Hongliang Zhang

Microembolic Signals Detected with Transcranial Doppler Sonography Differ between Symptomatic and Asymptomatic Middle Cerebral Artery Stenoses in Northeast China

Although microembolus monitoring has been widely used for ischemic cerebrovascular disease, the clinical significance of microembolic signal (MES) in asymptomatic middle cerebral artery (MCA) stenosis remains unclear. We aim to investigate the frequency of MES and the value of MES in predicting ischemic stroke secondary to asymptomatic MCA stenosis. From June 2011 to December 2012, microembolus monitoring was performed in 83 asymptomatic and 126 symptomatic subjects. By comparing the demographics and risk factors between the symptomatic and asymptomatic subjects, we found that the ratio of male sexuality and smoking history differed (101/126 vs 43/83, and 88/126 vs 38/83, respectively, p<0.01). The frequency of MES was significantly higher in the symptomatic group than in the asymptomatic group (49/126 vs 2/108, p<0.01). Specifically, the frequency of MES in the symptomatic and asymptomatic groups with mild stenosis, moderate stenosis, severe stenosis and occlusion groups was 4/18 (22.22%) vs 0/30 (0), 13/31 (41.94%) vs 1/28 (3.57%), 30/62 (48.39%) vs 1/39 (2.56%), 2/15 (13.33%) vs 0/11 (0), respectively. Except for the occlusive group, the frequency of MES is correlated with stenosis degree and symptom. Two patients in the asymptomatic group were found positive for MES, and the MES number was 1 for both. During the one-year follow-up, neither of them developed ischemic stroke. In conclusion, MES detected with TCD differs between symptomatic and asymptomatic MCA stenoses. Due to the low frequency, the value of MES as a predictor of subsequent ischemic stroke in patients with asymptomatic MCA stenosis might be limited.

Multiphasic acute disseminated encephalomyelitis associated with atypical rubella virus infection

We read the case report by Shinoda and colleagues1 with great interest. They diagnosed multiphasic acute disseminated encephalomyelitis (ADEM) associated with atypical rubella virus infection in a 17-year-old male based on the clinical manifestations, laboratory investigations, the results of sequential magnetic resonance imaging (MRI) and the pathological findings.1 However, the diagnosis of relapsing–remitting multiple sclerosis (RRMS) could not be ruled out based on the current clinical data.

Neuritogenic Th17 cells in Guillain–Barré syndrome and experimental autoimmune neuritis

impacts of modification. For the latter, computer-basedmodeling offers an attractive option. We thus identified the need for easily applicable modeling options for PTMs. Results: We programmed a modelling plugin called PyTMs implemented with the commonly used visualization software PyMOL. PyTMs enables basic users to introduce a set of common PTMs into protein/peptide models and can be used to address research questions related to PTMs. Ten types of modification are currently possible to model, namely: acetylation, carbamylation, citrullination, cysteine oxidation, malondialdehyde adducts, methionine oxidation, methylation, nitration, proline hydroxylation and phosphorylation. Advanced settings define stereochemical alternatives and allow for basic structure optimization. Discussion: PyTMs is a useful, freely available modelling tool for the research community. Advantages include standardized generation of PTMs, rapid time-to-result and facilitated user control. Although modelling cannot replace conventional structure resolution it constitutes a useful tool that allows uncomplicated exploration of potential implications prior to experimental investments and basic explanation of experimental data.

Altered levels of IL-27 in the cerebrospinal fluid and plasma of patients with Guillain–Barré syndrome

Toxic leukoencephalopathy is usually a structural alteration of white matter of the brain secondary to various agents, without special clinical manifestations but usually has a typical radiologic image. Morantel is an anthelmintic used for prevention and control of ostertagiasis. It mainly targets at adult worms and developing larvae with low toxicity and has been widely used for all classes of cattle including lactating dairy cattle at any stage of lactation. So far, there has been no report on morantel-induced toxic leukoencephalopathy. We report herein a case of a 41-year-old man presenting with sluggishness in response and gradual consciousness disturbance without a history of drug abuse or poison exposure. The subsequent cranial magnetic resonance imaging (MRI) examination revealed widespread symmetrically reduced diffusion in the supratentorial and periventricular white matter, suggestive of toxic leukoencephalopathy. Morantel was further detected in the blood of the patient. Diagnosis of morantel-induced toxic leukoencephalopathy was thus established. Treatment with corticosteroid resulted in a complete resolution of the clinical symptoms and the MRI anomalies.

