Impact of Cilostazol Pharmacokinetics on the Development of Cardiovascular Side Effects in Patients with Cerebral Infarction.

This study investigated the impact of polymorphisms of metabolic enzymes on plasma concentrations of cilostazol and its metabolites, and the influence of the plasma concentrations and polymorphisms on the cardiovascular side effects in 30 patients with cerebral infarction. Plasma concentrations of cilostazol and its active metabolites, and CYP3A5*3 and CYP2C19*2 and *3 genotypes were determined. The median plasma concentration/dose ratio of OPC-13213, an active metabolite by CYP3A5 and CYP2C19, was slightly higher and the median plasma concentration rate of cilostazol to OPC-13015, another active metabolite by CYP3A4, was significantly lower in CYP3A5*1 carriers than in *1 non-carriers (p = 0.082 and p = 0.002, respectively). The CYP2C19 genotype did not affect the pharmacokinetics of cilostazol. A correlation was observed between changes in pulse rate from the baseline and plasma concentrations of cilostazol (R = 0.539, p = 0.002), OPC-13015 (R = 0.396, p = 0.030) and OPC-13213 (R = 0.383, p = 0.037). A multiple regression model, consisting of factors of the plasma concentration of OPC-13015, levels of blood urea nitrogen, and pulse rate at the start of the therapy explained 55.5% of the interindividual variability of the changes in pulse rate. These results suggest that plasma concentrations of cilostazol and its metabolites are affected by CYP3A5 genotypes, and plasma concentration of OPC-13015, blood urea nitrogen, and pulse rate at the start of therapy may be predictive markers of cardiovascular side effects of cilostazol in patients with cerebral infarction.

Isolated cortical vein thrombosis with hemorrhagic infarction during the application of a transdermal estradiol patch: A case report.

Isolated cortical vein thrombosis (ICVT) is a rarer subtype of cerebral venous sinus thrombosis (CVST) that involves only the cortical veins without any thrombosis in the major cerebral veins or sinuses. Among the known causes of CVST are factors, such as being a young female or the use of hormonal preparations. This study presents a case of a 35-year-old female who underwent endometrial polyp removal 5 days before symptom onset and started using a transdermal estradiol patch. After 4 days of using the transdermal estradiol patch, the patient developed recurrent seizures and sustained sensory aphasia. The head computed tomography revealed hemorrhagic infarction. Given her young age and the use of hormonal therapy, CVST was suspected. However, the initial diagnosis with magnetic resonance imaging (MRI) was inconclusive, and no venous sinus thrombosis could be identified on additional cerebral angiography. Instead, stasis of venous flow in the temporal vein was noted. It was difficult to determine whether these findings were due to hemorrhage or ICVT. Upon re-evaluation with MRI, signal changes suggestive of thrombosis in a cortical vein in the parietal region, which is different from the stasis observed in cerebral angiography, led to the diagnosis of ICVT. This is the first study to link the use of transdermal estradiol patches to ICVT. In cases where ICVT leads to cerebral hemorrhage, cerebral angiography may not be useful. Instead, a comprehensive diagnosis should be made based on imaging findings from various MRI sequences and the patient's medical history.

Mechanical Thrombectomy Using Double Stent Retriever Technique for Acute Ischemic Stroke Following Embolism From the Pulmonary Vein Stump After Left Upper Lobectomy: A Case Report.

