How different experimental models of secondary hyperalgesia change the nociceptive flexion reflex.

OBJECTIVE: In this neurophysiological study in healthy humans, we assessed how central sensitization induced by either high-frequency stimulation (HFS) or topical capsaicin application modulates features of the RIII reflex response. The ability of these stimuli to engage the endogenous pain modulatory system was also tested. METHODS: In 26 healthy participants we elicited an RIII reflex using suprathreshold stimulation of the sural nerve. Subsequently HFS or capsaicin were applied to the foot and the RIII reflex repeated after 15 minutes. Contact heating of the volar forearm served as the heterotopic test stimulus to probe activation of the endogenous pain modulatory system. RESULTS: HFS significantly reduced the pain threshold by 29% and the RIII reflex threshold by 20%. Capsaicin significantly reduced the pain threshold by 17% and the RIII reflex threshold by 18%. Both HFS and capsaicin left RIII reflex size unaffected. Numerical Rating Scale (NRS) pain scores elicited by the heterotopic noxious heat stimulus were unaffected by capsaicin and slightly increased by HFS. CONCLUSIONS: HFS and capsaicin similarly modulated the pain threshold and RIII reflex threshold, without a concomitant inhibitory effect of the endogenous pain modulatory system. SIGNIFICANCE: Our neurophysiological study supports the use of the RIII reflex in investigating central sensitization in humans.

Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy.

OBJECTIVE: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures. METHODS: In this retrospective cohort study, we measured the accumulation of large mtDNA deletions in skin biopsies from PWH recruited as part of the AIDS Clinical Trials Group (ACTG). Our cohort includes individuals with and without sensory neuropathy, as well as individuals with normal or abnormal skin biopsies. Skin biopsies, sural and peroneal nerve conduction studies, total neuropathy score, and deletion burden scores were measured, along with baseline demographic data such as age, CD4+ cell count, viral counts, and prior nucleoside reverse transcriptase inhibitor exposures. RESULTS: Sixty-seven PWH were enrolled in the study. The mean age of the cohort (n = 67) was 44 years (SD 6.8, range 32-65 years), and 9 participants were female. The mean CD4+ T-cell count was 168 cells/mm3 (SD 97 cells/mm3, range 1-416 cells/mm3) and mean viral load was 51,129 copies/mL (SD 114,586 copies/mL, range 147-657,775 copies/mL). We determined that there was a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) (r = -0.344, p = 0.04) and sural nerve amplitude (r = -0.359, p = 0.004). CONCLUSIONS: Both IENFD and sural nerve amplitude statistically correlate with mitochondrial mutation burden in PWH, specifically in those with HIV-associated sensory neuropathy as assessed by skin biopsy.

Bilirubin is inversely related to diabetic peripheral neuropathy assessed by sural nerve conduction study.

AIMS/INTRODUCTION: Diagnosis of diabetic peripheral neuropathy (DPN) depends on subjective findings, certain investigations for DPN risks have not been performed enough. Bilirubin protects against vascular complications by reducing oxidative stress in diabetes, but is not fully tested for DPN. This study aimed to evaluate sural nerve conduction impairments (SNCI) as an objective DPN marker and the contribution of bilirubin to SNCI. MATERIALS AND METHODS: Using DPN-Check® , SNCI was defined as a decline of amplitude potential or conduction velocity below the normal limit in 150 inpatients with diabetes. The correlations between SNCI and conventional DPN diagnosis criteria, the incidence of diabetic retinopathy/nephropathy, biomarkers for atherosclerosis, cardiac function by ultrasonic cardiogram, and bilirubin were statistically tested, followed by the comparison of logistic regression models for SNCI to find confounders with bilirubin. RESULTS: The incidence of SNCI was 72.0%. The sensitivity and specificity of SNCI for DPN prediagnosis by simplified criteria were 54.6 and 90.5%, respectively, and similarly corresponded with diabetic retinopathy and nephropathy (sensitivity 57.4 and 50.0%, respectively). SNCI significantly related to diabetes duration, declined estimated glomerular filtration rate, albuminuria and total bilirubin. SNCI incidence was attenuated in the higher bilirubin tertiles (89.8/65.3/54.8%, P < 0.001). Bilirubin was an independent inverse risk factor for SNCI, even after adjustment by known risk factors for DPN and markers for microvascular complications. CONCLUSIONS: SNCI is a comprehensive marker for diabetic complications. We first showed the independent inverse relationship between bilirubin and SNCI through the independent pathway with other complications, provably reducing oxidative stress, as previously reported.

