734

Intracerebral Haemorrhage And Angiographic
Beading Following Ingestion Of Catecholaminergics
A.J.

STOESSL, M.D.,

G.B.

YOUNG, M.D.,

AND T.E.

FEASBY,

M.D.

SUMMARY We report two cases of serious intracerebral haemorrhage occurring in young women
following their first use of oral medications containing catecholaminergic agents (phenylpropanolamine in
combination with ephedrine or pseudoephedrine). Both women were previously well, and there was no
evidence for systemic vasculitis, coagulopathy, aneurysm or arteriovenous malformation. Angiography in
both cases, performed approximately forty hours following drug ingestion, revealed the beading pattern
typical of that seen in previously reported cases of presumed amphetamine-induced "vasculitis." We believe
that this arteriographic abnormality is non-specific and should not be construed as necessarily indicative of
arteritis.
Stroke Vol 16. No 4. 1985
THE INGESTION OF AMPHETAMINES by either
oral or parenteral route has been associated with intracranial haemorrhage and with the angiographic appearance of "beading." 1 "' Following the demonstration
by Citron et al4 of a syndrome in drug abusers that is
clinically and pathologically reminiscent of polyarteritis nodosa, it has been usual to attribute such occurrences to drug-induced cerebral vasculitis. In many
instances, the pathological support for this contention
has been weak. We report two cases seen recently in
which haemorrhage following ingestion of amphetamine congeners could not reasonably be attributed to
an inflammatory angiopathy.

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Case Histories
Patient 1
This 20 year old woman, previously in good health,
ingested two capsules of a purported amphetamine
look-alike twelve hours prior to her admission to hospital. There was no history of previous drug intake.
Two hours later, she experienced severe headache and
nausea, and after another hour, she developed right
hemiparesis and aphasia, followed by progressive
drowsiness. On admission, her blood pressure was
130/70 and the general physical examination was normal. She was drowsy and mute, and her eyes opened in
response to voice. She had a right homonymous hemianopsia, deviation of her eyes to the left and a dense
right spastic hemiparesis.
Normal laboratory investigations included complete
blood count (CBC), sedimentation rate, prothrombin
time (PT), partial thromboplastin time (PTT), antinuclear antibody (ANA), rheumatoid factor, hepatitis
B surface antigen, C3, C4, CH50, Clq binding, urinary vanillylmandelic acid (VMA) metanephrine and
free catecholamines. Blood and urinary toxic screens
were negative. A computerized tomographic (CT)
scan (fig. 1) revealed a left external capsular haemorrhage with shift of the midline structures. Cerebral
angiography (fig. 2), performed 36 hours following
drug ingestion, showed alternating narrowing and dilaFrom the Department of Clinical Neurological Sciences. University
of Western Ontario, London. Ontario. Canada.
Address correspondence to: G.B. Young. M.D.. Department of
Clinical Neurological Sciences. Victoria Hospital. 375 South Street.
London. Ontario. Canada N6A-4G5.
Received October 26. 1984: accepted January 10. 1985.

tation of several branches of the middle cerebral artery.
Analysis of the capsules demonstrated the presence of
ephedrine, phenylpropanolamine and caffeine.
She was managed conservatively and made a slow
but incomplete recovery. Three years later, she had
minimal word-finding difficulty, normal visual fields
and was fully ambulatory with a moderately severe
spastic hemiparesis.
Patient 2
This 23 year old woman was previously in good
health. Fifteen hours prior to admission, she ingested a
single "black beauty" as a "wake-up" pill. She had not
used these or similar agents in the past. One hour later,
she experienced sudden headache, nausea and vomiting, and this was followed within an hour by aphasia
and right hemiparesis. On admission, her BP was
130/90 and the general physical examination was unremarkable. She was obtunded and had a non-fluent
aphasia, a right homonymous hemianopsia and a dense
spastic right hemiparesis.
Normal laboratory values included CBC, sedimentation ratio, PT, PTT, Bleeding Time, immunoglobulins, ANA, rheumatoid factor and VDRL. A CT scan
(fig. 3), showed a left ganglionic haemorrhage with
mass effect. Angiography (fig. 4), performed approximately 40 hours after drug ingestion, revealed an avascular mass and patchy areas of spasm in branches of
the middle and anterior cerebral arteries. Analysis of
the ingested capsules revealed caffeine, phenylpropanolamine, psudoephedrine and a barbiturate.
This woman was also managed conservatively and
made a modest improvement. One year later, her language was normal, but she still had a moderate right
arm paresis.
Discussion
The chronic abuse of drugs has been clearly associated with the development of a systemic necrotizing
vasculitis that may be difficult to distinguish from polyarteritis nodosa, and amphetamines have been identified as common agents among the multitude of preparations ingested.4 Intracranial haemorrhage and the
cerebral angiographic appearance of alternating narrowing and dilatation of vessels ("beading") have been
reported in association with the chronic use of amphet-

