Kentaro Toyama

Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia

Intravenous transplantation of human mesenchymal stem cells (hMSCs) expanded from adult bone marrow ameliorates functional deficits in rat cerebral infarction models. Several hypotheses to account for the therapeutic mechanisms have been suggested, but angiogenesis is thought to be of critical importance. Recently, we have reported the therapeutic benefits of hMSCs which have been transfected with the angiopoietin-1 gene in a rat permanent middle cerebral artery occlusion (MCAO) model. To potentially enhance the therapeutic effects of angiopoietin-1 gene-modified hMSC (Ang-hMSC), we transfected hMSCs with the angiopoietin-1 gene and the VEGF gene, and investigated whether the combination of Ang-1 and VEGF gene-modified hMSCs (Ang-VEGF-hMSC) contribute to functional recovery in a rat MCAO model. We induced MCAO using intraluminal vascular occlusion, and hMSCs, Ang-hMSCs, VEGF-hMSCs or Ang-VEGF-hMSCs were intravenously infused 6 h later. MRI and behavioral analyses revealed that rats receiving Ang-VEGF-hMSCs showed the greatest structural-functional recovery as compared to the other groups. These results suggest that intravenous administration of hMSCs transfected with the angiopoietin-1 and VEGF gene using a fiber-mutant adenovirus vector may represent a new strategy for the treatment of ischemia.

Dot‐Like Hemosiderin Deposition on T2*‐Weighted MR Imaging Associated with Nonhypertensive Intracerebral Hemorrhage

Background and Purpose. Microangiopathy, a disorder often related to hypertension, is an important cause of deep intracerebral hematoma (ICH). The microangiopathy is associated with dot‐like low‐intensity spots (a dot‐like hemosiderin spot: dotHS) on gradient‐echo T2*‐weighted MR images that have been histologically diagnosed as old microbleeds. The locations of dotHS are consistent with deep ICH. Methods. To investigate how dotHS or other risk factors contribute to nonhypertensive deep ICH, the number and location of dotHSs, as well as other risk factors were examined in 213 deep ICH patients (106 males, 107 females, age: 37‐94 (65.8 ± 11.2) years) consecutively admitted to Hakodate Municipal Hospital. Patients were divided into two subgroups according to the presence or absence of hypertension. DotHSs were also divided into deep and subcortical dotHS and investigated independently. Odds ratios (ORs) were estimated from logistic regression analyses. Furthermore, nonhypertensive ICH patients were compared with nonhypertensive healthy volunteers matched for age and sex. Results. No risk factors were identified in the 31 nonhypertensive deep ICH patients that differed from those found in the 182 hypertensive deep ICH patients. Deep dotHS ≥ 1 (OR: 25.5; 95% CI: 4.76‐137; P= .0002), subcortical dotHS ≥ 1 (OR: 9.0; 95% CI: 1.79‐44.9; P= .046), diabetes mellitus (OR: 9.0; 95% CI: 1.53‐52.3; P= .015), and smoking (OR, 9.6; 95% CI; 1.8‐49.8, P= .007) significantly elevated the risk of nonhypertensive ICH, compared to the healthy volunteers. Conclusions. Our findings suggest that deep and subcortical dotHSs may be risk factors for the development of non‐hypertensive deep ICH.

Incidence of Intracranial Arterial Dissection in Non-emergency Outpatients Complaining of Headache: Preliminary Investigation with MRI/MRA Examinations

PURPOSE Headache is recognized as one of the specific signs of intracranial arterial dissection (ICrAD). We clarified the incidence of ICrAD in non-emergency outpatients complaining of headache and the nature of headache observed in case of ICrAD. PATIENT POPULATION AND METHODS Consecutive non-emergency outpatients coming to the neurological and neurosurgical departments and who underwent MRI and MRA examinations were included in this study. The diagnosis of ICrAD was made when patients met the following two conditions: (1) pearl-and-string sign, pearl sign, or string sign on MRA, and (2) high arterial wall signal on T1 images or intimal flap on T2 images. If possible, cerebral angiography and/or black blood MRI and/or surface-image MRI was also performed in cases meeting these criteria. RESULTS (1) Headache group (172 patients): severe headache was seen in five patients and headache of sudden onset in three. Arterial dissection was diagnosed in eight patients (4.7%, including seven cases of asymptomatic vertebral dissection and one of basilar dissection). The headache noted in most cases of ICrAD was similar to that experienced in daily life. (2) Non-headache group (201 patients): complaints included vertigo/dizziness in 52 patients, gait disturbance in 28, weakness of the arm or leg in 20, and limb numbness in 18, syncope attack in 14, and others in 69. Arterial dissection was diagnosed in six patients (3.0%, including one case of asymptomatic basilar and two of vertebral artery dissection, symptomatic two vertebral and one basilar dissection). CONCLUSION We obtained no evidence of significant difference in the incidence of ICrAD in non-emergency outpatients with (4.7%) and without headache (3.0%). The nature of the headache in the cases of ICrAD was similar to that experienced in daily life. ICrAD with nonspecific headache is more common than previously thought.