Whole plantar nerve conduction study: A new tool for early diagnosis of peripheral diabetic neuropathy.

AIMS: Peripheral neuropathy (PN) affects two-thirds of type 2 diabetes patients (T2DM). According to diabetic PN length-dependent pattern, neurophysiological evaluation of foot-sole nerves might increase NCS diagnostic sensitivity, hence allowing early diagnosis of PN. Thus, we aim to assess the ability of whole plantar nerve (WPN) conduction in diabetic PN early diagnosis. METHODS: This is a single center prospective observational cohort study on 70 T2DM patients referred to Internal Medicine Unit of A.O.U. "Luigi Vanvitelli" between October 2019/October 2020. Primary endpoint was WPN efficacy assessment in PN early detection. As secondary, we evaluated (i) a potential cut-off of SNAPs amplitude by WPN and (ii) WPN diagnostic accuracy vs. gold-standard distal sural nerve conduction. RESULTS: ROC curve analysis allowed to establish two potential cut-offs for people aged ≤60 years (AUROC: 0.83, 95%CI: 0.69-0.96, p < 0.001) and ≤60 years (AUROC: 0.76, 95%CI: 0.59-0.93, p = 0.017). In depth, we fixed a cut-off of WPN-SNAP amplitude of 4.55 µV and 2.65 µV, respectively, with subsequent 48 patients classified as PN-T2DM. CONCLUSIONS: Our data support WPN conduction study reliability in characterizing the most distal sensory nerve fibers at lower limbs. Thus, WPN may represent an extremely useful diagnostic tool for diabetic PN early detection.

Performance analysis of noninvasive electrophysiological methods for the assessment of diabetic sensorimotor polyneuropathy in clinical research: a systematic review and meta-analysis with trial sequential analysis.

Despite the availability of various clinical trials that used different diagnostic methods to identify diabetic sensorimotor polyneuropathy (DSPN), no reliable studies that prove the associations among diagnostic parameters from two different methods are available. Statistically significant diagnostic parameters from various methods can help determine if two different methods can be incorporated together for diagnosing DSPN. In this study, a systematic review, meta-analysis, and trial sequential analysis (TSA) were performed to determine the associations among the different parameters from the most commonly used electrophysiological screening methods in clinical research for DSPN, namely, nerve conduction study (NCS), corneal confocal microscopy (CCM), and electromyography (EMG), for different experimental groups. Electronic databases (e.g., Web of Science, PubMed, and Google Scholar) were searched systematically for articles reporting different screening tools for diabetic peripheral neuropathy. A total of 22 studies involving 2394 participants (801 patients with DSPN, 702 controls, and 891 non-DSPN patients) were reviewed systematically. Meta-analysis was performed to determine statistical significance of difference among four NCS parameters, i.e., peroneal motor nerve conduction velocity, peroneal motor nerve amplitude, sural sensory nerve conduction velocity, and sural sensory nerve amplitude (all p < 0.001); among three CCM parameters, including nerve fiber density, nerve branch density, and nerve fiber length (all p < 0.001); and among four EMG parameters, namely, time to peak occurrence (from 0 to 100% of the stance phase) of four lower limb muscles, including the vastus lateralis (p < 0.001), tibialis anterior (p = 0.63), lateral gastrocnemius (p = 0.01), and gastrocnemius medialis (p = 0.004), and the vibration perception threshold (p < 0.001). Moreover, TSA was conducted to estimate the robustness of the meta-analysis. Most of the parameters showed statistical significance between each other, whereas some were statistically nonsignificant. This meta-analysis and TSA concluded that studies including NCS and CCM parameters were conclusive and robust. However, the included studies on EMG were inconclusive, and additional clinical trials are required.

The Effect of Total Hip Arthroplasty on the Sciatic Nerve: an Electrodiagnostic Evidence Study.

