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1.  Elevated Serum Vascular Cell Adhesion Molecule-1 Is Associated with Septic Encephalopathy in Adult Community-Onset Severe Sepsis Patients 
BioMed Research International  2014;2014:598762.
Background and Aim. Septic encephalopathy (SE) is a common complication of severe sepsis. Increased concentrations of circulating soluble adhesion molecules are reported in septic patients. This study aimed to determine whether serum adhesion molecules are associated with SE. Methods. Seventy nontraumatic, nonsurgical adult patients with severe sepsis admitted through ER were evaluated. Serum adhesion molecules were assessed for their relationship with SE, and compared with other clinical predictors and biomarkers. Results. Twenty-three (32.8%) patients had SE. SE group had higher in-hospital mortality (40% versus 11%, P = 0.009) and their sVCAM-1, sICAM-1, and lactate levels on admission were also higher than non-SE group. By stepwise logistic regression model, sVCAM-1, age, and maximum 24-hours SOFA score were independently associated with septic encephalopathy. The AUC analysis of ROC curve of different biomarkers showed that sVCAM-1 is better to predict SE. The sVCAM-1 levels in the SE group were significantly higher than those of the non-SE group at three time periods (Days 1, 4, and 7). Conclusions. Septic encephalopathy implies higher mortality in nontraumatic, nonsurgical patients with severe sepsis. VCAM-1 level on presentation is a more powerful predictor of SE in these patients than lactate concentration and other adhesion molecules on admission.
doi:10.1155/2014/598762
PMCID: PMC4032707  PMID: 24883317
2.  Clinical features and predictive factors of intraventricular rupture in patients who have bacterial brain abscesses 
Background
Intraventricular rupture of brain abscesses (IVRBA) remains a catastrophic and fatal complication of bacterial brain abscess (BBA). However, no information has been reported about the risk factors that are predictive of intraventricular rupture.
Methods
This study was undertaken to determine the potential risk factors that are predictive of intraventricular ruptures in patients with BBA but without intraventricular rupture when arriving at the hospital. A comparison is also made between patients who already have IVRBA at the time of admission (initial IVRBA) and those who have the episode during hospitalisation (subsequent IVRBA).
Results
62 patients, including 45 who had initial IVRBA and 17 who had subsequent IVRBA, were examined. Stepwise logistic regression analysis showed that the adjusted risk of intraventricular rupture during hospitalisation for patients with multiloculated brain abscesses had an odds ratio (OR) of 4.2 (95% confidence interval (CI) 1.24 to 14.3; p = 0.02) compared with those without multiloculated brain abscesses (referent); a reduction of 1 mm in the distance between the ventricle and brain abscesses would increase the rupture rate by 10% (p = 0.006, OR 0.9, 95% CI 0.83 to 0.97).
Conclusion
This study shows that if the abscess is deep seated, multiloculated and close to the ventricle wall, a reduction of 1 mm in the distance between the ventricle and brain abscesses will increase the rupture rate by 10%. Despite aggressive medical and surgical management shown in this series, many patients continue to progress poorly.
doi:10.1136/jnnp.2006.097808
PMCID: PMC2117635  PMID: 17012340
3.  The Roles of Biomarkers of Oxidative Stress and Antioxidant in Alzheimer's Disease: A Systematic Review 
BioMed Research International  2014;2014:182303.
Purpose. Oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). This paper aims to examine whether biomarkers of oxidative stress and antioxidants could be useful biomarkers in AD, which might form the bases of future clinical studies. Methods. PubMed, SCOPUS, and Web of Science were systematically queried to obtain studies with available data regarding markers of oxidative stress and antioxidants from subjects with AD. Results and Conclusion. Although most studies show elevated serum markers of lipid peroxidation in AD, there is no sufficient evidence to justify the routine use of biomarkers as predictors of severity or outcome in AD.
doi:10.1155/2014/182303
PMCID: PMC4053273  PMID: 24949424
4.  Association between Oxidative Stress and Outcome in Different Subtypes of Acute Ischemic Stroke 
BioMed Research International  2014;2014:256879.
Objectives. This study investigated serum thiobarbituric acid-reactive substances (TBARS) and free thiol levels in different subtypes of acute ischemic stroke (AIS) and evaluated their association with clinical outcomes. Methods. This prospective study evaluated 100 AIS patients, including 75 with small-vessel and 25 with large-vessel diseases. Serum oxidative stress (TBARS) and antioxidant (thiol) were determined within 48 hours and days 7 and 30 after stroke. For comparison, 80 age- and sex-matched participants were evaluated as controls. Results. Serum TBARS was significantly higher and free thiol was lower in stroke patients than in the controls on days 1 and 7 after AIS. The level of free thiol was significantly lower in the large-vessel disease than in the small-vessel disease on day 7 after stroke. Using the stepwise logistic regression model for potential variables, only stroke subtype, NIHSS score, and serum TBARS level were independently associated with three-month outcome. Higher TBARS and lower thiol levels in the acute phase of stroke were associated with poor outcome. Conclusions. Patients with large-vessel disease have higher oxidative stress but lower antioxidant defense compared to those with small-vessel disease after AIS. Serum TBARS level at the acute phase of stroke is a potential predictor for three-month outcome.
doi:10.1155/2014/256879
PMCID: PMC4034452  PMID: 24895559
5.  The Association between Autoantibodies and Peripheral Neuropathy in Lupus Nephritis 
BioMed Research International  2014;2014:524940.
Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy in patients with systemic lupus erythematosus (SLE) and nephritis (SLE-LN) remain unsatisfactory. This study aimed to determine the autoantibodies levels in SLE-LN patients with peripheral neuropathy. Methods. Data of 559 SLE-LN patients were collected retrospectively, including titers of autoantibodies, electrodiagnostic studies, and clinical manifestations. Results. The neurologic manifestations of the SLE-LN patients were diverse and nonspecific. The prevalence rate of peripheral polyneuropathy was 2.68%, of which about 73.33% was mixed sensory-motor polyneuropathy. Numbness and functional gastrointestinal problems were the most prevalent symptoms and these were noted in every subtype of peripheral neuropathy. Among all the serology markers, anti-Ro was significantly associated with neuropathy related to SLE (P = 0.009). Conclusion. Peripheral neuropathy among LN patients is rare and may be easily overlooked. This study demonstrated that positive anti-Ro antibody may imply neuropathy in LN patients. Thus, anti-Ro can be considered a biomarker that should be added to the panel of conventional autoantibodies in LN patients.
doi:10.1155/2014/524940
PMCID: PMC4017733  PMID: 24864250
6.  Serial Serum Leukocyte Apoptosis Levels as Predictors of Outcome in Acute Traumatic Brain Injury 
BioMed Research International  2014;2014:720870.
Background. Apoptosis associates with secondary brain injury after traumatic brain injury (TBI). This study posits that serum leukocyte apoptosis levels in acute TBI are predictive of outcome. Methods. Two hundred and twenty-nine blood samples from 88 patients after acute TBI were obtained on admission and on Days 4 and 7. Serial apoptosis levels of different leukocyte subsets were examined in 88 TBI patients and 27 control subjects. Results. The leukocyte apoptosis was significantly higher in TBI patients than in controls. Brief unconsciousness (P = 0.009), motor deficits (P ≤ 0.001), GCS (P ≤ 0.001), ISS (P = 0.001), WBC count (P = 0.015), late apoptosis in lymphocytes and monocytes on Day 1 (P = 0.004 and P = 0.022, resp.), subdural hemorrhage on initial brain CT (P = 0.002), neurosurgical intervention (P ≤ 0.001), and acute posttraumatic seizure (P = 0.046) were significant risk factors of outcome. Only motor deficits (P = 0.033) and late apoptosis in monocytes on Day 1 (P = 0.037) were independently associated with outcome. A cutoff value of 5.72% of late apoptosis in monocytes was associated with poor outcome in acute TBI patients. Conclusion. There are varying degrees of apoptosis in patients following TBI and in healthy individuals. Such differential expression suggests that apoptosis in different leukocyte subsets plays an important role in outcome following injury.
doi:10.1155/2014/720870
PMCID: PMC4016848  PMID: 24864256
7.  The Association between Serological Biomarkers and Primary Sjogren's Syndrome Associated with Peripheral Polyneuropathy 
BioMed Research International  2014;2014:902492.
Background and Aim. The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy of Sjogren's syndrome (SJS) patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating autoantibodies levels in SJS patients with peripheral neuropathy. Methods. Two hundred and fifty serological positive (either anti-Ro or anti-La positive) SJS patients' data were collected retrospectively. The titers of autoantibodies, electrophysiology reports, and clinical manifestation were reviewed. Results. The prevalence rate of peripheral neuropathy is 7.2% in our study. Regarding classification of peripheral neuropathy, 12 had mixed sensorimotor polyneuropathy, six had cranial neuropathy. After stepwise logistic regression analysis, anti-β2 glycoprotein I (aβ2GP I) and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) were significantly associated with peripheral neuropathy in serology positive SJS (P = 0.01, P = 0.046, resp.). Conclusion. The occurrence of peripheral neuropathy among SJS patients is not frequent and easily overlooked. Our study demonstrated that aβ2GP I and p-ANCA levels may imply the danger of the occurrence of neuropathy in SJS patients, and they can be considered a biomarker that should be added to the panel of conventional autoantibody in SJS patients.
doi:10.1155/2014/902492
PMCID: PMC4005097  PMID: 24822219
8.  Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury 
BioMed Research International  2014;2014:340936.
