In Vivo Reflectance Microscopy of Meissner Corpuscles and Bedside Measures of Large Fiber Sensory Function: A Normative Data Cohort

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013175
Author(s):  
Peter D Creigh ◽  
Khai Du ◽  
Elizabeth P Wood ◽  
Joan Mountain ◽  
Janet Sowden ◽  
...  

Background and Objectives:To establish age-, gender- and body dimension-adjusted normal cut-off values for Meissner’s corpuscle (MC) densities via in-vivo reflectance confocal microscopy (RCM), timed vibration sensory thresholds using a 128Hz tuning fork, and touch-pressure sensory thresholds using standardized monofilaments, for clinical and research application.Methods:77 prospectively recruited individuals without signs or symptoms of peripheral neuropathy or a condition or neurotoxin exposure that can alter sensory function underwent cross-sectional evaluation of MC densities via in-vivo RCM, monofilament touch-pressure sensory thresholds, and timed vibration sensory thresholds in non-dominant upper and lower extremities. Age-, gender-, and body dimension- (e.g., height) adjusted normal values were developed. The 5th percentile for MC densities and timed vibration thresholds and 95th percentile for MF touch-pressure thresholds were selected as normal cut-off points.Results:Subjects were aged 9 to 89 years old. Age and gender were uniformly distributed. Timed vibration and touch-pressure thresholds were less sensitive with increasing age and were more sensitive in the hand than in the leg or foot within individuals. Timed vibration thresholds did not differ by gender or body dimensions. Touch-pressure thresholds were lower (more sensitive) at the thenar eminence and digit V in the hand in women compared to men but otherwise did not differ by gender at other measurement locations. Body dimensions did not affect touch-pressure thresholds. There were no apparent age-related floor effects for the 5th and 95th percentile normal cutoff values for timed vibration or touch-pressure thresholds, respectively. MC densities also declined with age and were highest at digit V and lowest at the arch within individuals. MC densities were affected by gender or body dimensions at all imaging sites, with lower densities seen in males or larger individuals. MC densities were quantifiable in the hand of all participants and were associated with touch-pressure thresholds at all locations.Discussion:This study establishes age-, gender- and body dimension-adjusted normal cut-off values for two easily applied measures of large fiber sensory function and RCM assessment of MC densities for multiple limb locations. These results will aid in the detection and monitoring of peripheral sensory nerve disorders.

2019 ◽  
Author(s):  
Anni Hämäläinen ◽  
Natalie Phillips ◽  
Walter Wittich ◽  
Paul Mick ◽  
M Kathleen Pichora-Fuller

Sensory and cognitive function both tend to decline with increasing age. Sensory impairments are risk factors for age-related cognitive decline and dementia. One hypothesis about sensory-cognitive associations is that sensory loss results in social isolation which, in turn, is a risk factor for cognitive decline. We tested whether social factors are associated with cognitive and sensory function, and whether sensory-cognitive associations are mediated or moderated by social factors. We used cross-sectional data from 30,029 participants in the Canadian Longitudinal Study of Aging, aged 45-85 years, who had no reported cognitive impairment or diagnosis of dementia. We found strong independent associations of self-reported social variables with hearing (pure-tone audiometry), vision (pinhole-corrected visual acuity), and executive function and weaker associations with memory. The moderating and mediating effects of social variables on sensory-cognitive associations were weak and mostly non-significant, but social factors could be slightly more important for females and older people. Partial retirement (relative to full retirement or not being retired) may have protective effects on cognition in the presence of hearing loss. These findings confirm the association between social factors and sensory and cognitive measures. However, support is weak for the hypothesis that social factors shape sensory-cognitive associations.


2014 ◽  
Vol 307 (9) ◽  
pp. R1124-R1135 ◽  
Author(s):  
Anita D. Christie ◽  
Anne Tonson ◽  
Ryan G. Larsen ◽  
Jacob P. DeBlois ◽  
Jane A. Kent