OBJECTIVE: Objectively evaluate the incidence of sciatic nerve injury after a total hip arthroplasty (THA) performed through a posterolateral approach. METHODS: Patients scheduled to undergo THA were evaluated preoperatively and postoperatively with electrophysiologic studies, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) questionnaire and other methods described in the study. Patients older than 21 years with any of the following preoperative diagnoses: primary or secondary osteoarthritis, aseptic avascular necrosis, rheumatoid arthritis, and posttraumatic arthritis were included. Variables used for analysis were sex, age, and body mass index (BMI). The Mann-Whitney U and Wilcoxon tests and, Pearson and Spearman correlation statistics were used for analysis of categorical and continuous data respectively. RESULTS: Electrodiagnostic data showed alterations in 17 patients (70.8%). No signs of sciatic nerve injury. The mean preoperative and postoperative WOMAC scores were 40 and 74, respectively (p = 0.0001). Statistical differences were noted in sural sensory amplitude (SSA) and distal amplitude of the tibialis motor nerve in the female group (p=0.007; p=0.036, respectively). The SSA also demonstrated differences in the obese group (p=0.008). In terms of age, both the SSA (Pearson p=0.010 and Spearman p=0.024) and the proximal latency of the peroneal motor nerve (Pearson p=0.026 and Spearman p=0.046) demonstrated a decrease in amplitude and an increase in latency that was inversely related with age. CONCLUSION: According to our subclinical electrophysiological findings, surgeons that use the posterolateral approach in THA procedures must be conscious of the sciatic nerve's vulnerability to reduce possible clinical complications.

[A case of polyradiculoneuritis associated with disseminated herpes zoster].

A 34-year-old man developed right-dominant lower limb paraplegia, and then upper limb paresis with radicular pain following disseminated herpes zoster (HZ) in his right forehead, back of the trunk, and lumbar and right lower limb regions. Cerebrospinal fluid (CSF) findings revealed an increase in lymphocytes (32 cells/µl) and protein content (50 mg/dl), and polymerase chain reaction (PCR) for varicella-zoster virus (VZV) DNA was negative in CSF, but VZV antigen was positive in the patient's vesicle smear. Lumbar root MRI using 3D Nerve VIEW (Philips) imaging showed high-intensity lesions on the L2-L5 spinal roots with contrast enhancements, and cervical MRI showed similar findings on both sides at the C4-Th1. Peripheral nerve conduction study revealed prolonged distal latency to 4.9 ms, decreased MCV to 38 m/s, and complete loss of F-wave was seen in the right peroneal nerve study. Minimal F-wave latency was prolonged in the right tibial nerve. Thus, the patient was diagnosed with VZV polyradiculoneuritis caused by disseminated HZ. Regarding the possible pathogenesis of polyradiculoneuritis in this patient with disseminated HZ, we speculate that VZV reached by retrograde transmission from the involved peripheral nerves to the spinal ganglia, which, then, produced polyradiculoneuritis.

Charcot-Marie-Tooth disease type 1A: Longitudinal change in nerve ultrasound parameters.

BACKGROUND: This study aimed to elucidate the longitudinal changes in nerve ultrasound parameters of adult Charcot-Marie-Tooth disease type 1A (CMT1A) patients. METHODS: Fifteen adult patients with CMT1A prospectively underwent nerve ultrasound and clinical assessment (CMT neuropathy score [CMTNS]) at baseline and 5 y later. Nerve cross-sectional area (CSA) and echogenicity were measured in the median and sural nerves. Changes in ultrasound parameters and CMTNS and correlation between changes of ultrasound parameters and CMTNS were analyzed. RESULTS: Median and sural nerve CSAs did not change over 5 y, although CMTNS increased (P < .01). Nerve echogenicity in the sural nerve decreased over 5 y (P = .045). No correlations between changes in nerve ultrasound parameters and CMTNS were identified. CONCLUSIONS: No longitudinal changes in nerve size was detected in adult CMT1A. Exploring the factors that determine nerve size in childhood CMT1A may lead to the development of treatments.

MScanFit motor unit number estimation and muscle velocity recovery cycle recordings in diabetic polyneuropathy.

OBJECTIVE: Motor Unit Number Estimation (MUNE) methods may be valuable in tracking motor unit loss in diabetic polyneuropathy (DPN). Muscle Velocity Recovery Cycles (MVRCs) provide information about muscle membrane properties. This study aimed to examine the utility of the MScanFit MUNE in detecting motor unit loss and to test whether the MVRCs could improve understanding of DPN pathophysiology. METHODS: Seventy-nine type-2 diabetic patients were compared to 32 control subjects. All participants were examined with MScanFit MUNE and MVRCs in anterior tibial muscle. Lower limb nerve conduction studies (NCS) in peroneal, tibial and sural nerves were applied to diagnose large fiber neuropathy. RESULTS: NCS confirmed DPN for 47 patients (DPN + ), with 32 not showing DPN (DPN-). MScanFit showed significantly decreased MUNE values and increased motor unit sizes, when comparing DPN + patients with controls (MUNE = 71.3 ± 4.7 vs 122.7 ± 3.8), and also when comparing DPN- patients (MUNE = 103.2 ± 5.1) with controls. MVRCs did not differ between groups. CONCLUSIONS: MScanFit is more sensitive in showing motor unit loss than NCS in type-2 diabetic patients, whereas MVRCs do not provide additional information. SIGNIFICANCE: The MScanFit results suggest that motor changes are seen as early as sensory, and the role of axonal membrane properties in DPN pathophysiology should be revisited.

