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Transient Global Amnesia
Author: Bruce Landres, M. D.
Last Revised: Sun, 13-Apr-2003
Article Size: 19.47 KB

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Transient Global Amnesia

Bruce Landres, M. D.

Case Report

A 67-year-old male presented to the emergency department with acute
loss of recent memory. His wife provided the history, as the patient was not
cogent. On the day of admission, the patient awakened at Hour=\"5\">5: 30 AM with no complaints, showered and shaved, and then
complained of \"not feeling right\". He became confused and was not
oriented to time or place but could recall his name. He was not able to absorb
any new memories, and his questioning was redundant. His speech patterns were
normal and fluent, but his immediate recall was 0/ Hour=\"17\">3 after 5 minutes. He complained of a mild headache but
had no nausea or vomiting, stiff neck, vertigo, dysarthria, dysphagia, focal
motor or sensory loss, and there was no ataxia.

Approximately 15 years prior to this event the patient had had a similar
loss of memory that brought him to the emergency department. His symptoms had
resolved in 4-5 hours, and the only diagnostic study done at the time was a
head CT scan that was reported normal. There was no history of seizure disorder
nor observed seizures, no history of alcohol or drug use or any history or
prior stroke or arrhythmia. There was also no history of fever or altered food
or fluid intake prior to the event. There was a history of hypertension well
controlled with ACE inhibitors. Additionally he was taking aspirin and
omeprazole for a history of gastroesophageal reflux.

Over the next several hours, the patient had a gradual improvement in his
memory, but had no recall of the day\'s events. He was admitted to the hospital
for observation and studies.

His initial physical examination noted his blood pressure to be 196/ 108,
but this rapidly fell to 146/ 80. His heart rate was 90 and regular and his
respiratory rate was 16. The remainder of the examination including
neurological examination was completely normal, and by the time he was admitted
to the ward he was oriented x 4.

A non contrast CT scan of the head showed ethmoid sinusitis, and an EEG done
awake and drowsy showed no seizure activity. An EKG showed a right bundle
branch block pattern, and a non-contrast MRI of the brain showed mild atrophy
and dense anterior falx calcifications only. A chest x-ray was unremarkable as
was the CBC, protime, partial thromboplastin time and metabolic panel.

The patient was discharged home the next day with full recovery of his
mental capacity and with no neurological compromise. He has had no recurrent
problems for the subsequent 10 months.


Transient global amnesia (TGA) was first described in 1956, although it
likely was present, but unnamed preceding this date. In 1990, diagnostic
criteria for TGA were first established. 1,2 . They
included: (1) the attacks be witnessed and reported capably by an observer; (2)
there is clear cut anterograde amnesia during the attack; (3) there be no
clouding of consciousness or loss of identity; (4) there can be no associated
focal neurological symptoms or deficits either during or after the attack; (5)
there can be no features of epileps; (6) attacks must resolve within 24 hours;
(7) That patients with active epilepsy or recent head injuries be excluded.

Although TGAis characterized by the acute loss of memory with confusion and
repetitive questioning, the syndrome has many additional nuances. The
antero-grade amnesia (inability to recall new information) is generally
profound. Typically, both verbal and non-verbal inputs simply fail to imprint,
and even with coaching and repetition, new data cannot be committed to memory
without significant degradation. This condi-tion is also associated with an
observed higher level of anxiety and agitation, leading to perseveration.
Patients will ask the same questions over and over again, usually within
minutes of having received an answer. Commonly the intonation and syntax are
identical, \"as if a fragment of a sound track is being repeatedly
rerun.\" 3 The questions are generally of an orientating nature --\"How
did I get here?\" or \"Who are you?\"-- and
may persist for several hours. In contrast, observed patients show no evidence
of hysteresis, only concern and confusion for recent events. 4

In contrast, retrograde amnesia (memory for past events) while present, is
variable and can extend back-wards for a period of days to years. At the same
time there is an unaltered retention of knowledge of a personal nature, such as
one\'s name, address, age, or family names. Strangely, complex tasks, such as
driving, reading, playing soccer or playing music are unaffected. 2,5 The individual\'s level of consciousness is normal and the
patient is fully communicative and alert.

The time course of TGA is variable but is always limited. Usually this
condition will resolved itself substantially within 4-8 hours and seemingly
completely by 24 hours. 2,3,6 In fact, an amnesic
event extending longer than this time frame, strongly suggests another
etiology, such as a cerebral vascular accident or intra-cranial bleed. In
contrast, bouts of amnesia of less than one hour, similarly suggest that the
condition is not TGA, but more likely epileptic in nature. 1

The return of anterograde memory, while dramatic over the first 24 hours, is
not complete, and subtle alterations in memory may persist for several months
after the initial event, with observed difficul-ties in verbal and non-verbal
memory challenges. 4 In contrast retrograde memory improves over time, with
more distant memories returning at first, and events approaching the TGA event
coming later. However, it is common for the patient to have a persistent
inability to recall any memory of the amnesic episode or the hour or two
preceding the event regardless of the passage of time.

