Case of metastatic glioblastoma with primitive neuronal component to the lung.

Glioblastoma (GBM) with primitive neuronal component (GBM-PNC) is a rare GBM subtype recently categorized by the World Health Organization in the revised classification system of 2016. Extracranial metastases originating from GBM-PNC are rare and metastasis to solid organs has never been reported. Herein, we present the first case of metastasis of GBM-PNC to the lung. A 49-year-old man presenting with headache was diagnosed with multiple tumors adhering to the dura matter in the right temporal lobe. Despite surgery and chemoradiotherapy, 2 months after the initial therapy, the patient presented with CSF dissemination and lung metastases. The patient succumbed to the disease 12 months after the first surgery. We discuss the possibility that GBM-PNC may constitute a subtype of glioma with particularly poor prognosis, tending to dissemination and metastasis. Our results suggest that a complementary regular inspection of the whole body via CT may be recommended for the follow-up of patients with GBM- PNC.

Efficacy of cyst-cisternal shunt for refractory cyst regrowth of cystic vestibular schwannomas.

Vestibular schwannomas (VSs) are generally benign and slow-growing tumors, and microsurgical resection is the commonly recommended treatment. Some reports suggested that inserting a cystoperitoneal shunt was effective for treatment of cystic VSs; however, there was no report of a cyst-cisternal shunt which diverts cyst fluid into cistern. We report a case of cystic VS with repeated cyst regrowth within weeks after repeated surgeries. We prevented further recurrence using cyst-cisternal shunt. This technique may be a new treatment option for refractory cyst regrowth of cystic VSs.

[Stereotactic Biopsy in the Lateral Position Using a Neuronavigation System].

BACKGROUND: Stereotactic brain biopsy using a navigation system is minimally invasive because it can be performed under local anesthesia. However, there are problems due to the localization and accessibility of the tumor and instability of the airway under sedation. This study aimed to examine the differences in safety and surgical time between the supine and lateral position. METHODS: This study included 25 cases which underwent navigation-guided brain biopsies from May 2015 to March 2018 in the Kanazawa University Hospital. We compared tumor localization, operation time, standby time, intraoperative difficulties, and final diagnosis acquisition rates between the supine and lateral positions. Puncture sites were then examined by visualizing all biopsy trajectories simultaneously on a three-dimensional cerebral template. RESULTS: Biopsies of the tumor in all cerebrum lobes were possible in the lateral position. There were no significant differences in operating time or standby time between the supine and lateral positions. One case in the spine position required sedation by an anesthesiologist due to body movement, but there were no difficulties in any cases of lateral positioning. The final diagnosis acquisition rate was 100% in all cases. In the lateral position, stable breathing was maintained because the head and the trunk axes remined in the same line. CONCLUSION: Stereotactic brain biopsy in the lateral position can be safer and more useful than in the supine position under local anesthesia.

Glycogen synthase kinase-3ß is a pivotal mediator of cancer invasion and resistance to therapy.

Tumor cell invasion and resistance to therapy are the most intractable biological characteristics of cancer and, therefore, the most challenging for current cancer research and treatment paradigms. Refractory cancers, including pancreatic cancer and glioblastoma, show an inextricable association between the highly invasive behavior of tumor cells and their resistance to chemotherapy, radiotherapy and targeted therapies. These aggressive properties of cancer share distinct cellular pathways that are connected to each other by several molecular hubs. There is increasing evidence to show that glycogen synthase kinase (GSK)-3ß is aberrantly activated in various cancer types and this has emerged as a potential therapeutic target. In many but not all cancer types, aberrant GSK3ß sustains the survival, immortalization, proliferation and invasion of tumor cells, while also rendering them insensitive or resistant to chemotherapeutic agents and radiation. Here we review studies that describe associations between therapeutic stimuli/resistance and the induction of pro-invasive phenotypes in various cancer types. Such cancers are largely responsive to treatment that targets GSK3ß. This review focuses on the role of GSK3ß as a molecular hub that connects pathways responsible for tumor invasion and resistance to therapy, thus highlighting its potential as a major cancer therapeutic target. We also discuss the putative involvement of GSK3ß in determining tumor cell stemness that underpins both tumor invasion and therapy resistance, leading to intractable and refractory cancer with dismal patient outcomes.