Macroscopic changes in sural nerve after gastrocnemius recession: a cadaver study.

BACKGROUND: Gastrocnemius recession is a common foot and ankle procedure and various techniques that have been utilized are mainly delineated by the anatomic position of the gastrocnemius transection; the 2 common ones are the Baumann and Strayer procedure. Both can adversely affect the sural nerve. The objective of this study was to evaluate the macroscopic changes in the sural nerve following gastrocnemius recession, and to compare the efficacy of the two procedures, regarding the improvement of maximal ankle dorsiflexion. METHODS: Ten fresh-frozen, above knee cadaveric legs were assigned to one of two gastrocnemius recession techniques: Baumann (n = 5) or Strayer (n = 5). A goniometer was used to measure degree of ankle dorsiflexion before and after the surgery. The sural nerve was meticulously dissected and marked with two suture knots, 2 cm apart. The ankle was passively dorsiflexed from 90° to maximal dorsiflexion in 5° degree increments, and the distance between two suture knots was measured at each increment. The distance between the two cut ends of gastrocnemius muscle was measured with the ankle at 90° and at maximal dorsiflexion. RESULTS: Overall, a mean increase in length between the suture knots on the sural nerve was 0.2 cm, from 90° to maximum ankle dorsiflexion (130°); both the Baumann and Strayer techniques resulted in 0.2 cm increase. The mean improvement in maximal ankle dorsiflexion in the Baumann and Strayer group was 22.6° and 22°, respectively. The mean change in distance between the two cut ends of the gastrocnemius muscle in the Baumann and Strayer group was 1.0 cm and 0.9 cm, respectively. CONCLUSION: Increased dorsiflexion of the ankle following Strayer or Baumann gastrocnemius recession resulted in similar macroscopic change in the sural nerve, which may contribute to the development of sural neuritis. Further clinical studies are warranted to assess clinical implications of these findings.

Multifocal, hypoechogenic nerve thickening in Cerebrotendinous Xanthomatosis.

OBJECTIVE: To characterize peripheral nerve morphology in cerebrotendinous xanthomatosis (CTX) patients using high-resolution ultrasound (HRUS) in vivo. We hypothesized that nerve enlargements might be present in CTX as a result of accumulation of abnormal lipids with deposition also in peripheral nerves. METHODS: Four CTX patients were examined using HRUS to assess morphological abnormalities of peripheral nerves as well as cervical nerve roots 5 and 6. RESULTS: HRUS revealed mild to moderate, hypoechogenic thickening of sensorimotor nerves (ulnar nerve in 1/4, tibial nerve in 3/4, median nerve 4/4 patients) as well as mild enlargement of pure sensory nerves (sural nerve in 2/3, superficial FN in 2/4 patients). The vagal nerve was moderately enlarged in one patient, cervical roots showed moderate enlargements of C5 in two patients, one of which also showing thickening of C6 as well as in another patient. UPSS score was slightly to moderately abnormal in all patients. The Homogeneity score was not increased suggesting regional to inhomogeneous nerve enlargement. CONCLUSIONS: HRUS shows multifocal, hypoechogenic nerve thickening of peripheral nerves and nerve roots in CTX. SIGNIFICANCE: HRUS might serve as a valuable, additive and non-invasive bedside tool to assess peripheral nerve morphology in future clinical studies on CTX patients.

The influence of nociceptive and neuropathic pain states on the processing of acute electrical nociceptive stimulation: A dynamic causal modeling study.