While some papers will document a male or female predominance in the
incidence of TGA, most research shows that there is an even division between
the genders. Hodges documents 2 cases of familial occurrence of TGA, an
incidence of 1.75% in his study of 114 patients, but reports of such cases are
rare within the literature. 1 Also the literature univer-sally supports the
average age of onset of TGA to be 60-61 years, with a range of 40 to 80 years.
5 In fact, cases of TGA less than 40 years of age are suspect for other disease
states than TGA. 3 In his paper, Hodges is able to document only 1 case in 114
of an individual less than 40 years of age that meets the strict criteria for
\"pure TGA\". 1 Overall, the incidence of TGA has been reported to
range between 2.5 and 5.2 people per 100,000 population per year and 23.5 per
100,000 in persons older than 50 years. However, in Sweden,
the numbers were reported higher at 10 per 100,000 in the general population
and 32 per 100,000 in individuals older than 50 years. 2,7
Recurrence of a second or third attack of TGA is noted to be between 2-3% per
year. 1,5 And time intervals between attacks have been
noted to be as long as 19 years. 2

There are no bona fide precipitants of TGA, but there have been many
documented activities/conditions, associated with its onset. The literature is
replete with the onset of TGA in association with physical activity, swimming
or immersion in cold water, intercourse, acute pain, cerebral angiography, and
extreme \"stress.\" 8 In fact in Hodges work, signif-icant stressors
were found in relation to TGA in 14% of his reported cases. 1 Sandson reports
that 33% of cases of TGAare precipitated by the above activities. 2 However, no
one specific entity has yet been found to be a causative agent.

Given the noted strict criteria, any de novo neuro-logical deficit
automatically excludes a patient from the diagnosis of TGA. Hodges notes that
12.2% of his patients had an observed neurological abnormality, but all of
these were known to be pre-existing or attribut-able to another cause, such as
a prior stroke or diabetic peripheral neuropathy. 1 Despite this explicit
criteria, however, there remains in the literature a
large number of reported cases which include individual patients with acute
neurologic deficits ranging form subtle to overt which should be removed from
consideration of this diagnosis. There are, however, a constellation of other
symptoms associated with TGA. Reports of a dull headache, dizziness, neck pain
or nausea and vomiting have been reported with the onset of the amnesic event,
but they are noted in a minority of patients and their significance is not
clear. 3

Laboratory testing at the time of the acute event, has, with few exceptions,
been unproductive. Blood, urine, spinal fluid, x-rays of the skull and neck,
non-contrast CT and MRI scans of the head are all consis-tently unremarkable in
association with TGA. EEG is similarly normal except for non-specific abnormali-ties
seen in control populations. 2 In fact, there is one documented case of an EEG
being taken at the onset and during the evolution of an acute bout of TGA, with
no changes being noted. 9 Frederiks cites several other papers and his own work
in which intracranial and extracranial atherosclerotic abnormalities were found
in substantial numbers of patients with reported TGA. 3 However, in this same
paper, Frederiks reports that within his own series of patients, \"routine
neuro-logical examination during an attack often revealed transient mild
abnormalities\". Clearly this reflects lack of attentiveness to the strict
criteria for TGA and cast doubt upon the accuracy of his initial diagnosis.

However, cerebral blood flow studies have revealed reversible bilateral
global and focal temporal hypoperfusion. PET scanning has shown transiently
reduced mesial temporal lobe oxygen metabolism when compared to controls. Also
SPECT and PET scans during and after TGA show variable transient hypoperfusion
of either the bilateral medial temporal brain
structures, the thalamus, the frontal lobe, or the hippocampus. 5,10,11 Diffusion weighted (DW) MRI scans of the brain show
both hypo and hyperperfusion of the left temporal lobe of the brain with
bilateral signal abnormalities in the hippocampus. The DW MRI has been found to
be particularly sensitive to move-ments of water molecules and transport in
biological tissues. The authors feel that the observed changes are caused by
reduced diffusion of interstitial water owing to a relative decrease of the
interstitial space suggesting cellular swelling. 12 However, the changes are
not diag-nostic for any specific pathologic entity.

More recently, Sander, et al has examined jugular venous flow patterns in
patients with TGA using duplex ultrasonography, and showed that there were
significant increases in retrograde flow during Valsalva maneuvers and when
compared to controls. 6

Overall, TGA is not felt to be a risk factor for stroke. Numerous
retrospective studies have shows that the risk of CVA in patients who have
experienced TGA is similar to that of the general population and substantially
less than individuals with documented transient ischemic attacks. 3,5 In a sense, this belies one of the working hypotheses
that the etiology of TGA is ischemic. If TGA were indeed due to cerebral
vascular insufficiency the stroke incidence and mortality data should logically
be similar for both disease states. 3

The etiology of TGA remains enigmatic. Several hypothetical causes have been
proposed over the years, including focal ischemia, migraine equivalents,
epilepsy, Leao\'s spreading depression, and hysterical conversion reactions. 3
Drug or alcohol usage must also be considered as a cause of TGA and a drug
screen is reasonable as part of the workup. More recently Sander has postulated
increased jugular reflux with retrograde venous flow during valsalva maneuvers,
leads to venous congestion and venous ischemia of the hippocampal and
diencephalic regions of the brain. 6 In that many of the patients with TGA had
reported valsalva maneuver equivalents (lifting,
intercourse) prior to the onset of the initial event, this theory is of
interest but unproven.

