Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models.

Gemcitabine plus cisplatin (GC) combination chemotherapy is the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, most cases develop resistance to this therapy. We investigated whether drug resistance could be targeted through metabolic reprogramming therapies. Metabolomics analyses in our lab's gemcitabine- and cisplatin-resistant cell lines revealed increased phosphoglycerate dehydrogenase (PHGDH) expression in gemcitabine-resistant cells compared with parental cells. Isocitrate dehydrogenase 2 (IDH2) gain of function stabilized hypoxia-inducible factor1α (HIF1α) expression, stimulating aerobic glycolysis. In gemcitabine-resistant cells, elevated fumaric acid suppressed prolyl hydroxylase domain-containing protein 2/Egl nine homolog 1 (PHD2) and stabilized HIF1α expression. PHGDH downregulation or inhibition in gemcitabine-resistant BC cells inhibited their proliferation, migration, and invasion. Cisplatin-resistant cells showed elevated fatty acid metabolism, upregulating fatty acid synthase (FASN) downstream of tyrosine kinase. Using the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib, we inhibited malonyl-CoA production, which is crucial for fatty acid synthesis, and thereby suppressed upregulated HIF1α expression. Combination treatment with NCT503 and erdafitinib synergistically suppressed tumor cell proliferation and induced apoptosis in vitro and in vivo. Understanding these mechanisms could enable innovative BC therapeutic strategies to be developed.

LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer.

Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

Prevention of Postoperative Skin Disorders and Pressure Injuries in the Neurosurgical Park Bench Position Surgery: A Prospective Cohort Study.

Background In neurosurgical procedures where the park bench position is employed, the risk of perioperative pressure injuries is elevated due to the limited contact surface area, with the head and part of the upper torso extending beyond the surgical table. This study aimed to examine the effects of preventative measures against such injuries, proposing a potential standard for postural fixation in these surgeries. Methods Conducted at a medical center, from January 2017 to March 2023, this prospective cohort study involved participants aged 20 and above who underwent neurosurgical procedures in the park bench position under general anesthesia. The focus was on comparing the incidence of pressure injuries between intervention and control groups. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results Out of 65 patients enrolled, 28 were assigned to each of the intervention and control groups. The control group experienced 17 instances of postoperative pressure injuries and skin disorders in areas prone to pressure, such as the axillary and greater trochanter regions. Conversely, the intervention group reported no such incidents, underscoring the efficacy of meticulous surgical positioning and management of bodily pressure, temperature, humidity, and microclimate. Conclusion Implementing preventive measures in neurosurgical park bench procedures significantly reduces the incidence of postoperative pressure injuries and skin disorders. These findings advocate for the adoption of standardized postural fixation protocols in such surgeries, potentially influencing global clinical practices in neurosurgery.

Potential therapeutic target secretogranin II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma.

Multitargeted receptor tyrosine kinase inhibitors, including vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib, have been used as the primary targeted agents for patients with recurrent or distant metastasis of advanced renal cell carcinoma (RCC). However, endogenous or acquired sunitinib resistance has become a significant therapeutic problem. Therefore, we focused on mechanisms of sunitinib resistance in RCC. First, we undertook RNA sequencing analysis using previously established sunitinib-resistant RCC (SUR-Caki1, SUR-ACHN, and SUR-A498) cells. The results showed increased expression of secretogranin II (SCG2, chromogranin C) in SUR-RCC cells compared to parental cells. The Cancer Genome Atlas database showed that SCG2 expression was increased in RCC compared to normal renal cells. In addition, the survival rate of the SCG2 high-expression group was significantly lower than that of the RCC low-expression group. Thus, we investigated the involvement of SCG2 in sunitinib-resistant RCC. In vitro analysis showed that migratory and invasive abilities were suppressed by SCG2 knockdown SUR cells. As SCG2 was previously reported to be associated with angiogenesis, we undertook a tube formation assay. The results showed that suppression of SCG2 inhibited angiogenesis. Furthermore, coimmunoprecipitation assays revealed a direct interaction between SCG2 and hypoxia-inducible factor 1α (HIF1α). Expression levels of VEGF-A and VEGF-C downstream of HIF1α were found to be decreased in SCG2 knockdown SUR cells. In conclusion, SCG2 could be associated with sunitinib resistance through VEGF regulation in RCC cells. These findings could lead to a better understanding of the VHL/HIF/VEGF pathway and the development of new therapeutic strategies for sunitinib-resistant RCC.

