Selenium deficiency is associated with polyneuropathy in primary Sjögren's syndrome.

BACKGROUND: Selenium plays an important role in the regulation of the immune system. Selenium deficiency is associated with Hashimoto's thyroiditis, a common comorbidity in primary Sjögren's syndrome (pSS). Therefore we aimed to identify whether or not selenium deficiency is also associated with pSS. METHODS: 107 consecutive female patients with pSS and, as a control, 59 female patients with axial spondyloarthritis were recruited. Later, 11 male pSS patients, 5 of these suffering from polyneuropathy, and 15 male axSpA patients were additionally recruited in order to confirm the results from the female patients. All patients were consulted about their diet and food intolerances and their plasma selenium concentrations were analyzed. Current and previous extraglandular manifestations of pSS were recorded. Patients complaining of misperceptions and tingling paraesthesia underwent measurement of nerve conduction velocity. The proportion of patients and controls with a selenium deficiency was compared using Fisher's exact test. RESULTS: The proportion of female pSS patients with a low selenium concentration <0.63 µmol/L (22.4%) was significantly higher than of the controls (1.7%) (p < 0.001). Within the group of female patients with pSS, selenium deficiency was significantly associated with the presence of polyneuropathy (45.8% with vs 14.5% without polyneuropathy, p = 0.003) and particularly polyneuropathy with motor nerve involvement measured by nerve conduction velocity (41.7% with vs 10.8% without motor neuropathy, p = 0.001). The mean selenium concentrations of the 5 male pSS patients with polyneuropathy were significantly lower compared to the 6 pSS patients without polyneuropathy and to the 15 male axSpA controls. CONCLUSIONS: PSS and in particular its complication polyneuropathy is associated with selenium deficiency. Measurement of the selenium concentration in blood is advisable in patients with pSS and in particular in the subset of patients with polyneuropathy. Substitution of selenium may be a possible therapy of polyneuropathy associated with pSS.

Acute Enterovirus Encephalitis as a Cause for Isolated Visual and Auditory Hallucinations in a 22-Year-Old Patient.

Viral encephalitis often presents with severe illness, headache, fever, behavioral changes, altered level of consciousness, and focal neurologic deficits. One of the most feared kind of virus encephalitis is herpes simplex encephalitis; however, other central virus infections are also capable of presenting with psychiatric symptoms. Here, we report the case of a 22-year-old woman with first time visual and auditory hallucinations due to an acute enterovirus encephalitis with no cerebrospinal fluid abnormalities but a positive PCR result for enterovirus (ECHO). During treatment, the symptoms deteriorated, and she hat to be shifted to the sheltered ward because of imperative suicidal auditory hallucinations. Under treatment with risperidone and olanzapine, symptoms suddenly stopped and did not reoccur under subsequent reduction of the antipsychotic medication.

[Severe polyneuropathy in primary Sjögren's syndrome : Sjögren's syndrome should be considered in patients with motor neuropathy]. / Schwere Polyneuropathie bei primärem Sjögren-Syndrom : Bei Patienten mit motorischen Neuropathien auch an Sjögren-Syndrom denken!

A 64-year-old male patient developed over a period of 20 years a peripheral neuropathy symmetrically affecting the upper and lower limbs. The histological examination of a sural nerve biopsy revealed a severe axonal neuropathy. Despite extensive laboratory investigations including immunological and metabolic tests the origin could not be identified. Finally, a Schirmer test revealed xerophthalmia. A subsequent salivary gland biopsy from the lower lip revealed a grade III lymphocytic inflammation according to Chisholm and Mason and confirmed the diagnosis of Sjögren's syndrome.

[Neurological complications of infections with (novel) enteroviruses]. / Neurologische Komplikationen bei Infektionen mit (neuen) Enteroviren.