INTRODUCTION: Despite the worldwide increase in prevalence of chronic pain and the subsequent scientific interest, researchers studying the brain and brain mechanisms in pain patients have not yet clearly identified the exact underlying mechanisms. Quantifying the neuronal interactions in electrophysiological data could help us gain insight into the complexity of chronic pain. Therefore, the aim of this study is to examine how different underlying pain states affect the processing of nociceptive information. METHODS: Twenty healthy participants, 20 patients with non-neuropathic low back-related leg pain and 20 patients with neuropathic failed back surgery syndrome received nociceptive electrical stimulation at the right sural nerve with simultaneous electroencephalographic recordings. Dynamic Causal Modeling (DCM) was used to infer hidden neuronal states within a Bayesian framework. RESULTS: Pain intensity ratings and stimulus intensity of the nociceptive stimuli did not differ between groups. Compared to healthy participants, both patient groups had the same winning DCM model, with an additional forward and backward connection between the somatosensory cortex and right dorsolateral prefrontal cortex. DISCUSSION: The additional neuronal connection with the prefrontal cortex as seen in both pain patient groups could be a reflection of the higher attention towards pain in pain patients and might be explained by the higher levels of pain catastrophizing in these patients. CONCLUSION: In contrast to the similar pain intensity ratings of an acute nociceptive electrical stimulus between pain patients and healthy participants, the brain is processing these stimuli in a different way.

Neuromuscular ultrasound for taxane peripheral neuropathy in breast cancer.

BACKGROUND: Our study aim was to evaluate neuromuscular ultrasound (NMUS) for the assessment of taxane chemotherapy-induced peripheral neuropathy (CIPN), the dose-limiting toxicity of this agent. METHODS: This cross-sectional study of breast cancer patients with taxane CIPN measured nerve cross-sectional area (CSA) by NMUS and compared with healthy historical controls. Correlations were determined between CSA and symptom scale, nerve conduction studies, and intraepidermal nerve fiber density (IENFD). RESULTS: A total of 20 participants reported moderate CIPN symptoms at a median of 3.8 months following the last taxane dose. Sural nerve CSA was 1.2 mm2 smaller than healthy controls (P ≤ .01). Older age and time since taxane were associated with smaller sural nerve CSA. For each 1 mm2 decrease in sural nerve CSA, distal IENFD decreased by 2.1 nerve/mm (R2 0.30; P = .04). CONCLUSIONS: These data support a sensory predominant taxane neuropathy or neuronopathy and warrant future research on longitudinal NMUS assessment of CIPN.

Prevalence of denervation in the intrinsic foot muscles in patients with distal predominantly small fiber neuropathy.

BACKGROUND: We aimed to evaluate the significance of electromyographic findings in the intrinsic foot muscles (IFMs) of patients with skin biopsy proven small fiber neuropathy (SFN). METHODS: This was a single-center retrospective analysis of patients who underwent skin biopsy for intra-epidermal nerve fiber density (IENFD) measurement and electrodiagnostic (EDX) study for evaluation of polyneuropathy. RESULTS: A total of 1416 patents with normal lower extremity EDX studies proximal to the foot were included. Active denervation was seen in 16.1% of IFMs in patients with skin biopsy proven SFN and 4.1% of patients without SFN (P < .0001). Reinnervation changes without active denervation were observed in 30.4% of SFN patients and 23.8% of patients without SFN (P = .01). IENFD was lower in SFN patients with active denervation in IFMs than without (P < .0001). CONCLUSIONS: Evaluation of active denervation in the IFMs can reveal large fiber dysfunction in SFN patients with otherwise normal routine EDX findings.

Injury of Muscular but not Cutaneous Nerve Drives Acute Neuropathic Pain in Rats.

Acute pain is a common complication after injury of a peripheral nerve but the underlying mechanism is obscure. We established a model of acute neuropathic pain via pulling a pre-implanted suture loop to transect a peripheral nerve in awake rats. The tibial (both muscular and cutaneous), gastrocnemius-soleus (muscular only), and sural nerves (cutaneous only) were each transected. Transection of the tibial and gastrocnemius-soleus nerves, but not the sural nerve immediately evoked spontaneous pain and mechanical allodynia in the skin territories innervated by the adjacent intact nerves. Evans blue extravasation and cutaneous temperature of the intact skin territory were also significantly increased. In vivo electrophysiological recordings revealed that injury of a muscular nerve induced mechanical hypersensitivity and spontaneous activity in the nociceptive C-neurons in adjacent intact nerves. Our results indicate that injury of a muscular nerve, but not a cutaneous nerve, drives acute neuropathic pain.

The Slipping Slipper Sign: A Poor Man's Test for Severe Diabetic Peripheral Neuropathy.

