FNDC5/Irisin protects neurons through Caspase3 and Bax pathways.

Irisin is a glycosylated protein formed from the hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Recent studies have demonstrated that FNDC5/Irisin is involved in the regulation of glucose and lipid metabolism, it can inhibit inflammation and have neuroprotective effects. However, the effect and mechanism of FNDC5/Irisin on motor neuron-like cell lines (NSC-34) have not been reported. In this study, we used lipopolysaccharide to construct cellular oxidative stress injury models and investigated the potential roles of FNDC5/Irisin on neurons by different cellular and molecular pathways. Taken together, our findings showed that FNDC5/Irisin can protect neurons, and this effect might be associated with Caspase3 and Bax pathways. These results laid the foundation for neuronal protection and clinical translation of FNDC5/Irisin therapy.

Clinical features of Guillain-Barré syndrome with anti-neurofascin 155 antibody.

OBJECTIVE: Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients. MATERIALS & METHODS: Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected. RESULTS: Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p = .010), higher modified Erasmus GBS outcome score (p = .022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p = .002), higher frequency of prolonged F-wave latency (p < .001), lower frequency of abnormal sensory conduction velocity (p < .001) and sensory nerve action potential amplitude (p < .001), more axonal type (p = .040), and poorer therapeutic effect (p = .017). CONCLUSIONS: Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.

Role of lymphocyte-related immune-inflammatory biomarkers in detecting early progression of Guillain-Barré syndrome.

OBJECTIVES: This study aimed to investigate the role of peripheral neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR) in the progression and severity of the Guillain-Barré syndrome (GBS). METHODS: 47 GBS patients and 50 age and sex-matched healthy controls (HC) were retrospectively included. Demographic and clinical assessment data were reviewed and abstracted. NLR, MLR, and PLR were calculated based on the peripheral blood tests by reviewing clinical data. The relationship between the Hughes' score and NLR, MLR, PLR levels was investigated. RESULTS: The GBS patients had higher NLR levels (P < 0.001), MLR levels (P = 0.001) and PLR levels (P < 0.001) than those in HC. And patients with severe disability score (Hughes' score ≥ 3) had significantly higher NLR (P = 0.007), MLR (P = 0.04), PLR (P = 0.013). Spearman correlation analysis indicated that NLR was positively associated with the Hughes' score (r = 0.331, P = 0.023). In the patients with acute inflammatory demyelinating polyneuropathy (AIDP), Spearman correlation analysis indicated that NLR, MLR and PLR were positively associated to the Hughes' score (r = 0.825, P = 0.001 for NLR, r = 0.727, P = 0.005 for MLR, and r = 0.723, P = 0.005 for PLR). CONCLUSIONS: NLR, MLR, and PLR may be indicators of disease activity in patients with GBS or AIDP. These parameters may benefit the active treatment of GBS patients with a high degree of disability.

Serum irisin levels in patients with myasthenia gravis.

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disorder whose main symptoms are muscle weakness and fatigue. Irisin is a novel skeletal muscle-derived myokine participating in several physiological and pathological processes. The initial objective of the project was to explore serum levels of irisin in patients with MG, as well as its correlation with disease severity. METHODS: We retrospectively evaluated serum levels of irisin in 77 MG patients and 57 healthy controls (HCs) by enzyme-linked immunosorbent assay. Further, clinical parameters were measured properly. RESULTS: Serum irisin levels were significantly elevated in MG patients compared with HCs (p < 0.001). Furthermore, serum irisin levels were associated with the myasthenia gravis activities of daily living score in ocular myasthenia gravis (OMG) patients (r = 0.476, p = 0.004), but there was no relationship to be considered of any relevant value in generalized myasthenia gravis (GMG) patients. Acetylcholine receptor antibody-positive MG patients had higher serum irisin levels compared with HCs. Thymoma, endotracheal intubation, or intensive care unit treatments subsequently were not found to have effect on serum levels of irisin, but tendencies of increase were observed in negative ones. CONCLUSIONS: Serum irisin levels were elevated in patients with MG, suggesting its possible involvement in MG. And irisin is expected to be a signal to evaluate the activities of daily living of OMG patients, while its effect needs further study.

