Elevated plasma neurofilament light chain in immune-mediated neurological disorders (IMND) detected by immunomagnetic reduction (IMR).

BACKGROUND: In cases of immune-mediated neurological disorders (IMND), different syndromes are associated with antibodies against neuronal surface antigens, intra-neuronal antigens, astrocytic aquaporin, and gangliosides. These autoantibodies can be pathogenic or connected to neuroinflammation and resulting neuronal injuries. This study aims to identify a blood biomarker that can detect neuronal damage in individuals with IMND. To this end, we use immunomagnetic reduction (IMR) nanobead technology to measure plasma neurofilament light chain (NfL). METHODS: The patients with IMND were enrolled in the Chang Gung Memorial Hospital at Keelung from 2018 to 2023. Seronegative patients were excluded based on the results of antibody tests. The healthy controls (HC) were community-dwelling adults from the Northeastern Taiwan Community Medicine Research Cohort (NTCMRC) conducted by the Community Medicine Research Center of the Keelung CGMH from 2020 to 2022. IMR technique detects magnetic susceptibility via measuring magnetic signal reduction caused by antigen-antibody immunocomplex formation on magnetic nanobeads. The plasma level of NfL was determined by the magnetic susceptibility changes in IMR. RESULTS: The study enrolled 57 IMND patients from the hospital and 73 HC participants from the communities. The plasma NfL was significantly higher in the IMND than in the HC (11.022 ± 2.637 vs. 9.664 ± 2.610 pg/mL, p = 0.004), regardless of age effects on plasma NfL in an analysis of covariance (ANCOVA) (F = 0.720, p = 0.950). In the receiver of operation curve analysis, the area under curve for plasma NfL to discriminate IMND and HC was 0.664 (95% CI = 0.549 to 0.739, p = 0.005). The subgroup analysis of plasma NfL in the IMND patients showed no difference between peripheral immune-mediated neuropathy (IMN) and central immune-mediated encephalomyelitis (IMEM) (11.331 ± 2.895 vs. 10.627 ± 2.260 pg/mL, p = 0.322), nor between tumor and non-tumor IMND (10.784 ± 3.446 vs. 11.093 ± 2.391 pg/mL, p = 0.714). Additionally, the antibody class of ganglioside antibodies in IMN did not have an impact on plasma NfL level (p = 0.857). CONCLUSION: Plasma NfL measurement is a reliable indicator of axonal injuries in patients with IMND. It is equally effective in detecting nerve injuries in inflammatory peripheral neuropathies and central neuroinflammation. The IMR nanobead technology offers a feasible method of detecting plasma NfL, which helps identify axonal injuries in IMND.

Case Report: Plasma Biomarkers Reflect Immune Mechanisms of Guillain-Barré Syndrome.

This case series reported a group of patients with Guillain-Barré syndrome (GBS) and their plasma cytokine changes before and after immunotherapy. We aimed to understand GBS's pathogenesis and pathophysiology through observing the interval differences of the representative cytokines, which were the thymus and activation regulated chemokine (TARC) for T-cell chemotaxis, CD40 ligand (CD40L) for cosimulation of B and T cells, activated complement component C5/C5a, and brain-derived neurotrophic factor (BDNF) for survival and regenerative responses to nerve injuries. The fluorescence magnetic bead-based multiplexing immunoassay simultaneously quantified the five cytokines in a single sample. From June 2018 to December 2019, we enrolled five GBS patients who had completed before-after blood cytokine measurements. One patient was diagnosed with paraneoplastic GBS and excluded from the following cytokine analysis. The BDNF level decreased consistently in all the patients and made it a potential biomarker for the acute stage of GBS. Interval changes of the other four cytokines were relatively inconsistent and possibly related to interindividual differences in the immune response to GBS triggers, types of GBS variants, and classes of antiganglioside antibodies. In summary, utilizing the multiplexing immunoassay helps in understanding the complex immune mechanisms of GBS and the variation of immune responses in GBS subtypes; this method is feasible for identifying potential biomarkers of GBS.

Cytokine changes during treatment of anti-Caspr2 encephalitis: a case report.