Case report: Unruptured small middle cerebral artery aneurysm with perianeurysmal edema.

Background: Perianeurysmal edema (PAE) has a tendency to occur in embolized aneurysms but also in partially thrombosed, large, or giant aneurysms. However, there are only a few cases recorded in which PAE was detected in untreated or small aneurysms. We suspected that PAE might be an impending sign of aneurysm rupture in these cases. Herein, we presented a unique case of PAE that was related to an unruptured small middle cerebral artery aneurysm. Case description: A 61-year-old woman was referred to our institute due to a newly formed abnormal fluid-attenuated inversion recovery (FLAIR) hyperintense lesion in the right medial temporal cortex. Upon admission, the patient did not present with any symptoms or complaints; however, FLAIR and CT angiography (CTA) suggested an increased risk of aneurysm rupture. Aneurysm clipping was conducted, and no evidence of subarachnoid hemorrhage and hemosiderin deposits around the aneurysm and brain parenchyma was noted. The patient was discharged home without any neurological symptoms. MRI taken at eight months post-clipping revealed complete regression of the FLAIR hyperintense lesion around the aneurysm. Conclusion: PAE in unruptured, small aneurysm is thought to be an impending sign of aneurysm rupture. Early surgical intervention is critical even for small aneurysms with PAE.

Exosomal microRNA-1 and MYO15A as a target for therapy and diagnosis in renal cell carcinoma.

Exosomes are 40-100 nm nano-sized extracellular vesicles and are receiving increasing attention as novel structures that participate in intracellular communication. We previously found that miRNA-1 (miR-1) functions as a tumor suppressor in renal cell carcinoma (RCC). In this study, we investigated the function of exosomal miR-1 and the possibility that the exosome constitutes a tumor maker in RCC. First, we established the method to collect exosomes from cell lysates and human serum by a spin column-based method. Next, we assessed exosomes using Nanosight nanoparticle tracking analysis and Western blot analysis with exosome marker CD63. We confirmed that exosomes labeled with PKH26 fused with recipient cells. Moreover, miR-1 expression was elevated in RCC cells treated with exosomes derived from miR-1-transfected cells. Functional analyses showed that exosomal miR-1 significantly inhibited cell proliferation, migration and invasion compared to control treatment. Our analyses with TCGA database of RCCs showed that miR-1 expression was significantly downregulated in clinical RCC samples compared to that in normal kidney samples, and patients with low miR-1 expression had poorer overall survival in comparison to patients with high expression. Furthermore, RNA sequence analyses showed that expression levels of several genes were altered by exposure to exosomal miR-1. The analyses with TCGA database indicated that high expression of MYO15A was associated with a poorer outcome in RCC. In addition, RT-qPCR analysis of exosomes from clinical patients' sera showed that MYO15A was significantly upregulated in RCC patients compared to that in healthy controls. This study showed that treatment with exosomal miR-1 might be an effective approach to treating RCCs. In addition, exosomal MYO15A could be a diagnostic tumor marker in RCCs.

Unruptured cerebral aneurysms with the segmental duplicated middle cerebral artery formed a fenestrated structure at origin.

BACKGROUND: Middle cerebral artery (MCA) has a significantly lower incidence of anatomical variations than other intracranial arteries. We present an extremely rare case of unruptured aneurysms with the segmental duplicated MCA (d-MCA) formed a fenestrated structure at origin. CASE DESCRIPTION: A 55-year-old female underwent direct surgery for the unruptured aneurysms at the top of the right internal cerebral artery with d-MCA. The d-MCA branches separated at the right internal cerebral artery top and had comparable with that of the main MCA trunk. Moreover, there was an anastomosis between the d-MCA branches. We diagnosed this anastomosis as segmental d-MCA. Two aneurysmal domes were identified during surgery at the origin of the d-MCA, which the main dome protruding backward was wide necked and another small one was collapsed or thrombosed protruding forward. We used a fenestrated clip for the posterior projecting dome, and the aneurysms were successfully obliterated. CONCLUSION: Although cerebral aneurysms associated with d-MCA are rare, there are technical difficulties in the surgical management. A fenestrated clip might be most reasonable to obtain patency of the parent arteries for the posterior projecting aneurysms if the perforators can be avoided.

