Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

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 < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Long waiting time before tooth extraction may increase delayed wound healing in elderly Japanese.

In osteoporosis patients receiving antiresorptive medications, stopping the drug and delaying tooth extraction has been suggested to reduce the risk of osteonecrosis of the jaw (ONJ). However, postponing tooth extraction for ≥ 2 months was associated with an increased risk of delayed wound healing beyond 8 weeks after extraction, a risk factor for developing ONJ. INTRODUCTION: A long waiting time before tooth extraction could result from concern about a potential increased risk of osteonecrosis of the jaw (ONJ) in osteoporosis patients. We clarified whether a long waiting time before tooth extraction during the past year may be associated with an increased risk of delayed wound healing beyond 8 weeks after tooth extraction, which may be a risk factor of ONJ. METHODS: Of 5639 patients aged ≥ 60 years who visited our 20 clinics or hospitals and answered a structured questionnaire, 426 patients (151 men, 275 women) aged 60-96 years comprised the final participants in this study. Self-reported kyphosis was used as a surrogate marker of vertebral fractures. Stepwise logistic regression analysis, adjusted for covariates, was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) for the presence of delayed wound healing longer than 8 weeks after tooth extraction during the past year based on the duration before extraction. RESULTS: Subjects who had waited > 2 months for tooth extraction had a significantly higher risk of delayed wound healing compared with those whose tooth was extracted within 1 month (OR = 7.23; 95% CI = 2.19-23.85, p = 0.001) regardless if antiresorptive medications for osteoporosis were used. The presence of self-reported kyphosis was significantly associated with an increased risk of delayed wound healing (OR = 5.08; 95% CI = 1.11-23.32, p = 0.036). CONCLUSIONS: A long waiting time before tooth extraction may be a risk factor for delayed wound healing beyond 8 weeks after extraction in patients aged ≥ 60 years.

Outcomes of grafting intrasynovial tendons of the toes to the hands in 10 patients: a preliminary report.

Ten patients had intrasynovial tendon grafting harvested from the toes for secondary flexor tendon reconstruction in nine fingers and one thumb in our institutes from 2009 to 2014. These patients were followed for a mean of 15 (range: 8-36) months. The ranges of total active motion of the proximal and distal interphalangeal joints of these nine fingers were 143° (range: 108-175°) and of the metacarpophalangeal and interphalangeal joints of one thumb were 110°. In conclusion, this technique is feasible and gives a good result when successful but with a high complication rate. Level of Evidence IV.

Significant improvement of bone mineral density and bone turnover markers by denosumab therapy in bisphosphonate-unresponsive patients.

Bone mineral density (BMD) sometimes cannot be improved by long-term bisphosphonate (BP) therapy in osteoporosis (OP). This study showed that lumbar as well as hip BMD significantly increased after denosumab treatment in patients not responsive to BPs. Thus, denosumab may be a strong OP treatment option for BP-unresponsive patients. INTRODUCTION: BMD sometimes cannot be improved by long-term BP therapy. METHODS: We administered denosumab to osteoporotic patients with a poor response to BPs who had been taking them for 2 years or longer. Ninety-eight women with BP-poor responsive OP were enrolled in this study. Mean (standard deviation [SD]) age was 71.2 (6.9) years and mean (SD) duration of BP treatment was 59.9 (34.3) months. We distinguished BP responders from non-responders based on changes in BMD values at denosumab commencement (baseline) from 2 years beforehand. RESULTS: There were no significant differences in age, duration of BP use, bone turnover markers, or BMD at baseline between the groups. Prior to denosumab, BMD had increased significantly in responders and decreased significantly in non-responders. Bone turnover markers had decreased significantly at 4 months of denosumab treatment (P < 0.001) and lumbar and hip BMD were significantly increased at 1 year of therapy in both groups (P < 0.001). Simple correlation coefficients were -0.337 for lumbar and -0.339 for hip BMD changes (both P = 0.001) before and after denosumab treatment. Both at the lumbar spine and hips, decreased BMD before denosumab therapy was significantly associated with an increase in BMD at 1 year of treatment (spine, t value = -3.502, P = 0.001, R = 0.113; hip, t value = -3.526, P = 0.001, R = 0.115). CONCLUSIONS: These results suggest that denosumab may be a strong OP treatment option for BP-unresponsive patients.

Measurement of residual platelet thrombogenicity under arterial shear conditions in cerebrovascular disease patients receiving antiplatelet therapy.

