Effectiveness of hinge craniotomy as an alternative to decompressive craniectomy for acute subdural hematoma.

BACKGROUND: Acute subdural hematoma (ASDH) is a life-threatening condition, and hematoma removal is necessary as a lifesaving procedure when the intracranial pressure is highly elevated. However, whether decompressive craniectomy (DC) or conventional craniotomy (CC) is adequate remains unclear. Hinge craniotomy (HC) is a technique that provides expansion potential for decompression while retaining the bone flap. At our institution, HC is the first-line operation instead of DC for traumatic ASDH, and we present the surgical outcomes. METHODS: From January 1, 2017, to December 31, 2022, 372 patients with traumatic ASDH were admitted to our institution, among whom 48 underwent hematoma evacuation during the acute phase. HC was performed in cases where brain swelling was observed intraoperatively. If brain swelling was not observed, CC was selected. DC was performed only when the brain was too swollen to allow replacement of the bone flap. We conducted a retrospective analysis of patient demographics, prognosis, and subsequent cranial procedures for each technique. RESULTS: Of the 48 patients, 2 underwent DC, 23 underwent HC, and 23 underwent CC. The overall mortality rate was 20.8% (10/48) at discharge and 30.0% (12/40) at 6 months. The in-hospital mortality rates for DC, HC, and CC were 100% (2/2), 21.7% (5/23), and 13.0% (3/23), respectively. Primary brain injury was the cause of death in five patients whose brainstem function was lost immediately after surgery. No fatalities were attributed to the progression of postoperative brain herniation. In only one case, the cerebral contusion worsened after the initial surgery, leading to brain herniation and necessitating secondary DC. CONCLUSIONS: The strategy of performing HC as the first-line operation for ASDH did not increase the mortality rate compared with past surgical reports and required secondary DC in only one case.

A novel treatment strategy for bladder hypoplasia: A case of megaureter in a functional solitary kidney.

Introduction: We report a case of megaureter in a functional solitary kidney in which surgery was performed after bladder capacity was increased by home bladder cycling. Case presentation: A 6-day-old girl with a left megaureter, a right multicystic dysplastic kidney, and bladder hypoplasia underwent percutaneous left nephrostomy for obstructive renal failure. At 8 months, home bladder cycling was initiated to increase bladder capacity before the planned ureterocystoneostomy. Surgery was performed after bladder capacity increased. The left ureter was compressed by the left umbilical ligament, so ureteral end-to-end anastomosis was performed at 1 year and 4 months. At 2 years and 8 months, cystometry showed age-appropriate bladder capacity and improved bladder compliance. Conclusion: To the best of our knowledge, this is the first report of bladder hypoplasia treated by home bladder cycling.

Stent retrieval for free-floating thrombus attached to carotid artery stenosis: A report of two cases.

Background: We report two cases who underwent mechanical thrombectomy using a stent retriever in advance of urgent carotid artery stenting (CAS) for carotid artery stenosis with free-floating thrombus (FFT). Case Description: Two patients showing symptomatic carotid artery stenosis with FFT underwent urgent endovascular surgery due to progressive neurological symptoms. The first case showed an FFT with 70% internal carotid artery (ICA) stenosis. After the completion of the common and external carotid artery balloon and distal ICA filter protection, we deployed a 6-mm-diameter stent retriever in the distal part of the stenosis. The white thrombus was retrieved; the angiographic shadow of the FFT disappeared; and CAS was performed. In the second case, due to a 90% severe stenosis lesion with FFT, balloon angioplasty was performed on the lesion using the push wire of the stent retriever. After angioplasty, the stent retriever was smoothly retrieved, and CAS was performed. Postoperative magnetic resonance imaging showed an increase in cerebral embolism in the first case; however, the patient's neurological symptoms improved. The second case showed in-stent plaque protrusion and required two additional stent placements; the patient showed no worsening of his neurological symptoms. Conclusion: In cases of carotid artery stenosis with FFT, it is technically possible to retrieve a thrombus with a stent retriever. Although thrombus removal may help reduce the risk of ischemic complications in a series of urgent CAS procedures, there are concerns such as mechanical irritation to the carotid artery plaque, and its indications and alternative treatments should be carefully considered.