BACKGROUND: Cytokines are effective molecules of immune reactions. They work in inflammatory sites as well as circulate in the blood. Cytokines in the cerebrospinal fluid have been suggested to be markers of autoimmune encephalitis and reflect disease progression. However, studies on blood cytokines in autoimmune encephalitis are scarce. We report a case presenting with serial changes in blood cytokine levels in a male patient with anti-contactin-associated protein 2 (Caspr2) encephalitis. CASE PRESENTATION: A 61-year-old man without systemic disease presented with ataxia and speech disturbance 1 week. After admission, he further developed visual hallucinations, psychosis, and consciousness deterioration. Brain magnetic resonance imaging and infection and tumor surveillances were negative. 18F-fluorodeoxyglucose positron emission tomography of brain revealed frontal and occipital hypometabolism and anterior cingulate gyrus and mesial temporal hypermetabolism. Autoimmune studies confirmed Caspr2 antibodies in his blood. After receiving a diagnosis of anti-Caspr2 encephalitis, the patient received steroids, plasmapheresis, and zonisamide. He recovered well and was totally independent 6 months after disease onset. A cytokine profiler array kit was used to investigate neuroimmune mechanisms during the disease course. Several cytokines showed significant changes in plasma levels, such as B cell activating factor for B cell proliferation; thymus and activation-regulated chemokine for T cell chemoattraction; soluble CD40 ligand for Th2 cell mediation; C5/C5a for complement activation; brain-derived neurotrophic factor for neuronal survival response; and dipeptidyl peptidase 4, retinol binding protein, dickkopf-related protein, and epidermal growth factor for response to environmental provocation. The concentration of cytokines was verified using Luminex multiplexing assay. CONCLUSIONS: Due to their easy accessibility, blood cytokines are potential biomarkers of autoimmune encephalitis. Based on the investigating platform of this single case study, future larger scale studies are warranted.

Different FDG-PET metabolic patterns of anti-AMPAR and anti-NMDAR encephalitis: Case report and literature review.

INTRODUCTION: 18 F-fluorodeoxyglucose (FDG)-PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti-NMDAR and anti-AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis. METHODS: The cerebral glucose metabolism was evaluated by FDG-PET/CT during acute-to-subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z-score and visualized on three-dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities. RESULTS: The three-dimensional stereotactic surface projection displayed frontal-dominant hypometabolism in a 66-year-old female patient with anti-AMPAR encephalitis and occipital-dominant hypometabolism in a 29-year-old female patient with anti-NMDAR encephalitis. Receptor density maps revealed opposite frontal-occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG-PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti-NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery. CONCLUSIONS: The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG-PET of brain a valuable diagnostic tool.

The Differences of Serum Metabolites Between Patients With Early-Stage Alzheimer's Disease and Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is regarded as a transition phase between normal aging and Alzheimer's disease (AD). Identification of novel and non-invasive biomarkers that can distinguish AD at an early stage from MCI is warranted for therapeutic and support planning. The goal of this study was to identify the differences of serum metabolomic profiles between MCI and early-stage AD, which could be potential non-invasive biomarkers for early diagnosis of AD. Methods: The subjects enrolled in the study were classified into two diagnostic groups: MCI (n = 40) and early-stage AD (n = 40). Targeted metabolomics analysis of serum samples was performed using the Biocrates Absolute-IDQ P180 kit. Targeted metabolic data were analyzed by TargetLynx, and MetIDQ software was applied to integrate the metabolites by automated calculation of metabolite concentrations. Results: The datasets of targeted metabolite analysis were analyzed by the orthogonal-projection-to-latent-structure-discriminant-analysis (OPLS-DA) model. The OPLS-DA score plots demonstrated considerable separation between the MCI and early-stage AD patients. The levels of pimelylcarnitine, putrescine, SM (OH) C24:1, and SM C24:0 were significantly lower, whereas the levels of acetylornithine, methionine sulfoxide, and PC ae C44:3 were significantly higher in early-stage AD patients as compared with MCI patients. Receiver operating characteristic curve analysis of a combination of three lipid metabolites [SM (OH) C24:1, SM C24:0, and PC ae C44:3] showed an acceptable discrimination between the early-stage AD and MCI patients (area under the curve = 0.788). Conclusions: Our results characterized the differences of serum metabolic profiles between MCI and early-stage AD patients. The positive findings from this study indicate that the minimally invasive method of blood sampling may help to identify patients with AD at an early stage from those with MCI.

Association between gender and stoke recurrence in ischemic stroke patients with high-grade carotid artery stenosis.