We tested the hypothesis that older muscle has greater metabolic economy (ME) in vivo than young, in a manner dependent, in part, on contraction intensity. Twenty young (Y; 24 ± 1 yr, 10 women), 18 older healthy (O; 73 ± 2, 9 women) and 9 older individuals with mild-to-moderate mobility impairment (OI; 74 ± 1, 7 women) received stimulated twitches (2 Hz, 3 min) and performed nonfatiguing voluntary (20, 50, and 100% maximal; 12 s each) isometric dorsiflexion contractions. Torque-time integrals (TTI; Nm·s) were calculated and expressed relative to maximal fat-free muscle cross-sectional area (cm2), and torque variability during voluntary contractions was calculated as the coefficient of variation. Total ATP cost of contraction (mM) was determined from flux through the creatine kinase reaction, nonoxidative glycolysis and oxidative phosphorylation, and used to calculate ME (Nm·s·cm−2·mM ATP−1). While twitch torque relaxation was slower in O and OI compared with Y ( P ≤ 0.001), twitch TTI, ATP cost, and economy were similar across groups ( P ≥ 0.15), indicating comparable intrinsic muscle economy during electrically induced isometric contractions in vivo. During voluntary contractions, normalized TTI and total ATP cost did not differ significantly across groups ( P ≥ 0.20). However, ME was lower in OI than Y or O at 20% and 50% MVC ( P ≤ 0.02), and torque variability was greater in OI than Y or O at 20% MVC ( P ≤ 0.05). These results refute the hypothesis of greater muscle ME in old age, and provide support for lower ME in impaired older adults as a potential mechanism or consequence of age-related reductions in functional mobility.


1982 ◽  
Vol 19 (4) ◽  
pp. 379-398 ◽  
Author(s):  
K. G. Braund ◽  
J. A. McGuire ◽  
C. E. Lincoln

Qualitative histologic studies and quantitative measurements were made on cross-sectional preparations of common peroneal and ulnar nerves of 32 neuromuscular disease-free dogs from birth to 15 years of age, to provide normative data not available previously. Minimal lesions were seen in nerves of dogs from birth to seven years; however, in older dogs, the incidence of axonal degeneration and segmental demyelination and remyelination increased. Total fiber density of both nerves was over 40,000 fibers/mm2 at birth and declined rapidly during the first six to nine months to level off at about 10,000 fibers/mm2 by one year of age. Density of small (< 5 μm) and large (≥ 5 μm) diameter fibers attained adult values by one year of age. The frequency distribution of the myelinated fibers was unimodal at birth and became bimodal between three and six months of age. The peaks of the small and large fiber groups occurred at 3 μm and 6 μm, respectively. Larger diameter fibers (10 μm to 12 μm) reached adult values between nine months and one year of age. A 2.5 fold increase in mean fiber diameter occurred during the first year of life. There was no statistically significant change in any histometric parameter after maturity (approximately one year of age).


2012 ◽  
Vol 112 (12) ◽  
pp. 2087-2098 ◽  
Author(s):  
H. Weber ◽  
A. Rauch ◽  
S. Adamski ◽  
K. Chakravarthy ◽  
A. Kulkarni ◽  
...  

Age-related sarcopenia results in frailty and decreased mobility, which are associated with increased falls and long-term disability in the elderly. Given the global increase in lifespan, sarcopenia is a growing, unmet medical need. This report aims to systematically characterize muscle aging in preclinical models, which may facilitate the development of sarcopenia therapies. Naïve rats and mice were subjected to noninvasive micro X-ray computed tomography (micro-CT) imaging, terminal in situ muscle function characterizations, and ATPase-based myofiber analysis. We developed a Definiens (Parsippany, NJ)-based algorithm to automate micro-CT image analysis, which facilitates longitudinal in vivo muscle mass analysis. We report development and characterization of translational in situ skeletal muscle performance assay systems in rat and mouse. The systems incorporate a custom-designed animal assay stage, resulting in enhanced force measurement precision, and LabVIEW (National Instruments, Austin, TX)-based algorithms to support automated data acquisition and data analysis. We used ATPase-staining techniques for myofibers to characterize fiber subtypes and distribution. Major parameters contributing to muscle performance were identified using data mining and integration, enabled by Labmatrix (BioFortis, Columbia, MD). These technologies enabled the systemic and accurate monitoring of muscle aging from a large number of animals. The data indicated that longitudinal muscle cross-sectional area measurement effectively monitors change of muscle mass and function during aging. Furthermore, the data showed that muscle performance during aging is also modulated by myofiber remodeling factors, such as changes in myofiber distribution patterns and changes in fiber shape, which affect myofiber interaction. This in vivo muscle assay platform has been applied to support identification and validation of novel targets for the treatment of sarcopenia.


