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Intracerebral hemorrhage (ICH) is a common and severe neurological disorder associated with high morbidity and mortality rates. Despite extensive research into its pathology, there are no clinically approved neuroprotective treatments for ICH. Increasing evidence has revealed that inflammatory responses mediate the pathophysiological processes of brain injury following ICH. Experimental ICH was induced by direct infusion of 100 μL fresh (non‐heparinized) autologous whole blood into the right basal ganglia of Sprague–Dawley rats at a constant rate (10 μL/min). The simvastatin group was administered simvastatin (15 mg/kg) and the combination therapy group was administered simvastatin (10 mg/kg) and ezetimibe (10 mg/kg). Magnetic resonance imaging (MRI), the forelimb use asymmetry test, the Morris water maze test, and two biomarkers were used to evaluate the effect of simvastatin and combination therapy. MRI imaging revealed that combination therapy resulted in significantly reduced perihematomal edema. Biomarker analyses revealed that both treatments led to significantly reduced endothelial inflammatory responses. The forelimb use asymmetry test revealed that both treatment groups had significantly improved neurological outcomes. The Morris water maze test revealed improved neurological function after combined therapy, which also led to less neuronal loss in the hippocampal CA1 region. In conclusion, simvastatin–ezetimibe combination therapy can improve neurological function, attenuate the endothelial inflammatory response and lead to less neuronal loss in the hippocampal CA1 region in a rat model of ICH.

Cheng-Loong Liang,1,2 Shih-Wei Wang,1,3 Han-Jung Chen,1,2 Yu-Duan Tsai,1,2 Jui-Sheng Chen,1,2 Hao-Kuang Wang,1,2 Kuo-Wei Wang2,4 1Department of Neurosurgery, E-DA Hospital, Kaohsiung, Taiwan; 2School of Medicine, I-Shou University, Kaohsiung, Taiwan; 3Department of Rheumatology, E-DA Hospital, Kaohsiung, Taiwan; 4Department of Neurosurgery, E-Da Cancer Hospital, Kaohsiung, TaiwanCorrespondence: Kuo-Wei Wang Email wang11290713@hotmail.com.twBackground: After proper patient selection, anatomically correct pulsed radiofrequency of the lumbar facet joints provide long-term pain relief in a routine clinical setting. In the study, we performed an analysis of clinical and radiological predictive factors and provide the scientific basis for this promising modality.Methods: The study included 198 patients with lower back pain due to lumbar facet joint disease who underwent medial branch block and pulsed radiofrequency during the period 2015– 2019. According to the improvement in pain score, the patients were divided into good and poor outcome groups. Clinical and radiological data were collected and analyzed.Results: The multivariable analysis revealed the predictive factors, including lumbar lordosis, lower lumbar lordosis, pelvic tilt, the number of facet joints, old compression fracture with/without vertebroplasty, and post lumbar fusion procedures.Conclusion: With the results of this study, we demonstrated that the improved outcome after the surgery was related to lumbar lordosis, lower lumbar lordosis, pelvic tilt, the number of facet joints, old compression fracture with/without vertebroplasty, and the lumbar fusion procedures. Old compression fractures and lumbar fusion would change the radiological factors and cause refractory lumbar facet joint pain.Keywords: lumbar facet joint pain, pulsed radiofrequency, lumbar lordosis, lower lumbar lordosis, pelvic tilt angle, lumbar fusion

ObjectivesThe present nationwide population-based cohort study aims to assess the effectiveness of gamma knife radiosurgery (GKS) on ruptured and unruptured brain arteriovenous malformations (AVMs) by evaluating the haemorrhage rates.DesignA nationwide, retrospective cohort study.SettingTaiwan National Health Insurance Research Database (NHIRD).ParticipantsAn observational study of 1515 patients who were diagnosed with brain AVMs between 1997 and 2013 from the Taiwan NHIRD.Primary outcome and secondary outcome measuresWe performed a survival analysis using the Kaplan-Meier method. Multivariate Cox proportional hazards regression models were used to explore the relationship between treatment modalities (GKS vs non-GKS) and haemorrhage, adjusted for age and sex.ResultsThe GKS and non-GKS groups included 317 and 1198 patients, respectively. Patients in the GKS group (mean±SD, 33.08±15.48 years of age) tended to be younger than those in the non-GKS group (37.40±17.62) (p40 years of age (aHR 3.21; 95% CI 1.12 to 9.14).ConclusionsGKS is safe and it reduces the risk of haemorrhage in patients with ruptured AVMs. The administration of GKS to patients with unruptured AVMs who are above the age of 40 years old male might increase the risk of haemorrhage.