Reversible acute bilateral blindness resulting from a frontal brain tumor: a case report.

We experienced an unusual case of a 15-year-old girl who suffered acute bilateral blindness caused by a frontal lobe tumour. She underwent emergent operation, after which her vision recovered. This case emphasizes that a brain mass can cause sudden onset blindness and an emergency intervention might save the patient's sight.

The Characteristics of Withdrawal or Withholding of Life-Sustaining Treatment in Severe Traumatic Brain Injury: A Single Japanese Institutional Study.

Objectives: There is little evidence on the factors influencing the decision to withdraw or continue life-sustaining treatment in the setting of severe traumatic brain injury in Japanese institutions. We investigated the factors associated with the withdrawal or withholding of life-sustaining treatment (WLST) for severe traumatic brain injury at a single Japanese institution. Methods: A total of 161 patients with severe traumatic brain injury were retrospectively reviewed. Patient characteristics and injury types were compared between patients with and without the WLST. Results: Of the 161 patients, 87 (54%) died and 52 (32%) decided to undergo WLST. In 98% of the WLST cases, the decision was made within 24 h of admission. The mean duration between WLST and death was 2 days. The predicted probabilities for mortality and unfavorable outcomes were highest in patients with WLST within 24 h. Patients with WLST were older and had a higher frequency of falls on the ground, ischemic heart disease, and acute subdural hemorrhage than those without WLST. Conclusions: The decisions of almost all WLST cases were made within 24 h of admission for severe traumatic brain injury in a Japanese institution because of Japanese patients' religious and cultural backgrounds.

Intra-and peritumoral hemorrhage in the meningioma of a nonagenarian due to administration of direct oral anticoagulants after mechanical thrombectomy.

Background: Spontaneous intratumoral hemorrhage of meningiomas is rare, and their incidence due to anticoagulants is unclear. The incidence of both meningioma and cardioembolic stroke increases with age. We report the very elderly case of intra- and peritumoral hemorrhage in frontal meningioma induced by direct oral anticoagulant (DOAC) following mechanical thrombectomy, in whom, surgical resection was required 10 years after the tumor was first indicated. Case Description: A 94-year-old woman with independence in daily living who suffered sudden consciousness disturbance, total aphasia, and right hemiparesis was admitted to our hospital. Magnetic resonance imaging showed an acute cerebral infarction and left middle cerebral artery occlusion. There was also a left frontal meningioma with peritumoral edema, which was discovered 10 years prior, and the size and edema had remarkably increased. The patient underwent urgent mechanical thrombectomy, and recanalization was achieved. Administration of DOAC was initiated for the atrial fibrillation. Computed tomography (CT) revealed an asymptomatic intratumoral hemorrhage at postoperative day 26. The patient's symptoms gradually improved; however, she suffered sudden disturbance of consciousness and right hemiparesis on postoperative day 48. CT revealed intra- and peritumoral hemorrhages with compression of the surrounding brain. Therefore, we decided to perform tumor resection instead of conservative treatment. The patient underwent surgical resection, and the postoperative course was uneventful. It was diagnosed with transitional meningioma with no malignant features. The patient was transferred to another hospital for rehabilitation. Conclusion: Peritumoral edema representing a pial blood supply might be a significant factor associated with intracranial hemorrhage due to DOAC administration in patients with meningioma. The evaluation of hemorrhagic risk due to DOACs is important not only for meningioma but also for other brain tumor cases.

Patterns of failure in glioblastoma multiforme following Standard (60 Gy) or Short course (40 Gy) radiation and concurrent temozolomide.

