Search

Background: Recent pharmacological studies reveal imeglimin (Twymeeg) including dual mechanisms for stimulating insulin secretion and reducing insulin resistance. Case Presentation: The case is a 62-year-old male with type 2 diabetes (T2D). He showed HbA1c 6.4% and started imeglimin. After 5 weeks, a 75g oral glucose tolerance test (75gOGTT) was conducted, and the biomarkers were compared with that of 6 months ago. Insulinogenic index (IGI) 0-30min was stable, but insulin secretion was increased during 30-60min and 60-120min. Discussion: Previous studies of imeglimin revealed improved insulin secretion for GTT. Clinical progress will be followed up with detailed investigation of glucose and insulin variability.

The extracellular water-to-total body water ratio (ECW/TBW) is used in bioelectrical impedance analysis (BIA) for measuring muscle mass; however, ECW/TBW may be affected by several factors common in older individuals. Here, we assessed the relationships of ECW/TBW with handgrip strength, gait speed, and skeletal muscle mass index (SMI) in older women.In this cross-sectional study, 73 community-dwelling women aged ≥ 65 years who could independently perform activities of daily living were included. ECW/TBW was measured using direct segmental multifrequency BIA. The participants were divided into ECW/TBW 0.40 (n = 54) and ECW/TBW ≥ 0.40 (n = 19) groups, with the latter indicating overhydration. SMI was calculated as appendicular skeletal muscle mass/(height)The average age of participants was 77.6 ± 6.0 years. The SMI was significantly related to handgrip strength (partial correlation coefficient = 0.293, P = 0.016) but not to gait speed (partial correlation coefficient = - 0.183, P = 0.138). Similarly, the SMI of the ECW/TBW 0.40 group was significantly related to handgrip strength (partial correlation coefficient = 0.372, P = 0.009) but not gait speed (partial correlation coefficient = - 0.267, P = 0.066); however, the SMI of the ECW/TBW ≥ 0.40 group was not related to either variable.ECW/TBW represents a confounding factor, which should be considered when using BIA for sarcopenia diagnosis.

The authors and collaborators have continued practice of hospital art in the university and community hospitals and various research with experts. The material for hospital art is masking tape which is easily made and attached for everyone. Formerly, we have conducted artwork in front of the wall, which took a long time. Currently, we have tried to take the most advantage of the thin-film sheet. Our staff can prepare artwork with a size of 20 cm square in advance. Many square parts with double-sided attachment tape can be gathered together, which is completed and useful in a short time.

The case was 71-year-old male patient with type 2 diabetes mellitus (T2DM). He was diagnosed T2DM at the age of 61 associated with thirsty, polydipsia and fatigue. HbA1c value was 12.5% and blood glucose profile was 150-300 mg/dL. Just after starting low carbohydrate diet (LCD), his blood glucose kept under 150 mg/dL all day long. He continued good diabetic control as HbA1c 5.8-6.8% for 10 years. Some beneficial points are found: i) keeping LCD with the feeling not stressful but pleasant for observing the normal glucose level, ii) walking daily for 2 hours, iii) continuing educational activity in the walking association for DM and health care. iv) writing the diary for years every day, including exercise, meal, medicine, activities and so on, v) checking post-prandial hyperglycemia by meal tolerance test (MTT). For details of v), HbA1c was 6.5% in May 2021 and fasting glucose was 107mg/dL. Glucose values 45-min and 60-min after 3 meals showed 210-201-177mg/dL and 195-213-172mg/dL, respectively. His various continuing behaviors contributed satisfactory glycemic control. This article becomes reference in the diabetic practice and research.

The patient was a 74-year-old female with type 2 diabetes mellitus (T2DM) treated on Humalog mix 25 twice a day. As social history, she has worked long years for growing and harvesting lotus roots. It gives physically heavy loading, which brings unstable glycemic daily control. She had to titrate minute regulation every time. For stable glucose variability, the treatment was changed to Xultophy, which is a specific combined agent of Insulin Degludec and Liraglutide (IDeg/Lira) once a day. Then, detailed glucose monitoring showed a better daily profile of blood glucose, irrespective of heavy or light work. It showed the bio-psycho-social benefit of Xultophy.

