Conquering Mount Fuji: Resolution of Tension Pneumocephalus with a Foley Urinary Catheter

Tension pneumocephalus is the presence of air or gas in the cranium that is under pressure. It occurs due to disruption of the skull, including trauma to the head or face, after neurosurgical procedures and occasionally, spontaneously (Schirmer et al., 2010). Patients typically present with headache but can also have neurological deficits such as decreased mental status, numbness, and weakness (Schirmer et al., 2010). It is diagnosed by computerized tomography (CT) scan (Michel, 2010). The characteristic finding is that the two frontal poles of the brain are separated by air. After diagnosis, treatment is imperative for both symptomatic relief and preventing further compression. We present a case of a patient who presented with tension pneumocephalus and unconventional treatment that resulted in clinical improvement of his symptoms and radiographic resolution of his condition

Fourth Ventricular Schwannoma: Identical Clinicopathologic Features as Schwann Cell-Derived Schwannoma with Unique Etiopathologic Origins

Background. To our knowledge, this is the sixth reported case in the literature of fourth ventricular schwannoma. The etiology and natural history of intraventricular schwannomas is not well understood. A thorough review of potential etiopathogenic mechanisms is provided in this case report. Case Description. A 69-year-old man presented with an incidentally found fourth ventricular tumor during an evaluation for generalized weakness, gait instability, and memory disturbance. Magnetic resonance imaging (MRI) revealed a heterogeneously enhancing lesion in the fourth ventricle. A suboccipital craniotomy was performed to resect the lesion. Histopathological examination confirmed the diagnosis of schwannoma (WHO grade I). Conclusions. Schwannomas should be considered in the differential diagnosis of intraventricular tumors. Although the embryologic origins may be different from nerve sheath-derived schwannomas, the histologic, clinical, and natural history appear identical and thus should be managed similarly

Dose-dependent von Willebrand Factor inhibition by aptamer BB-031 correlates with thrombolysis in a microfluidic model of arterial occlusion

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational thromboelastometry was used to assess changes in hemostasis. BB-031 induced maximal inhibition at the highest dose (3384 nM) in VWF:Ac, and demonstrated dose-dependent responses in all other assays. BB-031, but not vehicle, induced recanalization in the microfluidic model. Maximal lytic efficacy in the microfluidic model was seen at 1692 nM and not 3384 nM BB-031 when assessed by surface area. Minor changes in ROTEM parameters were seen at 3384 nM BB-031. Targeted VWF inhibition by BB-031 results in clinically measurable impairment of VWF function, and specifically VWF-GPIb function as measured by VWF:Ac. BB-031 also induced thrombolysis as measured in a microfluidic model of occlusion and reperfusion. Moderate correlation between inhibition and lysis was observed. Additional studies are required to further examine off-target effects of BB-031 at high doses, however, these are expected to be above the range of clinical targeted dosing

Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke

Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here, we used fibroblasts nanotransfected with Etv2, Foxc2, and Fli1 (EFF) to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days after injection. MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Together, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., nonviral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke

A Novel Case of Transverse Sinus Stenting and Ticagrelor Use During Pregnancy for Idiopathic Intracranial Hypertension

Background Idiopathic intracranial hypertension (IIH) is prevalent among the US population, with exacerbation of symptoms during pregnancy. Transverse sinus stenting is a new effective treatment for IIH. Stenting is avoided in pregnancy largely due to the requirement of dual antiplatelet therapy. Methods We present a case of a pregnant patient in her first trimester with signs and symptoms of fulminant IIH, including progressive visual loss, who underwent placement of a transverse sinus stent and administration of dual antiplatelet therapy with ticagrelor. Results Ticagrelor was administered pre–operatively. The patient underwent venous sinus stenting for fulminant IIH. There were no complications. She had resolution of symptoms and underwent cesarean delivery without issues. Her child displayed no signs and symptoms of abnormalities. Conclusion Venous sinus stenting for IIH can be considered in pregnant patients presenting with new or worsening IIH with associated papilledema. The use of ticagrelor did not lead to any adverse outcomes for the patient or the fetus in our case

Case Report Fourth Ventricular Schwannoma: Identical Clinicopathologic Features as Schwann Cell-Derived Schwannoma with Unique Etiopathologic Origins

Background. To our knowledge, this is the sixth reported case in the literature of fourth ventricular schwannoma. The etiology and natural history of intraventricular schwannomas is not well understood. A thorough review of potential etiopathogenic mechanisms is provided in this case report. Case Description. A 69-year-old man presented with an incidentally found fourth ventricular tumor during an evaluation for generalized weakness, gait instability, and memory disturbance. Magnetic resonance imaging (MRI) revealed a heterogeneously enhancing lesion in the fourth ventricle. A suboccipital craniotomy was performed to resect the lesion. Histopathological examination confirmed the diagnosis of schwannoma (WHO grade I). Conclusions. Schwannomas should be considered in the differential diagnosis of intraventricular tumors. Although the embryologic origins may be different from nerve sheath-derived schwannomas, the histologic, clinical, and natural history appear identical and thus should be managed similarly

