Youming Long

Development of a cell-based assay for the detection of anti-aquaporin 1 antibodies in neuromyelitis optica spectrum disorders.

OBJECTIVEnTo develop a cell-based assay (CBA) to detect aquaporin 1 (AQP1) antibodies and determine sensitivity/specificity in patients with neuromyelitis optica (NMO) spectrum disorders.nnnMETHODSnA HEK-293T transfected cell model expressing AQP1 was established and detected to be serum AQP1 antibodies.nnnRESULTSnAQP1 antibodies were present in 73/98 (74.5%) AQP4 antibody-positive patients. Some AQP4 antibody-negative patients were also AQP1 antibody-positive. Test sensitivity was 74.5% in 98 AQP4 antibody-positive patients. Test specificity was 79.6% in 67 multiple sclerosis (MS) patients and 31 controls.nnnCONCLUSIONnA sensitive and simple CBA was developed to detect serum AQP1 antibodies. AQP1 antibodies were mainly present in NMO and its high-risk syndrome, but also in some MS patients.

Serum Thyroid-Stimulating Hormone and Anti-Thyroglobulin Antibody Are Independently Associated with Lesions in Spinal Cord in Central Nervous System Demyelinating Diseases

Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapseu200a=u200a128; remissionu200a=u200a115) of 178 patients with demyelinating diseases (NMO, nu200a=u200a25; TM, nu200a=u200a48; MS, nu200a=u200a105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, nu200a=u200a19; TM, nu200a=u200a25; MS, nu200a=u200a52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (pu200a=u200a0.001), TG-Ab (pu200a=u200a0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR] u200a=u200a33.994; p<0.0001), TG-Ab (ORu200a=u200a7.703; pu200a=u200a0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (ORu200a=u200a42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders.

Syndrome of inappropriate antidiuretic hormone secretion in patients with aquaporin-4 antibody.

The objective of this study was to analyze the frequency of syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with positive aquaporin-4 (AQP4) antibodies and evaluate the relationship between SIADH and hypothalamic lesions in patients with NMO and NMO spectrum disorder (NMOSD). AQP4 antibodies were tested by an indirect immunofluorescence assay employing HEK-293 cells transfected with recombinant human AQP4. Clinical data of patients were analyzed retrospectively. In total, 192 patients with AQP4 antibodies were certified, of which 41 patients (21.4xa0%) were included in the present study. Six patients (14.6xa0%, 6/41) met the criteria of SIADH, of which hyponatremia was mild in one patient, and severe in five. Five patients experienced confusion or decreased consciousness. Four patients were diagnosed with NMO and two were diagnosed with recurrent optic neuritis. Magnetic resonance imaging showed 11 of 41 patients (26.8xa0%) had hypothalamic lesions. All patients with SIADH had hypothalamic abnormalities. Hyponatremia resolved in all patients after intravenous methylprednisolone and intravenous immunoglobulin therapy. SIADH is not rare in patients with NMO/NMOSD, especially in patients with lesions close to the hypothalamus.

Brain gadolinium enhancement along the ventricular and leptomeningeal regions in patients with aquaporin-4 antibodies in cerebral spinal fluid

BACKGROUNDnAquaporin-4 (AQP4) is densely expressed in the ependymal region and leptomeninges, and it is susceptible to pathological responses triggered by antibodies from blood and cerebral spinal fluid (CSF). Therefore, enhancement of these regions may be related to neuromyelitis optica spectrum disorder (NMOSD).nnnMETHODSnMRI from a consecutive cohort of 84 subjects (NMOSD=47, multiple sclerosis [MS]=37) with AQP4 antibodies in serum and CSF were analyzed retrospectively.nnnRESULTSnThe brain was normal in five of the 47 patients with NMOSD and none of the MS patients showed a normal brain. Twelve patients in each group had parenchymal enhancing lesions. Of these, white matter enhancement was more frequently found in MS patients than in NMOSD patients (12/12 vs 4/12, p=0.001). Cloud-like enhancement was found in three NMOSD patients (3/12) and in one MS patient. Nine of the 12 NMOSD patients showed pencil-thin ependymal enhancement, whereas one of the 12 MS patients showed ependymal enhancement (p=0.003). Enhancement along the lateral ventricle was more frequently found in NMOSD patients than in MS patients (p=0.027), whereas enhancing lesions around the fourth ventricle tended to be more frequent in NMOSD patients than MS patients (p=0.097). Leptomeningeal enhancement around the brainstem was found in six (12.8%) NMOSD patients and in no MS patients (p=0.032).nnnCONCLUSIONnEnhancement of the leptomeninges and ventricular ependymal region more frequently occurs in NMOSD patients than in MS patients. This may be considered as characteristic clue in the diagnosis of NMOSD.

