Validity of Clinical Small–Fiber Sensory Testing to Detect Small–Nerve Fiber Degeneration

2018 ◽  
Vol 48 (10) ◽  
pp. 767-774 ◽  
Author(s):  
Colette Ridehalgh ◽  
Oliver P. Sandy-Hindmarch ◽  
Annina B. Schmid
Keyword(s):  
Nerve Fiber ◽  
Sensory Testing ◽  
Small Fiber ◽  
Small Nerve

Characterization of small nerve fibers in painful distal symmetric polyneuropathy and healthy controls

2015 ◽  
Vol 8 (1) ◽  
pp. 51
Author(s):  
P. Karlsson ◽  
S. Haroutounian ◽  
M. Polydefkis ◽  
J.R. Nyengaard ◽  
T.S. Jensen
Keyword(s):  
Nerve Fiber ◽  
Quantitative Sensory Testing ◽  
Nerve Fibers ◽  
Healthy Controls ◽  
Sensory Testing ◽  
Fiber Morphology ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Distal Symmetric Polyneuropathy ◽  
Small Nerve

AbstractAimsThe introduction of skin biopsies to examine small nerve fiber morphology together with functional measures such as quantitative sensory testing (QST) has led to an improvement in diagnosing patients with small fiber neuropathy (SFN). Quantification of intraepidermal nerve fiber density (IENFD) is an important measure in SFN. However, the relationship between structure and function is not straightforward and the morphological and functional fiber characteristics are still unclear. This study aimed to combine structural and functional measurements to improve the diagnosis of distal symmetric polyneuropathy and small fiber involvement. Additionally, we investigated whether patients and healthy controls have differential patterns of correlations between structural and functional nerve measurements.Methods17 patients with painful distal symmetric polyneu-ropathy (DSP) and 19 controls underwent comprehensive small fiber assessments that included quantitative sensory testing, response to topical capsaicin and analysis of skin biopsy samples (IENFD, epidermal and dermal nerve fiber length densities (eNFLD, dNFLD) and swellings).ResultsDSP patients had reduced sensitivity to cold and heat, diminished capsaicin response, and lower IENFD, eNFLD and dNFLD (all p < 0.0003).The correlation between structural and functional parameters was better in controls than in DSP. A diagnostic approach of combined IENFD and eNFLD utilization, increased DSP diagnostic sensitivity from 82.0% to 100% and specificity from 84.0% to 89.5%.ConclusionsA correlation is found between functional and structural small fiber parameters for DSP and controls, and an approach to improve diagnostic accuracy in DSP is suggested.

scholarly journals SCN11A Arg225Cys mutation causes nociceptive pain without detectable peripheral nerve pathology

2018 ◽  
Vol 4 (4) ◽  
pp. e255 ◽  
Author(s):  
Ryan Castoro ◽  
Megan Simmons ◽  
Vignesh Ravi ◽  
Derek Huang ◽  
Christopher Lee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Fiber ◽  
Sensory Neuropathy ◽  
Nociceptive Pain ◽  
Missense Mutations ◽  
Nociceptive Neurons ◽  
Small Fiber ◽  
Skin Biopsies ◽  
Electrophysiologic Studies ◽  
Small Nerve

ObjectiveThe SCN11A gene encodes the NaV1.9 sodium channel found exclusively in peripheral nociceptive neurons.MethodsAll enrolled participants were evaluated clinically by electrophysiologic studies, DNA sequencing, and punch skin biopsies.ResultsAll affected family members are afflicted by episodes of pain. Pain was predominantly nociceptive, but not neuropathic in nature, which led a diagnosis of fibromyalgia in some patients. All patients had normal findings in nerve conduction studies for detecting large nerve fiber neuropathies and skin biopsies for detecting small nerve fiber pathology.ConclusionsUnlike those patients with missense mutations in SCN11A, small fiber sensory neuropathy, and neuropathic pain, the Arg225Cys SCN11A in the present study causes predominantly nociceptive pain with minimal features of neuropathic pain and undetectable pathophysiologic changes of peripheral neuropathy. This finding is consistent with dysfunction of nociceptive neurons. In addition, since nociceptive pain in patients has led to the diagnosis of fibromyalgia, this justifies a future search of mutations of SCN11A in patients with additional pain phenotypes such as fibromyalgia to expand the clinical spectrum beyond painful small fiber sensory neuropathy.

scholarly journals Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?

