Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient series

Background and purpose:  North American studies have indicated a high prevalence of impaired glucose tolerance (IGT) in patients with sensory polyneuropathy. We searched for the occurrence of IGT in a Norwegian patient material with polyneuropathy.
Methods:  Seventy patients with symptoms and signs of sensory polyneuropathy were included. Cases with known causes of neuropathy were excluded. All patients underwent a 2 h oral glucose tolerance test (OGTT). Nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsy with assessment of intra-epidermal nerve fibre (IENF) density were performed.
Results:  Sixteen patients (23%) had impaired glucose metabolism (IGM): 2 (3%) were found to have diabetes, 9 (13%) had IGT, 3 (4%) had impaired fasting glucose (IFG) and 2 (3%) both IFG and IGT. About 62% of the patients with IGM and polyneuropathy and 50% of those with chronic idiopathic axonal polyneuropathy (CIAP) had abnormalities on NCS. Reduction of IENF occurred in 37% of the patients with IGM and 43% of those with CIAP.
Conclusions:  Patients with polyneuropathy and IGM had essentially the same degree of involvement of small and large nerve fibres as patients with CIAP. IGT seems less frequent in Norwegian patients with polyneuropathy than reported in North American populations.     

Painful sensory neuropathy: prospective evaluation using skin biopsy

OBJECTIVE: In patients presenting with painful, burning feet with minimal signs of neuropathy, the following questions were addressed: 1) How many of these patients have a peripheral neuropathy? 2) What is the role of skin biopsy in establishing a diagnosis of neuropathy? 3) What conditions are associated with the neuropathy? and 4) What laboratory studies are useful in this patient population? METHODS: A total of 117 consecutive patients referred for evaluation were prospectively studied. All underwent nerve conduction studies (NCS) and a battery of blood tests, including antinerve antibodies. If NCS were normal, a punch biopsy of the skin of the distal leg was performed to ascertain the intraepidermal nerve fiber (IENF) density. In a subset of 32 patients, the sensitivity of skin biopsy was compared to quantitative sudomotor axon test (QSART) and quantitative sensory tests (QST). Results: Three groups emerged. Group 1, with abnormal NCS (n = 60, 34 F/26 M, mean age 60 +/- 14 years), represented 51% of the cohort. The majority had neuropathies of undetermined cause, but 18 (30%) had associated conditions. Group 2, with normal NCS and reduced IENF density (n = 44, 29 F/15 M, mean age 57 +/- 14 years), represented 38% of the cohort. Three in this group had associated conditions. Group 3, with normal NCS and IENF density (n = 13, 6 F/7 M, mean age 53 +/- 13 years), represented 11% of the cohort; most had no diagnoses but two had MS. In a comparative subset analysis, skin biopsy was more sensitive than QSART or QST in diagnosing a neuropathy. CONCLUSIONS: Patients presenting with painful feet are heterogeneous, consisting of both large and small fiber sensory neuropathies. In rare cases, a central cause for pain can be found. Over one-third of patients required a skin biopsy to diagnose a small fiber sensory neuropathy. A limited battery of blood tests facilitated diagnosis, but serum antinerve antibodies were not helpful.     

Near-nerve needle sensory and medial plantar nerve conduction studies in patients with small-fiber sensory neuropathy

Background and purpose:  The aim of this prospective study was to show and compare the rate of large-fiber involvement with near-nerve needle sensory (NNNS) nerve conduction study (NCS) and with medial plantar NCS recorded with surface electrodes in a group of patients who had clinically pure small-fiber sensory neuropathy (SFSN) with reduced intra-epidermal nerve fiber density in skin biopsy and with normal routine NCS.
Methods and results:  The study included 19 patients with clinically pure SFSN with normal routine NCS results and 17 healthy volunteers. Routine NCS, skin biopsy, medial plantar NCS and NNNS NCS were performed. NNNS NCS data were evaluated both by using univariate analysis methods and by using a multivariate analysis method, principal components analysis (PCA). Eight patients (42%) had abnormal results for medial plantar NCS with surface electrodes. Seven patients (37%) had abnormal results for NNNS NCS with PCA, whilst only four patients with univariate analysis. We found a significant correlation between intra-epidermal nerve fiber densities, medial plantar NCS and PCA results of NNNS NCS.
Conclusions:  This study showed that large-nerve fibers are also involved in some patients with pure SFSN and medial plantar NCS can accurately diagnose neuropathy without a need for NNNS NCS in patients with normal routine NCS.     

