@article{BischoffRingstedPetersenetal.2014,
  author    = {Bischoff, Joakim M. and Ringsted, Thomas K. and Petersen, Marian and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan and Werner, Mads U.},
  title     = {A Capsaicin (8\%) Patch in the Treatment of Severe Persistent Inguinal Postherniorrhaphy Pain: A Randomized, Double-Blind, Placebo-Controlled Trial},
  series = {PLOS ONE},
  volume    = {9},
  journal   = {PLOS ONE},
  number    = {10},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0109144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115198},
  pages     = {e109144},
  year      = {2014},
  abstract  = {Background: Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8\% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Methods: Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8\% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0-10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P<0.01). Results: The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95\% CI]: 5.0 [0.09 to 9.9]; P=0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [-0.1 to 3.9] and 0.6 [-1.2 to 2.5] fibers/mm, respectively (P=0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. Conclusions: The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application.},
  language  = {en}
}
@article{SommerRichterRogauschetal.2011,
  author    = {Sommer, Claudia and Richter, Helmut and Rogausch, Jan P. and Frettloh, Jule and Lungenhausen, Margitta and Maier, Christoph},
  title     = {A modified score to identify and discriminate neuropathic pain: a study on the German version of the neuropathic pain symptom inventory (NPSI)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68716},
  year      = {2011},
  abstract  = {Background: Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain. Methods: We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles. Results: Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91\%) and acceptable specificity (70\%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct. Conclusions: The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.},
  subject      = {Neuralgie},
  language  = {en}
}
@article{HofmannKarlSommeretal.2017,
  author    = {Hofmann, Lukas and Karl, Franziska and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Affective and cognitive behavior in the alpha-galactosidase A deficient mouse model of Fabry disease},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0180601},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170745},
  pages     = {e0180601},
  year      = {2017},
  abstract  = {Fabry disease is an X-linked inherited lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A (α-Gal A) deficiency. Fabry patients frequently report of anxiety, depression, and impaired cognitive function. We characterized affective and cognitive phenotype of male mice with α-Gal A deficiency (Fabry KO) and compared results with those of age-matched male wildtype (WT) littermates. Young (3 months) and old (≥ 18 months) mice were tested in the na{\"i}ve state and after i.pl. injection of complete Freund`s adjuvant (CFA) as an inflammatory pain model. We used the elevated plus maze (EPM), the light-dark box (LDB) and the open field test (OF) to investigate anxiety-like behavior. The forced swim test (FST) and Morris water maze (MWM) were applied to assess depressive-like and learning behavior. The EPM test revealed no intergroup difference for anxiety-like behavior in na{\"i}ve young and old Fabry KO mice compared to WT littermates, except for longer time spent in open arms of the EPM for young WT mice compared to young Fabry KO mice (p<0.05). After CFA injection, young Fabry KO mice showed increased anxiety-like behavior compared to young WT littermates (p<0.05) and na{\"i}ve young Fabry KO mice (p<0.05) in the EPM as reflected by shorter time spent in EPM open arms. There were no relevant differences in the LDB and the OF test, except for longer time spent in the center zone of the OF by young WT mice compared to young Fabry KO mice (p<0.05). Complementary to this, depression-like and learning behavior were not different between genotypes and age-groups, except for the expectedly lower memory performance in older age-groups compared to young mice. Our results indicate that genetic influences on affective and cognitive symptoms in FD may be of subordinate relevance, drawing attention to potential influences of environmental and epigenetic factors.},