Background: The authors and colleagues have been involved in treatment and care for the elderly with rehabilitation, Integrative Medicine (IM), art in hospitals for artworks using masking tape. Combined together, we conducted a pilot study for medical application of masking tape art-work for elderly subjects. Subjects and Methods: Subjects enrolled were 12 elderly patients with dementia regularly coming to day care center for rehabilitation (M/F 3/9, 78-100 years, 88.3±6.0 years). As methods, masking tape has been known as Washi Tape (wa=Japanese and shi=paper), which is adhesive tape easily to stick and peel off for decorative work. Protocol included i) working 2-3 times a week, ii) sticking masking tape on a rough sketch paper, iii) evaluation of several biomarkers before and after the intervention. Results: i) Artworks were performed satisfactory for each case, ii) grasping power (right) showed increasing tendency from 13.5±7.7kg to 14.8±6.8kg (p=0.11), iii) vitality test showed significantly increase (p=0.02). Discussion and Conclusion: Artworks of masking tape seem to be beneficial for improving grasping power and psychological condition. This study included other biomarkers such as Mini-Mental State Examination (MMSE), pinch power, language word test and Barthel index. We plan to develop further detail analyses in the future research.

Case: The case is 86-year-old male hypertensive patient with anti-hypertensive drug for 5 years. He has been provided Amlodipine besilate 5mg at 0800h and doxazosin mesylate 2mg at 2300h for long. In June 2020, he noticed unstable fluctuation of Blood Pressure (BP) during morning, afternoon and night. Results: Then, he checked the circadian rhythm of BP, which showed higher BP in early morning, decreasing BP 0800-1000h, minimum BP during 1000-1400h, increasing BP during 1400-1800h and stable BP during 1800-2400h. Due to the result, he changed to take amlodipine at 2300h. Consequently, his BP gradually became stable during 24 hours after 2 weeks. Discussion: Some factors may exist for contributing improved BP fluctuation. They include a) pathophysiological characteristics of BP circadian rhythm, b) effective time for anti-hypertensive drug, c) accuracy of the obtained BP data and d) the social and psychological reliability of the patient. Regarding d) he was engaged in research and development work as a senior researcher at a chemical company. He has been also a member of New Elderly Association (NEA), which was established by Shigeaki Hinohara. He lives on the philosophy of Hinohara-ism for long, associated with stable mind and body.

Background Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist. Objective To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study. Methods Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr. Results A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively. Conclusion Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.

We aimed to investigate the incidence rate of unconsciousness related to shime-waza and the accompanying symptoms by age categories using video analysis of the Judo World Championships.Observational retrospective study.We included 6918 elite judo athletes and 7426 bouts from the Judo World Championships between 2015 and 2021. Incidence rates of matches settled using shime-waza and unconsciousness were calculated by age categories: cadet, junior, and senior. Furthermore, in cases of unconsciousness resulting from shime-waza, the duration of choking initiation and release, unconsciousness, and awareness were recorded from video analysis and compared by the presence of post-awareness symptoms. A relationship between the duration of shime-waza and the post-awareness symptoms was investigated using receiver operating characteristic analysis.Shime-waza was used to settle 307 (4.1 %) bouts comprising 6.0 %, 4.4 %, and 3.0 % of the cadet, junior, and senior bouts, respectively (p 0.001). The unconsciousness rates were 18.9 %, 14.6 %, and 4.3 % in the cadet, junior (p = 0.008), and senior bouts (p 0.001), respectively. Among the 39 unconsciousness cases, 24 (61.5 %) showed convulsions or staggers after awareness. The duration from unconsciousness to choking release in cases with and without symptoms was 5.0 ± 3.5 s and 2.4 ± 2.0 s, respectively (p = 0.009); moreover, this duration was significantly correlated with the duration from unconsciousness to awareness (ρ = 0.480, p = 0.002). The cut-off point for symptom occurrence was a duration from unconsciousness to choking release of ≥4 s (area under the curve = 0.746, p = 0.003, odds ratio = 6.7).Considering the risk of unconsciousness and accompanying symptoms resulting from shime-waza, appropriate education and responses are required.