[Asymptomatic Aplastic or Twig-Like Middle Cerebral Artery Associated with Unruptured Cerebral Aneurysms at the Origin (A1) of a Collateral Artery and the Anterior Communicating Artery: A Case Report with Multiple Intracranial Atherosclerotic Stenoses].

We report a rare case of asymptomatic aplastic or twig-like middle cerebral artery (Ap/T-MCA) with small unruptured aneurysms at the origin (A1) of the anomalous collateral artery containing plexiform (twig-like) networks and in the anterior communicating artery. In Ap/T-MCA, other cerebrovascular systems are usually considered to exhibit normal findings not associated with atherosclerosis. At first admission, atherosclerotic M1 occlusion was suspected because of the patient's risk factors and multiple stenoses in major intracranial arteries. Cerebral blood flow (CBF) studies revealed reduction of resting CBF and vascular reserve in the ipsilateral MCA territory. After 5 years, a diagnosis of Ap/T-MCA was reached based on detailed image examination and intraoperative findings during aneurysm clipping in combination with extracranial-intracranial (EC-IC) bypass. It should be noted that atherosclerosis can coexist with Ap/T-MCA, which is considered a congenital anomaly in which bleeding often occurs due to a ruptured aneurysm within the fragile collateral vessels. In previous reports, A1 aneurysms at the origins of the collateral arteries ruptured even when they were small. Aggressive radical surgery using EC-IC bypass can be considered for the treatment of unruptured aneurysms associated with Ap/T-MCA, but further research is needed. (Received September 14, 2020; Accepted November 4, 2020; Published 1 April, 2021).

[Orbital Compartment Syndrome Perhaps Secondary to Intra-Orbital Fluid Retention and Orbital/Palpebral Emphysema Following Frontotemporal Craniotomy for an Unruptured Cerebral Aneurysm:A Case Report].

A 58-year-old woman underwent left frontotemporal craniotomy for clipping of an unruptured cerebral aneurysm. A small defect was accidentally created in the orbital roof intraoperatively. The patient developed left eyelid edema and ocular pain after recovery from anesthesia. The following day, the eyelid edema worsened, and she had difficulty opening her eyes. On the 9th postoperative day, she noticed diminished visual acuity and diplopia in her left eye when she was able to spontaneously open her eyes. Ophthalmological evaluation revealed mild left visual loss, decreased light reflex, ophthalmoplegia, ptosis, and chemosis. Computed tomography(CT)/magnetic resonance imaging revealed left proptosis, optic nerve stretching, intra-orbital fluid retention, and orbital/palpebral emphysema. She was diagnosed with orbital compartment syndrome(OCS)and received conservative treatment;however, her visual acuity did not improve. OCS observed after cerebral aneurysm surgery is rare;to date, only 24 cases have been reported in the available literature. Although the mechanism of OCS after craniotomy is unclear, it may be attributed to ocular compression by a muscle flap or increased intra-orbital pressure secondary to venous congestion. In the present case, the left superior ophthalmic vein and cavernous sinus were not clearly visualized on CT angiography. Therefore, we concluded that the right superior ophthalmic vein and superficial facial veins underwent dilatation and served as collateral circulation of the left orbital venous system. We speculate that OCS occurred secondary to increased intra-orbital pressure, possibly caused by inflow of cerebrospinal fluid with air into the orbit through a small bone defect that was accidentally created during craniotomy in a setting of orbital venous congestion.

[A Case of M2 Segment Dissection of the Middle Cerebral Artery Presenting with Deep White Matter Infarction Triggered by Minor Head Injury].