Corneal confocal microscopy: A novel means to detect nerve fibre damage in idiopathic small fibre neuropathy

Patients with idiopathic small fibre neuropathy (ISFN) have been shown to have significant intraepidermal nerve fibre loss and an increased prevalence of impaired glucose tolerance (IGT). It has been suggested that the dysglycemia of IGT and additional metabolic risk factors may contribute to small nerve fibre damage in these patients.Twenty-five patients with ISFN and 12 aged-matched control subjects underwent a detailed evaluation of neuropathic symptoms, neurological deficits (Neuropathy deficit score (NDS); Nerve Conduction Studies (NCS); Quantitative Sensory Testing (QST) and Corneal Confocal Microscopy (CCM)) to quantify small nerve fibre pathology.Eight (32%) patients had IGT. Whilst all patients with ISFN had significant neuropathic symptoms, NDS, NCS and QST except for warm thresholds were normal. Corneal sensitivity was reduced and CCM demonstrated a significant reduction in corneal nerve fibre density (NFD) (P < 0.0001), nerve branch density (NBD) (P < 0.0001), nerve fibre length (NFL) (P < 0.0001) and an increase in nerve fibre tortuosity (NFT) (P < 0.0001). However these parameters did not differ between ISFN patients with and without IGT, nor did they correlate with BMI, lipids and blood pressure.Corneal confocal microscopy provides a sensitive non-invasive means to detect small nerve fibre damage in patients with ISFN and metabolic abnormalities do not relate to nerve damage.     

Superficial peroneal sensory and sural nerve conduction studies in peripheral neuropathy.

The objective of this study was to prospectively evaluate sensory nerve conduction studies (NCS) in the distal lower limbs in the electrodiagnosis of peripheral neuropathy. We prospectively studied 316 consecutive patients with surface stimulation and recording, in comparison with 90 control subjects. A total of 310 patients were found to have lower limb sensory NCS abnormalities. In these patients, the rate of detection of peripheral neuropathy with superficial peroneal NCS (88.5%) was significantly higher (P<0.001) compared with sural NCS (75%). The superficial peroneal NCS appeared to have a higher detection rate for peripheral neuropathy in our study, and its study can be adjunctive to sural NCS.     

Porphyric neuropathies in an acute intermittent porphyria family

The objective of this study was to investigate two patients with porphyric neuropathy in a family with acute intermittent porphyria. Molecular analysis of the porphobilinogen deaminase (PBGD) gene was performed. We analyzed the clinical course of peripheral neuropathy and serial changes in nerve conduction studies (NCS) of the two patients. We also examined the pathological findings of sural nerve biopsy in one patient. Molecular analysis of the PBGD gene revealed a missense mutation (Arg26His) in exon 2 for two patients and their family members. Distal polyneuropathy was noted in the patients with chronic porphyric neuropathy. In the follow‐up NCS, recovery was relatively poor in the lower limb in one patient with severe polyneuropathy, and NCS evidence of deterioration was found following frequent hormone‐related porphyric attacks in another patient. The sural nerve biopsy showed marked loss of myelinated and unmyelinated fibers in one patient with chronic porphyric neuropathy. In contrast to radial and fibular motor nerves in acute porphyric neuropathy, the sural nerve is vulnerable to involvement in chronic porphyric neuropathy following repeated porphyric attack as seen in the NCS.     

