Spinal epidural arteriovenous fistula with an intraosseous shunt arising in a compression fracture vertebra: illustrative case.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEAVFs) with intraosseous shunts are rare, and their underlying pathophysiological mechanisms remain unclear. OBSERVATIONS: A female in her 70s presented with rapidly progressive weakness in both lower extremities and urinary retention. Lumbar spine magnetic resonance imaging revealed spinal cord edema and flow voids due to venous dilation and compression fractures of the L1 and L2 vertebral bodies. Spinal angiography revealed ventral and dorsal somatic branches of the lumbar arteries at L1 and L2 flowing into the shunt. High-resolution cone-beam computed tomography revealed a shunt within the compression-fractured vertebral body bone of L2. The intravertebral shunt blood flowed into the ventral epidural venous plexus (VEVP) and returned into the perimedullary vein (PMV). Transarterial embolization was performed using N-butyl cyanoacrylate and Onyx-18 for feeder L1 and feeder L2, respectively. Onyx-18 was injected from the VEVP into the PMV, and complete occlusion of the shunt was achieved. The patient showed symptomatic improvement postoperatively. LESSONS: Vertebral compression fractures are common but rarely associated with SEAVFs. https://thejns.org/doi/10.3171/CASE2457.

Investigator-initiated clinical trial of stabilizer device: A novel intracranial exchange guidewire for neuroendovascular treatments.

BACKGROUND: Neuroendovascular procedures, especially those involving significant vessel tortuosity, giant intracranial aneurysms, or distally located lesions, frequently necessitate exchange methods. However, exchange maneuvers pose a risk of inadvertent vessel injury. To address these challenges, a Stabilizer device was developed and evaluated for its efficacy and safety. This clinical trial aimed to assess the efficacy and safety of the Stabilizer device in facilitating the navigation of neuroendovascular devices to target lesions in cases where the exchange technique was necessary. METHODS: This was a single-arm, prospective, open-label, multicenter clinical trial performed at nine different sites. It focused on investigating the use of the Stabilizer device for treating intracranial aneurysms and atherosclerosis. RESULTS: A total of 31 patients were enrolled across nine centers in Japan from July 21, 2022, to March 10, 2023. The study enrolled 24 (77.4%) patients with intracranial aneurysms and seven (22.6%) patients with intracranial artery stenosis. Majority of the target lesions were in the middle cerebral artery territory (83.9%). The Stabilizer device was used to exchange for 0.027-inch catheters, intermediate catheters, PTA balloons, and Wingspan stent system. The Stabilizer device demonstrated 100% technical success rate. While three complications related to the treatment were noted, there were no complications related to the device, including any vascular damage. CONCLUSIONS: This is the first multicenter clinical trial that investigated and demonstrated technical efficacy as well as overall safety profile of the Stabilizer device in neuroendovascular procedures where the use of an exchange method was necessary.

Efficient breeding system of infertile Niemann-Pick disease type C model mice by in vitro fertilization and embryo transfer.

Niemann-Pick disease type C (NPC) is a lethal genetic disease with mutations in NPC1 or NPC2 gene. Npc1-deficient (Npc1-/-) mice have been used as a model for NPC pathogenesis to develop novel therapies for NPC. However, Npc1-/- mice are infertile; thus, securing sufficient numbers for translational research is difficult. Hence, we attempted reproductive engineering techniques such as in vitro fertilization (IVF) and sperm cryopreservation. For the first time, we succeeded in producing fertilized oocytes via IVF using male and female Npc1-/- mice. Fertilized oocytes were also obtained via IVF using cryopreserved sperm from Npc1-/- mice. The obtained fertilized oocytes normally developed into live pups via embryo transfer, and they eventually exhibited NPC pathogenesis. These findings are useful for generating an efficient breeding system that overcomes the reproductive challenges of Npc1-/- mice and will contribute to developing novel therapeutic methods using NPC model mice.

Coexistence of anti-KS and anti-TIF1-γ antibodies in clinically amyopathic dermatomyositis presenting with rapid progression of interstitial lung disease.

