Transient global amnesia, cerebral veins, and the need to find the 'smoking gun'.

See related article, pages ●●●–●●●. Now Thomas one of the Twelve, was not with the disciples when Jesus came. So the other disciples told him, “We have seen the Lord!” But he said to them, “Unless I see the nail marks in his hands and put my finger where the nails were, and put my hand into his side, I will not believe.” John 20:24–29. Several arguments have been proposed to reject a substantial role of alterations in venous drainage of the brain in the genesis of transient global amnesia (TGA). However, these criteria are not routinely applied in other common medical conditions. Studies examining cerebral veins do not demonstrate alterations in patients who have had an episode of TGA. Dislodgment of a clot from the left atrium and subsequent pass of the embolus through various cerebral vessels ending with occlusion of an intracranial artery is widely accepted as the mechanism causing ischemic stroke in patients with atrial fibrillation. However, a clot in the left atrium using echocardiography, emboli passing through the vessels in transcranial Doppler examination, and the impacted particle in MRI T2* sequence are seldom found soon after the stroke. Rupture of a cerebral aneurysm is the most commonly accepted cause of spontaneous subarachnoid hemorrhage. However, digital substraction angiography immediately after the event usually does not reveal a leaking vessel. TGA usually consists on a single episode in the lifetime of most patients, whereas structural cervical veins alterations are permanent. Hypertension, diabetes mellitus, and smoking strongly predispose subjects to stroke. Nevertheless, subjects with these conditions remain asymptomatic most days and strokes occur just once in the lifetime in the majority of patients. Most patients with carotid stenosis have no or one vascular event during their lifetime. Many similar scenarios can be described following these patterns in several medical conditions. Should always the proposed mechanism be demonstrated with the available diagnostic tools to infer an association? Probably not. When there is robust evidence of a frequent abnormal finding in patients with a condition compared with patients without this condition, does the absence of certain findings at certain time points definitely rules out a pathogenic association? Probably not. In this issue of Stroke,1 Baracchini et al, in a very well-executed investigation, confirm a strong association between TGA and internal jugular valve insufficiency. The authors also explored, using ultrasonography, various cerebral veins at rest and during Valsalva maneuver in subjects with TGA and control subjects. They were also able to study several subjects after onset but still during the period of memory loss. They did not find evidence of intracranial reflux in patients or control subjects. The absence of reflux in every subject, although raising concerns about the sensitivity of the method used, appears to confirm a lack of a substantial reversal of flow in this setting. The authors do not discuss comprehensively on the consistent, although not statistically significant, 20% to 30% diminution of intracranial veins blood flow velocity during a Valsalva maneuver in patients and control subjects. The possibility of a Type II error may be evaluated in the future by studying a larger group of patients and control subjects. A potential detrimental effect of a reduction of flow velocity during a Valsalva maneuver triggering TGA in patients with internal jugular valve insufficiency may have been overseen with the methods used. The study of several patients during the episode is a formidable achievement. However, it may not represent the conditions just before, at onset, or triggering the event. TGA is a syndrome probably associated with different conditions.2,3 Internal jugular valve insufficiency appears to be the most prevalent abnormal finding in these patients.1,4 Interestingly, another common finding in TGA is the presence of transient hyperintense lesions in the hippocampus on MRI using diffusion-weighted sequences.5 Apparent diffusion coefficient reversal without persistent symptoms or T2 changes is uncommon.6 Cerebral vein disease, mainly cerebral vein thrombosis, is the condition most frequently described in this setting.6,7 Future research should explore a potential association between venous flow abnormalities and transient diffusion-weighted imaging changes in patients with TGA. In conclusion, Baracchini et al confirmed prior findings and provided new valuable information and insights in the pathogenesis of TGA. However, they did not definitely refute a role of cerebral veins in the pathogenesis of at least some TGA events.