Current Concepts of Cerebrovascular Disease — Stroke
Transient Global Amnesia
WILLIAM LOGAN, M . D . ,

AND D A V I D G.

TRANSIENT global amnesia (TGA) is a syndrome
occurring in the middle-aged or older patient, mani­
fested by the sudden transient loss of ability to lay
down new memories with associated mild to moderate
retrograde amnesia without other neurological signs.
Bender first described a patient with this syndrome in
1956, but it was Fisher and Adams in 1958 who de­
fined the clinical picture in a series of patients and
coined the term "transient global a m n e s i a . "
Since
that time more than 100 papers and case descriptions
have been published in an attempt to categorize this
puzzling e n t i t y .
The purpose of this review is to
examine the natural history, proposed pathogenesis,
and prognosis of this syndrome.
TGA is not a rare illness. Although reported infre­
quently, there are surely numerous cases which do not
come to medical attention, either because of its tran­
sient nature or its misdiagnosis. Most cases occur in
the sixth and seventh decades (age range 21 to 92
years). There is no apparent sex difference. The pa­
tients are generally in good health without significant
cardiac or cerebrovascular disease. At times the patient
notices the abrupt onset and a s k s , ' ' W h a t ' s wrong? I ' m
not thinking w e l l , " but more often, only a close ob­
server notes its manifestations. Pallor and anxiety are
occasionally seen, but other systemic and focal neuro­
logical signs are conspicuously absent. Most striking is
the patient's complete inability to learn new informa­
tion coupled with apparently intact immediate recall.
There is always some degree of retrograde amnesia
which tends to be maximum at the beginning of an
attack and rapidly recedes over time, leaving a short
period (usually hours) of total or near total amnesia.
Patients often repeat phrases over and over, such as,
" W h e r e am I, and what day is t o d a y ? " A typical
episode lasts minutes to hours but no longer than a day.
After recovery there is amnesia only for the involved
time of the attack. The patient is otherwise again nor­
mal.

SHERMAN,

M.D.

