Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain.

Cell replacement therapy is expected as a new and more radical treatment against brain damage. We previously reported that transplanted human cerebral organoids extend their axons along the corticospinal tract in rodent brains. The axons reached the spinal cord but were still sparse. Therefore, this study optimized the host brain environment by the adeno-associated virus (AAV)-mediated expression of axon guidance proteins in mouse brain. Among netrin-1, SEMA3, and L1CAM, only L1CAM significantly promoted the axonal extension of mouse embryonic brain tissue-derived grafts. L1CAM was also expressed by donor neurons, and this promotion was exerted in a haptotactic manner by their homophilic binding. Primary cortical neurons cocultured on L1CAM-expressing HEK-293 cells supported this mechanism. These results suggest that optimizing the host environment by the AAV-mediated expression of axon guidance molecules enhances the effect of cell replacement therapy.

Factors associated with the new appearance of cerebral microbleeds after endovascular treatment for unruptured intracranial aneurysms.

PURPOSE: Endovascular treatment of unruptured intracranial aneurysms may increase cerebral microbleeds (CMBs) in postprocedural T2*-weighted MRIs, which may be a risk for future intracerebral hemorrhage. This study examined the characteristics of postprocedural CMBs and the factors that cause their increase. METHODS: The patients who underwent endovascular treatment for unruptured intracranial aneurysms from April 2016 to February 2018 were retrospectively analyzed. Treatment techniques for endovascular treatment included simple coiling, balloon-assisted coiling, stent-assisted coiling, or flow diverter placement. To evaluate the increase in CMBs, a head MRI including diffusion-weighted imaging and T2*-weighted MRIs was performed on the preprocedural day; the first postprocedural day; and at 1, 3, and 6 months after the procedure. RESULTS: Among the 101 aneurysms that were analyzed, 38 (37.6%) showed the appearance of new CMBs. In the multivariate analysis examining the causes of the CMB increases, chronic kidney disease, a higher number of preprocedural CMBs, and a higher number of diffusion-weighted imaging-positive lesions on the first postprocedural day were independent risk factors. Furthermore, a greater portion of the increased CMBs was found in cortical and subcortical lesions of the treated vascular perfusion area within 1 month after the procedure. CONCLUSION: In endovascular treatment for unruptured intracranial aneurysms, CMBs tended to increase in patients with small vessel disease before the procedure, and it was also implicated in hemorrhagic changes after periprocedural microinfarction.

Symptomatic Cavernous Internal Carotid Artery Aneurysm Complicated by Simultaneous Rapid Growth of the Intra-aneurysmal and Parent Artery Thromboses.

Cavernous internal carotid artery (ICA) aneurysm complicated by simultaneous and spontaneous formation of thromboses in the aneurysm and the parent artery is a rare clinical condition. Although the majority of patients have good outcomes, some patients experience severe ischemic stroke. Here, we report a case of symptomatic large cavernous ICA aneurysm complicated by rapid growth of an intra-aneurysmal thrombosis with simultaneous parent artery thrombosis. A 68-year-old female presented with sudden-onset diplopia, right ptosis, right conjunctival hyperemia, and paresthesia of the right face. Magnetic resonance imaging (MRI) and digital subtract angiography (DSA) revealed the presence of a large partially thrombosed aneurysm in the cavernous portion of the right ICA. We planned endovascular embolization using a flow-diverting (FD) stent. Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel was started 2 weeks prior to treatment. Although the neurological state was stable, DSA conducted on the day of the endovascular treatment showed rapid growth of an intra-aneurysmal thrombosis and de novo thrombosis in the parent artery. Direct aspiration was performed via a distal support catheter with proximal blood flow arrest using a balloon-guide catheter, and the FD stent was successfully deployed. The patient's symptoms improved postoperatively and DSA obtained 12 months after the procedure confirmed complete occlusion of the aneurysm. Although the exact mechanism of simultaneous thrombosis formation of the aneurysm and its parent artery remains unclear, it is important to recognize that rapid growth of the thrombosis increases the risk of ischemic stroke.

Treatment of Aneurysms in Persistent Primitive Trigeminal Arteries with Stent-Assisted Coil Embolization.

