Kenzo Tsunetoshi

Transdifferentiation of bone marrow-derived endothelial progenitor cells into the smooth muscle cell lineage mediated by tansforming growth factor-β1

OBJECTIVE The aim of this study was to investigate the transdifferentiation of bone marrow (BM)-derived endothelial progenitor cells (EPCs) into the smooth muscle cell (SMC) lineage in vitro and in vivo. METHODS AND RESULTS EPCs were obtained from BM of rats and cultured on fibronectin-coated dishes for 15 days. Treatment of EPCs with transforming growth factor (TGF)-beta1 for 7 days changed morphology of EPCs, reduced the expression of endothelial markers in EPCs, induced the expression of SMC markers, and enhanced their proliferation. EPCs expressed TGF-beta receptor type II (TGF-beta RII) and TGF-beta1 induced the phosphorylation of Smad 2 in EPCs. TGF-beta1-induced transdifferentiation was specifically inhibited by neutralizing antibody against TGF-beta and gene silencing of TGF-beta RII. Local transplantation of autologous EPCs enhanced intimal hyperplasia of the balloon-injured artery on day 28. Transplanted EPCs were localized near the endothelial layer on day 14 but widely distributed within the hypertrophic neointima on day 28 differentiating toward SMC lineage. Neither expression of growth factors such as TGF-beta1 nor early inflammatory reactions within the denuded arteries were promoted by transplantation of EPCs. CONCLUSIONS TGF-beta1 induced the transdifferentiation of BM-derived EPCs toward SMC lineage mediated by TGF-beta RII. The augmentation of intimal hyperplasia by transplantation of EPCs was probably due to the transdifferentiation and proliferation of EPCs induced by TGF-beta1.

Intraoperative Computed Tomography for Cervicomedullary Decompression of Foramen Magnum Stenosis in Achondroplasia: Two Case Reports

The authors report two cases of cervicomedullary decompression of foramen magnum (FM) stenosis in children with achondroplasia using intraoperative computed tomography (iCT). A 14-month-old girl with myelopathy and retarded motor development, and a 10-year-old girl who had already undergone incomplete FM decompression was presented with myelopathy. Both patients underwent decompressive sub-occipitalcraniectomy and C1 laminectomy without duraplasty using iCT. It clearly showed the extent of FM decompression during surgery, which finally enabled sufficient decompression. After the operation, their myelopathy improved. We think that iCT can provide useful information and guidance for sufficient decompression for FM stenosis in children with achondroplasia.

Intraoperative and pathological findings of intramedullary amputation neuroma associated with spinal ependymoma

Amputation neuromas typically arise in injured peripheral nerves; rarely, however, they arise in the spinal cord. We report a rare case of intramedullary amputation neuroma associated with ependymoma in the cervical spinal cord. A 73-year-old woman presented with a 5-year history of progressive gait disturbance. Neurological examination revealed complete motor deficit of her hands and legs. Magnetic resonance imaging of the cervical spine revealed an enhancing mass within the spinal cord at the C6/7 level. The patient underwent C5–C7 laminectomy surgery. During resection of the spinal tumor, we found a whitish string resembling an aberrant nerve root or schwannoma with adhesion to the tumor on the ventral side of the spinal cord. After resecting the tumor, the surgical specimen was cut and separated into a soft greyish tumor (spinal tumor) and the tough whitish string. Histopathological and immunohistochemical examination revealed the former was a spinal ependymoma and the latter was a neuroma. An intramedullary amputation neuroma associated with a spinal ependymoma is rare, and this is the first known case in which intraoprerative findings were clearly shown. Neurosurgeons should be aware that spinal ependymomas might coexist with neuromas.