begin his chores. The temperature was 0°F. After feed­
ing the cattle, he drove the tractor to the barn where he
and his wife moved a large amount of hay. At about
10:00 AM she returned to the house and 15 minutes
later heard her husband drive the tractor to the front of
the house and leave it running. When she greeted him
at the doorway, he first asked what time it was, then
what day. He had no complaints at all, and his wife
noticed nothing abnormal. He was concerned as to the
whereabouts of the tractor and the necessity to move
the hay. She assured him that they had just finished
working with the hay and that the tractor was waiting
outside. Within two or three minutes he asked the same
questions again, and on three occasions he went to the
front window to view the tractor. Finally, he went out
and drove the tractor into the barn only to arrive back in
the house and ask her where the tractor was!
Throughout this time he had no complaints of weak­
ness, nor had his wife noticed convulsive movements,
agitated behavior, or loss of consciousness. As his
wife drove him to the emergency room at 12:30 P M , he
asked her what had become of his fingers on his left
hand, evidently not remembering that they had been
traumatically amputated by farm machinery four
months earlier. When they drove past his sister's
home, he was able to identify it correctly but could not
remember the names of several members of his wife's
family. On arrival at the emergency room 30 minutes
later, his physical examination was normal, and his
memory was beginning to return. A serum glucose was
normal, and he was discharged home. Since then his
only deficit is persistent, near total, amnesia for a
three-hour period from 9:30 to 12:30 that morning.
The above description is quite typical for the major­
ity of patients with T G A . TGA has been associated
with a number of other disorders including mi­
graine, intracerebral t u m o r , diazepam overdose,
cardiac arrhythmia, presumed embolism during coro­
nary angiography, cerebral i n f a r c t i o n ,
dissecting
aortic aneurysm, myxomatous degeneration of the
Numerous case histories have been recorded. Per­
mitral v a l v e , and polycythemia rubra v e r a . Precipi­
haps the most eloquent are those by Fisher and Ad­
tating factors or events occurring in proximity to the
a m s . A representative history is offered from our
onset of the amnesia have included swimming in cold
files:
water, driving an automobile, participating in strenu­
O.T. was a 69-year-old farmer with a history of
ous sports, and sexual i n t e r c o u r s e .
Medical ill­
hypertension. On the morning of January 28, 1982, he
nesses common to patients with T G A have included
was feeling well when he went outside at 8:00 A M to
hypertension, ischemic heart disease, and, on occa­
sion, hyperlipidemia and diabetes. In the pure form of
Reprinted from Current Concepts of Cerebrovascular Disease —
TGA, the neurological examination is normal. Several
Stroke, May-June, 1983, Edited by Frank M. Yatsu, M.D., Depart­
ment of Neurology, University of Texas Health Sciences Center at
authors have reported TGA in association with other
Houston, Houston, Texas, 77030, published and copyrighted by the
neurological deficits, but this probably represents a
American Heart Association, Dr. William Logan and Dr. David G.
different syndrome with a different natural h i s t o r y .
Sherman are with the Department of Medicine, Division of Neurology,
Laboratory evaluation has been unrevealing. HemoUniversity of Texas Health Science Center, San Antonio, Texas.
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globin, hematocrit, serum electrolytes, and fasting
blood sugar have been normal. Abnormalities, if pres­
ent, tend to occur in angiographic and encephalographic examinations. Angiography has been per­
formed in a number of cases, and while some authors
have found a propensity for significant cerebrovascu­
lar disease (particularly of the vertebrobasilar circula­
tion),' others have not. Electroencephalographic ab­
normalities have been noted anywhere from 0 to 80%
of the time. In earlier studies only routine awake trac­
ings using standard electrodes were performed. Often
the EEG was performed days to weeks after the epi­
sode. Not surprisingly, few abnormalities were
seen. ' n More recently, however, several groups have
reported a higher frequency of changes with the use of
sleep deprivation and nasopharyngeal electrodes. The most common abnormalities have been frontotemporal slow waves with or without mesial temporal
spikes and sharp transients. Most abnormalities clear
over several days, but there are reports of persistent
slowing. Computerized tomography (CT) of patients
with TGA has shown no abnormality or only atrophy
in about half of the patients studied. The most com­
mon abnormalities are hypodense lesions in the tempo­
ral or occipital regions. Thalamic lesions have also
been noted. These hypodense lesions, presumably in­
farctions, are most often left-sided but occasionally
bilateral.
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Before discussing the proposed theories of patho­
genesis, a brief review of memory and its proposed
anatomical correlates would be helpful. Memory can
be broken down into three major areas: (1) immediate
recall or the ability to reproduce after at most a few
minutes a given set of information, (2) remote mem­
ory, i.e., the ability to retrieve previously learned ma­
terial from the past, and finally, (3) recent memory or
the ability to learn new information. It is the last type
that is almost exclusively and totally affected in T G A .
Certainly, there is not a clear demarcation between
recent and remote memory, and in fact, a striking
retrograde amnesia is almost always seen in T G A . The
exact anatomical site of memory is not known. Certain
areas of the brain, if damaged, will show memory loss,
including the hippocampus, mammillary bodies, for­
nix, medial temporal lobes, and possibly the dorsomedial nucleus of the thalamus. For the most part these
are paired structures, and it is of note that except in rare
instances unilateral destruction will not result in sig­
nificant memory loss. An episode of transient global
amnesia is felt to represent a dysfunction in all or part
of these areas.
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Fisher and Adams felt that this syndrome was more
likely epileptogenic in origin. The abruptness of onset,
brevity, and reversibility of the episodes, coupled with
the occasional abnormalities in the EEG led them to
suspect a form of epilepsy. Indeed, more recent work
by other investigators has shown a striking increase in
EEG abnormalities with more refined techniques. Al­
though the epileptic theory is almost impossible to
disprove, other features of the disease, such as the
length of the attack (hours, not minutes), the otherwise
clear faculties of the patient, the lack of generalized
convulsion or even convulsive movements during or
subsequent to the attacks, and its general lack of recur­
rence, make epilepsy less appealing.
Most authors feel that T G A represents a form of
ischemia to structures of the deep limbic system on the
basis of thromboembolic cerebrovascular disease.
Amnesic strokes (infarctions) usually occur in the dis­
tribution of the posterior cerebral arteries, often with
other neurological signs. Certainly, transient ischemic
attacks (TIA's) could occur in the same distribution.
The benign course of TGA is especially difficult to
explain. Recurrent episodes of TGA are uncommon,
and progression to more widespread posterior circu­
lation TIA's and stroke is even more uncommon.
Furthermore, why are other symptoms and signs so
uncommon in a circulation so prone to multiple symp­
tomatology? Perhaps this is not a posterior circulation
event at all but instead related to anterior circulation
ischemia, such as the recurrent artery of Heubner, as
has been suggested by Bender. Or perhaps this is not
an atherosclerotic embolus at all but another type of
lacuna.
Whichever theory one chooses, it must incorporate
in its structure an explanation for the benign nature of
this disorder. By far, the most common presentation is
that of a single episode of amnesia without recurrence.
In the initial series by Bender and by Fisher and Ad­
ams, there were no recurrences in an average followup of three months. The incidence of TIA and stroke is
minimally (if at all) increased over that of the general
population. In some series, however, the incidence of
recurrence has been as high as 50 to 6 0 % and the
occurrence of stroke and TIA much higher. These
studies consisted of patients with a higher incidence of
initial neurological abnormalities than the original
studies and most subsequent ones. It would seem more
reasonable to classify these patients as a different sub­
group more prone to suffer long-term sequelae. Al­
though initial observations indicated that there were no
persistent memory changes, more recent studies have
suggested a persistent decrease in verbal long-term
memory and verbal IQ can occur after even one epi­
sode of T G A . Other studies have documented an
even more profound change with recurrent episodes.
However, it would seem that striking changes in mem­
ory or personality with a single episode of TGA are
quite uncommon.

The known causes of amnesia are limited. Trauma,
drug intoxication, alcoholism, most metabolic
changes, and CNS infections are quickly excluded by
the history, physical, and routine studies. Hypoglyce­
mia and migraine are more difficult to disprove but
certainly must not be common. However, migraine has
been shown by one group to occur frequently in their
series of patients with T G A . - - The two theories
In summary, transient global amnesia may be de­
proposed most often are epileptogenic and cerebrovas­
fined as the abrupt onset of the inability to store new
cular (ischemic) causes. In their original description
memories, almost always associated with transient,
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TRANSIENT GLOBAL AMNESIA/Logan
although at times striking, retrograde amnesia without
other neurological signs, lasting less than 24 hours.
The subsequent course is benign, with recurrence un­
common and TIA and stroke rare. The etiology is
presumed to be ischemia of the medial temporal lobes,
particularly the hippocampus, mammillary bodies,
fornix, and the thalamus. The occurrence of TGA in
association with other neurological symptoms may
represent more severe involvement by the same patho­
logical process, or it may be an entirely different ill­
ness. It would appear that long-term memory changes
do occur, but the relative frequency and severity are
not clear. At this time the benign prognosis does not
warrant vigorous treatment.
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and

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Transient global amnesia.
W Logan and D G Sherman
Stroke. 1983;14:1005-1007
doi: 10.1161/01.STR.14.6.1005
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1983 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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