Evaluation of Serial Intra-Arterial Indocyanine Green Videoangiography in the Surgical Treatment of Cranial and Craniocervical Junction Arteriovenous Fistulae: A Case Series.

BACKGROUND AND OBJECTIVES: Intravenous indocyanine green (IV-ICG) videoangiography is commonly performed to detect blood flow in the microscopic view. However, intra-arterial ICG (IA-ICG) videoangiography provides high-contrast imaging, repeatability within a short period of time, and clear-cut separation of the arterial and venous phases compared with IV-ICG. These features are useful for detecting retrograde venous drainage (RVD) and shunt occlusion in arteriovenous fistulae (AVF) surgery. This study aimed to investigate whether IA-ICG videoangiography can be repeatable within a short period of time and be useful for detecting RVD and shunt occlusion in cranial- and craniocervical junction (CCJ)-AVF surgery. METHODS: Between January 2012 and December 2022, 50 patients were treated with endovascular or surgical intervention for cranial- and CCJ-AVF at Tokushima University Hospital. Of these, 5 patients (6 lesions) underwent open surgery with IA-ICG videoangiography in a hybrid operating room. We analyzed the data of these 5 patients (6 lesions). RESULTS: There were 4/patient (median, range 2-12) and 3.5/lesion (median, range 2-10) intraoperative IA-ICG runs. IA-ICG videoangiography detected RVD in all patients. Clearance of IA-ICG-induced fluorescence was achieved within 30 seconds in all patients at each region of interest. After the disconnection of the fistulae, IA-ICG videoangiography and intraoperative digital subtraction angiography (DSA) confirmed the disappearance of RVD in all patients. There were no complications associated with IA-ICG videoangiography. CONCLUSION: This study showed that IA-ICG videoangiography is repeatable within a short period of time before and after obliteration and can be useful for detecting RVD and shunt occlusion in cranial- and CCJ-AVF surgery. IA-ICG videoangiography also allows intraoperative DSA studies in a hybrid operating room. Considering the recent advancements in hybrid operating rooms, combining IA-ICG videoangiography with intraoperative DSA is a useful strategy for cranial- and CCJ-AVF surgery.

Activation of the NLRP3/IL-1ß/MMP-9 pathway and intracranial aneurysm rupture associated with the depletion of ERα and Sirt1 in oophorectomized rats.

OBJECTIVE: Subarachnoid hemorrhage (SAH) due to intracranial aneurysm (IA) rupture is often a devastating event. Since the incidence of SAH increases especially in menopause, it is crucial to clarify the detailed pathogenesis of these events. The activation of vascular nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes has been studied in ischemic stroke and cardiovascular disease. However, the role of NLRP3 in IA rupture still needs to be explained. The authors sought to test their hypothesis that, under estrogen-deficient conditions, activation of NLRP3 inflammasomes via downregulation of the estrogen receptor (ER) facilitates IA rupture. METHODS: Ten-week-old female Sprague Dawley rats with and without oophorectomy were subjected to hemodynamic changes and hypertension (OVX+/HT and OVX-/HT, respectively) and fed a high-salt diet. Separately, using human brain endothelial cells (HBECs) and human brain smooth muscle cells (HBSMCs), the authors tested the effect of NLRP3 under estrogen-free conditions and in the presence of estradiol or of ER agonists. RESULTS: In OVX+/HT rats, the frequency of IA rupture was significantly higher than in OVX-/HT rats (p = 0.03). In the left posterior cerebral artery prone to rupture in OVX+/HT rats, the levels of the mRNAs encoding ERα and Sirt1, but not of that encoding ERß, were decreased, and the levels of the mRNAs encoding NLRP3, interleukin-1ß (IL-1ß), and matrix metalloproteinase 9 (MMP-9) were elevated. Immunohistochemical analysis demonstrated that the expression profiles of these proteins correlated with their mRNA levels. Treatment with an ER modulator, bazedoxifene, normalized the expression profiles of these proteins and improved SAH-free survival. In HBECs and HBSMCs under estrogen-free conditions, the depletion of ERα and Sirt1 and the accumulation of NLRP3 were counteracted by exposure to estradiol or to an ERα agonist but not to an ERß agonist. CONCLUSIONS: To the authors' knowledge, this work represents the first demonstration that, in an aneurysm model under estrogen-deficient conditions, the depletion of ERα and Sirt1 may contribute to activation of the NLRP3/IL-1ß/MMP-9 pathway, facilitating the rupture of IAs in the estrogen-deficient rat IA rupture model.

Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage.

Cerebral ischemia triggers inflammatory changes, and early complications and unfavorable outcomes of endovascular thrombectomy for brain occlusion promote the recruitment of various cell types to the ischemic area. Although anti-inflammatory M2-type macrophages are thought to exert protective effects against cerebral ischemia, little has been clarified regarding the significance of post-ischemic phase-dependent modulation of M2-type macrophages. To test our hypothesis that post-ischemic phase-dependent modulation of macrophages represents a potential therapy against ischemic brain damage, the effects on rats of an M2-type macrophage-specific activator, Gc-protein macrophage-activating factor (GcMAF), were compared with vehicle-treated control rats in the acute (day 0-6) or subacute (day 7-13) phase after ischemia induction. Acute-phase GcMAF treatment augmented both anti-inflammatory CD163+ M2-type- and pro-inflammatory CD16+ M1-type macrophages, resulting in no beneficial effects. Conversely, subacute-phase GcMAF injection increased only CD163+ M2-type macrophages accompanied by elevated mRNA levels of arginase-1 and interleukin-4. M2-type macrophages co-localized with CD36+ phagocytic cells led to clearance of the infarct area, which were abrogated by clodronate-liposomes. Expression of survival-related molecules on day 28 at the infarct border was augmented by GcMAF. These data provide new and important insights into the significance of M2-type macrophage-specific activation as post-ischemic phase-dependent therapy.

Efficacy of Utilizing Both 3-Dimensional Multimodal Fusion Image and Intra-Arterial Indocyanine Green Videoangiography in Cerebral Arteriovenous Malformation Surgery.

OBJECTIVE: An understanding of the complex morphology of an arteriovenous malformation (AVM) is important for successful resection. We have previously reported the utility of intra-arterial indocyanine green (ICG) videoangiography for this purpose, but that method cannot detect the angioarchitecture covered by brain tissue. 3-dimensional (3D) multimodal fusion imaging is reportedly useful for this same purpose, but cannot always visualize the exact angioarchitecture due to poor source images and processing techniques. This study examined the results of utilizing both techniques in patients with AVMs. METHODS: Both techniques were applied in 12 patients with AVMs. Both images were compared with surgical views and evaluated by surgeons. RESULTS: Although evaluations for identifying superficial feeders by ICG videoangiography were high in all cases, the more complicated the AVM, the lower the evaluation by 3D multimodal fusion imaging. Conversely, evaluation of the estimated range of the nidus was high in all cases by 3D multimodal fusion imaging, but low in all but one case by ICG videoangiography. Nidus flow reduction was recognized by Flow 800 analysis obtained after ICG videoangiography. CONCLUSIONS: These results showed that utilizing both techniques together was more useful than each modality alone in AVM surgery. This was particularly effective in identifying superficial feeders and estimating the range of the nidus. This technique is expected to offer an optimal tool for AVM surgery.

An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture.

BACKGROUND AND PURPOSE: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3). METHODS: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet. RESULTS: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05). CONCLUSIONS: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.

Efficacy of intraarterial indocyanine green videoangiography in surgery for arteriovenous fistula at the craniocervical junction in a hybrid operating room: illustrative cases.

