Introduction

   Delayed cerebral ischemia and cerebral vasospasm remain the most common deliberating neurological complications following aneurysmal subarachnoid hemorrhage (SAH).¹²⁾ It has been considered a strong correlation between cerebral vasospasm in large arteries and cerebral ischemia.¹⁰⁾ Symptomatic vasospasm leading to delayed ischemic neurologic deficits (DINDs) occurs in 19~46% of SAH.⁸⁾ However, several studies revealed that vasospasm doesn't always bring on hemodynamic cerebral ischemia.¹⁾¹¹⁾ Recently there have been some researches that trying to find other causes of DINDs after SAH. 
   We report two cases representing that thromboembolism is regarded as a cause of DIND after aneurysmal SAH. 

Case Report 

Case 1 
   A 45-year-old man presented with 3 days history of headache, vomiting, and lethargy. Computed tomography (CT) angiography revealed a left-feeding saccular aneurysmal sac on the anterior communicating artery (ACoA). (Fig. 1A, B) Surgical obliteration of aneurysm and immediate postoperative course were uneventful. He received routine postoperative treatment including hyperdynamic therapy, also known as triple-H therapy with anti-vasospasm regimen. Twenty one days after operation, he suffered from severe headache and confusion. Transcranial Doppler (TCD) ultrasonography showed normal flow velocities, above 90 cm/second at anterior cerebral artery (ACA) and 120 cm/second at middle cerebral artery (MCA). However, diffusion magnetic resonance (MR) images demonstrated newly developed multifocal acute small infarcts on the both frontoparietal regions (Fig. 1C). He was treated with clopidogrel 75mg per day additionally. Two weeks later, his symptoms resolved and discharged without neurological deficits. 

Case 2 
   A 48-year-old man presented with a Hunt-Hess grade II SAH from a ruptured ACoA saccular aneurysm, which fed mainly from the right ACA (Fig. 2A, B). After uneventful aneurysmal clipping, the patient recovered without any neurological deficit. Postoperative treatment was done chiefly to prevent vasospasm, and usual prophylactic antivasospasm regimens were provided. On postoperative 14th day, the patient complained severe headache, right hemiparesis, and motor dysphasia. Presuming that it might be resulted from vasospasm, we carried out TCD ultrasonography and CT angiography, and there wasn't any evidence of vasospasm. However we detected multifocal acute small infarcts which were scattered on left frontoparietal region through diffusion MR images 15 days after operation (Fig. 2C). Antithrombotic agent with steroid regimen was added for one week. He became free from the foregoing symptoms and discharged. 

Discussion 

   There are four patterns of cerebral vasospasm-related infarcts. Weidauer et al.¹⁴⁾ demonstrated that moderate and severe vasospasm involving large cerebral arteries caused watershed and territorial type. They explained that lacunar and laminar cortical types are due to vasoconstriction of distal small arteries although they weren't detected easily by cerebral angiography or TCD ultrasonography. There are reports which insist that large cerebral arteries have minor effect on the regulation of cerebral blood flow (CBF) and CBF can remain normal following marked constriction of large cerebral arteries.²⁾³⁾ Recently, Stein et al.¹¹⁾ summarized the evidence against hemodynamic vasospasm by thorough reviewing literatures: 1) the relatively limited role that large arteries play in control of CBF; 2) a lack of correspondence between the sites and severity of angiographically confirmed vasospasm and cerebral ischemia; 3) the appearance of cerebral infarcts at autopsy; and 4) the disappointing clinical effects of vasospasm therapy. Aforementioned things suggest the possibility that there may be other causes bearing on small arteries and arterioles. Small focal cortical infarcts may result from cortical spreading ischemia with neuronal depolarization waves triggering episodes of acute severe vasoconstriction,²⁾ and the course proximal cerebral vasospasm combined with variable types of distal collateral flow could lead to cortical or subcortical infarcts.¹¹⁾ Weidauer et al.¹⁴⁾ have pointed the role of local toxic effects of sulcal clots as the origin of cortical infarcts. However, theses mechanisms can't explain the widespread and scattered, small infarcts like our cases. As the result, we suggest the possible role of thromboembolism as the cause of DINDs in this study. 
   Activation of tissue thromboplastin or endothelial injury can result in thromboembolism, and the two prothrombotic mechanisms fortify each other.¹³⁾ It is well known that the brain has the body's highest concentrations of tissue thromboplastin, or tissue factor, much of it localized in the adventitia of cerebral arteries and perivascular astrocytes.⁶⁾ Aneurysm rupture which is rapidly followed by activation of both platelets and many clotting factors consumption could result in coagulopathy.⁷⁾ SAH also damages the vascular endothelium, resulting in desquamation and causes the blood-brain barrier dysfunction and platelet accumulation.⁴⁾ To these cascades, small arterioles would be more liable to thromboses than large arteries. It was supported by the TCD measurements that detected microembolic signals in many patients with ruptured aneurysms, even in regions where there was no proximal vasospasm.⁵⁾ Several authors agreed that these thromboembolic events reasonably explain multiple small infarcts have documented a 44 to 67% incidence in patients with SAH,^2)5)8)10) and theses microembolic signals are strongly related to DINDs and outcome of patients.⁹⁾ Authors also agreed that overall possible factors including vasospasm should be considered: general cerebral ischemic state from initial hemorrhage, blood toxicity, displacement of cerebral vessels by brain traction during operation, a raised intracranial pressure, hydrocephalus, diffuse brain edema, and additional intraparenchymal hemorrhage. These things can initiate or aggravate thromboembolism and result in DINDs. 
   Hyperdynamic therapy, also known as triple-H therapy with anti-vasospasm regimen is well established method against hemodynamic vasospasm. Additionally, we recommend the use of antithrombotic agents in DIND patients. Now contemplating the role of thromboembolism, we should closely observe patients even after the period of vasospasm and try to seek the strategy against thromboembolism. Diffusion MR is also important, because lesions of distal small arteries and arterioles leading to small infarcts aren't perceived through cerebral angiography. 

Conclusion 

   From these cases, authors point out that thromboembolism should be weighed as a feasible cause of DINDs in patients with aneurysmal SAH. We would like to emphasize two things: One is to perform the diffusion MR images in DIND patients because cerebral angiography doesn't sufficiently represent narrowing or obstruction of small vessels; another is that anti-thrombotic therapy should be considered to prevent DINDs. 

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