UNLABELLED: Essentials A consensus methodology for assessing the effects of antiplatelet agents has not been established. Measuring platelet thrombus formation (PTF) for evaluating antiplatelet effects was assessed. PTF differentially reflected antiplatelet effects compared to other tests. PTF may be associated with the severity of carotid or intracranial arterial stenosis. Click to hear a presentation on platelet function testing in the clinic by Gresele and colleagues SUMMARY: Background A consensus methodology for assessing the effects of antiplatelet agents has not been established. Objective We investigated the usefulness of directly measuring platelet thrombus formation (PTF) using a microchip-based flow chamber system for evaluating antiplatelet therapy. Patients/Methods Platelet thrombus formation in the whole blood of 94 patients with ischemic cerebrovascular disease treated with clopidogrel and/or aspirin was measured in a flow chamber system at a shear rate of 1500 s(-1) and was compared with the results of assays for agonist-induced platelet aggregability, phosphorylation of vasodilator-stimulated phosphoprotein, platelet p-selectin expression (PS), and platelet-monocyte complexes. Results In all patients tested, area under the flow pressure curve (AUC10), which represents platelet thrombogenicity, showed weak correlation with platelet aggregation induced by either adenosine diphosphate or collagen. In addition, AUC10 was lower in patients treated with dual antiplatelet therapy (median 79.4) compared with patients treated with aspirin or clopidogrel alone (217.7 and 301.0, respectively), whereas the parameters evaluated by the other assays did not reflect the combined treatment efficacy. In clopidogrel monotherapy patients, AUC10 was associated with the severity of arterial stenosis (R(2) = 0.127, ß = 1.25), and AUC10 and PS were higher in patients with severe carotid or intracranial arterial stenosis than in those with mild stenosis. Conclusions Platelet thrombus formation measurement using a flow-chamber system was useful for evaluating the efficacy of treatment with aspirin and clopidogrel, both alone and in combination. The present findings indicate that high residual platelet thrombogenicity in patients treated with clopidogrel may be associated with the severity of carotid or intracranial arterial stenosis.

Arthroscopic assistance does not improve the functional or radiographic outcome of unstable intra-articular distal radial fractures treated with a volar locking plate: a randomised controlled trial.

There is no consensus on the benefit of arthroscopically assisted reduction of the articular surface combined with fixation using a volar locking plate for the treatment of intra-articular distal radial fractures. In this study we compared the functional and radiographic outcomes of fluoroscopically and arthroscopically guided reduction of these fractures. Between February 2009 and May 2013, 74 patients with unilateral unstable intra-articular distal radial fractures were randomised equally into the two groups for treatment. The mean age of these 74 patients was 64 years (24 to 92). We compared functional outcomes including active range of movement of the wrist, grip strength and Disabilities of the Arm, Shoulder, and Hand scores at six and 48 weeks; and radiographic outcomes that included gap, step, radial inclination, volar angulation and ulnar variance. There were no significant differences between the techniques with regard to functional outcomes or radiographic parameters. The mean gap and step in the fluoroscopic and arthroscopic groups were comparable at 0.9 mm (standard deviation (SD) 0.7) and 0.7 mm (SD 0.7) and 0.6 mm (SD 0.6) and 0.4 mm (SD 0.5), respectively; p = 0.18 and p = 0.35). Arthroscopic reduction conferred no advantage over conventional fluoroscopic guidance in achieving anatomical reduction of intra-articular distal radial fractures when using a volar locking plate.

Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time.

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (SE 0.16)) and the no-ALN group (3.1 months (SE 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.

Usefulness of 4D-CTA in the detection of cerebral dural sinus occlusion or stenosis with collateral pathways.

In time-resolved CT angiography (4D-CTA), it is of substantial merit to detect the veins and sinuses of the whole brain with the simultaneous demonstration of the natural drainage flow in order to find occlusion or stenosis of the dural sinuses with collateral pathways. As preoperative information for patients with brain tumors, it is important to detect feeding arteries, incidentally found aneurysms or other vascular lesions, and to detect patency of the dural sinuses and the important cortical veins, whether they are compressed by tumors or not. On the other hand, cerebral venous thrombosis (CVT) may occur in patients due to various causes, which has not been unusual in recent years. For patients with acute symptomatic or chronic non-symptomatic CVT, identification of dural sinus occlusion (DSO) or dural sinus stenosis (DSS) and compensatory collateral pathways is necessary for suitable thrombolytic therapy or careful investigation to avoid further CVT. This study reviews our experiences in 116 cases of 4D-CTA for 90 patients with brain tumors and 26 other patients including 11 with arteriovenous malformation, and four with acute CVT and other conditions. 4D-CTA presented DSO/DSS with compensatory venous collateral pathways, which was helpful to detect the severity of the venous abnormality, and see whether it was compressed by brain tumors, or due to other causes in patients with symptomatic or non-symptomatic CVT. 4D-CTA is a useful non-invasive diagnostic tool to detect cerebral venous abnormalities as an alternative to DSA.