Toxic leukoencephalopathy caused by morantel: A case report

Toxic leukoencephalopathy is usually a structural alteration of white matter of the brain secondary to various agents, without special clinical manifestations but usually has a typical radiologic image. Morantel is an anthelmintic used for prevention and control of ostertagiasis. It mainly targets at adult worms and developing larvae with low toxicity and has been widely used for all classes of cattle including lactating dairy cattle at any stage of lactation. So far, there has been no report on morantel-induced toxic leukoencephalopathy. We report herein a case of a 41-year-old man presenting with sluggishness in response and gradual consciousness disturbance without a history of drug abuse or poison exposure. The subsequent cranial magnetic resonance imaging (MRI) examination revealed widespread symmetrically reduced diffusion in the supratentorial and periventricular white matter, suggestive of toxic leukoencephalopathy. Morantel was further detected in the blood of the patient. Diagnosis of morantel-induced toxic leukoencephalopathy was thus established. Treatment with corticosteroid resulted in a complete resolution of the clinical symptoms and the MRI anomalies.

Guillain–Barré syndrome in northeast China: A retrospective analysis of 516 cases

Toxic leukoencephalopathy is usually a structural alteration of white matter of the brain secondary to various agents, without special clinical manifestations but usually has a typical radiologic image. Morantel is an anthelmintic used for prevention and control of ostertagiasis. It mainly targets at adult worms and developing larvae with low toxicity and has been widely used for all classes of cattle including lactating dairy cattle at any stage of lactation. So far, there has been no report on morantel-induced toxic leukoencephalopathy. We report herein a case of a 41-year-old man presenting with sluggishness in response and gradual consciousness disturbance without a history of drug abuse or poison exposure. The subsequent cranial magnetic resonance imaging (MRI) examination revealed widespread symmetrically reduced diffusion in the supratentorial and periventricular white matter, suggestive of toxic leukoencephalopathy. Morantel was further detected in the blood of the patient. Diagnosis of morantel-induced toxic leukoencephalopathy was thus established. Treatment with corticosteroid resulted in a complete resolution of the clinical symptoms and the MRI anomalies.

Augmented Th17 cells and IL-17A are associated with severity of experimental autoimmune neuritis

Myasthenia gravis (MG) is a heterogeneous disease with respect to presence of auto-antibodies (ab). Pathogenic ab against the acetylcholine receptor (AChR) are present in the main group of the patients (AChR-MG), whereas another subgroup has ab against muscle specific kinase (MuSK-MG). Cytokines may have regulating effects in the differentiation of B cells and the production of ab in MG subgroups which has not been studied intensively. Cytokines were measured in plasma and in anti-CD3 stimulated or non-stimulated PBMC in 46 AChR-MG, 23 MuSK-MG patients and 42 healthy controls (CON) using multiplex arrays. Gene expression in the isolated CD4T cells were determined by relative quantification. All patients had generalized disease without thymoma and 35–62% were on immunosuppressive (IS) treatment. The levels of T helper cell related IFN-g, IL-12p40, IL-13, IL-17A and IL-10 in plasma and mRNA levels of IL10, IFNG, IL17A and IL21 in CD4T cells were not different between AChR-MG, MuSK-MG and CON groups. The expression of CD40L in isolated CD4 T cells was lower both in AChR-MG and MuSK-MG groups than CON (p = 0.005 and p = 0.003). The transcription factors TBET, RORC, GATA3 and PRDM1 for Th1, Th17, Th2 and Tfh cell subsets were expressed at similar levels in disease subgroups. IL-21 production of un-stimulated as well as stimulated PBMC was higher in MuSK-MG group than CON (p= 0.018 and p= 0.006). AntiCD3 stimulation induced higher IL-21 also in AChR-MG (p= 0.045), while IL-17A production was increased in MuSK-MG compared to CON (p= 0.04). IS treatment of patients decreased spontaneous IFN-g (p = 0.003) in AChR-MG patients. In the treated group, spontaneous IL-10 secretion levels were higher in AChR-MG thanMuSK-MG and CON (p= 0.001, p = 0.031).An inducing effect of IS treatment has been observed by the increase of IL-6 production of AChR-MG compared to untreated patients (p= 0.036) and MuSK-MG (p= 0.008). In the plasma, a decrease of IL-12p40 level was also observed in IS treated AChR-MG patients compared to untreated (p = 0.003). These findings implicate a role for IL-21 and IL-17A from stimulated T cells in regulating the ab production inMuSK-MG.IL-10 and IL-6 seem to be up-regulated, while IFN-g and IL12p40 are suppressed in IS treated patients. Lower expression of CD40L by CD4T cells in patients and down-regulation of cytokines with inflammatory effects by treatment may participate in the functional balance between cytokine related activities in the disease course. This study is supported by TUBITAK (106S223 and 109S353).