PURPOSE: The purpose of this study was to analyze the patterns of failure in patients with glioblastoma multiforme (GBM) treated using chemoradiotherapy in the Standard radiotherapy (60 Gy/30 fractions; Standard) or Short course (40 Gy/15 fractions: Short). MATERIALS AND METHODS: Ninety-three consecutive patients with newly diagnosed glioblastoma treated at our hospital between April 2007 and December 2016, and 68 patients who could be followed up were included. All patients underwent surgical resection followed by radiotherapy with concurrent temozolomide. We retrospectively analyzed treatment outcomes and recurrence patterns. RESULTS: The median follow-up period of the surviving patients was 82.8 months (range: 46.0-158.9 months). Of the 68 patients, 58 patients (85%) had recurrences, 34 underwent the Standard and 24 Short course. The Standard course was seen in younger age groups and had a better Karnofsky performance status (KPS) than the Short course. The median survival time (MST) was 25.8 months for the Standard and 15.4 months with the Short in all cases. Standard course had significantly longer MST than the Short (p = 0.001) course. For recurrent cases only, there was no significant difference between Standard and Short courses in OS (p = 0.06). The recurrences occurred at the radiation fields alone (Standard/Short: 85%/83%), only at distant sites (Standard/Short: 12%/13%), and at both the radiation fields and distant sites (Standard/Short: 3%/4%). There was no significant difference in recurrence pattern and frequency between the two protocols (p = 0.11). CONCLUSIONS: Standard course tended to be significant in younger age groups and have a better KPS than the Short course; therefore, the Standard course has a longer OS, but the recurrence pattern of the Short course is similar to that of the Standard treatment.

A spinal epidural hematoma with symptoms mimicking cerebral stroke.

A spontaneous cervical epidural hematoma (SCEH) is a rare condition, which usually requires urgent treatment. However, unusual manifestations, such as hemiparesis, may lead to a misdiagnosis. We herein report a case of SCEH that presented with pure motor hemiparesis to discuss the appropriate and prompt diagnosis and treatment of such cases. An 84-year-old female was brought to our emergency department complaining of nuchal pain, followed by right hemiparesis. A contrast-enhanced computed tomography (CT) scan of the neck demonstrated a spinal epidural hematoma right posterolateral to the spinal cord, extending from C2 to C3. She was managed conservatively and her symptoms improved significantly. The authors emphasize that cervical spinal lesions should be considered in the differential diagnosis for patients with acute onset of hemiparesis, when they are associated with neck pain. Even though magnetic resonance imaging is the gold standard, a CT scan is also useful for quick screening for SCEH.

Blister-like aneurysm of the anterior communicating artery treated with only Low-profile Visualized Intraluminal Support Junior stent.

BACKGROUND: Endovascular treatment is becoming a mainstream treatment for blister-like aneurysms in recent years. Blister-like aneurysms are usually located in the internal carotid artery, whereas that of the anterior communicating artery (AcomA) are very rare. We report the first case of blister-like aneurysm of AcomA that was treated solely with a neck bridging stent that resulted in complete occlusion without complication. CASE DESCRIPTION: A 50- year- old woman was admitted to our hospital due to a subarachnoid hemorrhage. Digital subtraction angiography showed a very small aneurysm in the dorsal side of the AcomA. We considered it a blister-like aneurysm based on its size and shape. She underwent endovascular treatment under general anesthesia on day 15 after vasospasm period. Dual antiplatelet therapy was administrated 1 week prior. A Low-profile Visualized Intraluminal Support Junior stent was implanted from the left A2 to the right A1, covering the AcomA. The postoperative course was uneventful, and she was discharged with no neurological deficit. The aneurysm remained unchanged on postoperative day 14; however, complete occlusion was achieved 3 months after the treatment. CONCLUSION: Monotherapy with a neck bridging stent is an effective treatment option for blister-like aneurysms. Treatment with a single stent could achieve complete occlusion especially if the aneurysms occur elsewhere than the internal carotid artery. We should consider immediate additional treatment if the aneurysm grows within 1 month after initial treatment.

Ring enhanced aneurysm due to vasa vasorum of aneurysm wall mimicking a metastatic brain tumor.

BACKGROUND: A spherical intracranial mass can be occasionally misdiagnosed due to the lack of typical radiographic features. Completely thrombosed intracranial aneurysms (CTIA) are uncommon, but a possible differential diagnosis must be considered to guarantee the best surgical approach for these lesions. CASE DESCRIPTION: Here, we report an extremely rare case of a right frontal mass mimicking a brain tumor, in which the surgery unveiled a CTIA of the right middle cerebral artery (MCA). A 56-year-old woman presented with right hemiparesis and mild headache. Magnetic resonance imaging (MRI) revealed a right frontal mass with peripheral edema. The lesion enhanced on initial and follow-up MRI of the brain. Subsequent vascular studies and metastatic workup were negative. A temporal craniotomy with neuronavigation (Brain Lab AG, Germany) was performed and an intraoperative diagnosis of a thrombosed aneurysm along the branch of the MCA was established. The aneurysm was successfully trapped and resected. The patient did not exhibit any postoperative neurological deficits. CONCLUSION: This is the rare report of a ring enhanced completely thrombosed aneurysm due to vasa vasorum which is misdiagnosed as metastatic brain tumor. In case of an intracranial ring enhanced mass with signs of intralesional hemorrhage and peripheral edema, CTIA should be considered as a possible differential diagnosis.

