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 (21.4 %) were included in the present study. Six patients (14.6 %, 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 (26.8 %) 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.

Antineutrophil cytoplasmic antibodies in patients with idiopathic inflammatory-demyelinating diseases.

OBJECTIVE: We assessed the clinical significance of antineutrophil cytoplasm antibodies (ANCA) in patients with idiopathic inflammatory-demyelinating disease (IIDD). METHODS: A consecutive cohort of 269 subjects with IIDD and 595 controls was analyzed retrospectively. RESULTS: Among all subjects, ANCA positivity rates were low [9.5% in a perinuclear pattern (pANCA) and 2.3% in a cytoplasmic pattern (cANCA)]. One of the 117 patients with multiple sclerosis (MS) had cANCA and 2 had pANCA. Ten patients with neuromyelitis optica (NMO; 13.9%) had pANCA and 3 (4.2%) had cANCA. Four patients with recurrent longitudinal extensive transverse myelitis (RLETM; 19.0%) had pANCA and 1 (4.8%) had cANCA. In monophasic TM, 22.9% were pANCA seropositive. Among patients with brainstem syndromes, 14.3% were pANCA seropositive. Patients with NMO, RLETM or monophasic TM had higher pANCA levels than patients with MS. There was a positive association between spinal cord (SC) lesions and ANCA, and especially between longitudinal extensive transverse myelitis and ANCA. Among anti-aquaporin 4 antibody-positive patients, ANCA-positive patients (n = 16) were older and had higher Expanded Disability Status Scale scores, more antinuclear antibodies, longer SC lesions and fewer brain abnormalities than the ANCA-negative patients (n = 68). In the NMO subgroup, ANCA-positive patients were older and had more antinuclear antibodies and longer SC lesions than ANCA-negative patients. CONCLUSION: Among the IIDDs, we found a higher occurrence of ANCA in patients with NMO spectrum disorders than in patients with MS. Therefore, ANCA is another interesting marker of autoimmunity in IIDD patients, especially those with anti-aquaporin 4 antibody.

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 ß-actin and ß-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 potent different risk factors for cerebral infarction in young patients with and without type 2 diabetes: subanalysis of the Young Cerebral Infarction Study (YCIS).

BACKGROUND: To compare risk factors, stroke characteristics, and short-term prognosis between diabetic and nondiabetic young ischemic stroke patients to provide information for patient management, counseling, and future research in these patient groups. METHODS: All consecutive patients between the ages of 18 and 45 years with first-ever cerebral infarction during 2001-2010 were recruited to participate in the study. Using multivariate logistic regression modeling, demographic characteristics, cerebrovascular risk factors, clinical events, stroke subtypes, and outcome in ischemic stroke patients with and without diabetes were compared. RESULTS: Logistic regression analysis adjusted for confounders confirmed the following independent susceptibility markers: in a substudy of young patients with and without diabetes, the predictors of short-term outcome were more likely to be TOAST subtype, initial stroke severity and serum uric acid, and age at onset, dyslipidemia, initial stroke severity and serum fibron levels correlate with a higher risk for incident stroke in young with diabetes. CONCLUSION: Our findings suggest that diabetic and nondiabetic ischemic stroke patients exhibit a distinct risk-factor and etiologic profile and may help clinicians to assess prognosis more accurately.

Different independent susceptibility markers for first-ever cerebral infarction and myocardial infarction in young patients.

Cerebral infarction (CI) and myocardial infarction (MI) share some common features, but there are other differences in risk factors. The aim of our study is to determine whether there are some significantly independent susceptibility markers for them. All consecutive patients between the ages of 18 and 45 years with first-ever CI and MI during 2001-2010 were recruited to participate in the study. Using multivariate logistic regression modeling, we explore many different data, such as age at onset, sex ratio, numbers of patients with history of hypertension, smoking, drinking, and serum lipid, uric acid, prealbumin (PA), and white blood cell (WBC) count levels. Logistic regression analysis adjusted for confounders confirmed the following independent susceptibility markers for young CI patients: hypertension, admission serum PA levels, daily alcohol [odds ratio (OR), 0.251; 95% confidence interval (CI), 0.097-0.648, p = 0.004; OR, 0.994; 95% CI, 0.988-0.999, p = 0.031; OR, 0.150; 95% CI, 0.047-0.473, p = 0.001], and for MI patients: age at onset, current smoking, serum WBC, and glucose levels (OR, 1.293; 95% CI, 1.146-1.457, p = 0.000; OR, 8.914; 95% CI, 3.575-22.231, p = 0.000; OR, 1.344; 95% CI, 1.169-1.544, p = 0.000; OR, 1.149; 95% CI, 1.022-1.291, p = 0.020). We conclude that there are some significantly different independent susceptibility markers for young CI and MI patients.

