If an “Unknown Stroke Mechanism” Is the Problem, Is an FDG PET CT Scan the Solution?

Sir, Cryptogenic stroke is still considered around 40% of stroke etiology. Determination of exact stroke etiology is important for appropriate treatment and the best possible outcome. An FDG PET CT (Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography scan) may be an answer to our problems. How? The following explanations may be reasonable: While CT angiography is useful for plaques, it is not satisfactorily sensitive for vulnerable plaques responsible for strokes. It can detect disrupted plaques in about 81% of cases and necrotic cores in 76% of cases, but it struggles to find thin-cap fibroatheromas.[1] Interestingly, FDG PET demonstrates higher FDG uptake in the carotid artery ipsilateral to the stroke, reliably higher in hypodense plaque (less than 30 HU detected by CT angiogram) and the surface of the hypodense area.[1] It also correlates well with the degree of luminal stenosis and plaque thickness. Almost 44% of patients initially classified as cryptogenic strokes had significant plaques in their carotid arteries as detected by FDG PET.[1] Hence, this imaging modality may identify vulnerable plaques missed by our standard imaging. PET CT gives supporting information to the findings of standard angiograms in doubtful situations and may provide confirmation of our assumptions. Among all etiologies of strokes, cardioembolic etiologies have the highest mortality rate (27%). Atrial fibrillation (AF) is the most common cause of cardioembolism, but we are yet to be sure about the duration and timing of AF responsible for a stroke. In fact, AF may be caused by the stroke itself (like when the insular cortex is involved) or may simply have occurred coincidentally at the time of the stroke. Thus, all AF does not have a causal association with a stroke. Now, if we get additional evidence to prove AF to be a real reason for a stroke, our stroke management will be more appropriate and easier. FDG PET/CT is probably one such investigation. It can detect areas of atrial endothelial damage secondary to AF, which are considered strongly pathognomonic for stroke.[2] Atrial walls do not normally exhibit FDG uptake because metabolism derived from carbohydrates is lower in the atrium compared to the ventricles. However, if we do an FDG PET scan while on a high-fat, low-carbohydrate diet, there is increased FDG uptake in the atrium during AF, which indicates inflammation related to strokes is in the process.[2] This is an effective instrument for evaluating myocardial metabolic alterations and inflammation, both of which may be implicated in AF. Thus, FDG PET can assist in identifying cases of AF that are genuinely associated with strokes and may serve as an additional test to confirm the cardioembolic etiology. It can also identify cryptic AF not identified by standard ECG.[2] The results not only will help in finding a real cause for an unknown stroke but also may guide us not to have a false impression of the cardiac etiology of stroke when the real source lies elsewhere. On one hand, this modality will help us prevent patients from getting unnecessarily exposed to oral anticoagulants and yet having recurrent strokes; on the other hand, it will help us identify cryptic AF, which may act as silent killers. Patients aged between 15 and 49 years have an almost five times increased chance of having cancer within the first year of stroke diagnosis.[3] In a Canadian study involving more than 30,000 patients with an age between 45 and 85 years, cancer was diagnosed almost 2.5 times higher than individuals without stroke.[3] In fact, thromboembolism was detected to a maximum extent just a month before a cancer was diagnosed.[3] Cancer patients have a high chance of embolic stroke, especially among those stamped as “cryptogenic stroke”, compared to patients with conventional stroke mechanisms (57.9% vs 33.3%).[3] With newer advancements, the sensitivity of PET CT in cancer detection has reached new heights, and a PET CT scan of the whole body is justified before we stamp a stroke as having a cryptogenic etiology and avoid missing an unknown cancer which may get surfaced shortly. This will not only help us provide definite stroke treatment but also, in certain cases, detect an indolent and hidden harbinger of havoc (cancer). PET/CT scans that use fluorodeoxyglucose (FDG) are important for diagnosing and checking large vessel vasculitis because they can spot inflammation in large arteries and monitor the disease’s activity and treatment effectiveness.[4] It can detect inflammation early, before structural changes in the vessels are visible on other imaging techniques, helping us not to miss even seronegative vasculitis before it is too late.[4] It provides a whole-body view of the vascular system, allowing for a comprehensive assessment of inflammation. FDG PET may complement MRI in detecting cerebral small vessel disease. It can differentiate between vascular and degenerative cognitive impairment and help assess the pathophysiology of cerebral small vessel disease. This imaging modality can identify underlying dementia even before there is clinical manifestation. A PET scan involves a modest amount of radiation exposure. The effective dose is typically around 25 mSv, which is equivalent to about 8 years of background radiation exposure. The amount of radiation varies depending on the type of scan and the patient, but it is generally considered safe. But when a whole-body FDG PET CT scan complements a CT angiogram, an extra radiation exposure may be a concern; but the PET scanners equipped with high-sensitivity detectors and advanced reconstruction algorithms can improve image quality while reducing the amount of radiation needed.[5] By reducing the amount of radiotracer injected, we can further minimize radiation. Thus, along with the standard imaging modalities for stroke, a PET CT scan of the whole body may be an indispensable investigation in stroke management, especially in the following instances: In the arena of cryptogenic stroke. Recurrent stroke in a patient with a family history of cancer or a past history of cancer where the stroke itself may hint at an increased prothrombotic state in the process secondary to an active malignancy. The patient is taking anticoagulants for AF but continues to experience recurrent strokes. We are uncertain whether AF is the actual cause of the strokes. FDG-PET scans also offer several advantages in acute stroke treatment, like in identifying penumbral tissue, helping in taking decisions for acute stroke intervention. It also helps in stroke rehabilitation, including assessing metabolic activity in the brain, identifying potentially salvageable tissue, and possibly predicting stroke recovery. More studies are welcome, including this imaging modality, for deeper understanding of stroke etiology for the best possible stroke care. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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