Limb-shaking syndrome derived from the contralateral hemisphere following unilateral revascularisation for moyamoya disease.

BACKGROUND: Moyamoya disease is a rare chronic steno-occlusive cerebrovascular disease. It may have variable clinical symptoms associated with cerebral stroke, including motor paralysis, sensory disturbances, seizures, or headaches. However, patients with moyamoya disease rarely present with involuntary movement disorders, including limb-shaking syndrome, with no previous reports of limb-shaking syndrome occurring after revascularization procedures for this disease. Although watershed shifts can elicit transient neurological deterioration after revascularisation, symptoms originating from the contralateral hemisphere following the revascularization procedure are rare. Here, we report the case of moyamoya disease wherein the patient developed limb-shaking syndrome derived from the contralateral hemisphere after unilateral revascularisation. CASE DESCRIPTION: A 16-year-old girl presented with transient left upper and lower limb numbness and headache. Based on digital subtraction angiography, she was diagnosed with symptomatic moyamoya disease. Single-photon emission computed tomography (SPECT) showed decreased cerebral blood flow (CBF) on the right side, and she underwent direct and indirect bypasses on this side. Involuntary movements appeared in her right upper limb immediately postoperatively. SPECT showed decreased CBF to the bilateral frontal lobes. Subsequently, the patient was diagnosed with limb-shaking syndrome. After performing left-hemispheric revascularisation, the patient's symptoms resolved, and SPECT imaging confirmed improvements in CBF to the bilateral frontal lobes. CONCLUSION: Revascularization for moyamoya disease can lead to watershed shifts, which can induce limb-shaking syndrome derived from abnormalities in the contralateral hemisphere of the revascularized side. For patients with new-onset limb-shaking syndrome after moyamoya revascularisation procedures, additional revascularization may be warranted for treatment of low perfusion areas.

Potential therapeutic effect of glycogen synthase kinase 3beta inhibition against human glioblastoma.

PURPOSE: Glioblastoma represents the malignant brain tumor that is most refractory to treatment and in which the identification of molecular target(s) is urgently required. We investigated the expression, activity, and putative pathologic role of glycogen synthase kinase 3beta (GSK3beta), an emerging therapeutic target for neurodegenerative diseases, in human glioblastoma. EXPERIMENTAL DESIGN: The active fraction of GSK3beta that is phosphorylated at the tyrosine 216 residue (pGSK3betaY216) was identified in glioblastoma cell lines. GSK3beta activity for phosphorylating its substrate was detected in these cells by nonradioisotopic in vitro kinase assay. RESULTS: Higher expression levels of GSK3beta and pGSK3betaY216 were frequently detected in glioblastomas compared with nonneoplastic brain tissues. Inhibition of GSK3beta activity by escalating doses of a small-molecule inhibitor (AR-A014418) or inhibition of its expression by RNA interference induced the apoptosis and attenuated the survival and proliferation of glioblastoma cells in vitro. Inhibition of GSK3beta was associated with increased expression of p53 and p21 in glioblastoma cells with wild-type p53 and with decreased Rb phosphorylation and expression of cyclin-dependent kinase 6 in all glioblastoma cell lines. Administration of AR-A014418 at a low dose significantly sensitized glioblastoma cells to temozolomide and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea, chemotherapeutic agents used in the clinical setting, as well as to ionizing radiation. CONCLUSION: These results indicate that GSK3beta exerts a pathologic role by promoting the survival and proliferation of glioblastoma cells and by protecting them from apoptosis via the inactivation of p53- and/or Rb-mediated pathways. Consequently, we propose that GSK3beta provides a potential therapeutic target in glioblastoma.

