Background Alagille syndrome is characterized by intrahepatic cholestasis and abnormalities in the cardiovascular system, eyes, and vertebrae, along with a characteristic facial appearance. The genes responsible are JAG1 and NOTCH2. Although craniosynostosis occurs in approximately 1 % of patients with Alagille syndrome, its pathogenesis remains unclear. We report a case of Alagille syndrome, with late-onset craniosynostosis, which was associated with JAG1 gene mutation. Case presentation A 6 years and 5 months old boy presented with severe headache and vomiting. Magnetic resonance (MR) and computed tomography (CT) imaging revealed cerebellar tonsillar herniation and craniosynostosis of the sagittal, bilateral lambdoid, and coronal sutures. Cranial radiography showed marked digital impressions, and ophthalmological assessment revealed bilateral papilledema and reduced visual acuity, resulting in increased intracranial pressure (ICP). The patient was diagnosed with Alagille syndrome, associated with JAG1 gene mutation (heterozygosis c.1492_1495delAATG p.Asn498Glyfs*65). The same pathogenic variant was confirmed in his mother and sister. Although he had a mild hepatic disorder and pulmonary artery stenosis, he had grown uneventfully without developmental delays or growth disorders. Two weeks after the first visit, wide coronal craniotomy was performed to reduce the ICP. The headache and vomiting disappeared immediately after surgery, and the visual acuity and papilledema gradually improved. Conclusion The NOTCH signaling pathway involving JAG1 and NOTCH2 genes interacts with fibroblast growth factor receptors and the TWIST1 gene contributing to syndromic craniosynostosis. It is important to consider the possibility of craniosynostosis and manage increased ICP early in Alagille syndrome, even at school-going age.

Perimedullary arteriovenous fistulas (PMAVFs) are rare spinal vascular lesions, particularly in pediatric patients. We present a pediatric case of a ruptured cervical PMAVF, successfully treated with endovascular embolization, along with a review of relevant literature. A 10-year-old boy with no significant medical history initially presented with neck pain and fatigue, progressing to paralysis in his upper limbs and eventually all extremities. His condition further deteriorated, leading to impaired consciousness and respiratory distress, necessitating transfer to our pediatric intensive care unit for intubation and management. Head magnetic resonance images revealed medullary edema and dilated veins in the posterior cranial fossa. At the same time, contrast-enhanced computed tomography of the neck showed an intramedullary hematoma centered at C4, with edema extending from the medulla oblongata to T3 and dilated vessels surrounding the lesion. Angiography confirmed a varix rupture of the PMAVF with feeders from the right C4 dorsal root artery and the right ascending cervical artery. Endovascular embolization was performed using 33% n‑butyl‑2-cyanoacrylate through a microcatheter placed just beyond the fistula. The shunt was successfully occluded. Postoperatively, following a tracheotomy, the patient was gradually weaned off the ventilator. With rehabilitation, he showed significant improvement in spinal cord function, including regaining the ability to transfer with a walker. Endovascular embolization is a viable treatment option for pediatric PMAVF, as demonstrated in this case, where a single-stage procedure achieved successful occlusion and significant neurological recovery.

OBJECTIVE:Craniosynostosis surgery is highly invasive, often resulting in significant blood loss and high transfusion rates (87%-95%) in pediatric patients. This retrospective study aimed to identify factors associated with lower transfusion requirements to improve perioperative management and reduce complications. METHODS:We analyzed 69 craniosynostosis surgeries performed from 2013 to 2023. A transfusion threshold of Hb < 7 g/dL was used. Surgical methods basically varied by age: endoscopic suturectomy for infants under 7 months and calvarial vault remodeling or distraction osteogenesis for older children. Blood conservation strategies included acute normovolemic hemodilution, intraoperative autologous blood recovery (Cell Saver), oral iron supplements, and tranexamic acid. Receiver operating characteristic curve analysis was used to determine key transfusion-reducing factors. RESULTS:The transfusion rate was 34.8%. Significant factors associated with reduced transfusion included blood loss, patient age, and preoperative iron supplementation. In subgroup analysis, for patients weighing ≥10 kg, autologous blood recovery was effective, while for those <10 kg, preoperative iron supplementation improved hemoglobin levels, reducing transfusion requirements. For patients weighing ≥10 kg, blood loss ≤8.8 mL/kg were identified as critical thresholds. Blood loss ≤8.3 mL/kg and preoperative Hb ≥ 9.2 g/dL were optimal for avoiding transfusion in patients weighing <10 kg. CONCLUSIONS:Minimizing blood loss, optimizing preoperative hemoglobin levels, and using autologous blood recovery can significantly reduce transfusion rates. Implementing multiple strategies lowered the overall transfusion rate to 34.8%, potentially reducing complications and improving patient outcomes in pediatric craniosynostosis surgery.