Olfactory dysfunction is related to several clinical neurodegenerative diseases, such as Alzheimer’s disease, multiple sclerosis, degenerative ataxias, Parkinson’s disease, and so on. Owing to the individual difference in the sensory adaption of human smell function, the olfactory responses usually exhibit large inter-individual difference and change over time after repeated stimulations. The traditional analysis tools, such as statistical parametric mapping (SPM) in functional magnetic resonance imaging technique (fMRI) analysis, utilize the paradigm-based linear correlation and statistical techniques to discriminate the activation areas from background activities. However, these traditional approaches extract olfactory-induced responses using the stereotypic template or paradigm generated model. The olfactory-induced hemodynamic responses affected by internal/external events, such as changes of smell fatigue and attention, are not considered and therefore could result in misleading results. In this paper, owing to the stochastic characteristic of olfactory-induced responses, we adopted multivariate empirical mode decomposition (MEMD) to extract olfactory-induced hemodynamic responses in MRI blood-oxygen-level dependent (BOLD) signals. The MEMD is an efficient data-driven approach to extract nonlinear and non-stationary signals, which is an improved method to expand traditional empirical mode decomposition (EMD) from one channel to multi-channel processing. We applied MEMD to decompose time series of BOLD signals from each slice into multivariate intrinsic mode functions (IMF). The MEMD enables common features of different scales in an image slice to be arranged in distinct IMFs. Each IMF is an analytic, self-constructed, well-defined, and data-driven function with time-varying frequencies. Each IMF was examined by checking its correlation with the paradigm-generated template. The task-related IMFs were chosen to reconstruct olfactory-induced hemodynamic responses. The group analysis of MEMD-processed data showed olfactory-induced activations in the anterior cingulate cortex and middle frontal gyrus.

This population-based study was designed to estimate and compare the risk of Alzheimer’s disease (AD) between patients with primary Sjögren’s syndrome (SS) and non-SS patients during a 10-year follow-up period. This is a retrospective cohort study. Data were obtained from the Taiwan’s National Health Insurance Research Database. We identified 4463 primary SS patients and 22,315 non-SS patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied to identify the subsequent manifestation of AD. Cox proportional hazard regression was used to study the subsequent manifestation of AD, and Kaplan-Meier survival curves were used to compare survival probability. During the 10-year follow-up period, 7 primary SS and 13 non-SS patients developed AD. During the 10-year follow-up period, the risk of AD was 2.68-fold higher in the primary SS cohort with an overall adjusted hazard ratio (HR) of 2.69 (95% CI 1.07–6.76), after adjusting for demographics and comorbidities. Within the 10-year period, patients with primary SS showed a 2.69-fold increased risk of developing AD. This risk increases with time, and the relative risk of AD is higher in older patients with primary SS.

Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in traditional medicine. Previous findings have shown that the extracts of Pluchea indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis activity. The aim of this study was to demonstrate the anticancer activity of the hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells using flow cytometric and western blot analysis. The results shoewd that, H-PIRE suppressed the growth of glioblastoma cells in a dose-dependent manner. H-PIRE treatment markedly decreased the population of cells in S and G2/M phases. The significant upregulation of acidic vesicular organelle (AVO) was detected during H-PIRE treatment. The expression levels of microtubule-associated light chain 3-II (LC3-II) protein, phosphorylated JNK and phosphorylated p38 were significantly increased, confirming the occurrence of autophagy during the process. Finally, the combination treatment of H-PIRE and LY294002, a pan PI3K inhibitor, further decreased cell viability, suggesting an additive anticancer effect. Taken together, our results suggest that H-PIRE suppresses the proliferation of glioblastoma cells by inducing cell cycle arrest and autophagy.

During a spinal cord injury (SCI), mechanical trauma rapidly leads to a blood-spinal cord barrier (BSB) disruption, neural cell damage, axonal damage, and demyelination, followed by a cascade of secondary inflammatory reactions. These inflammatory responses spread the damage to the neural cells and impair the recovery of neurological functions. In the present study, we evaluated the efficacy of simvastatin and a simvastatin-ezetimibe combination therapy in managing the endothelial inflammatory response in an SCI rat model. Adult male Sprague-Dawley rats were group-housed and SCI was induced by using the modified weight-drop method. The animals were divided into 4 groups: (1) sham group, laminectomy only (n=6); (2) no-treatment group, SCI without therapy (n=8); (3) simvastatin group (n=8), and (4) ezetimibe and simvastatin combination therapy group (n=8). A high dose (15 mg/kg) of simvastatin was given to the simvastatin group, and 10 mg/kg simvastatin and 10 mg/kg ezetimibe were given to the combination group. Neurological function was assessed using the Basso, Beattie, and Bresnahan locomotor scale score. Intercellular adhesion molecule-1 (ICAM-1) level was used as an SCI biomarker. ICAM-1 level was the highest at 72 hours after SCI in the no-treament group. The treatment groups showed significant reduction in ICAM-1 levels at 72 hours. The treatment groups, especially the combination treatment group, showed better neurological function scores. Simvastatin and simvastatin- ezetimibe all could improve the neurological function and attenuate the endothelial inflammatory response after spinal cord injury in rat.