Autoimmune glial fibrillary acidic protein astrocytopathy in Chinese patients: a retrospective study

The aim was to describe the clinical, radiological and pathological features of an autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Serum anticardiolipin antibodies in patients with neuromyelitis optica spectrum disorder

The presence of anticardiolipin antibodies (ACLA) in multiple sclerosis (MS) patients has been reported, but there are some debates on the relationship between ACLA and MS. We assessed the clinical features of neuromyelitis optica spectrum disorders (NMOSD) patients with ACLA. A consecutive cohort of 480 subjects with NMOSD (nxa0=xa070), MS (nxa0=xa090) and control (nxa0=xa0220) were analysed retrospectively. Patients’ serum was tested by a dot-immunogold filtration assay for the presence of ACLA-IgG, IgM and IgA antibodies. In MS patients, 5 (5.6xa0%) of the 90 patients showed ACLA-IgG reactivity in the serum. In NMOSD patients, 32 (45.7xa0%) of the 70 patients showed ACLA reactivity in the serum, among which ACLA-IgG seropositivity was 45.7xa0% (32/70), ACLA-IgGxa0+xa0IgM seropositivity was 8.6xa0% (6/70), and ACLA-IgGxa0+xa0IgA seropositivity was 4.3xa0% (3/70). NMOSD patients were higher in ACLA-IgG (pxa0<xa00.0001) and ACLA-IgGxa0+xa0IgM (pxa0=xa00.006) than the MS patients. NMOSD patients had higher ACLA-IgG than the control patients (pxa0<xa00.0001). In comparison with the controls, the MS patients were lower in ACLA for IgG (pxa0=xa00.014) and IgM (pxa0=xa00.004). Seropositive ACLA patients increased in age (pxa0=xa00.013) and had higher D-dimer levels (DD) (pxa0=xa00.002) than the seronegative NMOSD patients. Furthermore, positive ACLA-IgGxa0+xa0IgM patients were increased in age (pxa0=xa00.001), had higher baseline EDSS (pxa0=xa00.001), antithrombin III activity (pxa0=xa00.04), and DD levels (pxa0=xa00.005) than the pure positive ACLA-IgG NMOSD patients. Patients with NMOSD had more occurrences of ACLA than patients with MS. NMOSD patients with positive ACLA-IgGxa0+xa0IgM had a worse outcome that may be associated with elder age and abnormal coagulation parameters in blood.

Is serum total bilirubin useful to differentiate cardioembolic stroke from other stroke subtypes

Abstract Background: Previous studies have reported that the total bilirubin (TB) level is associated with coronary artery disease, heart failure and atrial fibrillation. These heart diseases can produce cardiogenic cerebral embolism and cause cardioembolic stroke. However, whether the serum TB could be a biomarker to differentiate cardioembolic stroke from other stroke subtypes is unclear. Methods: Our study consisted of 628 consecutive patients with ischaemic stroke. Various clinical and laboratory variables of the patients were analysed according to serum TB quartiles and stroke subtypes. Results: The higher TB quartile group was associated with atrial fibrillation, larger left atrium diameter, lower left ventricular fractional shortening and cardioembolic stroke (Pu2009<u20090.001, Pu2009=u20090.001, Pu2009=u20090.033, Pu2009<u20090.001, respectively). Furthermore, serum TB was a statistically significant independent predictor of cardioembolic stroke in a multivariable setting (Continuous, per unit increase ORu2009=u20091.091, 95%CI: 1.023–1.164, Pu2009=u20090.008). Conclusions: Serum TB level was independently associated with cardioembolic stroke. The combination of clinical data and serum TB may be a feasible strategy to diagnose cardioembolic stroke in the acute phase.