Focal ischemia is discussed above and appears unlikely because of the
differential survival curves between documented cerebral vascular ischemia and
TGA. However, migraine syndromes are observed at a substantially higher rate in
individuals with TGA. 3 In fact, Sandson reports an incidence of 14%-33% in
persons having an episode of TGA. 2 Additionally, a dull headache and nausea
and vomiting is reported in a small subset of patients presenting with TGA. 5
However, migraine is a disease more commonly seen in individ-uals less than 50
years of age, and the overwhelming number of reported
patients have
no manifestations of migraine whatsoever, making this
unlikely. 3

Epilepsy is unlikely given that multiple EEG studies have revealed no
abnormalities even in the midst of he TGA attack.
However, here too, there may be a subset of presenting individuals in whom
epilepsy ultimately is found to be the causative agent. Hodges reports that
9.2% of his 153 patients later went on to develop epilepsy with symptoms of
amnesia as part of the post-ictal state. 1 Sandson reports the figure to be 7%.
2 Risk factors for the development of epilepsy were individuals found to have
more than one bout of amnesia (35.3% inci-dence), and individuals with episodes
of TGA lasting less than one hour (50% incidence). When both features were
present, the predictive value was felt to be 100%.

Hysteria is more classically seen in a younger population who manifest less
agitation and persevera-tion about their status and in whom a greater level of
indifference towards their condition is noted. There may also be a greater
likelihood of psychiatric illness or prior psychological consultation.

The PET, SPECT, and DW-MRI findings are notably consistent with but not
diagnostic of Leao\'s spreading depression. Investigators postulate that intense
stimuli of an emotional or physical nature trigger the release of glutamate in
the hippocampus leading to spreading depression and transient hippocampal
dysfunction. 8,11 The mechanism of action is this
phenomena is similar to that of migraine headaches and the increased incidence
of migraine history in patients who have had TGA is notable in this regard.
However, this hypothesis while inter-esting, is also
as yet unproven.

While the studies to date clearly document a dysfunction of the limbic
system of the brain, they fail to elucidate the exact nature of this disorder.
However, regardless of the etiology of TGA, it is universally felt to be a
benign condition which requires no further treatment other than reassurance to
the patient and their family. Indeed, no treatment has been shown to affect the
recurrence of TGA. 2 The patient should be told that while TGA, while
obvi-ously appearing to be threatening, is not a
predecessor to a stroke or a tumor and that the recurrence rate of future
amnesic events is low. This condition does not require suspension or canceling
of a patient\'s drivers license or an extensive workup
when the presentation meets the criteria for pure TGA. 5 This having been said,
recurrent episodes of TGA or bouts of TGA lasting less than 1 hour, or TGA
observed in a patient less than 40 years of age will merit a more extensive
work-up to rule out any underlying disease state.


Hodges JR, Warlow CP. Syndromes of transient amnesia:
towards a classification. A study of 153 cases. J Neurol Neurosurg Psychiatry. 1990 Oct; 53class=GramE>( 10): 834-843.

2. Sandson TA, Price BH. Transient global amnesia.
Semin Neurol. 1995 Jun; 15( 2): 183-187.

3. Frederiks JA. Transient global amnesia. Clin
Neurol Neurosurg.
1993 Dec; 95( 4): 265-283.

4. Hodges JR, Ward CD. Observations during transient
global amnesia.
A behavioural and neuropsychological
study of five cases.
Brain. 1989
Jun; 112( Pt 3): 595-620.

5. Zeman AZ, Hodges JR. Transient global amnesia. Br J Hosp Med. 1997
Sep 17-30; 58( 6): 257-260.

6. Sander D, Winbeck K, Etgen T, Knapp R, Klingelhofer J, Conrad B. Disturbance
of venous flow patterns in patients with transient global amnesia. Lancet. 2000 Dec 9; 356(
): 1982-1984.

7. Koski KJ, Marttila RJ. Transient global amnesia: incidence in an
urban population. Acta Neurol Scand. 1990 Apr; 81( 4):

8. Lewis SL. Aetiology of transient global amnesia.
Lancet. 1998 Aug 1; 352( 9125): 397-399.

9. Cole AJ, Gloor P, Kaplan R. Transient global amnesia: the
elec-troencephalogram at onset. Ann Neurol. 1987 Dec; 22(6): 771-772.

10. Warren JD, Chatterton B, Thompson PD. A SPECT
study of the anatomy of transient global amnesia.
Clin Neurosci.
2000 Jan; 7( 1):

11. Hodges JR. Unraveling the enigma of transient global amnesia. Ann
1998 Feb; 43( 2): 151-153.

12. Strupp M, Bruning R, Wu RH, Deimling M, Reiser M, Brandt T. Diffusion-weighted
MRI in transient global amnesia: elevated signal intensity in the left mesial
temporal lobe in 7 of 10 patients. Ann Neurol. 1998 Feb; 43( 2): 164-170.

Transient Global Amnesia
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