ASURA (PHB2) interacts with Scc1 through chromatin.

Sister chromatid cohesion mediated by the cohesin complex is essential for faithful chromosome segregation. Previously we reported that PHB2 (prohibitin2/ASURA), a multifunctional protein, has a role in sister chromatid cohesion. Nevertheless, how ASURA is involved in sister chromatid cohesion still remains unclear. The present co-immunoprecipitation analysis reveals that ASURA interacts with cohesin subunit Scc1 in vivo. We show that ASURA associates with chromatin in a similar manner as Scc1 throughout the cell cycle. Furthermore, our observation using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system indicates that ASURA is important for cohesin maintenance at early mitosis. We have also identified that the conserved PHB domain is responsible for chromatin targeting of ASURA. Our results suggest that the regulation of sister chromatid cohesion is mediated by ASURA binding to chromatin, where ASURA might be involved in cohesin protection through ASURA-Scc1 interactions.

Taste disorders in myasthenia gravis: a multicenter cooperative study.

BACKGROUND AND PURPOSE: The purpose of the present study was to investigate the prevalence and clinical characteristics of taste disorders in patients with myasthenia gravis (MG). METHODS: We studied 371 Japanese patients with MG (127 men and 244 women; mean age, 56.6±16.9years) consecutively evaluated between May and September 2010 in six neurological centers comprising the East Japan MG Study Group. Ninety-three patients (25%) had thymoma. We interviewed all patients to determine whether they had taste disorders during the clinical course of MG and then further evaluated the patients with MG, who reported having taste disorders, using a questionnaire. RESULTS: Taste disorders were observed in 16 (4.3%) of the 371 patients with MG. We concluded that taste disorders in 2.4% of patients with MG excluding other factors were associated with MG itself. All patients had thymoma with seropositivity for anti-acetylcholine receptor antibodies. Thymoma tended to be advanced, and four patients with Masaoka stage IVa required radiation therapy or chemotherapy. Five patients noticed taste disorders 2-3 months before the onset of MG. Sweet taste loss was more common than salty, bitter, and sour taste loss. CONCLUSIONS: This was the first systematic survey of taste disorders in patients with MG by a multicenter study. Taste disorders were more common in the present sample of patients with MG than in the general population.

PP139. The elective prematurity birth and its perinatal effects of syndromes in hypertensive pregnancy.

INTRODUCTION: The hypertensive pregnancy disorders affect 7.5% of Brazilian women, being a major cause of maternal and perinatal morbidity and mortality, affecting 6-10% of primigravidae. They represent a significant cause of prematurity birth, with elective responsible for 20-30% of premature births, with higher incidence of neonatal morbidity due to high rates of complications in short and long term. OBJECTIVES: Identify the repercussions in a short time, on caused by elective obstetric parity decisions in women with hypertensive neonatals pregnancy syndromes. METHODS: Retrospective analysis of medical records of pregnant women admitted to Hospital Guilherme Álvaro, in the city of Santos/SP - Brazil, between Jan/2005 to Jan/2012. Calculations were performed for dichotomous variables and an epidemiological analysis with data obtained on pregnant women with hypertension with a single fetus, subjected to delivery before 37 weeks. Classification of Hypertensive Syndromes followed the criteria of the NHBPEP - 2000, after blood pressure measurements were calibrated following standard technique: Chronic hypertension (CH), Pre-eclampsia, superimposed pre-eclampsia and late gestational hypertension and multiple births were excluded, premature labor and fetal malformations, totaling 102 cases. RESULTS: Throughout the study, it was observed that 67.6% are appropriate for gestational age, birth weight 1500-2500grams (43.1%). Support in the neonatal were excluded ICU was necessary in the vast majority (75.7%), and length of stay exceeding 28 days in 29.3% of cases. The main indication was respiratory distress syndrome (63.6%) requiring intubation orotraquel and jaundice in 18.2% of premature infants was a common comorbidity (39.4%). Even with all the support in-hospital, the neonatal mortality was present in 8.1% of cases. The main indication of the resolution was for obstetric maternal complications (61.8%) where pre-eclampsia and preeclampsia superimposed were expressions which caused more frequent (42.2 and 40.2% respectively), showing the level of proteinuria between two -4.9g (32.1%). Gestational age at delivery was 32-34 weeks (43.1%), corticosteroid therapy was not performed (54.9%) and cesarean delivery was (94.1%). The most frequent age group was 20-34 years (53.9%), Caucasian (54.9%), primigravida (62.7%) and less than five prenatal visits (36.3%) were performed. CONCLUSION: The hypertensive pregnancy are risk factors for preterm elective delivery and is more frequent before 34 weeks, resulting in high perinatal morbidity and mortality, especially in cases of preeclampsia with severe clinical presentation and long hospital stays, with consequent costs and conducting excessive procedures in the neonate. Enable early referral to specialist services and consequent prenatal follow up, enables the adoption of early action, such as clinical support in a timely manner to facilitate the handling of cases which are still stable, optimizing the opportunity for administration of antenatal corticosteroids. It is necessary to review decisions about the mode of delivery in prematurity related to hypertension cases, with the aim of increasing the occurrence of vaginal deliveries.