  language  = {en}
}
@article{KarlNandiniColacoSchulteetal.2019,
  author    = {Karl, Franziska and Nandini Cola{\c{c}}o, Maria B. and Schulte, Annemarie and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Affective and cognitive behavior is not altered by chronic constriction injury in B7-H1 deficient and wildtype mice},
  series = {BMC Neuroscience},
  volume    = {20},
  journal   = {BMC Neuroscience},
  doi       = {10.1186/s12868-019-0498-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200540},
  pages     = {16},
  year      = {2019},
  abstract  = {Background Chronic neuropathic pain is often associated with anxiety, depressive symptoms, and cognitive impairment with relevant impact on patients` health related quality of life. To investigate the influence of a pro-inflammatory phenotype on affective and cognitive behavior under neuropathic pain conditions, we assessed mice deficient of the B7 homolog 1 (B7-H1), a major inhibitor of inflammatory response. Results Adult B7-H1 ko mice and wildtype littermates (WT) received a chronic constriction injury (CCI) of the sciatic nerve, and we assessed mechanical and thermal sensitivity at selected time points. Both genotypes developed mechanical (p < 0.001) and heat hypersensitivity (p < 0.01) 7, 14, and 20 days after surgery. We performed three tests for anxiety-like behavior: the light-dark box, the elevated plus maze, and the open field. As supported by the results of these tests for anxiety-like behavior, no relevant differences were found between genotypes after CCI. Depression-like behavior was assessed using the forced swim test. Also, CCI had no effect on depression like behavior. For cognitive behavior, we applied the Morris water maze for spatial learning and memory and the novel object recognition test for object recognition, long-, and short-term memory. Learning and memory did not differ in B7-H1 ko and WT mice after CCI. Conclusions Our study reveals that the impact of B7-H1 on affective-, depression-like- and learning-behavior, and memory performance might play a subordinate role in mice after nerve lesion.},
  language  = {en}
}
@article{HansenKahnZelleretal.2015,
  author    = {Hansen, Niels and Kahn, Ann-Kathrin and Zeller, Daniel and Katsarava, Zaza and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Amplitudes of pain-related evoked potentials are useful to detect small fiber involvement in painful mixed fiber neuropathies in addition to quantitative sensory testing - an electrophysiological study},
  series = {Frontiers in Neurology},
  volume    = {6},
  journal   = {Frontiers in Neurology},
  doi       = {10.3389/fneur.2015.00244},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124824},
  pages     = {244},
  year      = {2015},
  abstract  = {To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy: n = 6; vasculitic neuropathy: n = 3; chronic axonal ­neuropathy: n = 2). The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN.},
  language  = {en}
}
@article{DopplerSchusterAppeltshauseretal.2019,
  author    = {Doppler, Kathrin and Schuster, Yasmin and Appeltshauser, Luise and Biko, Lydia and Villmann, Carmen and Weishaupt, Andreas and Werner, Christian and Sommer, Claudia},
  title     = {Anti-CNTN1 IgG3 induces acute conduction block and motor deficits in a passive transfer rat model},
  series = {Journal of Neuroinflammation},
  volume    = {16},
  journal   = {Journal of Neuroinflammation},
  number    = {73},
  doi       = {10.1186/s12974-019-1462-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200476},
  year      = {2019},
  abstract  = {Background: Autoantibodies against the paranodal protein contactin-1 have recently been described in patients with severe acute-onset autoimmune neuropathies and mainly belong to the IgG4 subclass that does not activate complement. IgG3 anti-contactin-1 autoantibodies are rare, but have been detected during the acute onset of disease in some cases. There is evidence that anti-contactin-1 prevents adhesive interaction, and chronic exposure to anti-contactin-1 IgG4 leads to structural changes at the nodes accompanied by neuropathic symptoms. However, the pathomechanism of acute onset of disease and the pathogenic role of IgG3 anti-contactin-1 is largely unknown. Methods: In the present study, we aimed to model acute autoantibody exposure by intraneural injection of IgG of patients with anti-contacin-1 autoantibodies to Lewis rats. Patient IgG obtained during acute onset of disease (IgG3 