The association between gender and stroke outcome in patients with high-grade internal carotid artery (ICA) stenosis remains unclear. We investigate gender differences in clinical characteristics and outcomes in ischemic stroke patients with high-grade ICA stenosis. Three-hundred and seventy-two acute ischemic stroke patients with high-grade ICA stenosis were enrolled and followed up for 5 years. Demographic features, vascular risk factors, co-morbidities, and outcomes were compared between male and female genders. Two-hundred and seventy-three (73.4%) patients were males and 99 (26.6%) patients were females. The prevalence of diabetes mellitus and atrial fibrillation was higher in females (P = 0.031 and P = 0.043), whereas the prevalence of smoking was higher in males (P < 0.001). The 5-year mortality rate was not different between males and females (P = 0.437), whereas the 5-year recurrent stroke rate was significantly higher in males (OR, 2.14; 95% CI, 1.22-3.75; P = 0.004). After adjusting for the established clinical predictors of adverse outcomes, the multivariate Cox regression revealed that male gender is a significant predictor of recurrent ischemic stroke (HR, 1.95; 95% CI, 1.19-3.20; P = 0.008). In conclusion, male gender is associated with increased risk of recurrent ischemic stroke in patients with high-grade ICA stenosis during 5-year follow-up. Further prospective trial to assess whether male gender may benefit from more aggressive vascular risk factors control and treatment strategies for stroke prevention is warranted.

Association Between Total Cholesterol and 5 year Mortality in Patients with Carotid Artery Stenosis and Poststroke Functional Dependence.

BACKGROUND: Aggressive lipid-lowering treatment reduces the risk of cardiovascular events, but remains controversial in stroke patients. We investigate the influence of total cholesterol level on 5-year outcomes of ischemic stroke patients with high-grade internal carotid artery (ICA) stenosis and poststroke functional dependence. METHODS: One-hundred and ninety-six acute ischemic stroke patients with high-grade ICA stenosis and modified Rankin Scale score ≥ 3 upon discharge were enrolled and prospectively observed for 5 years. Patients were divided into 2 groups according to total cholesterol level at admission: ≥200 mg/dL or <200 mg/dL. Demographic features, vascular risk factors, co-morbidities, and outcomes were compared between the 2 groups. RESULTS: 117 (59.7%) patients had higher and 79 (40.3%) patients had lower total cholesterol levels. The prevalence of older age and atrial fibrillation was significantly higher in patients with lower total cholesterol; the prevalence of diabetes mellitus was higher in patients with higher total cholesterol. After adjusting for the established clinical predictors of adverse outcomes, the multivariate Cox regression revealed that lower total cholesterol level is a significant predictor of 5-year mortality (HR (hazard ratio) = 1.88, 95% CI (confidence interval) = 1.09-3.23, P = .023). CONCLUSIONS: Lower total cholesterol level is associated with increased risk of 5-year mortality in ischemic stroke patients with high-grade ICA stenosis and post-stroke functional dependence. Aggressive treatment of hyperlipidemia should be carefully considered in these patients although it could reduce the risk of atherosclerotic cardiovascular diseases and stroke recurrence in some stroke patients.

Association Between Stroke Severity and 5-Year Mortality in Ischemic Stroke Patients with High-Grade Stenosis of Internal Carotid Artery.

BACKGROUND: The clinical presentations and outcomes of patients with high-grade stenosis of internal carotid artery (ICA) are highly variable. We investigate the influence of different stroke severity on outcomes of ischemic stroke patients with high-grade stenosis of ipsilateral ICA. METHODS: 372 acute first-ever ischemic stroke patients with high-grade stenosis (70%-99%) or occlusion of ipsilateral ICA were enrolled and followed up for 5years. Stroke severities of the enrolled patients were grouped according to the Oxfordshire Community Stroke Project classification system as total anterior circulation infarcts (TACI) or non-TACI. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between the 2 groups. RESULTS: A total of 71 patients (19.1%) were presented with TACI. Of laboratory data, the values of white blood cell count and high-sensitivity C-reactive protein were significantly higher in patients with TACI (P = .008 and P = .003, respectively). Of clinical course, the occurrence of initial impaired conscious, stroke-in-evolution, pneumonia, gastrointestinal bleeding, and urinary tract infection were significantly higher in patients with TACI. The prevalence of dependent functional status was higher in patients with TACI. Multivariate Cox regression revealed that TACI is a significant predictor of 5-year all-cause mortality in first-ever ischemic stroke patients with high-grade stenosis of ipsilateral ICA (HR [hazard ratio] = 3.66, 95% confidence interval = 2.23-6.00, P < .001). CONCLUSIONS: TACI is associated with increased risk of 5-year mortality in ischemic stroke patients with high-grade stenosis of ipsilateral ICA. Intensive medical treatment for stroke prevention in patients with severe carotid artery stenosis is warranted.