The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI.
doi:10.1155/2014/340936
PMCID: PMC3996315  PMID: 24804213
9.  The Prognostic Values of Leukocyte Rho Kinase Activity in Acute Ischemic Stroke 
BioMed Research International  2014;2014:214587.
Objective. It has been reported that leukocyte ROCK activity is elevated in patients after ischemic stroke, but it is unclear whether leukocyte ROCK activity is associated with clinical outcomes following acute stroke events. The objective of this study is to investigate if leukocyte ROCK activity can predict the outcomes in patients with acute ischemic stroke. Materials and Methods. We enrolled 110 patients of acute ischemic stroke and measured the leukocyte ROCK activity and plasma level of inflammatory cytokines to correlate the clinical outcomes of these patients. Results. The leukocyte ROCK activity at 48 hours after admission in acute ischemic stroke patients was higher as compared to a risk-matched population. The leukocyte ROCK activity significantly correlated with National Institute of Health Stroke Scale (NIHSS) difference between admission and 90 days after stroke event. Kaplan-Meier survival estimates showed lower stroke-free survival during follow-up period in patients with high leukocyte ROCK activity or plasma hsCRP level. Leukocyte ROCK activity independently predicted the recurrent stroke in patients with atherosclerotic stroke. Conclusions. This study shows elevated leukocyte ROCK activity in patients with ischemic stroke as compared to risk-matched subjects and is an independent predictor for recurrent stroke.
doi:10.1155/2014/214587
PMCID: PMC3955656  PMID: 24716192
10.  Structural and cognitive deficits in chronic carbon monoxide intoxication: a voxel-based morphometry study 
BMC Neurology  2013;13:129.
Background
Patients with carbon monoxide (CO) intoxication may develop ongoing neurological and psychiatric symptoms that ebb and flow, a condition often called delayed encephalopathy (DE). The association between morphologic changes in the brain and neuropsychological deficits in DE is poorly understood.
Methods
Magnetic resonance imaging and neuropsychological tests were conducted on 11 CO patients with DE, 11 patients without DE, and 15 age-, sex-, and education-matched healthy subjects. Differences in gray matter volume (GMV) between the subgroups were assessed and further correlated with diminished cognitive functioning.
Results
As a group, the patients had lower regional GMV compared to controls in the following regions: basal ganglia, left claustrum, right amygdala, left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated with decreased perceptual organization and processing speed function. Those CO patients characterized by DE patients had a lower GMV in the left anterior cingulate and right amygdala, as well as lower levels of cognitive function, than the non-DE patients.
Conclusions
Patients with CO intoxication in the chronic stage showed a worse cognitive and morphologic outcome, especially those with DE. This study provides additional evidence of gray matter structural abnormalities in the pathophysiology of DE in chronic CO intoxicated patients.
doi:10.1186/1471-2377-13-129
PMCID: PMC3850907  PMID: 24083408
Carbon monoxide intoxication; Cognitive deficits; Delayed encephalopathy; Magnetic resonance imaging; Voxel-based morphometry
11.  Ultrasonographic assessment of carpal tunnel syndrome of mild and moderate severity in diabetic patients by using an 8-point measurement of median nerve cross-sectional areas 
BMC Medical Imaging  2012;12:15.
Background
Using high-resolution ultrasonography (US) to measure the median nerve cross-sectional areas (CSAs) such as in the “inching test” conducted in nerve conduction studies is a valuable tool to assess carpal tunnel syndrome (CTS). However, using this US measurement method to assess the median nerve CSA in diabetic patients with CTS has rarely been reported. Therefore, we used this US measurement method in this study to measure median nerve CSAs and to compare the CSAs of idiopathic, diabetic and diabetic polyneuropathy (DPN) patients with CTS.
Methods
124 hands belonging to 89 participants were included and assigned into four groups: control (32), idiopathic (38), diabetic (38) and DPN (16) CTS. In the latter two groups, only patients with mild and moderately severe CTS were included. The median nerve CSAs were measured at 8 points marked as i4, i3, i2, i1, w, o1, o2, and o3 in the inching test. The measured CSAs in each group of participants were compared.
Results
Compared with the CSAs of the control group, enlarged CSAs were found in the idiopathic, diabetic and DPN CTS groups. The CSAs were larger at i4, i3 and i2 in the diabetic CTS group compared to the idiopathic CTS group. The CSAs measured at the i1 and w levels of the DPN CTS group were smaller than those of the diabetic CTS group. In the diabetic CTS group, the cut-off values of CSAs measured at the inlet, wrist crease, and outlet were 15.3 mm2, 13.4 mm2 and 10.0 mm2, respectively, and 14.0 mm2, 12.5 mm2 and 10.5 mm2, respectively, in the DPN CTS group.