OBJECTMultilevel long-segment lumbar fusion poses a high risk for future development of adjacent-segment degeneration (ASD). Creating a dynamic transition zone with an interspinous process device (IPD) proximal to the fusion has recently been applied as a method to reduce the occurrence of ASD. The authors report their experience with the Device for Intervertebral Assisted Motion (DIAM) implanted proximal to multilevel posterior lumbar interbody fusion (PLIF) in reducing the development of proximal ASD.METHODSThis retrospective study reviewed 91 cases involving patients who underwent 2-level (L4–S1), 3-level (L3–S1), or 4-level (L2–S1) PLIF. In Group A (42 cases), the patients received PLIF only, while in Group B (49 cases), an interspinous process device, a DIAM implant, was put at the adjacent level proximal to the PLIF construct. Bone resection at the uppermost segment of the PLIF was equally limited in the 2 groups, with preservation of the upper portion of the spinous process/lamina and the attached supraspinous ligament. Outcome measures included a visual analog scale (VAS) for low-back pain and leg pain and the Oswestry Disability Index (ODI) for functional impairment. Anteroposterior and lateral flexion/extension radiographs were used to evaluate the fusion status, presence and patterns of ASD, and mobility of the DIAM-implanted segment.RESULTSSolid interbody fusion without implant failure was observed in all cases. Radiographic ASD occurred in 20 (48%) of Group A cases and 3 (6%) of Group B cases (p < 0.001). Among the patients in whom ASD was identified, 9 in Group A and 3 in Group B were symptomatic; of these patients, 3 in Group A and 1 in Group B underwent a second surgery for severe symptomatic ASD. At 24 months after surgery, Group A patients fared worse than Group B, showing higher mean VAS and ODI scores due to symptoms related to ASD. At the final follow-up evaluations, as reoperations had been performed to treat symptomatic ASD in some patients, significant differences no longer existed between the 2 groups. In Group B, flexion/extension mobility at the DIAM-implanted segment was maintained in 35 patients and restricted or lost in 14 patients, 5 of whom had already lost segmental flexion/extension mobility before surgery. No patient in Group B developed ASD at the segment proximal to the DIAM implant.CONCLUSIONSProviding a dynamic transition zone with a DIAM implant placed immediately proximal to a multilevel PLIF construct was associated with a significant reduction in the occurrence of radiographic ASD, compared with PLIF alone. Given the relatively old age and more advanced degeneration in patients undergoing multilevel PLIF, this strategy appears to be effective in lowering the risk of clinical ASD and a second surgery subsequent to PLIF.

Background To investigate the association between primary insomnia and dementia using a Taiwanese population-based database. Methods This case-control study involved a subset of Taiwan’s National Health Insurance Research Database of reimbursement claims. We included 51,734 patients who were diagnosed with primary insomnia from 2002 to 2004 as the test group and 258,715 nonprimary insomnia participants aged 20 years or older as the reference group. We excluded patients under 20 and those with depression, post-traumatic stress disorder, and/or sleep disorders caused by organic lesion(s), drugs, or alcohol. We used a Cox proportional hazards model to assess the primary insomnia on the risk of developing dementia after adjusting for sociodemographic characteristics and comorbidities. Results The primary insomnia cohort had a higher prevalence of diabetes, dyslipidemia, hypertension, coronary heart disease, chronic liver disease, and chronic kidney disease at baseline. After adjusting for select comorbidities, primary insomnia remained a significant predisposing factor for developing dementia, and was associated with a 2.14-fold (95% confidence interval, 2.01–2.29) increase in dementia risk. We also found a higher risk of dementia in younger patients. Conclusions Taiwanese patients with primary insomnia, especially those under 40, had a higher risk of developing dementia than those without primary insomnia.

Event-related desynchronization/synchronization (ERD/ERS) is a technique to quantify subject's nonphase-locked neural activities underlying specific frequency bands, reactive to external/internal stimulus. However, conventional ERD/ERS studies usually utilize fixed frequency band determined from one or few channels to filter whole-head EEG/MEG data, which may inevitably include task-unrelated signals and result in underestimation of reactive oscillatory activities in multichannel studies. In this study, we adopted multivariate empirical mode decomposition (MEMD) to extract beta-related oscillatory activities in performing self-paced right and left index-finger lifting tasks. The MEMD extracts common modes from all channels in same-index intrinsic mode functions (IMFs) which allows the temporal-frequency features among different channels can be compared in each subband. The beta-band oscillatory activities were further bandpass filtered within trial-specific beta bands determined from sensorimotor-related channels (C3 and C4), and then rectified using amplitude modulation method to detect trial-by-trial beta rebound (BR) values in ERS time courses. The validity of the MEMD approach in BR values extraction has been demonstrated in multichannel EEG study which showed larger BR values than conventional ERS technique. The MEMD-based method enables the trial-by-trial extraction of sensorimotor oscillatory activities which might allow the exploration of subtle brain dynamics in future studies.