Objective: Persistent primitive trigeminal artery (PPTA) is a rare condition in which a fetal carotid-basilar anastomosis persists into adulthood. PPTA aneurysms often necessitate endovascular treatment and adjunctive techniques, such as stent- or balloon-assisted techniques, are sometimes selected. This case report describes two women in their sixties with unruptured right PPTA aneurysms who underwent stent-assisted coil embolization procedures, with consideration of the anatomical features in each case. Case Presentations: One patient presented with an aneurysm at the bifurcation of the PPTA and the basilar artery (BA), which was classified as Saltzman type 1 with a hypoplastic vertebral artery (VA)-BA system. A stent was deployed from the BA to the PPTA to cover the neck of the aneurysm and coil embolization was performed. The second patient presented with an aneurysm at the bifurcation of the PPTA and the internal carotid artery (ICA), which was classified as Saltzman type 2 with a hypoplastic VA-BA system. A stent was deployed from the PPTA to the petrous segment of the ICA covering the neck of the aneurysm and coil embolization was performed. In both patients, the 1-year follow-up digital subtraction angiography (DSA) showed that the aneurysms had not recurred. Conclusion: The PPTA aneurysms were successfully treated with stent-assisted coil embolization. The treatment strategy should be devised in accordance with both the lesion site and the PPTA variant.

Effect of treatment modality and cerebral vasospasm agent on patient outcomes after aneurysmal subarachnoid hemorrhage in the elderly aged 75 years and older.

OBJECTIVE: We sought to examine whether the effect of treatment modality and drugs for cerebral vasospasm on clinical outcomes differs between elderly and non-elderly subarachnoid hemorrhage (SAH) patients in Japan. METHODS: We analyzed the J-ASPECT Study Diagnosis Procedure Combination database (n = 17,343) that underwent clipping or coiling between 2010 and 2014 in 579 hospitals. We stratified patients into two groups according to their age (elderly [≥75 years old], n = 3,885; non-elderly, n = 13,458). We analyzed the effect of treatment modality and anti-vasospasm agents (fasudil hydrochloride, ozagrel sodium, cilostazol, statin, eicosapentaenoic acid [EPA], and edaravone) on in-hospital poor outcomes (mRS 3-6 at discharge) and mortality using multivariable analysis. RESULTS: The elderly patients were more likely to be female, have impaired levels of consciousness and comorbidity, and less likely to be treated with clipping and anti-vasospasm agents, except for ozagrel sodium and statin. In-hospital mortality and poor outcomes were higher in the elderly (15.8% vs. 8.5%, 71.7% vs. 36.5%). Coiling was associated with higher mortality (odds ratio 1.43, 95% confidence interval 1.2-1.7) despite a lower proportion of poor outcomes (0.84, 0.75-0.94) in the non-elderly, in contrast to no effect on clinical outcomes in the elderly. A comparable effect of anti-vasospasm agents on mortality was observed between non-elderly and elderly for fasudil hydrochloride (non-elderly: 0.20, 0.17-0.24), statin (0.63, 0.50-0.79), ozagrel sodium (0.72, 0.60-0.86), and cilostazol (0.63, 0.51-0.77). Poor outcomes were inversely associated with fasudil hydrochloride (0.59, 0.51-0.68), statin (0.84, 0.75-0.94), and EPA (0.83, 0.72-0.94) use in the non-elderly. No effect of these agents on poor outcomes was observed in the elderly. CONCLUSIONS: In contrast to the non-elderly, no effect of treatment modality on clinical outcomes were observed in the elderly. A comparable effect of anti-vasospasm agents was observed on mortality, but not on functional outcomes, between the non-elderly and elderly.

Variant Type of Posterior Reversible Encephalopathy Syndrome Associated with Deep Brain Hemorrhage: Case Report and Review of the Literature.

