• Annals of Clinical Neurophysiology
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• v.24 no.1
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• pp.1-6
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• 2022

Small fiber neuropathy is a painful neuropathy that cannot be assessed using nerve conduction studies. A skin biopsy and quantitative sensory testing (QST) are the gold standards for small fiber neuropathy diagnosis. However, a skin biopsy is invasive and commercially unavailable in Korea. QST is a method involving a thermal threshold, but its results can be affected by cognition as well as lesions of the central nervous system. Quantitative sudomotor axon reflex test (QSART) is a quantitative method of assessing sweat glands innervated by small fibers. In this review, we assessed the utility of QSART in evaluating small fiber neuropathy.

• Annals of Clinical Neurophysiology
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• v.17 no.2
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• pp.53-60
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• 2015

Skin biopsy with investigation of small nerve fiber in human epidermis and dermis has been proven to be a useful method for demonstration of small fiber neuropathy. Quantification of intraepidermal nerve fiber density using anti-Protein Gene Product 9.5 (PGP 9.5) antibody is standardized method to diagnose the small fiber neuropathy. Skin biopsy method also makes it possible to differentiate the type of nerve fibers by using different antibodies. Quantification of dermal structures with different type of nerve fibers could be used to invest pathophysiologic mechanism of diseased state.

• Annals of Clinical Neurophysiology
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• v.20 no.1
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• pp.3-11
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• 2018

Skin biopsy and staining the specimens with immuno-reactive markers has been proven to be a useful method to demonstrate the pathologic status of small nerve fibers. Quantification of intraepidermal nerve fiber density using anti-protein gene product 9.5 antibody is a standard method to diagnose small fiber neuropathy. Skin biopsy also makes it possible to differentiate the nerve fibers according to their function by using different markers. Quantification of dermal structures with different types of nerve fibers could reveal the pathophysiologic mechanism of the disease state.

• Annals of Clinical Neurophysiology
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• v.5 no.1
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• pp.1-10
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• 2003

Small-fiber neuropathy (SFN) is a common clinical problems. The disorder is a generalized peripheral polyneuropathy that selectively involves small-diameter myelinated and unmyelinated nerve fibers. It is often idiopathic and typically presents with painful feet in patients over the age of 60. And autoimmune mechanisms are often suspected, but rarely identified. The clinical features consisted of painful dysesthesias and postganglionic sympathetic dysfunction, as well as reduced pinprick and temperature sensation. Although affected patients complain of neuropathic pain, this condition is often difficult to diagnose because of the few objective physical signs and normal nerve conduction studies. Diagnosis of SFN is made on the basis of the clinical features, normal nerve conduction studies, and abnormal specialized tests of small fiber function. These specialized studies include assessment of epidermal nerve fiber density as well as sudomotor, quantitative sensory, and cardiovagal testing. Unless an underlying disease is identified, treatment is usually directed toward alleviation of neuropathic pain.

• Journal of Electrodiagnosis and Neuromuscular Diseases
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• v.20 no.2
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• pp.77-83
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• 2018

Small fiber neuropathy (SFN) mainly affects thinly myelinated $A{\delta}$-fibers and unmyelinated C-fibers presented with neuropathic pain like burning feet or numbness. Many conditions are known as a causes of SFN, metabolic derangement, especially glucose intolerance, is the most frequent cause of SFN. It has been hard to diagnose SFN because there has been lack of specialized test for small nerve fiber. Quantification of intraepidermal nerve fiber density using skin biopsy is promising method to diagnose SFN. A skin biopsy also could give helps to research pathophysiology of SFN by specialized stain method.

• Journal of the Korean neurological association
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• v.36 no.4
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• pp.318-321
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• 2018

We describe a 44-year-old woman with paresthesia, fatigue, and palpitation, 10 days after human papillomavirus (HPV) vaccination. The quantitative sensory test showed abnormal detection threshold in her foot. Tilt test result indicated postural orthostatic tachycardia syndrome. Symptoms were improved after immunomodulating therapy, pain control drug, and oral beta blocker medication. This is first case report for small fiber neuropathy and autonomic dysfunction after HPV vaccination in Korea.

