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Diabetes polyneuropathy is an important complication of diabetes polyneuropathy, and its notable sequelae of foot ulceration, autonomic dysfunction, and neuropathic pain are associated with significant morbidity and mortality. Despite the major impact on quality of life and health economic costs, it remains underdiagnosed until late in its natural history, and there is lack of any intervention that can reverse its clinical progress. Assessment of small fiber neuropathy (SFN) in diabetes offers an opportunity to detect abnormalities at an early stage so that both interventional studies and preventative measures can be enacted to prevent progression to the devastating complications of foot ulceration and cardiac dysautonomic death. Over the last two decades, significant advances have been made in understanding the pathophysiology of diabetes neuropathy and its assessment. In this review, we discuss limitations of the screening methods recommended in current clinical guidelines which are based on large nerve fiber assessments. Thereafter, we discuss in detail the various methods currently available to assess small fiber structure and function and examine their individual strength and limitations. Finally, we discuss the reasons why despite the considerable body of evidence available, legislators and global experts have yet to incorporate the assessment of SFN as routine clinical surveillance in diabetes management. We hope that these insights will stimulate further discussion and be instrumental in the early adoption of these methods so as to reduce the burden of complications arising due to diabetes polyneuropathy.

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non-classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose., (© 2020 Peripheral Nerve Society.)

Objective: To present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research., Methods: The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria., Results: An iDSP diagnosis requires at least 1 small fiber (SF) or large fiber (LF) symptom, at least 1 SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intraepidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least 1 of the above clinical features is SF and 1 clinical feature is LF with abnormalities in sensory NCS or IENFD. Diagnostic criteria for iSFN require at least 1 SF symptom and at least 1 SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least 1 LF symptom and at least 1 LF sign with normal IENFD, abnormal sensory NCS, and absence of SF symptoms and signs., Conclusion: Adoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs., (© 2020 American Academy of Neurology.)

The diagnosis of polyneuropathy (PNP) is based on the anamnesis and description of complaints of the patient and clinical findings. The type of distribution as well as known diseases and drug toxic factors can provide indications. Electromyography and electroneurography can be used to differentiate between axonal and demyelinating PNP. The laboratory examinations are initially directed towards frequent and treatable causes. These are then expanded depending on the suspected diagnosis. Analysis of cerebrospinal fluid (CSF) is facultative and should be carried out when there is a suspicion of a certain form of PNP with CSF findings indicative of the diagnosis. Nerve biopsy is indicated when the etiology of a severe or progressive PNP cannot be clarified by less invasive means and can have consequences for the treatment. A genetic investigation can be meaningful with a positive family anamnesis or with typical signs of hereditary PNP. Depending on the neuropathy and context, the diagnostic approach is structured differently. The special diagnostics for small fiber neuropathy and amyloid neuropathy as well as for diabetes and alcohol abuse are dealt with in detail in this article. Numerous cases of polyneuropathy remain unexplained and regularly have a favourable prognosis.

Objective: To determine the comparative diagnostic characteristics of neuropathy measures in an obese population., Methods: We recruited obese participants from the University of Michigan's Weight Management Program. Receiver operative characteristic analysis determined the area under the curve (AUC) of neuropathy measures for distal symmetric polyneuropathy (DSP), small fiber neuropathy (SFN), and cardiovascular autonomic neuropathy (CAN). The best test combinations were determined using stepwise and Score subset selection models., Results: We enrolled 120 obese participants. For DSP, seven of 42 neuropathy measures (Utah Early Neuropathy Score (UENS, N = 62), Michigan Neuropathy Screening Instrument (MNSI) reduced combined index, MNSI examination, nerve fiber density (NFD) leg, tibial F response, MNSI questionnaire, peroneal distal motor latency) had AUCs ≥ 0.75. Three of 19 small fiber nerve measures for SFN (UENS, NFD leg, Sudoscan feet (N = 70)) and zero of 16 CAN measures had AUCs ≥ 0.75. Combinations of tests performed better than individual tests with AUCs of 0.82 for DSP (two parameters) and 0.84 for SFN (three parameters)., Conclusions: Many neuropathy measures demonstrate good test performance for DSP in obese participants. Select few small fiber nerve measures performed well for SFN, and none for CAN., Significance: Specific combinations of tests should be used for research studies to maximize diagnostic performance in obese cohorts., (Published by Elsevier B.V.)