Association between gastrointestinal bleeding and 3-year mortality in patients with acute, first-ever ischemic stroke.

The influence of gastrointestinal bleeding on clinical presentation and outcomes of patients with acute ischemic stroke remains controversial. We investigate the effect of gastrointestinal bleeding on the outcomes of patients with acute, first-ever ischemic stroke. We enrolled 934 patients with acute, first-ever ischemic stroke and followed up them for 3years. Patients were divided into 2 groups according to the presence or absence of gastrointestinal bleeding during acute stroke stage. Clinical presentation, stroke risk factors, laboratory data, co-morbidities, and outcomes were recorded. Seventy-six (8.1%) patients had gastrointestinal bleeding at admission. The prevalence of old age, atrial fibrillation, and previous transient ischemic attack was higher in patients with gastrointestinal bleeding (P<0.001, P=0.038, and P=0.018, respectively). Total anterior circulation syndrome occurred more frequently among patients with gastrointestinal bleeding (P<0.001). The mean length of acute ward stay, initial impaired consciousness, and stroke in evolution were higher in patients with gastrointestinal bleeding (P<0.001, P<0.001, and P<0.001, respectively). The occurrence of pneumonia and dependent functional outcome were higher in patients with gastrointestinal bleeding (P<0.001 and P<0.001, respectively). A multivariate Cox regression analysis revealed that gastrointestinal bleeding is a significant risk factor for 3-year all-cause mortality (hazard ratio=2.76; 95% confidence interval=1.61-4.72; P<0.001). In conclusion, gastrointestinal bleeding is associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke. Prophylactic therapies for gastrointestinal bleeding might improve ischemic stroke outcome.

Risk factor analysis for meralgia paresthetica: A hospital-based study in Taiwan.

Recognizing the cause is essential for the management of meralgia paresthetica (MP), also known as lateral femoral cutaneous neuropathy. The aim of this study was to investigate the etiologies of MP and their influence on each other. This retrospective study enrolled referral patients with electromyographic studies who fulfilled the clinical and electrodiagnostic criteria of MP from January 2003 to December 2013. Data including age, gender, body weight, body height, occupation, and relevant medical history were collected. The etiological analysis was based on age and gender. A total of 50 patients (30 males and 20 females) were enrolled. The average age (±standard deviation) at diagnosis was 49.8±12.8years. Risk factors were identified in 29 cases (58.0%). More patients younger than 50years of age were male (73.1%, p=0.049). Peaks of age occurred between 41-50years in men and 51-60years in women. More males had a body mass index≥24kg/m2 (69.2% vs. 31.6%, p=0.012) and ≥27kg/m2 (34.6% vs. 0.0%, p=0.006). Overweight and obese patients were more vulnerable to occupational factors (50.0% vs. 19.0%, p=0.030). Only one case had diabetes mellitus (2%). Male middle-aged patients with a higher body mass index and certain occupations had an increased risk of MP. In contrast to the peak age distribution of the male patients, the frequency of developing MP was relatively even among the women at all ages. The cause was often obscure.

Association between Atrial Fibrillation and Three-Year Mortality in Nondiabetic Patients with Acute First-Ever Ischemic Stroke.

BACKGROUND: Diabetes mellitus (DM) is a risk factor for atrial fibrillation (AF) and is known to be an important risk factor for death from stroke. The influence of AF on long-term outcomes in patients with ischemic stroke remains controversial. To clarify the exact influence of AF on stroke outcome and exclude the effect from DM, we investigated the influence of AF on the 3-year outcomes of nondiabetic patients with acute first-ever ischemic stroke. METHODS: Five-hundred seventy-four nondiabetic patients with acute first-ever ischemic stroke were enrolled and had been followed for 3 years. Patients were divided into 2 groups according to whether AF was diagnosed or not. Clinical presentations, risk factors for stroke, laboratory data, comorbidities, and outcomes were recorded. RESULTS: A total of 107 patients (18.6%) had AF. The age was significantly older in patients with AF. Total anterior circulation syndrome occurred more frequently among patients with AF (P < .001). The mean length of stay in the acute ward was significantly higher in patients with AF (P < .001). Furthermore, dependent functional status following discharge was higher in patients with AF (P < .001). Multivariate Cox regression revealed that AF is a significant predictor of 3-year all-cause mortality (hazard ratio = 1.98, 95% confidence interval = 1.07-3.67, P = .022). CONCLUSIONS: AF is associated with increased risk of 3-year mortality in nondiabetic patients with acute first-ever ischemic stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.