Background and purpose A transient ischemic attack (TIA) can occur without self‐awareness of symptoms. We aimed to investigate characteristics of patients with a tissue‐based diagnosis of TIA but having no self‐awareness of their symptoms and whose symptoms were witnessed by bystanders. Methods We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self‐awareness of their TIA symptoms. Results Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self‐awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self‐awareness. Patients without self‐awareness of symptoms arrive at hospitals earlier than those with self‐awareness (P, Graphical Table of Contents Among 896 patients (559 men, median age of 70 years) with diagnosis of a tissue‐based transient ischemic attack (TIA), 59 (6.6%) were unaware of their symptoms but had their symptoms witnessed by bystanders. The cumulative incidence rate of occurrence of ischemic stroke after 1 year from TIA was higher in patients without self‐awareness than those with self‐awareness (16.3% vs. 6.9%, log‐rank; P = 0.010).

Art therapy has attracted attention in the medical field. Among them, authors have been engaged in various activities including art in hospitals. We have started the artworks using masking tape, which has various colors and the pattern. It can be also used for craft making, wrapping, decoration, and original goods such as art exhibitions. Our current work was performed on the corridor and staircase walls of Tokushima University hospital. It has psychologically three important perspectives, which are i) healing: relieving anxiety, healing the mind, ii) comfort: creating a pleasant and comfortable image, iii) wayfinding system: the wall sign can give a walk direction guide without confusion such as pilgrim walking. We plan to develop the performance in various opportunities.

Background As of October 2021, sports activities require preventive measures against coronavirus disease 2019 (COVID-19) infection. Judo, a close-contact sport, demands careful prevention with great consideration to the risk of infection. The All Japan Judo Federation Medical Science Committee (AJJF) designed COVID-19 prevention protocols from a medical perspective and developed policies for safe regular practices and tournaments. Objective and Methods We aim to examine the efficacy of health surveys and polymerase chain reaction (PCR) tests prior to judo tournaments, as mandated by the tournament policy. Infection prevention managers were installed prior to tournaments. Two weeks prior to each tournament, these managers drafted health inventory forms for athletes and related parties to check for COVID-19-associated symptoms. Although PCR testing prior to tournaments was not required by policy, the AJJF conducted them (directly and by mail) prior to six tournaments from October 2020 to September 2021 for athletes whose health inventory forms listed no symptoms. Results One of the athletes was not tested and was unable to participate in a tournament due to the symptoms indicated in their health inventory form. Testing began in October 2020 and was conducted until September 2021 for 2,073 athletes over the duration of six tournaments. The SARS-CoV-2 virus was detected in 11 (0.29%) athletes. In tournaments held until April 2021, SARS-CoV-2 was detected in only one of the 1,173 (0.08%) athletes tested. However, prior to tournaments held from July 2021 onward, when variants became prevalent, SARS-CoV-2 was detected in 10 (1.1%) of the 900 athletes tested (p < 0.05). No clusters were reported in association with any tournament. Conclusion We believe that drafting health inventory forms two weeks prior to judo tournaments was essential and kept the participants alert. However, as variants emerged, some participants who were positive could not be detected through their inventory forms; this demonstrates the need for caution when relying on health inventory forms alone.