Y-39983, a Selective Rho-Kinase Inhibitor, Attenuates Experimental Autoimmune Encephalomyelitis via Inhibition of Demyelination

Objective: Rho-associated kinase (ROCK) is a serine/threonine kinase and a major downstream effector of the small GTP-binding protein, Rho. Rho-ROCK triggers an intracellular signaling cascade that controls actin cytoskeleton and is essential for cell motility and adhesion, neurite outgrowth and retraction. In chronic disabling disease, multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), demyelination and axonal damage are the major pathological changes contributing to neurological disability. We investigated the protective effect of a specific ROCK inhibitor, Y-39983, on demyelination and axonal damage in chronic EAE. Methods: Western blotting for myelin proteins, electron microscopy and solochrome cyanine staining was performed to evaluate demyelination while neurofilament proteins and cytoskeletal proteins including β-actin and β-tubulin were used to determine axonal damage in a chronic mouse model of EAE treated with Y-39983. Results: Y-39983 significantly suppressed clinical symptoms of EAE and prevented its relapse while increasing the amount of myelin proteins. No significant changes in neurofilaments and cytoskeletal proteins were observed compared with control EAE mice. The inhibition of demyelination by Y-39983 was confirmed by solochrome cyanine staining and electron microscopy. To further study the effect of Y-39983 on demyelination in EAE, we tested three major ROCK substrates, including myosin light chain phosphorylation, LIMK2 and collapsin response mediator protein-2. The activity of these molecules was decreased in EAE animals treated with Y-39983. Conclusion: The inhibitory effect of Y-39983 on demyelination is probably due to the inactivation of ROCK substrates, which are important for neurite outgrowth, growth cone collapse and demyelination of oligodendrocytes.

The Effects of Statins on Infections after Stroke or Transient Ischemic Attack: A Meta-Analysis

Background Previous studies have reported that statins can prevent infections, and these findings were ascribed to the anti-inflammatory and immunomodulatory properties of statins. However, the effects of statins on the risk of infection after stroke or transient ischemic attack (TIA) remain controversial. The aim of this study was to evaluate the relationship between statins and the risk of infection after stroke or TIA by means of a meta-analysis. Methodology and Findings Studies were found by searching major electronic databases using key terms and restricting the results to studies published in English language and human studies. Pooled odds ratio (OR) for the association between infection and statins were analyzed using Stata software. A total of five studies that included 8,791 stroke or TIA patients (3,269 patients in the statin use group and 5,522 in the placebo group) were eligible and abstracted. Pooled analysis demonstrated that statins did not significantly affect the incidence of infection after stroke or TIA compared with a placebo (OR 0.819, 95% CI 0.582–1.151, I2 = 64.2%, p= 0.025). Sensitivity analyses showed that the removal of any single study did not significantly affect the pooled OR. Cumulative meta-analysis showed that the incidence of infection did not vary by publication year. No statistical evidence of publication bias was found among the studies selected, based on the results of Egger’s (p = 1.000) and Begg’s (p = 0.762) tests. Conclusions This meta-analysis does not support the hypothesis that statins reduce the risk of infections in stroke or TIA patients.

Cerebral venous sinus thrombosis may be associated with hepatitis B virus infection: a preliminary finding.

Abstract Objective: To assess the clinical significance of hepatitis B virus (HBV) infection in patients with cerebral venous sinus thrombosis (CVST). Methods: Twenty-two patients with CVST confirmed by magnetic resonance venography (MRV) or digital subtraction angiography (DSA) and 743 controls with ischemic stroke confirmed by magnetic resonance imaging (MRI) were analyzed retrospectively. Results: Among all researches, HBV surface antigen (HBsAg)-positive rate was high. Six of the 22 (27·3%) confirmed cases had HBsAg. However, HBsAg-positive rate in patients with ischemic stroke was only 45 of the 743 cases (6·1%), closed to the average prevalence in China (∼8·6%), but much lower than the positive rate in CVST patients (27·3 vs 6·1%, P u200a=u200a 0·002). Odd ratio (OR) value between HBsAg-positive CVST patients (27·3%) and HBsAg-positive ischemic stroke patients (6·1%) was 5·78. The OR value between HBsAg-positive CVST patients (27·3%) and average prevalence of HBV infection in China (8·6%) was nearly 3·99. It meant that HBV infection might be a risk factor for CVST. However, there existed no statistically significant difference in HBV surface antibody (HBsAb), HBV e antigen (HBeAg), HBV e antibody (HBeAb), and HBV central antibody (HBcAb)-positive rate. The HBV surface antigen (HBsAg)-positive CVST patients did not show worse liver function. Most of them were inactive HBV carriers. Conclusion: Hepatitis B virus infection may be a risk factor for CVST.