C2 vertebroplasty is more challenging than transpedicular percutaneous vertebroplasty in the thoracic and lumbar spine.We report an anterior ascending approach for C2 percutaneous vertebroplasty to avoid potential injury to vital structures surrounding the C2 vertebra.A technique note with 5 consecutive cases.Neurosurgery department of a university hospital.Fluoroscopically guided manual compression was applied using 3 fingers at the C5 level between the muscle and trachea. The larynx and trachea were displaced medially and the carotid artery laterally. The anterior cervical spine was palpated, and a 15-gauge 4-inch bone marrow biopsy needle was introduced through an anterior ascending approach. When the tip touched the intervertebral disc between C2 and C3, the needle was pushed through the disc until it penetrated into the C2 vertebral body. After confirming adequate needle insertion, vertebroplasty was performed.Pain relief was achieved in 4/5 (80%) patients. One patient possibly did not benefit from percutaneous vertebroplasty, and asymptomatic cement extravasation was detected in 2 patients.Sample size; impossibility of placebo control.An anterior ascending approach for C2 percutaneous vertebroplasty is a valuable alternative for relieving pain caused by metastatic spinal tumors. This approach is familiar to surgeons performing anterior cervical discectomies, percutaneous nucleoplasty, or odontoid screw placement surgeries.Vertebroplasty, pain, axis, cement leak, metastases, palliative medicine, spine, fracture.

SummaryBackgroundThe efficacy of PRF for lumbar facet joint pain is not well established because comparative studies with other modes of management are sparse.AimThe purpose of this study was to compare the efficacy of conventional radiofrequency (CRF) and pulsed radiofrequency (PRF) denervation in the treatment of lumbar facet joint pain.MethodsLumbar facet joint pain was confirmed in 40 patients undergoing double medial branch blocks. Among them, 16 patients received CRF for pain management and 18 patients were offered PRF. Outcome was assessed before treatment and 3 months and 6 months after treatment. Changes in pain intensity were evaluated using a visual analog scale (VAS). Physical functioning was evaluated using a Revised Oswestry Disability Index (ODI).ResultsIn the CRF group, the VAS scores after treatment were significantly lower than before treatment at 3 months (p

Summary Background Percutaneous vertebroplasty has gained widespread popularity to treat painful osteoporotic vertebral compression fractures (VCFs). Radiation exposure during these operations has become the major concern in recent years. Aims Traditional percutaneous vertebroplasty for VCFs is associated with high operator radiation exposure. However, these procedures can be performed by fluoroscopy-based image guidance, which decreases the radiation exposure during vertebroplasty for VCFs. Methods The study subjects were divided into two groups: one underwent traditional vertebroplasty and the other had the C-Arm fluoroscopy-based, image-guided procedure. Four patients in the first group underwent traditional vertebroplasty using repeated intermittent anteroposterior and lateral fluoroscopy to position the cannula used for the vertebroplasty. Six patients in the second group had C-Arm fluoroscopy-based, image-guided surgery. The dose area product values, obtained by thermoluminescent dosimeters, were measured in both groups. Results The accuracy of the non-invasive fluoroscopy-based image-guided surgery was high, with a maximum error of 2 mm. The mean dose area product values of the operator’s eyes, hands, neck and chest were 20.28 mGy, 20.34 mGy, 21.87 Gy and 18.27 mGy in the first group, and 3.51 mGy, 3.70 mGy, 3.02 mGy and 3.68 mGy in the second group, respectively, with fluoroscopy-based, image-guided surgery; the differences were statistically significant ( p Conclusion The results of this preliminary study showed that noninvasive, fluoroscopy-based, image-guided surgery was accurate and was associated with reduced radiation exposure to medical personnel during percutaneous vertebroplasty procedures for VCFs.

Objective. The present study was performed to ascertain whether sacroiliac joint (SIJ) pain represents a potential source of pain in patients who have undergone lumbar or lumbosacral fusions. Design. Prospective cohort study. Patients and Methods. Between June 2007 and June 2009, 130 patients who underwent lumbar or lumbosacral fusions were evaluated for SIJ pain. Fifty-two patients for whom positive findings were obtained on at least three of the provocating tests for SIJ pain were selected to receive dual diagnostic blocks. Outcome Measures. A positive response was defined as characteristic pain reduction of 75% for 1–4 hours following the SIJ blocks. Predictive factors for a positive response to the SIJ blocks were also investigated. Results. Among the 52 patients, 21 were considered to have SIJ pain on the basis of two positive responses to diagnostic blocks. Univariate analysis revealed that the predictive factors related to positive responses were unilateral pain ( P = 0.002), more than three positive responses to provocating maneuvers ( P = 0.02), and postoperative pain with characteristics different from those of preoperative pain ( P = 0.04). Conclusions. SIJ pain is a potential source of pain after lumbar and lumbosacral fusion surgeries. Provocating SIJ maneuvers represent reliable tests for SIJ pain. The characteristics of postoperative SIJ pain frequently differ from those of preoperative pain.

