Refine
Has Fulltext
- yes (78)
Is part of the Bibliography
- yes (78)
Year of publication
Document Type
- Journal article (78) (remove)
Language
- English (78) (remove)
Keywords
- Fabry disease (12)
- neuropathic pain (8)
- cytokines (5)
- fibromyalgia syndrome (5)
- pain (5)
- Parkinson's disease (4)
- skin punch biopsy (4)
- Fabry-associated pain (3)
- Medizin (3)
- autoantibodies (3)
- depression (3)
- enzyme replacement therapy (3)
- gene expression (3)
- mouse model (3)
- small fiber neuropathy (3)
- B7-H1 (2)
- CIDP (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)
- 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)
- 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 pain (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)
- 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)
- PATH (1)
- PD-L1 (1)
- PET (1)
- PRIMA (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)
- 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)
- diagnosis in Fabry disease (1)
- diagnostic markers (1)
- disability (1)
- disorder (1)
- efficacy (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)
- 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)
- hernia repair (1)
- hippocampus (1)
- human muscle-cells (1)
- humans (1)
- hyperalgesia (1)
- hyperekplexia (1)
- idiopathic inflammatory myopathies (1)
- immune system (1)
- immunofluorescence (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)
- periperal nerve (1)
- peripheral blood mononuclear cells (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)
- tumor necrosis factor-α (1)
- validation (1)
- vasculitis (1)
- white blood cells (1)
Institute
- Neurologische Klinik und Poliklinik (77)
- Institut für Klinische Neurobiologie (8)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (7)
- Medizinische Klinik und Poliklinik I (6)
- 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)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Frauenklinik und Poliklinik (1)
- Institut für Humangenetik (1)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (1)
- Klinik und Poliklinik für Nuklearmedizin (1)
- Neurochirurgische Klinik und Poliklinik (1)
- Pathologisches Institut (1)
Sonstige beteiligte Institutionen
Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with potential severe consequences. Its pathogenesis involves hyperglycemia-linked mechanisms, which may include changes in the expression of neurotrophic growth factors. We analyzed the expression of 29 factors potentially related to nerve degeneration and regeneration in skin biopsies from 13 type 1 diabetic pancreas and kidney recipients with severe DPN including severe depletion of intraepidermal nerve fibers (IENF) in lower limb skin biopsies (group Tx1 1st examination). The investigation was repeated after a median 28-month period of normoglycemia achieved by pancreas transplantation (group Tx1 2nd examination). The same tests were performed in 13 stable normoglycemic pancreas and kidney recipients 6-12 years posttransplantation (group Tx2), in 12 matched healthy controls (group HC), and in 12 type 1 diabetic subjects without severe DPN (group DM). Compared to DM and HC groups, we found a significantly higher (p < 0.05-0.001) expression of NGF (nerve growth factor), NGFR (NGF receptor), NTRK1 (neurotrophic receptor tyrosine kinase 1), GDNF (glial cell-derived neurotrophic factor), GFRA1 (GDNF family receptor alpha 1), and GFAP (glial fibrillary acidic protein) in both transplant groups (Tx1 and Tx2). Enhanced expression of these factors was not normalized following the median 28-month period of normoglycemia (Tx1 2nd examination) and negatively correlated with IENF density and with electrophysiological indices of DPN (vibration perception threshold, electromyography, and autonomic tests). In contrast to our expectation, the expression of most of 29 selected factors related to neural regeneration was comparable in subjects with severe peripheral nerve fiber depletion and healthy controls and the expression of six factors was significantly upregulated. These findings may be important for better understanding the pathophysiology of nerve regeneration and for the development of intervention strategies.
Fibromyalgia syndrome (FMS) is a heterogeneous chronic pain syndrome characterized by musculoskeletal pain and other key co-morbidities including fatigue and a depressed mood. FMS involves altered functioning of the central and peripheral nervous system (CNS, PNS) and immune system, but the specific molecular pathophysiology remains unclear. Anti-cholinergic treatment is effective in FMS patient subgroups, and cholinergic signaling is a strong modulator of CNS and PNS immune processes. Therefore, we used whole blood small RNA-sequencing of female FMS patients and healthy controls to profile microRNA regulators of cholinergic transcripts (CholinomiRs). We compared microRNA profiles with those from Parkinson's disease (PD) patients with pain as disease controls. We validated the sequencing results with quantitative real-time PCR (qRT-PCR) and identified cholinergic targets. Further, we measured serum cholinesterase activity in FMS patients and healthy controls. Small RNA-sequencing revealed FMS-specific changes in 19 CholinomiRs compared to healthy controls and PD patients. qRT-PCR validated miR-182-5p upregulation, distinguishing FMS patients from healthy controls. mRNA targets of CholinomiRs bone morphogenic protein receptor 2 and interleukin 6 signal transducer were downregulated. Serum acetylcholinesterase levels and cholinesterase activity in FMS patients were unchanged. Our findings identified an FMS-specific CholinomiR signature in whole blood, modulating immune-related gene expression.
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.