Endodermal Cyst with a Non-enhancing Nodule in the Quadrigeminal Cistern Developed in an Octogenarian.

BACKGROUND: Intracranial endodermal cysts are congenital lesions that generally develop in the cerebellopontine angle and ventral brainstem of the posterior fossa, whereas endodermal cysts in the quadrigeminal cistern are very rare. We report a rare case of an endodermal cyst in the quadrigeminal cistern with a non-enhancing nodule that developed in patient over 80 years of age. CASE DESCRIPTION: An 85-year-old man presented to our hospital with progressing gait disturbance and urinary incontinence. Preoperative images showed a cystic mass lesion with a nodule in the quadrigeminal cistern and hydrocephalus. There was no enhanced portion in the lesion, and the intensity of the cyst on magnetic resonance imaging revealed a high protein concentration. Subtotal resection was performed due to the adhesion of the cyst to the brainstem. It was diagnosed as an endodermal cyst. The postoperative course was uneventful, and hydrocephalus improved. CONCLUSIONS: This is a rare case of an intracranial endodermal cyst in terms of location and age of onset compared with previous reports. This case demonstrates that endodermal cysts should be considered as a differential diagnosis for lesions in the quadrigeminal cistern with high protein concentration in the cyst and nodule representing chronic inflammation, regardless of enhancing effects.

Recurrent Spinal Intramedullary Arachnoid Cyst: Case Report and Literature Review.

BACKGROUND: Symptomatic intramedullary arachnoid cysts are rarely observed lesions, particularly in the pediatric age group. Treatment includes cyst fenestration or resection of the cyst wall, and recurrence after surgery has never been reported. We report a rare case of a spinal intramedullary arachnoid cyst, which recurred after cyst fenestration and required reoperation after a certain period. CASE DESCRIPTION: A 4-year-old boy presented to our hospital with tetraparesis and bladder and rectum disorder. A cystic intramedullary lesion in the cervical spinal cord was detected in preoperative imaging. An emergency fenestration of cyst was performed, and his symptoms were resolved immediately. One month after the operation, the symptoms and cyst recurred. The symptoms improved in the natural course without reoperation. However, the cyst increased in size and the symptoms recurred after 27 months from the first relapse and the cyst was removed urgently. The diagnosis was an arachnoid cyst. After the reoperation, the cyst has disappeared and not recurred. CONCLUSIONS: To the best of our knowledge, this is the first report of recurrence of an intramedullary arachnoid cyst. This case indicates the importance of considering the resection of cyst wall as possible because of the probability of cyst recurrence after fenestration, while careful observation is the option in the short term, especially for children or high-risk cases.

Effect of Unilateral Carotid Artery Stenting on Cognitive Function in Patients with Severe Bilateral Stenosis.

CASE DESCRIPTION: An 82-year-old man with dementia, gait disturbance, and a small cerebral infarction owing to severe bilateral carotid artery stenosis was successfully treated with carotid artery stenting (CAS). Preoperative cerebral vascular reactivity was reduced in the bilateral cerebral hemispheres. We performed CAS to treat right internal carotid artery stenosis. Following CAS, cerebral vascular reactivity showed an increase in the bilateral cerebral hemispheres. Memory, fluency, and attention also showed improvement. CONCLUSIONS: This case illustrates the potential benefit of single-stage CAS for cognitive function in severe bilateral carotid artery stenosis without hyperperfusion syndrome.

Ossified peripheral middle cerebral artery aneurysm in a 30-year-old man.

A 30-year-old man presented with a history of several convulsive episodes. A CT scan showed a calcified focus in the right temporal lobe. Cerebral angiography yielded no abnormal findings. At craniotomy, the M3 portion of the middle cerebral artery was found to terminate with a blind end at the junction with the calcified mass. A pathological diagnosis of an ossified cerebral aneurysm was made. Calcified cerebral aneurysms are not rare; they are thought to be the result of intra-aneurysmal thrombosis or degenerative changes in the aneurysmal wall. However, complete mural ossification of a cerebral aneurysm is seldom seen, and ossified peripheral middle cerebral artery aneurysms are extremely rare in young individuals. The ossified aneurysm that we report developed over a prolonged period and may have arisen during childhood.

Bright spot analysis for photodynamic diagnosis of brain tumors using confocal microscopy.