Spinal endoscopy combined with selective CT myelography for dural closure of the spinal dural defect with superficial siderosis: technical note

The authors describe a new procedure to detect the tiny dural hole in patients with superficial siderosis (SS) and CSF leakage using a coronary angioscope system for spinal endoscopy and selective CT myelography using a spinal drainage tube. Under fluoroscopy, surgeons inserted the coronary angioscope into the spinal subarachnoid space, similar to the procedure of spinal drainage, and slowly advanced it to the cervical spine. The angioscope clearly showed the small dural hole and injured arachnoid membrane. One week later, the spinal drainage tube was inserted, and the tip of the drainage tube was located just below the level of the dural defect found by the spinal endoscopic examination. This selective CT myelography clarifies the location of the dural defect. During surgery, the small dural hole could be easily located, and it was securely sutured. It is sometimes difficult to detect the actual location of the small dural hole even with thin-slice MRI or dynamic CT myelography in patients with SS. The use of a coronary angioscope for the spinal endoscopy combined with selective CT myelography may provide an effective examination to assess dural closure of the spinal dural defect with SS in cases without obvious dural defects on conventional imaging.

Microsurgical Findings of Tolosa-Hunt Syndrome

BACKGROUND Tolosa-Hunt syndrome (THS), a nonspecific chronic inflammation of the cavernous sinus, is a rarely needed surgical manipulation, even for diagnosis, because corticosteroid therapy is markedly effective against this condition. METHODS A 59-year-old man presented with left trigeminal neuralgia and right abducens nerve palsy 2 months after the improvement of right oculomotor nerve palsy by corticosteroid therapy. Radiological examinations showed a mass lesion in the left cavernous sinus. The clinical course indicated THS; however, hematological examination showed a positive tuberculous test. We performed a biopsy to rule out tuberculoma in the cavernous sinus. RESULTS The biopsy was via a left frontotemporal interdural approach. The dura propria over the cavernous sinus was thickened and tightly adhered to the inner layer. The cavernous sinus was occupied by whitish elastic-hard tissue, and it was partially resected through the anterolateral triangle. Histopathological examination showed thick fibrous tissue with numerous degenerated cells and partial inflammatory cell infiltrations without any findings of tuberculoma. The final diagnosis was THS, and corticosteroid therapy was effective despite the chronic fibrous change of the cavernous sinus lesion. CONCLUSIONS This article presents details of surgical findings of THS that have not been demonstrated in any previous reports.

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages

Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aβ antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.

Evaluation of obliteration of arteriovenous malformations after stereotactic radiosurgery with arterial spin labeling MR imaging

Abstract Purpose: Complete obliteration of treated arteriovenous malformations (AVMs) can be diagnosed only by confirming the disappearance of arterio-venous (A-V) shunts with invasive catheter angiography. The authors evaluated whether non-invasive arterial spin labeling (ASL) magnetic resonance (MR) imaging can be used to diagnose the obliteration of AVMs facilitate the diagnosis of AVM obliteration after treatment with stereotactic radiosurgery (SRS). Material and methods: Seven patients with a cerebral AVM treated by SRS were followed up with ASL images taken with a 3T-MR unit, and received digital subtraction angiography (DSA) after the AVM had disappeared on ASL images. Three patients among the seven received DSA also after the postradiosurgical AVM had disappeared on conventional MR images but A-V shunt was residual on ASL images. Four patients among the seven received contrast-enhanced (CE) MR imaging around the same period as DSA. Results: ASL images could visualize postradiosurgical residual A-V shunts clearly. In all seven patients, DSA after the disappearance of A-V shunts on ASL images demonstrated no evidence of A-V shunts. In all three patients, DSA after the AVM had disappeared on conventional MR images but not on ASL images demonstrated residual A-V shunt. CE MR findings of AVMs treated by SRS did not correspond with DSA findings in three out of four patients. Conclusions: Findings of radiosurgically treated AVMs on ASL images corresponded with those on DSA. The results of this study suggest that ASL imaging can be utilized to follow up AVMs after SRS and to decide their obliteration facilitate to decide the precise timing of catheter angiography for the final diagnosis of AVM obliteration after SRS.

Deflation of a Rathke cleft cyst triggered rupture of a superior hypophyseal artery aneurysm: a case report

Abstract A 57-year-old woman was diagnosed as a Rathke cleft cyst (RCC). Endoscopic transsphenoidal surgery (TSS) was performed uneventfully. She developed subarachnoid haemorrhage on postoperative day 3. The vessels adhered the cyst had been pulled into the pituitary fossa, causing an aneurysm.