2019 ◽  
Vol 8 (10) ◽  
pp. 1533
Author(s):  
Oana Maria Vanta ◽  
Nicoleta Tohanean ◽  
Sebastian Pintea ◽  
Lacramioara Perju-Dumbrava

(1) Background: Increased attention has lately been given to polyneuropathy in Parkinson’s Disease (PD). Several papers postulated that large-fiber neuropathy (PNP) in PD is related to vitamin B12 deficiency and L-Dopa exposure. (2) Methods: Using a cross-sectional, observational study, we evaluated 73 PD patients without a previously known cause of PNP using clinical scores (UPDRS II and III and Toronto Clinical Scoring System), biological evaluation of vitamin B12 and folic acid, and nerve conduction studies to assess the prevalence and features of PNP. (3) Results: The prevalence of PNP was 49.3% in the study group. In the L-Dopa group, the frequency of PNP was 67.3% as compared to PNP in the non-L-Dopa group, where one subject had PNP (χ2 = 23.41, p < 0.01). PNP was predominantly sensory with mild to moderate axonal loss. Cyanocobalamin correlated with L-Dopa daily dose (r = −0.287, p < 0.05) and L-Dopa duration of administration (r = −0.316, p < 0.05). L-Dopa daily dose correlated with the amplitudes of sensory nerve action potentials of the superficial peroneal and radial nerves (r = −0.312, p < 0.05) (r = −0.336, p < 0.05), respectively. (4) Conclusions: PNP is more frequent in L-Dopa-treated patients than in L-Dopa-naïve patients. The results imply that longer exposure to high doses of L-Dopa may cause vitamin B12 and folate imbalance and PNP, secondarily.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mattias Andréasson ◽  
Neil Lagali ◽  
Reza A. Badian ◽  
Tor Paaske Utheim ◽  
Fabio Scarpa ◽  
...  

AbstractSmall fiber neuropathy (SFN) has been suggested as a trigger of restless legs syndrome (RLS). An increased prevalence of peripheral neuropathy has been demonstrated in Parkinson’s disease (PD). We aimed to investigate, in a cross-sectional manner, whether SFN is overrepresented in PD patients with concurrent RLS relative to PD patients without RLS, using in vivo corneal confocal microscopy (IVCCM) and quantitative sensory testing (QST) as part of small fiber assessment. Study participants comprised of age- and sex-matched PD patients with (n = 21) and without RLS (n = 21), and controls (n = 13). Diagnosis of RLS was consolidated with the sensory suggested immobilization test. Assessments included nerve conduction studies (NCS), Utah Early Neuropathy Scale (UENS), QST, and IVCCM, with automated determination of corneal nerve fiber length (CNFL) and branch density (CNBD) from wide-area mosaics of the subbasal nerve plexus. Plasma neurofilament light (p-NfL) was determined as a measure of axonal degeneration. No significant differences were found between groups when comparing CNFL (p = 0.81), CNBD (p = 0.92), NCS (p = 0.82), and QST (minimum p = 0.54). UENS scores, however, differed significantly (p = 0.001), with post-hoc pairwise testing revealing higher scores in both PD groups relative to controls (p = 0.018 and p = 0.001). Analysis of all PD patients (n = 42) revealed a correlation between the duration of l-dopa therapy and CNBD (ρ = −0.36, p = 0.022), and p-NfL correlated with UENS (ρ = 0.35, p = 0.026) and NCS (ρ = −0.51, p = 0.001). Small and large fiber neuropathy do not appear to be associated with RLS in PD. Whether peripheral small and/or large fiber pathology associates with central neurodegeneration in PD merits further longitudinal studies.


2009 ◽  
Vol 107 (3) ◽  
pp. 880-886 ◽  
Author(s):  
C. Couppé ◽  
P. Hansen ◽  
M. Kongsgaard ◽  
V. Kovanen ◽  
C. Suetta ◽  
...  

Age-related loss in muscle mass and strength impairs daily life function in the elderly. However, it remains unknown whether tendon properties also deteriorate with age. Cross-linking of collagen molecules provides structural integrity to the tendon fibrils and has been shown to change with age in animals but has never been examined in humans in vivo. In this study, we examined the mechanical properties and pyridinoline and pentosidine cross-link and collagen concentrations of the patellar tendon in vivo in old (OM) and young men (YM). Seven OM (67 ± 3 years, 86 ± 10 kg) and 10 YM (27 ± 2 years, 81 ± 8 kg) with a similar physical activity level (OM 5 ± 6 h/wk, YM 5 ± 2 h/wk) were examined. MRI was used to assess whole tendon dimensions. Tendon mechanical properties were assessed with the use of simultaneous force and ultrasonographic measurements during ramped isometric contractions. Percutaneous tendon biopsies were taken and analyzed for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), pentosidine, and collagen concentrations. We found no significant differences in the dimensions or mechanical properties of the tendon between OM and YM. Collagen concentrations were lower in OM than in YM (0.49 ± 0.27 vs. 0.73 ± 0.14 mg/mg dry wt; P < 0.05). HP concentrations were higher in OM than in YM (898 ± 172 vs. 645 ± 183 mmol/mol; P < 0.05). LP concentrations were higher in OM than in YM (49 ± 38 vs. 16 ± 8 mmol/mol; P < 0.01), and pentosidine concentrations were higher in OM than in YM (73 ± 13 vs. 11 ± 2 mmol/mol; P < 0.01). These cross-sectional data raise the possibility that age may not appreciably influence the dimensions or mechanical properties of the human patellar tendon in vivo. Collagen concentration was reduced, whereas both enzymatic and nonenzymatic cross-linking of concentration was elevated in OM vs. in YM, which may be a mechanism to maintain the mechanical properties of tendon with aging.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anni Hämäläinen ◽  
Natalie Phillips ◽  
Walter Wittich ◽  
M. Kathleen Pichora-Fuller ◽  
Paul Mick