Association between pneumonia in acute stroke stage and 3-year mortality in patients with acute first-ever ischemic stroke.

The influence of pneumonia in acute stroke stage on the clinical presentation and long-term outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of pneumonia in acute stroke stage on the 3-year outcomes of patients with acute first-ever ischemic stroke. Nine-hundred and thirty-four patients with acute first-ever ischemic stroke were enrolled and had been followed for 3years. Patients were divided into two groups according to whether pneumonia occurred during acute stroke stage or not. Clinical presentations, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. The result showed that a total of 100 patients (10.7%) had pneumonia in acute stroke stage. The prevalence of older age, atrial fibrillation was significantly higher in patients with pneumonia in acute stroke stage. Total anterior circulation syndrome and posterior circulation syndrome occurred more frequently among patients with pneumonia in acute stroke stage (P<0.001 and P=0.009, respectively). Multivariate Cox regression revealed that pneumonia in acute stroke stage is a significant predictor of 3-year mortality (hazard ratio=6.39, 95% confidence interval=4.03-10.11, P<0.001). In conclusion, pneumonia during the acute stroke stage is associated with increased risk of 3-year mortality. Interventions to prevent pneumonia in acute stroke stage might improve ischemic stroke outcome.

Association between renal dysfunction and 3-year mortality in patients with acute first-ever ischemic stroke.

OBJECTIVE: The influence of renal dysfunction on the clinical presentation and outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of renal dysfunction on the outcomes of patients with acute first-ever ischemic stroke. METHODS: Nine-hundred thirty-four patients with acute first-ever ischemic stroke were enrolled and followed for 3 years. Renal function was assessed using the equation of the Modification Diet for Renal Disease for estimated glomerular filtration rate (eGFR). Serum creatinine levels were obtained within 3 days of acute stroke onset. Reduced eGFR was defined as eGFR<60ml/min/1.73m(2). Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. RESULTS: Total 264 patients (28.3%) had a reduced eGFR. The prevalence of older age, hypertension, and atrial fibrillation was significantly higher in patients with a reduced eGFR. Total anterior circulation syndrome occurred more frequently among patients with a reduced eGFR (P=0.010). Multivariate Cox regression revealed that a reduced eGFR is a significant predictor of 3-year mortality (HR=1.67, 95% CI=1.06-2.62, P=0.026). CONCLUSION: Reduced eGFR during the acute stroke stage is associated with increased risk of 3-year mortality. Furthermore, risk of acute complications and poor functional outcomes following discharge was significantly higher in patients with a reduced eGFR.

Pituitary gigantism presenting with depressive mood disorder and diabetic ketoacidosis in an Asian adolescent.

Hyperglycemia is seldom described in young patients with pituitary gigantism. Here, we describe the case of a 17-year-old Taiwanese boy who developed depressive mood disorder and diabetic ketoacidosis (DKA) at the presentation of pituitary gigantism. The boy complained of lethargy and dysphoric mood in June 2008. He presented at the emergency department with epigastralgia and dyspnea in January 2009. Results of laboratory tests suggested type 1 diabetes mellitus with DKA. However, serum C-peptide level was normal on follow-up. Although he had no obvious features of acral enlargement, a high level of insulin-like growth factor 1 was detected, and a 75 g oral glucose suppression test showed no suppression of serum growth hormone levels. A pituitary macroadenoma was found on subsequent magnetic resonance imaging. The pituitary adenoma was surgically removed, followed by gamma-knife radiosurgery, and Sandostatin long-acting release treatment. He was then administered metformin, 500 mg twice daily, and to date, his serum glycohemoglobin has been <7%.

Less favorable neurological recovery after acute stroke in patients with hypercholesterolemia.