CATECHOLAMINERGIC INGESTION/5w«^/ et al

735

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FIGURE 2 Left Carotid Angiogram (patient I) reveals alternating narrowing and dilatation of several middle cerebral artery branches.
FIGURE 1 CT Scan (patient 1) showing a large left external
capsular haemorrhage with mass effect.

amines and have been attributed to cerebral vasculitis.1-3
More recently, intracranial haemorrhage has been
seen following the use of phenylpropanolamine'16 and
as a complication of pseudoephedrine overdose.7 Reports have also implicated the chronic abuse of nasal
decongestant sprays8 and abuse of ephedrine.9 These
drugs are used as decongestants, stimulants and appetite suppressants, and are readily available without prescription. Angiography has again demonstrated beading;7"9 in one case, this was seen following single-time
use. 7
The appearance of beading is non-specific, and has
been noted in meningitis and encephalitis,10 and following aneurysmal subarachnoid haemorrhage." In
adult rhesus monkeys, transient angiographic changes
were seen within ten minutes of intravenous administration of methamphetamine.12 The abnormalities reverted to normal by 24 hours, but were again noted at
one week. Further analysis suggests, however, that
such animal studies are not truly representative of the
human disorder, in that all of the monkeys experienced
significant hypertension, and there was a high incidence of cardiac dysrhythmia, focal cerebral ischaemia and diffuse cerebral edema, as well as gross subarachnoid haemorrhage. Angiographic evidence of

FIGURE 3 CT Scan (patient 2): left ganglionic haemorrhage
with mass effect.

736

STROKE

VOL 16, No 4, JULY-AUGUST

1985

In our own cases, the early appearance of haemorrhage and associated angiographic changes following
single use of oral catecholaminergics in systemically
healthy young women does not support the diagnosis
of an immunopathologic illness such as vasculitis. The
beading is more likely to result from catecholaminemediated vasospasm in part directly related to the
drugs, and possibly also secondary to the haemorrhage, which may have been due to transient hypertension.
We feel that the angiographic appearance of beading
associated with ingestion of catecholaminergics is
non-specific and subject to over-interpretation. Furthermore, we share the concerns expressed by others6' l6 ' l7 regarding the potential risks of such readily
and often legally available agents.
Editor's Note:
This article was guest edited by J.P. Mohr in accordance with Stroke policy.
References

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I

FIGURE 4

Left Carotid Angiogram (patient 2): patchy areas

of spasm in anterior and middle cerebral artery branches.

spasm has also been seen acutely following the intracisternal injection of norepinephrine.'3
Although extracerebral angiitis has been well demonstrated in drug abusers,4 14 few attempts have been
made to correlate cerebral arteriographic changes with
histopathology. In 16 amphetamine-related haemorrhages reviewed by Delaney and Estes,3 10 patients
underwent angiography and beading was demonstrated
in only 4. Of these, pathological study was lacking in
3, and necrotizing cerebral angiitis was demonstrated
in the remaining patient." All 4 patients had subarachnoid haemorrhage.
In the case of ephedrine-related haemorrhage recently reported by Wooten and colleagues,9 beading
was not seen on the initial angiogram, but was found atfollowup study. The second angiogram was, however,
complicated by symptoms of ischaemia in the distribution of the injected artery (left carotid), and the beading may therefore have been related to contrast-induced spasm.

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