Herein, we report a rare case of a dissecting aneurysm of the M2 segment of the middle cerebral artery(MCA), presenting with a deep white matter infarction triggered by minor head injury. A 31-year-old woman was admitted to our hospital with headache and vomiting 3 hours after a mild head impact. A magnetic resonance angiogram obtained 10 months earlier, when the patient had complained of sudden headache, showed mild fusiform dilatation of the left M2 segment. On admission, computed tomography angiography(CTA)revealed irregular fusiform dilatation of the superior trunk of the left M2. Magnetic resonance imaging showed an intramural hematoma on the wall of the left M2 and acute infarction in the left deep white matter. Eight days after admission, CTA revealed further dilation of the aneurysm, and it was diagnosed as a dissecting aneurysm. The patient was successfully treated with proximal clipping and superficial temporal artery(STA)-MCA(M4)bypass on day 15. Bypass to a cortical M4 recipient was performed after the efferent M4 was identified using indocyanine green videoangiography. Four weeks postoperatively, the patient was discharged without any neurological deficits. The M2 dissecting aneurysm gradually regressed, and the bypass remained patent for 10 months postoperatively. To our knowledge, this is the first case of a dissecting M2 aneurysm treated by proximal clipping and STA-MCA bypass. This procedure seems a feasible option when the distal portion of the dissected MCA is difficult to expose.

[Early Development of a Symptomatic Expanding Porencephalic Cyst in the Hematoma Cavity after Subcortical Hematoma Removal in an Adult:A Case Report].

A 69-year-old woman presented on an emergency basis, with headache and left hemiparesis. Initial head CT at the time of admission revealed a large subcortical hematoma with perihematomal edema extending from the right parietal to the occipital lobe. A small part of the hematoma extended toward the trigone of the right lateral ventricle. CT angiography revealed no vascular abnormalities. Emergency craniotomy was erformed, and the patient's initial postoperative course was unremarkable. However, the patient's neurological symptoms worsened 10 days postoperatively, and CT revealed a new low-density cystic lesion with perifocal edema at the site of hematoma removal, in addition to severe cerebral compression. We performed a reoperation, and intraoperatively we observed hematoma fluid mixed with cerebrospinal fluid without any abnormal blood vessels or neoplastic lesions in the hematoma cavity. We identified the choroid plexus deep within the surgical field, and slight leakage of cerebrospinal fluid was detected from the ventricular aspect, indicating the formation of a small passage between the hematoma cavity and the ventricle. After the second operation, her postoperative course was uneventful without recurrent cyst formation. An early symptomatic expanding porencephalic cyst in the hematoma cavity after removal of an intracerebral hematoma is rare, and only a few cases have been reported in the literature. Based on literature review and considering the likely mechanism of cyst development, we speculated that progressive cyst expansion could be attributed to a check valve mechanism between the ventricle and the cavity from which the hematoma was removed, as observed in the present case.

[Ruptured Cerebral Aneurysm Associated with Arachnoid Cyst].

Cerebral aneurysms and arachnoid cysts are relatively common cerebral malformations and the use of recent modalities has increased their detection rates. However, cerebral aneurysms associated with arachnoid cysts are unusual. We describe two cases of ruptured cerebral aneurysms associated with arachnoid cysts. According to previous reports, clinical presentation may sometimes be unusual, as cysts can prevent subarachnoid hemorrhage. Moreover, in some cases, CT may reveal typical arachnoid cysts without subarachnoid hemorrhage, without intracystic hematoma, or with subdural hematoma alone. These clinical presentations and radiologic findings can lead to delayed diagnosis of subarachnoid hemorrhage. Therefore, we should consider the coexistence of arachnoid cyst in case of a warning sign of aneurysm rupture.

[Task-shifting Carried out by an Emergency Department's Stroke Hotline and Medical Care Support Conducted by Nurse Practitioners].