Objective. To compare the efficacy of percutaneous vertebroplasty (PV) with conservative therapy for patients with acute vertebral compression fractures. Design. Prospective, nonrandomized, comparison study. Background. The efficacy of PV has not been well established because there have been few comparative studies with conservatively treated control groups. Patients and Methods. Fifty-five consecutive patients (8 men and 47 women, age 47–94) with osteoporosis and symptomatic acute vertebral compression fractures were enrolled. Thirty-two patients received PV, whereas 23 received conservative therapy. Outcome Measures. Changes in pain intensity, physical functioning, and pain medication requirement were evaluated. Results. Both PV and conservative therapy provided pain reduction ( P < 0.001), improvements in physical functioning ( P < 0.001), and decreased medication ( P < 0.001). Reductions in visual analogue pain scores were more significant in the vertebroplasty group at 1 ( P < 0.001) and 4 weeks ( P < 0.001) but not at 12 months. Improvements in physical functioning were significant at 1 ( P < 0.001) and 4 weeks ( P < 0.001). Medication requirements were lower in the vertebroplasty group at all three time points. Conclusions. Pain relief, physical functioning improvement, and medication requirement after vertebroplasty are immediately and significantly better when compared with conservative therapy.

To derive an optimal strategy for reservoir operations to assist the decision-making process, we propose a methodology that incorporates the constrained genetic algorithm (CGA) where the ecological base flow requirements are considered as constraints to water release of reservoir operation when optimizing the 10-day reservoir storage. Furthermore, a number of penalty functions designed for different types of constraints are integrated into reservoir operational objectives to form the fitness function. To validate the applicability of this proposed methodology for reservoir operations, the Shih-Men Reservoir and its downstream water demands are used as a case study. By implementing the proposed CGA in optimizing the operational performance of the Shih-Men Reservoir for the last 20 years, we find this method provides much better performance in terms of a small generalized shortage index (GSI) for human water demands and greater ecological base flows for most of the years than historical operations do. We demonstrate the CGA approach can significantly improve the efficiency and effectiveness of water supply capability to both human and ecological base flow requirements and thus optimize reservoir operations for multiple water users. The CGA can be a powerful tool in searching for the optimal strategy for multi-use reservoir operations in water resources management.

Dear editor We read with great interest the article by Liang et al “Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study”.1 In their study, the authors investigated the factors possibly associated with new vertebral compression fractures in patients who previously had vertebral augmentation procedures. They reported that osteoporosis (OP) was not observed as a risk factor for repeat vertebral augmentation. Among multiple chronic diseases, hypertension (HT) was reported as one factor associated with new vertebral fractures. Among the medications used to treat or prevent OP, they reported calcium/vitamin D, bisphosphonates, and calcitonin were associated with not having repeat vertebral augmentation. However, steroids, paracetamol, and nonsteroidal anti-inflammatory drugs were associated with having repeat vertebral augmentation. We would like to comment on their article. The authors described OP as a bone mineral density (BMD) of 2.5 standard deviations below the mean peak bone mass as measured by dual-energy X-ray absorptiometry. However, the National Osteoporosis Foundation reported the diagnosis of OP as low BMD measurements or the occurrence of adulthood hip or vertebral fracture in the absence of major trauma.2 Vertebral compression fractures would be the only indicator of OP in patients with normal BMD scores. This might have led to underdiagnosis of OP. Furthermore, both vertebral degenerative changes and fractures may cause misinterpretation of BMD scores as normal when there is significant OP. We suggest that using “low BMD score” would be better than “OP” as nonassociated with new vertebral compression fracture. In line with our comments, Table 2 shows that 34,500 patients have a diagnosis of OP; however, as indicated in Table 3, 57,568 patients are undergoing treatment for OP. This inconsistency could mean that the rate of OP is more than determined in this study. It may also mean that multiple OP medications were used concomitantly by some of the patients. This point should be clarified. The authors reported that the HT and diabetes mellitus were associated with repeat vertebral augmentation. However, it is not discussed how HT may be related to repeat vertebral augmentation. In the elderly, one of the important factors underlying falls may be overtreatment of HT leading to hypotension and/or orthostatic hypotension and consequent falls.3,4 Consideration of patients with low blood pressure levels or clinically significant orthostatism on antihypertensive medications would help the authors to interpret this association. Another factor that would be associated with having repeat vertebral augmentation is “falls” which could not be estimated in this study database. It would be useful to search “vertigo” or “syncope” as a predisposing risk factor for falling.5 Although it is rarely diagnosed on clinical grounds, sarcopenia is prevalent in elderly people (between 3% and 52%).6 Sarcopenia is commonly seen in patients with dementia, cerebrovascular accidents, and diabetes, and is a strong risk factor for both OP and falls.2,7 We suggest that sarcopenia which is not included in the discussion, should be considered as an important factor underlying the increased risk of vertebral augmentation in these patients. Finally, regarding the association between the use of analgesics and repeat vertebral augmentation, the authors discussed that the increase in fracture risk in these patients may stem from changes in postural balance or dizziness (a side effect of nonsteroidal anti-inflammatory drugs). In this regard, dizziness is not a known adverse event associated with paracetamol. Therefore, we suggest that there may be an indirect association between analgesics, in particular paracetamol, and repeat vertebral augmentation: patients having more severe fractures and more severe pain might have used these agents more frequently. It is also possible that subjects having pain more commonly visited their physician and pain could be a common indication for repeat vertebral augmentation procedures. We suggest that the findings of the present study should be interpreted in view of aforementioned considerations.

