Adult classical glioblastoma with a BRAF V600E mutation.

The B-Raf proto-oncogene serine/threonine kinase (B-Raf) is a member of the Raf kinase family. The BRAF V600E mutation occurs frequently in certain brain tumors such as pleomorphic xanthoastrocytoma, ganglioglioma, and pilocytic astrocytoma, and less frequently in epithelioid and giant cell glioblastoma. BRAF V600E mutation in these cases has been canonically detected using Sanger sequencing or immunohistochemistry but not with next-generation sequencing (NGS). Moreover, to our knowledge, there is no detailed report of the BRAF V600E mutation in an adult glioblastoma with classical histologic features (c-GBM). Therefore, we performed NGS analysis to determine the mutational status of BRAF of 13 glioblastomas (GBMs) (11 primary and 2 secondary cases) and detected one tumor harboring the BRAF V600E mutation. We report here the detection of the BRAF V600E mutation in a patient with c-GBM and describe the patient's clinical course as well as the results of histopathological analysis.

Hybrid surgery of ventral intermediate nucleus thalamotomy using magnetic resonance-guided focus ultrasound and modulation by deep brain stimulation controls bilateral essential tremor.

Objective: Medication-resistant essential tremor requires surgical treatment. Deep brain stimulation to the thalamic ventral intermediate nucleus is an established procedure to diminish tremors. Tremor on both sides needs dual deep brain stimulation implantation. Nowadays, magnetic resonance-guided focus ultrasound is broaden to treat essential tremor. However, the safety of magnetic resonance-guided focus ultrasound against dual ventral intermediate is still under discussion, since bilateral thalamotomy causes speech disturbance or ataxia. Patient and Methods: A 66-year-old right-handed man had medication-resistant essential tremor at bilateral upper extremities superior to the left arm. A treatment of magnetic resonance-guided focus ultrasound was performed by using the ExAblate transcranial system against the left ventral intermediate. One year after magnetic resonance-guided focus ultrasound treatment, the stereotactic implantation of a deep brain stimulation electrode into the right ventral intermediate was done. Results: Clinical rating scale for tremor in the right arm was reduced from 12 to 0 points by magnetic resonance-guided focus ultrasound against the left ventral intermediate. The clinical rating scale for tremor in the left arm was reduced from 23 to 1 point by deep brain stimulation to the right ventral intermediate. Conclusion: Hybrid surgery of magnetic resonance-guided focus ultrasound and deep brain stimulation refined bilateral essential tremor, without any neurological deficiencies. This combined surgery would be useful to manage medication-resistant bilateral essential tremor patients who are carrying some difficulties to introduce deep brain stimulation on the bilateral side.

Outcome of Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Appropriately Selected Patients with Acute Ischemic Stroke.

Background: Endovascular treatment is the preferred treatment for acute ischemic stroke (AIS) due to main artery steno-occlusive disease, but it has temporal and technical limitations. Moreover, there is no established treatment for progressive stroke. Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass is sometimes considered as a treatment option. Objective: The objective of this paper is to review the treatment outcomes of patients with AIS undergoing urgent STA-MCA bypass. Methods and Material: This was a retrospective study including 32 patients diagnosed with AIS treated with urgent STA-MCA bypass at our facility. The patients had small infarct volumes and a large diffusion-perfusion mismatch. Results: New ischemic lesions in postoperative diffusion-weighted images were detected in 15 patients (46.9%), but only four (12.5%) developed paralysis. Hyperperfusion occurred in nine patients (28.1%), and five (15.6%) had bypass occlusion at 1 week. Delayed wound healing were found in four patients (12.5%). Neurological outcome was measured 3 months after onset: Manual Muscle Testing (MMT), 3-5 in 27 patients (84.4%); modified Rankin scale (mRS), 0-2 in 17 patients (53.1%); and 0-3 in 26 patients (81.3%). Prognosis was better in patients who underwent surgery after 24 h of stroke onset (mRS, 0-2 in 56.0% cases and 0-3 in 88.0% at 3 months). Statistical analyses revealed that MMT before surgery had a significant association with favorable outcomes (P = 0.041). Conclusions: Urgent STA-MCA bypass for progressive stroke may result in a good prognosis if the right patients are selected and may play an important role in cases treated 24 h after onset in whom endovascular treatment is ineffective.

Early initiation of rivaroxaban after reperfusion therapy for stroke patients with nonvalvular atrial fibrillation.

