A Spontaneous Extracranial Internal Carotid Artery Dissection with Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review.

Background and Objectives: Non-cystic manifestation of autosomal dominant polycystic kidney disease (ADPKD) is an important risk factor for cerebral aneurysms. In this report, we describe a rare spontaneous internal carotid artery (ICA) dissection in a patient with ADPKD. Observations: A 38-year-old woman with a history of ADPKD and acute myocardial infarction due to coronary artery dissection experienced severe spontaneous pain on the left side of her neck. Magnetic resonance imaging (MRI) revealed a severe left ICA stenosis localized at its origin. Carotid plaque MRI showed that the stenotic lesion was due to a subacute intramural hematoma. Close follow-up by an imaging study was performed under the diagnosis of spontaneous extracranial ICA dissection, and spontaneous regression of the intramural hematoma was observed uneventfully. Conclusions: When patients with a history of ADPKD present with severe neck pain, it is crucial to consider the possibility of a spontaneous ICA dissection. A carotid plaque MRI is beneficial in the differential diagnosis. Conservative management may benefit patients without ischemic symptoms.

Correlation between magnetic resonance imaging characteristics and BRAF alteration status in individuals with optic pathway/hypothalamic pilocytic astrocytomas.

BACKGROUND AND PURPOSE: Most individuals with optic pathway/hypothalamic pilocytic astrocytoma (OPHPA) harbor either the BRAF V600E mutation or KIAA1549-BRAF fusion (K-B). This study aimed to investigate the imaging characteristics of OPHPA in relation to BRAF alteration status. MATERIALS AND METHODS: Seven cases of OPHPA harboring either the BRAF V600E mutation or K-B fusion were included in the study. Preoperative magnetic resonance imaging (MRI) was assessed for degree of T2 hyperintensity on T2-weighted images (T2WI) and the ratio of nonenhancing T2 or fluid-attenuated inversion recovery (FLAIR) hyperintense area to the contrast enhanced area (CE) on gadolinium-enhanced-T1 weighted images (T2/FLAIR-CE mismatch). The T2 signal intensity was normalized to cerebrospinal fluid (T2/CSF) for both the V600E and K-B group and compared. T2/FLAIR-CE mismatch was assessed by calculating the proportion of the tumor volume of nonenhancing high T2 signal intensity to the whole lesion (nonenhancing and enhancing components). RESULTS: Four and three cases of OPHPA harboring the BRAF V600E mutation and K-B, respectively, were analyzed. The T2/CSF value was higher in the K-B group than in the V600E group. Moreover, the V600E group had a larger T2/FLAIR-CE mismatch than the K-B group. CONCLUSIONS: The BRAF alteration status in individuals with OPHPA was associated with preoperative MRI by focusing on T2 signal intensity and T2/FLAIR-CE mismatch. The BRAF V600E mutation was associated with a lower T2/CSF value and larger T2/FLAIR-CE mismatch, whereas K-B fusion was associated with a higher T2/CSF value and smaller T2/FLAIR-CE mismatch.

[Risk Factors for Adverse Events after Implantation of BCNU Wafers in High-grade Gliomas].

BACKGROUND: In Japan, patients with malignant glioma have been treated with BCNU wafers (Gliadel®) since January 2013. Several adverse events(AEs)associated with implantation of BCNU wafers, including cerebral edema or cyst formation, are recognized. Here, we report a retrospective review of the experience with implantation of BCNU wafers in our institutions and our findings regarding the risk factors for the AEs. METHODS: We reviewed the records of patients with malignant glioma who were implanted with BCNU wafers between April 2013 and September 2014. Their AEs were examined clinically and radiologically and evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) grading. For investigating the association between risk factors and incidence of AEs, histological diagnosis, extent of resection, and period of BCNU wafers implantation surgery were selected as possible risk factors. RESULTS: Twenty-one patients were included in this investigation. There were no associations among incidence of AEs and histological diagnosis or extent of tumor resection. However, regarding the period of BCNU wafers implantation, additional resection for newly diagnosed tumors and resection for recurrent tumors tended to increase the rate and severity of AEs, especially cerebral edema, compared to primary resection. CONCLUSION: In cases of BCNU wafers implantation, the incidence and degree of AEs might increase if additional resection for newly diagnosed tumors or resection for recurrent tumors is performed. Our investigation revealed that AEs associated with implantation of BCNU wafers tend to occur in the repeated glioma surgery.