2021 ◽  
Vol 29 (1) ◽  
pp. 1-8
Author(s):  
Mariia V. Lukashenko ◽  
Natalia Y. Gavrilova ◽  
Anna V. Bregovskaya ◽  
Lidiia A. Soprun ◽  
Leonid P. Churilov ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Skin Biopsy ◽  
Nerve Fiber ◽  
Small Fiber Neuropathy ◽  
Fiber Damage ◽  
Advantages And Disadvantages ◽  
Small Fiber ◽  
Corneal Confocal Microscopy ◽  
Common Causes ◽  
Small Nerve

Chronic pain may affect 30–50% of the world’s population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.

scholarly journals Alpha-synuclein oligomers and small nerve fiber pathology in skin are potential biomarkers of Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Elena Vacchi ◽  
Camilla Senese ◽  
Giacomo Chiaro ◽  
Giulio Disanto ◽  
Sandra Pinton ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Nerve Fiber ◽  
Temporal Dynamics ◽  
Alpha Synuclein ◽  
Small Fiber Neuropathy ◽  
Proximity Ligation Assay ◽  
Anatomical Site ◽  
Small Fiber ◽  
Intraepidermal Nerve Fiber Density ◽  
Small Nerve

AbstractThe proximity ligation assay (PLA) is a specific and sensitive technique for the detection of αSyn oligomers (αSyn-PLA), early and toxic species implicated in the pathogenesis of PD. We aimed to evaluate by skin biopsy the diagnostic and prognostic capacity of αSyn-PLA and small nerve fiber reduction in PD in a longitudinal study. αSyn-PLA was performed in the ankle and cervical skin biopsies of PD (n = 30), atypical parkinsonisms (AP, n = 23) including multiple system atrophy (MSA, n = 12) and tauopathies (AP-Tau, n = 11), and healthy controls (HC, n = 22). Skin biopsy was also analyzed for phosphorylated αSyn (P-αSyn) and 5G4 (αSyn-5G4), a conformation-specific antibody to aggregated αSyn. Intraepidermal nerve fiber density (IENFD) was assessed as a measure of small fiber neuropathy. αSyn-PLA signal was more expressed in PD and MSA compared to controls and AP-Tau. αSyn-PLA showed the highest diagnostic accuracy (PD vs. HC sensitivity 80%, specificity 77%; PD vs. AP-Tau sensitivity 80%, specificity 82%), however, P-αSyn and 5G4, possible markers of later phases, performed better when considering the ankle site alone. A small fiber neuropathy was detected in PD and MSA. A progression of denervation not of pathological αSyn was detected at follow-up and a lower IENFD at baseline was associated with a greater cognitive and motor decline in PD. A skin biopsy-derived compound marker, resulting from a linear discrimination analysis model of αSyn-PLA, P-αSyn, αSyn-5G4, and IENFD, stratified patients with accuracy (77.8%), including the discrimination between PD and MSA (84.6%). In conclusion, the choice of pathological αSyn marker and anatomical site influences the diagnostic performance of skin biopsy and can help in understanding the temporal dynamics of αSyn spreading in the peripheral nervous system during the disease. Skin denervation, not pathological αSyn is a potential progression marker for PD.

scholarly journals Validation of a Brazilian quantitative sensory testing (QST) device for the diagnosis of small fiber neuropathies

2011 ◽  
Vol 69 (6) ◽  
pp. 943-948 ◽  
Author(s):  
Pedro Schestatsky ◽  
Luciana Cadore Stefani ◽  
Paulo Roberto Sanches ◽  
Danton Pereira da Silva Júnior ◽  
Iraci Lucena Silva Torres ◽  
...  
Keyword(s):  
Quantitative Sensory Testing ◽  
Stimulus Change ◽  
Heat Pain ◽  
Thermal Perception ◽  
Sensory Testing ◽  
Brazilian Sample ◽  
Small Fiber ◽  
Normal Individuals ◽  
Nociceptive Pathway

Quantitative sensory testing (QST) is defined as the determination of thresholds for sensory perception under controlled stimulus. Our aim was to validate a new QST device for Brazilian sample. In 20 healthy adults, thermoalgesic thresholds were assessed using a QST prototype (Heat Pain Stimulator-1.1.10; Brazil). A 30 × 30 mm² thermode with a 1°C/s stimulus change rate were applied. Thresholds of three consecutive stimuli were averaged in two different sessions separated by at least two weeks. Additionally long thermal heat pain stimulus was performed. To evaluate the consistency of our method we also analyzed 11 patients with small fiber neuropathy. Results showed good reproducibility of thermal perception thresholds in normal individuals and plausible abnormal thresholds in patients. We conclude that our QST device is reliable when analyzing the nociceptive pathway in controls and patients.

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