Thrombin activity in cerebrospinal fluid after subarachnoid hemorrhage.

Abstract

1181In all our patients, we discarded other causes of nonfocal cerebral dysfunction of a vascular origin such as syncopes, and we performed a CT scan to discard other causes of sudden focal neurological deficit. Stroke is clinically defined as the occurrence of symptoms and signs with sudden (within seconds) or at least rapid (within hours) onset, which corresponds to the affectation of vascular areas in the brain.2 All our patients met these conditions and displayed one-sided neurological signs, which strongly supports the clinical diagnosis of stroke.Having proposed in our article 3 that cerebral cysticercosis preferably affects the small vessels, it is not surprising that we do not have CT evidence of cerebral infarction in a high percentage of our patients. In other patients with lesions in small vessels, such as those with lacunar infarcts in routine CT scans, there is a positivity of between 30% and 50% of cases 4 ; even with repeat CT scans and magnetic resonance imaging, the positivity attains a rate of 89%.4 These facts and the angiographic evidence in one of our vasculitis patients, in whom the CT scan did not show infarct, 3 reassert our thesis.In two patients without risk factors and with cortical infarcts, we established that the vascular affectation mechanism could be caused by its proximity to cerebrospinal fluid reflecting meningeal inflammation. We do not know with certainty whether the damage from cerebral cysticercosis is directly on the cerebral blood vessels or if it is mediated by other mechanisms. The neurocysticercosis could be an associated or independent risk factor for stroke.3 The risk factor contributes to the susceptibility to stroke and may or may not be the cause of stroke. There is no doubt, however, that in some of our 31 patients, the cause of stroke was not established.Our major concern was to show that cerebral cysticercosis is a risk factor for stroke. We have studied patients with stroke in whom we have been unable to demonstrate vasculitis by angiography but have been able to do so with intracranial surgery or autopsy. On the other hand, we have studied patients with cerebral cysticercosis without stroke in whom we have found severe vasculitis by means of angiography and surgery. These patients undoubtedly have a potential risk for stroke.We agree that there are new, demonstrable causes of stroke among young patients, especially in a subgroup with no known risk factors for stroke, 5 and that some of the patients of our series could have one of these causes. In November 1988, we modified our standard protocol for stroke to improve research among young patients, and we have been able to establish that cerebral cysticercosis was the attributable cause of stroke in only 3% of them.There is a probable association between cerebral cysticercosis and susceptibility to stroke. It is, therefore, a possible risk factor for stroke that should be taken into account, particularly among young and middle-aged patients; and in some cases, it is the attributable cause of stroke.

Intrathecal Administration of Thrombin Inhibitor Ameliorates Cerebral Vasospasm

“…This suggests that such an imbalance between TF and TFPI in the CSF tends to promote thrombin generation under normal physiological conditions and also after SAH. Our preliminary study also found that thrombin activity was extremely elevated in the CSF of patients with SAH, and correlated well with the occurrence of delayed cerebral vasospasm [16, 17]. These observations suggested to us that thrombin activation in the CSF after SAH causes vasospasm.…”

“…Vasospasm is believed to continue for a relatively long time after SAH (up to several days), and our clinical data showed that extremely high levels of thrombin persisted for two weeks after SAH [16, 17], suggesting that thrombin is present at a high level in this experimental model. Therefore, we developed an experimental design to evaluate the influence of long-term inhibition of thrombin by hirudin.…”

Activation of Protease-Activated Receptor-1 Triggers Astrogliosis after Brain Injury

“…Given their possible entry into brain tissue during cerebrovascular insult, the effects of blood-derived proteases such as thrombin in the CNS have come under increasing scrutiny (Akiyama et al, 1992;Cunningham et al, 1993;Nishino et al, 1993;Lee et al, 1996;. Preliminary data show that subdural hematoma can elevate thrombin levels 250-fold in CSF from 100 pM to 25 nM for a period of Ͼ1 week (Suzuki et al, 1992), suggesting that appreciable amounts of thrombin can be generated and persist at sites of cerebrovascular injury. When bleeding occurs directly , and ␤-actin transcripts.…”

Broad-Spectrum and Selective Serine Protease Inhibitors Prevent Expression of Platelet-Derived Growth Factor–BB and Cerebral Vasospasm After Subarachnoid Hemorrhage

“…[31][32][33] After SAH, it has been reported that levels of thrombin-antithrombin III complex and F1ϩ2, molecular markers of thrombin activation in the CSF, were elevated and correlated well with the clinical severity of SAH at the onset and occurrence of cerebral vasospasm. 11,12,34,35 Recently, it has been reported that intrathecal placement of collagen pellets releasing thrombin inhibitor prevented the development of canine vasospasm. 36 Although vascular endothelial and smooth muscle cells are capable of expressing thrombin receptor, 37 and thrombin causes the immediate contraction of smooth muscle cells via activated thrombin receptor, 38,39 the peak thrombinantithrombin III complex concentration in the CSF of SAH patients was apparently earlier (on days 2 to 5) than the development of human cerebral vasospasm, which indicated that thrombin activation and its vasoconstrictive effect were not a direct cause of cerebral vasospasm.…”