Idiopathic neuropathy patients are at high risk for metabolic syndrome

BACKGROUND: Idiopathic neuropathy patients are at high risk of impaired glucose tolerance (IGT). Hyperglycemia, low high density lipoprotein (HDL), elevated triglycerides (TRG), hypertension and central obesity co-associate and constitute the metabolic syndrome. Patients with hyperglycemia are at high risk of having the syndrome and each of its features. Our null hypothesis was that patients with neuropathy and IGT would have a higher prevalence of other metabolic syndrome features than those without hyperglycemia. The primary objective was to determine if metabolic syndrome features other than hyperglycemia increase neuropathy risk. METHODS: The prevalence of metabolic syndrome features was determined among 219 sequential patients with idiopathic peripheral neuropathy. Subjects were classified as having IGT or normoglycemia. The prevalence of metabolic syndrome was compared to published population prevalence data. To compensate for potential referral bias, data were also compared for175 diabetic subjects without neuropathy, given the well-recognized risk of metabolic syndrome among diabetic individuals. RESULTS: Contrary to our hypothesis, neuropathy patients with normoglycemia and IGT shared a similarly elevated prevalence of metabolic syndrome features compared to published normal populations. Compared to diabetic subjects without neuropathy, the normoglycemic neuropathy patients had significantly higher total and LDL cholesterol, and a higher prevalence of abnormal HDL and triglycerides. The prevalence of obesity and hypertension was similar among patient groups. Normoglycemic neuropathy subjects had significantly more features of metabolic syndrome (other than hyperglycemia) than diabetics. CONCLUSIONS: These findings demonstrate an association between neuropathy and metabolic syndrome features other than hyperglycemia. Lipid abnormalities are particularly prevalent among neuropathy subjects.     

皮肌炎和多发性肌炎175例神经传导检测

目的 研究皮肌炎(dermatomyositis,DM)和多发性肌炎(polymyositis,PM)合并神经传导检测(NCS)异常患者的临床和电生理特点以及病因探讨.方法 收集2005年1月到2008年9月中国医学科学院北京协和医院病房收治的DM或PM确诊病例175例,对其临床和NCS结果进行回顾性分析.结果 175例患者中,NCS异常者66例,其中明确的周围神经病32例(48.5%),不能肯定为周围神经损害者34例(51.5%).合并周围神经损害的DM或PM患者恶性肿瘤(3/32,9.3%)、其他免疫病(6/32,18.8%)的发生率较无周围神经损害的DM或PM患者(4/109,3.7%;7/109,6.4%)有明显增加(X2=13.653,P=0.003).结论 合并周围神经损害的DM或PM患者恶性肿瘤、其他免疫病的发生率明显增加,NCS可以为临床早期诊断提供更多的提示和帮助.     

皮肌炎和多发性肌炎175例神经传导检测

目的 研究皮肌炎(dermatomyositis,DM)和多发性肌炎(polymyositis,PM)合并神经传导检测(NCS)异常患者的临床和电生理特点以及病因探讨.方法 收集2005年1月到2008年9月中国医学科学院北京协和医院病房收治的DM或PM确诊病例175例,对其临床和NCS结果进行回顾性分析.结果 175例患者中,NCS异常者66例,其中明确的周围神经病32例(48.5%),不能肯定为周围神经损害者34例(51.5%).合并周围神经损害的DM或PM患者恶性肿瘤(3/32,9.3%)、其他免疫病(6/32,18.8%)的发生率较无周围神经损害的DM或PM患者(4/109,3.7%;7/109,6.4%)有明显增加(X2=13.653,P=0.003).结论 合并周围神经损害的DM或PM患者恶性肿瘤、其他免疫病的发生率明显增加,NCS可以为临床早期诊断提供更多的提示和帮助.     

Medial plantar and dorsal sural nerve conduction studies increase the sensitivity in the detection of neuropathy in diabetic patients.

OBJECTIVE: Clinical utility of nerve conduction studies (NCS) of the medial plantar and dorsal sural nerves in the early detection of polyneuropathy have already been shown separately. However, at present, there is no data about the combined assessment of these two nerves in distal sensory neuropathy. In the present study, we aimed to evaluate the medial plantar and dorsal sural NCS in a group of diabetic patients with distal sensory neuropathy (DSN) and in healthy controls. METHODS: Thirty healthy and 30 diabetic adult patients were included. In all subjects, peripheral motor and sensory NCS were performed bilaterally with surface electrodes on the lower limbs including medial plantar and dorsal sural nerves. In addition, motor and sensory nerves were studied unilaterally on the upper limb. RESULTS: In all patients, nerve action potential (NAP) amplitudes of sural and superficial peroneal nerves were within normal ranges, but in the patient group mean value was significantly lower than in the controls. Among clinically defined 30 DSN patients, medial plantar NAP amplitude was abnormal in 18 (60%) and dorsal sural nerve amplitude was abnormal in 13 (40%) of the patients bilaterally. Additionally, the onset NCV of the dorsal sural nerve was significantly slower in patients than controls (P=0.038). Evaluation of both of these nerves increased the sensitivity up to 70% in the detection of neuropathy. CONCLUSIONS: Bilateral NCS assessment of both of the medial plantar and dorsal sural nerves together increases the rate of diagnosis of diabetic distal sensory neuropathy compared to assessment of either of these nerves. SIGNIFICANCE: Assessment of medial plantar in addition to dorsal sural NCS together increases the sensitivity in the detection of neuropathy and allows earlier diagnosis, especially when routine NCS are normal.     