Acute CO2-independent vasodilatation of penetrating and pre-capillary arterioles in mouse cerebral parenchyma upon hypoxia revealed by a thinned-skull window method.

AIM: Investigating spatio-temporal relationship between regional metabolic changes and microvascular responses in hypoxic brain is critical for unravelling local O(2) -sensing mechanisms. However, no reliable method to examine the relationship has been available because of inherent disadvantages associated with use of a conventional cranial window preparation. We aimed to devise a method to solve the problem. METHODS: Anaesthetized mice were equipped with either a conventional cranial window with craniotomy or a thinned-skull preparation. Mice were mechanically ventilated to avoid hypercapnia and exposed to systemic isobaric hypoxia for 30 min. Using two-photon laser scanning microscopy, nicotinamide adenine dinucleotide, reduced form (NADH) autofluorescence and diameter changes in penetrating and pre-capillary arterioles within the parenchyma were visualized to examine their temporal alterations. RESULTS: With the conventional cranial window preparation, marked vertical displacement of the tissue occurred through oedema within 30 s after inducing hypoxia. With a thinned-skull preparation, however, such hypoxia-induced displacement was diminished, enabling us to examine acute spatio-temporal changes in diameters of penetrating and pre-capillary arterioles and NADH autofluorescence. Vasodilatation of these microvessels was evoked within 1 min after hypoxia, and sustained during the entire observation period despite the absence of hypercapnia. This event coincided with parenchymal NADH elevation, but the onset and peak dilatory responses of the penetrating arterioles preceded the local metabolic response of the parenchyma. CONCLUSION: Observation of hypoxia-exposed brain by the thinned-skull preparation combined with two-photon intra-vital microscopy revealed rapid vasodilatory responses in penetrating arterioles preceding parenchymal NADH elevation, suggesting the presence of acute hypoxia-sensing mechanisms involving specific segments of cortical arterioles within the neurovascular unit.

Differences in odor identification among clinical subtypes of Parkinson's disease.

OBJECTIVE: Olfactory dysfunction is a non-motor symptom in idiopathic Parkinson's disease (PD). We investigated whether this dysfunction differs among clinical subtypes of PD. METHODS: Participants comprised of 90 patients with idiopathic PD and without dementia. Olfactory function was evaluated using the odor stick identification test for Japanese, which evaluated the detection of 12 odorants familiar to Japanese participants. Patients were divided into tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT) PD subgroups using part III of the Unified Parkinson's Disease Rating Scale. RESULTS: Fifty-five patients were classified as ART, 21 as MXT, and 14 as TDT. There were no differences in age, sex, or duration of illness among the subtypes. Subjective symptoms of impaired sense of smell were significantly higher (P<0.05) in the ART than in the TDT. Mean odor identification score was 4.3 in the ART, 5.2 in MXT, and 6.6 in TDT. It was significantly lower in the ART than in the TDT (P<0.01). CONCLUSION: Olfactory dysfunction differed among the clinical subtypes of PD. This suggests that olfactory function might relate to prognosis of patients with PD.