Background Auditory steady-state response (ASSR) induced by repetitive auditory stimulus is commonly used for audiometric testing. ASSR can be measured using electro-encephalography (EEG) and magnetoencephalography (MEG), referred to as steady-state auditory evoked potential (SSAEP) and steady-state auditory evoked field (SSAEF), respectively. However, the signal level of SSAEP and SSAEF are weak so that signal processing technique is required to increase its signal-to-noise ratio. In this study, a complementary ensemble empirical mode decomposition (CEEMD)-based approach is proposed in MEG study and the extraction of SSAEF has been demonstrated in normal subjects and tinnitus patients. Methods The CEEMD utilizes noise assisted data analysis (NADA) approach by adding positive and negative noise to decompose MEG signals into complementary intrinsic mode functions (IMF). Ten subjects (five normal and five tinnitus patients) were studied. The auditory stimulus was designed as 1 kHz carrier frequency with 37 Hz modulation frequency. Two channels in the vicinities of right and left temporal areas were chosen as channel-of-interests (COI) and decomposed into IMFs. The spatial distribution of each IMF was correlated with a pair of left- and right-hemisphere spatial templates, designed from each subject’s N100m responses in pure-tone auditory stimulation. IMFs with spatial distributions highly correlated with spatial templates were identified using K-means and those SSAEF-related IMFs were used to reconstruct noise-suppressed SSAEFs. Results The current strengths estimated from CEEMD processed SSAEF showed neural activities greater or comparable to those processed by conventional filtering method. Both the normal and tinnitus groups showed the phenomenon of right-hemisphere dominance. The mean current strengths of auditory-induced neural activities in tinnitus group were larger than the normal group. Conclusions The present study proposes an effective method for SSAEF extraction. The enhanced SSAEF in tinnitus group echoes the decreased inhibition in tinnitus’s central auditory structures as reported in previous studies.

Cheng-Loong Liang,1 Hao-Kwan Wang,1 Fei-Kai Syu,2 Kuo-Wei Wang,1 Kang Lu,1 Po-Chou Liliang1 1Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 2Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan Purpose: Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation.Methods: We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD) of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure) and repeat vertebral augmentation. Kaplan–Meier and stratified Cox proportional hazard regressions were performed for analyses.Results: The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10–2.36), advanced age (AOR=1.60; 95% CI: 1.32–2.08), diabetes mellitus (AOR=4.31; 95% CI: 4.05–5.88), cerebrovascular disease (AOR=4.09; 95% CI: 3.44–5.76), dementia (AOR=1.97; 95% CI: 1.69–2.33), blindness or low vision (AOR=3.72; 95% CI: 2.32–3.95), hypertension (AOR=2.58; 95% CI: 2.35–3.47), and hyperlipidemia (AOR=2.09; 95% CI: 1.67–2.22). Patients taking calcium/ vitamin D (AOR=2.98; 95% CI: 1.83–3.93), bisphosphonates (AOR=2.11; 95% CI: 1.26–2.61), or calcitonin (AOR=4.59; 95% CI: 3.40–5.77) were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32–8.08), acetaminophen (AOR=3.54; 95% CI: 2.75–4.83), or nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR=6.14; 95% CI: 5.08–7.41) were more likely to undergo repeat vertebral augmentation.Conclusion: We conclude that the incidence of repeat vertebral augmentation is rather high. An understanding of risk factors predicting repeat vertebral augmentation provides valuable basis to improve health care for geriatric populations. Keywords: vertebroplasty, kyphoplasty, comorbidity, bisphosphonate, old ageTwo Letters to the Editor have been recieved and publishedÄ°lhan et alWilson et al&nbsp

Owing to the diversity in cause and damage, there is no standard surgical treatment method for a complicated penetrating craniofacial injury. The treatment of a complicated penetrating head injury caused by a steel bar is presented here. A 66-year-old woman fell onto a steel bar at a construction site and it penetrated the mandible, entered the sinus and orbital cavities, and reached the base of the frontal bone. A multi-disciplinary team including a neurosurgeon, otolaryngologist, and plastic surgeon was involved in removing the steel bar. The patient survived without sequelae except for blindness in the right eye. Despite the lack of standardized surgical treatment for a complicated penetrating craniofacial injury, aggressive treatment by a multidisciplinary team can result in good outcomes. Language: en