predominant) and IgG from the chronic phase of disease (IgG4 predominant) were studied in comparison. Results: Conduction blocks were measured in rats injected with the "acute" IgG more often than after injection of "chronic" IgG (83.3\% versus 35\%) and proved to be reversible within a week after injection. Impaired nerve conduction was accompanied by motor deficits in rats after injection of the "acute" IgG but only minor structural changes of the nodes. Paranodal complement deposition was detected after injection of the "acute IgG". We did not detect any inflammatory infiltrates, arguing against an inflammatory cascade as cause of damage to the nerve. We also did not observe dispersion of paranodal proteins or sodium channels to the juxtaparanodes as seen in patients after chronic exposure to anti-contactin-1. Conclusions: Our data suggest that anti-contactin-1 IgG3 induces an acute conduction block that is most probably mediated by autoantibody binding and subsequent complement deposition and may account for acute onset of disease in these patients. This supports the notion of anti-contactin-1-associated neuropathy as a paranodopathy with the nodes of Ranvier as the site of pathogenesis.},
  language  = {en}
}
@article{AppeltshauserBrunderHeiniusetal.2020,
  author    = {Appeltshauser, Luise and Brunder, Anna-Michelle and Heinius, Annika and K{\"o}rtv{\´e}lyessy, Peter and Wandinger, Klaus-Peter and Junker, Ralf and Villmann, Carmen and Sommer, Claudia and Leypoldt, Frank and Doppler, Kathrin},
  title     = {Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy},
  series = {Neurology: Neuroimmunology \& Neuroinflammation},
  volume    = {7},
  journal   = {Neurology: Neuroimmunology \& Neuroinflammation},
  number    = {5},
  doi       = {10.1212/NXI.0000000000000817},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230079},
  year      = {2020},
  abstract  = {Objective To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples. Methods We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barre syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively. Results We detected antiparanodal autoantibodies with a prevalence of 4.3\% (7/161), more often in A-CIDP (4/23, 17.4\%) compared with GBS (3/114, 2.6\%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4. Conclusion Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.},
  language  = {en}
}
@article{StengelVuralBrunderetal.2019,
  author    = {Stengel, Helena and Vural, Atay and Brunder, Anna-Michelle and Heinius, Annika and Appeltshauser, Luise and Fiebig, Bianca and Giese, Florian and Dresel, Christian and Papagianni, Aikaterini and Birklein, Frank and Weis, Joachim and Huchtemann, Tessa and Schmidt, Christian and K{\"o}rtvelyessy, Peter and Villmann, Carmen and Meinl, Edgar and Sommer, Claudia and Leypoldt, Frank and Doppler, Kathrin},
  title     = {Anti-pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy},
  series = {Neurology: Neuroimmunology \& Neuroinflammation},
  volume    = {6},
  journal   = {Neurology: Neuroimmunology \& Neuroinflammation},
  number    = {5},
  doi       = {10.1212/NXI.0000000000000603},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202462},
  year      = {2019},
  abstract  = {Objective To identify and characterize patients with autoantibodies against different neurofascin (NF) isoforms. Methods Screening of a large cohort of patient sera for anti-NF autoantibodies by ELISA and further characterization by cell-based assays, epitope mapping, and complement binding assays. Results Two different clinical phenotypes became apparent in this study: The well-known clinical picture of subacute-onset severe sensorimotor neuropathy with tremor that is known to be associated with IgG4 autoantibodies against the paranodal isoform NF-155 was found in 2 patients. The second phenotype with a dramatic course of disease with tetraplegia and almost locked-in syndrome was associated with IgG3 autoantibodies against nodal and paranodal isoforms of NF in 3 patients. The epitope against which these autoantibodies were directed in this second phenotype was the common Ig domain found in all 3 NF isoforms. In contrast, anti-NF-155 IgG4 were directed against the NF-155-specific Fn3Fn4 domain. The description of a second phenotype of anti-NF-associated neuropathy is in line with some case reports of similar patients that were published in the last year. Conclusions Our results indicate that anti-pan-NF-associated neuropathy differs from anti-NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti-NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response.},