Carpal tunnel pressure measurement during two-portal endoscopic carpal tunnel release.

BACKGROUND: Although there remain concerns of median nerve damage during endoscopic carpal tunnel release for carpal tunnel syndrome, carpal tunnel pressure variations during Chow's two-portal technique have not been well investigated. METHODS: We performed a modified two-portal endoscopic carpal tunnel release on 30 patients by inserting a catheter pressure transducer into the carpal tunnel for continuous pressure measurement during the procedure. Grip and pinch strengths, Semmes-Weinstein monofilament test, and nerve conduction studies were examined preoperatively and at postoperative 1, 3, and 6 months. Numbness and the Disabilities of the Arm, Shoulder and Hand score were also evaluated pre and postoperatively. FINDINGS: Subjective symptoms and nerve conduction study findings improved uneventfully. The pressure was always observed to be maximum pressure immediately before the cannula was withdrawn from the exit portal, and carpal tunnel pressure >300 mm Hg was recorded in most of the patients. INTERPRETATION: A transient increase in the carpal tunnel pressure occurred in all the patients; however, it did not correlate with their clinical outcome or with increased risk of peri-operative complications. Since time-pressure threshold of the median nerve during endoscopic carpal tunnel release is still unknown, our results did not guarantee its safety.

Riluzole use during pregnancy in a patient with amyotrophic lateral sclerosis: a case report.

Pregnancy with amyotrophic lateral sclerosis (ALS) is rare and generally considered dangerous. Riluzole is the only drug approved for use in ALS, but the effect on maternal and fetal health is unknown. We describe the case of an ALS patient taking riluzole throughout pregnancy. A 34-year old Japanese woman, who had been diagnosed with probable ALS 4 years earlier, visited our hospital for abdominal distension, without knowing that she was pregnant. The patient had been taking riluzole for 2 years, inclusive of her gestational months, and we decided to continue administration of the medication. The patient delivered a normal female infant transvaginally at 38 weeks gestation. The patient's neurological status was stable 1 year after delivery and the baby had developed normally. We found that, in this case, riluzole did not cause any side-effects to the pregnant woman or her fetus.

Correlation between Magnetic Resonance Imaging Findings and Pathological Observations in Tumefactive Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Tumefactive MS (TMS) is a subtype of MS characterized by solitary or multiple mass lesions with open-ring enhancement on brain magnetic resonance imaging (MRI). Three TMS cases, diagnosed histopathologically by brain biopsy, that were difficult to distinguish from brain tumors or brain abscesses on MRI are presented. On T2-weighted imaging (T2WI) the lesions were high intensity in the center and periphery, with open-ring contrast enhancement at the periphery; iso- to low intensity areas ("T2 low rim") were seen in the surrounding region. Histopathological examination revealed the characteristic features of TMS: severe central demyelination and focal necrosis, peripheral neovascularization and perivascular inflammatory cell infiltration, and perifocal edema. On immunochemistry, both the endothelial cells of the neovasculature and the surrounding macrophages in the periphery expressed vascular endothelial growth factor and monocyte chemoattractant protein-1, which mediate inflammation and angioneogenesis and increase vascular permeability. These findings correspond to the T2 low rim co-localizing with the site of gadolinium enhancement on MRI. Thus, the present study clearly demonstrates the correlation between the radiological features and the pathophysiological aspects of TMS, which may contribute to more precise diagnosis of TMS.

Extensor tendon rupture associated with osteoarthritis of the distal radioulnar joint.

Non-rheumatoid osteoarthritis of the distal radioulnar joint can cause extensor tendon rupture. We analysed the radiographic morphology of the distal radioulnar joint to identify the risk factors for this complication. Forty-one wrist X-rays of 37 patients with extensor tendon rupture caused by distal radioulnar joint osteoarthritis were evaluated retrospectively for the severity of osteoarthritis by the Kellgren/Lawrence scoring system. Measurements were obtained from posteroanterior views. All but one wrist had severe osteoarthritic changes exceeding grade 3. The radiographic features that were different from those of the contralateral wrists included deepening and widening of the sigmoid notch, radial shift of the ulnar head and dorsal inclination of the sigmoid notch. There was no significant association between tendon rupture and the morphology of the ulnar head or ulnar variance. The scallop sign, dorsal inclination of the sigmoid notch and radial shift of the ulnar head are radiological risk factors for extensor tendon ruptures.