OBJECTIVES: We aimed to investigate the effect of hypercholesterolemia on recovery after acute ischemic stroke. METHODS: Data of 3048 patients admitted for acute ischemic stroke from January to December 2009 were collected from the Stroke Registry in the Chang Gung Healthcare System. Baseline characteristics of patients with and without hypercholesterolemia were compared. The association of hypercholesterolemia with neurological severity and recovery was analyzed using multivariate logistic regression. The patients were then divided on the basis of age for subgroup analysis. RESULTS: The number of patients with and without a history of hypercholesterolemia was 474 (15.6%) and 2574 (84.4%), respectively. Univariate analysis showed that patients with hypercholesterolemia had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission (p=0.004). However, during hospitalization, these patients displayed less improvement in their NIHSS score (p=0.002). These results remained significant in multivariate logistic regression analysis (p<0.001 and p=0.002, respectively). Subgroup analysis showed a similar association for hypercholesterolemia in both younger (age<70) and older (age≥70) age groups. CONCLUSIONS: Acute ischemic stroke in patients with hypercholesterolemia was correlated with reduced severity on admission and less favorable recovery during hospitalization, regardless of age.

Association of hyponatremia in acute stroke stage with three-year mortality in patients with first-ever ischemic stroke.

BACKGROUND: Hyponatremia is the most common electrolyte disorder in hospitalized patients, and is frequently a marker of a significant underlying disease. The prognostic value of hyponatremia in patients with acute first-ever ischemic stroke is not known. We aimed to analyze whether hyponatremia in the acute stroke stage contributed to the risk of mortality or recurrent stroke in these patients. METHODS: We studied 925 patients presenting with acute first-ever ischemic stroke between 2002 and 2004. Sodium levels were obtained on arrival at the emergency room within 3 days of acute stroke onset. Hyponatremia was defined as a serum sodium concentration of 134 mmol/l or less. Clinical presentation, stroke risk factors, associated medical disease, and outcome were recorded. All patients were followed for 3 years for survival analysis. A multivariate Cox proportional hazards model was used to identify risk factors for 3-year mortality in these patients. We also constructed Kaplan-Meier survival curves, and compared groups with hyponatremia and normonatremia by means of log rank tests for significant differences. RESULTS: Among the patients with acute first-ever ischemic stroke, 107 (11.6%) were hyponatremic. Among stroke risk factors, the prevalence of diabetes mellitus was significantly higher among hyponatremic patients (p < 0.001). Prevalence of chronic renal insufficiency was also higher in the hyponatremic group (p = 0.002). Clinical presentations, such as the length of acute ward stay, initial impaired consciousness, and clinical course in acute stroke were similar among normo- and hyponatremic patients. Among the complications, pneumonia and urinary tract infection were significantly higher in hyponatremic than in normonatremic patients. After multivariate logistic regression analysis, diabetes mellitus and chronic renal insufficiency were associated with hyponatremia in these patients. Kaplan-Meier analysis indicated that the survival rate was significantly lower in hyponatremic patients than in normonatremic patients (log rank test; p value <0.001). After multivariate Cox proportional hazards model analysis, hyponatremia was a significant predictor of 3-year mortality in these patients after adjustment for related variables (p value = 0.003, hazard ratio = 2.23, 95% confidence interval: 1.30-3.82). CONCLUSION: Hyponatremia in the acute stroke stage is a predictor of 3-year mortality in patients with acute first-ever ischemic stroke that is independent of other clinical predictors of adverse outcome.

Higher leukocyte count is associated with higher risk of 3-year mortality in non-diabetic patients with first-ever ischemic stroke.

Leukocyte count predicted the risk of first-time myocardial infarction and ischemic stroke. The aim of this study was to determine the role of elevated leukocyte count in non-diabetic patients admitted for acute first-ever ischemic stroke on clinical presentation and 3-year mortality. We studied 462 patients with acute first-ever ischemic stroke without diabetes mellitus or active infection at admission. Patients were classified into 2 groups according to their leukocyte count. A white blood cell (WBC) count ≥ 10,000/µL was defined as an elevated leukocyte count, otherwise as normal. Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. 64 patients (13.9%) had elevated leukocytes. Multivariate logistic regression showed that an elevated platelet count was positively associated with the elevated leukocyte count, while a low serum sodium level was negatively associated with an elevated leukocyte count (P=0.008, P=0.003, respectively). An elevated leukocyte count was associated with a higher risk of a stroke in evolution (P=0.021). Multivariate Cox regression analysis revealed that an elevated leukocyte count is a significant predictor of 3-year mortality [P=0.010, HR=3.26 (1.33-7.98)]. In conclusion, higher leukocyte counts during the acute stroke stage are associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke.