The prevalence of anti-neurofascin-155 antibodies in patients with neuromyelitis optica spectrum disorders.

Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.

Elevated cerebrospinal fluid ß2-microglobulin levels in patients with neuromyelitis optica spectrum disorders.

Cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) levels elevated in patients with multiple sclerosis (MS). We examined the levels of ß2-MG in serum and cerebrospinal fluid (CSF) from 46 patients with neuromyelitis optica spectrum disorders (NMOSD), in serum from 21 healthy controls (HC), in CSF from 25 disease controls with non-inflammatory neurological diseases (NIND) with normal CSF results. CSF ß2-MG levels were significantly higher in patients with NMOSD than controls and with weak association with the number of white blood cells, protein and lactate levels in CSF. CSF ß2-MG is thus one more, non-specific indicator of inflammation in NMOSD.

Elevated cerebrospinal fluid levels of beta-2-microglobulin in patients with Guillain-Barré syndrome and their correlations with clinical features.

BACKGROUNDS: Beta-2-microglobulin (ß2-MG) levels vary in many infectious and autoimmune diseases. We investigated plasma and cerebrospinal fluid (CSF) ß2-MG levels in patients with Guillain-Barré syndrome (GBS) and their correlations with clinical parameters. METHODS: CSF samples from 50 patients with GBS including 19 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 10 acute motor-sensory axonal neuropathy (AMSAN), 7 Miller-Fisher syndrome (MFS), and 8 unclassified patients were collected. Moreover, 23 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 42 enrolled patients and 29 healthy individuals were also collected. The ß2-MG levels were measured by immunoturbidimetry on automatic biochemical analyser. Besides, clinical data were extracted from electronic patient documentation system. RESULTS: CSF levels of ß2-MG, lactate dehydrogenase (LDH), and lactate were significantly increased in patients with GBS (p = 0.004, p = 0.041, p = 0.040, respectively), particularly in patients with AIDP (p < 0.001, p = 0.001, p = 0.015, respectively), whereas no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were positively correlated with Hughes functional score (r = 0.493, p = 0.032), LDH (r = 0.796, p < 0.001), and lactate (r = 0.481, p = 0.037) but not with protein (r = - 0.090, p = 0.713) in AIDP patients. CONCLUSIONS: CSF ß2-MG levels may help identify AIDP and indicate clinical severity. CSF LDH and lactate levels correlate with CSF ß2-MG levels; interaction among these biomarkers would need further investigation.

Increased serum IL-27 concentrations and IL-27-producing cells in MG patients with positive AChR-Ab.

OBJECTIVE: This study aims to explore the serum levels of IL-27 and the percentages of IL-27-producing cells in MG patients with positive acetylcholine receptor antibody (AChR-MG). METHODS: A total of 17 AChR-MG patients and 22 sex- and age- matched healthy controls (HCs) were recruited. Serum IL-27 levels were determined by enzyme linked immunosorbent assay. The percentages of IL-27+ cells, IL-27-producing T (CD3+IL-27+) cells, and IL-27-producing B (CD19+IL-27+) cells were measured by flow cytometry. RESULTS: Serum IL-27 levels in AChR-MG were significantly higher than those in HCs (13.44 ± 0.89 vs 7.14 ± 0.75 pg/mL, P < 0.0001), and were decreased after intravenous immunoglobulin (IVIG) treatment (P = 0.004). Moreover, the frequencies of IL-27+ lymphocytes were significantly elevated in AChR-MG patients than those in HCs (P = 0.011), and were decreased after IVIG treatment (P = 0.014). Furthermore, the frequencies of IL-27-producing T cells (P = 0.017) and IL-27-producing B cells (P = 0.015) were significantly elevated in AChR-MG patients as compared to those in HCs. Meanwhile, we observed positive correlations between the frequencies of IL-27+ lymphocytes and MG-ADL score (P = 0.030, r = 0.527). By contrast, no significant correlation was found between IL and 27 serum levels and MG-ADL score (P = 0.099, r = -0.414). CONCLUSION: IL-27 may play an important role in the pathological process in AChR-MG patients, and the frequencies of IL-27-producing (CD3+IL-27+) T cells may be a potential biomarker for predicting the severity of AChR-MG.

