Stroke Systems of Care During the COVID-19 Epidemic in Kobe City.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) outbreak raised concerns over healthcare systems' ability to provide suitable care to stroke patients. In the present study, we examined the provision of stroke care in Kobe City during the COVID-19 epidemic, where some major stroke centers ceased to provide emergency care. METHODS: This was a cross-sectional study. The Kobe Stroke Network surveyed the number of stroke patients admitted to all primary stroke centers (PSCs) in the city between March 1 and May 23, 2020, and between March 3 and May 25, 2019. In addition, online meetings between all PSC directors were held regularly to share information. The survey items included emergency response system characteristics, number of patients with stroke hospitalized within 7 days of onset, administered treatment types (IV rt-PA, mechanical thrombectomy, surgery, and endovascular therapy), and stroke patients with confirmed COVID-19. RESULTS: During the period of interest in 2020, the number of stroke patients hospitalized across 13 PSCs was 813, which was 15.5% lower than that during the same period of 2019 (p = 0.285). The number of patients admitted with cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage decreased by 15.4% (p = 0.245), 16.1% (p = 0.659), and 14.0% (p = 0.715), respectively. However, the rates of mechanical thrombectomy and surgery for intracerebral hemorrhage were slightly increased by 12.1% (p = 0.754) and 5.0% (p = 0.538), respectively. PSCs that ceased to provide emergency care reported a decrease in the number of stroke cases of 65.7% compared with the same period in 2019, while other PSCs reported an increase of 0.8%. No case of a patient with stroke and confirmed COVID-19 was reported during the study period. CONCLUSION: Kobe City was able to maintain operation of its stroke care systems thanks to close cooperation among all city PSCs and a temporal decrease in the total number of stroke cases.

Impact of Additional Lipid-Lowering Therapy on New Ischemic Lesions of Diffusion-Weighted Imaging in Carotid Artery Stenting.

BACKGROUND: New ischemic lesions on diffusion-weighted imaging (DWI) are frequently found after carotid artery stenting (CAS) and sometimes cause neurologic deficit. We investigated the rate and the potential factor of new DWI lesions during the perioperative period of CAS in symptomatic patients at our institution. MATERIALS AND METHODS: Of 187 consecutive patients who underwent CAS (April 2013-August 2016), we investigated 60 symptomatic patients with artery-to-artery embolism from carotid plaque. During hospitalization for ischemic stroke, patients with more than 120 mg/dL of plasma low-density lipoprotein cholesterol (LDL-C) level or more than 100 mg/dL of LDL-C level in case of coronary artery disease were administered additional lipid-lowering therapy (ALL therapy), for example, the same statin as patients took or evolocumab for patients with the maximum tolerated dose of statin. All patients were implanted the same type of carotid stent by the same procedure as we predefined. We implemented data analysis to identify factors on new DWI lesions. RESULTS: New DWI lesions were observed in 17 patients (28%). Baseline plasma triglyceride level was found to be the factor of new DWI lesions. ALL therapy was administered to 26 patients, including 8 patients of evolocumab. The average period from the start of ALL therapy to CAS was 15 days. New DWI lesions occurred in 11.5% of patients with ALL therapy and 41.2% of patients without ALL therapy (P = .019). Multivariate logistic analysis showed that ALL therapy was an independent predictor of absence of new DWI lesions (P = .029). CONCLUSIONS: ALL therapy before CAS may reduce new DWI lesions.

Incidence and Outcomes of Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Registry-based Descriptive Trial in Kobe City.

The current study aims to evaluate the incidence and results of aneurysmal subarachnoid hemorrhage (aSAH) throughout Kobe City. Based on a multicenter retrospective registry-based descriptive trial involving all 13 primary stroke centers in Kobe City, patients with aSAH treated between October 2017 and September 2019 were studied. A total of 334 patients were included, with an estimated age-adjusted incidence of 11.12 per 100,000 person-years. Curative treatment was given to 94% of patients, with endovascular treatment (51%) preferred over surgical treatment (43%). Of the patients, 12% were treated by shunt surgery for sequential hydrocephalus with a worse outcome at 30 days or discharge (14% vs. 46%, odds ratio (OR): 0.19, 95% confidence interval (CI): 0.088-0.39, p-value <0.001). As for vasospasm and delayed cerebral ischemia, most patients were given intravenous fasudil infusion (73%), with endovascular treatment for vasospasm in 24 cases (7.2%). The fasudil group had more good outcomes (42% vs. 30%, OR: 1.64, 95% CI: 0.95-2.87, p-value = 0.075) and significantly less death (3.3% vs. 35%, OR: 0.064, 95% CI: 0.024-0.15, p-value <0.001) at 30 days or discharge. Mortality rose from 12% at 30 days or discharge to 17% at 1 year, but neurological function distribution improved over time (modified Rankin Scale 0-2 was 39% at 30 days or discharge, 53% at 60 days, and 63% at 1 year). Our retrospective registered trial presented various statistics on aSAH, summarizing the current treatment status and prognosis.

