infarcts associated with occlusive internal carotid
artery disease. Arch Neural 1990;47:953-957.
16. Pessin MS, Duncan GW, Mohr JP, Poskanzer DC. Clinical
and angiographic features of carotid transient ischaemic
attacks. N Engl J Med 1977;296:358-362.
17. Harrison MJG, Marshall J, Thomas DJ. Relevance of duration of transient ischemic attacks in carotid territory. Br
Med J 1978;1:1578-1579.
18. Friberg L, Olsen TS. Cerebrovascular instability in a subset
of patients with stroke and transient ischaemic attack. Arch
0-8

Neural 1991;48:1026-1031.
19. Burger SK, Saul RF, Selhorst JB, Thurston SE. Transient
monocular blindness caused by vasospasm. N Engl J Med
1991;325:870-873.
20. Fisher CM. The arterial lesions underlying lacunes. Acta
Neuropathol (Berl) 1969;12:1-15.
21. Fisher CM. Capsular infarcts: t h e underlying vascular
lesions. Arch Neural 1979;36:65-73.
22. Fisher CM, Caplan LR. Basilar artery branch occlusion-a
cause of pontine infarction. Neurology 1971;21:900-905.
23. Dobkin BH. Heparin for lacunar stroke i n progression.
Stroke 1983;14:421-423.
-8

Olfactory testing
differentiates between progressive
supranuclear palsy and idiopathic
Parkinson’s disease
R.L. Doty, PhD; L.I. Golbe, MD; D.A. McKeown, BA; M.B. Stern, MD; C.M. Lehrach, BS;
and D. Crawford, MS

Article abstract-Olfactory dysfunction occurs in most patients with idiopathic Parkinson’s disease (PD). In this
study, we sought t o determine whether such dysfunction is also present in progressive supranuclear palsy (PSP), a
condition which shares a number of motor symptoms with PD and is commonly misdiagnosed as PD. We administered
the University of Pennsylvania Smell Identification Test, a standardized test of odor identification ability, to 21 PSP
patients; 17 also received a forced-choice odor detection threshold test. We compared the olfactory test scores to those
obtained from PD patients and normal controls matched to the PSP patients on the basis of age, sex, and smoking
habits. Overall, the olfactory function of the PSP patients was markedly superior to that of the PD patients and did not
differ significantly from that of the normal controls. There was no association in either the PSP or PD patient groups
between (1)the olfactory test scores and ( 2 ) measures of motor symptom severity, disease stage, and medication usage.
These findings demonstrate that patients with PSP and PD differ markedly in their ability to smell and suggest that
olfactory testing may be useful in their differential diagnosis.
NEUROLOGY 1993;43:962-965

Progressive supranuclear palsy (PSP) accounts for
nearly 5% of patients who manifest parkinsonian
sympt0ms.l Although this syndrome is frequently
characterized by bradykinesia and rigidity early in
its progression, tremor is rarely present. The distinguishing feature of this disorder is vertical-gaze
paresis (especially downgaze paresis) which can be
overcome by the oculocephalic maneuver. Another
prominent feature of PSP is a slowing of thought

processes.2 Because this disorder shares a number
of motor symptoms with idiopathic Parkinson’s disease (PD), i t is commonly misdiagnosed a s PD.
Unlike PD, however, its parkinsonian features are
less responsive t o anti-PD medication^.^
Furthermore, PSP differs from PD in additional
neuronal loss within the basal ganglia, cerebellum,
and the upper brainstem4 and more severe frontal
lobe dy~function.~
A considerable body of evidence

From the Smell and Taste Center, Department of Otorhinolaryngology: Head and Neck Surgery (Dr. Doty, C.M. Lehrach, and D.A. McKeown), and the
Department of Neurology (Dr. Stern), School of Medicine, University of Pennsylvania, and the Graduate Hospital (Dr. Stern), Philadelphia, PA; and the
Department of Neurology Dr. Golbel, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ.
Supported by grant R 0 1 AG 08148 from the National Institute on Aging and grant PO1 DC 00161 from the National Institute on Deafness and Other
Communication Disorders.
Received July 8, 1992. Accepted for publication in final form September 30, 1992
Address correspondence and reprint requests to Dr. Richard L. Doty, Smell and Taste Center, 5 Ravdin Institute, Hospital of the University of
Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283.
962 NEUROLOGY 43 May 1993

The capsular warning syndrome: Pathogenesis and clinical features
G. A. Donnan, H. M. O'Malley, L. Quang, et al.
Neurology 1993;43;957
DOI 10.1212/WNL.43.5.957
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