Thalamic pain can be understood as a network reorganization disorder. This study aimed to investigate functional connectivity (FC) in human patients and a macaque model of thalamic pain. In humans, functional brain activity was compared between patients with thalamic pain and healthy individuals. Furthermore, functional brain activity was compared in macaques, before and after the induction of thalamic pain in the same individuals. FCs between the amygdala of the unaffected hemisphere and the brainstem was significantly higher in patients with thalamic pain. More specifically, a significant FC higher was observed between the basolateral amygdala (BLA) and the ventral tegmental area, which also significantly predicted the value of a visual analog scale of pain intensity in individual patients. The macaque model of thalamic pain also exhibited a significant FC higher between the amygdala of the unaffected hemisphere and the brainstem, particularly between the BLA and the midbrain. Furthermore, the previously reported significant FC higher between the amygdala and the mediodorsal nucleus of the thalamus in macaques with thalamic pain was also reproduced in the human patients. Therefore, the present results suggest that the FC changes in the regions associated with emotion, memory, motivation, and reward are part of the underlying mechanisms of thalamic pain onset present in both human patients and model macaques. This cross-species convergence provides new insights into the neurological mechanisms underlying thalamic pain, paving the way for further studies and the development of therapeutic strategies. Perspective This article presents that the functional connectivity changes in the regions associated with emotion, motivation, and reward are part of the underlying mechanisms of thalamic pain in humans and macaques.

Endovascular treatment for isolated dural arteriovenous fistula (DAVF) in the middle cranial fossa (MCF) with pure cortical venous drainage poses challenges, including the absence of a safe access route for transvenous embolization (TVE) and the risk of ischemia to neuro feeding vessels and dangerous anastomosis at the sphenoid wing. Therefore, surgical treatment involving direct blockage of venous reflux via craniotomy is typically preferred. We describe the case of a 63-year-old woman presented with generalized seizures and was diagnosed with a Borden III left MCF-DAVF. Initial TVE was unsuccessful due to an occluded inferior petrosal sinus and a lack of connection between the cavernous sinus and the shunt point. After reducing the shunt flow with transarterial embolization, retrograde TVE through cortical drainage enabled successful treatment for the DAVF. We used a triple coaxial system (4-French guiding sheath, 3.2-French intermediate distal access catheter, and 1.5-French microcatheter) to retrogradely navigate a microcathter from the right jugular vein through the superior sagittal sinus, the vein of Trolard, and into the superficial middle cerebral vein, ultimately achieving shunt occlusion using several coils. This case demonstrates that TVE for MCF-DAVFs with pure cortical venous drainage is feasible when a safe anatomical route is established using appropriate strategies and instruments and provides a safe and effective treatment option for similar cases.

Organized chronic subdural hematoma (OCSDH) is a rare condition lacking standardized treatment protocols. Middle meningeal artery (MMA) embolization has recently demonstrated promising outcomes in managing chronic subdural hematoma (CSDH). We present 2 cases of OCSDH treated with endovascular embolization and minimal evacuation surgery. The first case involved an 83-year-old male with a history of left CSDH drainage, admitted urgently due to right hemiplegia and dysarthria. CT scans confirmed recurrent CSDH. A small craniotomy was performed to decompress the thick hematoma, followed by drain placement. Postoperative magnetic resonance imaging (MRI) indicated OCSDH. Seven days later, MMA embolization with 25% n-butyl-2-cyanoacrylate (NBCA) was performed under local anesthesia. The patient's symptoms improved, and the hematoma resolved within 6 months without recurrence. The second case involved a 76-year-old male with right CSDH and thrombocytopenia (platelet count of 19,000/µL), diagnosed with immune thrombocytopenia. MRI indicated OCSDH. Due to the risk associated with craniotomy, a burr hole perforation and MMA embolization were planned, accompanied by a platelet transfusion. Left MMA embolization with 20% NBCA was performed, followed by burr hole enlargement for decompression and drain placement. The patient's symptoms improved postoperatively, and his platelet count stabilized with steroid therapy and thrombopoietin. The hematoma resolved within 3 months without recurrence. These cases indicate that MMA embolization combined with small craniotomy or perforation may be an effective treatment strategy for OCSDH.

The occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2 weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting blood in the subarachnoid space of control rats and rats with altered GM. We evaluated EBI indicators such as neurological score, brain water content, Evans blue extravasation, and neuronal injury. Additionally, we studied inflammatory cells using immunohistochemistry, immunocytochemistry, quantitative PCR, and flow cytometry. EBI was significantly averted by alterations in GM using antibiotics. The altered GM significantly prevented neutrophil infiltration into the brain among inflammatory cells, and this anti-inflammatory effect was observed immediately following SAH onset. The altered GM also prevented neutrophil extracellular trap formation in the brain and blood, indicating the systemic protective effect. The cause of the protective effect was attributed to a significant decrease in aged neutrophils (CXCR4 high CD62L low ) by the altered GM. These protective effects against EBI disappeared when the altered GM was recolonized with normal flora. Our findings demonstrated that EBI following SAH is associated with GM, which regulated neutrophil infiltration.

Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP.

Objectives: As the number of patients with left ventricular assist device (LVAD) implantation has been increasing, treatment of LVAD-related ischemic stroke is becoming a critical issue. We sought to clarify the features of mechanical thrombectomy in LVAD-related stroke with large vessel occlusion. Methods: In a multi-center, retrospective case-control study, we compared 20 LVAD-related strokes with 33 nonLVAD strokes, all of which had large vessel occlusion in the anterior circulation treated with mechanical thrombectomy. A comparative histopathological examination of the retrieved thrombi was also performed. Results: Successful reperfusion was achieved in 75% of the LVAD-related strokes. The time from onset to reperfusion was similar to that of non-LVAD strokes, but the total number of device passes required for reperfusion (median, 2.5 versus 1, P = 0.01) and the incidences of post-procedural parenchymal and subarachnoid hemorrhage (25% versus 3%, P = 0.02 and 55% versus 15%, P = 0.01, respectively) were higher in LVAD-related strokes. Symptomatic intracranial hemorrhage occurred in 4 patients (20%) with LVAD-related strokes. The histopathological analysis revealed that the ratio of erythrocyte components was significantly lower in thrombi retrieved from patients with LVAD-related stroke than in those with non-LVAD stroke (19 +/- 6% versus 41 +/- 17%, P = 0.01). Conclusions: Mechanical thrombectomy is feasible in patients with LVAD-related stroke. However, repetitive device passes are needed to achieve successful reperfusion mainly because of the structurally organized thrombi, and the higher risk of hemorrhagic complications should be considered, while offering this therapeutic alternative.

The novel infection of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019 in China and is now widely spread worldwide. COVID-19 commonly presents with respiratory symptoms including cough and dyspnea. However, the neuroinvasive propensity through the angiotensin-converting enzyme 2 (ACE2) receptor [1], which is expressed in glial cells and neurons as well, and the cerebrovascular complication because of the hypercoagulable state are also reported as a feature of COVID-19 [2].

Background Embolic stroke with large vessel occlusion (LVO) is a major adverse event during ventricular assist device (VAD) support. In this study we aimed to clarify the efficacy of, and problems associated with, endovascular treatment (EVT) of LVO in patients with VAD support. Methods We retrospectively reviewed EVT for LVO in patients with VAD support between 2006 and 2017 at our institute and evaluated baseline characteristics, treatment variables, outcomes, and complications. Results The study cohort comprised 12 consecutive patients (age 35.4 +/- 20.4 years), with 15 LVO events involving 20 arterial occlusions, who had undergone EVT. The median Alberta Stroke Program Early CT score was 10 and good collaterals were observed in 10 of 17 occluded middle cerebral artery areas. No study patients had received intravenous thrombolysis therapy. EVT was performed on 18 of the 20 occluded arteries and mechanical thrombectomy on 13 vessels. The successful reperfusion (modified Thrombolysis in Cerebral Infarction grade >= 2 b) rate was 67% in all EVTs and 85% with mechanical thrombectomy. Histological analysis showed fibrin-rich thrombi in four of five samples. Seven of 12 patients (58%) maintained their neurological function (modified Rankin Scale score <= 2 or equal to pre-stroke score) at 90 days. Periprocedural complications comprised two symptomatic intracranial hemorrhages and the 90-day mortality rate was 13%. Seven of 10 cardiac transplant candidates (70%) returned to the waiting list and three of them received transplants. Conclusions Endovascular therapy for acute LVO stroke is feasible even in patients with VAD support.