BACKGROUND: Sufficient understanding of the angioarchitecture of an arteriovenous fistula (AVF) at the craniocervical junction (CCJ) is crucial to surgical treatment but is often difficult because of the complex vascular anatomy. Intraarterial indocyanine green (ICG) videoangiography has emerged as a more useful option for understanding the vascular anatomy than intravenous ICG videoangiography. This report describes two cases of CCJ AVFs successfully treated by surgery using intraarterial ICG videoangiography and describes the efficacy of this technique. OBSERVATIONS: Case 1 involved a 71-year-old man presenting with tetraparesis after sudden onset of severe headache due to subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) demonstrated CCJ epidural AVF. Intraarterial ICG videoangiography revealed the drainer, which had been difficult to identify. The AVF disappeared after disconnection of the drainer. Case 2 involved a 68-year-old man presenting with severe headache due to SAH. DSA showed multiple AVFs at the CCJ and cerebellar tentorium. Intraarterial ICG videoangiography demonstrated concomitant perimedullary AVF and dural AVF at the CCJ. All AVFs disappeared postoperatively. LESSONS: Intraarterial ICG videoangiography was useful for definitive diagnosis of CCJ AVF, facilitating identification of feeders and drainers with bright and high phase contrast and allowing repeated testing to confirm flow direction.

Involvement of Neutrophil Extracellular Traps in Cerebral Arteriovenous Malformations.

BACKGROUND: Cerebral arteriovenous malformations (cAVMs) represent tangles of abnormal vasculature without intervening capillaries. High-pressure vascular channels due to abnormal arterial and venous shunts can lead to rupture. Multiple pathways are involved in the pathobiology of cAVMs including inflammation and genetic factors such as KRAS mutations. Neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs), plays a multifunctional role in infection, inflammation, thrombosis, intracranial aneurysms, and tumor progression. However, the relationship between NETs and the pathobiology of cAVMs remains unknown. We tested whether NETs play a role in the pathobiology of cAVMs. METHODS: We analyzed samples from patients who had undergone surgery for cAVM and immunohistochemically investigated expression of citrullinated histone H3 (CitH3) as a marker of NETs. CitH3 expression was compared among samples from cAVM patients, epilepsy patients, and normal human brain tissue. Expressions of thrombotic and inflammatory markers were also examined immunohistochemically in samples from cAVM patients. RESULTS: Expression of CitH3 derived from neutrophils was observed intravascularly in all cAVM samples but not other samples. Nidi of AVMs showed migration of many Iba-I-positive cells adjacent to the endothelium and endothelial COX2 expression, accompanied by expression of IL-6 and IL-8 in the endothelium and intravascular neutrophils. Unexpectedly, expression of CitH3 was not necessarily localized to the vascular wall and thrombus. CONCLUSIONS: Our results offer the first evidence of intravascular expression of NETs, which might be associated with vascular inflammation in cAVMs.

Cytoskeleton integrity influences XRCC1 and PCNA dynamics at DNA damage.

On induction of DNA damage with 405-nm laser light, proteins involved in base excision repair (BER) are recruited to DNA lesions. We find that the dynamics of factors typical of either short-patch (XRCC1) or long-patch (PCNA) BER are altered by chemicals that perturb actin or tubulin polymerization in human cells. Whereas the destabilization of actin filaments by latrunculin B, cytochalasin B, or Jasplakinolide decreases BER factor accumulation at laser-induced damage, inhibition of tubulin polymerization by nocodazole increases it. We detect no recruitment of actin to sites of laser-induced DNA damage, yet the depolymerization of cytoplasmic actin filaments elevates both actin and tubulin signals in the nucleus. While published evidence suggested a positive role for F-actin in double-strand break repair in mammals, the enrichment of actin in budding yeast nuclei interferes with BER, augmenting sensitivity to Zeocin. Our quantitative imaging results suggest that the depolymerization of cytoplasmic actin may compromise BER efficiency in mammals not only due to elevated levels of nuclear actin but also of tubulin, linking cytoskeletal integrity to BER.

Efficacy of Intra-arterial Indocyanine Green Videoangiography in Hemangioblastoma Surgery: A Case Report.