Significance of blood aspiration in carotid artery stenting with Angioguard XP.

BACKGROUND AND PURPOSE: In some patients, angiographic flow impairment is observed during carotid artery stenting (CAS) using Angioguard XP (AGXP), resulting in neurological symptoms. CAS was thus modified to improve clinical outcome. METHODS: Ninety-seven patients were treated with CAS using AGXP from January 2008 to October 2009. In period I (January-December 2008; n = 53), blood aspirations were performed only in no-flow cases. In period II (January-October 2009; n = 44), blood aspirations were performed in no-flow and slow-flow cases. Clinical outcome, detection of microembolic lesions on diffusion-weighted imaging (DWI) and flow impairment during CAS were examined between these two periods before and after modifying the CAS procedure. RESULTS: Periprocedural transient ischemic attacks occurred in 10 patients (18.9%) and one patient (2.27%) in periods I and II, respectively (P = .018). Minor and major strokes were observed in two patients in each period (P = .849). New ipsilateral DWI lesions were detected in 25 patients (47.2%) and 11 patients (25.0%) in periods I and II, respectively (P = .024). Among 18 slow-flow cases, new DWI lesions were detected in one patient (9.09%) and five patients (71.4%) with (n = 11) and without (n = 7) blood aspirations, respectively (P = .013). Neurological symptoms were observed only in three of seven patients (42.9%) without aspirations, compared to one of 11 patients (9.1%) with aspirations (P = .043). CONCLUSION: Postoperative symptomatic stroke and new DWI lesions are significantly associated with blood flow impairment during CAS using AGXP. When flow impairment occurs, blood aspiration should be performed.

Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury.

Umbilical cord blood (UCB) is a rich source of hematopoetic stem cells (HSCs). We have isolated a novel cell line population of stem cells from human UCB that exhibit properties of self-renewal, but do not have cell-surface markers that are typically found on HSCs. Analysis of transcripts revealed that these cells express transcription factors Oct-4, Rex-1, and Sox-2 that are typically expressed by stem cells. We refer to these novel cells as nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs). Previous studies have shown that the intravenous infusion of UCBCs can ameliorate neurological deficits arising from ischemic brain injury. The identity of the cells that mediate this restorative effect, however, has yet to be determined. We postulate that nh-UCBSCs may be a source of the UCB cells that can mediate these effects. To test this hypothesis, we intravenously injected one million human nh-UCBSCs into rats 48 h after transient unilateral middle cerebral artery occlusion. Animals in other experimental groups received either saline injections or injections of RN33b neural stem cells. Animals were tested for neurological function before the infusion of nh-UCBSCs and at various time periods afterwards using a battery of behavioral tests. In limb placement tests, animals treated with nh-UCBSCs exhibited mean scores that were significantly better than animals treated with RN33b neural stem cells or saline. Similarly, in stepping tests, nh-UCBSC-treated animals again exhibited significantly better performance than the other experimental groups of animals. Analysis of infarct volume revealed that ischemic animals treated with nh-UCBSCs exhibited a 50% reduction in lesion volume in comparison to saline-treated controls. Histological analysis of brain tissue further revealed the presence of cells that stained for human nuclei. Some human nuclei-positive cells were also co-labeled for NeuN, indicating that the transplanted cells expressed markers of a neuronal phenotype. Cells expressing the human nuclei marker within the brain, however, were rather scant, suggesting that the restorative effects of nh-UCBSCs may be mediated by mechanisms other than cell replacement. To test this hypothesis, nh-UCBSCs were directly transplanted into the brain parenchyma after ischemic brain injury. Sprouting of nerve fibers from the nondamaged hemisphere into the ischemically damaged side of the brain was assessed by anterograde tracing using biotinylated dextran amine (BDA). Animals with nh-UCBSC transplants exhibited significantly greater densities of BDA-positive cells in the damaged side of the brain compared to animals with intraparenchymal saline injections. These results suggest that restorative effects observed with nh-UCBSC treatment following ischemic brain injury may be mediated by trophic actions that result in the reorganization of host nerve fiber connections within the injured brain.

