Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment.

The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.

Assessment of language lateralization in epilepsy patients using the super-selective Wada test.

BACKGROUND: The classical Wada test (cWada), performed by injecting a short-acting anesthetic through the intracarotid route, helps determine language dominance. In the cWada, adverse effects are observed in 10-30% of trials, hindering accurate assessments. In this study, we assessed the effectiveness of the super-selective Wada test (ssWada), a more selective approach for anesthetic infusion into the middle cerebral artery (MCA). METHODS: We retrospectively examined the data of 17 patients with epilepsy who underwent ssWada via anesthetic injection into one M1 segment of the MCA and at least one contralateral trial. RESULTS: The ssWada identified 12 patients with left language dominance, 3 with right language dominance, and 2 with bilateral language distribution. Nine trials on the language dominant side resulted in global aphasia for patients with left- or right language dominance. Of the 13 trials conducted on the non-dominant language side, 12 revealed intact language function and one resulted in confusion. Among these, the outcomes of global aphasia or no language impairment were confirmed in the contralateral trials. Among the 22 trials of unilateral M1 injections in patients with unilateral language dominance, 21 (95.5%) showed either global aphasia or no language impairment, indicating language dominance. CONCLUSIONS: The ssWada yields clear results, with a high rate of over 90% in determining the language dominant hemisphere with few side effects.

The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

[Academia-Industry Alliance: Recent Trend].

Industry-academia Collaboration is an academic activity within academia(educational institutions such as universities, research institutes, etc.)formed to research and develop new technologies, create new businesses and knowledge, and recruit outsourcing human resources. There is a collaboration between an industry(a private company, a group that engages in broad commercial activities and links research and development directly to economic activity)and academia. Amidst the dramatic changes in the environment surrounding the goals of research and development of new technologies and the creation of new businesses, there are changes in what academia can do complementarily. We will outline the changes and current situation, including the efforts of the Tohoku University Hospital.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

Paradoxical worsening of ocular symptoms after transvenous embolization of cavernous sinus dural arteriovenous fistula due to coil-induced perifocal inflammation: A case report.

Ocular symptoms usually completely resolve after successful transvenous embolization of cavernous sinus dural arteriovenous fistulas (CS-dAVFs). Herein, we report a case of CS-dAVF in which sinus packing of the superior ophthalmic vein (SOV) caused coil-induced inflammation in orbital tissue, leading to deteriorating ocular symptoms. A 73-year-old woman presented with right-eye exophthalmos and chemosis. Cerebral angiography demonstrated right CS-dAVF, which retrogradely drained into the right SOV. We conducted sinus packing with coils via the right inferior petrosal sinus, resulting in obliteration of the shunts. One day after sinus packing, right exophthalmos and chemosis progressed, suggesting dAVF recurrence. However, no residual angiographic shunts were observed. Orbital magnetic resonance imaging (MRI) revealed edema in intraorbital tissue and gadolinium contrast enhancement of SOV wall. We presumed that the coils in SOV induced perifocal inflammation at the venous wall and surrounding orbital tissue, leading to aggravation of ocular symptoms. Following steroid therapy for 2 months, ocular symptoms and contrast enhancement on orbital MRI significantly improved without anticoagulant treatment. Posttreatment paradoxical worsening of ocular symptoms could be caused by coil-induced inflammation of the SOV wall near the orbital tissue. Steroid therapy could be effective in reducing orbital inflammatory reactions.

Bilateral and asymmetrical localization of language function identified by the superselective infusion of propofol in an epilepsy patient with a mild malformation of cortical development: illustrative case.

BACKGROUND: Atypical localization of language function can result in unexpected postsurgical deficits after cortical resection, but it is difficult to predict the risk in the presurgical evaluation. The authors experienced a rare case of the bilateral and independent existence of different components of language function identified by segmented evaluation of anatomical anterior and posterior language areas using the superselective infusion of propofol. OBSERVATIONS: A 32-year-old right-handed female presented with drug-resistant epilepsy. Comprehensive epilepsy evaluation suggested that the epileptic foci involved the whole left frontal lobe but provided less evidence of structural abnormality. To estimate the extent of functional deterioration likely to be caused by an extended left frontal lobectomy, the authors evaluated segmented cortical function in the ipsi- and contralateral hemispheres by the superselective infusion of propofol into the branches of the intracranial artery. The results revealed bilateral and asymmetrical localization of language function because the patient presented with different components of aphasia in each hemisphere. Based on the authors' assessment of her functional tolerance, an extended left frontal lobectomy was performed and resulted in neurological deficits within the anticipated range. LESSONS: An accurate understanding of the correlations between vascular and functional anatomy and the highly specific evaluation of language function provides more advanced presurgical assessment, allowing more tailored planning of cortical resection.

Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and ß cell proliferation.

The enhancement of insulin secretion and of the proliferation of pancreatic ß cells are promising therapeutic options for diabetes. Signals from the vagal nerve regulate both processes, yet the effectiveness of stimulating the nerve is unclear, owing to a lack of techniques for doing it so selectively and prolongedly. Here we report two optogenetic methods for vagal-nerve stimulation that led to enhanced glucose-stimulated insulin secretion and to ß cell proliferation in mice expressing choline acetyltransferase-channelrhodopsin 2. One method involves subdiaphragmatic implantation of an optical fibre for the photostimulation of cholinergic neurons expressing a blue-light-sensitive opsin. The other method, which suppressed streptozotocin-induced hyperglycaemia in the mice, involves the selective activation of vagal fibres by placing blue-light-emitting lanthanide microparticles in the pancreatic ducts of opsin-expressing mice, followed by near-infrared illumination. The two methods show that signals from the vagal nerve, especially from nerve fibres innervating the pancreas, are sufficient to regulate insulin secretion and ß cell proliferation.

Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury.

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

Language MEG predicts postoperative verbal memory change in left mesial temporal lobe epilepsy.

OBJECTIVE: To clarify whether preoperative language magnetoencephalography (MEG) predicts postoperative verbal memory (VM) changes in left mesial temporal lobe epilepsy (LMTLE). METHODS: We reviewed 18 right-handed patients with LMTLE who underwent anterior temporal lobectomy or selective amygdala hippocampectomy, 12 with (HS+) and 6 without hippocampal sclerosis (HS-). Patients underwent neuropsychological assessment before and after surgery. MEG was measured with an auditory verbal learning task in patients preoperatively and in 15 right-handed controls. Dynamic statistical parametric mapping (dSPM) was used for source imaging of task-related activity. Language laterality index (LI) was calculated by z-score of dSPM in language-related regions. LI in the region of HS+ and HS- was compared to controls. The correlation between LI and postoperative VM change was assessed in HS+ and HS-. RESULTS: Preoperative LI in supramarginal gyrus showed greater right-shifted lateralization in both HS+ and HS- than in controls. Right-shifted LI in supramarginal gyrus was correlated with postoperative VM increase in HS+ (p = 0.019), but not in HS-. CONCLUSIONS: Right-shifted language lateralization in dSPM of MEG signals may predict favorable VM outcome in HS+ of LMTLE. SIGNIFICANCE: Findings warrant further investigation of the relation between regional language laterality index and postoperative verbal memory changes.

Cerebral infarction following administration of andexanet alfa for anticoagulant reversal in a patient with traumatic acute subdural hematoma.

Background: Anticoagulants prevent thrombosis in patients with atrial fibrillation (AF) and venous thromboembolism but increase the risk of hemorrhagic complications. If severe bleeding occurs with anticoagulant use, discontinuation and rapid reversal are essential. However, the optimal timing for resuming anticoagulants after using reversal agents remains unclear. Here, we report early cerebral infarction following the use of andexanet alfa (AA), a specific reversal agent for factor Xa inhibitors, in a patient with traumatic acute subdural hematoma (ASDH). The possible causes of thromboembolic complication and the optimal timing for anticoagulant resumption are discussed. Case Description: An 84-year-old woman receiving rivaroxaban for AF presented with impaired consciousness after a head injury. Computed tomography (CT) revealed right ASDH. The patient was administered AA and underwent craniotomy. Although the hematoma was entirely removed, she developed multiple cerebral infarctions 10 h after the surgery. These infarctions were considered cardiogenic cerebral embolisms and rivaroxaban was therefore resumed on the same day. This case indicates the possibility of early cerebral infarction after using a specific reversal agent for factor Xa inhibitors. Conclusion: Most studies suggest that the safest time for resuming anticoagulants after using reversal agents is between 7 and 12 days. The present case showed that embolic complications may develop much earlier than expected. Early readministration of anticoagulant may allow for adequate prevention of the acute thrombotic syndromes.

Six-month Outcomes after PulseRider- and Conventional Single Stent-assisted Embolization for Bifurcation Aneurysms: A Propensity-adjusted Comparison.