Enterovirus (EV) infections are frequent and predominantly affect children. Neurological manifestations are rare but can induce severe consequences. Since 2014 a global rise in EV-D68 and EV-71 infections manifesting with neurological complications, namely rhombencephalitis (EV-71) and acute flaccid myelitis (EV-D68), has been observed with an increased distribution in Europe and isolated occurrences in Germany. Typically prodromes with respiratory infections and gastrointestinal conditions precede neurological symptoms. In these cases, an EV infection should be considered as the underlying cause and appropriate diagnostic tests should be performed. Other than the typical inflammatory signs in cerebrospinal fluid (CSF), the changes on magnetic resonance imaging (MRI) in particular are seminal; however, confirmation of the virus is often not possible in the CSF so that other specimens from, e.g. feces or the respiratory tract are required. To date there are no causal therapies for either of these EV infections; therefore, a comprehensive supportive therapy is of major significance. In Taiwan some beneficial effects could be observed by administration of intravenous immunoglobulins; however, a reliable study has not yet been published.

Remyelination after cuprizone induced demyelination is accelerated in mice deficient in the polysialic acid synthesizing enzyme St8siaIV.

Polysialic acid (PSA) is a carbohydrate polymer added post-translationally on the neural cell adhesion molecule (NCAM) affecting its adhesion properties. It has been suggested that the presence of PSA in demyelinated lesions in multiple sclerosis could prevent axon-glia interactions inhibiting spontaneous remyelination. The enzyme St8siaIV is one of the two polysialyltransferases responsible for PSA synthesis, and it is predominantly active during adult life. Here we treated 8-10-weeks old St8siaIV deficient and wild-type mice for 5 weeks with cuprizone, which is a reliable model for de- and remyelination in the corpus callosum and cortex. Developmental myelination of the St8siaIV knock-out mice was not disturbed and adult mice showed normal myelin protein expression. Demyelination did not differ between transgenic and wild-type mice but early myelin protein re-expression and thus remyelination were accelerated in St8siaIV knock-out mice during the first week after withdrawal of the toxin. This was mainly due to enhanced oligodendrocyte precursor cells (OPC) differentiation and to a lesser extent to OPC recruitment. These data are proof of principle that PSA expression interferes at least to some extent with remyelination in vivo.

Polyclonal immunoglobulins (IVIg) induce expression of MMP-9 in microglia.

In multiple sclerosis (MS) matrix metalloproteinases (MMP) are believed to be involved in the disruption of the blood brain barrier and demyelination. MMP-9 is increased in the cerebrospinal fluid of MS patients and expressed in MS lesions, indicating an involvement in MS pathogenesis. It is known that activated microglia secrete MMP. Modulation of MMP may thus be of interest for treatment in particular since MMP knock-out mice are less susceptible to experimental allergic encephalomyelitis. In this study we show that intact polyclonal immunoglobulins for intravenous use (IVIg) lead to increased secretion of MMP-9 in unstimulated microglia whereas F(ab')(2) fragments or stimulation with lipopolysaccharide (LPS) had no effect on MMP production at all. We could not detect MMP-2, MMP-3, MMP-7, MMP-10, MMP-11, and MMP-12 by RT-PCR with and without stimulation with LPS. IVIg differentially modulate MMP-9 production in resting and activated microglia suggesting an activation-dependent immune response.

Normal sensitivity to excitotoxicity in a transgenic Huntington's disease rat.

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. Excitotoxic cell damage by excessive stimulation of glutamate receptors has been hypothesized to contribute to the pathogenesis of HD. Transgenic mouse models of HD have shown variable sensitivity to excitotoxicity. The models differ in the genetic background, the type and length of the promoter driving the transgene expression, the CAG repeat length and/or the HD gene construct length. Furthermore, one has to differentiate whether transgenic or knock-in models have been used. All these factors may be involved in determining the responsiveness to an excitotoxic insult. Here, we explored the responsiveness to excitotoxic damage using a transgenic HD rat model carrying 22% of the rat HD gene which is driven by the rat HD promoter and which harbors 51 CAG repeats. 3 and 18 months old transgenic HD rats and their wild-type littermates received unilateral intrastriatal injections of the glutamate analogue quinolinic acid. Lesion size was assessed 7 days later using the degenerative stain Fluoro-Jade and by immunohistochemistry for the neuronal protein NeuN. No difference in susceptibility to excitotoxicity was found between the groups. Our study supports mouse data showing maintained susceptibility to excitotoxicity with the expression of around 25% of the full HD gene. Differences in sensitivity to excitotoxicity between genetic animal models of HD may be dependent on the length of the expressed HD gene although additional factors are also likely to be important.

CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model.

CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.