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Background and Aims: Polyneuropathy is a common neurological disorder with many potential causes. An essential part in screening, diagnosis, and follow-up evaluation of polyneuropathy is testing of the sensory function including vibratory sensation. The graduated Rydel-Seiffer tuning fork and the biothesiometer have been developed to quantify vibratory sensation through detection thresholds. The aim of this study is to compare the vibration detection thresholds determined by the two instruments regarding intraindividual temporal changes, interindividual variation in healthy subjects and comparison of the diagnostic value in patients with a clinical suspicion of polyneuropathy., Methods: Ninety-four healthy subjects, 98 patients with and 97 patients without a diagnosis of polyneuropathy were included. Quantitative sensory testing including biothesiometry, structured clinical examination, and nerve conduction studies were performed three times during 52 weeks in healthy subjects and once in patients., Results: There were no significant changes over time for neither the Rydel-Seiffer tuning fork nor the biothesiometer, and both had larger between-subject variation than within-subject variation. Relative intertrial variability was largest for the biothesiometer. Diagnostic value (sensitivity, specificity, positive predictive value, and negative predictive value) was moderate for both methods (Rydel-Seiffer tuning fork: 58%, 74%, 70%, 64%; biothesiometer: 47%, 77%, 68%, 59%)., Interpretation: The Rydel-Seiffer tuning fork and the biothesiometer have a low test-retest and time dependent variation. They perform almost equally as diagnostic tools in patients with suspected polyneuropathy with a tendency toward better performance of the tuning fork., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Oxaliplatin-induced peripheral neuropathy negatively affects the quality of life for patients with gastrointestinal cancers and may cause neuropathic pain. Measures of peripheral nerve structure or function, such as intraepidermal nerve fiber density (IENFD) during treatment could reduce neuropathy severity through individualized dose reduction., Objective: The aim was to evaluate the predictive values of IENFD, quantitative sensory testing (QST), and nerve conduction studies (NCS) for significant neuropathy and neuropathic pain., Methods: Fifty-five patients were examined prospectively before, during, and six months following treatment using skin biopsies, QST and NCS. Clinically significant neuropathy six months after treatment was defined as reduced Total Neuropathy Score of more than five and neuropathic pain was assessed according to International Association for the Study of Pain criteria., Results: Thirty patients had a clinically significant neuropathy, and 14 had neuropathic pain. Vibration detection threshold (VDT) before treatment was correlated with clinically significant neuropathy six months after treatment (OR 0.54, p = 0.01) and reductions in cold detection threshold (CDT) after 25% of treatment (OR 1.38, p = 0.04) and heat pain threshold (HPT) after 50% of treatment (OR 1.91, p = 0.03) with neuropathic pain. Cut off values of 5 for baseline VDT and changes of more than -0.05 °C and -0.85 °C in CDT and HPT were estimated. Sensitivity and specificity was low to moderate. There was no correlation between changes in IENFD or NCS and significant neuropathy or neuropathic pain., Conclusions: Vibration detection thresholds and thermal detection thresholds may be useful for prediction of clinically significant and painful neuropathy, respectively. However, low to moderate sensitivity and specificity may limit the predictive value in clinical practice.

Purpose: To examine the association between use of statins and risk of deterioration of peripheral nerve function., Methods: We prospectively followed patients who initiated statin treatment and compared them with statin never-users (non-users). At the time of inclusion and at 1-year follow-up, participants underwent tests for peripheral nerve function (ie nerve conduction studies, quantitative sensory testing), skin biopsies and ratings of symptoms and signs of neuropathy. We selected five tests of nerve function and the intraepidermal nerve fibre density (IENFD) a priori as primary outcomes. We used linear regression to test for differences between statin users and non-users with Holm-Bonferroni-corrected statistical significance level of .05., Results: Comparisons were based on 57 statin users and 46 non-users. Changes in nerve function test results during follow-up were not uniform with regard to direction and were statistically not significant with the exception of IENFD (change in IENFD: statin users 1 fibre/mm vs. non-statin users -2 fibres/mm; P-value = .006). None of the participants developed overt peripheral neuropathy. However, five statin users developed neuropathy-like symptoms and a post hoc analysis showed a significant decrease in vibration sensitivity compared to asymptomatic statin users., Conclusion: Statin use was not clearly associated with increased risk of deterioration of peripheral nerve function analysed at a group level. However, given the sample size limitations of our study and the findings of our post hoc analysis, we cannot preclude that peripheral nerve function may be affected in some individuals exposed to statins., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background and Purpose: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy., Methods: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison., Results: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD., Conclusions: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment., (© European Academy of Neurology 2019.)

Background: Cold-induced peripheral neuropathy has been described in individuals exposed to severe cold resulting in pain, hypersensitivity to cold, hyperhidrosis, numbness, and skin changes. Nerve conduction studies and thermal detection thresholds are abnormal in symptomatic patients, and intraepidermal nerve fiber density (IENFD) in skin biopsies is reduced., Case Presentation: A 41-year-old male was included as a healthy subject in a study of the spontaneous variability of quantitative sensory testing (QST), nerve conduction studies (NCS), and IENFD. Unexpectedly, IENFD was significantly reduced, whereas the rest of the examination was normal except for reduced vibration detection threshold. The results were confirmed at follow-up examination. The subject had been repeatedly exposed to severe cold resulting in short lasting numbness and paresthesia while living in the eastern part of Greenland and the northern part of Norway., Conclusion: Loss of intraepidermal nerve fibers caused by exposure to severe cold may be asymptomatic, and their function assessed by thermal detection thresholds may be preserved. This case illustrates that QST and IENFD are complementary tests and that subclinical cold-induced peripheral neuropathy may be prevalent in subjects living in or near polar regions which could have implications for the recruitment of healthy subjects.

Aim: In a previous study, we found a positive association between statin use and polyneuropathy risk. Other studies reported equivocal results. The present study aimed to confirm our findings with a design similar to that used in our previous study but with a larger data set., Methods: We searched medical registry data to identify patients diagnosed with incident polyneuropathy of no known cause (idiopathic polyneuropathy) between 1999 and 2013; we verified diagnoses through medical records. For each case, we recruited 20 general population controls with no previous history of polyneuropathy. Controls were matched to their respective case for age and gender. We ascertained the prior statin use of cases and controls through a prescription registry. Based on this information, exposure to statins was categorized into 'ever use' or 'never use'. Ever use of statins was classified by how recently they had been used ('current use' or 'past use'); current use was further classified into long-term use (5+ years) and high- or low-intensity use. We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to examine associations between polyneuropathy and statin use., Results: We included 370 validated cases and 7400 controls. Ever use of statins was not associated with an elevated risk of polyneuropathy (OR 1.14, 95% CI 0.84, 1.54). Similarly, we found no associations between polyneuropathy risk and current use (OR 1.11, 95% CI 0.79, 1.53), long-term use (OR 1.13, 95% CI 0.66, 1.92) or high-intensity statin use (OR 1.05, 95% CI 0.59, 1.84)., Conclusion: Statin use was not associated with an increased risk of idiopathic polyneuropathy., (© 2017 The British Pharmacological Society.)