Small fibers involvement in Friedreich's ataxia

Nolano, Maria; Provitera, Vincenzo; Crisci, C.; Saltalamacchia, Anna Maria; Wendelschafer‐Crabb, Gwen; Kennedy, William R.; Filla, Alessandro; Santoro, Lucio; Caruso, Giuseppe

doi:10.1002/ana.1283

Cited by 74 publications

(52 citation statements)

References 31 publications

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“…Response amplitudes (in particular for ABR wave V) were, however, significantly lower, suggesting reduced neural populations in the auditory brainstem. This finding is consistent with reports of axonal degeneration in other sensory systems for individuals with FRDA [Hughes et al, 1968;Nolano et al, 2001].…”

supporting

confidence: 83%

“…Desynchronization may occur through demyelination of the auditory nerve [Waxman, 1977] or disrupted synaptic transmission between cochlear inner hair cells and the auditory nerve [Glowatzki and Fuchs, 2002]. In listeners with FRDA, auditory pathway disruption is likely due to axonal degeneration [Hughes et al, 1968;Nolano et al, 2001] rather than desynchronization (hence, the reduced ABR amplitudes -but normal response latencies -observed in our subjects who still had an ABR at the time of testing). Zeng et al [2005] have, however, suggested that the response from a reduced number of neural elements to a subtle timing cue could be difficult to detect because of its similarity to background spontaneous activity.…”

Section: Discussionmentioning

confidence: 92%

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Auditory Perception in Individuals with Friedreich’s Ataxia

et al. 2009

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Introduction: Friedreich’s ataxia (FRDA) is an inherited ataxia with a range of progressive features including axonal degeneration of sensory nerves. The aim of this study was to investigate auditory perception in affected individuals. Methods: Fourteen subjects with genetically defined FRDA participated. Two control groups, one consisting of healthy, normally hearing individuals and another comprised of subjects with sensorineural hearing loss, were also assessed. Auditory processing was evaluated using structured tasks designed to reveal the listeners’ ability to perceive temporal and spectral cues. Findings were then correlated with open-set speech understanding. Results: Nine of 14 individuals with FRDA showed evidence of auditory processing disorder. Gap and amplitude modulation detection levels in these subjects were significantly elevated, indicating impaired encoding of rapid signal changes. Electrophysiologic findings (auditory brainstem response, ABR) also reflected disrupted neural activity. Speech understanding was significantly affected in these listeners and the degree of disruption was related to temporal processing ability. Speech analyses indicated that timing cues (notably consonant voice onset time and vowel duration) were most affected. Conclusion: The results suggest that auditory pathway abnormality is a relatively common consequence of FRDA. Regular auditory evaluation should therefore be part of the management regime for all affected individuals. This assessment should include both ABR testing, which can provide insights into the degree to which auditory neural activity is disrupted, and some functional measure of hearing capacity such as speech perception assessment, which can quantify the disorder and provide a basis for intervention.

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confidence: 83%

Section: Discussionmentioning

confidence: 92%

Auditory Perception in Individuals with Friedreich’s Ataxia

et al. 2009

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“…4 More recently, reduced MC density, distorted MC structure, focal thinning or loss of myelin, and short myelin internodes coupled with decreased sensitivity to touch have been reported. [5][6][7] Functional studies of touch conveyed by cutaneous mechanoreceptors in glabrous skin found that detection of small raised dots (bumps) on a smooth surface using the finger pad was signaled by MCs. 8,9 Based on these studies, we devised a simple device called the Bumps to quantify tactile sensitivity on the finger pads.…”