Conclusions
Compared with the median nerve CSAs of the control and idiopathic CTS groups, the median nerve CSAs of the diabetic patients with CTS were significantly enlarged. However, compared with the diabetic CTS group, the CSAs were significantly smaller in the DPN CTS group. This US 8-point measurement method can be of value as an important complementary tool for CTS studies and diagnosis among diabetic patients.
doi:10.1186/1471-2342-12-15
PMCID: PMC3490711  PMID: 22768921
12.  Sweat output measurement of the post-ganglion sudomotor response by Q-Sweat Test: a normative database of Chinese individuals 
BMC Neuroscience  2012;13:62.
Background
Q-Sweat is a model used for evaluating the post-ganglionic sudomotor function by assessing sweat response. This study aimed to establish the normative database of Q-Sweat test among Chinese individuals since this type of information is currently lacking.
Results
One hundred and fifty (150) healthy volunteers, 76 men and 74 women with age range of 22–76 years were included. Skin temperature and sweat onset latency measured at the four sites (i.e., the forearm, proximal leg, distal leg, and the foot) did not significantly correlate with age, gender, body height (BH), body weight (BW), and body mass index (BMI) but the total sweat volume measured in all four sites significantly correlated with sex, BH, and BW. Except for the distal leg, the total sweat volume measured at the other three sites had a significant correlation with BMI. In terms of gender, men had larger total sweat volume, with median differences at the forearm, proximal leg, distal leg, and foot of 0.591 μl, 0.693 μl, 0.696 μl, and 0.358 μl, respectively. Regarding BW difference (≥62 and < 62 Kg), those with BW ≥62 Kg had larger total sweat volume. Median differences at the forearm, proximal leg, distal leg, and foot were 0.538 μl, 0.744 μl, 0.695 μl, and 0.338 μl, respectively. There was an uneven distribution of male and female participants in the two BW groups. In all conditions, the total sweat volume recorded at the foot site was the smallest.
Conclusion
This is the first report to show the normative database of sweat response in Chinese participants evaluated using Q-Sweat device. This normative database can help guide further research on post-ganglionic sudomotor or related clinical practice involving a Chinese population.
doi:10.1186/1471-2202-13-62
PMCID: PMC3444327  PMID: 22682097
Age; Body height; Body mass index; Body weight; Chinese; Gender; Normative database; Q-Sweat; Sweat output
13.  Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy 
BMC Neurology  2012;12:15.
Background
Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored.
Methods
Thirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels.
Results
Compared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (p < 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (p < 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, p < 0.01), and inversely with memory scores in the late registration (σ = −0.276, p = 0.01) and early recall score (σ = −0.304, p = 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, p = 0.007) after controlling for the effect of age.
Conclusions
Our results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.
doi:10.1186/1471-2377-12-15
PMCID: PMC3342103  PMID: 22417223
Biomarkers; Neuropsychological performances; Temporal lobe epilepsy; Gray matter atrophy; Heat shock proteins
14.  Clinical characteristics and prognosis of acute bacterial meningitis in elderly patients over 65: a hospital-based study 
BMC Geriatrics  2011;11:91.
Background
To examine the clinical characteristics of bacterial meningitis in elderly patients.
Methods
261 patients with adult bacterial meningitis (ABM), collected during a study period of 11 years (2000-2010), were included for study. Among them, 87 patients aged ≥ 65 years and were classified as the elderly group. The clinical and laboratory characteristics and prognostic factors were analyzed, and a clinical comparison with those of non-elderly ABM patients was also made.
Results
The 87 elderly ABM patients were composed of 53 males and 34 females, aged 65-87 years old (median = 71 years). Diabetes mellitus (DM) was the most common underlying condition (34%), followed by end stage renal disease (7%), alcoholism (4%) and malignancies (4%). Fever was the most common clinical manifestation (86%), followed by altered consciousness (62%), leukocytosis (53%), hydrocephalus (38%), seizure (30%), bacteremia (21%) and shock (11%). Thirty-nine of these 87 elderly ABM patients had spontaneous infection, while the other 48 had post-neurosurgical infection. Forty-four patients contracted ABM in a community-acquired state, while the other 43, a nosocomial state. The therapeutic results of the 87 elderly ABM patients were that 34 patients expired and 53 patients survived. The comparative results of the clinical and laboratory characteristics between the elderly and non-elderly ABM patients showed that only peripheral blood leukocytosis was significant. Presence of shock and seizure were significant prognostic factors of elderly ABM patients.
Conclusions
Elderly ABM patients accounted for 34.8% of the overall ABM cases, and this relatively high incidence rate may signify the future burden of ABM in the elderly population in Taiwan. The relative frequency of implicated pathogens of elderly ABM is similar to that of non-elderly ABM. Compared with non-elderly patients, the elderly ABM patients have a significantly lower incidence of peripheral blood leukocytosis. The mortality rate of elderly ABM remains high, and the presence of shock and seizures are important prognostic factors.
doi:10.1186/1471-2318-11-91
PMCID: PMC3282677  PMID: 22204457
15.  Ultrasonographic median nerve cross-section areas measured by 8-point "inching test" for idiopathic carpal tunnel syndrome: a correlation of nerve conduction study severity and duration of clinical symptoms 
BMC Medical Imaging  2011;11:22.