Sex differences in risk factors, etiology, and short-term outcome of cerebral infarction in young patients.

Investigations to date have demonstrated that the underlying etiology, causes and burden of stroke may be different for women and men. However, data regarding sex differences among young cerebral ischemic stroke patients remains scarce. We conducted this study in 669 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Stepwise multiple logistic regression analysis confirmed that NIHSS score (OR 1.277; 95% CI 1.179-1.383, p=0.000), diabetes mellitus (OR 0.121; 95% CI 0.0209-0.718, p=0.020) and serum glucose levels on admission (OR 1.135; 95% CI 0.997-1.293, p=0.046) independently predict short-term outcomes at discharge in young female patients with acute stroke, but the significant variables related to male patients appeared to be Apo A1 (OR 0.165; 95% CI 0.035-0.776, p=0.023) and NIHSS score on admission (OR 1.458; 95% CI 1.325-1.605, p=0.000). In our series, our data suggest that there are several sex differences for risk of cerebral infarction in young patients, which have important implications for the diagnosis, management and prognosis of stroke in young adults.

Admission markers predict lacunar and non-lacunar stroke in young patients.

Stroke in young adults is an important cause of lifelong morbidity. The aim of this study was to explore some possible admission indicator of subsequent lacunar or non-lacunar strokes. We enrolled 626 patients with the first young cerebral strokes and divided them into lacunar and non-lacunar stroke based on clinical presentation and neuroradiological findings; and the analyses were adjusted for the effects of potential confounders. Hypertension, hyperlipidemia, atrial fibrillation, cerebral vascular moyamoya malformation were significantly more frequent in non-lacunar patients than lacunar patients (respectively P=0.005, 0.048, 0.000, 0.015, 0.030). Serum BUN, Triglyceride, Cholesterol, HDL, UA, White cell count, Fibrinogen, INR and bilirubin (including Total bilirubin, Direct bilirubin, Indirect bilirubin) levels on admission were higher in non-lacunar strokes than in lacunar strokes. Serum white blood cell count (Odds Ratio 1.097; 95% Confidence Interval 1.006-1.195, P=0.035), lower high-density lipoprotein levels (defined as HDL<0.9 mmol/L) (Odds Ratio 1.884; 95% Confidence Interval 1.035-3.285, P=0.038) and serum total bilirubin (Odds Ratio 1.054; 95% Confidence Interval 1.019-1.091, P=0.003) were associated with increased risk for non-lacunar stroke, whereas lacunar stroke was related to age at onset (Odds Ratio 0.929; 95% Confidence Interval 0.888-0.972, P=0.001) and SUA (Odds Ratio 0.997; 95% Confidence Interval 0.995-0.999, P=0.015). The excess risks were blood WBC, lower HDL and total bilirubin levels for non-lacunar strokes, and serum UA and age at onset for lacunar strokes in young Chinese patients.

Serum prealbumin (transthyretin) predict good outcome in young patients with cerebral infarction.

Low serum protein and albumin are considered to significantly associate with malnutrition, impaired functional status, poor outcome, and mortality. We hypothesized that serum prealbumin (transthyretin, PA) was a reliable and robust survival marker in young cerebral infarction patients and attempted to test the foregoing hypothesis. We analyzed the relationship between serum PA and stroke severity as determined by the modified Rankin Scale at discharge in 585 young cerebral infarction patients. By multivariate logistic regression modeling, we determined the influence of prealbumin on stroke severity, and the analyses were adjusted for the effects of potential confounders. Patients with a severe stroke had significantly more often prealbumin on admission in the lowest quintile (P = 0.031). Those cardiogenic cerebral infarction patients had significantly lower serum prealbumin concentrations and higher mRS scores. A logistic regression adjusted for confounders confirmed the following independent (odds ratio, 95% CI) good outcome predictors: uric acid (-0.002, 0.996-1.000) and prealbumin (-0.003, 0.995-1.000). Prealbumin is an independent predictor of the good clinical outcome of young cerebral infarction patients. The serum prealbumin may be a useful prognostic indicator for judging the prognosis of cerebral infarction.

