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This study evaluates for the first time the quantitative measurability of GFAP (glial fibrillary acidic protein), NfL (neurofilament light chain), UCH-L1 (ubiquitin carboxy-terminal hydrolase L1) and t-tau (total tau) in urine of patients with acute cerebral damage.Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single molecule arrays (Simoa®). Glomerular barrier function was assessed based on albumin-creatinine-ratio (ACR); biomarker-creatinine ratios were calculated for correction of urine dilution.93 urine-serum pairs in the target and 10 urine-serum pairs in the control group were measured. Mean absolute concentration ± SD in urine of the target and control group was 184.7 ± 362.4 pg/ml and 27.3 ± 24.1 pg/ml for GFAP (r = 0.3 [Wilcoxon effect size], p = 0.007), 17.5 ± 38.6 pg/ml and 0.9 ± 0.3 pg/ml for NfL (r = 0.4, p 0.005), 320.2 ± 443.3 pg/ml and 109.6 ± 116.8 pg/ml for UCH-L1 (r = 0.26, p = 0.014), and 219.5 ± 255.8 pg/ml and 21.1 ± 27.1 pg/ml for t-tau (r = 0.37, p 0.005), respectively, whereas biomarker-creatinine ratio was significantly different only for NfL (r = 0.29, p = 0.015) and t-tau (r = 0.32, p 0.01). In patients with intact glomerular barrier ( 30 mg/g), only NfL in urine between target and control group was significantly different and showed a significant correlation with the respective serum concentrations (r = 0.58 [Pearson's correlation-coefficient], p 0.005).All four investigated biomarkers could be measured in urine, whereas NfL and t-tau showed the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.

Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers. We analyzed the myelinated fibers of skin biopsies of 35 patients with DNP, 17 patients with diabetes mellitus (DM) without neuropathy, and 30 normal controls. Immunofluorescence of skin sections with antibodies against Caspr, neurofascin, sodium channels, and myelin basic protein was performed to assess paranodal/nodal architecture, segmental demyelination, and myelinated nerve fibers. Staining with antibodies against protein gene product 9.5 was used to quantify unmyelinated nerve fibers. There was an increase of elongated Ranvier nodes and a dispersion of neurofascin at the distal leg in patients with DM with and without neuropathy and at the finger in patients with DNP. An increased dispersion of Caspr was only found in biopsies of the finger in patients with DNP. Skin biopsy may be an appropriate tool to analyze nodes of Ranvier in patients with DM. Structural nodal changes are detectable in DNP and even in diabetic patients without neuropathy.