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This report is on a 22-year-old male vegetarian with acute polyneuropathy secondary to vitamin B(12) deficiency. He presented with weakness and numbness of the distal limbs and absent deep tendon reflex in all four extremities. Nerve conduction study (NCS) showed an axonal type sensori-motor polyneuropathy. Serum biochemical studies revealed vitamin B(12) level of 119 pg/mL (reference range 185-710 pg/mL), with elevated creatine kinase (CK) (719 U/L) and homocysteine (Hcy) (24.04 μmol/L) levels. Anti-parietal cell antibody test was positive. The patient received both oral and intramuscular injection of vitamin B(12). The amplitude of the median and ulnar motor NCS increased 2.5 months later, while muscle power of the ankle plantar flexion and dorsiflexion recovered after 3.5 and 5.5 months, respectively. Follow-up NCS after 14.5 months showed response in sural NCS, but not the peroneal NCS. Follow-up also showed decreased serum Hcy and CK to 9.6 μmol/L and 198 U/L, respectively, and increasing amplitude of response. Recovery sequence involved muscle power of the proximal muscles, hands, plantar flexion, and dorsiflexion of the feet, and followed by sensory conduction. [ABSTRACT FROM AUTHOR]

Introduction: Serum concentrations of adhesion molecules may be connected to the pathogenesis of secondary brain injury after spontaneous intracerebral hemorrhage (ICH). This study posits the hypothesis that levels of adhesion molecules substantially increase after ICH and are decreased thereafter, and that they can predict treatment outcomes.Methods: Two hundred and thirty-nine blood samples were collected from 60 consecutive patients admitted within 24 hours after onset of spontaneous ICH and 60 blood samples were collected from 60 volunteers. Additional samples were obtained on Days 4, 7, 10, and 14 after onset of ICH regardless of clinical deterioration.Results: Upon discharge, the therapeutic outcomes of the 60 spontaneous ICH cases based on the modified Rankin Disability Scale (mMRS) showed that 17 had no disability while 8.3% developed delayed cerebral infarction (DCI). Statistical analysis of adhesion molecules between patient groups with good outcome (mMRS = 0 or 1) and poor outcome (mMRS ≥2) revealed significant differences in diabetes mellitus (P=0.049), hyperlipidemia (P=0.012), mentality change (P=0.043), ICH volume and intraventricular hemorrhage on admission (P=0.036 and 0.006, respectively), Glasgow Coma Scale (GCS) on admission (P≤0.001), neuro-surgical intervention (P=0.003), and sE-selectin and soluble intercellular cell adhesion-molecule-1 (sICAM-1) levels on admission (P=0.036 and 0.019, respectively). Multiple logistic regression analysis of these significant variables showed that GCS on admission, hyperlipidemia, and sICAM-1 (P=0.039, 0.042, and 0.022, respectively) were independently associated with outcome of acute spontaneous ICH.Conclusion: Increased sICAM-1 and sE-selectin levels may imply poor therapeutic outcomes for the treatment of spontaneous ICH during hospitalization. These early inflammatory responses may cause whole-brain injury immediately after spontaneous ICH and offer a potential therapeutic target for such patients. The importance of these findings is that they offer a potential therapeutic target for patients with spontaneous ICH. [ABSTRACT FROM AUTHOR]

Introduction: Myasthenia gravis (MG) is a chronic neuromuscular disease leading to significant disease burden. This study aimed to investigate the epidemiology of MG in Taiwan., Methods: A retrospective study was conducted using the Taiwan National Health Insurance Research Database. Prevalent patients with MG diagnosis (either ocular or generalized MG) from 2013 to 2019 were identified, and 2813 patients with initial MG diagnosis from 2014 to 2019 were further defined as the incident cohort. Patient characteristics, treatment patterns, and the occurrence of MG-related events were analyzed., Results: The number of prevalent patients with MG increased from 4476 in 2013 to 5752 in 2019, with the prevalence rate increasing from 19 to 24 per 100,000 population. The incidence rate also slightly increased from 1.9 to 2.3 per 100,000 population during the study period. Almost all incident patients (99%, n = 2791) received MG-related treatment during the follow-up period. Among 1876 patients who received monotherapy as their initial treatment in the outpatient setting, the mean time from the index date to initial treatment was 48.8 (standard deviation 164.3) days, and most patients received acetylcholinesterase inhibitors (88.5%, n = 1661) as their initial treatment. During the first year after the index date, 133 (4.7%) incident patients experienced their first myasthenic crisis, and 96.2% of these events occurred within 3 months., Conclusion: The prevalence of MG increased steadily in Taiwan, and the treatment of patients with MG was consistent with guidelines. Despite a high treatment rate, patients still experienced MG-related events, highlighting the limitation of current treatments and emphasizing the need for early intervention and novel treatment approaches., (© 2024. The Author(s).)