  language  = {en}
}
@article{EvdokimovDinkelFranketal.2020,
  author    = {Evdokimov, Dimitar and Dinkel, Philine and Frank, Johanna and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Characterization of dermal skin innervation in fibromyalgia syndrome},
  series = {PLoS One},
  volume    = {15},
  journal   = {PLoS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0227674},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229299},
  year      = {2020},
  abstract  = {Introduction We characterized dermal innervation in patients with fibromyalgia syndrome (FMS) as potential contribution to small fiber pathology. Methods Skin biopsies of the calf were collected (86 FMS patients, 35 healthy controls). Skin was immunoreacted with antibodies against protein gene product 9.5, calcitonine gene-related peptide, substance P, CD31, and neurofilament 200 for small fiber subtypes. We assessed two skin sections per patient; on each skin section, two dermal areas (150 x 700 mu m each) were investigated for dermal nerve fiber length (DNFL). Results In FMS patients we found reduced DNFL of fibers with vessel contact compared to healthy controls (p<0.05). There were no differences for the other nerve fiber subtypes. Discussion We found less dermal nerve fibers in contact with blood vessels in FMS patients than in controls. The pathophysiological relevance of this finding is unclear, but we suggest the possibility of a relationship with impaired thermal tolerance commonly reported by FMS patients.},
  language  = {en}
}
@article{AsterEvdokimovBraunetal.2022,
  author    = {Aster, Hans-Christoph and Evdokimov, Dimitar and Braun, Alexandra and {\"U}{\c{c}}eyler, Nurcan and Kampf, Thomas and Pham, Mirko and Homola, Gy{\"o}rgy A. and Sommer, Claudia},
  title     = {CNS imaging characteristics in fibromyalgia patients with and without peripheral nerve involvement},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-022-10489-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300562},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{UeceylerBikoHoseetal.2016,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Biko, Lydia and Hose, Dorothea and Hoffmann, Lukas and Sommer, Claudia},
  title     = {Comprehensive and differential long-term characterization of the alpha-galactosidase A deficient mouse model of Fabry disease focusing on the sensory system and pain development},
  series = {Molecular Pain},
  volume    = {12},
  journal   = {Molecular Pain},
  number    = {1744806916646370},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147562},
  year      = {2016},
  abstract  = {Fabry disease is an X-linked lysosomal storage disorder due to impaired activity of alpha-galactosidase A with intracellular accumulation of globotriaosylceramide. Associated small fiber pathology leads to characteristic pain in Fabry disease. We systematically assessed sensory system, physical activity, metabolic parameters, and morphology of male and female mice with alpha-galactosidase A deficiency (Fabry ko) from 2 to 27 months of age and compared results with those of age- and gender-matched wild-type littermates of C57Bl/6J background. Results From the age of two months, male and female Fabry mice showed mechanical hypersensitivity (p < 0.001 each) compared to wild-type littermates. Young Fabry ko mice of both genders were hypersensitive to heat stimulation (p < 0.01) and developed heat hyposensitivity with aging (p < 0.05), while cold hyposensitivity was present constantly in young (p < 0.01) and old (p < 0.05) Fabry ko mice compared to wild-type littermates. Stride angle increased only in male Fabry ko mice with aging (p < 0.01) in comparison to wild-type littermates. Except for young female mice, male (p < 0.05) and female (p < 0.01) Fabry ko mice had a higher body weight than wild-type littermates. Old male Fabry ko mice were physically less active than their wild-type littermates (p < 0.05), had lower chow intake (p < 0.001), and lost more weight (p < 0.001) in a one-week treadmill experiment than wild-type littermates. Also, Fabry ko mice showed spontaneous pain protective behavior and developed orofacial dysmorphism resembling patients with Fabry disease. Conclusions. Mice with alpha-galactosidase A deficiency show age-dependent and distinct deficits of the sensory system. alpha-galactosidase A-deficient mice seem to model human Fabry disease and may be helpful when studying the pathophysiology of Fabry-associated pain.},