BACKGROUND: In a previous study of photodynamic tumor diagnosis using 5-aminolevulinic acid (5-ALA), the authors proposed using fluorescence intensity and bright spot analyses under confocal microscopy for the precise discrimination of tumorous brain tissue (such as glioblastoma, GBM) from normal tissue. However, it remains unclear if bright spot analysis can discriminate infiltrating tumor in the boundary zone and whether this method is suitable for GBM with no 5-ALA fluorescence or for other tumor types. METHODS: Brain tumor tissue resected from 5-ALA-treated patients was sectioned to evaluate bright spots under confocal microscopy with a 544.5 - 619.5 nm band-pass filter, which eliminated the fluorescence induced by 5-ALA. Border regions and adjacent normal tissues were observed for differences in bright spot distribution. Histopathology was also conducted by hematoxylin and eosin (H&E) staining of serial slices from the same samples to confirm the locations of tumorous, infiltrating, and normal regions. Bright spot areas were then calculated for the same regions evaluated by histopathology. This method was applied for GBM with and without 5-ALA-induced fluorescence as well as for lower-grade gliomas and other brain tumor types. RESULTS: The bright spot area was substantially smaller in the GBM body than in normal brain tissues. Bright spot area was also smaller in infiltrating tumors than in normal tissue at the margin. The same bright spot pattern was observed in tumorous tissues with no 5-ALA-induced fluorescence and in non-GBM tumors. The bright spot fluorescence is suggested to arise from lipofuscin based on emission spectra (mainly within 544.5 - 619.5 nm) and optimum excitation wavelength (about 405 nm). CONCLUSIONS: Bright spot analysis is useful for discriminating infiltrating tumor from bordering normal tissue as an alternative or complement to photodynamic diagnosis with 5-ALA. This method is also potentially useful for tumors with no 5-ALA-derived red fluorescence and other nervous system tumors.

Intratumoral continuous facial nerve stimulation for surgical resection of cystic vestibular schwannoma: Technical note.

BACKGROUND: Cystic vestibular schwannomas (CVSs) account for about 10% of VS. The efficacy of continuous facial nerve stimulation (CFS) was previously reported; however, it is often difficult to place the electrode at the root exit zone (REZ) in the early stage of surgical resection. We proposed a new method of intratumoral CFS (ICFS) by searching for the facial nerve through the cyst wall and leaving the spherically shaped electrode at this point. METHODS: The cyst wall was opened, and the ventral side of the tumor wall was stimulated to search for the positive point of facial nerve stimulation and place the spherically shaped electrode for continuous stimulation at this point through the cyst cavity (intensity: 0.2-1.5 mA, frequency: 1 Hz). Safe surgical resection could be performed under ICFS in all three cases. RESULTS: Good preservation of the facial nerve and extent of resection that was estimated preoperatively was achieved in all cases. CONCLUSION: ICFS is suitable for the preservation of facial nerve function in surgical resection of CVS in cases in which electrode placement at the REZ is difficult.

Ligand-dependent EphB4 activation serves as an anchoring signal in glioma cells.

Of the erythropoietin-producing human hepatocellular receptors (Ephs), EphB4 has recently emerged as a potential target in several cancers due to its roles in modified cell migration and invasion. As little is known about the roles of EphB4 in glioma, we sought to investigate its function in glioma by in vitro cell migration and invasion assays, immunoblotting and immunostaining. EphB4 was expressed in glioma cell lines and stem-like cell lines. The stimulation of glioma cells with ephrin-B2, the sole ligand of EphB4, conducted EphB4 phosphorylation and suppressed migration and invasion that downregulation of EphB4 using small interfering RNA abrogated. The stimulation also suppressed the phosphorylation of Akt. We confirmed by immunostaining that EphB4-positive cells existing only in the tumor core, whereas ephrin-B2-positive cells widespread in both the tumor core and the invasive area signifying that EphB4-ephrin-B2 reaction occurred only at the tumor core. Taken together, our data suggest that ephrin-B2-dependent EphB4 phosphorylation acts as an anchoring signal to reduce the malignancy by inhibiting Akt phosphorylation in the glioma core, whereas the scarcity of signaling in the tumor periphery promotes invasion into the surrounding brain.