Acute ischemic stroke (AIS) following pulmonary lobectomy, which is traditionally attributed to air embolism and atrial fibrillation (AF), may occur after thrombus formation in the pulmonary vein stump (PVS). Herein, we document the mechanical thrombectomy (MT) of a carotid bifurcation occlusion post-left upper lobectomy (LUL) to manage AIS. A 76-year-old male with a history of diabetes, dyslipidemia, and a treated dural arteriovenous fistula at the transverse sigmoid junction, with no history of AF, successfully underwent LUL for a pulmonary tumor. The patient independently walked on postoperative day 1. He developed right hemiparesis and total aphasia on the morning of the second day after surgery, which was discovered by the nursing staff. A magnetic resonance imaging (MRI) confirmed an occlusion of the left common carotid artery (CCA). Tissue plasminogen activator (t-PA) was not administered owing to recent surgery. An urgent MT using multiple MT techniques carried out 90 minutes after the discovery of symptoms only achieved partial recanalization. Subsequently, a double stent retriever technique (DSRT) addressed the occlusion in the common and cervical internal carotid artery (ICA). Following this, a T occlusion was encountered, which was addressed with a combined approach using a single stent retriever (SR), achieving a thrombolysis in cerebral infarction (TICI) grade 2b result. However, postoperative aphasia and severe right hemiparesis remained. Postoperative imaging showed a significant left cerebral hemisphere infarction and a thrombus in the PVS. Oral edoxaban was administered, and PVS thrombosis did not recur. The patient was transferred to a rehabilitation facility 190 days post-embolization with a modified Rankin Scale score of 4. In this report, we demonstrate the challenging case of the DSRT in addressing AIS after LUL, which led to the formation of a massive thrombus and occlusion of the carotid artery, as revealed by the PVS. This case emphasizes the importance of collaborative efforts between thoracic surgeons and all staff involved in stroke care in managing such complex scenarios.

Remote hemorrhage after burr-hole surgery for chronic subdural hematoma: A report of two cases.

BACKGROUND: The standard neurosurgical procedure for chronic subdural hematoma is a burr-hole surgery. Postoperative hemorrhage is one of the complications after burr-hole surgery. The hemorrhage generally occurs at the surgical site; however, remote hemorrhage is rare. Here, we report two cases of remote hemorrhage after burr-hole surgery for chronic subdural hematoma and discuss the possible mechanism underlying this rare complication. CASE DESCRIPTION: Two patients presented remote hemorrhages after burrhole surgery for chronic subdural hematoma. In the first case, hemorrhage occurred in the interhemispheric fissure and contralateral subdural space. In the second case, hemorrhage occurred in the subdural space of the posterior fossa. CONCLUSION: Postoperative remote hemorrhage is a rare complication, and it can occur after both craniotomy surgery and burr-hole surgery. Neurosurgeons should consider the possibility of this rare complication, and sufficient care should be taken to select the most appropriate surgical procedure to prevent remote hemorrhage.

A novel technique to visualize true lumen in endovascular treatment of the occlusive carotid dissection and the usefulness of external-internal carotid collateral channel.

Background Dissection of the internal carotid artery (ICA) can cause occlusion or severe stenosis and is known to be one of the major causes of ischemic stroke in the young. Endovascular treatment is one of the useful options for carotid dissections, but passing the guidewire through the occlusion (lesion-cross) and confirmation of the true lumen are sometimes difficult. Case presentation A 40-year-old right-handed man complaining of dysarthria and gait disturbance consulted our hospital. Magnetic resonance imaging and angiography revealed right ICA dissection. Because of worsening symptoms with conservative treatment, we performed endovascular treatment. Prior to the lesion-cross, a microcatheter was navigated to the third segment of the internal maxillary artery and a balloon-guiding catheter was navigated to the proximal ICA. Under balloon occlusion of the ICA, superselective angiography via the ipsilateral maxillary artery and slow evacuation from the balloon-guiding catheter were performed. Thereafter, the course of the true lumen was clearly visualized, and we were able to navigate another microcatheter without difficulty. Subsequently, angioplasty and stent placement were successfully accomplished. Conclusion We presented a case of ICA dissection and demonstrated a novel technique for a safe lesion-cross for occlusive ICA dissection.

Fatal cerebral swelling immediately after cranioplasty: A case report.

BACKGROUND: Cranioplasty is a standard neurosurgical procedure which is performed after decompressive craniotomy. Fatal complications associated with this procedure are not well documented. Here, we report a case of fatal cerebral swelling after cranioplasty and discuss the possible mechanism of this complication. CASE DESCRIPTION: A 64-year-old man was admitted with the diagnosis of cerebral hemorrhage, and emergency surgery for hemorrhage removal and decompressive craniotomy were performed. One month after surgery, cranioplasty was performed using a titanium mesh plate. Sixteen hours after the surgery, the patient became comatose with bilateral dilated pupils followed by blood pressure lowering. Computed tomography of the brain showed bilateral massive cerebral edema. The titanium mesh plate was immediately removed, however, the patient's neurological condition did not recover and he died 7 days after the surgery. We speculated that the negative pressure difference and increase in cerebral blood flow after cranioplasty may have attributed to the fatal cerebral swelling. CONCLUSION: Fatal cerebral swelling after cranioplasty is a rare but devastating complication. Although it is rare, neurosurgeons should keep in mind that this fatal complication can follow cranioplasty.