• Annals of Clinical Neurophysiology
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• v.10 no.1
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• pp.33-37
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• 2008

Diabetic polyneuropathy (DPN) is the most common form of diabetic neuropathy, and causes a significant morbidity with an impact on the quality of life in the patients with diabetes. Since DPN frequently induces foot deformity and ulceration, which finally leads to foot amputation, the early detection and treatment is very important for the prevention of a permanent structural change. In the early stage of DPN, the diagnostic methods which can evaluate the function or structure of small nerve fibers should be employed because small nerve fibers are first involved in the course of DPN. However, the nerve conduction study cannot reflect the function of the small nerve fibers, and thus, has a definite limitation in the early diagnosis of DPN. For the early detection of DPN, electrodiagnostic data should be interpreted on a clinical context, along with the careful evaluation of the small nerve fiber functions using the tests such as the analysis of intraepidermal nerve fiber density.

• Annals of Clinical Neurophysiology
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• v.9 no.2
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• pp.43-50
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• 2007

Analysis of intraepidermal nerve fibers using skin biopsy is a recently developed technique, providing diagnostic information on small fiber neuropathies. The specimens are obtained by 3 mm punch biopsy, which is safe and minimally invasive. Immunohistochemical staining by Protein gene product (PGP) 9.5 demonstrate not only intraepidermal nerve fibers but dermal structures, such as sweat gland and erector papillae. Up to now, many studies agree that intraepidermal nerve fiber density is dramatically reduced in various sensory neuropathies. The utility of density measure was confirmed with high sensitivity in the diagnosis of sensory neuropathy, comparable to sural nerve biopsy or quantitative sensory testing. Besides quantitative methods, morphological changes like axonal swelling and fragmentation can be used as predegenerative markers. This article reviews the technique of skin biopsy and clinical and experimental usefulness of skin biopsy in diagnosing and monitoring peripheral neuropathies.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.327-335
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• 2022

Background: The pathophysiology of fibromyalgia (FM) involves many mechanisms including central nervous system sensitization theory, autonomic nervous system (ANS) dysfunction, and recently small fiber neuropathy. While the small fiber neuropathy itself can cause ANS dysfunction and neuropathic pain (NP), it is still unknown whether ANS problems have an association with severity of disease and NP in patients with FM. The aim of this study was to evaluate ANS dysfunction in FM patients and to explore possible associations of ANS dysfunction with disease severity and NP. Methods: Twenty-nine FM patients and 20 healthy controls were included in this cross-sectional study. Participants were tested using sympathetic skin responses (SSR) and R-R interval variation analyses for sympathetic and parasympathetic ANS dysfunction, respectively. Disease severity and somatic symptoms of patients with FM were evaluated using the ACR-2010 scales and Fibromyalgia Impact Questionnaire, and NP symptoms were evaluated using the Pain Detect Questionnaire and Douleur Neuropathique questionnaire. Results: FM patients were found to have ANS dysfunction characterized by increased sympathetic response and decreased parasympathetic response. SSR amplitudes were found to be correlated with a more severe disease. Although nonsignificant, NP severity tended to be associated with a decrease in sympathetic and parasympathetic activities. Conclusions: ANS dysfunction may play a role in the pathophysiology of FM. The trend of decreased ANS functions in FM patients exhibiting NP contradicts the notion that FM is a sympathetically maintained NP and may be explained with small fiber involvement.

• Annals of Clinical Neurophysiology
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• v.10 no.1
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• pp.29-32
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• 2008

Although various criteria on the diagnosis of diabetic neuropathy are applied from trial to trial, being tailored in concert with its purpose, the utmost evidences of the diagnosis are subjective symptoms and objective signs of neurologic deficit. The application and interpretation of auxiliary electrophysiological test including nerve conduction study (NCS) should be made on the context of clinical pictures. The evaluation of the functions of small, thinly myelinated or unmyelinated nerve fibers has been increasingly stressed recently with the advent of newer techniques, e.g., measurement of intraepidermal fiber density, quantitative sensory testing, and autonomic function test. And the studies with those techniques have shed light to the nature of the evolution of diabetic neuropathy. The practical application of these techniques to the diagnosis of diabetic neuropathy in the individual patients, however, should be made cautiously due to several shortcomings: limited accessibility, wide overlapping zone between norm and abnormality with resultant unsatisfactory sensitivity and specificity, difficulty in performing subsequent tests, unproven quantitative correlation with clinical deficit, and invasiveness of some technique. NCS, as an extension of clinical examination, is still the most reliable electrophysiological test in evaluating neuropathy and gives the invaluable information about the nature of neuropathy, whereas the newer techniques need more refinement of the procedure and interpretation, and the accumulation of large scaled data of application to be considered as established diagnostic tools of peripheral neuropathy.