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.

Increased plasma plasmin-α2-plasmin inhibitor complex levels correlate with postoperative rebleeding after endoscopic surgery for spontaneous intracerebral hemorrhage.

BACKGROUND: Postoperative rebleeding (PR) is one of the most severe complications of endoscopic surgery, often performed to remove spontaneous intracerebral hemorrhage (sICH). However, the risk factors for PR remain unclear. OBJECTIVE: This study retrospectively investigated whether increased preoperative plasma plasmin-α2-plasmin inhibitor complex (PIC) levels, indicating activation of fibrinolysis, are associated with PR. METHODS: A total of 101 patients underwent endoscopic surgery to evacuate sICH at our institution from January 2010 to June 2019, and 79 patients who underwent examinations of plasma PIC levels at admission with available radiographical data were included. Correlations between PR and increased plasma PIC levels were retrospectively evaluated. RESULTS: PR occurred in eight patients (10.1%), and high PIC levels (≥ 4 or 6 µg/ml) were significantly associated with PR. The sensitivities employing high PIC levels of ≥ 4 µg/ml and ≥ 6 µg/ml were both 0.63, and the specificities using the same PIC levels were 0.86 and 0.92, respectively. Multivariable analyses showed that high plasma PIC levels of ≥ 4 µg/ml (odds ratio (OR), 12.77; 95% confidence interval (CI), 1.65-98.77; p = 0.02) or ≥ 6 µg/ml (OR, 18.33; 95% CI, 2.32-144.82; p = 0.006) were independent predictors of PR. CONCLUSIONS: This study found that increased plasma PIC levels were associated with PR following the endoscopic evacuation of sICHs, indicating that increased plasma PIC levels could be potentially used to predict PR. Further studies are needed to establish new surgical strategies and adjuvant treatments to improve surgical outcomes in patients with sICH prone to PR.

Potential of Hybrid Assistive Limb Treatment for Ataxic Gait Due to Cerebellar Disorders Including Hemorrhage, Infarction, and Tumor.

Cerebellar hemorrhage (CH) is a severe life-threatening disorder, and surgical treatment is often required in an emergency situation. Even in cases in which the surgical procedure is successful, functional recovery is likely to be delayed because of cerebellar symptoms such as ataxia and gait disturbance. Here, we briefly review the efficacy of hybrid assistive limb (HAL) treatment in neurosurgical practice and propose a new comprehensive treatment strategy for CH to facilitate early neurological recovery. We have experienced cases of ataxic gait due to various etiologies, treated with rehabilitation using the HAL, and our data showed that HAL treatment potentially improves ataxic gait and balance problems. HAL treatment seems to be an effective and promising treatment modality for selected cases. Future studies should evaluate gait appearance and balance, in addition to walking speed, to assess improvement in cerebellar symptoms.

Cerebral and spinal cavernomas associated with Klippel-Trenaunay syndrome: case report and literature review.

Klippel-Trenaunay-Weber syndrome (KTWS) involves a triad of conditions, including cutaneous hemangiomas, venous varicosities, and osseous and soft-tissue hypertrophy of the affected limb. We describe a rare case of multiple cavernomas in the central nervous system in a patient with KTWS. A-64-year-old man with KTWS and a previous brain hemorrhage presented with sudden onset of gait and vesicorectal disturbance. The magnetic resonance imaging scan showed a cavernoma associated with hemorrhage in his lumbosacral spinal cord. Moreover, numerous cavernomas were identified in his brain. He was treated conservatively with no adverse events. Gait disturbance improved, but vesicorectal disturbance did not improve.

Treatment of Unruptured Cerebral Aneurysms with the Mineralocorticoid Receptor Blocker Eplerenone-Pilot Study.

BACKGROUND: Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients. METHODS: Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms. RESULTS: Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%. CONCLUSION: Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed.

Bazedoxifene, a selective estrogen receptor modulator, reduces cerebral aneurysm rupture in Ovariectomized rats.

