Transcondylar fossa approach for the large, high-flow, and diffuse arteriovenous malformation of the posterior fossa.

Posterior fossa high-grade arteriovenous malformations (AVMs) are challenging diseases. This video presents the treatment of a patient with a diffuse, high-flow AVM of the posterior fossa on the tonsil and cerebellopontine angle (4 cm in diameter) and deep draining veins. The patient had an intraventricular and cerebellar hemorrhage. After conservative treatment, total resection of the AVM was performed with embolization and surgery. The authors resected the nidus after the endovascular embolization, on the same day. The postoperative course was uneventful, and the patient was discharged with almost full recovery. The video can be found here: https://youtu.be/logCCn3uKUc.

High-Flow Bypass with Internal Carotid Artery to Middle Cerebral Artery Bypass Using Radial Artery Graft Through the Supramandibular-Subzygomatic Route for Giant Internal Carotid Aneurysm: Technical Case Report.

BACKGROUND: A unique case of an internal carotid artery (ICA) giant aneurysm treated by high-flow bypass is presented. This patient had some anatomic variations in the neck region that posed problems for the high-flow bypass, and a new approach to address them is presented. CASE DESCRIPTION: A 55-year woman presented with diplopia, abducens nerve palsy, severe headache, and disordered consciousness. She had a giant ICA aneurysm (diameter, 32 mm). Although high-flow bypass was considered, this patient had 3 anatomic issues that posed problems: an elongated styloid process, a high carotid bifurcation, and a meandering external carotid artery. Thus, some changes had to be introduced to proceed with the high-flow bypass. A tunnel radial artery (RA) graft was made between the supramandibular and subzygomatic areas, and an ICA-RA-M2 anastomosis was performed. The patient's preoperative symptoms improved gradually after surgery. Magnetic resonance imaging and computed tomography showed good patency of the RA graft and no ischemic change. She was discharged without neurological deficits. CONCLUSIONS: This case provided 2 new methods for high-flow bypass: RA graft route and the anastomosis of the ICA in carotid bifurcation. To our knowledge, this is the first case report of a high-flow bypass with a tunnel created for the RA graft (supramandibular-subzygomatic route) and an ICA-RA-M2 anastomosis.

Neuroendoscopic surgery for ventriculitis and hydrocephalus after shunt infection and malfunction: Preliminary report of a new strategy.

If not controlled in the early stage, ventriculitis is difficult to treat neurosurgically and can lead to serious sequelae, a long course of treatment, and hospitalization. We report two cases of ventriculitis and progressive hydrocephalus after shunt infection. Both were successfully treated by neuroendoscopic septostomy in combination with thorough intraventricular irrigation through a single burr hole followed by single shunt revision. Although surgical intervention has not been established as a first-choice treatment for ventriculitis, including early-stage ventriculitis, prompt neuroendoscopic surgery appears effective for the management of ventriculitis and hydrocephalus after shunt infection. The strategy described in this report might be useful to avoid recurrent shunt infections and malfunctions, simplify a shunt, and reduce the overall duration of hospitalization.

Chronic subdural hematoma in patients over 90 years old in a super-aged society.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common diseases in neurosurgical practice, particularly among aged patients. With the continuing increase in the aged population, further increases in incidence are expected. However, few studies have focused on CSDH in super-aged patients over 90 years old. METHODS: We retrospectively reviewed medical records for 20 consecutive patients over 90 years old with CSDH treated in our department between 2007 and 2013. The diagnosis of CSDH was confirmed by computed tomography (CT). Patients were divided into a surgery group and a conservative group. Surgical procedures included burr-hole surgery followed by insertion of a subdural drain under local anesthesia. Clinical data were compared and analyzed. Neurological status was evaluated according to the modified Rankin Scale at three time points: before suffering from CSDH; at the time of referral or admission to our department; and at discharge or 1 month after the first referral. Statistical tests were used to analyze data and values of P < 0.05 were considered significant. RESULTS: Mean age for the 20 cases was 92.6 years (range, 90 - 96 years). The leading symptoms in this population were hemiparesis and gait disturbance, followed by disturbance of consciousness and speech disturbance. Twelve patients underwent burr-hole surgery. Mean maximum thickness of subdural hematoma as measured on CT was significantly higher in the surgery group (28.2 ± 5.4 mm) than in the conservative group (17.0 ± 3.8 mm; P < 0.01). Postoperatively, mean neurological status was significantly improved in the surgery group (P < 0.01). After surgery, 66.7% of patients could return home directly from hospital. No significant perioperative complications directly related to surgery were encountered in the surgery group, except for transient postoperative restlessness and bruising of extremities due to falls. CONCLUSIONS: Surgery for CSDH is safe and positively recommended even in super-aged patients over 90 years old if the patient's physical status is fair. Pre-illness status is the most important factor for considering operative indications and represents a limiting factor for postoperative outcomes in this age population.

Proteasome inhibitor MG132 induces NAG-1/GDF15 expression through the p38 MAPK pathway in glioblastoma cells.

The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is regulated by the p53 and Egr-1 tumor suppressor pathways. Many anti-cancer drugs and chemicals induce NAG-1 expression, but the mechanisms are not fully understood. Transgenic mice expressing human NAG-1 are resistant to intestinal and prostate cancer, suggesting that NAG-1 is a tumor suppressor. Proteasome inhibitors exhibit anti-glioblastoma activities in preclinical studies. Here, we show that the proteasome inhibitors MG132 and bortezomib induced NAG-1 expression and secretion in glioblastoma cells. MG132 increased NAG-1 expression through transcriptional and post-transcriptional mechanisms. At the transcriptional level, the induction of NAG-1 required the -133 to +41 bp region of the promoter. At post-transcriptional levels, MG132 stabilized NAG-1 mRNA by increasing the half-life from 1.5 h to >8 h. Because of the dramatic increase in mRNA stability, this is likely the major contributor to MG132-mediated NAG-1 induction. Further probing into the mechanism revealed that MG132 increased phosphorylation of the p38 MAPK pathway. Consequently, inhibiting p38 phosphorylation blocked activation of the NAG-1 promoter and decreased mRNA stability, indicating that p38 MAPK activation mediates both MG132-dependent promoter activation and mRNA stabilization of NAG-1. We propose that the induction of NAG-1 by p38 MAPK is a potential contributor to the anti-glioblastoma activity of proteasome inhibitors.

DNA methylation-mediated silencing of nonsteroidal anti-inflammatory drug-activated gene (NAG-1/GDF15) in glioma cell lines.

Nonsteroidal anti-inflammatory drug-activated gene, NAG-1, a transforming growth factor-ß member, is involved in tumor progression and development. The association between NAG-1 expression and development and progression of glioma has not been well defined. Glioblastoma cell lines have lower basal expression of NAG-1 than other gliomas and normal astrocytes. Most primary human gliomas have very low levels of NAG-1 expression. NAG-1 basal expression appeared to inversely correlate with tumor grade in glioma. Aberrant promoter hypermethylation is a common mechanism for silencing of tumor suppressor genes in cancer cells. In glioblastoma cell lines, NAG-1 expression was increased by the demethylating agent, 5-aza-2'-deoxycytidine. To investigate whether the NAG-1 gene was silenced by hypermethylation in glioblastoma, we examined DNA methylation status using genomic bisulfite sequencing. The NAG-1 promoter was densely methylated in several glioblastoma cell lines as well as in primary oligodendroglioma tumor samples, which have low basal expression of NAG-1. DNA methylation at two specific sites (-53 and +55 CpG sites) in the NAG-1 promoter was strongly associated with low NAG-1 expression. The methylation of the NAG-1 promoter at the -53 site blocks Egr-1 binding and thereby suppresses Nag-1 induction. Treatment of cells with low basal NAG-1 expression with NAG-1 inducer also did not increase NAG-1. Incubation with a demethylation chemical increased Nag-1 basal expression and subsequent incubation with a NAG-1 inducer increased NAG-1 expression. We concluded from these data that methylation of specific promoter sequences causes transcriptional silencing of the NAG-1 locus in glioma and may ultimately contribute to tumor progression.

Reversible cortical auditory dysfunction caused by cerebral vasospasm after ruptured aneurysmal subarachnoid hemorrhage and evaluated by perfusion magnetic resonance imaging. Case report.

A 52-year-old woman developed subarachnoid hemorrhage (SAH) caused by a ruptured right internal carotid artery (ICA) aneurysm. Because of the aneurysm configuration, the authors decided to delay surgery and instead undertook serial imaging studies of the aneurysm. The patient remained alert but developed acute bilateral deafness on Day 7. Audiological examination and auditory brainstem responses suggested that the hearing disturbance was cortical in origin. Three-dimensional computed tomography (CT) angiography showed severe vasospasm in the right middle cerebral artery (MCA) and moderate vasospasm in the left ICA and MCA. Three-tesla magnetic resonance (MR) imaging was performed 2 days after the onset of symptoms. Diffusion-weighted and T2-weighted MR images showed an acute infarction in the right insular cortex caused by vasospasm. Perfusion-weighted MR imaging, particularly mean transit time mapping, revealed hypoperfusion in both temporal lobes including the auditory cortex and right auditory radiation. The vasospasm was treated with induction of mild hypertension and hypervolemia. Follow-up MR images, 3D CT angiograms, and audiometry performed 2 weeks after the first examination showed recovery of vasospasm and resolution of perfusion abnormality and hearing disturbance. On Day 26, the aneurysm was successfully occluded with clips and the patient was discharged with no deficits. To the authors' knowledge, this is the first reported case of reversible cortical auditory dysfunction purely due to bilateral cerebral vasospasm detected using perfusion MR imaging after SAH.