AbstractSensory and cognitive function both tend to decline with increasing age. Sensory impairments are risk factors for age-related cognitive decline and dementia. One hypothesis about sensory-cognitive associations is that sensory loss results in social isolation which, in turn, is a risk factor for cognitive decline. We tested whether social factors are associated with cognitive and sensory function, and whether sensory-cognitive associations are mediated or moderated by social factors. We used cross-sectional data from 30,029 participants in the Canadian Longitudinal Study of Aging, aged 45–85 years, who had no reported cognitive impairment or diagnosis of dementia. We found strong independent associations of self-reported social variables with hearing (pure-tone audiometry), vision (pinhole-corrected visual acuity), and executive function and weaker associations with memory. The moderating and mediating effects of social variables on sensory-cognitive associations were weak and mostly non-significant, but social factors could be slightly more important for females and older people. Partial retirement (relative to full retirement or not being retired) may have protective effects on cognition in the presence of hearing loss. These findings confirm the association between social factors and sensory and cognitive measures. However, support is weak for the hypothesis that social factors shape sensory-cognitive associations.


Author(s):  
Sujuan Liu ◽  
Chunxia Yu ◽  
Lingjian Xie ◽  
Yanmei Niu ◽  
Li Fu

Abstract Sarcopenia, the age-related loss of skeletal muscle mass and function, contributes to high morbidity and mortality in the older population. Regular exercise is necessary to avoid the initiation and progression of sarcopenia, in which the underlying molecular mechanism is still not clear. Our data revealed that the outcomes induced by sarcopenia, including muscle mass and strength loss, decreased cross-sectional area of gastrocnemius fiber, chronic inflammation, and increased dysfunctional mitochondria, were reversed by regulation exercise. Knockout or silencing of Sestrin2 (Sesn2) resulted in imbalanced mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy damage in vivo and in vitro, which was attenuated by aerobic exercise or overexpression of Sesn2. Moreover, we found that the effects of Sesn2 on mitochondrial function are dependent on AMP-activated protein kinase α2 (AMPKα2). This study indicates that aerobic exercise alleviates the negative effects resulting from sarcopenia via the Sesn2/AMPKα2 pathway and provides new insights into the molecular mechanism by which the Sesn2/AMPKα2 signaling axis mediates the beneficial impact of exercise on sarcopenia.


Author(s):  
Cesar D. Fermin ◽  
Hans-Peter Zenner

Contraction of outer and inner hair cells (OHC&IHC) in the Organ of Corti (OC) of the inner ear is necessary for sound transduction. Getting at HC in vivo preparations is difficult. Thus, isolated HCs have been used to study OHC properties. Even though viability has been shown in isolated (iOHC) preparations by good responses to current and cationic stimulation, the contribution of adjoining cells can not be explained with iOHC preparations. This study was undertaken to examine changes in the OHC after expossure of the OHC to high concentrations of potassium (K) and sodium (Na), by carefully immersing the OC in either artifical endolymph or perilymph. After K and Na exposure, OCs were fixed with 3% glutaraldehyde, post-fixed in osmium, separated into base, middle and apex and embedded in Araldite™. One μm thick sections were prepared for analysis with the light and E.M. Cross sectional areas were measured with Bioquant™ software.Potassium and sodium both cause isolated guinea pig OHC to contract. In vivo high K concentration may cause uncontrolled and sustained contractions that could contribute to Meniere's disease. The behavior of OHC in the vivo setting might be very different from that of iOHC. We show here changes of the cell cytosol and cisterns caused by K and Na to OHC in situs. The table below shows results from cross sectional area measurements of OHC from OC that were exposed to either K or Na. As one would expect, from the anatomical arrangement of the OC, OHC#l that are supported by rigid tissue would probably be displaced (move) less than those OHC located away from the pillar. Surprisingly, cells in the middle turn of the cochlea changed their surface areas more than those at either end of the cochlea. Moreover, changes in surface area do not seem to differ between K and Na treated OCs.


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