To model peripheral nerve degeneration and investigate molecular mechanisms of neurodegeneration, we established a cell system of induced pluripotent stem cell (iPSC)-derived sensory neurons exposed to vincristine, a drug that frequently causes chemotherapy-induced peripheral neuropathy. Sensory neurons differentiated from iPSCs exhibit distinct neurochemical patterns according to the immunocytochemical phenotypes, and gene expression of peripherin (PRPH, hereafter referred to as Peri) and neurofilament heavy chain (NEFH, hereafter referred to as NF). The majority of iPSC-derived sensory neurons were PRPH positive/NEFH negative, i.e. Peri(+)/NF(-) neurons, whose somata were smaller than those of Peri(+)/NF(+) neurons. On exposure to vincristine, projections from the cell body of a neuron, i.e. neurites, were degenerated quicker than somata, the lethal concentration to kill 50% (LC50) of neurites being below the LC50 for somata, consistent with the clinical pattern of length-dependent neuropathy. We then examined the molecular expression in the MAP kinase signaling pathways of, extracellular signal-regulated kinases 1/2 (MAPK1/3, hereafter referred to as ERK), p38 mitogen-activated protein kinases (MAPK11/12/13/14, hereafter referred to as p38) and c-Jun N-terminal kinases (MAPK8/9/10, hereafter referred to as JNK). Regarding these three cascades, only phosphorylation of JNK was upregulated but not that of p38 or ERK1/2. Furthermore, vincristine-treatment resulted in impaired autophagy and reduced autophagic flux. Rapamycin-treatment reversed the effect of impaired autophagy and JNK activation. These results not only established a platform to study peripheral degeneration of human neurons but also provide molecular mechanisms for neurodegeneration with the potential for therapeutic targets., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Objectives: The underlying etiology of Meniere's disease (MD) is not completely clear, but the precipitated triggers may alter the circadian clock in patients with MD. This study aims to survey the expression of circadian clock genes in peripheral blood (PB) leukocytes of MD patients., Methods: We investigated the expression of nine circadian clock genes in the PB leukocytes of patients with MD and normal controls using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)., Results: We observed significantly lower expression of PER1 gene and higher expression of CLOCK gene in MD patients than those in normal controls ( p  < 0.05). PER1 did not associate with the degree of dizziness handicap in the patients with MD, but a lower expression of PER1 was significantly correlated with higher pure tone average (PTA) and speech reception threshold of the affected ear ( p  < 0.05). Patients with PTA > 30 dB had significantly lower PER1 expression than those with PTA ≤30 dB in the affected ear ( p  < 0.05). Our qRT-PCR result was validated by fewer positively stained leukocytes for PER1 protein in the MD patients using the immunocytochemical study., Conclusion: Our study implies the alteration of the circadian clock in patients with MD. In particular, the downregulation of PER1 correlated with the degree of hearing loss in the affected ear. PER1 in PB leukocytes may be a potential marker for the progression of hearing loss in MD., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: The association between increased neutrophil-to-lymphocyte ratio (NLR) and multiple sclerosis has been demonstrated in several studies. The monocyte-to-lymphocyte ratio (MLR) is an emerging biomarker for disease monitoring. Moreover, there has not been a published Taiwanese study to date., Aim: To investigate the correlation of NLR, MLR and white blood cell (WBC) count as possible biomarkers for predicting a 2-year relapse in patients with multiple sclerosis (MS)., Materials and Methods: A total of 641 Taiwanese patients with MS were enrolled in the present study between January 1, 2001, and December 31, 2018. We collected data on NLR, MLR, WBC count, disease-modifying therapy (DMT) use, and the time between first diagnosis and first relapse in all patients within a 2-year duration., Results: In the relapse group, there were significantly more patients with NLR >median or MLR >median (p = 0.006 and p = 0.020, respectively). There were also more patients with WBC count >median, although the difference was not statically significant (p = 0.069). The adjusted hazard ratio for relapse and NLR >median was 1.61(p = 0.008). The adjusted hazard ratio for relapse and MLR >median was 1.43 (p = 0.044). Patients with NLR >median or MLR >median had a significantly (p = 0.008 and p = 0.039, respectively) increased risk of MS relapse in the 2 years, compared with those who had NLR

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare neuroimmunology disorder predominantly affecting the East Asia population, the reason for this preference remains unknown. Genetic factors such as polymorphisms in human leukocyte antigen (HLA) and interleukins (IL) genes have been reported. Although the familial occurrence of NMOSD is rare, it supports that genetic factors may play a role., Methods: Whole exome sequencing (WES) study was performed on the affected mother and daughter, as well as the unaffected father in a Taiwanese family with NMOSD. A cohort of 19 sporadic patients with aquaporin 4 antibody (AQP4-Ab) positive NMOSD was also recruited; all fulfilled the 2015 International NMOSD Diagnosis Criteria. Sanger sequencing was performed on exon 4 of the CD33 gene on the sporadic NMOSD cohort., Results: WES study revealed a 19 base pair deletion in exon 4 of the CD33 gene, resulting in frameshift premature truncating protein, which segregated with the affected status. CD33 was the most likely candidate gene due to its known function in immune regulation. A total of 19 sporadic NMOSD patients were tested using Sanger sequencing, including 3 patients with other concomitant autoimmune disorders. Two additional NMOSD patients were found to have the same CD33 frameshift variant, which accounts for 19.04% of all NMOSD patients, and 15% following correction for the familial cases; compared to 2% in Taiwanese population controls., Conclusion: In this study, we identified a 19 base pair deletion in the CD33 gene may be a potential risk locus for NMOSD, which is predicted to cause loss of function of CD33. The loss of CD33 inhibitory function may affect the regulation of the immune system in NMOSD patients. This finding requires further larger cohorts of NMOSD patients and functional study to corroborate., Competing Interests: Conflicts of interest All authors reported no conflicts of interest associated with this publication and there has no financial support for this work that could influence the study outcome., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: The effect of 3-month respiratory muscle training (RMT) on pulmonary and autonomic function and functional outcomes has been demonstrated in patients with Parkinson's disease (PD); however, there is a paucity of information on the durability of the training effect. In this study, we monitored the pulmonary and cardiovascular autonomic function and clinical severity scales until 18 months after the cessation of RMT to elucidate the detraining effect after RMT. Methods: All patients with PD receiving RMT were assessed with clinical severity scales as well as pulmonary and autonomic function tests at four different stages (baseline on enrollment, immediately after 3 months of RMT, and 6 and 18 months after cessation of RMT). A control group of PD patients who did not receive RMT was also recruited for comparison. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP), were assessed. Cardiovascular autonomic function was assessed using measures including heart rate response to deep breathing (HRDB), Valsalva ratio, and baroreflex sensitivity. Clinical severity scores were also measured using the Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale (UPDRS). Results: The results showed significant improvements in MIP, MEP, HRDB, and UPDRS immediately after RMT. Despite some decay, the improvements in pulmonary function (MIP and MEP) and functional outcomes (UPDRS) remained significant until 6 months of detraining (9 months after enrollment). However, the improvement in cardiovascular autonomic function (HRDB) was reversed after 6 months of detraining. Conclusions: Based on these findings, we recommend that RMT may be repeated after at least 6 months after previous session (9 months after enrollment) for patients with PD to maintain optimal therapeutic effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Lai, Wu, Kuo, Cheng, Tsai, Kung, Chiang and Lu.)

Background: Myasthenia gravis (MG) is an autoimmune disease involving the neuromuscular junction. Myasthenic crisis (MC), which is characterized by respiratory failure and the requirement of mechanical ventilation in patients with MG, is still a medical emergency despite the decrease in mortality with the advances in acute management. Hemogram is a cost-effective test for evaluating hematological complications and systemic inflammation, and hemogram data have been used to predict various clinical outcomes of several diseases. The relationship between hemogram and MG has been discussed, but the role of hemogram data in predicting the prognosis of MC patients has not been established., Methods: To identify whether hemogram data can predict in-hospital mortality in patients with MC, we retrospectively investigated 188 myasthenic crisis events from the Chang Gung Research Database between April 2001 and March 2019. Demographic and clinical characteristics were collected, as well as hemogram data before intubation and extubation. The endpoints were mortality during mechanical ventilation and mortality after extubation., Results: The overall in-hospital mortality rate was 22%. Multivariate logistic regression analysis for predicting mortality during mechanical ventilation showed that old age at MC onset (OR = 1.039, p = 0.022), moderate-to-severe anemia (OR = 5.851, p = 0.001), and extreme leukocytosis (OR = 5.659, p = 0.022) before intubation were strong predictors of mortality, while acute management with plasma exchange or double-filtration plasmapheresis (PE/DFPP) significantly decreased mortality (OR = 0.236, p = 0.012). For predicting mortality after extubation, moderate-to-severe anemia before extubation (OR = 8.452, p = 0.017) and non-treated with disease-modifying therapy before MC (OR = 5.459, p = 0.031) were crucial predictive factors., Conclusion: This study demonstrated that both old age at MC onset and moderate-to-severe anemia are important predictors of in-hospital mortality in patients with MC, and extreme leukocytosis is another crucial predictor of mortality during mechanical ventilation. The suggested mechanism is that anemia-induced hypoxia may enhance the release of proinflammatory cytokines, exacerbate systemic inflammation, and lead to multiple organ dysfunction syndrome and, finally, mortality., (© 2021. The Author(s).)

