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.

Case of Cerebrospinal Fluid Leakage Nine Years after Pituitary Gamma Knife Surgery for Poststroke Thalamic Pain Syndrome.

Pituitary gamma knife surgery (GKS) is a treatment option for poststroke thalamic pain syndrome. Complications such as hypopituitarism, transient enuresis, and transient hyponatremia have been reported. However, cerebrospinal fluid (CSF) leakage has not yet been reported as a complication of pituitary GKS for poststroke thalamic pain syndrome. Herein, we report a case of delayed CSF rhinorrhea that developed 9 years after GKS for poststroke thalamic pain syndrome. A 64-year-old man presented to our hospital with bacterial meningitis and CSF rhinorrhea. Pituitary GKS for poststroke thalamic pain had been performed 9 years prior to his admission to our hospital. Computed tomography revealed pneumocephalus, fluid in the sphenoid and maxillary sinuses, and a partial bony defect of the sella turcica floor with communication between the paranasal and intracranial spaces. The CSF rhinorrhea resolved with bed rest and a lumbar CSF drain but recurred several days later. The patient underwent direct endoscopic surgical repair of the skull base. The sellar floor was covered with an autologous fascia graft harvested from the rectus sheath, and the sphenoid sinus was packed with abdominal fat grafts. The patient recovered, and the CSF rhinorrhea has not recurred for 2 years. Long-term follow-up is necessary after pituitary GKS, considering the complication of delayed CSF leakage.

Transarterial embolization for convexity dural arteriovenous fistula with or without pial arterial supply: A report of four patients.

Background: Convexity dural arteriovenous fistulae (dAVF) usually reflux into cortical veins without involving the venous sinuses. Although direct drainage ligation is curative, transarterial embolization (TAE) may be an alternative treatment. Case Description: Between September 2018 and January 2021, we encountered four patients with convexity dAVFs. They were three males and one female; their age ranged from 36 to 73 years. The initial symptom was headache (n = 1) or seizure (n = 2); one patient was asymptomatic. In all patients, the feeders were external carotid arteries with drainage into the cortical veins; in two patients, there was pial arterial supply from the middle cerebral artery. All patients were successfully treated by TAE alone using either Onyx or N-butyl cyanoacrylate embolization. Two patients required two sessions. All dAVFs were completely occluded and follow-up MRI or angiograms confirmed no recurrence. Conclusion: Our small series suggests that TAE with a liquid embolic material is an appropriate first-line treatment in patients with convexity dAVFs with or without pial arterial supply.

Elevated cellular PpIX potentiates sonodynamic therapy in a mouse glioma stem cell-bearing glioma model by downregulating the Akt/NF-κB/MDR1 pathway.

Glioblastoma (GBM) has high mortality rates because of extreme therapeutic resistance. During surgical resection for GBM, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is conventionally applied to distinguish GBM. However, surgical intervention is insufficient for high invasive GBM. Sonodynamic therapy (SDT) combined with low-intensity ultrasonication (US) and PpIX, as a sonosensitizer, is an emerging and promising approach, although its efficacy is limited. Based on our previous study that down-regulation of multidrug resistant protein (MDR1) in GBM augmented the anti-tumor effects of chemotherapy, we hypothesized that elevation of cellular PpIX levels by down-regulation of MDR1 enhances anti-tumor effects by SDT. In high invasive progeny cells from mouse glioma stem cells (GSCs) and a GSC-bearing mouse glioma model, we assessed the anti-tumor effects of SDT with a COX-2 inhibitor, celecoxib. Down-regulation of MDR1 by celecoxib increased cellular PpIX levels, as well as valspodar, an MDR1 inhibitor, and augmented anti-tumor effects of SDT. MDR1 down-regulation via the Akt/NF-κB pathway by celecoxib was confirmed, using an NF-κB inhibitor, CAPÉ. Thus, elevation of cellar PpIX by down-regulation of MDR1 via the Akt/NF-κB pathway may be crucial to potentiate the efficacy of SDT in a site-directed manner and provide a promising new therapeutic strategy for GBM.

