Refine
Has Fulltext
- yes (77)
Is part of the Bibliography
- yes (77)
Year of publication
Document Type
- Journal article (77)
Language
- English (77)
Keywords
- Fabry disease (11)
- neuropathic pain (8)
- cytokines (5)
- fibromyalgia syndrome (5)
- pain (5)
- Parkinson's disease (4)
- autoantibodies (4)
- skin punch biopsy (4)
- Fabry-associated pain (3)
- Medizin (3)
- depression (3)
- enzyme replacement therapy (3)
- gene expression (3)
- mouse model (3)
- small fiber neuropathy (3)
- B7-H1 (2)
- Fibromyalgia syndrome (2)
- Langerhans cells (2)
- Neuropathy (2)
- antibodies (2)
- anxiety (2)
- autoantibody (2)
- biomarker (2)
- chronic pain (2)
- diagnosis (2)
- expression (2)
- glycine receptor (2)
- inflammation (2)
- inflammatory neuropathy (2)
- microRNA (2)
- mouse models (2)
- nerve fibers (2)
- neurofascin (2)
- neurology (2)
- neuropathy (2)
- opioids (2)
- passive transfer (2)
- polyneuropathy (2)
- renal system (2)
- skin biopsy (2)
- 65-kda isoform (1)
- A-delta fibers (1)
- Agalsidase beta therapy (1)
- Alpha galactosidase (1)
- Anderson-Fabry Disease (1)
- Antiparanodal Autoantibodies (1)
- Anxiety (1)
- Arterial Diameters (1)
- Axonal degeneration (1)
- Aδ- and C-fibers (1)
- Beta-glucocerebrosidase (1)
- CCI (1)
- CIDP (1)
- CLN3 (1)
- CNS imaging (1)
- CRPS (1)
- Charcot–Marie–Tooth disease type 1A (1)
- CholinomiRs (1)
- Clinical manifestations (1)
- Cognitive behavior (1)
- Corneal confocal microscopy (1)
- Cytokines (1)
- D313Y genotype (1)
- Delphi procedure (1)
- Demyelinating peripheral neuropathy (1)
- Diabetes mellitus (1)
- Diabetic polyneuropathy (1)
- Diagnose (1)
- Diagnosis (1)
- Disease (1)
- English version (1)
- Enzyme replacement therapy (1)
- Epilepsy (1)
- FOSMN (1)
- Fabry (1)
- Fabry cardiomyopathy (1)
- Fabry genotype (1)
- Fabry nephropathy (1)
- Fabry phenotype (1)
- Factor messenger-RNA (1)
- Fibromyalgie (1)
- Gene-expression (1)
- Gland (1)
- Glutamic-acid decarboxylase anxiety (1)
- Guillain-Barre-Syndrome (1)
- Guillain-Barré syndrome (1)
- Heat Hyperalgesia (1)
- IENFD (1)
- IL-15 (1)
- IL-4 (1)
- IVIg (1)
- Identification (1)
- IgG4 (1)
- Immune system (1)
- Innervation (1)
- Interleukin-6 (1)
- Interleukin-6-Deficient mice (1)
- LIMP-2 (1)
- Leukemia Inhibitory Factor (1)
- MDL-28170 (1)
- MIBG scintigraphy (1)
- MIC ligands (1)
- MMP9 (1)
- Mechanisms (1)
- Mediated Inflammatory Hyperalgesia (1)
- Merkel cell density (1)
- Mice (1)
- Migräne (1)
- Monopolar depression (1)
- Motor nerve biopsy (1)
- NF-κB (1)
- NKG2D (1)
- NKG2D ligands (1)
- NMOSD (1)
- NPSI (1)
- Necrosis-factor-Alpha (1)
- Nerve growth-factorcopy (1)
- Neuralgie (1)
- Neurotrophic factors (1)
- Nodo-parandopathy (1)
- Oncostatin-M-Receptor (1)
- Opioid receptor (1)
- Outcome survey (1)
- PD-L1 (1)
- PET (1)
- Pain (1)
- Pain questionnaire (1)
- Pain-related evoked potentials (1)
- Peripheral Inflammation (1)
- Pharmacological management (1)
- Quality of life (1)
- RECK (1)
- RNA extraction (1)
- Randomized controlled trial (1)
- Rat Sensory Neurons (1)
- Receptors (1)
- Rheumatoid-Arthritis (1)
- Rochester diabetic neuropathy (1)
- SNI (1)
- Schwann cell (1)
- Schwann-cells (1)
- Serotonin (1)
- Sjorgens-syndrome (1)
- Skin biopsy (1)
- Small fiber neuropathy (1)
- Small-fiber neuropathy (1)
- T cell activation (1)
- TNFα (1)
- Thermal Hyperalgesia (1)
- Treatment (1)
- Tryptophan hydroxylase-2 (Tph2) (1)
- X-chromosomal inactivation (1)
- adsorption (1)
- afferents (1)
- aggression (1)
- algorithm (1)
- allodynia (1)
- allotype (1)
- alpha-galactosidase A (1)
- alpha-synuclein (1)
- amygdala (1)
- amyotrophic-lateral-sclerosis (1)
- analgesia (1)
- animal behavior (1)
- antagomir (1)
- anti-contactin-1 (1)
- aquaporin 4 (1)
