HypothesisAetiology of transient global amnesia
Section snippets
Transient ischaemic attacks
Studies have shown that patients with TGA have fewer risk factors for thromboembolic disease than patients with transient ischaemic attacks; and that the prognosis for vascular events and mortality in patients with TGA is significantly better than in patients with transient ischaemic attacks.5, 9 These findings suggest that arterial thromboembolic disease is an unlikely explanation for TGA.
Epilepsy
Although some patients with epilepsy may have episodes resembling TGA, there is little evidence that epilepsy causes TGA.
Migraine
A migrainous disturbance of brain function, causing spreading depression of cerebral activity,11 has also been proposed, and is a popular hypothesis.2, 5 Spreading depression is a short-lasting wave of depolarisation that moves across the cortex at a rate of 3-5 mm/min and can be observed in experimental animals, in which it is induced by local stimulation. Spreading depression has been proposed as the cause of the aura of migraine.12 According to the spreading-depression hypothesis, emotional
Precipitants of TGA
None of the mechanisms suggested above explain the absence of other neurological signs or symptoms during TGA, or that TGA is often associated with distinct trigger events, which, I observe, would be expected to result in marked increases in venous return from the arms to the superior vena cava. People with TGA also often have a Valsalva manoeuvre at the onset.
Effect of an increased venous return and simultaneous Valsalva
Commonly observed triggers of TGA may result in increased venous flow toward the superior vena cava. A simultaneous Valsalva would be expected to block venous return to the heart, with high venous pressure from the arms retrogradely transmitted to the cerebral venous system. This venous back pressure may be sufficiently high to cause venous ischaemia in hemispheric or deep-brain structures. Venous ischaemia to brain regions is known to occur in venous hypertension when cerebral blood flow falls
Hypothesis
I suggest that transient retrograde venous congestion and venous ischaemia to bilateral diencephalic or hippocampal structures is the cause of TGA.
If transient venous ischaemia causes TGA, why does the memory deficit last for hours?
Triggers for TGA are often very brief yet the memory disturbance persists for hours in the absence of any other neurological signs or symptoms,3 suggesting that a transient disruption of short-term memory mechanisms may be all that is required to disrupt the normal function of this mechanism for several hours.
If venous ischaemia is the cause of TGA why are there no other focal neurological symptoms or signs?
Although the structures involved in memory may be more susceptible to venous ischaemia for anatomical and haemodynamic reasons, the absence of other focal neurological symptoms might also be explained by the very brief nature of the venous hypertensive trigger, sufficient to disrupt memory but other deficits (if any) would be momentary and likely to go unnoticed. Headache and vomiting, reported in some patients with TGA,2 would be consistent with venous hypertension.20
If TGA is caused by transient venous hypertension, why is it not more common?
Several factors may be involved in producing TGA, including the duration and suddenness of the precipitating event, and the size of the rise in venous pressure (influenced by blood volume, venous capacitance, and sympathetic nervous system activity14). Other factors may be variations in cerebral venous (and arterial) anatomy, and the absence or incompetence of jugular venous valves, which may make people with raised intrathoracic pressure more prone to cerebral venous congestion.23
Are the results of imaging studies in TGA consistent with venous ischaemia?
Hodges6 reviewed the results of the ten studies involving 13 patients who underwent positron emission tomography (PET) or single-photon emission computed tomography (SPECT) scanning during or soon after TGA. In most cases there was temporal-lobe or thalamic hypoperfusion. Reversible hypoperfusion on SPECT scans has been shown in patients with venous ischaemia.16, 17 Ito and colleagues16 showed reversible bilateral thalamic hypoperfusion on SPECT scanning of a patient who presented with a memory
Why is TGA not associated with other circumstances that increase cerebral venous pressure?
In most patients with superior vena cava syndrome or cerebral venous sinus thrombosis, the process of venous pressure elevation is gradual and progressive. In superior vena cava obstruction, for example, Gonzalez-Fajardo and colleagues27 showed, in dogs, that acute superior vena cava obstruction may lead to cerebral venous hypertension and infarction. In the usual clinical setting of superior vena cava syndrome, however, the process is gradual, leading to the development of collateral pathways
Testing the hypothesis
Increased susceptibility to retrograde jugular venous flow could be tested for in patients with TGA, by seeing if their jugular venous valves are competent. Competency of jugular valves in TGA patients can be tested by doppler ultrasound assessment of retrograde flow through the jugular veins during Valsalva, in comparison with an age-matched control population. A significant proportion of incompetent jugular valves in the TGA group would support this hypothesis. In addition, case studies
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