Quantitative evaluation of callosal abnormalities in relapsing-remitting multiple sclerosis using diffusion tensor imaging: A systemic review and meta-analysis.

BACKGROUND: Although the changes of diffusion tensor imaging (DTI) in corpus callosum (CC) in patients with relapsing-remitting multiple sclerosis (RRMS) has been reported, the results are controversial. We aimed to determine the damage to the CC in patients with RRMS using DTI. MATERIAL AND METHODS: A systematic search of English databases (PubMed, Embase, Cochrane Library, and Scopus) was performed. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values of DTI were compared between RRMS patients and healthy controls (HC) using Stata 12.0. RESULTS: A total of 461 patients and 365 HC from 15 studies were included. Compared with HC, the FA values of the whole CC (SMD -1.894, P < 0.001), genu (SMD -0.830, P < 0.001) and splenium (SMD -1.431, P < 0.001) of CC were significantly reduced in patients with RRMS. Moreover, the MD values of the whole CC (SMD 1.213, P < 0.001), genu (SMD 0.657, P < 0.001) and splenium (SMD 0.830, P < 0.001) of CC were significantly increased in patients with RRMS. Additionally, the AD values (SMD 0.635, P < 0.001) and RD values (SMD 1.480, P < 0.001) were significantly increased in the whole CC in patients with RRMS. The meta-regression analysis revealed that the male ratio showed a significant effect on the FA reduction in the splenium CC in RRMS patients. CONCLUSIONS: These results indicated that DTI parameters were potential biomarkers with increased sensitivity for detecting pathological damage in the CC in patients with RRMS.

Increased Cerebrospinal Fluid Uric Acid Levels in Guillain-Barré Syndrome.

Uric acid (UA) is a natural scavenger for peroxynitrite and can reflect antioxidant activity and oxidative stress in several neurological disorders. Changes in serum and cerebrospinal fluid (CSF) levels of UA have been reported in patients with multiple sclerosis and neuromyelitis optica spectrum disorders. The levels of UA in CSF are relatively poorly understood in patients with Guillain-Barré syndrome (GBS). It remains unclear whether UA can play an antioxidant role and reflect oxidative stress in GBS. The purpose of this study is to investigate CSF and serum UA levels in patients with GBS and their relationship with clinical characteristics. The CSF and serum UA levels were detected in 43 patients with GBS, including 14 acute inflammatory demyelinating polyneuropathy (AIDP), 6 acute motor axonal neuropathy (AMAN), 13 with acute motor and sensory axonal neuropathy (AMSAN), 7 Miller Fisher syndrome (MFS), and 3 unclassified, and 25 patients with non-inflammatory neurological disorders (NIND) as controls. Moreover, serum UA levels were also detected in 30 healthy controls. The levels of UA were measured using uricase-based methods with an automatic biochemical analyzer. CSF UA levels were significantly increased in patients with GBS (p = 0.011), particularly in patients with AIDP (p = 0.004) when compared with NIND. Among patients with GBS, CSF UA levels were higher in those with demyelination (p = 0.022), although the difference was not significant after multiple testing correction. CSF UA levels in GBS were positively correlated with serum UA levels (r = 0.455, p = 0.022) and CSF lactate (r = 0.499, p = 0.011). However, no significant correlations were found between CSF UA levels and GBS disability scores. There were no significant differences in serum UA levels among GBS, NIND, and healthy controls. These results suggest that CSF UA may be related to the pathogenesis of demyelination in patients with GBS and may be partially determined by serum UA and the impaired blood-nerve barrier.

Comparisons Between Infectious and Autoimmune Encephalitis: Clinical Signs, Biochemistry, Blood Counts, and Imaging Findings.