Polymyositis/Dermatomyositis (PM/DM) is an idiopathic inflammatory myopathy (IIM) manifesting mainly as symmetrical proximal muscle weakness and/or typical cutaneous features due to autoimmune mechanisms. Clinically amyopathic dermatomyositis (CADM) is a subset of DM that exhibits only the typical cutaneous features without any clinical muscle symptoms. Several autoantibodies have been found specifically in patients with PM/DM, including CADM patients. Anti-KS antibody is one of a group of anti-aminoacyl transfer RNA (ARS) antibodies that are mainly associated with fever, Raynaud's phenomenon, polyarthritis, and interstitial lung disease (ILD), whereas anti-TIF1-γ antibody is frequently found in DM patients with malignancy. Here, we report a CADM patient having both anti-KS antibody and anti-TIF1-γ antibody. This patient developed an acute exacerbation of ILD and was successfully treated with high dose corticosteroid pulse therapy together with immunosuppressive agents. Although earlier experience had indicated that the seminal characteristic of anti-KS-positive ILD was slowly developing disease onset with little or no progression over the clinical course, the present patient suffered rapidly progressive disease.

Binocularly suppressed stimuli induce brain activities related to aesthetic emotions.

Introduction: Aesthetic emotions are a class of emotions aroused by evaluating aesthetically appealing objects or events. While evolutionary aesthetics suggests the adaptive roles of these emotions, empirical assessments are lacking. Previous neuroscientific studies have demonstrated that visual stimuli carrying evolutionarily important information induce neural responses even when presented non-consciously. To examine the evolutionary importance of aesthetic emotions, we conducted a neuroscientific study using magnetoencephalography (MEG) to measure induced neural responses to non-consciously presented portrait paintings categorised as biological and non-biological and examined associations between the induced responses and aesthetic ratings. Methods: MEG and pre-rating data were collected from 23 participants. The pre-rating included visual analogue scales for object saliency, facial saliency, liking, and beauty scores, in addition to 'biologi-ness,' which was used for subcategorising stimuli into biological and non-biological. The stimuli were presented non-consciously using a continuous flash suppression paradigm or consciously using binocular presentation without flashing masks, while dichotomic behavioural responses were obtained (beauty or non-beauty). Time-frequency decomposed MEG data were used for correlation analysis with pre-rating scores for each category. Results: Behavioural data revealed that saliency scores of non-consciously presented stimuli influenced dichotomic responses (beauty or non-beauty). MEG data showed that non-consciously presented portrait paintings induced spatiotemporally distributed low-frequency brain activities associated with aesthetic ratings, which were distinct between the biological and non-biological categories and conscious and non-conscious conditions. Conclusion: Aesthetic emotion holds evolutionary significance for humans. Neural pathways are sensitive to visual images that arouse aesthetic emotion in distinct ways for biological and non-biological categories, which are further influenced by consciousness. These differences likely reflect the diversity in mechanisms of aesthetic processing, such as processing fluency, active elaboration, and predictive processing. The aesthetic processing of non-conscious stimuli appears to be characterised by fluency-driven affective processing, while top-down regulatory processes are suppressed. This study provides the first empirical evidence supporting the evolutionary significance of aesthetic processing.

Intracerebroventricular 2-hydroxypropyl-γ-cyclodextrin alleviates hepatic manifestations without distributing to the liver in a murine model of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a lysosomal lipid storage disorder characterized by progressive neurodegeneration and hepatic dysfunction. A cyclic heptasaccharide, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), is currently under clinical investigation for NPC, but its adverse events remain problematic. We previously identified that a cyclic octasaccharide, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), also ameliorated NPC manifestations with higher biocompatibility than HP-ß-CD. However, preclinical studies describing the associations between the biodistribution and pharmacodynamics of these compounds, which are essential for clinical application, are still lacking. Here, we investigated these properties of HP-γ-CD by measuring its organ biodistribution and therapeutic effect after systemic and central administration. The effect of HP-γ-CD on disturbed cholesterol homeostasis appeared within several hours after exposure and persisted for several days in NPC model cells and mice. Tissue distribution indicated that only a small fraction of subcutaneously administered HP-γ-CD rapidly distributed to peripheral organs and contributed to disease amelioration. We found that a subcutaneous dose of HP-γ-CD negligibly ameliorated neurological characteristics because it has limited penetration of the blood-brain barrier; however, an intracerebroventricular microdose unexpectedly attenuated hepatic dysfunction without the detection of HP-γ-CD in the liver. These results demonstrate that central administration of HP-γ-CD can indirectly attenuate peripheral manifestations of NPC.

Trends and Progress in Neuroendovascular Treatment in Japan: Japanese Registry of Neuroendovascular Therapy (JR-NET) 4. Main Report.