Background
Anderson–Fabry disease (FD) is an X-linked lysosomal storage disorder with varying organ involvement and symptoms, depending on the underlying mutation in the alpha-galactosidase A gene (HGNC: GLA). With genetic testing becoming more readily available, it is crucial to precisely evaluate pathogenicity of each genetic variant, in order to determine whether there is or might be not a need for FD-specific therapy in affected patients and relatives at the time point of presentation or in the future.
Methods
This case series investigates the clinical impact of the specific GLA gene variant c.376A>G (p.Ser126Gly) in five (one heterozygous and one homozygous female, three males) individuals from different families, who visited our center between 2009 and 2021. Comprehensive neurological, nephrological and cardiac examinations were performed in all cases. One patient received a follow-up examination after 12 years.
Results
Index events leading to suspicion of FD were mainly unspecific neurological symptoms. However, FD-specific biomarkers, imaging examinations (i.e., brain MRI, heart MRI), and tissue-specific diagnostics, including kidney and skin biopsies, did not reveal evidence for FD-specific symptoms or organ involvement but showed normal results in all cases. This includes findings from 12-year follow-up in one patient with renal biopsy.
Conclusion
These findings suggest that p.Ser126Gly represents a benign GLA gene variant which per se does not cause FD. Precise clinical evaluation in individuals diagnosed with genetic variations of unknown significance should be performed to distinguish common symptoms broadly prevalent in the general population from those secondary to FD.
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.
Background
The role of cytokines in the pathophysiology, diagnosis, and prognosis of small fiber neuropathy (SFN) is incompletely understood. We studied expression profiles of selected pro- and anti-inflammatory cytokines in RNA from white blood cells (WBC) of patients with a medical history and a clinical phenotype suggestive for SFN and compared data with healthy controls.
Methods
We prospectively recruited 52 patients and 21 age- and sex-matched healthy controls. Study participants were characterized in detail and underwent complete neurological examination. Venous blood was drawn for routine and extended laboratory tests, and for WBC isolation. Systemic RNA expression profiles of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-2, IL-8, tumor necrosis factor-alpha (TNF) and the anti-inflammatory cytokines IL-4, IL-10, transforming growth factor beta-1 (TGF) were analyzed. Protein levels of IL-2, IL-8, and TNF were measured in serum of patients and controls. Receiver operating characteristic (ROC)-curve analysis was used to determine the accuracy of IL-2, IL-8, and TNF in differentiating patients and controls. To compare the potential discriminatory efficacy of single versus combined cytokines, equality of different AUCs was tested.
Results
WBC gene expression of IL-2, IL-8, and TNF was higher in patients compared to healthy controls (IL-2: p = 0.02; IL-8: p = 0.009; TNF: p = 0.03) and discriminated between the groups (area under the curve (AUC) ≥ 0.68 for each cytokine) with highest diagnostic accuracy reached by combining the three cytokines (AUC = 0.81, sensitivity = 70%, specificity = 86%). Subgroup analysis revealed the following differences: IL-8 and TNF gene expression levels were higher in female patients compared to female controls (IL-8: p = 0.01; TNF: p = 0.03). The combination of TNF with IL-2 and TNF with IL-2 and IL-8 discriminated best between the study groups. IL-2 was higher expressed in patients with moderate pain compared to those with severe pain (p = 0.02). Patients with acral pain showed higher IL-10 gene expression compared to patients with generalized pain (p = 0.004). We further found a negative correlation between the relative gene expression of IL-2 and current pain intensity (p = 0.02). Serum protein levels of IL-2, IL-8, and TNF did not differ between patients and controls.
Conclusions
We identified higher systemic gene expression of IL-2, IL-8, and TNF in SFN patients than in controls, which may be of potential relevance for diagnostics and patient stratification.
CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement
(2022)
We tested the hypothesis that reduced skin innervation in fibromyalgia syndrome is associated with specific CNS changes. This prospective case–control study included 43 women diagnosed with fibromyalgia syndrome and 40 healthy controls. We further compared the fibromyalgia subgroups with reduced (n = 21) and normal (n = 22) skin innervation. Brains were analysed for cortical volume, for white matter integrity, and for functional connectivity. Compared to controls, cortical thickness was decreased in regions of the frontal, temporal and parietal cortex in the fibromyalgia group as a whole, and decreased in the bilateral pericalcarine cortices in the fibromyalgia subgroup with reduced skin innervation. Diffusion tensor imaging revealed a significant increase in fractional anisotropy in the corona radiata, the corpus callosum, cingulum and fornix in patients with fibromyalgia compared to healthy controls and decreased FA in parts of the internal capsule and thalamic radiation in the subgroup with reduced skin innervation. Using resting-state fMRI, the fibromyalgia group as a whole showed functional hypoconnectivity between the right midfrontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. The subgroup with reduced skin innervation showed hyperconnectivity between the inferior frontal gyrus, the angular gyrus and the posterior parietal gyrus. Our results suggest that the subgroup of fibromyalgia patients with pronounced pathology in the peripheral nervous system shows alterations in morphology, structural and functional connectivity also at the level of the encephalon. We propose considering these subgroups when conducting clinical trials.
Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies
(2022)
Background and Objectives
Nodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM).
Methods
We retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1–associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections.
Results The frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31–6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti–contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected.
Discussion
We report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.