Historically speaking, hospitals had grown out of hostels, where pilgrims, old and sick people were treated. During the Middle Ages in Europe, the art was indispensable factor of the hospitals. Art in hospitals (hospital art) has been recently known and recognized as beneficial method. Authors performed the art in hospitals in the rehabilitation hospital, which was completed by using various colorful masking tape. The composition consisted of 4 artworks for four seasons on the wall of the corridor. Many patients are trained walking with always looking them every day. Art in hospitals may be called as art and health, and it has a power to make patients bring out positive attitude and energy. Its further development would be expected.

Carotid endarterectomy (CEA) is widely used for cervical artery stenosis. In Japan, primary closure after endarterectomy has been a standard technique. Recently, the patch closure has been shown to be superior to the primary suture for the prevention of restenosis and ipsilateral stroke. This study evaluated the 5- and 10-year outcomes following CEA with patch graft closure in our institution. Between January 2000 and March 2013, 134 patients, who underwent CEA with patch graft closure were investigated in the current retrospective study. Among these patients, 102 CEAs in 97 patients were followed up for 5 years and 66 CEAs in 61 patients were for 10 years after the procedure. Restenosis was defined as >50% recurrent luminal narrowing at the endarterectomy site. In 5 years, symptomatic restenosis exhibited minor stroke in one patient at 58 months after CEA (restenosis rate 1.0%). The ipsilateral minor stroke occurred in three patients including the above case (2.9%). In 10 years, asymptomatic restenosis occurred in three patients in addition to the above symptomatic case (restenosis rate 6.1%), and the ipsilateral minor stroke occurred in four patients (6.1%). Carotid endarterectomy with patch graft exerted a high protective effect from restenosis up to 5 and 10 years in our institution. The number of carotid artery stenting is increasing all over the world but we speculated that the established surgical procedure of patched CEA prevented restenosis and ipsilateral stroke.

Background Recent prospective registration studies of transient ischemic attack in Western countries demonstrated that large artery atherosclerosis is the highest risk etiology for early stroke recurrence under urgent evaluation and treatment. On the other hand, some limited transient ischemic attack studies from East Asian countries showed transient ischemic attack patients due to small vessel occlusion were at a higher early stroke risk. Aims We aimed to assess the risk for early stroke in small vessel occlusion-transient ischemic attack patients in a Japanese large transient ischemic attack registry. Methods We analyzed the data of a prospective Japanese transient ischemic attack registry including 1320 transient ischemic attack patients within seven days after onset. Small vessel occlusion-transient ischemic attack was defined as the presence of lacunar transient ischemic attack syndrome, without other etiologies. The outcome measure was recurrent stroke within 30 days after transient ischemic attack. The predictors of 30-day recurrent stroke were estimated using the Cox proportional hazards model. Results The study population had a mean age of 69 ± 12 years and 470 were women. Recurrent stroke was observed in 61 patients (4.6%), and the highest rate was observed with small vessel occlusion-transient ischemic attack (7.8%), followed by large artery atherosclerosis (5.4%). In multivariate analysis, recurrent stroke was independently associated with small vessel occlusion-transient ischemic attack (hazard ratio (HR): 2.01, 95% confidence interval (CI): 1.19–3.35), higher systolic blood pressure (HR: 1.18, 95% CI: 1.08–1.28), and presentation within 3 h after onset (HR: 2.21, 95% CI: 1.27–4.04). Furthermore, small vessel occlusion-transient ischemic attack with acute small deep infarct on diffusion-weighted imaging was a stronger predictor of recurrent stroke (HR: 4.87, 95% CI: 2.09–10.0). Conclusion Small vessel occlusion-transient ischemic attack, especially with acute small deep infarct, had a higher early stroke risk compared with other etiologies in Japanese transient ischemic attack patients who received early management.

The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training.

Background Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. Objective To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. Methods We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. Results There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. Conclusion In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.

