TY  - JOUR
A1  - Stengel, Helena
A1  - Vural, Atay
A1  - Brunder, Anna-Michelle
A1  - Heinius, Annika
A1  - Appeltshauser, Luise
A1  - Fiebig, Bianca
A1  - Giese, Florian
A1  - Dresel, Christian
A1  - Papagianni, Aikaterini
A1  - Birklein, Frank
A1  - Weis, Joachim
A1  - Huchtemann, Tessa
A1  - Schmidt, Christian
A1  - Körtvelyessy, Peter
A1  - Villmann, Carmen
A1  - Meinl, Edgar
A1  - Sommer, Claudia
A1  - Leypoldt, Frank
A1  - Doppler, Kathrin
T1  - Anti–pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy
JF  - Neurology: Neuroimmunology & Neuroinflammation
N2  - 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.
KW  - neurology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202462
VL  - 6
IS  - 5
ER  - 
TY  - JOUR
A1  - Evdokimov, Dimitar
A1  - Frank, Johanna
A1  - Klitsch, Alexander
A1  - Unterecker, Stefan
A1  - Warrings, Bodo
A1  - Serra, Jordi
A1  - Papagianni, Aikaterini
A1  - Saffer, Nadine
A1  - Meyer zu Altenschildesche, Caren
A1  - Kampik, Daniel
A1  - Malik, Rayaz A.
A1  - Sommer, Claudia
A1  - Üceyler, Nurcan
T1  - Reduction of skin innervation is associated with a severe fibromyalgia phenotype
JF  - Annals of Neurology
N2  - Objective: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS).

Methods: One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women.

Results: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MDP: 10%, controls: 18%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05).

Interpretation: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS.
KW  - fibromyalgia
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206168
VL  - 86
IS  - 4
ER  -