BACKGROUND: Estrogen deficiency is thought to be responsible for the higher frequency of aneurysmal subarachnoid hemorrhage in post- than premenopausal women. Estrogen replacement therapy appears to reduce this risk but is associated with significant side effects. We tested our hypothesis that bazedoxifene, a clinically used selective estrogen receptor (ER) modulator with fewer estrogenic side effects, reduces cerebral aneurysm rupture in a new model of ovariectomized rats. METHODS: Ten-week-old female Sprague-Dawley rats were subjected to ovariectomy, hemodynamic changes, and hypertension to induce aneurysms (ovariectomized aneurysm rats) and treated with vehicle or with 0.3 or 1.0 mg/kg/day bazedoxifene. They were compared with sham-ovariectomized rats subjected to hypertension and hemodynamic changes (HT rats). The vasoprotective effects of bazedoxifene and the mechanisms underlying its efficacy were analyzed. RESULTS: During 12 weeks of observation, the incidence of aneurysm rupture was 52% in ovariectomized rats. With no effect on the blood pressure, treatment with 0.3 or 1.0 mg/kg/day bazedoxifene lowered this rate to 11 and 17%, almost the same as in HT rats (17%). In ovariectomized rats, the mRNA level of ERα, ERß, and the tissue inhibitor of metalloproteinase-2 was downregulated in the cerebral artery prone to rupture at 5 weeks after aneurysm induction; the mRNA level of interleukin-1ß and the matrix metalloproteinase-9 was upregulated. In HT rats, bazedoxifene restored the mRNA level of ERα and ERß and decreased the level of interleukin-1ß and matrix metalloproteinase-9. These findings suggest that bazedoxifene was protective against aneurysmal rupture by alleviating the vascular inflammation and degradation exacerbated by the decrease in ERα and ERß. CONCLUSIONS: Our observation that bazedoxifene decreased the incidence of aneurysmal rupture in ovariectomized rats warrants further studies to validate this response in humans.

Intra-arterial high signals on arterial spin labeling perfusion images predict the occluded internal carotid artery segment.

PURPOSE: Arterial spin labeling (ASL) involves perfusion imaging using the inverted magnetization of arterial water. If the arterial arrival times are longer than the post-labeling delay, labeled spins are visible on ASL images as bright, high intra-arterial signals (IASs); such signals were found within occluded vessels of patients with acute ischemic stroke. The identification of the occluded segment in the internal carotid artery (ICA) is crucial for endovascular treatment. We tested our hypothesis that high IASs on ASL images can predict the occluded segment. METHODS: Our study included 13 patients with acute ICA occlusion who had undergone angiographic and ASL studies within 48 h of onset. We retrospectively identified the high IAS on ASL images and angiograms and recorded the occluded segment and the number of high IAS-positive slices on ASL images. The ICA segments were classified as cervical (C1), petrous (C2), cavernous (C3), and supraclinoid (C4). RESULTS: Of seven patients with intracranial ICA occlusion, five demonstrated high IASs at C1-C2, suggesting that high IASs could identify stagnant flow proximal to the occluded segment. Among six patients with extracranial ICA occlusion, five presented with high IASs at C3-C4, suggesting that signals could identify the collateral flow via the ophthalmic artery. None had high IASs at C1-C2. The mean number of high IAS-positive slices was significantly higher in patients with intra- than extracranial ICA occlusion. CONCLUSION: High IASs on ASL images can identify slow stagnant and collateral flow through the ophthalmic artery in patients with acute ICA occlusion and help to predict the occlusion site.

Cryptic Recanalization of Chronic Vertebral Artery Occlusion by Head Rotation.

BACKGROUND: Chronic vertebral artery occlusion (VAO) can be associated with ischemic stroke, as thrombi formed under blood flow stagnation around the stump of the VAO may migrate into the brain. We report a new mechanism of chronic VAO-associated ischemic stroke and a patient with cryptic recanalization of chronic VAO by head rotation. CASE DESCRIPTION: A 74-year-old man presented with chronic right VAO and repeated ischemic embolic stroke in the posterior circulation despite antiplatelet therapy. He also manifested vertigo with 30° leftward head rotation, indicative of rotational vertebrobasilar insufficiency due to mechanical compression of the patent left vertebral artery (VA) at the C4-C5 level. Surgical decompression of the vessel via the anterior approach resulted in the disappearance of his rotational vertebrobasilar insufficiency. Adequate decompression of the VA on the left side was confirmed on postoperative computed tomography angiography scans obtained with his head rotated more to the left than on preoperative scans. Unexpected partial recanalization of his right chronic VAO was observed at the C5-C6 level. VAO was due to VA compression by osteophytes at neutral head position; it was released by head rotation. We suspected that his repeated brain infarcts were attributable to head rotation-related opening and closing of the VA lumen and these decompressed the left VA by removing the implicated osteophyte via the anterior approach. CONCLUSIONS: Cryptic recanalization of chronic VAO by head rotation contributed to repeated infarcts in the posterior circulation and was resolved by surgical decompression.

Investigation modalities for evaluation of esophageal clearance function.