We reported the main results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 4, a nationwide surveillance of therapy (NET) in Japan from January 2015 to December 2019. JR-NET 4 registered consecutive patients who underwent NETs by Japan Society of Neuroendovascular Therapy (JSNET) -certified specialists. The primary endpoint was functional independence (mRS score of 0-2) at 30 days post-NET, with secondary endpoints focusing on technical success and major adverse events within 30 days.A total of 63,230 patients and 60,354 NET procedures from 166 participating centers were analyzed. During the study period, NET cases have consistently increased, with an increase in the proportion of elderly patients. A significant trend shift was observed in the distribution of NET procedures, with endovascular treatment for acute ischemic stroke that showed a dramatic increase in 5 years. This trend aligns with key randomized clinical trials from 2015 that presented the efficacy of this treatment. Clinical outcomes at 30 days posttreatment revealed that endovascular treatment for acute ischemic stroke and other NETs maintained safety and effectiveness despite varying prevalence of functional independence between target diseases. The study also observed a steady increase in emergency treatment cases, reflecting the increase in acute ischemic stroke, a time-sensitive medical condition.This comprehensive surveillance highlights the trend of NET practices in Japan, driven by clinical evidence and advancements in treatment devices. Although these findings were specific to Japan, they offer valuable insights into the broader trends in NETs and acute stroke care.

Real-World Outcomes of Carotid Artery Stenting in Symptomatic and Asymptomatic Patients With Carotid Artery Stenosis.

BACKGROUND: The effectiveness and safety of carotid artery stenting (CAS) are comparable to those of carotid endarterectomy in both symptomatic and asymptomatic patients with carotid artery stenosis, but real-world outcomes are not well-known. OBJECTIVES: The purpose of this study was to investigate the real-world clinical outcomes of CAS in symptomatic and asymptomatic patients with carotid artery stenosis. METHODS: We conducted a nationwide retrospective registry study of 156 centers between January 2015 and December 2019. We enrolled consecutive patients with CAS managed by certified specialists from the Japanese Society of Neuroendovascular Therapy. Outcomes between symptomatic and asymptomatic patients were compared. The primary outcome was a composite of ischemic stroke and all-cause death at 30 days after CAS. Secondary outcomes were ischemic stroke, all-cause death, intracranial hemorrhage (ICH), and procedural complications. RESULTS: We analyzed 9,792 patients (symptomatic, n = 5,351; asymptomatic, n = 4,441). The mean age was 73.5 years, and men were dominant (86.4%). Embolism protection devices were used in 99% of patients. The primary outcome was not significantly different between the symptomatic and asymptomatic groups (120 [2.2%] vs 65 [1.5%]; adjusted OR: 1.30; 95% CI: 0.92-1.83). The incidences of symptomatic ICH, any ICH, acute in-stent occlusion, and hyperperfusion syndrome were significantly more prevalent in the symptomatic group (47 [0.9%] vs 8 [0.2%], aOR: 4.41 [95% CI: 1.68-11.6]; 73 [1.4%] vs 12 [0.3%], aOR: 3.56 [95% CI: 1.71-7.39]; 45 [0.8%] vs 19 [0.4%], aOR: 2.18 [95% CI: 1.08-4.40]; and 102 [1.9%] vs 36 [0.8%], aOR: 1.78 [95% CI: 1.17-2.71], respectively). Other secondary outcomes were not significantly different between the 2 groups. CONCLUSIONS: The complication rate after specialist-involved CAS at 30 days was low in real-world practice.

Sex differences in outcomes of carotid artery stenting.

OBJECTIVE: Existing evidence is inconclusive on whether women after carotid artery stenting (CAS) experience worse outcomes than men. METHODS: The outcomes of women and men were compared using the data from nationwide retrospective registry between 2015 and 2019. The primary outcome was the incidence of ischemic stroke and all-cause death. Secondary outcomes included the incidence of ischemic stroke, all-cause death, acute occlusion, and acute myocardial infarction. Functional outcomes were the achieving an mRS score of 0-1 and 0-2. Outcomes were assessed at 30 days after CAS. RESULTS: In total, 9792 patients (1330 women, 8862 men; mean age, 73.8 vs 73.5 years, p = 0.17) were analyzed. Symptomatic stenosis was common in men (52.0% vs. 55.1%; p = 0.03), while ≥50% stenosis after CAS was common in women (3.2% vs. 2.0%; p = 0.005). The primary outcome was no significantly difference in women and men (2.0% vs. 1.9%; adjusted odds ratio [aOR], 1.19; 95% confidence interval [95%CI], 0.75-1.88).The incidence of all-cause death was higher in women (0.9% vs. 0.5%; aOR, 2.45; 95%CI, 1.11-5.39). Functional outcomes were significantly less common in women than in men (mRS0-1, 72.6% vs. 74.8%; aOR, 0.77; 95%CI, 0.63-0.95; mRS0-2, 82.1% vs. 85.6%; aOR, 0.76; 95%CI, 0.60-0.95). CONCLUSIONS: This study suggests that there was no significant sex differences in the incidence of ischemic stroke and all-cause death at 30 days. However, women have higher rate of all-cause death and poorer functional outcomes at 30 days than men.