Endovascular treatment of wide-necked bifurcation aneurysms (WNBAs) remains challenging despite using a stent. PulseRider is a novel device specifically designed to treat WNBAs, protecting both daughter branches, but the outcomes have not been compared with conventional single stent-assisted embolization. This study aimed to compare the six-month outcomes of PulseRider and single stent-assisted embolization for intracranial unruptured WNBAs using propensity score adjustment. Between February 2012 and October 2021, 46 unruptured WNBAs (34 basilar and 12 middle cerebral arteries) smaller than 10 mm in diameter were treated with PulseRider-assisted embolization (n = 17) or single stent-assisted embolization (n = 29). The immediate and six-month outcomes were compared using inverse probability of treatment weighting analysis. The immediate adequate occlusion rates for the PulseRider- and single stent-assisted embolization were similar (47.1% vs. 62.1%). At six months, adequate occlusion rates for the two groups were also similar (94.1% vs. 86.2%). However, the complete obliteration rate was significantly high after PulseRider-assisted embolization (88.2% vs. 41.4%, adjusted OR 10.54, 95% CI 1.93-57.63). The angiographical improvement rate was also significantly high after PulseRider-assisted embolization (70.6% vs. 37.9%, adjusted OR 6.06, 95% CI 1.54-23.76). The neurologic thromboembolic complication rate was 0% after PulseRider-assisted embolization and 3.4% after single stent-assisted embolization. PulseRider-assisted embolization of WNBAs smaller than 10 mm in diameter was associated with complete obliteration and angiographical improvement at six months. The unique shape of the PulseRider might contribute to the improved midterm aneurysm occlusion.

Randomized placebo-controlled trial of CL2020, an allogenic muse cell-based product, in subacute ischemic stroke.

Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14-28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1-61.3) in the CL2020 group and 10.0% (0.3-44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke.Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103).

Distinct patterns of copy number alterations may predict poor outcome in central nervous system germ cell tumors.

We have previously reported that 12p gain may predict the presence of malignant components and poor prognosis for CNS germ cell tumor (GCT). Recently, 3p25.3 gain was identified as an independent predictor of poor prognosis for testicular GCT. Eighty-one CNS GCTs were analyzed. Copy number was calculated using methylation arrays. Five cases (6.2%) showed 3p25.3 gain, but only among the 40 non-germinomatous GCTs (NGGCTs) (5/40, 12.5%; p = 0.03). Among NGGCTs, those with a yolk sac tumor component showed a significantly higher frequency of 3p25.3 gain (18.2%) than those without (1.5%; p = 0.048). NGGCTs with gain showed significantly shorter progression-free survival (PFS) than those without (p = 0.047). The 3p25.3 gain and 12p gain were independent from each other. The combination of 3p25.3 gain and/or 12p gain was more frequent among NGGCTs with malignant components (69%) than among those without (29%; p = 0.02). Germinomas containing a higher number of copy number alterations showed shorter PFS than those with fewer (p = 0.03). Taken together, a finding of 3p25.3 gain may be a copy number alteration specific to NGGCTs and in combination with 12p gain could serve as a marker of negative prognosis or treatment resistance. Germinoma with frequent chromosomal instability may constitute an unfavorable subgroup.

Visualization of the lenticulostriate arteries, long insular arteries, and long medullary arteries on intra-arterial computed tomography angiography with ultrahigh resolution in patients with glioma.

PURPOSE: The anatomical association between the lesion and the perforating arteries supplying the pyramidal tract in insulo-opercular glioma resection should be evaluated. This study reported a novel method combining the intra-arterial administration of contrast medium and ultrahigh-resolution computed tomography angiography (UHR-IA-CTA) for visualizing the lenticulostriate arteries (LSAs), long insular arteries (LIAs), and long medullary arteries (LMAs) that supply the pyramidal tract in two patients with insulo-opercular glioma. METHODS: This method was performed by introducing a catheter to the cervical segment of the internal carotid artery. The infusion rate was set at 3 mL/s for 3 s, and the delay time from injection to scanning was determined based on the time-to-peak on angiography. On 2- and 20-mm-thick UHR-IA-CTA slab images and fusion with magnetic resonance images, the anatomical associations between the perforating arteries and the tumor and pyramidal tract were evaluated. RESULTS: This novel method clearly showed the relationship between the perforators that supply the pyramidal tract and tumor. It showed that LIAs and LMAs were far from the lesion but that the proximal LSAs were involved in both cases. Based on these results, subtotal resection was achieved without complications caused by injury of perforators. CONCLUSION: UHR-IA-CTA can be used to visualize the LSAs, LIAs, and LMAs clearly and provide useful preoperative information for insulo-opercular glioma resection.