Clinical characteristics of adult tetanus in a Taiwan medical center.

BACKGROUND/PURPOSE: Despite effective vaccine programs, tetanus is occasionally observed in adults. We reviewed clinical presentation data for adult patients with tetanus in the post-vaccine era in Taiwan. METHODS: We retrospectively reviewed the medical records of all adult patients (age >18 years) discharged from Chang-Gung Memorial Hospital at Lin-Ko (CGMHLK) after treatment for tetanus between January 1996 and July 2005. Data regarding demographic characteristics, clinical manifestation, treatment, and outcome were collected. To assess the features for different age groups, patients were divided into those aged ≥65 years and those aged <65 years. To identify risk factors for respiratory failure, the patients were classified as those with and without respiratory failure. RESULTS: Twenty-three patients with tetanus, 11 (48%) women and 12 (52%) men, were included in the study. The average age was 57 ± 18 years (range 18-84 years). Eighteen (78%) patients had a history of acute injury. The average incubation period was 8 ± 5 days. The most common clinical presentation at onset was trismus (78%). Thirteen (57%) patients developed respiratory failure and underwent endotracheal intubation. The most common complication was pneumonia (30%). All the patients survived and recovered. Age ≥65 years was significantly associated with trismus, dysphagia, dysarthria, and pneumonia. Generalized tetanus subtype and pneumonia were significant risk factors for respiratory failure. CONCLUSION: This study revealed several characteristics of adult tetanus cases in the post-vaccine era in Taiwan. Further serological studies and improved tetanus vaccinations may be needed to ensure better protection, especially for high-risk populations. The exceptionally good prognosis for our patients confirms that appropriate treatment, including wound care, early diagnosis, proper medication, and prevention of complications, is essential in managing this traditional curable disease.

The impact of smoking on the severity of acute ischemic stroke.

OBJECTIVES: This study investigated the impact of smoking on the initial severity of acute ischemic stroke and examined its subsequent outcome. METHODS: Patient data was collected from the Stroke Registry in the Chang Gung Healthcare System (SRICHS). A total of 2650 patients admitted for acute ischemic stroke from January to December 2009 were included. Baseline characteristics were compared between smokers and non-smokers. Factors affecting the initial severity and the recovery from neurological deficit were examined by logistic regression analysis. The patients were further divided according to stroke mechanism for subgroup analysis. RESULTS: The total number of smokers and non-smokers was 817 (31.9%) and 1833 (69.1%), respectively. Univariate analysis showed that smokers had lower NIHSS scores on admission than did non-smokers (P<0.001). In subgroup analysis, smokers with small-vessel occlusions frequently had higher NIHSS scores on admission than did non-smokers (P=0.001). However, smokers with cardioembolic stroke had lower NIHSS scores on admission as compared to non-smokers (P=0.024). No subgroup had smoking as a significant factor for neurological recovery during hospitalization. CONCLUSIONS: Smoking correlated with higher NIHSS scores on admission for small-vessel occlusion. Conversely, it was associated with lower NIHSS scores on admission for cardioembolism.

Pituitary adenoma apoplexy with initial presentation mimicking bacterial meningoencephalitis: a case report.

Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation of this condition includes severe headache, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Signs of meningeal irritation are very rare. However, if present and associated with headache, fever, and pleocytosis, meningeal irritation may lead to misinterpretation as infectious meningoencephalitis. To the best of our knowledge, pituitary apoplexy with an initial presentation mimicking infectious meningoencephalitis had rarely been reported in the literature. Here, we report a 57-year-old man who had acute severe headache, high fever, neck stiffness, disturbance in consciousness, and left ocular paresis. Laboratory data showed leukocytosis, an elevated C-reactive protein level, and neutrophilic pleocytosis in the cerebrospinal fluid. Because bacterial meningoencephalitis was suspected, empiric antibiotic therapy was administered but in vain. Further examinations indicated a diagnosis of pituitary adenoma with apoplexy. After the immediate administration of intravenous corticosteroid supplement and surgical decompression, the patient recovered.