Second edition

10.qxd 3/10/08 5:52 PM Page 448
448 Vascular disorders
engage in quite complex activity, such as playing an organ
piece, during the episode itself (Byer and Crowley 1980).
The neurologic examination is generally normal. The
episode itself generally lasts anywhere from 4 to 18 hours,
averaging about 6 hours, and terminates gradually.
After the episode has cleared, patients are once again able
to keep track of ongoing events, and their ability to recall
words after 5 minutes is fully restored. When they try and
recall what happened, however, they often find an ‘island’ of
amnesia that covers not only the duration of the event itself
but also any events that occurred anywhere from a few minutes
to an hour or so just before the onset of the episode.
Although clinically patients are thus fully restored, detailed
testing may reveal some subtle decrements in memory
(Guillery-Girard et al. 2006; Steinmetz and Vroom 1972).
Course
Long-term follow-up of approximately 5–6 years shows
that only about one-fifth to one-quarter of patients have a
recurrence (Gandolfo et al. 1992; Hinge et al. 1986; Miller
et al. 1987a).
Etiology
It appears that the amnesia seen in transient global amnesia
represents the effects of a similarly transient dysfunction of
medial temporal lobe structures. Single photon emission
computed tomography (SPECT) studies have revealed
hypoperfusion of the medial aspects of both temporal lobes
(Lampl et al. 2004), more so the left than the right, and
diffusion-weighted imaging has revealed punctate areas of
increased signal intensity in the hippocampus (Bartsch et al.
2006; Sedlaczek et al. 2004; Strupp et al. 1998); notably both
of these abnormal findings clear with time. Structural MRI
studies are generally normal (Bartsch et al. 2006); however,
one high-resolution MRI study found an increased number
of microcavities in the CA-1 subfield of the hippocampus,
suggesting that there may be some subtle permanent damage
(Nakada et al. 2005). Several mechanisms have been
proposed to account for these changes, including epileptic
activity, transient ischemia, migraine, and, recently, venous
reflux. Epileptic activity appears unlikely: EEGs obtained
during episodes of transient global amnesia do not display
ictal activity (Miller et al. 1987b), and the attacks themselves,
rather than ending abruptly, as is typical of a seizure, tend to
clear gradually. Transient ischemia has long been an attractive
hypothesis, but patients with transient global amnesia
generally have few risk factors for stroke (Hodges and
Warlow 1990; Lauria et al. 1998; Melo et al. 1992) and rarely
end up having stroke during follow-up (Zorzon et al. 1995).
Migraine may play a role: there is a definite association
between transient global amnesia and migraine (Crowell
et al. 1984; Hodges and Warlow 1990; Melo et al. 1992;
Schmidtke and Ehmsen 1998; Zorzon et al. 1995), and an
episode of ‘spreading depression of Leão’ confined to medial
temporal structures could, conceivably, cause amnesia.
Migraine, however, would not explain the SPECT and
diffusion-weighted imaging abnormalities described earlier.
The final proposed mechanism, namely venous reflux,
is quite interesting. To understand the theory of venous
reflux one must recall some anatomy. Normally the medial
temporal structures are drained by the deep veins of
Rosenthal. These veins, in turn, drain to the great vein of
Galen, which drains to the straight sinus. The straight
sinus, in turn, courses posteriorly to join the superior sagittal
sinus at the sinus confluens. The sinus confluens gives
rise to the left and right transverse sinuses, which in turn
drain to the sigmoid sinuses and eventually into the internal
jugular veins. Of note, and of particular importance to
the venous reflux theory, in the majority of individuals, the
straight sinus drains not into both transverse sinuses but
only into the left transverse sinus. Given this unique
drainage pattern, it is theoretically possible that venous
reflux confined to the left internal jugular vein could cause
venous stasis in the medial aspects of both the left and the
right temporal lobes. Recent studies have demonstrated
such reflux through incompetent valves (Maalikjy Akkawi
et al. 2003) in the left internal jugular vein in patients with
transient global amnesia, adding weight to this theory
(Chung et al. 2006; Sander et al. 2000). The reflux itself
could be related to a Valsalva-type maneuver, consistent
with some of the precipitating events mentioned earlier,
or, as indicated in one study, to intrathoracic compression
of the left brachiocephalic vein (Chung et al. 2006).
Differential diagnosis
Transient global amnesia, as discussed in Section 5.4, is best
conceived of as one of the episodic anterograde amnesias
and, as such, must be distinguished from TIAs, pure epileptic
amnesia, concussion, and substance-induced blackouts.
Transient ischemic attacks affecting the temporal lobes
may produce a syndrome quite similar to transient global
amnesia. However, when ischemia occurs in the area of
distribution of the posterior cerebral arteries, in addition
to amnesia one typically also sees evidence of ischemia of
the occipital lobes, such as hemianopia or cortical blindness,
findings not seen in transient global amnesia.
Pure epileptic amnesia is suggested by a sudden offset of
the episode, in contrast to the gradual offset of transient
global amnesia, and by the fact that patients in the midst of
an epileptic amnestic episode generally do not engage in
the anxious questioning typical of transient global amnesia.
Other distinguishing features include the occurrence of
other seizure types, such as complex partial or grand mal
seizures, and a pattern of frequent recurrence.
Concussion is immediately suggested by a history of
head injury, which, of course, must often be gained from
others. Furthermore, during concussion, patients may display
a degree of confusion.