BACKGROUND: The optimal timing of initiating oral anticoagulants after reperfusion therapy for ischemic stroke is unknown. Factors related to early initiation of rivaroxaban and differences in clinical outcomes of stroke patients with nonvalvular atrial fibrillation (NVAF) who underwent reperfusion therapy was investigated. METHODS: From data of 1,333 NVAF patients with ischemic stroke or transient ischemic attack (TIA) in a prospective multicenter study, patients who started rivaroxaban after intravenous thrombolysis and/or mechanical thrombectomy were included. The clinical outcomes included the composite of ischemic events (recurrent ischemic stroke, TIA, or systemic embolism) and major bleeding at 3 months. RESULTS: Among the 424 patients, the median time from index stroke to starting rivaroxaban was 3.2 days. On multivariable logistic regression analysis, infarct size (odds ratio [OR], 0.99; 95%CI, 0.99-1.00) was inversely and successful reperfusion (OR, 2.13; 95%CI, 1.24-3.72) was positively associated with initiation of rivaroxaban within 72 hours. 205 patients were assigned to the early group (< 72 hours) and 219 patients (≥ 72 hours) to the late group. Multivariable Cox regression models showed comparable hazard ratios between the two groups at 3 months for ischemic events (hazard ratio [HR], 0.18; 95%CI, 0.03-1.32) and major bleeding (HR, 1.80; 95%CI, 0.24-13.54). CONCLUSIONS: Infarct size and results of reperfusion therapy were associated with the timing of starting rivaroxaban. There were no significant differences in the rates of ischemic events and major bleeding between patients after reperfusion therapy who started rivaroxaban < 72 hours and ≥ 72 hours after the index stroke. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT02129920; URL: https://www.clinicaltrials.gov.

Vasospasm as a major complication after acute mechanical thrombectomy with stent retrievers.

OBJECTIVE: Mechanical thrombectomy using a stent retriever for acute large vessel occlusion is indispensable in stroke treatment, however, vasospasm may occur. The objective of this retrospective study was to investigate which cases are more likely to experience vasospasm after thrombectomy with stent retrievers. METHODS: We included 29 patients diagnosed with acute cardiogenic cerebral embolism who were treated with stent retrievers at our facility from December 2014 to December 2017. Atherothrombotic brain infarction cases were excluded because it was difficult to evaluate for vasospasms. Vasospasm was defined as reversible arterial narrowing of <80% of the normal vessel diameter after usage of the stent retriever. The age, sex, type of stent retriever, occlusion site, number of procedures, thrombolysis in cerebral infarction (TICI) grade, degree of vasospasm, intracranial hemorrhage by the procedure, and neurological outcomes were analyzed. RESULTS: Among the 29 cases, 12 (41.4%) resulted in vasospasm; nine cases were mild (20-50% stenosis) and 3 cases were severe (≥50% stenosis). Vasospasm frequently occurred in the distal part of the anterior circulation when compared to the proximal part. In addition, the frequency of vasospasm increased as the number of procedures increased. Pooled analysis showed significant difference in the intravenous tissue-type plasminogen activator group (P = 0.029). There was no significant difference in the other groups. CONCLUSION: Stent retrievers appear to cause vasospasm more than expected when including mild cases. Vasospasm tends to occur especially in cases with IV-tPA; prognosis is generally good, and it rarely requires any treatment.

Aberrant left subclavian artery occlusion in right-sided aortic artery associated with left cerebral infarction: A case report.

Purpose Right-sided aortic arch is a rare vessel anomaly with an incidence of 0.1% worldwide. Supra-aortic branches form a mirror image of the left-sided aortic arch or an aberrant left subclavian artery associated with Kommerell diverticulum. Most patients are diagnosed by a difference in blood pressure in each upper extremity or by the presence of left subclavian steal syndrome in their younger age. The diagnosis of onset of ischemic stroke in middle age is rare. Methods We present the case of a female patient who presented with an ischemic stroke in the left posterior circulation area. She had no history of congenital heart malformation. We performed head magnetic resonance imaging, cerebral angiography, and enhanced computed tomography of the aortic arch and major branches. Results The patient had a right-sided aortic arch and an aberrant left subclavian artery. The left subclavian artery was occluded at the proximal portion with a fibrous string. Collateral flow in the anterior cervical subcutaneous area supported left limb perfusion. Conclusion An atheromatous change reduced shunt flow via collateral networks at the anterior cervical region. Congenital subclavian steal supported the ischemic stroke.

A case of neuromyelitis optica diagnosed with a chronic subdural hematoma.