Background
Incremental palmar stimulation of the median nerve sensory conduction at the wrist, the "inching test", provides an assessment with reference to segments proximal and distal to the entrapment. This study used high-resolution ultrasonography (US) to measure the median nerve's cross-section areas (CSAs) like the "inching test" and to correlate with the nerve conduction study (NCS) severity and duration of carpal tunnel syndrome (CTS).
Methods
Two hundred and twelve (212) "CTS-hands" from 135 CTS patients and 50 asymptomatic hands ("A-hands") from 25 control individuals were enrolled. The median nerve CSAs were measured at the 8-point marked as i4, i3, i2, i1, w, o1, o2, and 03 in inching test. The NCS severities were classified into six groups based on motor and sensory responses (i.e., negative, minimal, mild, moderate, severe, and extreme). Results of US studies were compared in terms of NCS severity and duration of clinical CTS symptoms.
Results
There was significantly larger CSA of the NCS negative group of "CTS-hands" than of "A-hands". The cut-off values of the CSAs of the NCS negative CTS group were 12.5 mm2, 11.5 mm2 and 10.1 mm2 at the inlet, wrist crease, and outlet, respectively. Of the 212 "CTS-hands", 32 were NCS negative while 40 had minimal, 43 mild, 85 moderate, 10 severe, and two extreme NCS severities. The CSAs of "CTS-hands" positively correlated with different NCS severities and with the duration of CTS symptoms. By duration of clinical symptoms, 12 of the 212 "CTS-hands" were in the 1 month group; 82 in >1 month and ≤12 months group, and 118 in >12 months group. In "inching test", segments i4-i3 and i3-i2 were the most common "positive-site". The corresponding CSAs measured at i4 and i3, but not at i2, were significantly larger than those measured at points that were not "positive-site".
Conclusions
Using the 8-point measurement of the median nerve CSA from inlet to outlet similar to the "inching test" has positive correlations with NCS severity and duration of CTS clinical symptoms, and can provide more information on anatomic changes. Combined NCS and US studies using the 8-point measurement may have a higher positive rate than NCS alone for diagnosing CTS.
doi:10.1186/1471-2342-11-22
PMCID: PMC3292452  PMID: 22189264
16.  The impact of preoperative magnetic resonance images on outcome of cemented vertebrae 
European Spine Journal  2010;19(11):1899-1906.
Refracture of cemented vertebrae is often seen after percutaneous vertebroplasty. The purpose of this prospective study was to evaluate pre-procedural magnetic resonance images (MRI) for the prediction of further collapse and vertebral height loss after vertebroplasty. This study included 81 consecutive patients (73 women and 8 men) with osteoporotic compression fractures. MR studies were performed 1–5 days before vertebroplasty. Patients were followed to evaluate refracture for a minimum of 6 months after treatment. Cox proportional hazards model was used to evaluate relationships between clinical data, covariates on pre-procedural MRI, and the presence of cemented vertebrae refracture. The mean refracture rate was estimated with the Kaplan–Meier method. After a mean follow-up of 23.0 ± 8.2 months, 46 cemented vertebrae (57%) experienced refracture, and the mean loss of anterior vertebral height was 11.3%. The 1-year refracture rate after vertebroplasty was 7%, and rapid increased to 76% in the third year. Cox proportional analysis showed that any 1% decrease in signal intensity on T2-weighted images of the injured vertebra will increase the refracture rate by 0.74% (OR = 0.26, 95% CI 0.08–0.81, p = 0.02), and a 1% increase in the poorly enhanced volume ratio will increase the refracture rate by 4.3% (OR = 5.32, 95% CI 1.22–23.14, p = 0.03). Quantitative pre-procedural MRI appears to be useful in exploring vertebrae with poor bone marrow integrity, which effectively predicts the subsequent refracture of cemented vertebra.
doi:10.1007/s00586-010-1434-6
PMCID: PMC2989252  PMID: 20607571
Magnetic resonance imaging; Osteoporosis; Spine; Vertebral fracture; Vertebroplasty
17.  Neuromuscular abnormality and autonomic dysfunction in patients with cerebrotendinous xanthomatosis 
BMC Neurology  2011;11:63.
Background
Cerebrotendinous xanthomatosis (CTX) is a rare lipid-storage disease. Neuromuscular abnormality and autonomic system (ANS) dysfuction in CTX are rarely examined in large-scale studies in the literature. We studied the peripheral nervous system, myopathology, and autonomic system of four CTX patients and performed a literature review of the reported CTX patients with peripheral neuropathy.