Background: Serum concentrations of adhesion molecules and oxidative stress is thought to participate in the pathobiology of secondary brain injury after acute traumatic brain injury (TBI). We aimed to study the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the adhesion molecules levels and antioxidant capacity., Methods: Thirty blood samples from ten patients after acute TBI were obtained after injury and before and after HBOT. Four patients received early HBOT started two weeks after injury, four patients received late HBOT started ten weeks after injury and two patients did not receive HBOT and served as control in this study. The HBOT patients received total 30 times HBOT in six weeks period., Results: Those serum biomarkers in patients with TBI had not significantly difference in glutathione (GSH), thiobarbituric acid reactive substances (TBARS), soluble intercellular cell adhesion-molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations on admission between early HBOT, late HBOT, and control group ( p = 0.916, p = 0.98, p = 0.306, and p = 0.548, respectively). Serum GSH levels were higher at 10 weeks after injury in the early HBOT group than in the late HBOT group and control group (mean, 1.40 μmol/L, 1.16 μmol/L, and 1.05 μmol/L, respectively). Then the serum GSH level was increased at 18 weeks after injury in the late HBOT group (mean, 1.49 μmol/L). However, there was only statistically significant difference at Weeks 18 ( p = 0.916, p = 0.463, and p = 0.006, at Week 2, Week 10, and Week 18, respectively). Serum TBARS levels were decreased at 10 weeks after injury in the early HBOT group than in the late HBOT group and control group (mean, 11.21 μmol/L, 17.23 μmol/L, and 17.14 μmol/L, respectively). Then the serum TBARS level was decreased at 18 weeks after injury in the late HBOT group (mean, 12.06 μmol/L). There was statistically significant difference after HBOT ( p = 0.98, p = 0.007, and p = 0.018, at Week 2, Week 10, and Week 18, respectively). There was no statistically significant difference between the three groups on sICAM-1 and sVCAM-1 levels from Week 2 to Week 18., Conclusions: HBOT can improve serum oxidative stress in patients after TBI. These molecules may be added as evaluation markers in clinical practice. Perhaps in the future it may also become part of the treatment of patients after acute traumatic brain injury. Further large-scale study may be warrant.

Aims/introduction: Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics., Materials and Methods: Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score., Results: The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P < 0.0001). Multiple linear regression analysis also showed that feet ESC and SDNN value (P = 0.003 and P < 0.0001) were significantly associated with CAN score. Combining SDNN and feet ESC also can increase the diagnostic accuracy of CAN with respective to sensitivity and specificity by using receiver operating characteristic analysis., Conclusions: Combining the results of SDNN and feet ESC can not only assess, but also quantitatively reflect the progress or improvement of autonomic nerve function (including sympathetic and parasympathetic activity) in patients with T2DM., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objectives: Cardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke)., Methods: In this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE., Results: The overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio., Conclusions: Besides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Parkinson's disease (PD) is a common neurodegenerative disease associated with accumulation of misfolding proteins and increased neuroinflammation, which may further impair the glymphatic system. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship with systemic oxidative stress status in PD patients., Methods: Magnetic resonance imaging and neuropsychological tests were conducted on 25 PD patients with normal cognition (PDN), 25 PD patients with mild cognitive impairment (PD-MCI), 38 PD patients with dementia (PDD), and 47 normal controls (NC). Oxidative stress status was assessed by plasma DNA level. Differences in ALPS-index among the subgroups were assessed and further correlated with cognitive functions and plasma DNA levels., Results: The PD-MCI and PDD groups showed significantly lower ALPS-index compared to normal controls. The ALPS-index was inversely correlated with plasma nuclear DNA, mitochondrial DNA levels, and cognitive scores., Conclusions: Lower diffusivity along the perivascular space, represented by lower ALPS-index, indicates impairment of the glymphatic system in PD patients. The correlation between elevated plasma nuclear DNA levels and lower ALPS-index supports the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hsiu-Ling Chen et al.)

Background/purpose: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan., Methods: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR)., Results: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 10 3 /uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353., Conclusion: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Autonomic disorders have been recognized as an important non-motor feature in Parkinson's disease (PD). However, there is a paucity of information on the presence and severity of cardiovascular autonomic neuropathy (CAN) among different motor phenotypes. The aims of this study were to examine the feasibility of electrochemical skin conductance (ESC) measured by Sudoscan as a screening service for CAN in patients with PD and investigate the severity of CAN among different motor phenotypes. Design: This was a cross-sectional observational study that enrolled 63 patients with PD. Patients were divided into three phenotypes, postural instability/gait difficulty (PIGD), tremor-dominant (TD), and akinetic-rigid (AR), according to their motor symptoms. Cardiovascular autonomic function was measured, and the presence and severity of CAN was determined according to the composite autonomic scoring scale (CASS). Functional scores were measured by the Hoehn and Yahr (HY) stage and the Unified Parkinson's Disease Rating Scale (UPDRS). The median HY stage was 2.0 [1.5, 3.0]. Median UPDRS total score was 23.0 (17.5, 30.5), 10.0 (6.0, 11.0) and 14.0 (6.3, 23.8) in groups of PIGD, TD and AR, respectively ( p = 0.001). Mean CASS was 1.7 ± 1.3, 0.6 ± 0.4, and 1.8 ± 1.5 in groups of PIGD, TD and AR, respectively ( p = 0.204). Although the ESC was not strongly associated with the cardiovascular autonomic parameters, the CAN risk score provided by Sudoscan significantly correlated with parameters of cardiovascular autonomic function, including heart rate response to deep breathing (HR&#95;DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS). By receiver-operating characteristic (ROC) analysis, if a patient's CAN risk score is higher than 33.5 (%), it is recommended to be aware of the presence of CAN even in PD patients who are asymptomatic. The area under ROC curve was 0.704. Based on our results, CAN risk score may be used for screening of CAN in patients with PD before resorting to the more sophisticated and specific, but ultimately more time-consuming, complete autonomic function testing.

Background: Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes., Methods: The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value)., Results: A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS., Conclusions: Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.