The aim of this study was to investigate the effects of action observation treatment (AOT) on gait ability in patients with subacute to convalescent stroke. Sixteen patients with subacute stroke were divided into a control group (n = 8) and AOT group (n = 8) when admitted to the convalescent ward. The control group received a conventional rehabilitation only. In addition to conventional rehabilitation, the AOT received AOT for 3 months (30 min per day 5 times per week). The AOT involved observing the action of another subject in a comfortable gait situation from the front, sides, and back via video and conducting the actual action. All participants were assessed during the main-assessment period, which included a baseline (i.e., when admitted to the convalescent ward) and 1, 2, and 3 months after baseline. The sub-assessment period at 2 and 3 months after baseline was conducted with participants who could walk independently. The main outcomes of the main-assessment and sub-assessment periods were Functional Ambulation Classification (FAC) and the 10-m walk test (10MWT), respectively. With respect to the FAC, we used a split plot design analysis of covariance to test the interaction between assessment time and group. There was no significant interaction between assessment time and group in FAC. However, a significant improvement of the 10MWT in the sub-assessment period was observed in the AOT group, but not the control group. Our results indicate that AOT may be an effective therapy for patients with subacute to convalescent stroke who can walk independently.

Methods: This was a retrospective cohort study. Data from 165 patients, with middle cerebral occlusion before t-PA therapy (from the YAMATO study databank), were retrospectively evaluated. Patients...

Background and Purpose— Patients with transient ischemic attack (TIA) occasionally show nonfocal symptoms, such as unconsciousness, amnesia, and unsteadiness. The purpose of this study was to clarify the characteristics and prognosis of patients with TIA with nonfocal symptoms, using data from the PROMISE-TIA (Prospective Multicenter Registry to Identify Subsequent Cardiovascular Events After Transient Ischemic Attack). Methods— Patients with TIA within 7 days of onset were consecutively enrolled in the Japanese nationwide registry. Factors associated with nonfocal symptoms and 1-year risks of ischemic stroke and coronary artery diseases were assessed in multivariate-adjusted models. Results— We studied 1362 patients with TIA (879 men; mean age, 69±12 years), including 219 (16%) with nonfocal symptoms. Patients with TIA with nonfocal symptoms were more likely to show acute ischemic lesions in the posterior circulation on diffusion-weighted imaging (multivariate-adjusted odds ratio, 3.07; 95% confidence interval, 1.57–5.82) and arterial stenosis or occlusion in the posterior circulation on vascular examination (odds ratio, 1.94; 95% confidence interval, 1.19–3.09) than those without nonfocal symptoms. Although 1-year risk of ischemic stroke did not differ significantly between groups (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42–1.37), risk of coronary artery disease was higher in patients with TIA with nonfocal symptoms (hazard ratio, 3.37; 95% confidence interval, 1.14–9.03). Conclusions— Both acute ischemic lesions and arterial stenosis and occlusion in the posterior circulation were more frequently observed in patients with TIA with nonfocal symptoms.

Background Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear. Case Description We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved. Conclusions Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak.

Background Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients. Methods Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms. Results Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%. Conclusion Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed.

Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.

Objective Superficial temporal artery (STA)–to–middle cerebral artery (MCA) bypass is an established surgical technique for achieving revascularization. It is important to select the proper recipient artery of the MCA. Three-dimensional computed tomographic angiography (3D-CTA) and conventional angiography are useful in the selection process but need contrast agents. The authors have designed a coloring MRA technique that needs no agents to visualize the recipient artery. Retrospective evaluation of the efficacy and limitation for selection of the recipient artery and decision of the place and size of the craniotomy were carried out. Methods The authors performed the coloring MRA before operation since January 2013. Ninety-two patients underwent STA-MCA bypass for atherosclerotic stenosis or occlusion of internal carotid artery (ICA), MCA with reference to the coloring MRA. To evaluate the efficacy of coloring MRA, the control group consisted of 75 patients who underwent STA-MCA bypass between January 2012 to November 2013 with reference to 3D-CTA. The size of craniotomy was retrospectively calculated and compared. Results Neither additional craniotomy nor wrong selection of the recipient artery was done in either group. There was no significant difference in size between the 2 groups in both single and double bypass. Conclusions The coloring MRA technique was not inferior to 3D-CTA with respect to the size of craniotomy. This novel technique was found to be very helpful not only for the virtual identification of the proper recipient artery but also for preoperative simulation such as decisions about length of donor artery, location, and size of craniotomy.

