Neurology 27

Transient global amnesia

Transient global amnesia is widely regarded as one of the most remarkable neurological
conditions in terms of its history, symptoms and signs. It presents classically with a sudden
onset of severe anterograde amnesia.1 We describe here the epidemiology, clinical features,
and management of this poorly recognised condition.
Dr Mohit Mandiratta SHO, Russells Hall Hospital, Dudley, UK
Dr Abdul Salam Consultant Stroke Physician, Russells Hall Hospital, Dudley, UK
Dr A.K. Banerjee Clinical lead in Stroke Medicine, Russells Hall Hospital, Dudley, UK
Email: mohitmandiratta@nhs.net

Transient global amnesia is a

syndrome involving sudden and
complete disruption of short
term memory, with no other
neurological signs or symptoms.
It is often referred to physicians
and stroke teams in primary/
secondary care.

Epidemiology
It classically affects people
between the ages of 40 and 80
years with the average age of
onset being 62 years. 2,3 It has
an incidence of five per 100,000
population per year. There
has been no racial or sexual
predilection reported.4,5

Clinical history
Transient global amnesia is
widely regarded as one of the
most remarkable neurological
conditions in terms of its history,
symptoms and signs. It presents
classically with a sudden onset
of severe anterograde amnesia.
During the episode patients are
incapable of producing any new

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memories. The amnesia is so

profound that both verbal and
non-verbal memories cannot be
formed often despite repetition.
Immediate recall memory is
preserved as is that of remote
memories; however a degree of
retrograde amnesia has also been
reported in some cases.1,6,7
Due to the sudden and
alarming nature of the above
described events, patients are
often noted to have a high
level of agitation and anxiety.
This can lead to repetition
and perseveration with those
affected typically asking the
same questions again and again
in a very methodical manner,
and often with similar gestures
and vocal intonation. It has been
likened to a sound track being
repeatedly re-run.8
During the event patients
remain fully conscious and
alert. They can continue to
communicate and perform
complex tasks such as driving.
This suggests language, visuospatial skills, attention and social
skills are preserved.
Symptoms generally last
between two and eight hours,

and are always less than 24

hours.2,5
For trial purposes diagnostic
criteria have been set out by
Hodges et al and as a result
are often used for a clinical
diagnosis also.
These are:9
Witnessed event
Acute onset of anterograde
amnesia
No
other
cognitive
impairment
No alteration in conscious
level
No
associated
focal
neurological deficit
No associated features of
seizure like activity
No recent head injury
No active history of epilepsy
Symptoms should resolve
within 24 hours.

Differential diagnosis
Although such a striking
condition, many clinicians
have not encountered it in
their practice and hence it can
often be mislabelled. Patients
are often referred/admitted to

July/August 2012 | Midlife and Beyond | GM

28 Neurology

secondary care as this condition

is sometimes considered a stroke
mimic.
Subsequently TGA accounts
for many consultations in TIA
clinics. Differentials to consider
in patients with suspected TGA
include:
Acute confusional states
Epileptiform activity
Transient epileptic amnesia
Transient ischaemic attack/
cerebrovascular event
Atypical migraine
Syncopal episodes
Psychogenic amnesia.
The above should all be
considered and excluded through
careful history taking and
clinical examination, however
the unique nature of TGA and
its typical clinical presentation
described above means it is often
unmistakable.

Investigations
When suspecting TGA, it is
important to get a thorough
history as well as a reliable
collateral history from a witness.
This coupled with a normal
neurological examination is
sufficient to confirm the diagnosis
without further investigation.
Should there be any diagnostic
doubt it would be reasonable
to consider performing routine
blood screening including renal
function and inflammatory
markers to rule out an infective
cause of confusion.
A CT/MRI scan may also be
done to rule out cerebrovascular
disease or space occupying lesion
should risk factors be present. An
EEG is also useful should there
be repeated episodes or suspected
epileptiform focus.