Introduction: Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson's disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD., Objective: Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis., Methods: Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis., Results: The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation., Conclusion: Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Chiun-Chieh Yu et al.)

Purpose: Oxidative stress has been shown to reflect on the development of sepsis and disease severity. In the present study, we evaluated the effects of increased levels of oxidative stress and decreased antioxidant coactivity in patients with sepsis, and the importance of oxidative stress on treatment outcomes., Methods: Biomarkers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant capacity (glutathione peroxidase [GPx] and glutathione content [thiol]) were prospectively evaluated along with biochemical and clinical data in 100 patients with sepsis on days 1, 4, and 7 after admission., Results: The TBARS level of the non-survivor group was significantly higher than that of the survivor group on day 1 and day 4 and negatively correlated with thiol upon admission. However, thiol was positively correlated with lactate concentration. The TBARS and lactate levels upon admission were independent predictors of fatality., Conclusions: We conclude that a TBARS cut-off value of 18.30 μM can be used to predict fatality, and an increase in the TBARS concentration by 1 μM will increase the fatality rate by 0.94%. In the panel of biomarkers, the TBARS assay can be considered as a prognostic biomarker for the treatment of patients with sepsis.

Objectives: The condition of caregivers is important to the quality of care received by people with Parkinson's disease (PD), especially at the late disease stages. This study addresses the distress placed on caregivers by participants' neuropsychiatric symptoms at different stages of PD in Taiwan., Methods: This prospective study enrolled 108 people with PD. All participants were examined with the Unified Parkinson's Disease Rating Scale (UPDRS), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Clinical Dementia Rating (CDR) scale. Caregiver distress was measured using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D). Statistical analysis was used to explore the PD-related factors that contribute to caregiver distress., Results: The mean follow-up interval in the 108 PD participants were 24.0 ± 10.2 months with no participant lost to follow-up due to death. NPI-distress (the sum of NPI caregiver distress scale across the 12 domains of the NPI) was positively correlated with NPI-sum (the total score across the 12 domains of the NPI) (r = 0.787, p < 0.001), CDR (r = 0.403, p < 0.001), UPRDS (r = 0.276, p = 0.004), and disease duration (r = 0.246, p = 0.002), but negatively correlated with CASI (r = -0.237, p = 0.043) and MMSE (r = -0.281, p < 0.001). Multiple linear regression analysis showed that only NPI-sum and disease duration were independently correlated with NPI-distress., Conclusion: The disease duration and NPI-sum are independent predictors of caregiver distress in Taiwanese populations with PD. Early detection and reduction of neuropsychiatric symptoms in people with PD can help decrease caregiver distress.

MINI: In this study, respiratory function at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical spinal cord injury. Serum thiobarbituric acid-reactive substances level at admission can be a useful predictor for severity in acute cervical patients with spinal cord injury., Study Design: Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study., Objective: We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI., Summary of Background Data: Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI., Methods: Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared., Results: The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%)., Conclusion: In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients., Level of Evidence: 3.

Objective: In this study, we assessed plasma biomarkers to identify cognitive impairment in Parkinson's disease (PD) patients by applying ultra-sensitive immunomagnetic reduction-based immunoassay (IMR)., Methods: The study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Complete cognitive function assessments were performed on participants using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating. PD patients with an MMSE score of ≦26 were defined as having cognitive impairment. Meanwhile, a 99mTc-TRODAT-1 scan was performed and plasma levels of Aβ-40, Aβ-42, T-tau, and α-synuclein were evaluated using IMR, subsequent correlation analyses were then performed., Results: Compared with normal adults, PD patients have higher plasma levels of α-synuclein and T-tau, and a lower level of Aβ-40 ( p < 0.05). Plasma levels of α-synuclein ( r = -0.323, p = 0.002), Aβ-40 ( r = 0.276, p = 0.01), and T-tau ( r = -0.322, p = 0.002) are significantly correlated with MMSE scores. The TRODAT scan results, including visual inspection and quantification, revealed significant correlations between Aβ-40 and PD. Multiple regression analysis showed that the plasma levels of Aβ-40 (OR = 0.921, 95% CI = 0.879-0.962), α-synuclein (OR = 3.016, 95% CI = 1.703-5.339), and T-tau (OR = 1.069, 95% CI = 1.026-1.115) were independently associated with PD patients with cognitive impairment. The cutoff values for predicting cognitive deficits in PD patients were 45.101 pg/ml of Aβ-40, (Area under curve (AUC) = 0.791), 0.389 pg/ml of α-synuclein, (AUC = 0.790), and 30.555 pg/ml of T-tau (AUC = 0.726)., Conclusion: Plasma levels of α-synuclein, Aβ-40, and T-tau are potential biomarkers to detect cognitive impairment in PD patients., (Copyright © 2020 Chen, Chen, Li, Chang, Chen, Tsai, Yu, Yang, Lu and Lin.)

Background: Myasthenia gravis (MG) is an immune-mediated disorder characterized by muscle fatigue and fluctuating weakness. Impairment in respiratory strength and endurance has been described in patients with generalized MG. We tested the hypothesis that respiratory muscle training (RMT) can improve functional outcomes and reduce fatigue in patients with MG., Methods: Eighteen patients with mild to moderate MG participated in this study. The training group underwent home-based RMT three times a week for 12 weeks. Sixteen patients with MG without RMT were enrolled as a disease control group. Lung function, autonomic testing, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), and functional outcome measurement by using quantitative myasthenia gravis (QMG) score and myasthenia gravis composite (MGC) scale were measured before and after the 12-week RMT., Results: The 12-week RMT significantly increased forced vital capacity (FVC) from 77.9 ± 12.6% to 83.8 ± 17.7% ( p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% ( p = 0.03), forced expiratory volume in one second (FEV1) from 75.2 ± 18.3% to 83.3 ± 19.0% (., Conclusion: The home-based RMT is an effective pulmonary function training for MG patients. The RMT can not only improve short-term outcomes but also reduce fatigue in patients with mild to moderate generalized MG., Competing Interests: None of the authors has any commercial association, such as consultancies, stock ownership, or other equity interests or patent-licensing arrangements., (Copyright © 2020 Che-Wei Hsu et al.)