5-aminolevulinic acid-guided endoscopic biopsy with violet light-emitting diode flashlight in malignant glioma: Technical note.

Background: 5-aminolevulinic acid (5-ALA) photodynamic diagnosis (PDD) has enabled better identification of malignant tumor cells and real-time intraoperative guidance. Here, we report a reasonable procedure for 5-ALA-guided endoscopic biopsy with a violet light-emitting diode (LED) flashlight for deep-seated malignant gliomas. Methods: A 63-year-old man presented with a headache and left upper homonymous quadrantanopia. Imaging studies showed atypical lesions with non-significant and partial contrast enhancement in the right deep temporo-occipital lobe. An endoscopic biopsy was performed under the guidance of 5-ALA PDD with a violet LED flashlight. Results: The tumor tissues, which were difficult to distinguish from normal brain parenchyma under white light, were positive for 5-ALA fluorescence. The histopathological diagnosis was astrocytoma (the World Health Organization grade 3). The patient underwent adjuvant chemoradiation therapy. Headache and anopia improved, and no recurrence was observed at 12 months follow-up. Conclusion: This technique of neuroendoscopic biopsy guided by 5-ALA PDD fluorescence with a violet LED flashlight may allow a safe and accurate diagnosis of deep-seated malignant gliomas.

Treatment of new-onset primary central nervous system lymphoma in elderly patients using RMPV chemotherapy: a single-institution experience.

The prognosis of primary central nervous system lymphoma (PCNSL) in the elderly remains poor. We aimed to evaluate the outcome of rituximab, methotrexate, procarbazine, and vincristine (RMPV) chemotherapy in elderly patients with new-onset PCNSL. Twenty-eight patients aged ≥ 70 years treated for PCNSL between 2010 and 2020 were examined retrospectively. Nineteen patients received RMPV and nine did not qualify. Patients received five to seven cycles of RMPV plus response-adapted whole-brain radiotherapy (WBRT) and cytarabine. Ten of the 19 patients who received RMPV (52.6%) completed the induction, but only four patients (21.1%) completed RMPV chemotherapy, WBRT 23.4 Gy, and cytarabine. Median progression-free survival (PFS) and overall survival (OS) in the RMPV group was 54.4 and 85.0 months, respectively. Both PFS and OS were significantly longer in patients who received RMPV chemotherapy than in those who did not, and in patients who started but did not complete RMPV than in those who did not receive RMPV. Patients who received incomplete RMPV tended to have a favorable prognosis. Initial treatment with RMPV chemotherapy was effective in elderly patients with PCNSL. Adjusting the number of courses of RMPV may improve the prognosis of elderly patients with PCNSL, but further verification is necessary.

Hematoma expansion caused by trapped cerebrospinal fluid in subacute phase intracerebral hemorrhage: A case report.

Background: Although hematoma expansion (HE) is caused by active bleeding in patients with intracranial hemorrhage in most cases, cerebrospinal fluid (CSF) trapped in the hematoma cavity is not a well-known cause of HE. Case Description: We present a case of subcortical hemorrhage in an 80-year-old woman who experienced neurological deterioration in the subacute phase because of HE caused by CSF pooling in the hematoma cavity. The patient was transferred to our hospital from a previous hospital for surgical treatment because the consciousness disturbance was likely caused by the perihematomal edema that occurred 4 days after onset. Head computed tomography (CT) at admission to our hospital showed a blend sign, and a part of the low-density area of the hematoma was enlarged compared with the CT at admission to the previous hospital. Although the hematoma was located adjacent to the lateral ventricle, no intraventricular hemorrhage was observed. Emergent hematoma evacuation was performed, and intraoperative findings indicated that the enlarged hematoma cavity was caused by CSF pooling. The patient's postoperative course was uneventful. She was transferred to a rehabilitation hospital 16 days after admission to our hospital. Conclusion: Hematomas adjacent to the ventricle and showing a blend sign can expand in the subacute phase because of the trapped CSF.

Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain.

Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability. In this study, FUS/microbubble-assisted BBB opening was investigated for the intravenous delivery of mRNA-LNP to the brain. The intensity of FUS irradiation was optimized to 1.5 kW/cm2, at which BBB opening occurred efficiently without hemorrhage or edema. Exogenous protein (luciferase) expression by mRNA-LNP, specifically at the FUS-irradiated side of the brain, occurred only when FUS and microbubbles were applied. This exogenous protein expression was faster but shorter than that of plasmid DNA delivery. Furthermore, foreign protein expression was observed in the microglia, along with CD31-positive endothelial cells, whereas no expression was observed in astrocytes or neurons. These results support the addition of mRNA-LNP to the lineup of nanoparticles delivered by BBB opening.

Ruptured basilar artery perforator aneurysm: a novel mechanism of pure subarachnoid hemorrhage in moyamoya disease. Illustrative case.

BACKGROUND: Pure subarachnoid hemorrhage (SAH) in patients with moyamoya disease is a rare occurrence. Three underlying mechanisms have been described previously, except for ruptured aneurysm of the circle of Willis. Herein, the authors describe a novel mechanism: rupture of a perforator aneurysm in moyamoya disease. OBSERVATIONS: A 51-year-old man experienced sudden onset of severe headache and vomiting. Computed tomography showed diffuse SAH. Digital subtraction angiography (DSA) showed unilateral moyamoya disease without remarkable etiology of SAH. The patient underwent conservative management with antihypertensive agents. The second DSA on day 17 revealed a slow-filling aneurysm emerging from the basilar top perforating artery. The diagnosis of SAH due to unknown origin was changed to ruptured basilar artery perforator aneurysm (BAPA). The third follow-up DSA on day 159 revealed the resolution of BAPA. LESSONS: In the case of pure SAH, it is crucial to consider the possibility of perforator aneurysms due to hemodynamic stress caused by moyamoya disease. Repeated DSA is essential for detecting the lesion.

Stem Cell Therapy for Acute/Subacute Ischemic Stroke with a Focus on Intraarterial Stem Cell Transplantation: From Basic Research to Clinical Trials.

Stem cell therapy for ischemic stroke holds great promise for the treatment of neurological impairment and has moved from the laboratory into early clinical trials. The mechanism of action of stem cell therapy includes the bystander effect and cell replacement. The bystander effect plays an important role in the acute to subacute phase, and cell replacement plays an important role in the subacute to chronic phase. Intraarterial (IA) transplantation is less invasive than intraparenchymal transplantation and can provide more cells in the affected brain region than intravenous transplantation. However, transplanted cell migration was reported to be insufficient, and few transplanted cells were retained in the brain for an extended period. Therefore, the bystander effect was considered the main mechanism of action of IA stem cell transplantation. In most clinical trials, IA transplantation was performed during the acute and subacute phases. Although clinical trials of IA transplantation demonstrated safety, they did not demonstrate satisfactory efficacy in improving patient outcomes. To increase efficacy, increased migration of transplanted cells and production of long surviving and effective stem cells would be crucial. Given the lack of knowledge on this subject, we review and summarize the mechanisms of action of transplanted stem cells and recent advancements in preclinical and clinical studies to provide information and guidance for further advancement of acute/subacute phase IA stem cell transplantation therapy for ischemic stroke.

Ruptured aneurysm-induced pituitary apoplexy: illustrative case.

BACKGROUND: Pituitary apoplexy associated with aneurysmal rupture is extremely rare and may be misdiagnosed as primary pituitary adenoma apoplexy. The authors present a case of a patient with pituitary apoplexy caused by rupture of an anterior cerebral artery aneurysm embedded within a giant pituitary adenoma, and they review the relevant literature. OBSERVATIONS: A 78-year-old man experienced sudden headache with progressive vision loss. Magnetic resonance imaging (MRI) revealed a giant pituitary tumor with abnormal signal intensity. Magnetic resonance angiography immediately before surgery showed a right A1 segment aneurysm, suggesting coexisting pituitary apoplexy and ruptured aneurysm. The patient underwent urgent transsphenoidal surgery for pituitary apoplexy. The tumor was partially removed, but the perianeurysmal component was left behind. Subsequent cerebral angiography showed a 5-mm right A1 aneurysm with a bleb that was successfully embolized with coils. Retrospective review of preoperative dynamic MRI showed extravasation of contrast medium from the ruptured aneurysm into the pituitary adenoma. Histopathologic examination showed gonadotroph adenoma with hemorrhagic necrosis. Postoperatively, the patient's visual function improved. LESSONS: MRI identification of pituitary apoplexy caused by aneurysmal rupture has not been reported previously. Aneurysmal rupture should be considered in the differential diagnosis of pituitary apoplexy. When a ruptured aneurysm is encountered, the authors recommend treating it before addressing pituitary apoplexy.