  language  = {en}
}
@article{DopplerAppeltshauserKraemeretal.2015,
  author    = {Doppler, Kathrin and Appeltshauser, Luise and Kr{\"a}mer, Heidrun H. and King Man Ng, Judy and Meinl, Edgar and Villmann, Carmen and Brophy, Peter and Dib-Hajj, Sulayman D. and Waxman, Stephen G. and Weishaupt, Andreas and Sommer, Claudia},
  title     = {Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy},
  series = {PLoS One},
  volume    = {10},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0134274},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126156},
  pages     = {e0134274},
  year      = {2015},
  abstract  = {Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50\% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60\% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients' sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.},
  language  = {en}
}
@article{UeceylerBuchholzKewenigetal.2020,
  author    = {{\"U}{\c{c}}eyler, Nurcan and Buchholz, Hans-Georg and Kewenig, Susanne and Ament, Stephan-Johann and Birklein, Frank and Schreckenberger, Mathias and Sommer, Claudia},
  title     = {Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels - A Pilot Study},
  series = {Frontiers in Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Neuroscience},
  issn      = {1662-453X},
  doi       = {10.3389/fnins.2020.00512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204457},
  year      = {2020},
  abstract  = {Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients' systemic interleukin-4 (IL-4) gene expression. Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values. Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005). Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS.},
  language  = {en}
}
@article{KressEgenolfSommeretal.2023,
  author    = {Kreß, Luisa and Egenolf, Nadine and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Cytokine expression profiles in white blood cells of patients with small fiber neuropathy},
  series = {BMC Neuroscience},
  volume    = {24},
  journal   = {BMC Neuroscience},
  number    = {1},
  doi       = {10.1186/s12868-022-00770-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300619},
  year      = {2023},
  abstract  = {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.},
  language  = {en}
}
@article{GruenewaldLangeWerneretal.2017,
  author    = {Gr{\"u}newald, Benedikt and Lange, Maren D and Werner, Christian and O'Leary, Aet and Weishaupt, Andreas and Popp, Sandy and Pearce, David A and Wiendl, Heinz and Reif, Andreas and Pape, Hans C and Toyka, Klaus V and Sommer, Claudia and Geis, Christian},
  title     = {Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis},
  series = {eLife},
  volume    = {6},
  journal   = {eLife},
  number    = {e28685},
  doi       = {10.7554/eLife.28685},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170004},
  year      = {2017},
  abstract  = {Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3\(^{Δex1-6}\)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.},
  language  = {en}
}
@article{BrumbergKuzkinaLapaetal.2021,
  author    = {Brumberg, Joachim and Kuzkina, Anastasia and Lapa, Constantin and Mammadova, Sona and Buck, Andreas and Volkmann, Jens and Sommer, Claudia and Isaias, Ioannis U. and Doppler, Kathrin},
  title     = {Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy},
  series = {Neurobiology of Disease},
  volume    = {153},
  journal   = {Neurobiology of Disease},
  doi       = {10.1016/j.nbd.2021.105332},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260061},
  pages     = {105332},
  year      = {2021},
  abstract  = {Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [\(^{123}\)I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled. All patients underwent a standardized clinical workup including neurological evaluation, neurography, and blood samples. Skin biopsies were obtained from the distal and proximal leg, back, and neck for immunofluorescence double labeling with anti-p-alpha-synuclein and anti-PGP9.5. All patients underwent myocardial [\(^{123}\)I]-metaiodobenzylguanidine scintigraphy. Dermal p-alpha-synuclein was observed in 47.6\% of Parkinson's disease patients and was mainly found in autonomic structures. 