Early neurological changes following endovascular therapy for acute stroke due to intracranial atherosclerotic disease.

BACKGROUND: Endovascular therapy (EVT) reduces functional disability in patients with acute large vessel occlusion (LVO). However, the early neurological change after EVT may be limited in patients with intracranial atherosclerotic disease (ICAD). METHODS: We analyzed the Japanese Registry of NeuroEndovascular Therapy (JR-NET) 4 which was a retrospective, nationwide, multicenter registry of patients with LVO between 2015 and 2019. We compared the early neurological change, efficacy and safety of EVT for acute LVO in ICAD and other etiologies. The primary outcome was NIHSS improvement ≥10 points, and secondary outcome were NIHSS worsening ≥4 points 7 days after EVT, effective reperfusion rate, 30-day functional outcomes, and safety outcomes. RESULTS: Among the 6710 enrolled patients, 610 (9.1%) had ICAD. The ICAD group was younger (mean 72.0 vs. 75.8 years) and predominantly male (63.4% vs. 56.0%), had lower NIHSS scores before EVT (median 16 vs. 18), and underwent percutaneous transluminal angioplasty and stenting more frequently (43.0% vs. 4.4%, 12.3% vs. 4.4%). In the ICAD group, NIHSS improvement was significantly lower (adjusted odds ratio (aOR) [95% confidence interval (95%CI)] 0.52 [0.41-0.65]), NIHSS worsening was significantly higher (aOR [95%CI] 1.76 [1.31-2.34]), and effective reperfusion was significantly lower (aOR [95%CI] 0.47 [0.36-0.60]). Fewer patients with ICAD had modified Rankin scale 0-2 at 30 days (aOR [95%CI] 0.60 [0.47-0.77]). The risk of acute reocclusion was more prominent in the ICAD group (aOR [95%CI] 4.03 [1.98-8.21]). CONCLUSIONS: Improvement in neurological severity after EVT was lower in patients with LVO and ICAD.

Hypothermia increases adenosine monophosphate and xanthosine monophosphate levels in the mouse hippocampus, preventing their reduction by global cerebral ischemia.

Global cerebral ischemia (GCI) caused by clinical conditions such as cardiac arrest leads to delayed neuronal death in the hippocampus, resulting in physical and mental disability. However, the mechanism of delayed neuronal death following GCI remains unclear. To elucidate the mechanism, we performed a metabolome analysis using a mouse model in which hypothermia (HT) during GCI, which was induced by the transient occlusion of the bilateral common carotid arteries, markedly suppressed the development of delayed neuronal death in the hippocampus after reperfusion. Fifteen metabolites whose levels were significantly changed by GCI and 12 metabolites whose levels were significantly changed by HT were identified. Furthermore, the metabolites common for both changes were narrowed down to two, adenosine monophosphate (AMP) and xanthosine monophosphate (XMP). The levels of both AMP and XMP were found to be decreased by GCI, but increased by HT, thereby preventing their decrease. In contrast, the levels of adenosine, inosine, hypoxanthine, xanthine, and guanosine, the downstream metabolites of AMP and XMP, were increased by GCI, but were not affected by HT. Our results may provide a clue to understanding the mechanism by which HT during GCI suppresses the development of delayed neuronal death in the hippocampus.

A Case of Atypical Hemolytic Uremic Syndrome Triggered by Acute Pancreatitis in a Patient with a Membrane Cofactor Protein (CD46) Genetic Variant.

Atypical hemolytic uremic syndrome (aHUS) is a type of HUS. We herein report a case of aHUS triggered by pancreatitis in a patient with a heterozygous variant of membrane cofactor protein (MCP; P165S), a complement-related gene. Plasma exchange therapy and hemodialysis improved thrombocytopenia and anemia without leading to end-stage kidney disease. This MCP heterozygous variant was insufficient to cause aHUS on its own. Pancreatitis, in addition to a genetic background with a MCP heterozygous variant, led to the manifestation of aHUS. This case supports the "multiple hit theory" that several factors are required for the manifestation of aHUS.