- atrophy Kennedys-disease (1)
- autoantibody (aAb) (1)
- autoimmune nodopathy (1)
- back pain (1)
- behavioral disorders (1)
- binding (1)
- binding analysis (1)
- biopsies (1)
- biopsy (1)
- blood CSF barrier (1)
- blood flow (1)
- blood nerve barrier (1)
- brain (1)
- burning pain (1)
- calpain (1)
- capsaicin (1)
- care (1)
- celiac disease (1)
- cell binding assay (1)
- central nervous system (1)
- cerebral arteries (1)
- cerebrospinal fluid (1)
- cholinergic system (1)
- chronic constriction nerve injury (1)
- chronic constriction nerve injury (CCI) (1)
- chronic stress (1)
- classification (1)
- claudin-1 (1)
- clinical neurology (1)
- cognitive impairment (1)
- complement deposition (1)
- complex regional pain syndrome (1)
- contactin (1)
- coping (1)
- corneal confocal microscopy (1)
- cortical activation (1)
- criteria (1)
- crossover trial (1)
- cue (1)
- cutaneous innervation (1)
- cutaneous patch (1)
- cutting edge (1)
- dermal B cells (1)
- dermatology (1)
- diagnosis in Fabry disease (1)
- diagnostic markers (1)
- disability (1)
- disorder (1)
- enzyme assays (1)
- enzyme-linked immunoassays (1)
- epidermis (1)
- extracellular domain (1)
- facial pain (1)
- fear (1)
- fear memory (1)
- female Fabry patients (1)
- females (1)
- fibers (1)
- fibromyalgia (1)
- flotillin-1 lipid rafts (1)
- functional genetics (1)
- gene variant (1)
- gene-by-environment interaction (1)
- genetics (1)
- genotype/phenotype correlation (1)
- gephyrin (1)
- globotriaosylceramide (1)
- glucocerebrosidase mutation (1)
- glycine receptor (GlyR) (1)
- glycine receptor autoantibodies (1)
- glycosylation (1)
- guidelines (1)
- half-life (1)
- hernia repair (1)
- hippocampus (1)
- human muscle-cells (1)
- humans (1)
- hyperalgesia (1)
- hyperekplexia (1)
- idiopathic inflammatory myopathies (1)
- immune system (1)
- immunofluorescence (1)
- immunology (1)
- immunomodulation (1)
- inflammatory demyelinating polyradiculoneuropathy (1)
- inherited metabolic disorders (1)
- innervation (1)
- interference (1)
- intraepidermal nerve fiber density (1)
- intraepidermal nerve fibre density (1)
- intrathecal application (1)
- intravenous immunoglobulin (1)
- ion channels (1)
- ischemic stroke (1)
- learning (1)
- lesions (1)
- long-term pain (1)
- lymphokine-activated killer (1)
- lyso-Gb3 (1)
- lysosomal storage disease (1)
- macrophages (1)
- magnetic resonance imaging (1)
- management (1)
- mast cells (1)
- metaanalysis (1)
- miR-182-5p (1)
- miR-21 (1)
- miRNA (1)
- miRNA expression patterns (1)
- miRNA polymorphisms (1)
- miRNA-based analgesic (1)
- miRNA-based diagnostics (1)
- mice (1)
- migraineur (1)
- mixed fiber neuropathy (1)
- motor proteins (1)
- movement disorders (1)
- multiple sclerosis (1)
- multiple system atrophy (1)
- musk myasthenia gravis (1)
- mutation (1)
- near-infrared spectroscopy (1)
- nerve biopsy (1)
- nerve fibres (1)
- nerve tumor (1)
- nerve ultrasonography (1)
- nerve-fibers (1)
- neuralgia (1)
- neurofilament light chain (1)
- neuroleukemiosis (1)
- neurological examination (1)
- neuronopathy (1)
- neurons (1)
- nociceptive Schwann cells (1)
- nociceptor sensitization (1)
- node of ranvier (1)
- ontactin 1 (1)
- opioid (1)
- pain questionnaire (1)
- pain sensation (1)
- pain-associated behavior (1)
- pain-related evoked potentials (1)
- paranodopathy (1)
- pathology section (1)
- pathways (1)
- pemphigoid (1)
- pemphigus (1)
- periperal nerve (1)
- peripheral nerve involvement (1)
- peripheral nervous system (1)
- peripheral neuropathy (1)
- polymorphism (1)
- polymyositis (1)
- postherpetic neuralgia (1)
- presynaptic inhibition (1)
- progressive encephalitis with rigidity and myoclonus (PERM) (1)
- proinflammatory cytokine (1)