Is elevated SUA associated with a worse outcome in young Chinese patients with acute cerebral ischemic stroke?

BACKGROUND: Elevated serum uric acid (SUA) levels can enhance its antioxidant prosperities and reduce the occurrence of cerebral infarction. Significantly elevated SUA levels have been associated with a better prognosis in patients with cerebral infarction; however, the results from some studies on the relationship between SUA and the prognosis of patients with cerebral infarction remain controversial. METHODS: We analyzed the relationship between SUA and clinical prognosis of 585 young Chinese adults with acute ischemic stroke as determined by the modified Rankin Scale at discharge. Using multivariate logistic regression modeling, we explore the relationship between SUA levels and patient's clinical prognosis. RESULTS: Lower SUA levels at time of admission were observed more frequently in the lowest quintile for patients with severe stroke (P = 0.02). Patients with cerebral infarction patients caused by small-vessel blockage had higher SUA concentrations (P = 0.01) and the lower mRS scores (P < 0.01) were observed in, while the lowest SUA concentrations and the highest mRS scores were seen in patients with cardiogenic cerebral infarction patients. Logistic regression analysis adjusted for confounders confirmed the following independent predictors for young cerebral infarction: uric acid (-0.003: 95%CI 0.994 to 0.999) and platelet (0.004, 95%CI 0.993 to 0.996). CONCLUSION: Elevated SUA is an independent predictor for good clinical outcome of acute cerebral infarction among young adults.

The clinical study of POEMS syndrome in China.

OBJECTIVE: POEMS syndrome is a unique clinical entity. It was described by the presence of several typical characteristics as paraproteinemia, polyneuropathy, organomegaly, endocrinopathy, and skin changes. Few people reported characteristics of Chinese POEMS patients. PATIENTS AND METHODS: Retrospective evaluation of Chinese patients with POEMS syndrome was carried out to reveal clinical features and compare with foreign series reported previously. In addition to typical characteristics, Chinese patients often were presented with extravascular volume overload (84%), papilledema (44%), bone lesions (41%), raynaud phenomenon (31%) and Clubbing (22%). RESULTS: Clinical laboratory tests found most patients had increased erythrosedimentation rate, hyperlipidemia, liver disorder and renal involvement. 70% patients had hypothyroidism, including overt hypothyroidism (6 patients) and subclinical hypothyroidism (13 patients). High prevalence of positive antimitochondrial antibody (ANA) and positive antineutrophil cytoplasmic antibody (ANCA) was the more common phenomenon. Chinese patients with bone damage in the incidence are lower than in the West and Japanese reports. CONCLUSIONS: In summary, our study demonstrate the POEMS syndrome diagnostic criteria proposed by Dispenzieri et al is also more high applicability in the Chinese population.At the time of diagnosis, we should not pay attention on the typical characteristics of the disease, but also on the changes in thyroid, liver, kidney function and lipid metabolism.

Comparison of serum apolipoprotein A-I between Chinese multiple sclerosis and other related autoimmune disease.

BACKGROUND: Serum apolipoprotein (apo) A-I was considered to be an immune regulator and could suppress pro-inflammatory cytokines generated by activated T cell in some autoimmune diseases. However, the change of serum apoA-I levels in multiple sclerosis (MS) patients is unknown. METHODS: In the presentation we performed a study on serum apoA-I levels in the patients with MS. We enrolled some age and gender matched patients with MS, autoimmune demyelinating diseases (Guillain-Barre Syndrome and Clinically Isolated Syndrome), neuroinflammatory diseases (viral encephalitis), autoimmune connective diseases (rheumatoid arthritis and systemic lupus erythematosus) and healthy control groups, and tested their serum lipids levels: total cholesterol (TC), triglyceride (TG), high-density lipoproteins (HDL), apolipoproteinB100 (apoB100), apolipoproteinA-I (apoA-I). RESULTS: For all patients, age had no effect on serum apoA-I levels (P > 0.05). Meanwhile, we proved the highest serum apoA-I levels in MS patients and the lowest serum apoA-I levels in SLE patients. Serum apoA-I levels was significantly elevated in female MS patients (P = 0.033; P < 0.05). CONCLUSION: In short we believed that patients with MS and other autoimmune demyelination had significantly decreased serum levels of apo A-I.