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid.

Sonodynamic therapy (SDT) is used to treat various malignancies and can be applied to brain tumors using a transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) device. This study investigated the efficacy of 220-kHz TcMRgFUS combined with 5-aminolevulinic acid (5-ALA) on malignant glioma in vitro and in vivo. F98 cells were irradiated with focused ultrasound (FUS) (4000 J, 20 W, 240 s, 100% duty cycle, target medium temperature <40°C) after treatment with 200 µg/mL 5-ALA, and cell viability and apoptosis were evaluated with the water-soluble tetrazolium-1 assay, triple fluorescent staining and Western blot analysis 20 h later. The anti-tumor effects of 5-ALA combined with FUS (500 J, 18 W, 30 s, 100% duty cycle, 10 repeats, target tissue temperature ≤42°C) were assessed on the basis of changes in tumor volume determined by MRI and histopathological analysis before and after treatment. The FUS/5-ALA combination reduced cell viability by inducing apoptosis and suppressed tumor proliferation and invasion as well as angiogenesis in vivo, while causing minimal damage to normal brain tissue. SDT with 220-kHz TcMRgFUS and 5-ALA can be safely used for the treatment of malignant glioma.

Reliability of the Size Evaluation Method for Meningiomas: Maximum Diameter, ABC/2 Formula, and Planimetry Method.

BACKGROUND: To evaluate the accuracy of tumor size by maximum diameter, ABC/2 formula, and planimetry method using thick-slice and thin-slice magnetic resonance imaging (MRI). METHODS: Maximum diameter and tumor volume calculated using ABC/2 formula (V1) and planimetry method with thick-slice MRI (V2) and thin-slice MRI (V3) were examined in 83 meningiomas. Form factor (FF) analysis was performed to assess irregularity of the tumor. V3 values were considered as real tumor volumes. The accuracy of V1 and V2 was evaluated using ratio and difference from V3. Meningiomas were categorized by tumor locations: skull base (anterior, middle, and posterior) and non-skull base (calvaria and other sites). RESULTS: Correlation between maximum diameter and V3 was statistically significant (r = 0.91), but the error was significant in tumors with longer maximum diameters. Correlation between V1 and V3 was significant (r = 0.97). However, V1 tended to be larger in middle skull base meningiomas or in tumors with low FF values (R2 = 0.21). V2 represented relatively accurate volumes in both groups except in the case of small meningiomas. When tumors were demonstrated within 3 fractions on thick-slice MRI, the ratio of V2 to V3 showed significant variability. CONCLUSIONS: Using the ABC/2 formula, the volume of meningiomas in the middle skull base or meningiomas with low FF value might be calculated larger than the real tumor volume. The planimetry method with thick-slice MRI demonstrated relatively accurate volumes if the tumor was fractionated in >4 slices.

Improvement of cerebral hypometabolism after resection of radiation-induced necrotic lesion in a patient with cerebral arteriovenous malformation.

A 55-year-old woman underwent radiosurgery for a left cerebral hemisphere arteriovenous malformation (AVM) and developed radiation-induced necrosis causing a massive edema in the surrounding brain tissues. Despite various therapies, the edema expanded to the ipsilateral hemisphere and induced neurological symptoms. The radiation-induced necrotic lesion was surgically removed 4 years after radiosurgery. While the preoperative FDG PET revealed severe hypometabolism in the left cerebrum, the necrotomy significantly ameliorated the brain edema, glucose metabolism (postoperative FDG PET), and symptoms. This case indicates that radiation necrosis-induced neurological deficits may be associated with brain edema and hypometabolism, which could be reversed by appropriate necrotomy.