- quantitative sensory testing (1)
- qutenza (1)
- receptor (1)
- recommendations (1)
- reflex (1)
- reinnervation (1)
- religiosity (1)
- reproducible outcome measure (1)
- risk factors (1)
- scale (1)
- sciatic nerves (1)
- shingles (1)
- skin diseases (1)
- skin tumors (1)
- small-fiber neuropathy (1)
- spinal cord (1)
- spinal-cord-injury (1)
- startle disease (1)
- stiff-person syndrome (SPS) (1)
- stroke (1)
- substance-P (1)
- superficial peroneal nerve (1)
- sural nerve (1)
- swimming (1)
- switch (1)
- synaptic transmission (1)
- systematic review (1)
- tissue resident T cells (1)
- transient receptor potential vanilloid 1 (TRPV1) (1)
- trigeminal nerve (1)
- trigeminal neuropathy (1)
- tumor immunity (1)
- validation (1)
- vasculitis (1)
- white blood cells (1)
Institute
- Neurologische Klinik und Poliklinik (75)
- Institut für Klinische Neurobiologie (8)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (7)
- Medizinische Klinik und Poliklinik I (5)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (4)
- Institut für Klinische Epidemiologie und Biometrie (2)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (2)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (2)
- Rudolf-Virchow-Zentrum (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
Sonstige beteiligte Institutionen
Startle disease is a rare disorder associated with mutations in GLRA1 and GLRB, encoding glycine receptor (GlyR) α1 and β subunits, which enable fast synaptic inhibitory transmission in the spinal cord and brainstem. The GlyR β subunit is important for synaptic localization via interactions with gephyrin and contributes to agonist binding and ion channel conductance. Here, we have studied three GLRB missense mutations, Y252S, S321F, and A455P, identified in startle disease patients. For Y252S in M1 a disrupted stacking interaction with surrounding aromatic residues in M3 and M4 is suggested which is accompanied by an increased EC\(_{50}\) value. By contrast, S321F in M3 might stabilize stacking interactions with aromatic residues in M1 and M4. No significant differences in glycine potency or efficacy were observed for S321F. The A455P variant was not predicted to impact on subunit folding but surprisingly displayed increased maximal currents which were not accompanied by enhanced surface expression, suggesting that A455P is a gain-of-function mutation. All three GlyR β variants are trafficked effectively with the α1 subunit through intracellular compartments and inserted into the cellular membrane. In vivo, the GlyR β subunit is transported together with α1 and the scaffolding protein gephyrin to synaptic sites. The interaction of these proteins was studied using eGFP-gephyrin, forming cytosolic aggregates in non-neuronal cells. eGFP-gephyrin and β subunit co-expression resulted in the recruitment of both wild-type and mutant GlyR β subunits to gephyrin aggregates. However, a significantly lower number of GlyR β aggregates was observed for Y252S, while for mutants S321F and A455P, the area and the perimeter of GlyR β subunit aggregates was increased in comparison to wild-type β. Transfection of hippocampal neurons confirmed differences in GlyR-gephyrin clustering with Y252S and A455P, leading to a significant reduction in GlyR β-positive synapses. Although none of the mutations studied is directly located within the gephyrin-binding motif in the GlyR β M3-M4 loop, we suggest that structural changes within the GlyR β subunit result in differences in GlyR β-gephyrin interactions. Hence, we conclude that loss- or gain-of-function, or alterations in synaptic GlyR clustering may underlie disease pathology in startle disease patients carrying GLRB mutations.