Class of nerve fiber involvement in sensory neuropathies: clinical characterization and utility of the plantar nerve action potential

Nerve conduction studies (NCS) in diabetic sensorimotor polyneuropathy (DSP) are sensitive, noninvasive, and associated with small coefficients of variation, and correlate well with underlying peripheral nerve morphological change. For these reasons, the current reference standard for DSP involves multivariate instruments that emphasize NCS results. However, the interside symmetry of NCS findings in different stages of DSP are unknown, although requirement for symmetry has been suggested in clinical trials of DSP. We therefore aimed to determine the degree of symmetry of NCS findings in DSP of differing severity stages. A cohort of diabetic patients, including patients without neuropathy and those with mild to severe DSP, was studied. We also studied a series of nondiabetic, healthy subjects. A variation of stratified sampling by means of a clinical neuropathy score ensured that a broad spectrum of neuropathy was studied. A total of 478 subjects was ascertained; patient accrual was discontinued when the smallest clinical group consisted of 50 subjects. Nerve conduction studies were conducted prospectively and in a blinded fashion using surface recordings, averaging for sensory action potentials, control of limb temperature, and standardized techniques. Median and ulnar motor and sensory, peroneal and tibial motor, and sural NCS were performed. Interside symmetry, independent of neuropathy severity, was observed for all investigated nerves, except for the median sensory nerve action potential amplitude, which was lower on the right side. These results confirm that abnormal NCS findings consistent with DSP are reliably symmetrical with the exception of the amplitude of the median sensory nerve action potential. Thus, unilateral evaluation of NCS in DSP is sufficient as a reference standard in clinical trials. We also conclude that great degrees of asymmetry in NCS results are reason to question inclusion of DSP patients in clinical trials.     

Peroneal neuropathy after weight loss

The objectives of this study were to evaluate the clinical and electrophysiological findings in peroneal mononeuropathies following a weight-reduction diet. Thirty patients with acute peroneal palsy and weight loss were studied. Complete nerve conduction studies (NCS) were performed in upper and lower limbs. NCS showed conduction block (CB) of the peroneal nerve at the fibular head that recovered in 29 patients within 3 weeks to 3 months. Severity of CB was correlated with clinical weakness. Three patients had abnormalities consistent with polyneuropathy (PNP). NCS in asymptomatic relatives confirmed familial neuropathy. Nerve biopsy and molecular study were consistent with hereditary neuropathy with liability to pressure palsies (HNPP). One of these peroneal palsies (6 months) recovered after neurolysis. Weight loss might be a risk factor in peroneal mononeuropathies. NCS is a tool in the diagnosis of the site and severity of the nerve injury. Testing should be considered for relatives of patients with PNP because peroneal mononeuropathies may be the first expression of HNPP.     

Restless legs syndrome in diabetic neuropathy: a frequent manifestation of small fiber neuropathy