BACKGROUND: Various radiologic patterns of posterior reversible encephalopathy syndrome (PRES) have been reported. Among them, PRES involving brainstem, thalamus, or deep white matter and lacking parieto-occipital edema is rare. Although PRES in general has a benign course, PRES-related intracranial hemorrhage has been associated with a poor prognosis. We report a case of variant type of PRES associated with deep brain hemorrhage and discuss the characteristics of PRES-related intracranial hemorrhage via a literature review. CASE DESCRIPTION: A woman aged 41 years with a history of untreated hypertension presented to our hospital complaining of severe headache and with an elevated blood pressure of 237/142 mmHg. Computed tomography revealed a hemorrhage in the left thalamus and basal ganglia. Magnetic resonance imaging revealed remarkable hyperintensity in the left cerebellum, pons, bilateral temporal lobes, bilateral basal ganglia, and bilateral cerebral white matter on fluid-attenuated inversion recovery imaging, which represented vasogenic edema. The parieto-occipital regions were unremarkable. Given this clinical presentation, PRES associated with deep brain hemorrhage was suspected. The patient received strict blood pressure control treatment, which resulted in gradual symptom improvement. Magnetic resonance images obtained 1 month after admission demonstrated an almost complete resolution of the edema. CONCLUSIONS: Although hemorrhage in the thalamus, basal ganglia, or brainstem is uncommon in patients with PRES, it may occur in patients with variant type of PRES involving these lesions. It is important to recognize the presence of variant patterns of clinical features and radiologic findings of PRES to allow for early identification and appropriate treatment.

Long-term Outcomes After Intraprocedural Aneurysm Rupture During Coil Embolization of Unruptured Intracranial Aneurysms.

BACKGROUND: The long-term outcomes of patients with intraprocedural aneurysm rupture (IPR) during endovascular coiling of unruptured intracranial aneurysms (UIAs) remain unclear. We investigated the long-term outcomes and predictors of neurological outcomes in patients who sustained IPR during coil embolization of UIAs. METHODS: We retrospectively analyzed the medical record of 312 untreated UIAs in 284 patients who underwent endovascular coiling between April 2013 and July 2018. RESULTS: The mean follow-up period for the entire cohort was 25.6 months. Twelve patients (3.8%) experienced IPR. The mean aneurysm size in the IPR cohort was significantly smaller than that in the no-IPR cohort (P = 0.045). The IPR cohort had a higher percentage of earlier subarachnoid hemorrhage from another aneurysm (P = 0.019), anterior communicating artery (AComA) aneurysm (P < 0.001), and basilar artery (BA) aneurysm (P = 0.022) than the no-IPR cohort. Neurologic deterioration was observed in 3 patients. The morbidity and mortality rates of the IPR cohort were 25% and 8.3%, respectively. Patients with IPR during coil embolization for AComA aneurysm did not develop neurological deterioration. Two of the 3 patients (66.7%) with a BA aneurysm had neurological deterioration. The proportion of patients with an mRS score of 0-2 at the last follow-up did not differ between the 2 cohorts (P = 0.608). CONCLUSIONS: The proportion of functionally independent patients did not differ between patients with and without IPR. Patients with BA aneurysms who developed an IPR tended to exhibit more unfavorable clinical courses than patients with AcomA aneurysms.

Usefulness of Oral Xa Inhibitor for Management of Ischemic Stroke Associated with Thrombosis in the Pulmonary Vein Stump after Lung Resection.

OBJECTIVES: Brain infarction is a critical complication after lung resection using video-assisted thoracoscopic surgery. Recent reports have described its association with thrombosis in the pulmonary vein (PV) stump. However, the optimal management of this complication remains controversial. We describe serial 3 cases of brain infarctions associated with thrombosis in the PV stumps, which were successfully treated with the oral Xa inhibitor rivaroxaban. METHODS AND RESULTS: We retrospectively reviewed medical records of 3 patients. The first case was a 72-year-old man who underwent left upper lobectomy for treatment of lung adenocarcinoma. The second case was a 55-year-old man who underwent right lower segmentectomy for treatment of metastatic tumor from Barrett's esophageal carcinoma. The third case was a 73-year-old man who underwent left upper lobectomy for treatment of metastatic tumor from colon adenocarcinoma. In the first case, a large cerebellar infarction was developed and a decompressive craniotomy was performed on postoperative day 4. In the second and the third case, cerebral infarctions in the territories of right middle cerebral arteries occurred on postoperative day 2. In all cases, contrast-enhanced computed tomography demonstrated the thrombi in the stumps of the PVs. They were treated with oral administration of rivaroxaban without adverse effect, and the thrombi in the PVs disappeared within 1 month. DISCUSSION: Blood flow stasis in the long PV stump after lung resection might contribute to thrombosis development. Oral Xa inhibitor rivaroxaban appeared to be safe and useful for the management of ischemic stroke associated with PV thrombosis after lung resection.