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Pathophysiology
The underlying causes have
been extensively investigated,
and varying hypotheses exist. It
is however understood that the
areas of the brain affected are
likely to involve the mediobasal
temporal region, hippocampus
and parahippocampus which all
play an integral role in memory
formation.10, 11
Certain precipitants have also
been noted in a large proportion
of TGAs through case reporting.
These include:12
Vigorous exercise
Sudden temperature change
Emotional instability.
Epilepsy is thought to be
unlikely as a cause of TGA. This
is due to the fact that episodes
tend to occur in complete
consciousness and have a low
recurrence rate. Furthermore
EEG studies have been largely
unremarkable both during and
after events. Transient Epileptic
Amnesia (TEA) is thought to be
a separate condition in itself, but
one that can cause diagnostic
confusion. TEAs tend to affect
the young and episodes certainly
last less than one hour.12,13
Migraine has also been
mooted as a potential cause
of TGAs. The theory is based
around the release of glutamate
following emotional triggers,
which leads to hippocampal
dysfunction. Some studies have
reported an association of TGAs
occurring more frequently in
those who suffer with migraines,
but others have not found
this relationship. Again the
demographics of the affected
vary, with migraines affecting
a younger cohort. Only a small
minority of TGA cases have

reported a history of headache

preceding or during the event. 12,14
The relationship with
Valsalva triggers lead some to
believe TGAs may have been
due to a paradoxical embolus
through a patent foramen
ovale. This theory was refuted
as the prevalence of PFOs is no
higher in those affected by TGA.
However the sudden onset nature
of the symptoms means there
are still many proponents of a
vascular/ischaemic theory. Many
have speculated that it may well
be a form of a transient ischaemic
attack or cerebrovascular event,
however those who have been
affected by TGA have not been
found to be arteriopaths and
have no increased incidence
of myocardial infarctions,
peripheral vascular disease or
strokes.14, 15
Another theory suggests
that rather than arterial
ischaemia, venous ischaemia
may well be a causative factor.
Valsalva manoeuvres have
been shown to briefly raise
cerebral venous pressure. The
hippocampus has been found to
be especially sensitive to such
pressure changes, which reflects
potentially why symptoms
can occur without any other
neurological deficit. These
significant pressure changes
are often exacerbated with
jugular vein valve insufficiency
which leads to further venous
congestion, and selective
ischaemia. However this alone
does not fully explain the
mechanism as prevalence of
jugular insufficiency is no higher
in the TGA group than in the
general population.6,12,16,17
Other postulated theories
include drugs and alcohol. Some

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Neurology 29

suggested a relationship between

the use of statins and TGA but
no significant correlation was
found. It has been suggested
that psychological disturbances
are a key factor. A link to
psychiatric conditions and
certain personality traits has
also been put forward by some,
where others feel it may be
linked to hyperventilation
and consequential cerebral
vasoconstriction.2,7,12
The reality is that despite
much research and studies, the
exact aetiology remains elusive.
Much investigation using MRI
Diffusion Weighted Imaging,
PET scanning, SPECT and MR
spectroscopy have highlighted
the various areas of the brain
affected, but exactly how and
why remains unclear.

Management
Regardless of the causes behind
TGA it is widely felt to be a
benign condition requiring
no further treatment. The
mainstay is reassurance to the
patient and family. Naturally
patient concerns centre around
ruling out tumours and strokes.
Family members are often very
distressed and perturbed upon
witnessing their loved one go
from normal to being unable to
remember anything so acutely.

Prognosis
Episodes of TGA resolve
spontaneously and are selflimiting. Recurrence rates have
been reported varyingly with
figures varying from 3% to
20% having repeated episodes

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diseases revisited: Transient

in five years. The DVLA do
Global Amnesia. Postgrad Med J
not need to be informed about
2007; 83: 236
episodes of TGA and there are
7. Hodges JR. Unravelling the enigma
no implications on the ability to
of transient global amnesia. Ann
drive.2,6

Conclusion
Transient global amnesia
continues to cause much
diagnostic uncertainty, and
its exact aetiology remains
poorly understood. However it
is a remarkable and dramatic
condition presenting with
sudden onset memory loss
and an inability to retain
new information. It resolves
spontaneously, and is selflimiting with low risk of
recurrence. It requires no formal
treatment or follow-up.
Conflict of interest: none
declared
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