Summary Background Seizures are important neurological complications of bacterial meningitis, but no information about its epidemiology and the outcomes of seizures after community-acquired bacterial meningitis (CABM) in an adult population have been reported. Aims To determine the frequency, clinical relevance, subtypes of seizures during the acute phase of bacterial meningitis, and the long-term outcomes of seizure complicating adult CABM. Methods In this 12-year retrospective study, 117 adult patients were identified with culture-proven CABM. A comparison was made between the clinical data of the patients with and without seizures during hospitalization. Results Thirty-one patients had seizures during CABM, accounting for 27% (31/117) of the episodes. The time interval between the onset of bacterial meningitis and the seizures was 1–21 days (mean, 4 days). Furthermore, 80% (25/31) of the episodes occurred within 24h of presentation. Ten patients who had seizures progressed to status epilepticus. At follow-up after completing treatment, 10 patients completely recovered and were seizure-free, 19 died of meningitis during the acute stage and the other two progressed to chronic epilepsy. Conclusion A log-rank test demonstrated that the long-term outcome of adult CABM with acute seizures produced worse outcomes than for those who had no seizures, though no difference was noted between focal and generalized seizures. None of our patients without seizures in the acute phase of bacterial meningitis developed late seizures during the follow-up periods. Poor outcome in this study may attribute to neurological complications such as seizure, hydrocephalus, infection itself, or a combination of complications.

Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.

Traumatic brain injury (TBI) leads to important and deleterious inflammation, as evidenced by edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, the activation of cerebral vascular endothelial cells plays a crucial role in the pathogenesis of inflammation. In this study, we hypothesized that the activation of cerebral vascular endothelial cells plays a crucial role in the pathogenesis of inflammation and outcome after TBI. It may represent a key cellular target for statin therapy.In our study, cortical contusions were induced, and the effect of continuous treatment of simvastatin on behavior and inflammation in adult rats following experimental TBI was evaluated. The treatment group received 15 mg/kg of simvastatin daily for 3 days. Neurological function was assessed with the grip test.The results showed that the non-treatment control group had a significantly greater increase in ICAM-1 expression from pre-injury to the post-injury 72 h time point as compared to the expression in treatment group. The treatment group had better neurological function as evidenced in a grip test performed from baseline to 72 h. The analysis of a western blot test and pathology also demonstrated reduced ICAM-1 expression and a smaller area of damage and tissue loss.Our findings suggest that simvastatin could attenuate the activation of cerebral vascular endothelial inflammatory response and decrease the loss of neurological function and brain tissue.

White matter hyperintensities (WMHs) of presumed vascular origin are common in ageing population, especially in patients with acute cerebral infarction and the volume has been reported to be associated with mental impairment and the risk of hemorrhage from antithrombotic agents. WMHs delineation can be computerized to minimize human bias. However, the presence of cerebral infarcts greatly degrades the accuracy of WMHs detection and thus limits the application of computerized delineation to patients with acute cerebral infarction. We propose a computer-assisted segmentation method to depict WMHs in the presence of cerebral infarcts in combined T1-weighted, fluid attenuation inversion recovery, and diffusion-weighted magnetic resonance imaging (MRI). The proposed method detects WMHs by empirical threshold and atlas information, with subtraction of white matter voxels affected by acute infarction. The method was derived using MRI from 25 hemispheres with WMHs only and 13 hemispheres with both WMHs and cerebral infarcts. Similarity index (SI) and correlation were utilized to assess the agreement between the new automated method and a gold standard visually guided semi-automated method done by an expert rater. The proposed WMHs segmentation approach produced average SI, sensitivity and specificity of 83.142±11.742, 84.154±16.086 and 99.988±0.029% with WMHs only and of 68.826±14.036, 74.381±18.473 and 99.956±0.054% with both WMHs and cerebral infarcts in the derivation cohort. The performance of the proposed method with an external validation cohort was also highly consistent with that of the experienced rater.

Determination of the volumes of acute cerebral infarct in the magnetic resonance imaging harbors prognostic values. However, semiautomatic method of segmentation is time-consuming and with high interrater variability. Using diffusion weighted imaging and apparent diffusion coefficient map from patients with acute infarction in 10 days, we aimed to develop a fully automatic algorithm to measure infarct volume. It includes an unsupervised classification with fuzzy C-means clustering determination of the histographic distribution, defining self-adjusted intensity thresholds. The proposed method attained high agreement with the semiautomatic method, with similarity index 89.9 ± 6.5%, in detecting cerebral infarct lesions from 22 acute stroke patients. We demonstrated the accuracy of the proposed computer-assisted prompt segmentation method, which appeared promising to replace the laborious, time-consuming, and operator-dependent semiautomatic segmentation.