Thrombosis of Large Aneurysm Induced by Flow-Diverter Stent and Dissolved by Direct Factor Xa Inhibitor.

BACKGROUND: Antiplatelet agents are typically administered before and after treatment using flow-diverter stents (FDS) to prevent thrombotic complications, but the effects of anticoagulants are unclear. We present a patient with a giant aneurysm treated with an FDS. The thrombus within the aneurysm was dissolved when a direct factor Xa inhibitor was administered to treat lower limb venous thrombosis that occurred secondary to steroid use. CASE DESCRIPTION: A 60-year-old woman with a 30-mm giant thrombosed aneurysm in the cavernous segment of the right internal carotid artery presenting with headache and right abducens nerve palsy was treated by placing an FDS. Diplopia and increased pain in her right eye appeared on postoperative day 7, and both were alleviated by continuous oral administration of prednisolone. Angiography 3 months postoperatively revealed that the aneurysm thrombosis had progressed, and there were signs of healing. However, at the same time, lower limb venous thrombosis occurred, which was treated by continuous edoxaban. Six months after surgery, her headaches worsened and angiography showed that the aneurysm was again contrast enhanced and that the thrombus within the aneurysm had dissolved. After discontinuing edoxaban 9 months after surgery, the aneurysmal thrombosis had again rapidly progressed. CONCLUSIONS: Administration of a direct factor Xa inhibitor during healing after placing an FDS may cause dissolution of an existing thrombus; therefore factor Xa inhibitors must be used with caution.

The Influence of Age on the Outcomes of Traumatic Brain Injury: Findings from a Japanese Nationwide Survey (J-ASPECT Study-Traumatic Brain Injury).

BACKGROUND: The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients. METHODS: Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients. RESULTS: Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P < 0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at >7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P < 0.001), and incidence of acute subdural hematoma (OR, 1.89; P < 0.001) were associated with in-hospital mortality in elderly patients with TBI. CONCLUSIONS: Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

Multiple Sacral Perineurial Cysts Presented Symptoms Triggered by Nonaneurysmal Perimesencephalic Subarachnoid Hemorrhage.

The origin and pathogenesis of perineurial cysts remain unclear. Here, we report a rare case of multiple sacral perineurial cysts presented symptoms triggered by nonaneurysmal perimesencephalic subarachnoid hemorrhage (SAH). A 48-year-old male presented with a severe headache of sudden onset. Brain computed tomography revealed a SAH in the basal cistern; however, no abnormal vascular lesion was detected. Four days after the onset of the SAH, he suffered from left buttock pain, followed by urinary dysfunction and paresthesia in the left S2 and S3 dermatomes. Magnetic resonance (MR) imaging demonstrated multiple cystic lesions at the left S1 and bilateral S2 sacral roots. The two cysts at the S2 level exhibited high signal intensity on both T1- and T2-weighted images, suggesting the content of the cysts included a hematoma. He was treated with intravenous injections of steroids, and the symptoms recovered completely within 2 months. Follow-up MR imaging revealed remarkable shrinkage of the cysts. Sacral perineurial cysts should be listed in the differential diagnosis if the patient suffers from low back pain or sacral radiculopathy after the onset of SAH.

Emerging superconductivity hidden beneath charge-transfer insulators.

In many of today's most interesting materials, strong interactions prevail upon the magnetic moments, the electrons, and the crystal lattice, forming strong links between these different aspects of the system. Particularly, in two-dimensional cuprates, where copper is either five- or six-fold coordinated, superconductivity is commonly induced by chemical doping which is deemed to be mandatory by destruction of long-range antiferromagnetic order of 3d(9) Cu(2+) moments. Here we show that superconductivity can be induced in Pr2CuO4, where copper is four-fold coordinated. We induced this novel quantum state of Pr2CuO4 by realizing pristine square-planar coordinated copper in the copper-oxygen planes, thus, resulting in critical superconducting temperatures even higher than by chemical doping. Our results demonstrate new degrees of freedom, i.e., coordination of copper, for the manipulation of magnetic and superconducting order parameters in quantum materials.