Background
Although Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene (GLA), women may develop severe symptoms. We investigated X-chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women.
Patients and Methods
We included 95 women with mutations in GLA (n = 18 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X-chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity.
Results
43/95 (45%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., ≥75:25% distribution) in 6/87 (7%) mouth epithelial cell samples, 31/88 (35%) blood samples, and 9/27 (33%) skin fibroblast samples. Clinical phenotype, α-galactosidase A (GAL) activity, and lyso-Gb3 levels did not show intergroup differences when stratified for X-chromosomal skewing and activity status of the mutated X-chromosome.
Conclusions
X-inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.
Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with a characteristic pain phenotype. Impaired GLA production or function leads to the accumulation of the cell membrane compound globotriaosylceramide (Gb3) in the neurons of the dorsal root ganglia (DRG) of FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue of the GLA knockout (KO) mouse model of FD, we address the question of how Gb3 accumulation may contribute to FD pain and focus on the immune system and pain-associated ion channel gene expression. We show a higher Gb3 load in the DRG of young (<6 months) (p < 0.01) and old (≥12 months) (p < 0.001) GLA KO mice compared to old wildtype (WT) littermates, and an overall suppressed immune response in the DRG of old GLA KO mice, represented by a reduced number of CD206\(^+\) macrophages (p < 0.01) and lower gene expression levels of the inflammation-associated targets interleukin(IL)1b (p < 0.05), IL10 (p < 0.001), glial fibrillary acidic protein (GFAP) (p < 0.05), and leucine rich alpha-2-glycoprotein 1 (LRG1) (p < 0.01) in the DRG of old GLA KO mice compared to old WT. Dysregulation of immune-related genes may be linked to lower gene expression levels of the pain-associated ion channels calcium-activated potassium channel 3.1 (KCa3.1) and transient receptor potential ankyrin 1 channel (TRPA1). Ion channel expression might further be disturbed by impaired sphingolipid recruitment mediated via the lipid raft marker flotillin-1 (FLOT1). This impairment is represented by an increased number of FLOT1\(^+\) DRG neurons with a membranous expression pattern in old GLA KO mice compared to young GLA KO, young WT, and old WT mice (p < 0.001 each). Further, we provide evidence for aberrant behavior of GLA KO mice, which might be linked to dysregulated ion channel gene expression levels and disturbed FLOT1 distribution patterns. Behavioral testing revealed mechanical hypersensitivity in young (p < 0.01) and old (p < 0.001) GLA KO mice compared to WT, heat hypersensitivity in young GLA KO mice (p < 0.001) compared to WT, age-dependent heat hyposensitivity in old GLA KO mice (p < 0.001) compared to young GLA KO mice, and cold hyposensitivity in young (p < 0.001) and old (p < 0.001) GLA KO mice compared to WT, which well reflects the clinical phenotype observed in FD patients.