Previously we demonstrated benefits of inhibiting the extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway in spinal cord ischemia/reperfusion (I/R) injury. To further identify the underlying mechanisms, we investigated the impact of ERK inhibition on apoptosis and cellular protective mechanisms against cell death. Spinal cord I/R injury induced ERK1/2 phosphorylation, followed by neuronal loss through caspase 3-mediated apoptosis. Pre-treatment with U0126, a specific inhibitor of MAPK/ERK kinases 1/2 (MEK1/2), inhibited ERK1/2 phosphorylation, and significantly attenuated apoptosis and increased neuronal survival. MEK/ERK inhibition also induced I-kappaB phosphorylation and enhanced nuclear factor (NF)-kappaB/DNA binding activity, leading to expression of cellular inhibitors of apoptosis protein 2 (c-IAP2), a known nuclear factor-kappaB (NF-kappaB)-regulated endogenous anti-apoptotic molecule. Pyrrolidine dithiocarbamate, an NF-kappaB inhibitor, by blocking I-kappaB phosphorylation, NF-kappaB activation, and c-IAP2 synthesis, abolished the protective effects of U0126. The MEK/ERK pathway appears to mediate cellular death following I/R injury. The U0126 neuroprotection appears related to NF-kappaB-regulated transcriptional control of c-IAP2. MEK/ERK inhibition at the initial stage of I/R injury may cause changes in c-IAP2 gene expression or c-IAP2/caspase 3 interactions, resulting in long lasting therapeutic effects. Future research should focus on the possible cross-talk between the MEK/ERK pathway and the NF-kappaB transcriptional cascade.

Chryseobacterium meningosepticum is an uncommon pathogen causing adult bacterial meningitis. Herein, we report the case history of one 21-year-old woman with this uncommon central nervous system infection. A diagnosis of adult C. meningosepticum meningitis can only be confirmed by a positive cerebrospinal fluid (CSF) culture. The patient had insulin-dependent diabetes mellitus as the underlying condition associated with this infection. The clinical presentations were fever, headache, consciousness disturbance, and seizure. CSF analysis revealed a purulent inflammatory reaction. After a 21-day course of intravenous cefepime (6 g/day) treatment, this patient was discharged in a state of complete recovery.

To analyze the clinical features, causative pathogens and therapeutic outcomes of bacterial meningitis in hemodialyzed patients.Two hundred and sixty-seven patients,or = 16 yrs, were identified with culture-proven bacterial meningitis. In addition, the causative pathogens and therapeutic outcomes between uremic and non-uremic patients with adult bacterial meningitis were analyzed.Nine uremic patients with bacterial meningitis, accounting for 3% (9/267) of our adult patients with culture-proven bacterial meningitis had fever, disturbed consciousness and seizures. These were the three most common manifestations in our patients. The interval between the onset of symptoms and therapy start was 5-11 days (mean: 9 days). No patients were initially diagnosed with bacterial meningitis, two patients were initially suspected of having infection of unknown origin. In the non-uremic patient group, klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae were the most frequently detected pathogens, while pseudomonas aeruginosa and coagulase-negative Staphylococcus were the most prevalent in the uremic patients group. The overall mortality rates for the non-uremic and uremic patient groups were 33 and 78% respectively.The mortality rate for bacterial meningitis in the uremic patients group remained high. Due to non-specific manifestations and slow evolution, bacterial meningitis was commonly misdiagnosed as uremic encephalopathy. Therefore, effective treatment was usually delayed. To avoid treatment failure, early diagnosis, careful monitoring of clinical condition and appropriate antibiotic choices are necessary.

This retrospective chart review describes the clinical features, pathogens, and outcomes of 46 patients with cerebrospinal fluid (CSF) shunt infections collected over 16 years. The overall CSF shunt infection rate was 2.1%, broken down into 1.7 and 9.3% in adult and pediatric groups, respectively. Fever and progressive consciousness disturbance were the most clinical features in the adult patient group, whereas disturbance of consciousness and abdominal symptoms and signs were the two most common clinical features in the pediatric patient group. The most frequently isolated microorganisms were of the Staphylococcus spp., including Staphylococcus aureus and coagulase negative Staphylococcus, which accounted for 47% of the episodes. Furthermore, increases in polymicrobial and Gram-negative bacilli infections were observed in our study. Due to the high proportion of oxacillin-resistant Staphylococcus spp. and polymicrobial infections, we recommend initial empirical antibiotics with both vancomycin and a third-generation cephalosporin for cases in which the causative bacteria has not been identified or for which the results of antimicrobial susceptibility tests are not available. For patients who develop smoldering fevers, progressive disturbed consciousness, seizures, or abdominal fullness after ventriculoperitoneal shunt procedures, CSF shunt infections should be suspected. Although some infections have been managed successfully with antimicrobial therapy alone, the timely use of appropriate antibiotics according to antimicrobial susceptibility testing and the removal of the shunt apparatus are essential for successful treatment.

LUMBAR puncture is usually contraindicated in patients with increased intracranial pressure or space-occupying lesions because lumbar cerebrospinal fluid (CSF) drainage can increase the pressure gradient between the supratentorial and infratentorial compartments and thus result in rapid herniation. 1,2 Some authors have also suggested that epidural anesthesia is dangerous in patients with space-occupying lesions not only because of the risks associated with accidental dural puncture, but also because epidural drug and fluid injection can increase intracranial pressure. 3,4 We present a case of a pregnant woman with an occult brain tumor who received an epidural anesthetic for relief of labor pain, which was complicated by an inadvertent lumbar puncture. Several hours after delivery, she had fatal transtentorial brain herniation.