Ruptured thrombosed vertebral artery dissecting aneurysm treated with staged flow diverter after prediction of the rupture point by vessel wall MRI.

The safety and feasibility of using staged flow diverter (FD) for ruptured cerebral aneurysms, in which coil embolization is performed in the acute phase and FD is deployed in the subacute phase, has recently been reported. This strategy requires assuming the rupture point and performing coil embolization. Although vessel wall magnetic resonance imaging (VW-MRI) has been reported to be useful in predicting the rupture point of aneurysms, its use with staged FD has not yet been reported. We report the first case of staged FD with preoperative contrast-enhanced VW-MRI to predict the rupture point for partially thrombosed vertebral artery dissecting large aneurysm involving posterior inferior cerebellar artery (PICA) origin. This approach achieved a very good outcome, not only completely occluding the aneurysm, but also reconstructing the parent artery while maintaining the patency of the PICA.

Predictors of aneurysm shrinkage after flow diversion treatment for internal carotid artery aneurysms: quantitative volume analysis with MRI.

Background and purpose: Although aneurysm shrinkage often occurs after flow diversion treatment for intracranial aneurysms, no reports have addressed the factors associated with aneurysm shrinkage. Materials and methods: This retrospective single-center study was performed to examine patients with unruptured internal carotid artery aneurysms who were treated using flow diversion and followed up by imaging for at least 12 months. The study outcome was aneurysm shrinkage (volume reduction of ≥10%) 12 months after treatment. Aneurysm volume was quantitatively assessed using the MRIcroGL software. Patient and aneurysm characteristics were statistically analyzed. Results: This study involved 81 patients with 88 aneurysms. At the 6 months, 12 months, and last follow-ups, the proportion of aneurysms that had shrunk was 50, 64, and 65%, respectively. No adjunctive coiling (odds ratio, 56.7; 95% confidence interval, 7.03-457.21; p < 0.001) and aneurysm occlusion (odds ratio, 90.7; 95% confidence interval, 8.32-988.66; p < 0.001) were significantly associated with aneurysm shrinkage. In patients treated by flow diversion with adjunctive coiling, only the volume embolization rate was a factor significantly associated with aneurysm shrinkage (p < 0.001). Its cutoff value was 15.5% according to the receiver operating characteristic curve analysis (area under the curve, 0.87; sensitivity, 0.87; specificity, 0.83). Conclusion: The rate of aneurysm shrinkage after flow diversion increased during the first 12 months after treatment, but not thereafter. No adjunctive coiling and aneurysm occlusion were predictors of aneurysm shrinkage, respectively. If adjunctive coiling is required, a volume embolization rate of ≤15.5% may be suggested for aneurysm regression.

Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts

Para avaliar a capacidade alergizante do antígeno da Blomia tropicalis (Bt) a produção de IgE específica e não específica a antígeno Bt foi monitorada em camundongos BALB/c após exposição ao antígeno por via nasal. Foi evidenciado que Bt contem um alérgeno funcional em seus componentes. Os componentes alergênicos entretanto, quando administrados por via intra-nasal, sem qualquer adjuvante, não induzem resposta IgE durante um pequeno período. Por outro lado, a inoculação intra-nasal de antígenos Bt aumentou a resposta sérica de IgE em camundongos pré-tratados por uma injeção inicial sensibilizante sub-cutânea aos mesmos antígenos. A inoculação do antígeno Bt sem as injeções sensibilizantes iniciais induziu a produção de anticorpos IgE somente quando o antígeno foi administrado de maneira contínua, por um período longo de mais de 24 semanas. Mesmo quando as injeções sensibilizantes iniciais foram ausentes, o antígeno Bt inoculado com a toxina de cólera (CT) como adjuvante mucoso também aumentou de maneira significante a resposta IgE antígeno específica do Bt dependendo da dose de CT administrada conjuntamente. O presente estudo também demonstrou que camundongos inoculados com antígeno Bt/CT mostram aumento do nível IgE não específico no soro e médias de eosinófilos no sangue periférico sem qualquer elevação da contagem total de leucócitos. A análise por Immunoblot demonstrou cinco principais componentes antigênicos reativos aos anticorpos IgE induzidos. Estes componentes na posição 44-64 kilodaltons foram considerados importantes antígenos-candidatos para o diagnóstico da alergia relacionada ao ácaro.