Methods
Four biochemically and genetically confirmed CTX patients, belonging to two families, were included for study and all received nerve conduction study (NCS), muscle biopsy for histopathologic and ultrastructural study, skin biopsy for intraepidermal nerve fiber (INEF) density measurement, autonomic testings including sympathetic skin response, R-R interval variation and head-up tilt test using an automated tilt table to record the changes of blood pressure and heart rate in different postures. The Q-Sweat test was also applied for the detection of sweat amount and onset time of response. The clinical characteristics, study methods and results of 13 studies of peripheral neuropathy in CTX patients in the literature were also recorded for analysis.
Results
The results of NCS study showed axonal sensory-motor polyneuropathy in three CTX cases and mixed axonal and demyelinating sensor-motor polyneuropathy in one. The myopathological and histopathologic studies revealed mild denervation characteristics, but the ultrastructural study revealed changes of mitochondria and the membranous system, and increased amounts of glycogen, lipofuscin and lipid deposition. The ANS study revealed different degrees of abnormalities in the applied tests and the INEF density measurement showed small fiber neuropathy in three of the four CTX patients. The literature review of peripheral neuropathy in CTX revealed different types of peripheral neuropathy, of which axonal peripheral neuropathy was the most common.
Conclusions
Peripheral neuropathy, especially the subtype of axonal sensori-motor neuropathy, is common in patients with CTX. Evidence of lipid metabolic derangement in CTX can be reflected in ultrastructural studies of muscles. With an adequate multi-parametric evaluation, a high incidence of ANS abnormalities can be seen in this rare lipid-storage disease, and a high incidence of small fiber involvement is also reflected in the IENF density measurement of skin biopsies.
doi:10.1186/1471-2377-11-63
PMCID: PMC3119170  PMID: 21627786
18.  Clinical characteristics and therapeutic outcomes of nosocomial super-infection in adult bacterial meningitis 
BMC Infectious Diseases  2011;11:133.
Background
Super-infection in adult bacterial meningitis (ABM) is a condition wherein the cerebrospinal fluid (CSF) grows new pathogen(s) during the therapeutic course of meningitis. It is an uncommon but clinically important condition rarely examined in literature.
Methods
Twenty-seven episodes of super-infection states in 21 ABM patients collected in a 9.5-year study period (January 2001 to June 2010) were evaluated. The clinical characteristics, implicated pathogens, results of antimicrobial susceptibility tests, and therapeutic outcomes were analyzed.
Results
Twenty-one patients (13 men, 8 women) aged 25-73 years (median, 45 years) had post-neurosurgical state as the preceding event and nosocomial infection. The post-neurosurgical states included spontaneous intracranial hemorrhage (ICH) with craniectomy or craniotomy with extra-ventricular drainage (EVD) or ventriculo-peritoneal shunt (VPS) in 10 patients, traumatic ICH with craniectomy or craniotomy with EVD or VPS in 6 patients, hydrocephalus s/p VPS in 2 patients, and one patient each with cerebral infarct s/p craniectomy with EVD, meningeal metastasis s/p Omaya implant, and head injury. All 21 patients had EVD and/or VP shunt and/or Omaya implant during the whole course of ABM. Recurrent fever was the most common presentation and the implicated bacterial pathogens were protean, many of which were antibiotic resistant. Most patients required adjustment of antibiotics after the pathogens were identified but even with antimicrobial therapy, 33.3% (7/21) died. Morbidity was also high among survivors.
Conclusions
Super-infection in ABM is usually seen in patients with preceding neurosurgical event, especially insertion of an external drainage device. Repeat CSF culture is mandatory for diagnostic confirmation because most of the implicated bacterial strains are non-susceptible to common antibiotics used. Unusual pathogens like anaerobic bacteria and fungi may also appear. Despite antimicrobial therapy, prognosis remains poor.
doi:10.1186/1471-2334-11-133
PMCID: PMC3118143  PMID: 21592372
19.  Acute/subacute cerebral infarction (ASCI) in HIV-negative adults with cryptococcal meningoencephalitis (CM): a MRI-based follow-up study and a clinical comparison to HIV-negative CM adults without ASCI 
BMC Neurology  2011;11:12.
Background
Acute/subacute cerebral infarction (ASCI) in HIV-negative cryptococcal meningoencephalitis (CM) adults has rarely been examined by a series of MRI-based follow-up study. We studied a series of MRI follow-up study of CM adults and compared the clinical characters of those with ASCI and those without ASCI.
Methods
The clinical characteristics and a series of brain MRI findings of seven CM adults with ASCI were enrolled for analysis. The clinical characteristics of another 30 HIV-negative CM adults who did not have ASCI were also included for a comparative analysis.
Results
The seven HIV-negative CM adults with ASCI were four men and three women, aged 46-78 years. Lacunar infarction was the type of ASCI, and 86% (6/7) of the ACSI were multiple infarctions distributed in both the anterior and posterior cerebrovascular territories. The seven CM patients with ASCI were significantly older and had a higher rate of DM and previous stroke than the other 30 CM adults without ASCI. They also had a higher incidence of consciousness disturbance at presentation and had a poor prognosis.
Conclusion
ASCI was found in 18.9% (7/37) of HIV-negative CM adults. Serial MRI follow-up studies may allow a better delineation of ASCI in this specific group of infectious disease and multiple lacunar infarctions was the most common type. Older in age and presence of DM and previous stroke were the significant underlying conditions. CM patients with ASCI also had a poor therapeutic outcome.
doi:10.1186/1471-2377-11-12
PMCID: PMC3037868  PMID: 21269442
20.  Multi-parametric neuroimaging evaluation of cerebrotendinous xanthomatosis and its correlation with neuropsychological presentations 
BMC Neurology  2010;10:59.
Background
Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder. Recent studies show that brain damage in CTX patients extends beyond the abnormalities observed on conventional magnetic resonance imaging (MRI). We studied the MRI and 99 mTc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) findings of CTX patients and made a correlation with the neuropsychological presentations.
Methods
Diffusion tensor imaging (DTI) and 3D T1-weighted images of five CTX patients were compared with 15 age-matched controls. Voxel-based morphometry (VBM) was use to delineate gray matter (GM) and white matter (WM) volume loss. Fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues derived from DTI were used to detect WM changes and correlate with neuropsychological results. SPECT functional studies were used to correlate with GM changes.
Results
Cognitive results showed that aside from moderate mental retardation, the patient group performed worse in all cognitive domains. Despite the extensive GM atrophy pattern, the cerebellum, peri-Sylvian regions and parietal-occipital regions were correlated with SPECT results. WM atrophy located in the peri-dentate and left cerebral peduncle areas corresponded with changes in diffusion measures, while axial and radial diffusivity suggested both demyelinating and axonal changes. Changes in FA and MD were preceded by VBM in the corpus callosum and corona radiata. Cognitive results correlated with FA changes.
Conclusion
In CTX, GM atrophy affected the perfusion patterns. Changes in WM included atrophy, and axonal changes with demyelination. Disconnection of major fiber tracts among different cortical regions may contribute to cognitive impairment.
doi:10.1186/1471-2377-10-59
PMCID: PMC2909944  PMID: 20602799
21.  Diffusion Tensor Imaging Study of White Matter Damage in Chronic Meningitis 
PLoS ONE  2014;9(6):e98210.
Tuberculous meningitis (TBM) and cryptococcal meningitis (CM) are two of the most common types of chronic meningitis. This study aimed to assess whether chronic neuro-psychological sequelae are associated with micro-structure white matter (WM) damage in HIV-negative chronic meningitis. Nineteen HIV-negative TBM patients, 13 HIV-negative CM patients, and 32 sex- and age-matched healthy volunteers were evaluated and compared. The clinical relevance of WM integrity was studied using voxel-based diffusion tensor imaging (DTI) magnetic resonance imaging. All of the participants underwent complete medical and neurologic examinations, and neuro-psychological testing. Differences in DTI indices correlated with the presence of neuro-psychological rating scores and cerebrospinal fluid (CSF) analysis during the initial hospitalization. Patients with CM had more severe cognitive deficits than healthy subjects, especially in TBM. There were changes in WM integrity in several limbic regions, including the para-hippocampal gyrus and cingulate gyrus, and in the WM close to the globus pallidus. A decline in WM integrity close to the globus pallidus and anterior cingulate gyrus was associated with worse CSF analysis profiles. Poorer DTI parameters directly correlated with worse cognitive performance on follow-up. These correlations suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities. Abnormalities in the limbic system and globus pallidus, with their close relationship to the CSF space, may be specific biomarkers for disease evaluation.
doi:10.1371/journal.pone.0098210
PMCID: PMC4043527  PMID: 24892826
22.  The Association among Antioxidant Enzymes, Autoantibodies, and Disease Severity Score in Systemic Lupus Erythematosus: Comparison of Neuropsychiatric and Nonneuropsychiatric Groups 
BioMed Research International  2014;2014:137231.
Background. Antioxidative capacity plays an important role in the severity of systemic lupus erythematosus (SLE), which is characterized by autoantibodies. This study aimed to determine the relationship among autoantibody titers, antioxidative stress reserve, and severity of SLE. Methods. The autoantibody titers, clinical markers, antioxidant enzyme levels, and disease activity index (SLEDAI-2k) of 32 SLE patients and 16 healthy controls were compared. We also compared both the neuropsychiatric (NPSLE) and nonneuropsychiatric (non-NPSLE) groups. Results. Superoxide dismutase in red blood cells was significantly lower in the SLE than in the control group. CRP levels are significant higher in SLE patients than in control group (P = 0.034). Among the autoantibodies, anti-U1RNP (P = 0.008), a-Sm (P = 0.027), and anti-ribosomal p (P = 0.028) significantly negatively correlated with glutathione levels. There has no significant correlation between SLE disease activity indexes (SLEDAI) and levels of C3, C4, and antioxidant enzymes. Conclusions. Erythrocyte superoxide dismutase is significantly lower in both NPSLE and non-NPSLE groups. SLE patients have both higher CRP and autoantibodies level and decreased superoxide dismutase level than the healthy control group.