Background: Although greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes., Aim: To address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD)., Design: This prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center., Method: We designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study., Results: The patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2., Conclusion: We observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient's eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Both pulmonary function and autonomic function are impaired in patients with Parkinson's diseases (PD). This study tested the hypothesis that respiratory muscle training (RMT) can not only improve pulmonary function, but also simultaneously improve cardiovascular autonomic function and short-term functional outcomes in patients with PD. Pulmonary function was measured by the forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum inspiratory pressures (MIP), and maximum expiratory pressures (MEP). Cardiovascular autonomic function was measured by the heart rate response to deep breathing (HRDB), Valsalva ratio, baroreflex sensitivity, and spectral analysis. The functional and severity scores were measured by the Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS). These measures were evaluated in patients with PD before and after 3 months of RMT, compared with a control group of PD patients without RMT. The results showed significant improvement of clinical scores (total UPDRS and UPDRS I, II and III) after RMT ( p < 0.0001). Concerning pulmonary function, the parameters of MIP and MEP improved significantly. The parameters of cardiovascular function also improved after RMT, although only HRDB reached statistical significance. Based on the results of our study, RMT can not only improve both pulmonary and cardiovascular autonomic function, but can also improve short-term functional outcomes in patients with PD., Competing Interests: The authors declare that they have no competing interests.

Introduction: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN)., Methods: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity., Results: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028)., Discussion: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure., (© 2019 Wiley Periodicals, Inc.)

Objective: Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN., Method: A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS., Results: Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P < 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P < 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P < 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS., Conclusion: Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN., Significance: Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study., Methods: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin., Results: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups., Conclusions: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Atrial fibrillation (AF)-related stroke causes severe disability and poor prognosis. Adjunctive statin therapy has been recommended for atherosclerotic-related stroke but not AF-related stroke. This study investigated the effects of statin in AF patients who experienced acute ischemic stroke., Methods: Data from patients with AF experiencing first-ever ischemic stroke between 2001 and 2010 were collected from the Taiwan National Health Insurance Research Database and categorized into non-statin and statin groups. The statin group was further divided into pre-stroke statin (those who began statin therapy before stroke) and post-stroke statin (those who began statin therapy after stroke) groups. The risks for recurrent ischemic stroke, coronary artery disease (CAD), intracranial hemorrhage (ICH), and 1-year mortality were compared among the groups., Results: A total of 43,242 patients were in the non-statin, 2858 in the pre-stroke statin and 4640 in post-stroke statin groups. Comparing the risk for recurrent stroke and CAD among the three groups, the pre-stroke statin and post-stroke statin groups did not exhibit a significant difference compared with the non-statin group. In terms of ICH risk, the statin group had a lower risk for ICH (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.90; p = 0.0007) compared with the non-statin group. The overall 1-year mortality in both statin subgroups was lower than that in the non-statin group (pre-stroke statin, OR 0.55 [95% CI 0.49-0.61]; p < 0.0001 versus post-stroke statin, OR 0.53 [95% CI 0.48-0.58]; p < 0.0001)., Conclusions: Statin therapy reduced the risk of ICH and 1-year mortality in AF patients who experienced acute ischemic stroke., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background : Parkinson's disease (PD) is a neurodegenerative disease manifested by both motor and non-motor dysfunctions and co-existence of cognitive impairment and physical frailty is common. Given that research in this area is limited, a better understanding of associated factors with physical frailty could provide a focused screening method and facilitate early intervention in PD. Methods : Seventy-six patients with idiopathic PD were recruited and Fried's criteria of physical frailty were used to group all participants. Comprehensive cognitive tests and clinical characteristics were measured, and univariate and multivariate analysis was performed to explore the relationship between clinical factors or neuropsychological functions. Results : Twenty-nine patients with PD (38%) exhibited physical frailty. Compared to PD patients without frailty, PD patients with frailty were older in age and demonstrated worse disease severity and poorer cognitive functions, including attention, executive function, memory, speech and language, and visuospatial function ( p < 0.05). Further, stepwise logistic regression analysis revealed that disease severity by the Unified Parkinson's Disease Rating Scale (UPDRS) total score (OR: 1.065; 95% CI: 1.033-1.099) and executive function (OR: 0.724; 95% CI: 0.581-0.877) were independent risk factors for predicting physical frailty ( p = 0.003 and 0.002). The best cut-off points are 46 in UPDRS (sensitivity: 62.1%; specificity: 91.5%). Conclusions : Executive function impairment is an independent risk factor for the development of physical frailty with disease progression. Awareness of such comorbidity might provide a screening tool to facilitate investigation in their underlying etiology and early intervention for frailty prevention., (Copyright © 2019 Lin, Huang, Leong, Chen, Chen, Tsai, Tso, Chen and Lu.)

Background: Acute traumatic cervical spinal cord injury (SCI) is a leading cause of disability in adolescents and young adults worldwide. Evidence from previous studies suggests that circulating cell-free DNA is associated with severity following acute injury. The present study determined whether plasma DNA levels in acute cervical SCI are predictive of outcome., Methods: In present study, serial plasma nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) levels were obtained from 44 patients with acute traumatic cervical SCI at five time points from day 1 to day 180 post-injury. Control blood samples were obtained from 66 volunteers., Results: Data showed a significant increase in plasma nDNA and mtDNA concentrations at admission in SCI patients compared to the control group. Plasma nDNA levels at admission, but not plasma mtDNA levels, were significantly associated with the Japanese Orthopaedic Association (JOA) score and Injury Severity Score in patients with acute traumatic cervical SCI. In patients with non-excellent outcomes, plasma nDNA increased significantly at days 1, 14 and 30 post-injury. Furthermore, its level at day 14 was independently associated with outcome. Higher plasma nDNA levels at the chosen cutoff point (> 45.6 ng/ml) predicted poorer outcome with a sensitivity of 78.9% and a specificity of 78.4%., Conclusions: These results indicate JOA score performance and plasma nDNA levels reflect the severity of spinal cord injury. Therefore, the plasma nDNA assays can be considered as potential neuropathological markers in patients with acute traumatic cervical SCI.

Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20-86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The presence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Depressed baroreflex sensitivity (BRS) is reported in obstructive sleep apnea (OSA). Improvement of BRS short-term after surgical treatment is also reported. We tested the hypothesis that surgical treatment not only improves clinical outcomes, but also improves BRS after 18 months., Methods: Cardiovascular autonomic tests, polysomnography (PSG), and biochemical testing were prospectively evaluated in 54 OSA patients at three time points (preoperatively, 6 months and 18 months postoperatively) and compared with 20, age- and body mass index (BMI)-matched, healthy controls., Results: The BRS increased after surgical treatment at 18-month follow-up, with results similar to the healthy control. Additionally, average O 2 , mO 2 <90% (% per night), and lowest O 2 showed an increase after surgical treatment at the 18-month follow-up., Conclusions: Besides improvement in clinical outcomes, depressed BRS in OSA patients is reversible and these patients have the potential for total recovery of baroreflex function after 18 months of treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Both diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN., Method: All patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively., Results: Patients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR&#95;DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR&#95;DB., Conclusion: Sural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes., Significance: The independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: α -1-Acid glycoprotein (AGP) is an acute-phase protein that plays a role in first-line defense against infection and is therefore elevated in sepsis. We tested the hypothesis that AGP levels increase initially in sepsis and decrease after antimicrobial therapy and that these levels may predict treatment outcomes., Methods: AGP, biomarkers widely used in clinical practice, and maximum 24-h acute physiology and chronic health evaluation (APACHE)-II scores upon emergency department (ED) admission were prospectively evaluated and compared. We further examined changes in AGP concentrations 1, 4, and 7 days after admission and determined the value of AGP that may be used to accurately and reliably predict the prognosis in patients with sepsis., Results: Mechanical ventilation, white blood cell (WBC) counts, C-reactive protein (CRP) and lactate levels, maximum 24-h APACHE-II scores, and AGP concentrations were significantly higher upon admission in patients with sepsis who died. AGP and lactate concentrations were also significantly higher in non-survivors than in survivors on days 1, 4, and 7. As indicated by the stepwise logistic regression model analysis and area under the curve analysis, AGP was the best prognostic indicator, and the cut-off value for predicting fatality was 1307  μ g/mL, and any increase 1-ng/mL in AGP concentration would increase the fatality rate by 0.5%., Conclusion: Based on our observations, AGP may be a good prognostic predictor in patients with sepsis. In addition, serial AGP levels meet the requirements for predicting outcomes in patients with sepsis.