Synergistic effect of aptamers that inhibit exosites 1 and 2 on thrombin

Thrombin is a multifunctional protease that plays a key role in hemostasis, thrombosis, and inflammation. Most thrombin inhibitors currently used as antithrombotic agents target thrombin's active site and inhibit all of its myriad of activities. Exosites 1 and 2 are distinct regions on the surface of thrombin that provide specificity to its proteolytic activity by mediating binding to substrates, receptors, and cofactors. Exosite 1 mediates binding and cleavage of fibrinogen, proteolytically activated receptors, and some coagulation factors, while exosite 2 mediates binding to heparin and to platelet receptor GPIb-IX-V. The crystal structures of two nucleic acid ligands bound to thrombin have been solved. Previously Padmanabhan and colleagues solved the structure of a DNA aptamer bound to exosite 1 and we reported the structure of an RNA aptamer bound to exosite 2 on thrombin. Based upon these structural studies we speculated that the two aptamers would not compete for binding to thrombin. We observe that simultaneously blocking both exosites with the aptamers leads to synergistic inhibition of thrombin-dependent platelet activation and procoagulant activity. This combination of exosite 1 and exosite 2 inhibitors may provide a particularly effective antithrombotic approach

Dose-Dependent Von Willebrand Factor Inhibition by Aptamer BB-031 Correlates with Thrombolysis in a Microfluidic Model of Arterial Occlusion

Von Willebrand Factor (VWF) plays a critical role in thrombus formation, stabilization, and propagation. Previous studies have demonstrated that targeted inhibition of VWF induces thrombolysis when administered in vivo in animal models of ischemic stroke. The study objective was to quantify dose-dependent inhibition of VWF-platelet function and its relationship with thrombolysis using BB-031, an aptamer that binds VWF and inhibits its function. VWF:Ac, VWF:RCo, T-TAS, and ristocetin-induced impedance aggregometry were used to assess BB-031-mediated inhibition of VWF. Reductions in original thrombus surface area and new deposition during administration of treatment were measured in a microfluidic model of arterial thrombolysis. Rotational thromboelastometry was used to assess changes in hemostasis. BB-031 induced maximal inhibition at the highest dose (3384 nM) in VWF:Ac, and demonstrated dose-dependent responses in all other assays. BB-031, but not vehicle, induced recanalization in the microfluidic model. Maximal lytic efficacy in the microfluidic model was seen at 1692 nM and not 3384 nM BB-031 when assessed by surface area. Minor changes in ROTEM parameters were seen at 3384 nM BB-031. Targeted VWF inhibition by BB-031 results in clinically measurable impairment of VWF function, and specifically VWF-GPIb function as measured by VWF:Ac. BB-031 also induced thrombolysis as measured in a microfluidic model of occlusion and reperfusion. Moderate correlation between inhibition and lysis was observed. Additional studies are required to further examine off-target effects of BB-031 at high doses, however, these are expected to be above the range of clinical targeted dosing

Intravenous Drug Use‐Associated Endocarditis Leads to Increased Intracranial Hemorrhage and Neurological Comorbidities

Background The United States is experiencing a rapidly increasing rate of opioid drug abuse. Intravenous drug use (IVDU)‐related endocarditis can lead to significant neurological complications with high morbidity and mortality. When patient care necessitates anticoagulation, the standards for radiographic screening and the risk for intracranial hemorrhage are not clearly elucidated. Methods We conducted a retrospective cohort study involving patients treated for infective endocarditis at a single institution from 2014 to 2018. Patients were grouped based in history of IVDU and their demographics and clinical predictors for intracranial hemorrhage were analyzed. Results A total of 351 patients met inclusion criteria for this study, of whom 170 patients (48%) had a history of IVDU‐associated endocarditis. IVDU was associated with an increased prevalence of intracranial hemorrhage (25.9% versus 13.9%; P=0.005), including intraparenchymal hemorrhage (12.4% versus 5.1%; P=0.012), subarachnoid hemorrhage (17.6 versus 4.4%; P=0.001), and cerebral microbleeds (14.1% versus 7.2%; P=0.022). IVDU was also associated with an increased incidence of infectious intracranial aneurysm (10.6% versus 1.8%; P=0.001) and brain abscesses (4.7% versus 1.1%; P=0.025). Multivariate analysis showed that the presence of intracranial septic emboli (odds ratio [OR], 18.47 [8.4–40.250]; P=0.001) and infectious intracranial aneurysm (OR, 12.38 [3.24–47.28]; P=0.001) as significant predictive factors for intracranial hemorrhage after presenting with endocarditis. Conclusion The opioid epidemic has increased the incidence of infective endocarditis and resultant neurovascular complications. IVDU‐associated endocarditis is associated with increased hemorrhagic stroke and more frequent neurodiagnostic imaging