The clearance of the esophagus is to transport food boluses from the pharynx to the stom- ach through peristaltic motion. This occurs through the primary peristaltic wave, triggered by swallowing, passing from the upper to lower esophagus in a sequence of contractions and relaxations. Investigation modalities for evaluation of esophageal clearance function include esophageal manometry (included high resolution manometry), esophageal radiography (barium swallow), esophageal scintigraphy, ultrasonography, impedance methods and com- bination with transnasal endoscopy and manometry. Of these, evaluation of esophageal clear- ance is conducted quantitative assessment of esophageal motility as well as transient lower esophageal sphincter relaxation(TLESR) in reflux esophagitis.

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of cerebral blood flow autoregulation. This study identifies a smooth muscle cell autocrine/paracrine signaling network that augments myogenic tone in a murine model of experimental SAH: it links tumor necrosis factor-α (TNFα), the cystic fibrosis transmembrane conductance regulator, and sphingosine-1-phosphate signaling. METHODS: Mouse olfactory cerebral resistance arteries were isolated, cannulated, and pressurized for in vitro vascular reactivity assessments. Cerebral blood flow was measured by speckle flowmetry and magnetic resonance imaging. Standard Western blot, immunohistochemical techniques, and neurobehavioral assessments were also used. RESULTS: We demonstrate that targeting TNFα and sphingosine-1-phosphate signaling in vivo has potential therapeutic application in SAH. Both interventions (1) eliminate the SAH-induced myogenic tone enhancement, but otherwise leave vascular reactivity intact; (2) ameliorate SAH-induced neuronal degeneration and apoptosis; and (3) improve neurobehavioral performance in mice with SAH. Furthermore, TNFα sequestration with etanercept normalizes cerebral perfusion in SAH. CONCLUSIONS: Vascular smooth muscle cell TNFα and sphingosine-1-phosphate signaling significantly enhance cerebral artery tone in SAH; anti-TNFα and anti-sphingosine-1-phosphate treatment may significantly improve clinical outcome.

Surveillance of short-segment Barrett's esophagus using ultrathin transnasal endoscopy.

BACKGROUND AND AIM: Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. METHODS AND RESULTS: Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. CONCLUSION: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

PPARγ-Dependent and -Independent Inhibition of the HMGB1/TLR9 Pathway by Eicosapentaenoic Acid Attenuates Ischemic Brain Damage in Ovariectomized Rats.

High mobility group box 1 (HMGB1) elevation after cerebral ischemia activates inflammatory pathways via receptors such as the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) and leads to brain damage. Eicosapentaenoic acid (EPA), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, attenuates postischemic inflammation and brain damage in male animals. However, postischemic HMGB1 signaling and the effects of EPA on ovariectomized (OVX(+)) rats remain unclear. We hypothesized that EPA attenuates brain damage in OVX(+) rats via the inhibition of HMGB1 signaling in a PPARγ-dependent manner. Seven-week-old female Sprague-Dawley rats were divided into 3 groups; nonovariectomized (OVX(-)) rats and EPA-treated and EPA-untreated OVX(+) rats before cerebral ischemia induction. Another set of EPA-treated OVX(+) rats was injected with the PPARγ inhibitor GW9662. OVX(+) decreased the messenger RNA level of PPARγ and increased that of HMGB1, RAGE, TLR9, and tumor necrosis factor alpha (TNFα) in parallel with ischemic brain damage. EPA restored the PPARγ expression, downregulated the HMGB1 signal-related molecules, and attenuated the ischemic brain damage. Neither OVX(+) nor EPA affected the expression of TLR2 or TLR4. Interestingly, GW9662 partially abrogated the EPA-induced neuroprotection and the downregulation of RAGE and TLR9. In contrast, GW9662 did not affect HMGB1 or TNFα. These results suggest that EPA exerts PPARγ-dependent and PPARγ-independent effects on postischemic HMGB1/TLR9 pathway. The cortical infarct volume exacerbated by OVX(+) is associated with the upregulation of the HMGB1/TLR9 pathway. Suppression of this pathway may help to limit ischemic brain damage in postmenopausal women.

Improvement of Plasma Biomarkers after Switching Stroke Patients from Other Angiotensin II Type I Receptor Blockers to Olmesartan.

