99 research outputs found
a previously undescribed entity
Background: There are few studies describing periodic limb movement syndrome
(PLMS) in rapid eye movement (REM) sleep in patients with narcolepsy, restless
legs syndrome, REM sleep behavior disorder, and spinal cord injury, and to a
lesser extent, in insomnia patients and healthy controls, but no published
cases in multiple sclerosis (MS). The aim of this study was to investigate
PLMS in REM sleep in MS and to analyze whether it is associated with age, sex,
disability, and laboratory findings. Methods: From a study of MS patients
originally published in 2011, we retrospectively analyzed periodic limb
movements (PLMs) during REM sleep by classifying patients into two subgroups:
PLM during REM sleep greater than or equal to ten per hour of REM sleep (n=7)
vs less than ten per hour of REM sleep (n=59). A univariate analysis between
PLM and disability, age, sex, laboratory findings, and polysomnographic data
was performed. Results: MS patients with more than ten PLMs per hour of REM
sleep showed a significantly higher disability measured by the Kurtzke
expanded disability status scale (EDSS) (P=0.023). The presence of more than
ten PLMs per hour of REM sleep was associated with a greater likelihood of
disability (odds ratio 22.1; 95% confidence interval 3.5–139.7; P<0.0001),
whereas there were no differences in laboratory and other polysomnographic
findings. Conclusion: PLMs during REM sleep were not described in MS earlier,
and they are associated with disability measured by the EDSS
Drug reaction with eosinophilia and systemic symptoms after daclizumab therapy in MS
Currently, 12 cases (including our patient) of autoimmune encephalitis/encephalopathy after daclizumab therapy in MS are known worldwide and led to voluntary withdrawal of marketing authorization for daclizumab by the manufacturer Biogen (press release from European Medicines Agency, 07.03.2018).
Our findings suggest that early recognition of DRESS even with CNS manifestations and swift treatment with steroids and/or plasma exchange are essential to improve the longterm outcome
Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE
Most multiple sclerosis (MS) patients develop over time a secondary
progressive disease course, characterized histologically by axonal loss and
atrophy. In early phases of the disease, focal inflammatory demyelination
leads to functional impairment, but the mechanism of chronic progression in MS
is still under debate. Reactive oxygen species generated by invading and
resident central nervous system (CNS) macrophages have been implicated in
mediating demyelination and axonal damage, but demyelination and
neurodegeneration proceed even in the absence of obvious immune cell
infiltration, during clinical recovery in chronic MS. Here, we employ
intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH
oxidases (NOX1–4, DUOX1, 2) and, thus, to identify the cellular source of
oxidative stress in the CNS of mice affected by experimental autoimmune
encephalomyelitis (EAE) in the remission phase of the disease. This directly
affects neuronal function in vivo, as monitored by cellular calcium levels
using intravital FRET–FLIM, providing a possible mechanism of disease
progression in MS
Dimethylethanolamine Decreases Epileptiform Activity in Acute Human Hippocampal Slices in vitro
Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy with about 30% of patients developing pharmacoresistance. These patients continue to suffer from seizures despite polytherapy with antiepileptic drugs (AEDs) and have an increased risk for premature death, thus requiring further efforts for the development of new antiepileptic therapies. The molecule dimethylethanolamine (DMEA) has been tested as a potential treatment in various neurological diseases, albeit the functional mechanism of action was never fully understood. In this study, we investigated the effects of DMEA on neuronal activity in single-cell recordings of primary neuronal cultures. DMEA decreased the frequency of spontaneous synaptic events in a concentration-dependent manner with no apparent effect on resting membrane potential (RMP) or action potential (AP) threshold. We further tested whether DMEA can exert antiepileptic effects in human brain tissue ex vivo. We analyzed the effect of DMEA on epileptiform activity in the CA1 region of the resected hippocampus of TLE patients in vitro by recording extracellular field potentials in the pyramidal cell layer. Epileptiform burst activity in resected hippocampal tissue from TLE patients remained stable over several hours and was pharmacologically suppressed by lacosamide, demonstrating the applicability of our platform to test antiepileptic efficacy. Similar to lacosamide, DMEA also suppressed epileptiform activity in the majority of samples, albeit with variable interindividual effects. In conclusion, DMEA might present a new approach for treatment in pharmacoresistant TLE and further studies will be required to identify its exact mechanism of action and the involved molecular targets
Drug reaction with eosinophilia and systemic symptoms after daclizumab therapy in MS
Currently, 12 cases (including our patient) of autoimmune encephalitis/encephalopathy after daclizumab therapy in MS are known worldwide and led to voluntary withdrawal of marketing authorization for daclizumab by the manufacturer Biogen (press release from European Medicines Agency, 07.03.2018).