Our hospital serves as the main hub for eight remote island hospitals(RIHs)in Nagasaki Prefecture, Japan. The shortage of stroke physicians, which has led to overwork, is a major concern. Several "task-shifting" systems were adopted to avoid physician burnout. First, the emergency department established a hotline system for receiving emergency calls regarding a stroke, and which managed initial care until the stroke physicians arrived(called the Nagasaki Medical Center stroke hotline system: N-SHOT)in 2014. The rt-PA administration rate increased from 3.3% in the Pre-N-SHOT group to 6.7% in the N-SHOT group. Second, the 'isolated islands stroke hotline system(I-SHOT)', with which physicians in RIHs participate in cooperation with N-SHOT, was started in 2017. After I-SHOT was introduced, the number of patients treated with the drip and ship method using teleradiology and 24-h helicopter transportation increased from 20(2010-2016)to 29 cases in 2017-2018. Additionally, new information and communication technology(ICT)using smart devices was introduced into the teleradiology system for task support. Third, on behalf of stroke physicians, nurse practitioners(NP)helped bedridden patients who had been delivered from RIHs and who had received acute treatment, and returned to their islands by helicopter or airplane as transitions of care. N-SHOT is smoothly operated by each hospital department without reducing the quality of the stroke hotline. It has contributed to an increase in rt-PA and mechanical thrombectomy cases; I-SHOT has had the same effect. Task-shifting and task support with N- & I-SHOT, the smooth transfer system by NP, and the new ICT are considered to be useful for reducing the overall burden of stroke physicians.

[A Case of Radiation-induced Glioblastoma 29 Years after Treatments for Germinoma].

Intracranial germinomas are considered one of the most radiosensitive tumors and are curable by radiotherapy alone. Although patients can expect long-term survival, the adverse effects of radiotherapy and late sequelae in survivors are a major concern. Radiation-induced secondary neoplasms are one of those sequelae and are a serious concern because they are often connected directly with life prognosis. We describe a case of radiation-induced glioblastoma after radiotherapy for germinoma. An 11-year-old boy with basal ganglia germinoma was successfully treated with postoperative cranial irradiation. At the age of 40 years, he was admitted to our hospital for aphasia and memory disturbance. CT and MRI revealed a tumor in the left parietal lobe with dissemination. The tumor of the parietal lobe was removed surgically, and pathohistologically, it was diagnosed as glioblastoma. Long-term survivors who receive radiotherapy for germinomas in childhood are at risk for late complications, including radiation-induced neoplasms. Therefore, careful follow-up neurological examinations are recommended in these patients, even 20-30 years after radiotherapy.

[A Rare Case of Communicating Hydrocephalus with Intraparenchymal Pericatheter Cyst and Surrounding Edema in an Adult due to Accidental Change in the Pressure Setting of the Programmable Shunt System].

A 59-year-old woman suffering from memory impairment visited our hospital. She was discharged nine years ago without complications after undergoing neck clipping surgery for intracranial aneurysm rupture and a right ventricular peritoneal shunt using the CODMAN® HAKIM® programmable valve system(CHPV)for hydrocephalus. Initial CT/MRI revealed a cystic lesion with surrounding edema in the right frontal lobe around the proximal catheter, and a left frontal subacute subdural hematoma. The right ventricle was shown as a slit as before. The cystic portion presented with an MRI signal of the same intensity as the cerebrospinal fluid(CSF), and no enhancement effect was observed. It was thought to be a CSF cyst around the shunt catheter with interstitial CSF edema. Skull radiographs showed an accidental change in the CHPV pressure setting(100 to 190mmH2O), possibly due to head impact. We concluded that the newly set valve pressure caused sudden shunt dysfunction, resulting in CSF cyst formation and surrounding edema. Image findings and her symptoms were immediately improved on adjusting the shunt valve. This complication in adults associated with shunt dysfunction is very rare and only 10 cases have been reported to date. This is the first report of this complication due to an accidental reset of CHPV. To prevent the risk of misdiagnosing this condition as a tumor or abscess and performing unnecessary surgery, it is always necessary to suspect the possibility of this complication. For that purpose, detailed images, including diffusion-weighted images and contrast-enhanced MRI, should be done early in clinical practice.

[Falx Meningioma Presenting with Intratumoral Hemorrhage and Interhemispheric Acute Subdural Hematoma:A Case of Report].