81.0\% of multiple system atrophy patients had deposits with most of cases in somatosensory fibers. The [\(^{123}\)I]-metaiodobenzylguanidine heart-to-mediastinum ratio was lower in Parkinson's disease than in multiple system atrophy patients (1.94 +/- 0.63 vs. 2.91 +/- 0.96; p < 0.0001). Irrespective of the diagnosis, uptake was lower in patients with than without p-alpha-synuclein in autonomic structures (1.42 +/- 0.51 vs. 2.74 +/- 0.83; p < 0.0001). Rare cases of Parkinson's disease with p-alpha-synuclein in somatosensory fibers and multiple system atrophy patients with deposits in autonomic structures or both fiber types presented with clinically overlapping features. In conclusion, this study suggests that alpha-synuclein contributes to peripheral neurodegeneration and mediates the impairment of cardiac sympathetic neurons in patients with synucleinopathies. Furthermore, it indicates that Parkinson's disease and multiple system atrophy share pathophysiologic mechanisms of peripheral nervous system dysfunction with a clinical overlap.},
  language  = {en}
}
@article{AppeltshauserMessingerStarzetal.2022,
  author    = {Appeltshauser, Luise and Messinger, Julia and Starz, Katharina and Heinrich, David and Brunder, Anna-Michelle and Stengel, Helena and Fiebig, Bianca and Ayzenberg, Ilya and Birklein, Frank and Dresel, Christian and Dorst, Johannes and Dvorak, Florian and Grimm, Alexander and Joerk, Alexander and Leypoldt, Frank and M{\"a}urer, Mathias and Merl, Patrick and Michels, Sebastian and Pitarokoili, Kalliopi and Rosenfeldt, Mathias and Sperfeld, Anne-Dorte and Weihrauch, Marc and Welte, Gabriel Simon and Sommer, Claudia and Doppler, Kathrin},
  title     = {Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies},
  series = {Neurology: Neuroimmunology \& Neuroinflammation},
  volume    = {9},
  journal   = {Neurology: Neuroimmunology \& Neuroinflammation},
  number    = {3},
  doi       = {10.1212/NXI.0000000000001163},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300551},
  year      = {2022},
  abstract  = {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-Barr{\´e} 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.},
  language  = {en}
}
@article{EgenolfAltenschildescheKressetal.2021,
  author    = {Egenolf, Nadine and Altenschildesche, Caren Meyer zu and Kreß, Luisa and Eggermann, Katja and Namer, Barbara and Gross, Franziska and Klitsch, Alexander and Malzacher, Tobias and Kampik, Daniel and Malik, Rayaz A. and Kurth, Ingo and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan},
  title     = {Diagnosing small fiber neuropathy in clinical practice: a deep phenotyping study},
  series = {Therapeutic Advances in Neurological Disorders},
  volume    = {14},
  journal   = {Therapeutic Advances in Neurological Disorders},
  issn      = {1756-2864},
  doi       = {10.1177/17562864211004318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232019},
  year      = {2021},
  abstract  = {Background and aims: Small fiber neuropathy (SFN) is increasingly suspected in patients with pain of uncertain origin, and making the diagnosis remains a challenge lacking a diagnostic gold standard. Methods: In this case-control study, we prospectively recruited 86 patients with a medical history and clinical phenotype suggestive of SFN. Patients underwent neurological examination, quantitative sensory testing (QST), and distal and proximal skin punch biopsy, and were tested for pain-associated gene loci. Fifty-five of these patients additionally underwent pain-related evoked potentials (PREP), corneal confocal microscopy (CCM), and a quantitative sudomotor axon reflex test (QSART). Results: Abnormal distal intraepidermal nerve fiber density (IENFD) (60/86, 70\%) and neurological examination (53/86, 62\%) most frequently reflected small fiber disease. Adding CCM and/or PREP further increased the number of patients with small fiber impairment to 47/55 (85\%). Genetic testing revealed potentially pathogenic gene variants in 14/86 (16\%) index patients. QST, QSART, and proximal IENFD were of lower impact. Conclusion: We propose to diagnose SFN primarily based on the results of neurological examination and distal IENFD, with more detailed phenotyping in specialized centers.},
  language  = {en}
}
@article{KuzkinaBargarSchmittetal.2021,
  author    = {Kuzkina, Anastasia and Bargar, Connor and Schmitt, Daniela and R{\"o}ßle, Jonas and Wang, Wen and Schubert, Anna-Lena and Tatsuoka, Curtis and Gunzler, Steven A. and Zou, Wen-Quan and Volkmann, Jens and Sommer, Claudia and Doppler, Kathrin and Chen, Shu G.},