Background: Chronic subdural hematoma (CSDH) is often found in the elderly owing to slight head trauma and is associated with several neurological disorders. Neurological deficits are cured by a simple surgical removal of the hematoma; however, these deficits persist if there is insufficient hematoma removal. It is rare for patients to continue having neurological disorders once the hematoma is removed. Case report: A 61-year-old woman presented with gait disturbance. She was diagnosed with a subdural hematoma through head computed tomography. After hematoma irrigation, her gait disturbance exacerbated, and she developed urinary tract dysfunction. Ubiquitous neurodegeneration in the midbrain and spinal cord was suspected owing to a hyperintense signal on fluid-attenuated inversion recovery of magnetic resonance imaging. The anti-aquaporin 4 antibody was detected in the patient's serum, and she was diagnosed with neuromyelitis optica (NMO). Conclusions: Progressive NMO caused gait dysfunction and triggered head trauma, followed by CSDH. Although NMO rarely causes CSDH, it should be considered in uncommon cases of CSDH.

Intracranial hemorrhage during administration of a novel oral anticoagulant.

Objective: Oral anticoagulants are widely administered to patients with atrial fibrillation in order to prevent the onset of cardiogenic embolisms. However, intracranial bleeding during anticoagulant therapy often leads to fatal outcomes. Accordingly, the use of novel oral anticoagulants (NOACs), which less frequently have intracranial bleeding as a complication, is expanding. A nationwide survey of intracranial bleeding and its prognosis in Japan reported that intracranial bleeding of advanced severity was not common after NOAC administration. In this report, two cases from our institute are presented. Patients: Case 1 was an 85-year-old man with a right frontal lobe hemorrhage while under dabigatran therapy. Case 2 was an 81-year-old man who had cerebellar hemorrhage while under rivaroxaban therapy. Result: In both patients, the clinical course progressed without aggravation of bleeding or neurological abnormalities once anticoagulant therapy was discontinued. Conclusion: These observations suggest that intracranial hemorrhage during NOAC therapy is easily controlled by discontinuation of the drug. NOAC administration may therefore be appropriate despite the risk of such severe complications. Further case studies that include a subgroup analysis with respect to each NOAC or patient background will be required to establish appropriate guidelines for the prevention of cardiogenic embolisms in patients with atrial fibrillation.

Cerebral amyloid angiopathy with atypical imagingfindings of subarachnoid hemorrhage.

Cerebral amyloid angiopathy (CAA) is observed in most cases of nonhypertensive subcortical hemorrhage involving elderly patients. We herein describe the case of a female in whom a convexal subarachnoid hemorrhage was observed at 55 years of age. The cerebral hemorrhage occurred repeatedly; however, no obvious vascular lesions were observed on a cerebral angiography, and no signs of microbleeding or lesions in the deep white matter were identified on magnetic resonance imaging (MRI). Partial excision of the right frontal cortex and hematoma evacuation were performed, and histopathological examination showed deposition of an acidophilic substance with positive staining for Direct Fast Scarlet (DFS) in the cerebral vascular wall. Finally, brain hemorrhage due to CAA was diagnosed. This case suggests that CAA is an important differential diagnosis in patients with localized non-aneurysmal subarachnoid hemorrhage in the convexity sulcus.

Usefulness of interventional embolization of the middle meningeal artery for recurrent chronic subdural hematoma: Five cases and a review of the literature.

PURPOSE: Although several strategies against recurrent chronic subdural hematoma (CSDH) have been proposed, no consensus has been established. Recently, middle meningeal artery (MMA) embolization has been proposed as radical treatment for recurrent CSDH. We wanted to estimate the usefulness of MMA embolization for recurrent CSDH. METHODS: From February 2012 to June 2013, 110 patients with CSDH underwent single burr-hole surgery with irrigation and drainage. Among these patients, 13 showed recurrent hematoma formation and were retreated surgically. Furthermore, repeated recurrence of CSDH was observed in six patients. Five of these six patients underwent middle meningeal artery (MMA) embolization with polyvinyl alcohol particles. All five patients with interventional treatment were observed for four to 60 weeks. RESULTS: No more recurrence of CSDH was observed in any of the patients. During the follow-up period, no patients suffered from any side effects or complications from the interventional treatment. CONCLUSION: MMA embolization with careful attention paid to the procedure might be a treatment of choice for recurrent CSDH.

Association of Epstein-Barr virus with oral cancers.