Simulation of the occipital transtentorial approach incorporating visualization of the cerebellar tentorium using three-dimensional computed tomography angiography and gadolinium-enhanced T1-weighted magnetic resonance imaging: technical note.

The occipital transtentorial approach (OTA) is one of the useful approaches to the lesions of the pineal region, dorsal brainstem, and supracerebellar region. However, a wide operative field is sometimes difficult to obtain due to the tentorial sinus and bridging veins. This study evaluated the usefulness of preoperative simulation of OTA, specifically including the cerebellar tentorium in 9 patients. All patients underwent computed tomography angiography and venography and gadolinium-enhanced three-dimensional T1-weighted magnetic resonance images (Gd-3D-T1WI). The images were fused, and the cerebellar tentorium, vessels, and tumor were manually extracted from Gd-3D-T1WI to obtain the simulation images. Visualization of the cerebellar tentorium could discriminate between bridging veins from the occipital lobe and cerebellum, and recognize the site of bridging to the tentorial sinus and variants which may interfere with the tentorial incision. Simulation of the tentorial incision was also possible based on the relationships between the tumor, tentorial sinus, bridging vein, and cerebellar tentorium. The simulation suggested that safe tentorial incision was difficult in two sides because of the crossed tentorial sinus draining the left basal vein and draining veins from the glioblastoma. The OTA was performed in eight cases, and no difficulty was experienced in the tentorial incision in all cases. The simulation findings of the bridging vein and tentorial sinus were consistent with the intraoperative findings. Preoperative simulation including the cerebellar tentorium is useful for determining the optimum and safe side and required extent of the tentorial incision necessary for tumor resection with the OTA.

Local Delivery of Nimustine Hydrochloride against Brain Tumors: Basic Characterization Study.

Convection-enhanced delivery (CED) delivers agents directly into tumors and the surrounding parenchyma. Although a promising concept, clinical applications are often hampered by insufficient treatment efficacy. Toward developing an effective CED-based strategy for delivering drugs with proven clinical efficacy, we performed a basic characterization study to explore the locally delivered characteristics of the water soluble nitrosourea nimustine hydrochloride (ACNU). First, ACNU distribution after CED in rodent brain was studied using mass spectrometry imaging. Clearance of 14C-labeled ACNU after CED in striatum was also studied. ACNU was robustly distributed in rodent brain similar to the distribution of the hydrophilic dye Evans blue after CED, and locally delivered ACNU was observed for over 24 h at the delivery site. Subsequently, to investigate the potential of ACNU to induce an immunostimulative microenvironment, Fas and transforming growth factor-ß1 (TGF-ß1) was assessed in vitro. We found that ACNU significantly inhibited TGF-ß1 secretion and reduced Fas expression. Further, after CED of ACNU in 9L-derived intracranial tumors, the infiltration of CD4/CD8 lymphocytes in tumors was evaluated by immunofluorescence.CED of ACNU in xenografted intracranial tumors induced tumor infiltration of CD4/CD8 lymphocytes. ACNU has a robust distribution in rodent brain by CED, and delayed clearance of the drug was observed at the local infusion site. Further, local delivery of ACNU affects the tumor microenvironment and induces immune cell migration in tumor. These characteristics make ACNU a promising agent for CED.

Efficacy of selective transarterial chemoembolization for recurred liver metastases from intracranial meningioma: A case report.

Extracranial metastases from intracranial meningioma involve multiple organs with repeatedly recurrence. Due to the rarity of these metastases, management remains to be established, especially in cases that are not amenable to surgery, such as postsurgical relapse and multiple metastases. We present the case of a right tentorial meningioma with multiple extracranial metastases, including postsurgical recurrent liver metastases. The intracranial meningioma was surgically resected when the patient was 53 years of age. The patient was 66 years of age when the hepatic lesion was first revealed, for which an extended right posterior sectionectomy was performed. Histopathology demonstrated a metastatic meningioma. Twelve months after liver resection, multiple local recurrences in the right hepatic lobe were revealed. Because additional surgical resection would put the patient at risk of declining residual liver function, we performed selective transarterial chemoembolization, resulting in a reduction in size and good control without relapse. Selective transarterial chemoembolization for incurable liver metastatic meningiomas could be valuable in palliating patients unsuitable for surgery.

Formation of internal carotid artery aneurysms following gamma knife radiosurgery for pituitary adenomas: a case series and literature review.

Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far. Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic. The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought.