Takatoshi Sakurai

Localisation of sensory motor cortex during surgery by changes of cortical surface temperature after median nerve stimulation

Echoencephalography revealed residual tumour below the cortical surface. However, it was not possible precisely to identify whether the residual tumour was situated in the sensory or motor cortex. Moreover, it was also impossible to determine the border of the cortex because of difficulty in placing the multiple electrode arrays on the swollen and slightly injured cortical surface. Thermomapping was carried out by thermovision with digital image processing (TVS 100ME, Nippon Avionics, Japan) during stimulation by 0·5 ms constant-current pulses delivered to the median nerve at the wrist at an intensity capable of producing a moderate thumb twitch. The stimulus rate was 2/s. The thermovision camera included a 100 ms scanning time, with each scan consisting of the average of 16 measurements with a thermosensitivity of 0·01oC and a digitised thermoimage of 120 160 pixels. The rectal temperature of the patient was controlled at 36·5oC under general anaesthesia with isoflurane. The thermovision camera was focused on the cortical surface with a zoom lens. The figure shows typical changes in cortical temperature after contralateral median nerve stimulation. It was clearly shown that changes in cortical temperature corresponded strictly to contralateral median nerve stimulation. Namely, the temperature increased during stimulation and decreased immediately after interruption of stimulation. By thermovision monitoring, the area where changes in temperature were observed corresponding to median nerve stimulation was proved to be the site of metabolic response in the sensory cortex. As a result, the entire residual tumour under the identified sensory cortex could be removed without danger of postoperative motor paresis. The thermal response to median nerve stimulation is considered to be a neurovascular response. The molecular organisation of the radial blood vessels which are normally oriented to the cortical surface and have a regular distribution over it may result in highly efficient localisation of cortical heat transport by cerebral blood flow. The increase in cortical temperature results from initial metabolic activity and heating the sensory cortex following neuronal activities after stimulation of thalamic cortical tracts. From this mechanism, changes in cortical temperature can reflect cortical activities following noxious stimuli. We have shown that the sensory cortex can be identified by means of thermoimaging during neurosurgery.

Posttraumatic Cranial Cystic Fibrous Dysplasia

A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging (MRI) showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD). The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested that c-fos gene expression is a key mechanism in injury-induced FD.

Abstract 774: Notch pathway activation predicts resistance to bevacizumab therapy in glioblastoma

Glioblastoma, the most common adult glioma, is associated with a dismal prognosis. Treatment with bevacizumab has not significantly prolonged overall patient survival times. Glioblastoma resistance to angiogenesis inhibitors is attributed to multiple interacting mechanisms. We have thus embarked on a comprehensive effort to detecting expression signatures that are associated with response to the therapy and these signatures may allow prospective selection of patients with high likelihood of responding to therapy. Notch signaling pathway is an evolutionarily conserved pathway that plays an important role in multiple cellular and developmental processes including cell fate decision, differentiation, proliferation, survival, angiogenesis and migration. Analysis of The Cancer Genome Atlas expression dataset identified a group (43.9%) of tumors with proneural signature showing high Notch pathway activation. In this study, we compared CD133, Notch, and VEGF expressions in histological sections of primary and recurrent glioblastomas after radiotherapy and chemotherapy. Tumor samples were collected from 27 patients at the time of tumor recurrence. We used immunohistochemical techniques to compare expression of CD133, Notch-1 and VEGF. Expressions of CD133-, Notch-1-, and VEGF-positive glioma cells were higher in recurrent glioblastoma after radiotherapy and chemotherapy. To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy followed by a second surgery at recurrence. OS was significantly longer in cases with Notch-1 negativity (8.8 months) than in those with Notch-1 positivity (6.8 months). Electron microscopic observation of two autopsy cases revealed the effects of blood vessel normalization in Notch-1 positive glioblastoma. Electron microscopic images confirmed the presence of pericytes surrounding the vascular endothelium. Autopsied tumors exhibited marked proliferation of Notch-1 and VEGF positive cells around vessels. In tumor angiogenesis, vascular endothelial growth factor and Notch signaling induce sprouting angiogenesis and recruitment of vascular endothelial cells such as tip cells, stalk cells, and phalanx cells. Fully mature phalanx cells are in close contact with pericytes. These findings indicate that bevacizumab treatment promotes vascular normalization by recruiting mature pericytes and associated with resistance to bevacizumab therapy in glioblastoma with high Notch pathway activation. Citation Format: Norihiko Saito, Kazuya Aoki, Nozomi Hirai, Satoshi Fujita, Junya Iwama, Masashi Ikota, Haruo Nakayama, Morito Hayashi, Keisuke Ito, Takatoshi Sakurai, Satoshi Iwabuchi. Notch pathway activation predicts resistance to bevacizumab therapy in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 774. doi:10.1158/1538-7445.AM2017-774

Treatment of Moyamoya Syndrome Associated with Systemic Lupus Erythematosus and Hypothyroidism in an Adult by Encephaloduroarteriosynangiosis: A Case Report

A 54-year-old woman presented to our hospital with progressive motor weakness of the right arm. She had a medical history of systemic lupus erythematosus (SLE) and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction of the left hemisphere. Cervical echogram indicated severe stenosis of the internal carotid artery (ICA) without wall thickening. Cerebral angiography indicated left ICA occlusion, development of unilateral moyamoya vessels, and leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed after cerebral 99 mTechnetium-ethyl-cysteinate-dimer single-photon emission computed tomography indicated a decreased cerebral blood flow, diminished cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months after surgery. Moyamoya syndrome is a rare complication of both SLE and hypothyroidism, and the surgical indication remains controversial. By evaluating the decreased cerebral perfusion reserve capacity and the existence of leptomeningeal anastomosis, EDAS could be an efficient method for the treatment of moyamoya syndrome associated with SLE and hypothyroidism.