Background: Variability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years)., Methods: For each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively., Results: Those with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS., Conclusion: HbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.

Decompressive craniectomy (DC) has been performed increasingly to control medically refractory intracranial hypertension in patients with traumatic brain injury (TBI). Although DC is a potentially life-saving procedure and technically straightforward, it is associated with some significant complications that include subdural hygroma (SDG) and posttraumatic hydrocephalus (PTH). A retrospective analysis of 143 TBI patients who underwent unilateral DC was undertaken to investigate the incidence and risk factors of PTH and investigate the relationship between the types of SDG and PTH. Among these patients, the incidence of PTH was 30.1%. SDG was noted in 25 patients (58.1%) who developed PTH. SDG was noted in 27 patients (27%) without PTH. The patients with PTH had a significantly unfavorable outcome (p < 0.0001). After stepwise logistic regression analyses, only age (p = 0.004, odds ratio [OR] = 1.036, 95% confidence interval [CI] = 1.011-1.061) and contralateral SDG (p < 0.0001, OR = 5.613, 95% CI = 2.232-14.115) remained independently associated with PTH development, and PTH development rate increased by 3.6% with every 1-year increase in age. Close surveillance is indicated in older TBI patients with contralateral SDG after unilateral DC to prompt early detection and timely management of PTH., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Cerebellar hemorrhage is a potentially life-threatening condition and neurologic deterioration during hospitalization could lead to severe disability and poor outcome. Finds out the factors influencing neurologic deterioration during hospitalization is essential for clinical decision-making., Methods: One hundred fifty-five consecutive patients who suffered a first spontaneous cerebellar hemorrhage (SCH) were evaluated in this 10-year retrospective study. This study aimed to identify potential clinical, radiological and clinical scales risk factors for neurologic deterioration during hospitalization and outcome at discharge., Results: Neurologic deterioration during hospitalization developed in 17.4% (27/155) of the patient cohort. Obliteration of basal cistern (p≦0.001) and hydrocephalus (p≦0.001) on initial brain computed tomography (CT), median Glasgow Coma Scale (GCS) score at presentation (p≦0.001) and median intracerebral hemorrhage (ICH) score (P≦0.001) on admission were significant factors associated with neurologic deterioration. Stepwise logistic regression analysis showed that patients with obliteration of basal cistern on initial brain CT scan had an odds ratio (OR) of 9.17 (p = 0.002; 95% confidence interval (CI): 0.026 to 0.455) adjusted risk of neurologic deterioration compared with those without obliteration of basal cistern. An increase of 1 point in the ICH score on admission would increase the neurologic deterioration rate by 83.2% (p = 0.010; 95% CI: 1.153 to 2.912). The ROC curves showed that the AUC for ICH score on presentation was 0.719 (p = 0.000; 95% CI: 0.613-0.826) and the cutoff value was 2.5 (sensitivity 80.5% and specificity 73.7%)., Conclusion: Patients had obliteration of basal cistern on initial brain CT and ICH score greater or equal to 3 at admission implies a greater danger of neurologic deterioration during hospitalization. Cautious clinical assessments and repeated brain images study are mandatory for those high-risk patients to prevent neurologic deterioration during hospitalization.

Introduction: To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients., Methods: Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model., Results: The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV., Conclusion: Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients., Key Points: • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.

Background: Reduced baroreflex sensitivity (BRS) has been reported in patients with acute cardiovascular events. We tested the hypothesis that BRS varies in different subtypes of acute ischemic stroke (AIS) and that BRS is a predictor of clinical outcomes., Methods: We examined autonomic parameters in 34 patients with AIS, including the small deep hemisphere infarction, the large hemisphere infarction, and the brainstem infarction groups on Day 1, Day 7, and Day 30 after AIS. Autonomic parameters were also evaluated in 18 age- and sex-matched healthy volunteers as a control group. The clinical outcomes were analyzed using the modified Rankin scale at 30 days after stroke., Results: The BRS, Valsalva ratio, and heart rate response to deep breathing (HR-DB) were significantly lower in patients after AIS on admission than in controls ( p <0.01). The frequency domain of HRV (LF/HF ratio) was significantly increased in patients after AIS compared to controls ( p <0.05). BRS was significantly reduced in patients with large hemisphere infarction or brainstem infarction compared to patients with small deep hemisphere infarction on Day 1 after AIS ( p <0.01). Stepwise logistic regression showed that the levels of BRS and NIHSS are prognostic factors of 1-month outcomes in patients with AIS., Conclusion: Beside NIHSS score on admission, BRS is a potential prognostic factor of 1-month outcomes in patients with AIS. Patients with large hemisphere infarction or brainstem infarction have more blunting BRS than do those with lacunar infarction, which provides some insight into which patients may be expected to have a poor outcome.

