Management of tandem occlusions in patients who receive rtPA

Journal of Thrombosis and Thrombolysis - Tandem occlusions exist in 17–32% of large vessel occlusion (LVO) strokes. A significant concern is bleeding when carotid stenting is performed in...     

Long-term follow-up in children with functional hemispherectomy for Rasmussen’s encephalitis

Introduction Cerebral hemispherectomy has been performed for over 60 years. Multiple variations of functional hemispherectomy have been performed since its inception by Rasmussen. Long-term follow-up for these variations is lacking in the medical literature.Methods We review the long-term follow-up for five children with Rasmussens encephalitis who underwent a modification of functional hemispherectomy.Results The length of follow-up for this cohort ranged from 13 to 23 years (mean 15.6 years). All patients experienced immediate and complete elimination of seizures. Only one patient underwent ventriculoperitoneal shunt placement. All patients are capable of ambulating on their own. Many years following their procedures, this cohort of patients remains seizure free.     

Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor

Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agent's safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery.     

A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery.

Heparin and protamine are the standard anticoagulant-antidote regimen used in almost every cardiopulmonary bypass (CPB) procedure even though both are associated with an array of complications and toxicities. Here we demonstrate that an anticoagulant aptamer-antidote pair targeting factor IXa can replace heparin and protamine in a porcine CPB model and also limit the adverse effects on thrombin generation, inflammation, and cardiac physiology associated with heparin and protamine use. These results demonstrate that targeting clotting factors upstream of thrombin in the coagulation cascade can potentially reduce the perioperative pathologies associated with CPB and suggest that the aptamer-antidote pair to FIXa may improve the outcome of patients undergoing CPB. In particular, this novel anticoagulant-antidote pair may prove to be useful in patients diagnosed with heparin-induced thrombocytopenia or those who have been sensitized to protamine, particularly patients who have insulin-dependent diabetes.     

Correlation of serum brain natriuretic peptide with hyponatremia and delayed ischemic neurological deficits after subarachnoid hemorrhage

OBJECTIVE: Serum brain natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wasting), and may exacerbate delayed ischemic neurological deficits. We examined the temporal relationship between serum BNP elevation, hyponatremia, and the onset of delayed ischemic neurological deficits and determined whether serum BNP levels correlated with the 2-week outcome after SAH. METHODS: Serum BNP and sodium were measured prospectively every 12 hours for 14 days in 40 consecutive patients admitted with SAH. All patients remained euvolemic, underwent transcranial Doppler assessment every 48 hours, and underwent angiography at the onset of delayed neurological deficits. New-onset neurological deficits were attributed to vasospasm only in the absence of other causes and when supported by transcranial Doppler or cerebral angiography. RESULTS: Sixteen patients (40%) experienced symptomatic cerebral vasospasm after SAH. A more than threefold increase in admission serum BNP was associated with the onset of hyponatremia (P < 0.05). Mean BNP levels were similar between vasospasm and nonvasospasm patients fewer than 3 days after SAH (126 +/- 39 pg/ml versus 154 +/- 40 pg/ml; P = 0.61) but were elevated in the vasospasm cohort 4 to 6 days after SAH (285 +/- 67 pg/ml versus 116 +/- 30 pg/ml; P < 0.01), 7 to 9 days after SAH (278 +/- 72 pg/ml versus 166 +/- 45 pg/ml; P < 0.01), and 9 to 12 days after SAH (297 +/- 83 pg/ml versus 106 +/- 30 pg/ml; P < 0.01). BNP level remained independently associated with vasospasm adjusting for Fisher grade and Hunt and Hess grade (odds ratio, 1.28; 95% confidence interval, 1.1-1.6). In patients in whom vasospasm developed, mean serum BNP increased 5.4-fold within 24 hours after vasospasm onset and 11.2-fold the first 3 days after vasospasm onset. Patients with increasing BNP levels from admission demonstrated no change (0 +/- 3) in Glasgow Coma Scale score 2 weeks after SAH versus a 3.0 +/- 2 (P < 0.05) improvement in Glasgow Coma Scale score in patients without increasing serum BNP levels. CONCLUSION: Increasing serum BNP levels independently were associated with hyponatremia, significantly increased the first 24 hours after onset of delayed ischemic neurological deficits, and predicted the 2-week Glasgow Coma Scale score.     