Intraoperative Mapping and Monitoring of the Pyramidal Tract Using Endoscopic Depth Electrodes

OBJECTIVE To evaluate motor function during neuroendoscopic resectioning of deep-seated brain tumors using endoscopically guided depth electrodes. METHODS For 12 cases of thalamic tumors, including high-grade gliomas, germinomas, and malignant lymphomas, depth electrodes were inserted using endoscopic guides between the tumor and the pyramidal tract in the thalamus. Motor-evoked potentials (MEPs) were continuously recorded during neuroendoscopic resectioning of the tumors. RESULTS Monitoring of MEP responses using depth electrodes in all 12 cases was successful. The minimum stimulus intensity threshold required to induce MEP responses was 3 mA. Gross total or subtotal resections were successful with this technique for all patients with glioma. No additional neurologic impairments were found after surgery in any of the cases. CONCLUSIONS Continuous MEP measurement using depth electrodes can serve as a new monitoring technique for endoscopic resectioning of deep-seated brain tumors.

A case of posterior cerebral artery dissection presenting with migraine-like headache and visual field defect: usefulness of fast imaging employing steady-state acquisition (FIESTA) for diagnosis.

We report a 34-year-old woman with sudden onset of unilateral migraine-like headache and right homonymous hemianopsia. Fast imaging employing steady-state acquisition (FIESTA) of the posterior cerebral artery captured an intimal flap and a pseudolumen, leading to a diagnosis of posterior cerebral artery dissection. This case was considered a spontaneous posterior cerebral artery dissection causing migraine-like headache. The treatment of migraine-like headache hinges on correct diagnosis. In this case, FIESTA was very useful in diagnosing an intracranial artery dissection.

Effectiveness of intraoperative visual evoked potential in avoiding visual deterioration during endonasal transsphenoidal surgery for pituitary tumors

Postoperative visual function is a major concern in transsphenoidal surgery (TSS). Although several reports have demonstrated the importance of visual evoked potential (VEP) monitoring during TSS, the usefulness of VEP monitoring have been controversial because of its reproducibility. Efficacy of VEP was analyzed in 20 consecutive cases of patients who underwent endoscopic endonasal TSS surgery. We adapted a high-power light-emitting diode stimulator with electroretinography using venous anesthesia. In addition, we used black shield patch and braided codes to obtain reproducible VEP amplitudes. Stable and reproducible VEP waveforms were obtained in 38 of 39 eyes (97.4%) before surgery. Fifteen eyes had deteriorated VEP amplitude during operation, and nine eyes had improved VEP amplitude at the end of surgery, and six eyes had not improved VEP amplitude. But no postoperative visual impairment was observed in all cases by temporary halting the surgical manipulation when the VEP was deteriorated. In conclusion, VEP monitoring could be a warning sign to avoid postoperative visual dysfunction. We recommend VEP as a routine monitoring in TSS.

Endovascular Therapy for a Post-irradiated Cervical Pseudoaneurysm at the Carotid Stump: A Case Report

A nearly 80-year-old man with a history of radiotherapy (RT) and total laryngectomy for laryngeal cancer 25 years previously presented with a rapidly growing mass on the right side of his neck. A huge pseudoaneurysm (pseudoAN) was detected at the right carotid bifurcation, though angiography performed four years previously had shown total occlusion of the internal carotid artery. Stent-assisted coil embolization enabled aneurysm sac shrinkage. Clinicians must be aware that the stump of an arterial occlusion associated with RT can change into a pseudoAN over the long term and must provide follow-up in such cases.