Corneal confocal microscopy in small and mixed fiber neuropathy-Comparison with skin biopsy and cold detection in a large prospective cohort.

BACKGROUND AND AIMS: The diagnosis of small fiber neuropathy (SFN) is supported by reduced intraepidermal nerve fiber density (IENFD). The noninvasive method corneal confocal microscopy (CCM) has the potential to be a practical alternative. We aimed to estimate the diagnostic accuracy of CCM compared with IENFD and cold detection thresholds (CDT) in SFN and mixed fiber neuropathy (MFN). METHODS: CCM was performed in an unselected prospective cohort of patients with a clinical suspicion of polyneuropathy. Predefined criteria were used to classify SFN and MFN. Neuropathy scores, including the Utah early neuropathy scale (UENS), were used to describe severity. Patients with established other diagnoses were used for diagnostic specificity calculations. RESULTS: Data were taken from 680 patients, of which 244 had SFN or MFN. There was no significant difference in sensitivities [95%CI] of CCM (0.44 [0.38-0.51]), IEFND (0.43 [0.36-0.49]), and CDT (0.34 [0.29-0.41]). CCM specificity (0.75 [0.69-0.81]) was lower (p = .044) than for IENFD (0.99 [0.96-1.00]) but not than for CDT (0.81 [0.75-0.86]). The AUCs of the ROC curves of 0.63, 0.63 and 0.74 respectively, was lower for corneal nerve fiber density (p = .0012) and corneal nerve fiber length (p = .0015) compared with IENFD. While UENS correlated significantly with IENFD (p = .0016; R2 = .041) and CDT (p = .0002; R2 = .056), it did not correlate with CCM measures. INTERPRETATION: The diagnostic utility of CCM in SNF and MFN is limited by the low specificity compared with skin biopsy. Further, CCM is less suitable than skin biopsy and CDT as a marker for neuropathy severity.

The additional diagnostic value of motor nerve excitability testing in chronic axonal neuropathy.

OBJECTIVE: To explore potential differences in motor nerve excitability testing (NET) variables at group levels between patients with a clinical diagnosis of polyneuropathy (PNP), which did not fulfil diagnostic criteria of conventional nerve conduction studies (NCS) and patients without polyneuropathy. Such differences could support a role for NET in increasing the diagnostic sensitivity of NCS in chronic axonal PNP. METHODS: Motor NET was performed using the median nerve in patients with a clinical suspicion of PNP in addition to conventional NCS, skin biopsies, corneal confocal microscopy and structured clinical evaluation including scoring of neuropathy symptoms and signs. RESULTS: Of the 57 patients included, 32 had PNP, half of which had NCS, which fulfilled criteria for PNP (NCS+ PNP). There were no significant differences for any of the NET variables between PNP patients with non-diagnostic conventional NCS (NCS- PNP) and patients without PNP. Rheobase was increased, and Ted (undershoot) and subexcitability were decreased in NCS+ PNP. Sural amplitude, peroneal nerve F-wave latency and tibial nerve F-wave-latency were correlated with subexcitability, and tibial nerve motor amplitude was correlated with rheobase. CONCLUSIONS: NET was correlated with conventional NCS and no differences were found between NCS- PNP patients and patients without PNP. SIGNIFICANCE: NET does not seem to offer any additional diagnostic value in chronic mixed etiology neuropathy.

Test-retest and time dependent variation and diagnostic values of vibratory sensation determined by biothesiometer and the Rydel-Seiffer tuning fork.

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.