Subarachnoid Hemorrhage Due to Rupture of Vertebral Artery Dissecting Aneurysms: Treatments, Outcomes, and Prognostic Factors.

BACKGROUND: Mortality rate after subarachnoid hemorrhage due to rupture of vertebral artery dissecting aneurysms (VADAs) is high; endovascular coil trapping is the first-line therapy to prevent rerupture. To select optimal treatments, the positional relationship between the VADA and posterior inferior cerebellar artery (PICA) and the morphology of the contralateral vertebral artery must be considered, and outcome predictors of different treatment methods and their possible complications must be identified. METHODS: We retrospectively studied 44 patients with ruptured VADAs who had undergone endovascular or surgical treatment. VADA morphology was assessed on conventional preoperative angiograms, and VADAs were categorized based on their site in relation to the PICA. VADA site, treatment method, and complications were used to identify prognostic factors. RESULTS: The sites of the 44 VADAs were PICA-proximal (n = 3), PICA-distal (n = 22), PICA-absent (n = 7), and PICA-involved (n = 12). Treatments included internal coil trapping (n = 30), proximal coil occlusion (n = 5), and stent placement (n = 3); surgical flow alteration via an occipital artery-PICA bypass and ligation at the proximal vertebral artery and the PICA origin was performed in 6 patients. Periprocedural rebleeding was associated with a poor outcome. Internal coil trapping prevented the rerupture of PICA-proximal and PICA-absent VADAs, and flow alteration prevented rerupture of PICA-involved VADAs; there were no complications directly attributable to these procedures. CONCLUSIONS: Periprocedural rebleeding was a poor prognostic factor. Internal trapping of PICA-proximal and PICA-absent VADAs and flow alteration in PICA-involved VADAs prevented rerupture.

Transarterial Sinus Coiling for Dural Arteriovenous Fistula: Two Case Reports.

Objective: We report two cases of dural arteriovenous fistula (DAVF) treated by coil embolization of the affected sinus and fistula via a feeding artery instead of transvenous embolization (TVE) due to the difficulty of the transvenous approach. Case Presentation: An 82-year-old man was diagnosed with transverse sinus (TS) DAVF. A microcatheter was inserted into the isolated TS through the fistula via the middle meningeal artery (MMA), which was the feeding artery of the DAVF. The DAVF was occluded by coil embolization of the isolated sinus and fistula. A 79-year-old man was diagnosed with cavernous sinus (CS) DAVF. A microcatheter was inserted into the CS through the fistula via an accessory meningeal artery (AMA), which was the feeding artery of the DAVF. The DAVF was occluded by coil embolization of the affected sinus and fistula. Conclusion: These cases suggested that transarterial sinus coiling is one of the effective treatment options for DAVF.

[A Case Report of Subacute Thrombosis after Carotid Stenting Caused by Food Allergy].

An 89-year-old man underwent carotid artery stenting for symptomatic left internal carotid artery stenosis. His postoperative course was uneventful;however, on postoperative day 4, he developed a food allergy rash throughout his body after consuming sushi. He developed right hemiplegia and aphasia the following day, and magnetic resonance imaging revealed left internal carotid artery occlusion. Angiography revealed stent thrombosis, and endovascular thrombectomy achieved partial recanalization;however, right hemiplegia and aphasia persisted. Eosinophilia and increased platelet aggregation suggested allergic stent thrombosis(Kounis syndrome type 3).

Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma.

Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin+ stem cells, CD16+ or CD163+ macrophages and Iba-1+ microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects.

Ruptured Aneurysm Originating from a Posterior Inferior Cerebellar Artery Communicating Artery: A Case Report and Review of the Literature.