As the occurrence of restless legs syndrome (RLS) in diabetes is controversial, the aim of this study was to assess the prevalence of RLS in a cohort of patients with diabetic neuropathy and to analyze the features of the associated neuropathy. We investigated the occurrence of RLS diagnosed in accordance with the criteria of the International Restless Legs Syndrome Study Group in a cohort of patients with polyneuropathy and mononeuropathy multiplex associated with diabetes mellitus (DM), or impaired glucose tolerance (IGT), or impaired fasting glucose (IFG) in a retrospective study. RLS was present in 33/99 patients with neuropathy associated with DM/IGT/IFG (84 with distal polyneuropathy and 15 with multiple mononeuropathy). Comparing patients with or without RLS, small fiber sensory neuropathy was more common in the RLS patients (15/33 vs. 15/66), as were symptoms of burning feet (10/33 vs. 6/66). In several patients, RLS was responsive to neuropathic pain medications. The frequent occurrence of RLS in association with thermal dysesthesias may reflect the involvement of small sensory fibers in the form of hyperexcitable C fibers or A-delta fiber deafferentation. We suggest that RLS may be triggered by abnormal sensory inputs from small fibers, especially involved in neuropathy associated with DM/IGT/IFG. Our data show that RLS is a relevant feature of diabetic neuropathy, as a frequent and potentially treatable manifestation of small fiber involvement in the course of DM and IGT/IFG.     

Medial calcaneal neuropathy is associated with plantar fasciitis.

OBJECTIVE: To demonstrate a method of sensory nerve conduction study (NCS) for the medial calcaneal nerve (MCN) and confirm the medial calcaneal neuropathy in patients with plantar fasciitis (PF). METHODS: Twenty-six patients with clinical and ultrasonographic diagnosis of PF participated in the present study. An antidromic method for sensory NCS of MCN was performed in each patient and in 30 controls. The conduction latency, sensory nerve conduction velocity (SNCV) and amplitude of the sensory nerve action potential (SNAP) were measured and the correlation of the SNCV of MCN with both body weight and body mass index (BMI) was studied. RESULTS: The mean conduction latency obtained in the MCN was greater in the PF patients than in the normal controls. Mean SNCV and SNAP amplitude of the MCN were significantly less in the PF patients than in the normal controls. Body weight and BMI were greater in PF patients than in controls. Six patients were identified as having a medial calcaneal neuropathy by using the criteria of the lowest normal values of the NCS of MCN from the normal controls. CONCLUSIONS: Medial calcaneal neuropathy is associated with PF. The present method of sensory NCS is useful and objective in the diagnosis of the medial calcaneal neuropathy. SIGNIFICANCE: Medial calcaneal neuropathy was confirmed by the sensory NCS of MCN and shown to be associated with PF.     

Intraepidermal nerve fibre density, quantitative sensory testing and nerve conduction studies in a patient material with symptoms and signs of sensory polyneuropathy

Small diameter nerve fibre (SDNF) neuropathy is an axonal sensory neuropathy affecting unmyelinated (C) and thin myelinated (A-delta) fibres. We have evaluated 75 patients with symptoms and signs suggesting SDNF dysfunction with or without symptoms and signs of co-existing large diameter nerve fibre involvement. The patients were examined clinically and underwent skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS). The purpose of this study was to compare the relationship between the different methods and in particular measurements of thermal thresholds and intraepidermal nerve fibre (IENF) density in the same site of the distal leg. The main subdivision of the patient material was made according to the overall NCS pattern. Patients with normal NCS (38) had 6.4 +/- 3.8 and patients with abnormal NCS (37) had 4.4 +/- 3.4 IENF per mm (P = 0.02). Limen (difference between warm and cold perception thresholds) was significantly higher (more abnormal) in those with abnormal than in those with normal NCS (22.1 +/- 9.1 vs. 13.4 +/- 5.6, P < 0.0001). Cold perception threshold was more abnormal (P < 0.0001) than warm perception threshold (P = 0.002). Correlation between IENF and QST was statistically significant only when NCS was abnormal, and thus dependent of a more severe neuropathic process in SDNFs.     

Interdigital nerve conduction study of the foot for an early detection of diabetic sensory polyneuropathy.

OBJECTIVE: To report on the value of interdigital nerve (IDN) conduction study (NCS) of the foot for the recognition of diabetic sensory polyneuropathy with normal routine NCS and the nature of electrophysiological abnormality in early diabetic sensory polyneuropathy. METHODS: The sensory nerve conductions in the two digital and 4 IDNs of the foot were obtained orthodromically using the near-nerve needle and signal averaging technique. RESULTS: In 21 patients with diabetic sensory polyneuropathy with normal routine NCS, a definite neuropathy pattern (abnormalities in more than 3 of 6 tested nerves) was observed in 12 patients (57.1%). The most common abnormalities that were found were a low amplitude in the sensory compound nerve action potential and an absent potential, indicating that early diabetic sensory polyneuropathy is due to axonal degeneration. CONCLUSIONS: Interdigital NCS of the foot using near-nerve needle technique can identify neuropathy in diabetic sensory polyneuropathy with normal routine NCS. This technique offers a useful means of detecting nerve conduction abnormalities in the early stage of diabetic polyneuropathy.     