  title     = {Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study},
  series = {NPJ Parkinson's Disease},
  volume    = {7},
  journal   = {NPJ Parkinson's Disease},
  number    = {1},
  doi       = {10.1038/s41531-021-00242-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260451},
  year      = {2021},
  abstract  = {Skin alpha-synuclein deposition is considered a potential biomarker for Parkinson's disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of alpha-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of alpha-synuclein RT-QuIC assay of skin biopsy for diagnosing PD and to explore its correlation with clinical markers of PD in a two-center inter-laboratory comparison study. Patients with clinically diagnosed PD (n = 34), as well as control subjects (n = 30), underwent skin punch biopsy at multiple sites (neck, lower back, thigh, and lower leg). The skin biopsy samples (198 in total) were divided in half to be analyzed by RT-QuIC assay in two independent laboratories. The a-synuclein RT-QuIC assay of multiple skin biopsies supported the clinical diagnosis of PD with a diagnostic accuracy of 88.9\% and showed a high degree of inter-rater agreement between the two laboratories (92.2\%). Higher alpha-synuclein seeding activity in RT-QuIC was shown in patients with longer disease duration and more advanced disease stage and correlated with the presence of REM sleep behavior disorder, cognitive impairment, and constipation. The alpha-synuclein RT-QuIC assay of minimally invasive skin punch biopsy is a reliable and reproducible biomarker for Parkinson's disease. Moreover, alpha-synuclein RT-QuIC seeding activity in the skin may serve as a potential indicator of progression as it correlates with the disease stage and certain non-motor symptoms.},
  language  = {en}
}
@article{KarlGriesshammerUeceyleretal.2017,
  author    = {Karl, Franziska and Grießhammer, Anne and {\"U}{\c{c}}eyler, Nurcan and Sommer, Claudia},
  title     = {Differential Impact of miR-21 on Pain and Associated Affective and Cognitive Behavior after Spared Nerve Injury in B7-H1 ko Mouse},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {10},
  journal   = {Frontiers in Molecular Neuroscience},
  number    = {219},
  doi       = {10.3389/fnmol.2017.00219},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170722},
  year      = {2017},
  abstract  = {MicroRNAs (miRNAs) are increasingly recognized as regulators of immune and neuronal gene expression and are potential master switches in neuropathic pain pathophysiology. miR-21 is a promising candidate that may link the immune and the pain system. To investigate the pathophysiological role of miR-21 in neuropathic pain, we assessed mice deficient of B7 homolog 1 (B7-H1), a major inhibitor of inflammatory responses. In previous studies, an upregulation of miR-21 had been shown in mouse lymphocytes. Young (8 weeks), middle-aged (6 months), and old (12 months) B7-H1 ko mice and wildtype littermates (WT) received a spared nerve injury (SNI). We assessed thermal withdrawal latencies and mechanical withdrawal thresholds. Further, we performed tests for anxiety-like and cognitive behavior. Quantitative real time PCR was used to determine miR-21 relative expression in peripheral nerves, and dorsal root ganglia (DRG) at distinct time points after SNI. We found mechanical hyposensitivity with increasing age of na{\"i}ve B7-H1 ko mice. Young and middle-aged B7-H1 ko mice were more sensitive to mechanical stimuli compared to WT mice (young: p < 0.01, middle-aged: p < 0.05). Both genotypes developed mechanical and heat hypersensitivity (p < 0.05) after SNI, without intergroup differences. No relevant differences were found after SNI in three tests for anxiety like behavior in B7-H1 ko and WT mice. Also, SNI had no effect on cognition. B7-H1 ko and WT mice showed a higher miR-21 expression (p < 0.05) and invasion of macrophages and T cells in the injured nerve 7 days after SNI without intergroup differences. Our study reveals that increased miR-21 expression in peripheral nerves after SNI is associated with reduced mechanical and heat withdrawal thresholds. These results point to a role of miR-21 in the pathophysiology of neuropathic pain, while affective behavior and cognition seem to be spared. Contrary to expectations, B7-H1 ko mice did not show higher miR-21 expression than WT mice, thus, a B7-H1 knockout may be of limited relevance for the study of miR-21 related pain.},
  language  = {en}
}