OBJECTIVE: Infectious encephalitis (IE) and autoimmune encephalitis (AE) are symptomatically similar in clinic, however essentially different in pathogenesis. Therefore, the objective of this study was to identify specific features to distinguish the two types of encephalitis for early effective diagnosis and treatments through a comparative analysis. METHODS: Fifty-nine IE patients and 36 AE patients were enrolled. The patients with IE were divided into viral encephalitis (VE) and bacterial encephalitis (BE) according to the pathogens in cerebrospinal fluid (CSF). Patients with AE were categorized by with or without neural autoantibodies (NAAb). We further divided patients with NAAb into those with neural cell-surface antibodies (NSAbs) or intracellular antibodies (Abs). Clinical features, laboratory data, and imaging findings were compared between AE, IE, and subgroups. RESULTS: Memory deficits, involuntary movement, and seizures were relatively more commonly presenting symptoms in AE patients (p < 0.05). The positive rate of Pandy test was higher in IE patients (p = 0.007). Decreased leukocyte, erythrocyte, and platelet counts in blood were found in IE patients (p < 0.05). Lower serum calcium level was found in VE compared to BE (p = 0.027). Meanwhile, higher serum calcium level was found in patients with NSAbs compared with intracellular Abs (p = 0.034). However, higher levels of LDH in CSF were found in patients with intracellular Abs (p = 0.009). In magnetic resonance imaging, hippocampus lesions were more commonly present in patients with AE (p = 0.042). Compared with AE patients, more IE patients displayed the background electroencephalogram rhythm of slow-frequency delta (p = 0.013). CONCLUSION: Involuntary movement and memory deficits were more specifically present in AE patients. CSF Pandy, blood routine test and hippocampus lesions detections were potential markers for distinguishing AE and IE. Further, CSF LDH, and serum calcium levels were potentially useful to distinguish subgroups of encephalitis.

Different clinical characteristics of longitudinally extensive transverse myelitis with and without connective tissue disorders: a single-center retrospective study.

BACKGROUND AND OBJECTIVE: Autoimmune longitudinal extensive transverse myelitis (LETM) is often combined with connective tissue disorders (CTD). The purpose of this study was to compare the clinical characteristics of autoimmune LETM with and without CTD. METHODS: Ninety-two patients diagnosed with autoimmune LETM were enrolled from our clinical database and divided into two groups depending on whether they had a concomitant diagnosis of CTD. Differences in clinical, serological, and imaging characteristics between the two groups were evaluated and compared. RESULTS: Fifty-nine LETM patients without CTD and 33 LETM patients with CTD were included. LETM patients with CTD had higher Kurtzke Expanded Disability Status Scale at nadir and more severe sensory dysfunction (p < 0.05) than those without CTD. It was also found that LETM patients with CTD, compared with those without CTD, had elevated levels of immune inflammation markers such as IgG, IgA, and globulins (p < 0.05). These abovementioned characteristics were more prominent in patients with aquaporin-4 antibodies (AQP4-ab) than in those without them. In addition, the most common type of CTD in LETM was Sjögren syndrome (SS), which was usually diagnosed at the time of LETM or later. CONCLUSION: LETM patients with CTD, especially those with AQP4-ab, had greater sensory dysfunction and higher levels of inflammatory markers than did LETM patients without CTD. Multicenter cooperation and long-term follow-up are necessary to further study the inherent implications and prognosis of the disease.

Neuromyelitis optica spectrum disorders with and without connective tissue disorders.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) often coexist with connective tissue disorders (CTD). The aim of this study was to investigate and compare the features of NMOSD with and without CTD. METHODS: NMOSD patients with (n = 18) and without CTD (n = 39) were enrolled, and the clinical, laboratory, and magnetic resonance imaging (MRI) features of the two groups were assessed. RESULTS: Most of the demographic and clinical features examined were similar between NMOSD patients with and without CTD. Serum immunoglobulin G (IgG), percentage of γ-globulin and seropositivity for several other autoantibodies were significantly elevated in NMOSD patients with CTD (P < 0.05). NMOSD with CTD was marked by longer spinal cord lesions and a lower frequency of short transverse myelitis (TM) than NMOSD without CTD (P < 0.05). NMOSD with CTD also featured more T1 hypointensity and T2 bright spotty lesions (BSLs) on MRI than NMOSD without CTD (P = 0.001 and 0.011, respectively). There were no other differences in laboratory, MRI and clinical characteristics between different NMOSD subtypes. CONCLUSIONS: A few characteristics differed between NMOSD with and without CTD. NMOSD patients with CTD had higher serum IgG, longer spinal cord lesions, a lower frequency of short TM and more T1 hypointensity and T2 BSLs on spinal MRI than NMOSD patients without CTD.