A 68-year-old male with a sudden headache while defecation was transferred to our hospital. He was initially diagnosed with intracerebral hemorrhage in the right occipital lobe and acute subdural hematoma(ASDH)in the right interhemispheric fissure. A CT angiography(CTA)showed stenosis in the superior sagittal sinus(SSS)and the vein of Galen(VG)near the hematoma, which were considered to be due to compression of the hematoma. In the source image of CTA, the enhancement effect of the hematoma part was not clear. MRI revealed a heterogeneous mixed signal intensity in the hematoma area, suggesting a mixture of hematoma components that had bled at different times. Cerebral angiography performed two weeks after onset showed a tumor shadow imaged from the middle meningeal artery. Therefore, the presence of hemorrhagic meningioma was suspected. This was confirmed by contrast-enhanced MRI. One month after the onset, tumor resection was performed after the embolization of the feeding artery. Part of the tumor around the SSS and VG was left due to severe adhesion. Postoperatively, stenosis of the SSS and VG significantly improved. In this case, the increase in venous pressure may be related to the bleeding mechanism. Hemorrhagic onset meningioma with interhemispheric ASDH is extremely rare, and only 4 cases have been reported. It is easy to misdiagnose if only non-contrast CT is used. It should be noted that in cases of intratumoral hemorrhage, CTA may not show an enhancing effect in the acute phase. Since contrast-enhanced MRI may be useful for a definitive diagnosis, it should be performed at the time of initial imaging.

[Aplastic or Twig-like Middle Cerebral Artery with Cortical Subarachnoid Hemorrhage and Reversible Cerebral Vasoconstriction Syndrome during the Postpartum Period in a Juvenile Female:A Case Report].

A 17-year-old female in a lethargic state with mild dysarthria was transferred to our hospital after experiencing a generalized tonic seizure immediately after giving birth. Head CT showed a cortical subarachnoid hemorrhage(cSAH)in the left frontoparietal convexity. Three-dimensional rotational angiography(3D-RA)revealed multifocal narrowing of the cortical branches of the left middle cerebral artery(MCA)and severe stenosis of the left M1 segment with plexiform collateral networks, suggesting the presence of reversible vasoconstriction syndrome(RCVS)and aplastic or twig-like MCA(Ap/T-MCA). When 3D-RA was repeated on day 17, the narrowing of the cortical artery had resolved, and a new constriction of more proximal blood vessels was observed. The arterial spasm disappeared within 3 months, confirming the diagnosis of RCVS and Ap/T-MCA. Although non-aneurysmal SAH due to Ap/T-MCA is extremely rare, RCVS often complicates cSAH in the frontal/parietal region. It is suggested that RCVS triggers cSAH in the presence of incidental Ap/T-MCA. Ap/T-MCA is thought to be caused by developmental abnormalities during the embryonic period, but only 11 cases in children or adolescents have been reported. This suggests that there are a considerable number of asymptomatic young patients whose condition has not been detected. The majority of patients with Ap/T-MCA are from East Asia, suggesting that racial and genetic background differences are a factor. As this anomaly is more likely to present as a stroke in adulthood, long-term follow-up is recommended if it is found at a young age. There is no evidence that revascularization is effective in preventing stroke. Further studies are needed on how to manage this condition appropriately.

[Two Cases of Late-onset Brain Edema after Craniotomy for Unruptured Intracranial Aneurysms Suspected to be due to an Allergic Reaction to Arachnoid Plasty Material].

We report two rare cases of late-onset brain edema after craniotomy for clipping or coating of unruptured intracranial aneurysms, possibly due to an allergic reaction to topically applied fibrin glue or gelatin sponge used for arachnoid plasty to cover the opened sylvian cistern. Both patients were women in their 60s with an allergic predisposition and both followed a similar clinical course. A slight fever and headache persisted during the postoperative period. Five to six weeks after surgery without complications, MR images showed an extensive T2 prolongated region in the white matter around the operative field, indicative of vasogenic edema, with mass effect and meningeal enhancement around the sylvian fissure that had been covered with gelatin sponge and sprayed fibrin glue. Swelling of the cerebral cortex around the sylvian fissure subjected to arachnoid plasty was also observed. Blood tests showed the absence of an inflammatory reaction and cerebrospinal fluid examination showed lymphocytosis that was considered to be due to an aseptic meningeal reaction or meningitis. Clinical symptoms and imaging findings steadily improved with the administration of steroids and antiallergic agents. Delayed brain edema may occur around the arachnoid plasty area despite an uneventful chronic postoperative period, which could be due to an allergic reaction to locally administered fibrin glue or gelatin sponge. Thus, the application of arachnoid plasty using fibrin glue and gelatin sponge in patients with a predisposition to allergies needs to be carefully considered.