Background: The elderly, and especially those with an immuno-compromised status, are vulnerable to infectious diseases. The purpose of this study was to examine the clinical characteristics and therapeutic outcomes of cryptococcal meningitis (CM) in elderly patients in Taiwan., Methods: Ninety-nine adult patients with CM were identified during a 15-year study period (2002-2016), of whom 38 elderly (≥ 65 years) patients (16 men and 22 women, median age 72.9 years; range 65-86 years) were included for analysis. The clinical characteristics and therapeutic outcomes of these patients were analyzed and compared to non-elderly adult patients (< 65 years) with CM., Results: Among the 38 patients, diabetes mellitus was the most common underlying condition (15), followed by adrenal insufficiency (7), malignancy (6), hematologic disorders (5), chronic obstructive pulmonary disease (5), autoimmune diseases (3), liver cirrhosis (3) and acquired immunodeficiency syndrome (1). Altered consciousness (29), fever (21) and headache (17) were the leading clinical manifestations. Positive cerebrospinal fluid and blood cultures for Cryptococcus (C.) neoformans were found in 26 and 9 patients, respectively. There were significant differences in gender, altered consciousness and recent cerebral infarction between the elderly and non-elderly groups. The elderly group had a high mortality rate (36.8%, 14/38), and the presence of cryptococcemia was the most significant prognostic factor., Conclusions: This study offers a preliminary view of the clinical characteristics of CM in the elderly. The results suggest that elderly patients (≥ 65 years) are more vulnerable to CM than adults aged < 65 years. Compared to the non-elderly group, the elderly group had female predominance, higher rates of altered consciousness and recent cerebral infarction as the clinical presentation. The presence of cryptococcemia was a significant prognostic factor in the elderly group. This study is limited by the small number of patients, and further large-scale studies are needed to better delineate this specific infectious syndrome.

Objective: As cell-free DNA levels in the pleural fluid and serum of parapneumonic pleural effusion (PPE) patients have not been thoroughly explored, we evaluated their diagnostic potential., Methods: Twenty-two PPE and 16 non-PPE patients were evaluated. Serum and pleural fluids were collected, and cell-free DNA was quantified. All biomarkers were assessed for correlation with days after admission. Receiver operating characteristic (ROC) curve analysis was used to determine diagnostic accuracy and optimal cut-off point., Results: Nuclear and mitochondrial DNA levels in the pleural fluid and nuclear DNA levels in serum of PPE patients were significantly higher than in those of the non-PPE patients. However, only cell-free DNA levels in pleural fluid correlated with days after admission among PPE patients (r= 0.464, 0.538, respectively). ROC curve analysis showed that nuclear and mitochondrial DNA in pleural fluid had AUCs of 0.945 and 0.889, respectively. With cut-off values of 134.9 and 17.8 ng/ml for nuclear and mitochondrial DNA in pleural fluid, respectively, 96% sensitivity and 81% specificity were observed for PPE diagnosis., Conclusion: Nuclear and mitochondrial DNA in pleural fluid possess PPE diagnostic potential and correlated with disease severity. Serum nuclear DNA could also be used to distinguish freshly admitted PPE patients (Day 1) from non-PPE patients, but with less accuracy.

Background: Although corticosteroids are an effective anti-inflammatory adjuvant therapy, the role of adjunctive steroid therapy in treating adult bacterial meningitis in Taiwan remains controversial., Methods: Cases of acute bacterial meningitis were identified from the annual hospitalization discharge claims of the National Health Insurance Research Database using International Classification of Diseases, Ninth Revision codes from January 2000 to December 2013. Patients were classified into two groups: (1) steroid group (adjunctive steroids and empirical antibiotics) and (2) placebo group (empirical antibiotics only)., Results: There were 15,037 patients enrolled in this study; of these, 57% (7175/15,037) and 52% (7862/15,037) were placed in the placebo and steroid groups, respectively. The case-fatality rates were 11.5% (826/7175) in the placebo group and 19.9% (1562/7862) in the steroid groups during hospitalization (P = 0.77). Further, the hazard ratio (relative to placebo group) of in-hospital and one-year case fatality rate were 0.923 (95% confidence interval [CI]: 0.846-1.007, P = 0.073) and 1.514 (95% CI: 1.425-1.608, P < 0.0001) according to the multivariate Cox model after adjustment for age and sex., Conclusion: On the basis of these results, steroid group had a more fulminant clinical course (e.g., acute respiratory failure and pneumonia, etc.), and unfavorable outcomes than placebo group. Therefore, more prospective, randomized, double-blind trials are warranted to evaluate the efficacy of adjunctive steroid therapy in treating adult bacterial meningitis in Taiwan., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Variability in HbA1c is associated with a higher risk of cardiovascular disease and microvascular complications in patients with type 2 diabetes. The present study evaluated the severity of somatic nerve dysfunction at different stages of chronic glycemic impairment, and its correlation with different cardio-metabolic parameters. The study was conducted on 223 patients with type 2 diabetes. We calculated the intrapersonal mean, standard deviation (SD), and coefficient of variation of HbA1c for each patient using all measurements obtained for 3 years prior to the study. Patients were divided into quartiles according to the SD of HbA1c, and we constructed composite scores of nerve conduction as the severity of peripheral neuropathy. Linear regression analysis was performed to evaluate the influence of independent variables on mean composite scores. Those with higher SD-HbA1c had a higher body mass index, mean and index HbA1c, triglyceride and uric acid level, urinary albumin excretion and albumin-creatinine ratio, proportion of insulin therapy, and prevalence of hypertension as the underlying diseases, but lower estimate glomerular filtration rate (eGFR). In addition, those with higher SD-HbA1c showed lower amplitudes and reduced motor nerve conduction velocity in tested nerves, and lower sensory nerve conduction velocity in the sural nerve. Furthermore, those with higher SD-HbA1c had higher composite scores of low extremities. Multiple linear regression analysis revealed that diabetes duration, SD-HbA1c, and eGFR were independently associated with mean composite scores. Based on our results, HbA1c variability plus chronic glycemic impairment is strongly associated with the severity of peripheral neuropathy in patients with type 2 diabetes. Aggressively control blood glucose to an acceptable range and avoid blood glucose fluctuations by individualized treatment to prevent further nerve damage.

Background: Several comorbidities contribute to an increased risk of infections in Parkinson's disease (PD) as the disease progresses. However, few studies have examined the correlation between sepsis and PD., Aim: The aim of this study is to disclose the presentation and outcome of serious infection in patients with PD in the emergency department., Methods: This retrospective cohort study enrolled patients with PD who had serious infection and were admitted to the emergency department between January 2007 and December 2013. For clinical comparison, we compared the clinical features, laboratory data, and outcomes with those of age- and sex-matched patients who had serious infection but not PD., Results: There were a total of 1,200 episodes of infected PD patients and 2,400 age- and sex-matched infected patients without PD as disease controls. PD patients had fewer comorbidities and lower severity of infectious disease but longer hospital stays than control group patients. The incidences of respiratory tract and urinary tract infections were higher in PD patients. The levels of inflammatory and organ dysfunction biomarkers in PD were lower and compatible with the severity of infectious disease. A total of 86 (7.2%) infected PD patients died during the 28-day admission compared to 339 (14.1%) in non-PD patients. Serum C-reactive protein, bandemia, and lactate could be used to predict mortality in infected PD patients., Conclusions: In infected patients with PD, respiratory and urinary tract infections were the two most common infectious sources. Empiric therapy based on experience could treat both respiratory and urinary tract infections. Early diagnosis and treatment are essential for survival.

