Diagnostic dilemmas in a patient with multivascular embolic stroke

We describe a patient admitted to the intensive care unit with aphasia, which was due to an embolic ischaemic cerebral stroke associated with a previously unknown patent foramen ovale. Eventually, this finding during echocardiography led us to the diagnosis of pancreatic cancer. The thrombotic complications of pancreatic cancer, in combination with a large, patent foramen ovale, support the mechanism of a paradoxical embolism through the patent foramen ovale as the cause of cerebral ischaemic stroke.


Introduction
Paraneoplastic neurological manifestations in cancer patients are common and may precede the diagnosis of malignancy. In particular, the incidence of stroke in patients with cancer is notably higher than in the general population. Ischaemic stroke results mainly from a state of hypercoagulability, atherosclerosis or nonbacterial thrombotic endocarditis. However, a first-ever stroke revealing an undiagnosed, underlying malignancy is a very rare event with a poor outcome [1].  (Fig. 2). Because of the poor prognosis for this condition, further investigations were not conducted and palliative care was provided at home.

Discussion
In this case report, we demonstrate that TTE is a valuable tool in the diagnosis of unexplained, embolic, ischaemic, cerebral stroke in a patient with a hypercoagulable state due to an unknown cancer. The incidence of hypercoagulability in patients with cancer varies between 1 and 11 % clinically, and by up to 50 % in autopsy series [4]. Arterial thromboembolisms are very rare, but hypercoagulability, induced by malignancy, is a cause of unexplained intravascular thrombosis. Under these conditions, endothelial cells may express cytokine-regulated procoagulant factors, and elevated platelet reactivity due to platelet-tumour interactions may also contribute to the hypercoagulable state [5]. In 1865, Trousseau was the first to describe migratory, superficial thrombophlebitis. He linked this hypercoagulable state with malignancies, usually mucin-producing adenocarcinomas and digestive cancers [6]. In pancreatic cancers, there is a particularly high risk of a tumour in the corpus/cauda, compared with in the caput [7].
The presence of a paradoxical embolism through a PFO, which has a reported prevalence of up to 35 % of the normal population, might be responsible for more arterial embolic events than is currently understood. In our patient, signs of arterial or venous thromboembolisms were not present elsewhere.

Imaging
Screening for occult cancer in a patient with a first-ever stroke or thrombosis is not cost-effective; an active search for such cancer is only indicated in the subgroup of patients with a suspected malignancy [7]. However, echocardiography is essential in patients showing cerebral ischaemic stroke within different vascular territories. Echocardiography (sensitivity, 88 %; specificity, 97 %), initially coupled with lowerextremity venous Doppler ultrasound, is both simple and noninvasive, and should therefore be included in the diagnostic evaluation of a multivascular embolic stroke [8]. Unfortunately, due to the emergency setting, no proper data storage of the echocardiographic images was performed in our patient.

Conclusions
This was a rare case of a patient who had signs and symptoms of a first-ever embolic stroke as the initial presentation of pancreatic cancer; TTE was essential in establishing the diagnosis. In our patient, the only finding that was linked with the embolic, ischaemic stroke was the large PFO. This, in combination with the hypothesised hypercoagulability due to malignancy, makes a paradoxical embolism the probable cause of the stroke.  If a patient presents with signs and symptoms of embolic ischaemic stroke, a PFO with paradoxical embolism should be considered. Present guidelines suggest TTE as an optional diagnostic tool. However, in patients with multivascular embolic stroke, TTE is essential in establishing the diagnosis and should therefore be a standard procedure. Also, in an emergency setting, proper data storage is mandatory.
Funding None.

Conflict of interests None declared.
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