Objective An Arterial Stiffness Index (ASI) can be obtained by measuring finger photoplethysmogram using the SB200 pulse oximeter, giving a level between 1 and 6. However, it was unclear whether this method accurately reflected arterial stiffness. Brachial—Ankle Pulse Wave Velocity (baPWV) is an established method for the assessment of arterial stiffness, allowing us to compare baPWV and our own ASI. Methods We retrospectively collected data from 18 patients scheduled for neuroendovascular therapy in the Department of Neurosurgery at Osaka University Hospital between March 2016 and December 2016, for whom both baPWV and SB200 measurements were performed prior to their procedure. This allowed us to assess the relationship between the ASI and the baPWV. We defined patients with an ASI ≥ 3 on the SB200 as the progressed arterial stiffness group, while patients with a level of ≤2 were considered normal. BaPWV was compared across the two groups. We also analyzed the receiver operating characteristic curve for predicting baPWV values ≥ 1700 cm/s by the ASI measurement. Results The progressed arterial stiffness group showed significantly higher baPWV values ( p = 0.0087). The area under the curve for the ASI was 0.84. The ASI of 3 had a sensitivity of 71.4% and a specificity of 90.1% for predicting baPWV ≥ 1700 cm/s. Conclusion We conclude that the non-invasive and portable SB200 device successfully measured arterial stiffness.

Objective: Aggressive therapeutic intervention is recommended for infectious intracranial aneurysms (IIAs) because they have a higher hemorrhage risk than non-IIAs.In this study, we retrospectively reviewed patients with IIAs treated at our institution and evaluated the contents of treatment and the complications. Methods:We evaluated 13 patients diagnosed with IIA based on clinical symptoms and imaging findings between March 2004 and December 2014.Results: Endovascular treatment, direct surgery, and conservative management were performed in five, five, and three patients, respectively.In endovascular treatment patients, none developed any hemorrhagic or infectious complications.In the five direct surgery patients, we selected direct surgery because three patients needed hematoma evacuation, and the catheter navigation was not achievable in the remaining two patients. Conclusion:Since IIAs often occur in peripheral arteries and are accompanied by local infection, aneurysmectomy by direct surgery used to be preferred.However, as embolization of cortical branches using a flexible catheter and small coils has become technically possible by the improvements of endovascular devices, endovascular parent artery occlusion might be a reasonable alternative for IIAs.

Objective: The coil-assisted technique (CAT) for delivering the wire or catheter to the vessel distal to large wide-neck intracranial aneurysms is described.

Dural arteriovenous fistula (DAVF) in a sinus of the lesser sphenoid wing (SLSW) is rarely reported. Here, we report a case of an isolated SLSW DAVF treated by coils placed into the sinus through the feeding artery. A 68-year-old man was admitted to our hospital with headache. Magnetic resonance images and an angiogram showed a varix in the right middle cranial fossa. A DAVF, consisting of three main feeders and the isolated SLSW, was diagnosed based on the angiogram findings. Retrograde leptomeningeal venous drainage to the deep middle cerebral vein was observed. Given the remarkable extent of cortical venous ectasia together with the presence of headache and right abducens nerve paralysis, endovascular treatment was initiated. A transvenous approach through the right inferior petrosal sinus was not feasible because of difficulty associated with inserting the microcatheter into the SLSW. Thus, we tried a transarterial approach and were able to advance the microcatheter beyond the fistula into the isolated SLSW, through the artery of the foramen rotundum. The isolated sinus and feeding arteries were embolized with coils. The postoperative angiogram showed the total occlusion of the SLSW DAVF. This case demonstrates the feasibility of transarterial sinus packing for an isolated SLSW DAVF.