doi:10.1155/2014/137231
PMCID: PMC4024413  PMID: 24877055
23.  Peripheral Leukocyte Apoptosis in Patients with Parkinsonism: Correlation with Clinical Characteristics and Neuroimaging Findings 
BioMed Research International  2014;2014:635923.
Apoptosis of both brain neurons and peripheral blood leukocyte is believed to be an important biomarker for evaluating the functional status of Parkinson's disease (PD). However, their correlation remains unknown. A better understanding of the pathophysiology of neurodegeneration is essential for the treatment and prevention of PD. The present study demonstrated that leukocyte apoptosis is significantly higher in PD patients and is associated with central dopamine neuron loss by using 99mTc-TRODAT-1 SPECT. The leukocyte apoptosis and striatal dopamine transporter uptake ratios were further associated with increased severity and longer duration of disease. The interaction between brain and systemic inflammation may be responsible for the neurodegenerative disease progression.
doi:10.1155/2014/635923
PMCID: PMC3984850  PMID: 24795890
24.  Statin therapy reduces oxidized low density lipoprotein level, a risk factor for stroke outcome 
Critical Care  2014;18(1):R16.
Introduction
Statins are reported to have anti-inflammatory and anti-oxidative effects aside from cholesterol-lowering effects. This study aimed to evaluate the effects of statin therapy on oxidized LDL (Ox-LDL) and the clinical outcome of patients with acute ischemic stroke (AIS).
Methods
This prospective study enrolled 120 patients with AIS divided in the statin (n = 55) and non-statin (n = 65) groups. Eighty sex- and age- matched participants were recruited as risk controls. Ox-LDL was measured using a monoclonal antibody-based enzyme-linked immune-sorbent assay at different time points after AIS. The clinical outcomes were analyzed between the statin and non-statin groups.
Results
Plasma Ox-LDL was significantly higher in stroke patients than in the controls (P < 0.001). Plasma Ox-LDL level was significantly reduced in the statin group on day 7 and day 30 compared to the non-statin group (P < 0.01). The plasma Ox-LDL positively correlated with serum total cholesterol, LDL-cholesterol, and hemoglobin A1c (HbA1c). Among the potential risk factors, only National Institutes of Health stroke scale (NIHSS) score and Ox-LDL level on admission were independently associated with 3-month outcome.
Conclusions
Our study demonstrates that statin therapy reduces plasma Ox-LDL level after AIS. Plasma Ox-LDL may be a more powerful predictor than serum LDL, high-sensitivity C-reactive protein or white blood cell counts for stroke outcome. Therefore, assay of plasma Ox-LDL should be added as a predictor among the panel of conventional biomarkers in stroke outcome.
doi:10.1186/cc13695
PMCID: PMC4056016  PMID: 24423248
25.  Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma 
Background
Vascular abnormalities are the predominant histologic changes associated with radiation in nasopharyngeal carcinoma (NPC). This study examined if the duration after radiotherapy correlates with the progression of carotid intima-media thickness (IMT) and investigated its relationship with inflammatory markers.
Methods
One hundred and five NPC patients post-radiotherapy for more than one year and 25 healthy control subjects were examined by B-mode ultrasound for IMT measurement at the far wall of the common carotid artery (CCA). Surrogate markers including lipid profile, HbA1c, and high sensitive C-reactive protein (hs-CRP) were assessed.
Results
The IMT of CCA was significantly increased in NPC patients and carotid plaque was detected in 38 NPC patients (38/105, 36.2%). Significant risk factors for carotid plaques included age, duration after radiotherapy, and HbA1c levels. Age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count positively correlated with IMT. The cut-off value of age and duration after radiotherapy for the presence of plaque was 52.5 years and 42.5 months, respectively. In NPC subjects, multiple linear regression analysis revealed that age, gender, duration after radiotherapy and platelet counts were independently associated with CCA IMT. After adjustments for age, gender and platelet counts, IMT increased in a linear manner with duration after radiotherapy.
Conclusions
Radiation-induced vasculopathy is a dynamic and progressive process due to late radiation effects. Extra-cranial color-coded duplex sonography can be part of routine follow-up in NPC patients aged ≥50 years at 40 months post-radiotherapy.
doi:10.1186/1748-717X-8-261
PMCID: PMC3827874  PMID: 24196030
Atherosclerosis; Nasopharyngeal carcinoma; Radiotherapy; Risk factors

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