Moyamoya Disease: A Review of Clinical Research

About 5 decades have passed since the concept of moyamoya disease (MMD) was established in Japan. In that time, many clinical MMD studies have been performed from several different points of view, such as epidemiology, pathophysiology, surgical procedures, and prognosis. In addition, rapid developments in MMD genetic analysis have occurred. In light of all this activity, clinicians must continually update their knowledge of MMD in order to improve the prognosis of MMD patients. In this review article, we summarize the clinical MMD studies and introduce cutting-edge findings regarding MMD

Protein Transduction Method for Cerebrovascular Disorders

Many studies have shown that a motif of 11 consecutive arginines (11R) is one of the most effective protein transduction domains (PTD) for introducing proteins into the cell membrane. By conjugating this &#34;11R&#34;, all sorts of proteins can effectively and harmlessly be transferred into any kind of cell. We therefore examined the transduction efficiency of 11R in cerebral arteries and obtained results showing that 11R fused enhanced green fluorescent protein (11R-EGFP) immediately and effectively penetrated all layers of the rat basilar artery (BA), especially the tunica media. This method provides a revolutionary approach to cerebral arteries and ours is the first study to demonstrate the successful transductionof a PTD fused protein into the cerebral arteries. In this review, we present an outline of our studies and other key studies related to cerebral vasospasm and 11R, problems to be overcome, and predictions regarding future use of the 11R protein transduction method for cerebral vasospasm (CV).</p

Novel 3D-CT evaluation of carotid stent volume: greater chronological expansion of stents in patients with vulnerable plaques

Although self-expanding carotid stents may dilate gradually, the degrees of residual stenosis have been quantified by the NASCET criteria, which is too simple to reflect the configuration of the stented artery. We measured the volumes of the stent lumens chronologically by 3D-CT in patients after carotid artery stenting (CAS), and analyzed the correlations between the volume change and medical factors. Fourteen patients with carotid artery stenosis were treated using self-expanding, open-cell stents. All patients underwent preoperative plaque MRI (magnetization-prepared rapid acquisition gradient-echo, MPRAGE) and chronological 3D-CT examinations of their stents immediately after their placement and 1 day, 1 week, and 1 month after the procedure. The volume of the stent lumen was measured using a 3D workstation. The correlations between stent volume and various factors including the presence of underlying diseases, plaque characteristics, and the results of the CAS procedure were analyzed. Stent volume gradually increased in each case and had increased by 1.04-1.55 (mean, 1.25)-fold at 1 postoperative month. The presence of underlying medical diseases, plaque length, the degree of residual stenosis immediately after CAS, and plaque calcification did not have an impact on the change in stent volume. On the other hand, the stent volume increase was significantly larger in the patients with vulnerable plaques that demonstrated high MPRAGE signal intensity (P < 0.05). A 3D-CT examination is useful for precisely measuring stent volume. Self-expanding stents in carotid arteries containing vulnerable plaques expand significantly more than those without such plaques in a follow-up period

De novo vertebral artery dissecting aneurysm after internal trapping of the contralateral vertebral artery

We present the case of a de novo vertebral artery dissecting aneurysm (VADA) after endovascular trapping of a ruptured VADA on the contralateral side. The first ruptured VADA involved the posterior inferior cerebellar artery, which was successfully treated by endovascular internal trapping using a stent. A follow-up study at 3 months revealed a de novo VADA on the contralateral side. The second VADA was successfully embolized using coils while normal arterial flow in the vertebral artery was preserved using a stent. Increased hemodynamic stress may cause the development of a de novo VADA on the contralateral side

Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats

Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for "oxidative phosphorylation" was significantly upregulated while fourteen other gene sets including "apoptosis", "hypoxia" and "reactive oxygen species" showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis

Neoadjuvant Chemotherapy with or without Concurrent Hormone Therapy in Estrogen Receptor-Positive Breast Cancer:NACED-Randomized Multicenter Phase II Trial

Although in the neoadjuvant setting for estrogen receptor (ER)-positive breast cancers, chemotherapy or hormone therapy alone does not result in satisfactory tumor response, it is unknown whether concurrent chemo-endocrine therapy is superior to chemotherapy alone in clinical outcomes. We conducted a randomized phase II trial to test the responses of ER-positive patients to concurrent administration of chemo-endocrine therapy in the neoadjuvant setting. Women with stage II-III, ER-positive, invasive breast cancer (n=28) received paclitaxel followed by fluorouracil, epirubicin, cyclophosphamide (T-FEC) and were randomized to receive concurrent chemo-endocrine therapy consisting of goserelin administered subcutaneously for premenopausal women or an aromatase inhibitor for postmenopausal women. The primary endpoint was the pathological complete response (pCR) rate after neoadjuvant therapy. Twenty-eight patients were randomized. There were no significant differences in pCR rate between the concurrent group (12.5%;2/16) and the chemotherapy alone group (8.3%;1/12). Tumor size after therapy was significantly reduced in the concurrent therapy group (p=0.035), but not in the chemotherapy-alone group (p=0.622). Neoadjuvant chemotherapy with concurrent hormone therapy provided no significant improvement in pCR rate in ER-positive breast cancers. These preliminary results should be followed up by further studies

A comparison of the prevalence and risk factors of complications in intracranial tumor embolization between the Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and JR-NET3

BACKGROUND: The Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and 3 (JR-NET3) were nationwide surveys that evaluated clinical outcomes after neuroendovascular therapy in Japan. The aim of this study was to compare the prevalence and risk factors of complications of intracranial tumor embolization between JR-NET2 and JR-NET3. METHODS: A total of 1018 and 1545 consecutive patients with intracranial tumors treated with embolization were enrolled in JR-NET2 and JR-NET3, respectively. The prevalence of complications in intracranial tumor embolization and related risk factors were compared between JR-NET2 and JR-NET3. RESULTS: The prevalence of complications in JR-NET3 (3.69%) was significantly higher than that in JR-NET2 (1.48%) (p = 0.002). The multivariate analysis in JR-NET2 showed that embolization for tumors other than meningioma was the only significant risk factor for complication (odds ratio [OR], 3.88; 95% confidence interval [CI], 1.13-12.10; p = 0.032), and that in JR-NET3 revealed that embolization for feeders other than external carotid artery (ECA) (OR, 3.56; 95% CI, 2.03-6.25; p  CONCLUSIONS: Embolization for feeders other than ECA and use of liquid materials could increase the complication rate in intracranial tumor embolization