Epstein-Barr virus (EBV) persists in the epithelial cells of oral mucosa and often replicates on them. EBV is known to be a causative agent of nasopharyngeal carcinoma. We suspect that EBV may be associated with oral cancers, and thus examined EBV expression on 28 tongues and 9 other oral cancers. We also examined 6 metastatic lesions in the lymph nodes. All cancers were squamous cell carcinoma (SCC). We used mRNA in situ hybridization, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (RT-PCR), and polymerase chain reaction (PCR). The mRNA in situ hybridization using a probe comprising the transcripts of the BamHIW fragment of the EBV genome demonstrated EBV mRNA in the majority of tumor cells in all cases of oral cancer, but in none of the normal tissues. RNA in situ hybridization using an EBER1 probe detected RNAs in 16 out of 24 cancers. Also, mRNA in situ hybridization using a probe of the EBV-determined nuclear antigen-2 (EBNA2) region detected positive signals in 9 out of 12 cancers. Furthermore, EBNA2, latent membrane protein-1 (LMP1) and BZLF1 were detected in these cancers by immunofluorescence staining, but were not detected in any of the epithelial cells of the normal tissues. Four out of 6 metastatic tissues showed stronger fluorescence than that in the primary tissues. RT-PCR analysis also showed EBER1 expression in 1 of the 3 tongue cancers. PCR detected the BamHIW sequence of EBV DNA in all cases, including the normal tissues tested. These findings indicate that EBV may be involved in neoplastic transformation in oral cancers, such as nasopharyngeal carcinoma.

Usefulness of 11C-methionine positron emission tomography for detecting intracranial ameloblastic carcinoma: A case report.

Ameloblastic carcinoma, secondary type, is an extremely rare odontogenic malignant tumor. The present study reports the case of a 58-year-old male with ameloblastic carcinoma that extended into the intracranial space close to the internal carotid artery. Surgical excision was performed, as headaches were being caused via compression by the mass. Small remnants of the tumor remained surrounding the internal carotid artery following surgical resection. Although the remnant tissue was not detected on magnetic resonance imaging or 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), it was clearly visualized on 11C-methionine PET in the early post-operative follow-up period. No neurological deficits were exhibited during the follow-up period, and 11C-methionine PET was able to detect the remnant lesion distribution in the intracranial space. The current study presents a rare case of ameloblastic carcinoma that extended into the intracranial space. In addition, several diagnostic imaging tools were compared in order to determine the most suitable imaging modality. At present, the patient is continuing a therapeutic course of radiation and evident mass reduction has been observed. However, the therapeutic effects are currently under consideration. To the best of our knowledge, this is the first study on the effectiveness of using 11C-methionine PET for detecting ameloblastic carcinoma with intracranial extension.

Takotsubo-like myocardial dysfunction accompanied with cerebellar hemorrhage.

We report a 71-year-old woman with takotsubo-like myocardial dysfunction accompanied with cerebellar hemorrhage. On admission time, although she was unconscious by cerebellar hemorrhage, no obvious heart failure and serological disorder were observed. Three days later, operation for extraventricular drainage was performed. However, conscious level did not change. Four days after admission, the change of electrocardiogram wave pattern and the decrement of heart wall motion were detected. These findings revealed takotsubo-like myocardial dysfunction had occurred. Physical stresses by cerebellar hemorrhage and cranial operation might cause cardiac disorder. This is a remarkable case of takotsubo-like myocardial dysfunction, which is brought about cerebellar hemorrhage against subarachnoid hemorrhage.

Inhibition of human immunodeficiency virus type-1 (HIV-1) replication at a reverse transcription step by human cell factor(s).

Infection of human cell with human immunodeficiency virus type-1 (HIV-1) was suppressed by cellular genetic factor(s) at reverse transcription step. Although same amount of virus adsorbed on both cells, small amount of HIV-1 (IIIB strain) infected HeLa (MAGI/CCR5) cell, while large amount of HIV-1 infected HOS (GHOST/CXCR4) cell. Regulation of virus replication at postentry level by cellular factor(s) had an important role for low efficiency of HIV-1 infection to MAGI/CCR5 cell. Provirus DNA formation in MAGI/CCR5 cell was less efficient than in GHOST/CXCR4 cell. Once GHOST/CXCR4 cell was fused with MAGI/CCR5 cell, susceptibility against HIV-1 decreased. Further, HIV-1 reverse transcriptase (RT) activity was strongly inhibited by cytosolic protein, derived from MAGI/CCR5 cell, in vitro. This research cleared a certain human cell genetically carries some factor(s) which inhibits the activity of HIV-1 RT.