Small-Fiber Neuropathy Is Associated With Corneal Nerve and Dendritic Cell Alterations

Bucher, Franziska; Schneider, Christian A.; Blau, Tobias; Cursiefen, Claus; Fink, Gereon R.; Lehmann, Helmar C.; Heindl, Ludwig M.

doi:10.1097/ico.0000000000000535

Cited by 45 publications

(34 citation statements)

References 37 publications

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“…Applying CCM, lower CNFD was found in previous studies comparing SFN patients with healthy controls . Further findings in SFN patients were shorter CNFL, less nerve fiber branching, and higher corneal nerve tortuosity than in healthy controls. LC counts did not differ between SFN patients and controls .…”

Section: Discussionmentioning

confidence: 61%

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Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

Klitsch

Evdokimov

Frank

et al. 2020

J Peripheral Nervous Sys

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In our study, we aimed at investigating corneal langerhans cells (LC) in patients with fibromyalgia syndrome (FMS) and small fiber neuropathy (SFN) as potential contributors to corneal small fiber pathology. We enrolled women with FMS (n = 134) and SFN (n = 41) who underwent neurological examination, neurophysiology, prostaglandin analysis in tear fluid, and corneal confocal microscopy (CCM). Data were compared with those of 60 age‐matched female controls. After screening for dry eye disease, corneal LC were counted and sub‐classified as dendritic (dLC) and non‐dendritic (ndLC) cells with or without nerve fiber association. We further analyzed corneal nerve fiber density (CNFD), length (CNFL), and branch density (CNBD). Neurological examination indicated deficits of small fiber function in patients with SFN. Nerve conduction studies were normal in all participants. Dry eye disease was more prevalent in FMS (17%) and SFN (28%) patients than in controls (5%). Tear fluid prostaglandin levels did not differ between FMS patients and controls. While corneal LC density in FMS and SFN patients was not different from controls, there were fewer dLC in association with nerve fibers in FMS and SFN patients than in controls (P < .01 each). Compared to controls, CNFL was lower in FMS and SFN patients (P < .05 each), CNFD was lower only in FMS patients (P < .05), and CNBD was lower only in SFN patients (P < .001). There was no difference in any CCM parameter between patients with and without dry eyes. Our data indicate changes in corneal innervation and LC distribution in FMS and SFN, potentially based on altered LC signaling.

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Section: Discussionmentioning

confidence: 61%

“…Further findings in SFN patients were shorter CNFL, less nerve fiber branching, and higher corneal nerve tortuosity than in healthy controls. LC counts did not differ between SFN patients and controls . We showed lower CNFL and corneal nerve fiber branching in SFN patients than in controls, whereas CNFD did not differ.…”

Section: Discussionmentioning

confidence: 82%

Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

Klitsch

Evdokimov

Frank

et al. 2020

J Peripheral Nervous Sys

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“…Even though a formal cost-effectiveness analysis was beyond the scope of the present work, it is conceivable that this substantial minimization of examination time may enable more widespread screening for CAN. Interestingly, the present attempt at shortening the examination time is in the same context as the suggested simplification of nerve conduction study by the sural sensory/radial motor amplitude ratio [24] and some innovations in corneal confocal microscopy [25][26][27]. Nonetheless, it should by no means be suggested that a simple index like the 30:15 ratio, or a combination of the 30:15 ratio with the VR, the E/I/VR, and the rise in diastolic blood pressure, could currently replace the validated 5 Ewing tests.…”

Section: Discussionmentioning

confidence: 99%

Simplified Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Using Ewing's Battery

Pafili¹,

Trypsianis²,

Papazoglou³

et al. 2015

Rev Diabet Stud

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■ Abstract AIM:To find a potential simplification of the established Ewing's battery for the diagnosis of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes (T2D). METHODS:We included 152 patients (92 men) with mean age 64.51 ± 7.85 years and median diabetes duration of 12 years. Ewing's battery was used as the gold standard for the diagnosis of CAN. Against this, we compared the results from each test and their combinations. RESULTS: The 30:15 ratio exhibited the best diagnostic performance (AUC = 0.817, 95% CI: 0.730-0.903, p < 0.001), with 96% sensitivity, 65% specificity, and 94% negative predictive value (NPV). The corresponding values for the Valsalva ratio (VR) were 62%, 92%, and 85%, respectively. The 30:15 ratio was the strongest independent predictor of neuropathy in multivariate regression analysis; low levels yielded an odds ratio (OR) of 21.14 for CAN. The rise in diastolic blood pressure and the expiration/inspiration/VR ratio (E/I/VR) were also identified as independent predictors of CAN, with 9.45 and 10.79 ORs, respectively. CONCLUSIONS: The 30:15 ratio has the best diagnostic accuracy, primarily in the exclusion of CAN, by virtue of its very high sensitivity and NPV. If this ratio is positive for CAN, the VR, the rise in diastolic blood pressure, and the E/I/VR may be useful to increase diagnostic accuracy. This procedure is a simplified diagnostic approach that merits further evaluation to enable wider screening for CAN.

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“…This non-invasive technique uses a combination of corneal nerve fiber length, nerve branch density, and nerve fiber density to evaluate the corneal nerve plexus 175176. It has been shown to detect early small nerve fiber damage in many disorders 175177178179180181182. This technique has advantages over skin biopsy as it is rapid and non-invasive, but it is not yet widely available.…”

Section: Diagnostic Approachmentioning

confidence: 99%

Diagnosis and management of sensory polyneuropathy

Gwathmey

Pearson

2019

BMJ

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Sensory polyneuropathies, which are caused by dysfunction of peripheral sensory nerve fibers, are a heterogeneous group of disorders that range from the common diabetic neuropathy to the rare sensory neuronopathies. The presenting symptoms, acuity, time course, severity, and subsequent morbidity vary and depend on the type of fiber that is affected and the underlying cause. Damage to small thinly myelinated and unmyelinated nerve fibers results in neuropathic pain, whereas damage to large myelinated sensory afferents results in proprioceptive deficits and ataxia. The causes of these disorders are diverse and include metabolic, toxic, infectious, inflammatory, autoimmune, and genetic conditions. Idiopathic sensory polyneuropathies are common although they should be considered a diagnosis of exclusion. The diagnostic evaluation involves electrophysiologic testing including nerve conduction studies, histopathologic analysis of nerve tissue, serum studies, and sometimes autonomic testing and cerebrospinal fluid analysis. The treatment of these diseases depends on the underlying cause and may include immunotherapy, mitigation of risk factors, symptomatic treatment, and gene therapy, such as the recently developed RNA interference and antisense oligonucleotide therapies for transthyretin familial amyloid polyneuropathy. Many of these disorders have no directed treatment, in which case management remains symptomatic and supportive. More research is needed into the underlying pathophysiology of nerve damage in these polyneuropathies to guide advances in treatment.

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Small-Fiber Neuropathy Is Associated With Corneal Nerve and Dendritic Cell Alterations

Abstract: CCM provides parameters that reliably indicate injury to sensory afferents of the trigeminal nerve in patients with SFN. Our data suggest that CCM may serve both as a noninvasive diagnostic test and as a surrogate marker in SFN.

Cited by 45 publications

References 37 publications

Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

Reduced association between dendritic cells and corneal sub‐basal nerve fibers in patients with fibromyalgia syndrome

Simplified Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Using Ewing's Battery

Diagnosis and management of sensory polyneuropathy

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