Intravenous indocyanine green (ICG) videoangiography is reportedly useful for vascular neurosurgery, and for treating hemangioblastoma due to its high vascularity. Videoangiography obtained after intra-arterial ICG injection has emerged as a more useful option than that after intravenous injection. This report offers the first description of a case of hemangioblastoma successfully treated using intra-arterial ICG videoangiography, and describes the efficacy of this technique. A 20-year-old man presented with progressive cerebellar ataxia and dysphagia. Magnetic resonance imaging (MRI) revealed an enhanced solid tumor in the medulla oblongata. Digital subtraction angiography (DSA) showed a highly vascularized tumor. Surgery was performed to remove the tumor in a hybrid operating room. A catheter was introduced into the vertebral artery (VA) for intra-arterial ICG videoangiography. Superficial feeders and drainers were identified and flow dynamic changes in the tumor were assessed by intra-arterial ICG videoangiography. The tumor was removed after confirming lack of flow in the drainer. Intra-arterial ICG videoangiography was more useful than intravenous ICG videoangiography in hemangioblastoma surgery for identifying feeders and drainers and assessing flow dynamics in the tumor. Use of Flow 800 made these findings simpler and easier to evaluate.

Gelatin-thrombin Hemostatic Matrix-related Cyst Formation after Cerebral Hematoma Evacuation: A Report of Two Cases.

The gelatin-thrombin matrix, Floseal, is an excellent novel hemostatic agent that is used in various surgical fields. Thrombin is a serine protease, and the conversion of prothrombin to thrombin is an essential step in the coagulation cascade. However, thrombin can induce blood-brain barrier (BBB) disruption and vasogenic brain edema. This report describes two cases of gelatin-thrombin matrix-related cyst formation after cerebral hematoma evacuation. An 82-year-old man with a gelatin-thrombin matrix-related cyst was treated by cyst drainage and fenestration to the lateral ventricle. Histological evaluation of the cyst wall showed a gelatin-thrombin matrix reserve, marked infiltration of inflammatory cells, and foam cell accumulation. In addition, an 85-year-old woman with a gelatin-thrombin matrix-related cyst was treated with steroids and responded well. In both cases, the post-treatment course was uneventful. Cyst shrinkage and no recurrence were observed. The gelatin-thrombin matrix can cause cyst formation with brain edema. This is the first report demonstrating the cyst wall pathology and the steroid responsivity on cyst shrinkage. The mechanism of cyst formation is thought to be thrombin-induced BBB disruption. Excess gelatin-thrombin matrix should be carefully removed from the surgical beds, particularly those having a blinded space from the neurosurgical microscope.

High White Blood Cell Count Is a Risk Factor for Contrast-Induced Nephropathy following Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Although mechanical thrombectomy is a standard endovascular therapy for patients with acute ischemic stroke (AIS), the incidence of and risk factors for contrast-induced nephropathy (CIN) following mechanical thrombectomy are infrequently reported. OBJECTIVES: The aim of this study was to investigate the incidence and risk factors for CIN following mechanical thrombectomy for AIS, and whether the incidence of CIN is related to a poor prognosis. METHODS: We examined consecutive patients who underwent a mechanical thrombectomy in the period from January 2014 to March 2018. The patients' clinical backgrounds, treatments, and clinical prognoses were analyzed. CIN was defined as an increase in the serum creatinine level of ≥44.2 µmol/L (0.5 mg/dL) or 25% above baseline within 72 h after exposure to the contrast medium. RESULTS: In total, 80 patients (46 men and 34 women aged 74.5 ± 11.5 years) who met our inclusion criteria were analyzed. CIN occurred in 8.8% (7/80) of the patients following mechanical thrombectomy. Although no patients needed permanent dialysis, 1 required temporary dialysis. The median amount of contrast medium was 109 mL. A comparison between the groups with and without CIN showed a significant difference in white blood cell (WBC) count at the time of admission (11.6 ± 2.7 × 103/µL and 8.1 ± 2.7 × 103/µL; p < 0.01) and the cut-off value was 9.70 × 103/µL. In multivariate analysis, contrast volume/estimated glomerular filtration rate by creatinine and WBC count were significantly associated with the incidence of CIN, with odds ratios of 1.64 (95% CI 1.02-2.65; p = 0.04) and 1.61 (95% CI 1.15-2.25; p < 0.01), respectively. CONCLUSIONS: This study found that CIN occurred in 8.8% of patients with AIS following mechanical thrombectomy. High WBC count was associated with an increased risk of CIN and may be helpful for predicting CIN.