This report presents a rare case of such an aneurysm arising from such a communicating artery. A 66-year-old woman presented with a subarachnoid hemorrhage located predominantly in the cisterna magna with intraventricular hemorrhage. Angiography showed hypoplasia of the right posterior inferior cerebellar artery. Its vermian territory was supplied by the communicating artery from the posterior medullary segments of the left posterior inferior cerebellar artery. An aneurysm was on that communicating artery itself at a nonbranching site. The aneurysm was trapped the next day. Postoperative computed tomography showed no infarct in the right posterior inferior cerebellar artery territory. Trapping is applicable when other collateral vessels supply the contralateral posterior inferior cerebellar artery territory. J. Med. Invest. 67 : 197-199, February, 2020.

[A Case Report of Endovascular Thrombectomy for Internal Carotid Artery Thromboembolism after Left Upper Lobectomy of Lung Cancer].

A 76-year-old man underwent a left upper lobectomy due to lung cancer. On postoperative day 3, he developed a cerebral infarction(NIHSS:17). MR and right carotid angiography demonstrated a right internal carotid artery occlusion. The patient underwent an endovascular thrombectomy without intravenous administration of recombinant tissue plasminogen activator. Complete recanalization was achieved and the symptoms almost disappeared except for a slight dysarthria. The patient subsequently continued cancer treatment by administration of edoxaban. Reports of cerebral emboli due to a thrombus migrating from the stump of the pulmonary vein after a left upper lobectomy are increasing. Several reports indicate that left upper lobectomy carries a high risk of thromboembolism. The current prospective study demonstrates that a mechanical thrombectomy can significantly improve both neurological and cognitive functions of patients after acute ischemic stroke. Endovascular neurosurgeons should prepare for and await an opportunity for thrombectomy for patients undergoing pulmonary resection.

The risk of hemorrhage in stereotactic biopsy for brain tumors.

Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy. J. Med. Invest. 66 : 314-318, August, 2019.

[A Case of Spontaneous Intracranial Hypotension Successfully Treated with Repetitive Epidural Blood Patch after Warfarin Reversal].

We report a case of spontaneous intracranial hypotension successfully treated with repetitive epidural blood patch after warfarin reversal. A 75-year-old man presented with a 2-week history of headache. He was being treated with warfarin for atrial fibrillation. Neurological examination on admission showed mild disorientation. Prothrombin time-international normalized ratio(PT-INR)was elevated to 2.43. Initial magnetic resonance images of the brain demonstrated bilateral subdural hematomas, distortion of midbrain and diffuse pachymeningeal enhancement. Conservative treatments with bed rest and hydration were administered. On the third posthospital day, he became lethargic and emergently underwent epidural blood patch(EBP)at lumbar level. Consciousness disturbance improved immediately but reappeared 12 hours after the EBP. The second EBP was performed but consciousness level decreased again 12 hours later. The effect of warfarin was reversed by administration of vitamin K and fresh frozen plasma before the third EBP. After the procedure, he became alert. The findings of neurological examination did not change but a CT on day 12 revealed increase in volume of left-sided subdural hematoma. He underwent EBP and evacuation of hematoma. The neurological findings remained unchanged. A CT on the 17th posthospital day showed increase of right-sided subdural hematoma, and EBP and evacuation of hematoma were then performed. After the 5th EBP, the clinical course was uneventful. Predictors for successful EBP are not fully clarified. In patients who undergo anticoagulation therapy, EBP may be ineffective and normalization of coagulability required.

[A Case Report of Basilar Artery Thromboembolism from Severe Stenosis of the Vertebral Artery Ostium].

We report a case of basilar artery embolism from the large thrombus of the right vertebral artery with severe stenosis of the vertebral artery ostium. Intravenous recombinant tissue plasminogen activator treatment and thrombectomy by catheter with reverse blood flow using a proximal subclavian artery blocking balloon(intentional subclavian artery steal phenomenon)were performed. A large thrombus along with other small thrombi were removed by an aspiration catheter. Additional stent placement was performed for residual vertebral artery stenosis, at ten days after the thrombectomy. Finally, the patient was discharged without any neurological deficits.

Down-regulation of MDR1 by Ad-DKK3 via Akt/NFκB pathways augments the anti-tumor effect of temozolomide in glioblastoma cells and a murine xenograft model.

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. METHODS: GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. RESULTS: Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. CONCLUSIONS: Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.