Background: In neuroendovascular therapy, the effect of arterial stiffness on postprocedural cerebral thromboembolism is unknown. In this observational study, we examined the relationship between cerebral thromboembolism after carotid artery stenting and arterial stiffness. Methods: From April 2015 to February 2017, we enrolled consecutive patients undergoing scheduled carotid artery stenting in our institution. In all patients, preprocedural brachial-ankle pulse wave velocity was used to assess arterial stiffness, whereas the number of new cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging was assessed after treatment. We also analyzed patient data and details of procedures in patients with carotid artery stenting. Results: Twenty-one patients completed the study. The mean brachial-ankle pulse wave velocity was 1879 cm/s. There was no association of cerebral thromboembolisms with age, unstable plaque, protection device, or type of stent. However, the brachial-ankle pulse wave velocity was an independent predictor of cerebral thromboembolisms (P = .0017). Conclusions: Brachial-ankle pulse wave velocity is predictive of silent cerebral embolisms on diffusion-weighted magnetic resonance imaging after carotid artery stenting.

Objective. Although central poststroke pain (CPSP)might be understood as a network reorganization disorder that leads to a maladaptive central state, the mechanisms of CPSP are poorly understood. In this study, we investigated key structures to develop CPSP using voxel–based lesion mapping.

Spinal dural arteriovenous fistulas (DAVFs) are the most commonly encountered vascular malformation of the spinal cord and a treatable cause of progressive para- or tetraplegia. It is an elusive pathology that tends to be under-diagnosed, due to lack of awareness among clinicians, and affects males more commonly than females, typically between the fifth and eighth decades. Early diagnosis and treatment may significantly improve outcome and prevent permanent disability and even mortality. The purpose of our retrospective, single-center study was to determine the long-term clinical and radiographic outcome of patients who have received endovascular or surgical treatment of a spinal DAVF. In particular, during a 6-year period (2009-2014) 14 patients with a spinal DAVF were treated at our department either surgically (n = 4) or endovascularly (n = 10) with detachable coils and/or glue. There was no recurrence in the follow-up period (mean: 36 months, range 3-60 months) after complete occlusion with the endovascular treatment (n = 9; 90%), while only one patient (10%) had residual flow both post-treatment and at 3-month follow-up. All four surgically treated patients (100%) had no signs of residual DAVF on follow-up magnetic resonance angiography (MRA) and/or angiography (mean follow-up period of 9 months). Since improvement or stabilization of symptoms may be seen even in patients with delayed diagnosis and substantial neurological deficits, either endovascular or surgical treatment is always justified.

Objective. Although central poststroke pain (CPSP) might be understood as a network reorganization disorder that leads to a maladaptive central state, the mechanisms of CPSP are poorly understood. In this study, we investigated key structures to develop CPSP using voxel-based lesion mapping. Methods. Subjects were 98 CPSP patients with three-dimensional T1 weighted images (mean age, 61.4 +/- 8.8 years; thalamic lesion, n=45; putaminal lesion, n=41; brainstem lesion, n=9; cortical/subcortical lesion, n=3). The stroke lesion was segmented as a three-dimensional volume on MR images. These volumes of interest were spatially normalized, and group voxel-based analyses were performed with SPM12 to detect an overlap of the lesions. Results. The overlaps of the stroke lesion were localized in the two structures, the putamen and thalamus. The overlap in the putamen extended in an anteroposterior direction, and its peak was located at the most posterior part of the putamen. The damage of the posterior limb of the internal capsule has been thought to cause CPSP up to now, however the finding from this study suggested that the insular cortex, secondary somatosensory area, and neural connections toward these regions could be involved in development of CPSP. The peak of the thalamic lesion was located at the border of the ventral posterior nucleus and pulvinar. The posterior ventral medial nucleus of the thalamus, which was a proposed relay point for thermosensory and nociceptive fibers, could be also involved in development of CPSP. Conclusions. This study suggested that the specific lesions in the thalamus or putamen could develop CPSP, and the damage of the thalamic insular pathway was one of the key structure to develop CPSP.