Efficacy of intraarterial superselective indocyanine green videoangiography in cerebral arteriovenous malformation surgery in a hybrid operating room.

OBJECTIVE: Although intravenous indocyanine green (ICG) videoangiography has been reported to be useful when applied to cerebral arteriovenous malformation (AVM) surgery, the ICG that remains after the procedure makes it difficult to understand the anatomy, to evaluate nidus blood flow changes, and to repeat ICG videoangiography within a short time. Intraarterial ICG videoangiography has emerged as a way to overcome these limitations. The current study presents the results of intraarterial ICG videoangiography undertaken in patients with cerebral AVMs. METHODS: Intraarterial ICG videoangiography was performed in 13 patients with cerebral AVMs. Routine intraoperative digital subtraction angiography at the authors' institution is performed in a hybrid operating room during AVM surgery and includes the added step of injecting ICG to the contrast medium that is administered through a catheter. RESULTS: Predissection studies were able to visualize the feeder in 12 of 13 cases. The nidus was visualized in 12 of 13 cases, while the drainer was visualized in all cases. After total dissection of the nidus, there was no ICG filling in the drainers found in any of the cases. Washout of the ICG took 4.4 ± 1.3 seconds in the feeders, 9.2 ± 3.5 seconds in the drainers, and 20.9 ± 3.4 seconds in all of the vessels. Nidus flow reduction was confirmed during dissection in 9 of 9 cases. Flow reduction was easy to recognize due to each span being very short. Color-encoded visualization and objective data obtained by Flow 800 analysis reinforced these findings. CONCLUSIONS: The results showed that intraarterial ICG videoangiography was more useful than intravenous ICG videoangiography in cerebral AVM surgery. This was especially effective in the identification of the feeder, nidus, and drainer and in the assessment of the flow dynamics of the nidus. Use of Flow 800 made it simpler and easier to evaluate these findings.

Active Cancer and Elevated D-Dimer Are Risk Factors for In-Hospital Ischemic Stroke.

BACKGROUND AND PURPOSE: Little attention has been paid to the pathogenesis of in-hospital stroke, despite poor outcomes and a longer time from stroke onset to treatment. We studied the pathophysiology and biomarkers for detecting patients who progress to in-hospital ischemic stroke (IHS). METHODS: Seventy-nine patients with IHS were sequentially recruited in the period 2011-2017. Their characteristics, care, and outcomes were compared with 933 patients who had an out-of-hospital ischemic stroke (OHS) using a prospectively collected database of the Tokushima University Stroke Registry. RESULTS: Active cancer and coronary artery disease were more prevalent in patients with IHS than in those with OHS (53.2 and 27.8% vs. 2.0 and 10.9%, respectively; p < 0.001), the median onset-to-evaluation time was longer (300 vs. 240 min; p = 0.015), and the undetermined etiology was significantly higher (36.7 vs. 2.4%; p < 0.001). Although there was no significant difference in stroke severity at onset between the groups, patients with IHS had higher modified Rankin Scale (mRS) scores (3-6) at discharge (67.1 vs. 50.3%; p = 0.004) and rates of death during hospitalization (16.5 vs. 2.9%; p < 0.001). D-dimer (5.8 vs. 0.8 µg/mL; p < 0.001) and fibrinogen (532 vs. 430 mg/dL; p = 0.014) plasma levels at the time of onset were significantly higher in patients with IHS after propensity score matching. Multivariate logistic regression analysis revealed that active cancer (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.26-4.20), prestroke mRS scores 3-5 (OR 6.78; 95% CI 3.96-11.61), female sex (OR 1.57; 95% CI 1.19-2.08), and age ≥75 years (OR 2.36; 95% CI 1.80-3.08) were associated with poor outcomes. CONCLUSIONS: Patients with IHS had poorer outcomes than those with OHS because of a higher prevalence of active cancer and functional dependence before stroke onset. Elevated plasma levels of D-dimer and fibrinogen, especially with active cancer, can help identify patients who are at a higher risk of progression to IHS.

Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.

Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP+BM) rats. Three weeks later, they were ovariectomized (OVX/GFP+BM rats). We subjected 7-week-old Wistar male and 13-week-old OVX/GFP+BM rats to 90-min cerebral ischemia. Male and OVX/GFP+BM rats were divided into two groups, one was treated with PGZ (2.5 mg/kg/day) and the other served as the vehicle control (VC). In both male and OVX/GFP+BM rats, post-ischemia treatment with PGZ reduced neurological deficits and the infarct volume. In male rats, PGZ decreased the mRNA level of IL-6 and M1-like macrophages after 24 h. In OVX/GFP+BM rats, PGZ augmented the proliferation of resident stem cells in the subventricular zone (SVZ) and the recruitment of GFP+BM stem cells on days 7-14. Both types of proliferated stem cells migrated from the SVZ into the peri-infarct area. There, they differentiated into mature neurons, glia, and blood vessels in association with activated Akt, MAP2, and VEGF. Post-ischemia treatment with PGZ may offer a new avenue for stroke treatment through contribution to neuroprotection and neurogenesis.

Correction to: Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.

In the original publication of the article, the second author (Keiko T. Kitazato) was missing.

Material characterization and selection for 3D-printed spine models.

The two most popular models used in anatomical training for residents, clinicians, or surgeons are cadavers and sawbones. The former is extremely costly and difficult to attain due to cost, ethical implications, and availability, while the latter is said to not have the same tactile fidelity or mechanical properties as human bone. This study examined the potential use of 3D-printed phantoms to emulate cadaveric, human vertebrae, in hopes of acting as a future use over cadavers. In so doing, we developed 3D-printed MedPhantom®, with the intended use to offer similar tactile feel, mechanical characteristics, and visual appearance as human bone. In order to quantify tactility, a mechanical test was developed where a 5-mm diameter diamond-coated bur spinning at 75,000 RPM swept across the specimens while continuously recording the resultant forces (N) and moments (N-cm), The bur sweep motion is common in orthopedic surgery and neurosurgery. Since most 3D-prints do not offer internal, trabecular structure similar to bone, an algorithm was written to create a stochastic framework of internal mesh to mimic cancellous bone within an STL (stereolithography) file. The ranges of mesh parameters were chosen after several visits with the neurosurgeons participating in the project. In order to quantify structural combinations of wall thickness, gap sizes, and varying cylindrical radii within a print, 1000 RPM compression test with a 5-mm diamond-coated bur was performed with resultant forces (N). Two sample t-test shows statistical significance that samples are not equal to the vertebrae (p < 0.05). Results from the bur sweep test showed 15% Gypsum® powder mixed with 100% Clear® Formlabs resin and 10% Castable® resin mixed with 90% Clear® resin were nearest to human, cadaveric vertebrae, with the difference of force and moment in the x-direction at only 5 N and 7-9 N-cm, respectively. Structural compression results showed that a 2 mm cortical wall, 4 mm or 5 mm gap size between cylinders inside the structure, and 0.25 mm radius of internal cylinders were the best fit parameters to match human vertebrae.

[A Case Report of Congenital Protein C Deficiency with Cerebral Venous Sinus Thrombosis during Early Pregnancy Period].

A 35-year-old woman at eight weeks of gestation in her second pregnancy presented with generalized seizures. Magnetic resonance images revealed a small hemorrhagic infarction in the left frontal lobe, and magnetic resonance venography indicated cerebral venous sinus thrombosis. After hospitalization, anticoagulant therapy was continued, and a low protein C level was confirmed, which was also confirmed in both her mother and her sister. Follow-up magnetic resonance venography performed on day 27 confirmed that the cerebral venous sinuses had undergone recanalization. After a completed gestation period, the patient gave birth to healthy girl uneventfully.