Adenosine triphosphate accelerates recovery from hypoxic/hypoglycemic perturbation of guinea pig hippocampal neurotransmission via a P(2) receptor.

The present study was designed to assess the effects of adenosine triphosphate (ATP) on hippocampal neurotransmissions under the normal and hypoxic/hypoglycemic conditions. ATP reversely depressed population spikes (PSs), which were monitored in the dentate gyrus of guinea pig hippocampal slices, in a dose-dependent manner at concentrations ranged from 0.1 micro M to 1 mM. A similar depression was obtained with the P(2) receptor agonist, alpha,beta-methylene ATP (alpha,beta-MeATP), and the effect was inhibited by the P(2) receptor antagonists, suramin and PPADS. The inhibitory action of ATP or alpha,beta-MeATP was inhibited by the gamma-aminobutyric acid(A) (GABA(A)) receptor antagonist, bicuculline, but it was not affected by theophylline, a broad inhibitor of adenosine (P(1)) receptors, tetraethylammonium, a broad inhibitor of K(+) channels, or ecto-protein kinase inhibitors. ATP or alpha,beta-MeATP enhanced GABA release from guinea pig hippocampal slices, that was inhibited by deleting extracellular Ca(2+) or in the presence of tetrodotoxin, while ATP had no effect on GABA release from cultured rat hippocampal astrocytes or postsynaptic GABA-gated channel currents in cultured rat hippocampal neurons. Twenty-minutes deprivation of glucose and oxygen from extracellular solution abolished PSs, the amplitude recovering to about 30% of basal levels 50 min after returning to normal conditions. ATP or alpha,beta-MeATP accelerated the recovery after hypoxic/hypoglycemic insult (approximately 80% of basal levels). Adenosine diphosphate and adenosine monophosphate accelerated the recovery, but to a much lesser extent, and adenosine had no effect. The results of the present study thus suggest that ATP inhibits neuronal activity by enhancing neuronal GABA release via a P(2) receptor, perhaps a P2X receptor, thereby protecting against hypoxic/hypoglycemic perturbation of hippocampal neurotransmission.

[Chondroma of the lumbar spinal canal: a case report].

Chondroma is a benign cartilaginous tumor and fairly rare in the spine. A case of chondroma in the lumbar spine is presented. A male at age 66 was suffered from progressive low back pain associated with hypesthesia in his right leg. Radiographic examination showed an extradural mass in the dorsal part of spinal canal at L 5 level. No osteolytic change was noted by CT scan. MRI showed iso-intensity with marginal enhancement on T 1-weighted images and heterogeneous intensity on T 2-weighted image. The mass was totally removed by laminectomy and pathohistologically diagnosed as chondroma. Postoperative course was uneventful and the symptoms disappeared completely. One of the origin of chondroma is thought to be metaplasia of the connective tissue in contact with spine. This is why no pathological change was found in bone adjacent to the tumor. Careful preoperative diagnosis and total removal of the tumor is important since malignant transformation may happen in chondroma.

Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the sleeping beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glioblastoma.

Glioblastoma is a fatal brain tumor that becomes highly vascularized by secreting proangiogenic factors and depends on continued angiogenesis to increase in size. Consequently, a successful antiangiogenic therapy should provide long-term inhibition of tumor-induced angiogenesis, suggesting long-term gene transfer as a therapeutic strategy. In this study a soluble vascular endothelial growth factor receptor (sFlt-1) and an angiostatin-endostatin fusion gene (statin-AE) were codelivered to human glioblastoma xenografts by nonviral gene transfer using the Sleeping Beauty (SB) transposon. In subcutaneously implanted xenografts, co-injection of both transgenes showed marked anti-tumor activity as demonstrated by reduction of tumor vessel density, inhibition or abolition of glioma growth, and increase in animal survival (P = 0.003). Using luciferase-stable engrafted intracranial gliomas, the anti-tumor effect of convection-enhanced delivery of plasmid DNA into the tumor was assessed by luciferase in vivo imaging. Sustained tumor regression of intracranial gliomas was achieved only when statin-AE and sFlt-1 transposons were coadministered with SB-transposase-encoding DNA to facilitate long-term expression. We show that SB can be used to increase animal survival significantly (P = 0.008) by combinatorial antiangiogenic gene transfer in an intracranial glioma model.