BACKGROUND: Neuropathic feet are at very high risk for infection and amputation. The slipping slipper sign (SSS) is elicited by a simple questionnaire test reported to detect the presence of severe diabetic peripheral neuropathy. This test can be administered by non-medical staff. In this study, subjects with and without the SSS were evaluated by nerve conduction studies (NCS) and ultrasound measurements of the right sural nerve diameters as well as with traditional scoring systems for peripheral and autonomic neuropathy. OBJECTIVE: To demonstrate that the Slipping Slipper Sign can be used as an index of severe diabetic peripheral neuropathyMethod:This was a prospective cross sectional study in which 74 patients with diabetes (38 positive and 36 negative for SSS) underwent ultrasonography and NCS of the right sural nerve by an examiner blinded to SSS status. Findings were evaluated against demography, clinical history, anthropometry as well as traditional clinical and autonomic neuropathic scores. RESULTS: Patients without the SSS [median (IQR) = 10.0 years (4.0-20.3)] had a significantly shorter duration of diabetes compared with those with the SSS [median (IQR) = 15.0 years (8.5-25.0)], p = 0.028. The frequencies of retinopathy (36.8% vs 2.8%, p <  0.05) and cerebrovascular accidents (18.4% vs 13.9 %, p <  0.05) were higher among those with SSS compared with those without. Differences in nerve conduction characteristics were markedly significant. The amplitude of the sural sensory nerve action potential (SNAP) was ([median (IQR)] 0 microvolts vs 4.0 microvolts (0.0-10.8) p <  0.002) between those with and without SSS, respectively whilst none of patients with SSS had a recordable SNAP vs 78% without a SSS. Similarly, maximal thickness of the right sural nerve at the ankle 3.0 mm (2.3-3.4) vs 3.5 mm (3.0-3.9), and leg 3.4 mm (2.7-3.8) vs 3.9 mm (3.3-4.2) was reduced, p <  0.01 in patients with the SSS compared with those with a negative SSS. CONCLUSION: The SSS identifies feet with objective neurophysiological and imaging characteristics of severe neuropathy.

Sonographic assessment of nerve blood flow in diabetic neuropathy.

AIMS: To undertake sonographic assessment of nerve blood flow in people with Type 2 diabetes and correlate the findings with neuropathy severity scores and electrophysiological measurements. METHODS: Median and tibial nerve ultrasound scans were undertaken in 75 people with diabetes and 30 aged-matched controls without diabetes, using a high-resolution linear probe at non-entrapment sites. Nerve blood flow was quantified using power Doppler techniques to obtain the vessel score and the maximum perfusion intensity. Neuropathy severity was assessed using a total neuropathy score. RESULTS: Diabetic nerves had higher rates of nerve blood flow detection (28%) compared to the control group (P < 0.0001). Significant correlations were found between nerve blood flow measurements and nerve size (P <0.001), reported sensory symptoms (P < 0.05) and neuropathy severity scores (P < 0.001). The cohort with diabetes had significantly larger median (8.5 ± 0.3 mm2 vs 7.2 ± 0.1 mm2 ; P < 0.05) and tibial nerves (18.0 ± 0.9 mm2 vs 12.8 ± 0.5 mm2 ; P < 0.05) compared with controls. CONCLUSION: Peripheral nerve hypervascularity is detectable by ultrasonography in moderate to severe diabetic neuropathy with prominent sensory dysfunction.

Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs.

BACKGROUND AND PURPOSE: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. METHODS: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. RESULTS: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. CONCLUSIONS: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

A model to predict the probability of acute inflammatory demyelinating polyneuropathy.

OBJECTIVE: We aimed to develop a model that can predict the probabilities of acute inflammatory demyelinating polyneuropathy (AIDP) based on nerve conduction studies (NCS) done within eight weeks. METHODS: The derivation cohort included 90 Malaysian GBS patients with two sets of NCS performed early (1-20days) and late (3-8 weeks). Potential predictors of AIDP were considered in univariate and multivariate logistic regression models to develop a predictive model. The model was externally validated in 102 Japanese GBS patients. RESULTS: Median motor conduction velocity (MCV), ulnar distal motor latency (DML) and abnormal ulnar/normal sural pattern were independently associated with AIDP at both timepoints (median MCV: p = 0.038, p = 0.014; ulnar DML: p = 0.002, p = 0.003; sural sparing: p = 0.033, p = 0.009). There was good discrimination of AIDP (area under the curve (AUC) 0.86-0.89) and this was valid in the validation cohort (AUC 0.74-0.94). Scores ranged from 0 to 6, and corresponded to AIDP probabilities of 15-98% at early NCS and 6-100% at late NCS. CONCLUSION: The probabilities of AIDP could be reliably predicted based on median MCV, ulnar DML and ulnar/sural sparing pattern that were determined at early and late stages of GBS. SIGNIFICANCE: A simple and valid model was developed which can accurately predict the probability of AIDP.

Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.