Paired stimulation study of the median nerve sensory action potential in diabetic patients

Objectives –  Conventional nerve conduction studies (NCS) are not sensitive to detect mild diabetic neuropathy. In order to detect subtle changes, we compared the conventional NCS with the relative refractory period (RRP) measurement of the median sensory nerve action potential by a paired stimulation method.
Methods –  Subjects were 29 diabetic patients whose conventional NCS were all normal. They were divided into two groups: neurologically symptomatic and asymptomatic groups. Twenty-eight age-matched control subjects were also studied.
Results –  The RRP of the symptomatic diabetic patients (5.9 ± 0.5 ms) and that of the asymptomatic patients (5.6 ± 0.5 ms) was significantly longer than that of the control subjects (4.9 ± 0.6 ms). There was no significant difference in RRP between the symptomatic and asymptomatic patients. This may be due to the fact that NCS reflects mainly large myelinated fiber function and early symptoms represent mainly thin myelinated or unmyelinated fiber function.
Conclusions –  The RRP measurement could reveal some mild involvement of peripheral nerves undetectable by conventional NCS, even though they caused no clinical symptoms.     

Carpal tunnel syndrome in childhood: study of 6 cases

Six children, 4 girls and two boys, aged 5–14 years, with carpal tunnel syndrome (CTS) are reported. Median nerve entrapment had different aetiologies in each case. One patient developed unilateral CTS symptoms after intensive basketball training. He improved upon terminating this sporting activity. In 3 patients bilateral CTS was associated with Schwartz-Jampel syndrome, trigger finger and mucopolysaccharidosis I (MPS IS=Scheie syndrome), respectively. The latter subject, a boy aged 11 years who had severe bilateral muscle thenar weakness and atrophy, made a good recovery after surgery. Two cases with bilateral CTS had autosomal dominant disease. One of them showed familial CTS with thickening of the transverse carpal ligament. The other child (5 years old) presented early bilateral CTS as first manifestation of hereditary neuropathy with liability to pressure palsies (HNPP). His relatives were asymptomatic, but they showed electrophysiological and nerve biopsy changes consistent with HNPP. Nerve conduction studies (NCS) are diagnostic in paediatric CTS. Moreover, NCS is an objective method to evaluate the evolution of the nerve lesions after surgery. NCS must be performed in nerves of the propositus other than the median, as well as in first degree symptomatic and asymptomatic relatives in order to identify possible familial neuropathies.     

Peripheral neuropathy associated with chronic natural killer cell lymphocytosis

We report a patient with steroid-responsive peripheral neuropathy which developed with chronic natural killer cell lymphocytosis (CNKL). A 70-year-old female with a 2-week history of progressive motor and sensory neuropathy showed a marked increase of natural killer (NK) cells in the blood, and was diagnosed as having CNKL. Nerve conduction studies (NCS) revealed a mixed axonal and demyelinating neuropathy. A sural nerve biopsy revealed infiltration of NK cells into the nerve fascicles, and demyelinating changes with axonal degeneration. The infiltrating NK cells were adjacent to myelinated fibers, showing damage of Schwann cell membrane. Treatment with oral prednisolone resulted in rapid improvement of the sensory disturbance and weakness with a significant decrease of NK cells in the blood and disappearance of the conduction blocks in NCS. This is the first case of CNKL associated neuropathy in which infiltration of NK cells was demonstrated in the nerve fascicles. Our observations suggest that the infiltrating NK cells may directly damage myelin and Schwann cells, thus causing demyelination.     

Evaluation of dermal myelinated nerve fibers in diabetes mellitus

Skin biopsies have primarily been used to study the non‐myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non‐hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age‐matched healthy controls (age 29–73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.