Purpose of Review: This article describes the methods of diagnosis and management of the sensory-predominant polyneuropathies. To simplify the approach to this category of patients, sensory-predominant polyneuropathies are divided broadly into either small fiber (or pain-predominant) neuropathies and large fiber (or ataxia-predominant) neuropathies, of which the sensory neuronopathies (dorsal root ganglionopathies) are highlighted., Recent Findings: Physicians can now easily perform skin biopsies in their offices, allowing access to the gold standard pathologic diagnostic tool for small fiber neuropathies. Additional diagnostic techniques, such as corneal confocal microscopy, are emerging. Recently, small fiber neuropathies have been associated with a broader spectrum of diseases, including fibromyalgia, sodium channel mutations, and voltage-gated potassium channel antibody autoimmune disease., Summary: Despite advances in diagnosing small fiber neuropathies and sensory neuronopathies, many of these neuropathies remain refractory to treatment. In select cases, early identification and treatment may result in better outcomes. "Idiopathic" should be a diagnosis of exclusion and a thorough investigation for treatable causes pursued.

Aim: To quantify muscle strength and size in subjects with impaired glucose tolerance (IGT) in relation to intramuscular non-contractile tissue, the severity of neuropathy and vitamin D level., Methods: A total of 20 subjects with impaired glucose tolerance and 20 control subjects underwent assessment of strength and size of knee extensor, flexor and ankle plantar and dorsi-flexor muscles, as well as quantification of intramuscular non-contractile tissue and detailed assessment of neuropathy and serum 25-hydroxy vitamin D levels., Results: In subjects with impaired glucose tolerance, proximal knee extensor strength (P = 0.17) and volume (P = 0.77), and knee flexor volume (P = 0.97) did not differ from those in control subjects. Ankle plantar flexor strength was significantly lower (P = 0.04) in the subjects with impaired glucose tolerance, with no difference in ankle plantar flexor (P = 0.62) or dorsiflexor volume (P = 0.06) between groups. Intramuscular non-contractile tissue level was significantly higher in the ankle plantar flexors and dorsiflexors (P = 0.03) of subjects with impaired glucose tolerance compared with control subjects, and it correlated with the severity of neuropathy. Ankle plantar flexor muscle strength correlated significantly with corneal nerve fibre density (r = 0.53; P = 0.01), a sensitive measure of small fibre neuropathy, and was significantly lower in subjects with vitamin D deficiency (P = 0.02)., Conclusions: People with impaired glucose tolerance have a significant reduction in distal but not proximal leg muscle strength, which is not associated with muscle atrophy, but with increased distal intramuscular non-contractile tissue, small fibre neuropathy and vitamin D deficiency., (© 2016 Diabetes UK.)

A 42-year-old patient presented with acute allodynia and hyperalgesia in her distal limbs, most severe in the innervation area of the ulnar nerve. The patient developed critical illness myopathy/polyneuropathy after septic shock 5 months prior to her presentation. After exclusion of differential diagnosis, "late onset small fiber neuropathy" after critical illness was diagnosed. Recent studies showed small fiber lesions during critical illness and in follow-up exams, where additionally neuropathic pain were proved. Dysfunction of voltage-gated Sodium channels related to severe insulin resistance during critical illness might explain the pathophysiology, as seen in critical illness myopathy/polyneuropathy. Therefore we recommend cooling, pharmacotherapy with carbamazepin/oxcarbazepine, tricyclic antidepressive agents and peripheral nerve blocks to treat patients with "late onset small fiber neuropathy" after critical illness., (Georg Thieme Verlag KG Stuttgart · New York.)