Prevalence of antibodies to human herpesvirus 8 (HHV-8) in Saudi Arabian patients with and without renal failure

BACKGROUND: Kaposi's sarcoma (KS) is the most common cancer occurring in renal transplant recipients in Saudi Arabia, where the reported incidence of posttransplantation KS is 10 times higher than the incidence in the United States and Western Europe. The reason for the particularly high incidence of posttransplantation KS in this geographic area is unknown. METHODS: To explore the possibility that the high incidence of posttransplantation KS might be the result of widespread infection with human herpesvirus 8 (HHV-8), we determined the prevalence of antibodies to HHV-8 in 201 patients with end-stage renal disease (ESRD) and a comparison group of 358 individuals without renal disease who were similar in age, sex, and area of residence. Antibodies to lytic cycle antigens of HHV-8 were determined by indirect immunofluorescence and confirmed by immunoblots using tetradecanoyl phorbol ester acetate-induced BC-3 cell extracts and recombinant small viral capsid antigen (ORF65). RESULTS: Antibodies to HHV-8 were detected in serum samples from 14 (6.97%) of 201 ESRD patients and from 10 (3.88%) of 258 in the comparison group (P=0.14). HHV-8 seropositive individuals were on average 10 years older than seronegative subjects (55.3 years vs. 46.9 years). Among HHV-8 seropositive subjects, 71% were male and 29% were female. CONCLUSIONS: Serologic evidence of HHV-8 infection was numerically more common in men and in patients with ESRD. However, among patients with and without ESRD, the strongest association was with increasing age.     

Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: A multivariate analysis of an institutional experience

OBJECT: Impairment of endothelial nitric oxide synthase (eNOS), endothelium-dependent relaxation, and cerebrovascular autoregulation all occur in vasospastic cerebral arteries following subarachnoid hemorrhage (SAH). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, both improve endothelial function and increase eNOS messenger RNA, protein, and enzymatic activity threefold. Increasing experimental evidence in animal models of SAH suggests that statins may ameliorate cerebral vasospasm. The authors hypothesized that patients chronically treated with statins would have a decreased risk of symptomatic vasospasm after SAH. METHODS: The authors retrospectively reviewed the charts of 115 patients with SAH who were consecutively admitted to the Neuroscience Intensive Care Unit of Duke University between 1998 and 2001. The independent association of statin therapy to symptomatic vasospasm was assessed using multivariate logistic regression analysis. Fifteen patients (13%) admitted with SAH were receiving statin therapy for at least 1 month before admission. Forty-nine patients (43%) experienced symptomatic vasospasm a mean of 5.8 +/- 3 days after onset of SAH. Current statin therapy on admission (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.77) was independently associated with an 11-fold reduction in the risk of symptomatic vasospasm. Fisher Grade 3 SAH (OR 2.82, 95% CI 1.50-5.71) and rupture of anterior cerebral or internal carotid artery aneurysm (OR 3.77, 95% CI 1.29-10.91) were independently associated with an increased risk of symptomatic vasospasm. CONCLUSIONS: In this retrospective case series, patients who received statin therapy for at least 1 month demonstrated an 11-fold decrease in the risk of developing symptomatic vasospasm after SAH.     

History of bipolar coagulation

Bipolar coagulation heralded an age of improved hemostasis for microneurosurgery. This, coupled with an improved understanding of microsurgical anatomy, has allowed access to areas of the brain once considered inaccessible. In this review, we trace the history of bipolar coagulation.