Spontaneous and chronic epidural hematoma (SSEH) in the lumbar spine is rare, and idiopathic and chronic SSEH in the lumbar spine is extremely rare disease. Most of lumbar SSEH were acute and secondary with trauma, hematologic disorders, drug, and surgical procedure. Only 20 cases of chronic SSEH in the lumbar spine have been reported and 14 cases among them were considered to be idiopathic. Definitive guidelines for management of this condition are not clear and surgical total evacuation was performed in most of the cases. Some authors reported the epidural bleeding originates in the rupture of Batson's plexus due to a rise in intra-abdominal pressure, but the mechanism is not clearly clarified. We report a surgical case of idiopathic and chronic SSEH. A 61-year-old woman suffered a sudden onset of severe lumbar pain during sleep. She had no history of trauma, spinal surgery, or hypertension. Magnetic resonance imaging revealed a lumbar chronic epidural hematoma which compressed the dural sac behind and extended from L2 to L5. This patient underwent the partial evacuation of the hematoma with partial hemilaminectomy on left at L2/3, resulting in immediate pain relief and resolution of symptoms and almost absorption of the hematoma within 1 week of the procedure. We presented this rare case and reviewed idiopathic and chronic epidural hematoma in the lumbar spine.

Surgery for- and endovascular treatment of vertebral artery (VA) dissecting aneurysms involving the origin of the posterior inferior cerebellar artery (PICA) remain challenging. Their ideal treatment is complete isolation of the aneurysm by surgical or endovascular trapping plus PICA reconstruction. However, postoperative lower cranial nerve palsy and medullary infarction are potential complications. We report four patients with VA dissecting aneurysms involving the PICA origin who were treated by occipital artery (OA)-PICA bypass followed by proximal occlusion of the VA and clip ligation of the PICA origin instead of trapping. There were no procedural or ischemic complications. In all patients, angiography performed 2–3 weeks later showed good patency of the bypass graft and complete obliteration of the aneurysm. During the follow-up period ranging from 1 to 14 years, none experienced bleeding. Although retrograde blood flow to the dissecting aneurysm persisted in the absence of trapping, iatrogenic lower cranial nerve injury could be avoided. The decrease in aneurysmal flow might elicit spontaneous thrombosis and prevent aneurysmal rerupture. Our technique might be less invasive than aneurysmal trapping and help to prevent rebleeding.

Purpose: We evaluated the utility of arterial spin labeling (ASL) imaging of tumor blood flow (TBF) for grading non-enhancing astrocytic tumors. Materials and Methods: Thirteen non-enhancing astrocytomas were divided into high-grade (n = 7) and low-grade (n = 6) groups. Both ASL and conventional sequences were acquired using the same magnetic resonance machine. Intratumoral absolute maximum TBF (TBFmax), absolute mean TBF (TBFmean), and corresponding values normalized to cerebral blood flow (TBFmax and TBFmean ratios) were measured. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were used to assess the accuracy of TBF variables for tumor grading. Results: Compared with low-grade astrocytoma, high-grade astrocytoma exhibited significantly greater absolute TBFmax (90.93 ± 24.96 vs 46.94 ± 20.97 ml/100 g/min, P < 0.001), TBFmean (58.75 ± 19.89 vs 31.16 ± 17.63 ml/100 g/min, P < 0.001), TBFmax ratio (3.34 ± 1.22 vs 1.35 ± 0.5, P < 0.001), and TBFmean ratio (2.15 ± 0.94 vs 0.88 ± 0.41, P < 0.001). The TBFmax ratio yielded the highest diagnostic accuracy (sensitivity 100%, specificity 86.3%), while absolute TBFmean yielded the lowest accuracy (sensitivity 85.7%, specificity 70.1%) by ROC analysis. Conclusion: Parameters from ASL perfusion imaging, particularly TBFmax ratio, may be useful for distinguishing high-grade from low-grade astrocytoma in cases with equivocal conventional MRI findings.

Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP+BM) rats. Three weeks later, they were ovariectomized (OVX/GFP+BM rats). We subjected 7-week-old Wistar male and 13-week-old OVX/GFP+BM rats to 90-min cerebral ischemia. Male and OVX/GFP+BM rats were divided into two groups, one was treated with PGZ (2.5 mg/kg/day) and the other served as the vehicle control (VC). In both male and OVX/GFP+BM rats, post-ischemia treatment with PGZ reduced neurological deficits and the infarct volume. In male rats, PGZ decreased the mRNA level of IL-6 and M1-like macrophages after 24 h. In OVX/GFP+BM rats, PGZ augmented the proliferation of resident stem cells in the subventricular zone (SVZ) and the recruitment of GFP+BM stem cells on days 7–14. Both types of proliferated stem cells migrated from the SVZ into the peri-infarct area. There, they differentiated into mature neurons, glia, and blood vessels in association with activated Akt, MAP2, and VEGF. Post-ischemia treatment with PGZ may offer a new avenue for stroke treatment through contribution to neuroprotection and neurogenesis.

Microvascular decompression (MVD) is a widely used, safe, and effective treatment for trigeminal neuralgia (TGN). However, the extent of application of this therapeutic method and its outcomes in Japan are currently unclear. To address these questions, the authors analyzed the use of MVD for the treatment of TGN during the 33-month period from July 2010 to March 2013, using data contained in the Diagnosis Procedure Combination database. The analysis revealed that MVD was used for the treatment of TGN in 1619 cases (608 men, 1011 women), with approximately 1.66 times more women treated than men. MVD for TGN was most frequently performed in individuals 60 to 79 years of age; of particular note was the remarkable increase in the number of women in this particular category. The overall number of procedures performed per 100,000 population/year in Japan was 0.46. The number of procedures was larger in prefectures with higher populations, with a tendency toward a higher number of MVD procedures performed in the area designated West than in the East. Discharge outcomes indicated that cure and improvement were achieved in 97.6% of cases, with a mortality rate of 0.2%, and no differences in discharge outcomes between men and women. The mean length of hospital stay in patients undergoing MVD for TGN was 14.8 days. This analysis revealed discernable trends in the use of MVD for the treatment of TGN in Japan.

Objective As the extracellular-to-intracellular water (ECW/ICW) ratio of the thigh is negatively associated with knee extension strength or gait speed in the elderly, an increase in the total body ECW/ICW ratio in the elderly is considered to be related to a decrease in physical function. However, these relationships have not been properly investigated. The aim of this study was to investigate the relationship of handgrip strength and gait speed with the total body ECW/ICW ratio in community-dwelling elderly women. Methods The present study used a cross-sectional design. We enrolled 71 community-dwelling women, ≥65 y of age, who could independently perform activities of daily living. The total body ECW/ICW ratio was measured using bioelectrical impedance analysis. Relationships between the total body ECW/ICW ratio and grip strength and gait speed were assessed using Pearson's correlation coefficient. Additionally, stepwise multiple regression analysis was used to identify the factors that were independently associated with handgrip strength and gait speed. The independent variables considered were the total body ECW/ICW ratio, age, body mass index, number of medications, presence of pain, and a history of certain conditions. Results The results indicated that an increased total body ECW/ICW ratio in community-dwelling elderly women was associated with a decreased handgrip strength and gait speed. Furthermore, the total body ECW/ICW ratio was significantly, independently associated with handgrip strength even after adjusting for confounding factors. Conclusion These findings suggest that the total body ECW/ICW ratio may indicate health conditions in community-dwelling elderly women.