Our findings suggest that early recognition of DRESS even with CNS manifestations and swift treatment with steroids and/or plasma exchange are essential to improve the longterm outcome
Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder
Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD).
Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14-CD15(high) and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16(hi) LDGs. Clinical data on disease course, medication, and antibody status were obtained.
Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group.
Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD
Anti-CD20 Depletes Meningeal B Cells but Does Not Halt the Formation of Meningeal Ectopic Lymphoid Tissue
Objective To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (alphaCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS). Methods We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. alphaCD20 mAbs were administered in either a preventive or a treatment regimen. The extent and cellular composition of mELT was assessed by histology and immunohistochemistry. Results alphaCD20 mAb, applied in a paradigm to either prevent or treat EAE, did not alter the disease course in either condition. However, alphaCD20 mAb depleted virtually all B cells from the meningeal compartment but failed to prevent the formation of mELT altogether. Because of the absence of B cells, mELT was less densely populated with immune cells and the cellular composition was changed, with increased neutrophil granulocytes. Conclusions These results demonstrate that, in CNS autoimmune disease, meningeal inflammatory infiltrates may form and persist in the absence of B cells. Together with the finding that alphaCD20 mAb does not ameliorate spontaneous chronic EAE with mELT, our data suggest that mELT may have yet unknown capacities that are independent of B cells and contribute to CNS autoimmunity
In vivo imaging of lymphocytes in the CNS reveals different behaviour of naïve T cells in health and autoimmunity
<p>Abstract</p> <p>Background</p> <p>Two-photon laser scanning microscopy (TPLSM) has become a powerful tool in the visualization of immune cell dynamics and cellular communication within the complex biological networks of the inflamed central nervous system (CNS). Whereas many previous studies mainly focused on the role of effector or effector memory T cells, the role of naïve T cells as possible key players in immune regulation directly in the CNS is still highly debated.</p> <p>Methods</p> <p>We applied <it>ex vivo </it>and intravital TPLSM to investigate migratory pathways of naïve T cells in the inflamed and non-inflamed CNS. MACS-sorted naïve CD4+ T cells were either applied on healthy CNS slices or intravenously injected into RAG1 -/- mice, which were affected by experimental autoimmune encephalomyelitis (EAE). We further checked for the generation of second harmonic generation (SHG) signals produced by extracellular matrix (ECM) structures.</p> <p>Results</p> <p>By applying TPLSM on living brain slices we could show that the migratory capacity of activated CD4+ T cells is not strongly influenced by antigen specificity and is independent of regulatory or effector T cell phenotype. Naïve T cells, however, cannot find sufficient migratory signals in healthy, non-inflamed CNS parenchyma since they only showed stationary behaviour in this context. This is in contrast to the high motility of naïve CD4+ T cells in lymphoid organs. We observed a highly motile migration pattern for naïve T cells as compared to effector CD4+ T cells in inflamed brain tissue of living EAE-affected mice. Interestingly, in the inflamed CNS we could detect reticular structures by their SHG signal which partially co-localises with naïve CD4+ T cell tracks.</p> <p>Conclusions</p> <p>The activation status rather than antigen specificity or regulatory phenotype is the central requirement for CD4+ T cell migration within healthy CNS tissue. However, under inflammatory conditions naïve CD4+ T cells can get access to CNS parenchyma and partially migrate along inflammation-induced extracellular SHG structures, which are similar to those seen in lymphoid organs. These SHG structures apparently provide essential migratory signals for naïve CD4+ T cells within the diseased CNS.</p
COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis
Background: The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism.
Case presentation: Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2).
Conclusion: Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice
Successful plasmapheresis and immunoglobulin treatment for severe lipid storage myopathy: Doing the right thing for the wrong reason
Three consecutive skeletal muscle biopsies during a several months time-frame, showing different degrees of neutral lipid storage. This is highlighted by Oil-red-O stains (D, E, F) and electron microscopy (G, H, I). Note the impact on mitochondrial morphology with so called 'parking lots (K, L). Zooming 'in and out' into the ultrastructure, using the nanotomy platform provides interesting detailled information (http://nanotomy.org).
- …