A diagnosis of neuropathy can typically be determined through clinical assessment and focused investigation. With technological advances, including significant progress in genomics, the role of nerve biopsy has receded over recent years. However, making a specific and, in some cases, tissue-based diagnosis is essential across a wide array of potentially treatable acquired peripheral neuropathies. When laboratory investigations do not suggest a definitive diagnosis, nerve biopsy remains the final step to ascertain the etiology of the disease. The present review highlights the utility of nerve biopsy in confirming a diagnosis, while further illustrating the importance of a tissue-based diagnosis in relation to treatment strategies, particularly when linked to long-term immunosuppressive therapies,
Background and Objective
This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non‐cancer neuropathic pain.
Databases and Data Treatment
Clinicaltrials.gov, CENTRAL, PubMed and PsycINFO were searched from October 2013 to June 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks double‐blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD). We added four new studies with 662 participants for a total of 16 included studies with 2,199 participants. Study duration ranged between 4 and 12 weeks. Studies with a parallel and cross‐over design: Based on low to moderate quality evidence, opioids (buprenorphine, hydromorphone, morphine, oxycodone, tramadol) provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo. Enriched enrolment randomized withdrawal design: Based on low to moderate quality evidence, tapentadol provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo in diabetic polyneuropathy. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by tapentadol compared to placebo.
Conclusions
Some opioids provided a short‐term substantial pain relief in highly selected patients in some neuropathic pain syndromes.
Significance
Some opioids (buprenorphine, morphine, oxycodone, tramadol, tapentadol) provide substantial pain relief compared to placebo in postherpetic neuralgia and peripheral neuropathies of different aetiologies for 4–12 weeks. There is insufficient evidence to support or refute the suggestion that these drugs are effective in other neuropathic pain conditions. The safety of opioids with regards to abuse and deaths in the studies analysed cannot be extrapolated to routine clinical care.
Relevance of Religiosity for Coping Strategies and Disability in Patients with Fibromyalgia Syndrome
(2022)
Coping strategies are essential for the outcome of chronic pain. This study evaluated religiosity in a cohort of patients with fibromyalgia syndrome (FMS), its effect on pain and other symptoms, on coping and FMS-related disability. A total of 102 FMS patients were recruited who filled in questionnaires, a subgroup of 42 patients participated in a face-to-face interview, and data were evaluated by correlation and regression analyses. Few patients were traditionally religious, but the majority believed in a higher existence and described their spirituality as "transcendence conviction". The coping strategy "praying-hoping" and the ASP dimension "religious orientation" (r = 0.5, P < 0.05) showed a significant relationship independent of the grade of religiosity (P < 0.05). A high grade of belief in a higher existence was negatively associated with the choice of ignoring as coping strategy (r = - 0.4, P < 0.05). Mood and affect-related variables had the highest impact on disability (b = 0.5, P < 0.05). In this cohort, the grade of religiosity played a role in the choice of coping strategies, but had no effects on health and mood outcome.
Heterozygous mutations in the glucocerebrosidase gene (GBA1) represent the most common genetic risk factor for Parkinson's disease (PD) and are histopathologically associated with a widespread load of alpha-synuclein in the brain. Therefore, PD patients with GBA1 mutations are a cohort of high interest for clinical trials on disease-modifying therapies targeting alpha-synuclein. There is evidence that detection of phospho-alpha-synuclein (p-syn) in dermal nerve fibers might be a biomarker for the histopathological identification of PD patients even at premotor or very early stages of disease. It is so far unknown whether dermal p-syn deposition can also be found in PD patients with GBA1 mutations and may serve as a biomarker for PD in these patients. Skin biopsies of 10 PD patients with different GBA1 mutations (six N3705, three E326K, one L444P) were analyzed by double-immunofluorescence labeling with anti-p-syn and anti-protein gene product 9.5 (PGP9.5, axonal marker) to detect intraaxonal p-syn deposition. Four biopsy sites (distal, proximal leg, paravertebral Th10, and C7) per patient were studied. P-syn was found in six patients (three N370S, three E326K). P-syn deposition was mainly detected in autonomic nerve fibers, but also in somatosensory fibers and was not restricted to a certain GBA1 mutation. In summary, dermal p-syn in PD patients with GBA1 mutations seems to offer a similar distribution and frequency as observed in patients without a known mutation. Skin biopsy may be suitable to study p-syn deposition in these patients or even to identify premotor patients with GBA1 mutations.