Background: To identify the vulnerable areas associated with systemic oxidative stress and further disruption of these vulnerable areas by measuring the associated morphology and functional network alterations in Parkinson's disease (PD) patients with and without cognitive impairment., Methods: This prospective study was approved by the institutional review board of KCGMH, and written informed consent was obtained. Between December 2010 and May 2015, 41 PD patients with different levels of cognitive functions and 29 healthy volunteers underwent peripheral blood sampling to quantify systemic oxidative stress, as well as T1W volumetric and resting state functional MRI (rs-fMRI) scans. Rs-fMRI was used to derive the healthy intrinsic connectivity patterns seeded by the vulnerable areas associated with any of the significant oxidative stress markers. The two groups were compared in terms of the functional connectivity correlation coefficient (fc-CC) and gray matter volume (GMV) of the network seeded by the vulnerable areas., Results: The levels of oxidative stress markers, including leukocyte apoptosis and adhesion molecules, were significantly higher in the PD group. Using whole-brain VBM-based correlation analysis, the bilateral mesial temporal lobes (MTLs) were identified as the most vulnerable areas associated with lymphocyte apoptosis (P < 0.005). We found that the MTL network of healthy subjects resembled the PD-associated atrophy pattern. Furthermore, reduced fc-CC and GMV were further associated with the aggravated cognitive impairment., Conclusion: The MTLs are the vulnerable areas associated with peripheral lymphocyte infiltration, and disruptions of the MTL functional network in both architecture and functional connectivity might result in cognitive impairments in Parkinson's disease.

Background: Peritoneal dialysis (PD) is an increasingly popular therapeutic option for patients with advanced renal failure. However, intra-abdominal adhesions (IAA) represent a major unsolved problem in adequate PD performance. In this study, we investigated the role of previous abdominal surgery on the presence of subsequent IAA as well as outcomes in those patients with PD who had subsequent IAA., Methods: Two hundred and two patients who received continuous ambulatory peritoneal dialysis were prospectively enrolled in this study. We compared the PD adequacy indices and outcomes for technical failure in patients with and without subsequent IAA at presentation and a minimum of 2 years of follow-up., Results: Subsequent IAA accounted for 19% (38/202) of patients. Patients who had previous abdominal surgery had higher risks of subsequent IAA especially those patients who had higher mean ages (P=0.023). PD adequacy indices including both 24-hour dialysate volume and peritoneal WCcr L/week/1.73 m 2 were significantly lower in patients who had, as compared to those who did not have subsequent IAA (P=0.003 and 0.018, respectively). Although patients who had subsequent IAA had decreased PD adequacy, the development of technical failures during PD maintenance did not show significant differences at the 2-year minimum follow-up study., Conclusions: Subsequent IAA is not rare, especially in high-risk patients including those with previous abdominal surgery and higher mean ages. Although decreased PD adequacy after IAA was found, the development of technical failures was not significantly different at the 2-year minimum follow-up study.

Background: Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity., Methods: The numbers of circulating EPCs [CD133 + /CD34 + (%), KDR + /CD34 + (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT). The biomarkers and clinical scores were compared with those of 25 age- and sex-matched disease controls., Results: The numbers of KDR + /CD34 + (%) in the HBOT group following HBOT increased significantly, whereas the numbers of CD133 + /CD34 + (%) also showed a tendency to increase without statistical significance. The mean high-sensitivity C-reactive protein levels showed significant decrease post-HBOT follow-up in the HBOT group. The changes in KDR + /CD34 + EPC (%) numbers were positively correlated with changes in clinical outcomes scores (BI, NIHSS, and MRS) in the HBOT group., Conclusions: Based on the results of our study, HBOT can both improve short-term clinical outcomes and increase the number of circulating EPCs in patients with acute non-cardioembolic stroke.

The prognostic significance of clinical characteristics and neuroimaging features, especially cranial magnetic resonance imaging (MRI)-based neuroimaging features, in patients with human immunodeficiency virus (HIV)-negative cryptococcal meningitis (CM) has rarely been examined in the literature. We analyzed the clinical characteristics and MRI findings of 65 HIV-negative patients (43 men, 22 women, age 19-86 years) collected during a study period of 15 years (January 2001-December 2015). Their underlying conditions included diabetes mellitus, liver cirrhosis, hematologic disorders, autoimmune disorders, malignancy, chronic obstructive pulmonary disease, adrenal insufficiency and organ transplantation, and their clinical presentations included headache, altered consciousness, fever, seizure, visual disturbance and hearing impairment. The main cranial MRI findings were basal meningeal enhancement (44.6%, 29/65), dilated Virchow-Robin space/pseudocyst (43.1%, 28/65), "dirty" cerebrospinal fluid sign (38.5%, 25/65), hydrocephalus (36.9%, 21/65), acute/subacute cerebral infarct (ASCI, 21.5%, 14/65), cryptococcoma (9.2%, 6/65), and hazy brain base (1.5%, 1/65). The therapeutic results of the 65 patients were evaluated using the Glasgow Outcome Scale (GOS). A comparison of the good outcome group (GOS score = 4-5, n = 37) and poor outcome group (GOS score = 1-3, n = 28) revealed that both the presence of seizures and ASCI were significantly associated with the prognosis. A comparison of the groups with ASCI (n = 14) and without ASCI (n = 51) revealed that the presence of basal meningeal enhancement was a significant factor for the development of ASCI, and that this correlation may be associated with intense basal meningeal inflammation in adjacent small vessels., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Shunt procedures used to treat cryptococcal meningitis complicated with hydrocephalus and/or increased intracranial pressure (IICP) could result in cerebrospinal fluid (CSF) overdrainage, thereby presenting therapeutic challenges., Methods: We analyzed the clinical features and neuroimaging findings after the ventriculoperitoneal (VP) shunt procedure in 51 HIV (Human Immunodeficiency Virus)-negative patients with cryptococcal meningitis, to assess the risk factors associated with post-shunt CSF overdrainage., Results: Symptomatic CSF overdrainage occurred in 12% (6/51) of patients with cryptococcal meningitis who underwent the shunt procedure. Rapid deterioration of neurological conditions was found in 6 patients after the shunt procedure was performed, including disturbed consciousness, quadriparesis, and dysphasia in 5 patients and severe ataxia in 1. The mean duration of CSF overdrainage after the shunting procedure was 2-7 days (mean 4 days). The mean interval between meningitis onset to shunting procedure remained independently associated with CSF overdrainage, and the cut-off value for predicting CSF overdrainage in interval between meningitis onset to shunting procedure was 67.5 days., Conclusions: CSF overdrainage after the VP shunt procedure is not rare, especially in patients with a high-risk of cryptococcal meningitis who also have a prolonged duration of hydrocephalus and/or IICP., (Copyright © 2017. Published by Elsevier B.V.)