BACKGROUND: Managing hypertension is crucial for preventing stroke recurrence. Some stroke patients experience resistant hypertension. In our experimental stroke model, olmesartan increased the expression of angiotensin (Ang) II converting enzyme-2. We hypothesized that switching to olmesartan affects biomarkers and the blood pressure (BP) in stroke patients whose BP is insufficiently controlled by standard doses of Ang II type I receptor blockers (ARBs) other than olmesartan. METHODS: We recruited 25 patients to study our hypothesis. All had a history of stroke or silent cerebral infarction. We switched them to olmesartan (10-40 mg per day) for 12 weeks and determined their plasma level of Ang-(1-7), peroxiredoxin, oxidized low-density lipoprotein (oxLDL)/ß-2-glycoprotein I (ß2GPI) complex, adiponectin, high mobility group box 1 (HMGB1), and tumor necrosis factor-α (TNFα) and recorded their BP before and after olmesartan treatment. RESULTS: After switching the patients to olmesartan, their plasma level of Ang-(1-7) as a vasoprotective indicator and adiponectin regulating metabolic syndrome was increased, and peroxiredoxin and the oxLDL/ß2GPI complex indicating its antioxidative stress and its proatherogenicity were lower than their baseline. This suggests that olmesartan may be more effective than other ARBs to improve these conditions. Neither HMGB1 nor TNFα reflecting an inflammatory response was affected, suggesting that the anti-inflammatory effects of olmesartan are similar to those of other ARBs. The recommended BP (<140/90) was obtained in 10 of the 25 patients after switching to olmesartan. No adverse events occurred. CONCLUSIONS: Switching from other ARBs to olmesartan may be a promising therapeutic option in patients with resistant hypertension.

[Effect of H2-receptor antagonist and proton pomp inhibitor on the treatment of acid-related disease].

We summarized proton pump inhibitors(PPI) and histamine H2-receptor antagonist (H2B) with reference to acid-related disease. The both drugs act process of gastric acid secretion in parietal cell of stomach. Inhibition of H2B is reversible, but that of PPI is irreversible, so period of acting in PPI is longer than that in H2B. PPI is more effective than H2B in treatment of acid-related disease. Especially PPI is recommended the first choice in GERD and NSAID ulcer.

Comparison of hemostasis using bipolar hemostatic forceps with hemostasis by endoscopic hemoclipping for nonvariceal upper gastrointestinal bleeding in a prospective non-randomized trial.

BACKGROUND: We previously reported on the safety and efficacy of bipolar hemostatic forceps for treating nonvariceal upper gastrointestinal (UGI) bleeding. However, no prospective or randomized studies have evaluated the efficacy of bipolar hemostatic forceps. The aim of this study was to evaluate the hemostatic efficacy of using bipolar hemostatic forceps compared with the hemostatic efficacy of the commonly used method of endoscopic hemoclipping for treating nonvariceal UGI bleeding. METHODS: A total of 50 patients who required endoscopic hemostasis for UGI bleeding were divided into two groups: those who underwent endoscopic hemostasis using bipolar hemostatic forceps (Group I) and those who underwent endoscopic hemostasis by endoscopic hemoclipping (Group II). We compared the two groups in terms of hemostasis success rate and time required to achieve hemostasis and stop recurrent bleeding. RESULTS: All (100 %) of 27 patients in Group I and 18 (78.2 %) of 23 patients in Group II were successfully treated using bipolar hemostatic forceps or by endoscopic hemoclipping alone, respectively, indicating a significantly higher success rate for Group I than for Group II (p < 0.05). The time required to achieve hemostasis was 6.8 ± 13.4 min for Group I and 15.4 ± 17.0 min for Group II. One patient in Group I (3.7 %) and four patients in Group II (22.2 %) experienced recurrent bleeding. CONCLUSION: Bipolar hemostatic forceps was more effective than endoscopic hemoclipping for treating nonvariceal UGI bleeding.

Mucosal cutting biopsy technique for histological diagnosis of suspected gastrointestinal stromal tumors of the stomach.

BACKGROUND AND AIM: The Japanese Gastrointestinal Stromal Tumor (GIST) therapeutic guidelines recommend endoscopic ultrasound-guided fine-needle aspiration biopsy for histological diagnosis. However, before 2010, this technique was only carried out at a minority of medical institutions in Japan. In the present study, we investigated the usefulness of mucosal cutting biopsy. METHODS: In 18 asymptomatic gastric submucosal tumors, mucosal cutting biopsies were carried out. We examined tumor size, tumor site (lower third: L; middle third: M; upper third: U), histopathological diagnostic yield and complications. In cases that proceeded to surgical resection with a diagnosis of GIST, we compared the pre- and postoperative histopathological diagnosis, and the histological degrees of malignancy. RESULTS: The tumors had a mean size of 20.3 mm and were located at the L site in five cases, M in four, and U in nine. Histological diagnosis of submucosal tumor was obtained in all the cases. (GIST, n = 13; heterotopic pancreas, n = 2; and leiomyoma, n = 3). No complications (e.g. bleeding, perforation or peritonitis) were seen after this procedure. In all 11 patients with GIST who underwent surgical resection, the histopathological findings from the mucosal cutting biopsy specimens were similar to those from the surgically resected specimens, with agreement between the immunostaining findings and the histological degree of malignancy (90.9%) in 10 patients. CONCLUSIONS: The mucosal cutting biopsy technique is a useful diagnostic modality for the diagnosis of gastric GIST and for selection of the appropriate treatment.