Anti-CD73 antibodies are sufficient to prevent rather than treat experimental autoimmune neuritis

Histopathological analyses revealed a significant reduction in demyelination, as well as numbers of both T cells and activated microglia/ macrophages within the spinal cord in anti-TNFR1-treated animals. Furthermore, mice treated with anti-TNFR1 had significantly less axonal degeneration than controls. Our results demonstrate the beneficial effects of TNFR1 inhibition in EAE and highlight the potential of this strategy as a future therapy for MS.

Comparative study on fulminant and sporadic Guillain–Barré syndrome in northeast China

Histopathological analyses revealed a significant reduction in demyelination, as well as numbers of both T cells and activated microglia/ macrophages within the spinal cord in anti-TNFR1-treated animals. Furthermore, mice treated with anti-TNFR1 had significantly less axonal degeneration than controls. Our results demonstrate the beneficial effects of TNFR1 inhibition in EAE and highlight the potential of this strategy as a future therapy for MS.

More severe manifestations and poorer short-term prognosis of ganglioside-associated Guillain–Barré syndrome in northeast China

Ganglioside as a neurotrophic drug has been hitherto widely used in China, although Guillain–Barré syndrome (GBS) following intravenous ganglioside treatment was reported in Europe several decades ago, leading to its withdrawal from European market. We identified 7 patients who developed GBS after intravenous use of gangliosides (the ganglioside+ group) and compared their clinical data with those of 77 non-ganglioside-associated GBS patients (the ganglioside− group) in 2013, aiming at gaining the distinct features of ganglioside-associated GBS. Although the mean age, the protein levels in cerebrospinal fluid (CSF) and the frequency of cranial nerve involvement were similar between the two groups, the Hughes Functional Grading Scale (HFGS) score and the Medical Research Council (MRC) sum score at nadir significantly differed (4.86 versus 3.64; 7.71 versus 36.87, both p b 0.001), indicating a higher disease severity of gangliosideassociated GBS. This was further evidenced by a significantly higher ratio of patients with ganglioside-associated GBS who required mechanical ventilation (85.71% versus 15.58%, p b 0.01). The short-term prognosis of ganglioside-associated GBS, as measured by the HFGS score and the MRC sum score at discharge, was poorer (4.29 versus 2.82; 17.29 versus 45.96, both p b 0.001). All the patients in the ganglioside+ group presented an axonal form of GBS, namely acute motor axonal neuropathy (AMAN). When compared with the AMAN patients in the ganglioside− group, more severe functional deficits at nadir and poorer recovery after standard treatment were still prominent in ganglioside-associated GBS. Anti-GM1 and anti-GT1a antibodies were detectable in patients with AMAN while not in patients with the demyelinating subtype of GBS. The concentrations of these antibodies in patients with AMAN were insignificantly different between the ganglioside+ and the ganglioside− groups. In sum, ganglioside-associated GBS is a devastating side effect of intravenous use of ganglioside, which usually manifests a more severe clinical course and poorer outcome.