Section: Discussionmentioning

confidence: 99%

A new device to quantify tactile sensation in neuropathy

Kennedy¹,

Selim²,

Brink³

et al. 2011

Neurology

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Objective: To devise a rapid, sensitive method to quantify tactile threshold of finger pads for early detection and staging of peripheral neuropathy and for use in clinical trials.Methods: Subjects were 166 healthy controls and 103 patients with, or at risk for, peripheral neuropathy. Subjects were screened by questionnaire. The test device, the Bumps, is a checkerboard-like smooth surface with 12 squares; each square encloses 5 colored circles. The subject explores the circles of each square with the index finger pad to locate the one circle containing a small bump. Bumps in different squares have different heights. Detection threshold is defined as the smallest bump height detected. In some subjects, a 3-mm skin biopsy from the tested finger pad was taken to compare density of Meissner corpuscles (MCs) to bump detection thresholds. Results:The mean (ϮSEM) bump detection threshold for control subjects was 3.3 Ϯ 0.10 m.Threshold and test time were age related, older subjects having slightly higher thresholds and using more time. Mean detection threshold of patients with neuropathy (6.2 Ϯ 0.35 m) differed from controls (p Ͻ 0.001). A proposed threshold for identifying impaired sensation had a sensitivity of 71% and specificity of 74%. Detection threshold was higher when MC density was decreased. Conclusions:These preliminary studies suggest that the Bumps test is a rapid, sensitive, inexpensive method to quantify tactile sensation of finger pads. It has potential for early diagnosis of tactile deficiency in subjects suspected of having neuropathy, for staging degree of tactile deficit, and for monitoring change over time. Reduced tactile sensation (numbness) is a common symptom of patients with peripheral neuropathy. A need exists for efficient techniques to diagnose and quantify tactile deficiency early, when treatment has the greatest potential of success. Furthermore, evaluation of therapeutic benefits from advances in molecular biology, genetics, pharmacology, and other sciences will require more precise measurements than are currently available.Meissner corpuscles (MCs) are sensitive organs for touch recognition on glabrous skin of the hands and fingers. Early studies showed lower MC density in older persons 1-3 and in neuropathy. 4 More recently, reduced MC density, distorted MC structure, focal thinning or loss of myelin, and short myelin internodes coupled with decreased sensitivity to touch have been reported. [5][6][7] Functional studies of touch conveyed by cutaneous mechanoreceptors in glabrous skin found that detection of small raised dots (bumps) on a smooth surface using the finger pad was signaled by MCs. 8,9 Based on these studies, we devised a simple device called the Bumps to quantify tactile sensitivity on the finger pads. The Bumps test determines the tactile detection threshold by having the subject rub the finger pad over a smooth surface to locate single, coin-shaped bumps of different heights. Using this device, we found a difference in detection thresholds between control subject...

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“…24 However, some of our findings (warm threshold abnormalities and ENF loss) also suggest an involvement of C fibers in CMT1A, although we cannot have morphologic evidence, since it is not possible to distinguish between C and A-d fibers, whose cutaneous terminal branches are both unmyelinated. 25,26 The involvement of small fibers in conditions affecting mainly large fibers has been previously reported, [27][28][29] implying that congenital or acquired mechanisms underlying the degeneration of large fibers may also affect small fibers. In CMT1A, abnormalities of the interaction between axon and Schwann cells may play a causative role in the distal degeneration of unmyelinated fibers, since PMP22 is also present in the plasma membrane of nonmyelinating Schwann cells.…”

Section: Statistical Analysis We Used Student T Test For Unpaired Datamentioning

confidence: 94%

Small nerve fiber involvement in CMT1A

et al. 2015

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Objective: To assess the involvement of small nerve fibers in Charcot-Marie-Tooth type 1A (CMT1A). Methods:We used indirect immunofluorescence and confocal microscopy on punch biopsies from glabrous (fingertip) and hairy (thigh and leg) skin of 20 unrelated patients with CMT1A to quantify somatic and autonomic nerve fibers. In particular, we quantified epidermal nerve fibers (ENF), Meissner corpuscles (MC), intrapapillary myelinated endings (IME), and sudomotor nerves. We correlated morphologic data with findings from quantitative sensory testing, sudomotor output, sympathetic skin response, and cardiovascular reflexes. A control population of healthy ageand sex-matched controls was included with a matching ratio of 1:2.Results: We found a length-dependent loss of ENFs that worsened with aging. We also observed a loss of MCs, IMEs, and sudomotor nerves. The loss of ENF at distal leg correlated with the increase in heat-pain thresholds (p , 0.05) and with tactile thresholds (p , 0.05). Sudomotor nerve fiber loss correlated with ENF density (p , 0.05) and sweating output (p , 0.001). Conclusions:We demonstrated through morphologic, physical, and psychophysical testing that small somatic and autonomic fibers are abnormal and cause symptoms in patients with CMT1A. Awareness of such symptoms by the clinician could lead to better treatment. Neurology ® 2015;84:407-414 GLOSSARY ANS 5 autonomic nervous system; CGRP 5 calcitonin gene-related peptide; CMT 5 Charcot-Marie-Tooth; CMT1A 5 Charcot-Marie-Tooth type 1A; CMTNS 5 Charcot-Marie-Tooth neuropathy score; Col IV 5 collagen IV; CVR 5 cardiovascular reflexes; DST 5 dynamic sweat test; ENF 5 epidermal nerve fibers; IME 5 intrapapillary myelinated endings; LEP 5 laser-evoked potentials; MC 5 Meissner corpuscles; PGP 5 protein gene product; PMP22 5 peripheral myelin protein 22 kD; QST 5 quantitative sensory testing; SFN-SIQ 5 Small Fiber Neuropathy Symptoms Inventory Questionnaire; SSR 5 sympathetic skin response; SubP 5 substance P; VIP 5 vasoactive intestinal peptide.Charcot-Marie-Tooth (CMT) diseases are a heterogeneous group of inherited motor and sensory neuropathies with a general prevalence of 1:2,500.

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Small fibers involvement in Friedreich's ataxia

Cited by 74 publications

References 31 publications

Auditory Perception in Individuals with Friedreich’s Ataxia

Auditory Perception in Individuals with Friedreich’s Ataxia

A new device to quantify tactile sensation in neuropathy

Small nerve fiber involvement in CMT1A

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