Acromegaly is caused by excessive growth hormone secretion, usually from pituitary adenomas. Somoatostatin analogues are widely used as primary or adjunctive therapy in the management of acromegaly. In this report, we present a case with remarkable shrinkage of a tumor after relatively short-term octreotide long-acting release (LAR) administration. During the 30-month follow-up after starting octreotide LAR, there was no recurrence of acromegaly with remarkable shrinkage of the tumor on pituitary magnetic resonance imaging. A literature review of the predictors for tumor shrinkage after the administration of somatostatin analogues in patients with acromegaly is also discussed in relation to this case.

MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our analysis found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the numbers and sizes of colon tumors. These effects were associated with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histological scores and was positively correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Additionally, activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.

To accurately and rapidly screen for higher brain dysfunction, we developed a screening test named the "higher brain dysfunction screening test" (HIBRID-ST). Previous studies have reported a decrease in higher brain function with age. However, whether HIBRID-ST can detect a decrease in higher brain function in healthy persons remains unclear. We aimed to assess the usefulness of HIBRID-ST for evaluating higher brain function in healthy persons. We recruited 60 persons without physiological abnormalities and divided them into six equal groups based on their age (20s-70s). HIBRID-ST addresses orientation, short-term memory, word recall, situational awareness, visual short-term memory, and graphic replication and includes the Trail Making and Kana-hiroi tests. There was a significant negative correlation between the participants' age and their total HIBRID-ST score (ρ = -0.68, p < 0.01). The total HIBRID-ST score of participants in their 70s was significantly lower than that of participants in their 20s-60s; the total HIBRID-ST score of participants in their 60s was significantly lower than that of participants in their 20s-50s. Our findings show that HIBRID-ST accurately detects an age-related decline in higher brain function. Further studies are needed to examine the usefulness of HIBRID-ST in patients with higher brain dysfunction. J. Med. Invest. 64: 280-285, August, 2017.

Background In some patients with acute ischemic stroke, neurological deterioration (ND) is observed, and it is difficult to predict at the time of admission. Especially in some patients with large-artery atherosclerosis (LAA), aggressive medical treatments and surgical interventions might be helpful to prevent ND. Therefore, we investigated factors associated with ND in patients with LAA. Methods We studied patients with LAA who were admitted to our hospital. We divided them into 2 groups with (group 1) and without deterioration (group 2), and evaluated their medical records, risk factors, and radiological findings, such as number of diffusion-positive lesion and degree of stenosis. Results Our study population consisted of 171 patients; 71 (41.5%) did and 100 (58.5%) did not suffer deterioration. By univariate analysis, blood pressure (BP), heart rate, National Institutes of Health Stroke Scale (NIHSS) score, number of diffusion-positive lesion, count of red blood cell, high-density lipoprotein, and degree of stenosis differed significantly between the 2 groups. By multivariate analysis, systolic BP (≥170 mm Hg, odds ratio: 7.20, P .001) was associated with ND. Furthermore, number of diffusion-weighted image (DWI)–positive lesion (≥8), degree of stenosis (>80.0%), and NIHSS score (≥4) were also independent factors associated with ND. Conclusions High BP, severity of neurological deficit at the time of admission, and radiological findings, such as degree of stenosis and number of DWI-positive lesion, are independently associated with ND in patients with LAA.

The Fifth International Conference on Concussion in Sport was held in Berlin in October 2016. A series of 12 questions and subquestions was developed and the expert panel members were required to perform a systematic review to answer each question. Following presentation at the Berlin meeting of the systematic review, poster abstracts and audience discussion, the summary Consensus Statement was produced. Further, a series of tools for the management of sport-related concussion was developed, including the Sport Concussion Assessment Tool Fifth edition (SCAT5), the Child SCAT5, and the Concussion Recognition Tool Fifth edition. This paper elaborates on this process, the outcomes, and explores the implications for neurosurgeons in the management of sport-related concussion.