Surgical treatment of sural nerve entrapment aided by imaging- and electrography-based diagnosis: illustrative case.

BACKGROUND: The sural nerve (SN) is a cutaneous sensory nerve that innervates the posterolateral side of the distal third of the leg and lateral side of the foot. The SN has wide variation in its course and is fixed to the subcutaneous tissue and superficial fascia. Idiopathic spontaneous SN neuropathy is rarely surgically treated because of the difficulty in detecting SN entrapment. OBSERVATIONS: Herein, the authors present a rare case of surgically treated spontaneous SN neuropathy. A 67-year-old male patient presented with right foot pain for several years. Magnetic resonance imaging and ultrasonography showed SN entrapment slightly proximal and posterior to the lateral malleolus. A nerve conduction study showed SN disturbance. After undergoing neurolysis, the patient's foot pain was alleviated. LESSONS: Idiopathic SN neuropathy can be treated surgically when SN entrapment is detected with comprehensive evaluation methods.

Preoperative examination and intraoperative cerebrospinal fluid leakage test for minimally invasive surgery of spinal extradural arachnoid cysts: illustrative case.

BACKGROUND: Spinal extradural arachnoid cysts (SEACs) are rare and can cause spinal dysfunction. Total cyst removal and duraplasty via multiple laminectomies are commonly performed. However, to avoid postoperative spinal deformity and axial pain, a minimally invasive surgery via selective laminectomy may be optimal. Therefore, preoperative detection of the dural fistula site is required. OBSERVATIONS: A 25-year-old male presented with a 2-month history of progressive gait disturbance and back pain. Conventional magnetic resonance imaging (MRI) revealed SEACs at the T9 to L2 level but did not reveal the dural fistula. Further examinations were performed using sagittal time-spatial labeling inversion pulse MRI and cone-beam computed tomography myelography with a spinal intrathecal catheter, which indicated a dural fistula on the left side at the T12 level. On the basis of these results, dural repair was performed via selective laminectomy. Furthermore, an intraoperative cerebrospinal fluid leakage test by intrathecally injecting saline via a spinal catheter confirmed complete closure of the dural fistula, with no other fistulas. LESSONS: These comprehensive pre and intraoperative examinations may be useful for minimally invasive and selective surgeries in patients with SEACs.

Effect of decreased platelets on postoperative recurrence of chronic subdural hematoma.

Introduction: Chronic subdural hematoma (CSDH) is commonly treated using simple burr hole surgery. However, postoperative recurrence occurs at a relatively high rate of 10-20%. A decrease in platelet count (PC) may be associated with recurrence via a hemostasis disorder; however, this association has not been well-studied. Therefore, this study aimed to investigate the association between PC and postoperative CSDH recurrence. Methods: We retrospectively reviewed the data for CSDHs in 488 cerebral hemispheres of 431 patients who underwent burr hole surgery at our institution between January 2013 and December 2022. The association between preoperative PC and postoperative CSDH recurrence was investigated. We used the first quartile of PC, PC < 170 × 103/µL to define a threshold for decreased PC. Results: In total, 459 cerebral hemispheres with CSDHs in 405 patients were followed up postoperatively for at least 3 months or until CSDH disappeared. CSDH recurred in 39 (8.5%) cerebral hemispheres. The recurrence rate was gradually increased in parallel with a decreasing PC. Among 109 CSDHs with a decreased PC (<170 × 103/µL), 15 (13.8%) recurred, whereas only 24 (6.9%) of 350 CSDHs without a decreased PC recurred (p = 0.03). In univariable logistic analysis, eosinophil-rich blood (≥100/µL eosinophils in peripheral blood) and a decreased PC were significant risk factors. Multivariable analysis showed that eosinophil-rich blood (adjusted odds ratio, 2.51; 95% confidence interval, 1.26-4.99; p = 0.009) and a decreased PC (adjusted odds ratio, 2.15; 95% confidence interval, 1.07-4.35; p = 0.03) were independent risk factors for recurrence. Conclusion: Our study showed that a decrease in PC was associated with postoperative CSDH recurrence. Patients with CSDH and a decreased PC require careful postoperative follow-up.

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.