Sodium 5, 6-benzylidene-L-ascorbate induces in vitro neuronal cell differentiation accompanying apoptosis and necrosis.

Antiproliferative activity through induction of differentiation by chemotherapeutic agents is required for certain types of cancers. Here, we report that a potent antitumor agent, sodium 5, 6-benzylidene-L-ascorbate (SBA), could induce morphological change of human neuroblastoma IMR-32 cells into a ganglion-like cell aggregate (pseudoganglion) having many neurites and the property of cholinergic neurons. Simultaneously with neuronal differentiation, substantial apoptosis and necrosis/type 2 physiological cell death, which is independent of apoptosis and resistant to a broad-spectrum caspase inhibitor, Z-Asp-CH2-DCB, were also observed. These data indicated that SBA could suppress tumor cell growth through the induction of three different physiological pathways such as differentiation, apoptosis and necrosis by which tissues and organs regulate their own development and maintenance.

Protection of anastomotic pathways to the vertebral artery during stenting of external carotid artery stenosis.

A 61-year-old man presented with a severe external carotid artery (ECA) stenosis with concomitant ipsilateral internal carotid artery (ICA) occlusion manifesting as amaurosis fugax. The left ophthalmic artery was supplied from the left ECA. The left intracranial ICA was supplied by the collateral flow from the contralateral ICA and ipsilateral ECA through the ophthalmic artery. The left vertebral artery also participated in the latter collateral pathway through the left occipital artery and ascending pharyngeal artery. Percutaneous revascularization of the ECA was performed using a nitinol self-expanding stent. To prevent embolic complications through the ophthalmic or vertebral arteries, distal protection was performed using a balloon. During a 22-month follow-up period, the patient was completely free from any ocular or neurological symptoms. The present case of severe ECA stenosis with ipsilateral ICA occlusion showed that percutaneous balloon angioplasty with stenting is feasible and effective. This intervention requires cautious evaluation of the anastomotic pathways connecting the ECA to the cerebral circulation to avoid embolic complications.

Involvement of the mouse Prp19 gene in neuronal/astroglial cell fate decisions.

The molecular mechanisms involved in neuronal/astroglial cell fate decisions during the development of the mammalian central nervous system are poorly understood. Here, we report that PRP19beta, a splice variant of mouse PRP19alpha corresponding to the yeast PRP19 protein, can function as a neuron-astroglial switch during the retinoic acid-primed neural differentiation of P19 cells. The beta-variant possesses an additional 19 amino acid residues in-frame in the N-terminal region of the alpha-variant. The forced expression of the alpha-variant RNA caused the down-regulation of oct-3/4 and nanog mRNA expression during the 12-48 h of the late-early stages of neural differentiation and was sufficient to convert P19 cells into neurons (but not glial cells) when the cells were cultured in aggregated form without retinoic acid. In contrast, the forced expression of the beta-variant RNA suppressed neuronal differentiation and conversely stimulated astroglial cell differentiation in retinoic acid-primed P19 cells. Based on yeast two-hybrid screening, cyclophilin A was identified as a specific binding partner of the beta-variant. Luciferase reporter assay mediated by the oct-3/4 promoter revealed that cyclophilin A could act as a transcriptional activator and that its activity was suppressed by the beta-variant, suggesting that cyclophilin A takes part in the induction of oct-3/4 gene expression, which might lead to neuroectodermal otx2 expression within 12 h of the immediate-early stages of retinoic acid-primed neural differentiation. These results show that the alpha-variant gene plays a pivotal role in neural differentiation and that the beta-variant participates in neuronal/astroglial cell fate decisions.