[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.

[Cerebral Venous Sinus Thrombosis Following Cisplatin-Based Chemotherapy for Testicular Tumor].

A man in his 30s who presented with an enlarged right testicle was diagnosed with a germ cell tumor via orchiectomy. Adjuvant chemotherapy with cisplatin, etoposide and bleomycin(BEP)was initiated. He developed a headache 8 days later, followed by neurological deficits 10 days later. Magnetic resonance imaging(MRI)and magnetic resonance venography(MRV)showed thrombotic occlusion at the superior sagittal sinus. Anticoagulant therapy with heparin was initiated. However, a generalized epileptic seizure occurred 11 days later, and an antiepileptic drug therapy was initiated. The headache and neurological deficits gradually improved, and MRI findings showed that the superior sagittal sinus had re-canalized. The main cause of the sinus thrombosis in this patient was considered dehydration and cisplatin-induced hypercoagulability. Five courses of BEP therapy were carried out with care to avoid dehydration. The patient has remained free of testicular tumor recurrence, metastasis, and cerebral sinus thrombosis for 2 years. Cisplatin-based chemotherapy is an established risk factor for venous thromboembolism(VTE), and cerebral sinus thrombosis is a rare but dangerous complication. Therefore, cerebral sinus thrombosis should be considered when patients with testicular cancer who undergo cisplatin-based chemotherapy start to develop neurological symptoms. Clinicians should be aware of this treatable complication.

Blocking COX-2 induces apoptosis and inhibits cell proliferation via the Akt/survivin- and Akt/ID3 pathway in low-grade-glioma.

Approximately half of surgically-treated patients with low-grade-glioma (LGG) suffer recurrence or metastasis. Currently there is no effective drug treatment. While the selective COX-2 inhibitor celecoxib showed anti-neoplastic activity against several malignant tumors, its effects against LGG remain to be elucidated. Ours is the first report that the expression level of COX-2 in brain tissue samples from patients with LGG and in LGG cell lines is higher than in the non-neoplastic region and in normal brain cells. We found that celecoxib attenuated LGG cell proliferation in a dose-dependent manner. It inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. We also show that celecoxib hampered the activation of the Akt/survivin- and the Akt/ID3 pathway in LGGs. These findings suggest that celecoxib may have a promising therapeutic potential and that the early treatment of LGG patients with the drug may be beneficial.

Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: comparison of clinical results obtained with BNCT and conventional treatment.

The purpose of this study was to evaluate the clinical outcome of boron neutron capture therapy (BNCT) and conventional treatment in patients with newly diagnosed glioblastoma. Since 1998 we treated 23 newly-diagosed GBM patients with BNCT without any additional chemotherapy. Their median survival time was 19.5 months; the 2-, 3-, and 5-year survival rates were 31.8%, 22.7%, and 9.1%, respectively. The clinical results of BNCT in patients with GBM are similar to those of recent conventional treatments based on radiotherapy with concomitant and adjuvant temozolomide.

Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma.

Interferon-beta (IFN-ß) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-ß, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN-ß-induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.

Ruptured distal accessory anterior cerebral artery aneurysm--case report.

A 48-year-old man presented with an extremely rare aneurysm arising from an accessory anterior cerebral artery (ACA) manifesting as sudden onset of headache lasting for 5 days. Neurological examination on admission revealed no abnormalities. Computed tomography showed subarachnoid hemorrhage of the interhemispheric fissure and intraparenchymal hematoma of the left cingulate gyrus. Magnetic resonance and cerebral angiography revealed a saccular aneurysm of the distal portion of the accessory ACA classified as the bihemispheric type. Neck clipping of the aneurysm was performed via an interhemispheric approach 17 days after symptom onset. The patient made a good postoperative recovery without neurological deficit. Distal accessory ACA aneurysms tend to arise from the first bifurcation and supply parietal branches. The aneurysms tend to occur on the bihemispheric type of distal accessory ACA. Hemodynamic stress may contribute to formation or development of these aneurysms.