Distal Calf Research Articles

Vascular and nerve biomarkers in thigh skin biopsies differentiate painful from painless diabetic peripheral neuropathy

BackgroundIdentifying distinct mechanisms and biomarkers for painful diabetic peripheral neuropathy (DPN) is required for advancing the treatment of this major global unmet clinical need. We previously provided evidence in calf skin biopsies that disproportion between reduced sensory small nerve fibers and increased blood vessels may distinguish painful from non-painful DPN. We proposed that overexposure of the reduced nerve fibers in DPN to increased hypoxemia-induced vasculature and related algogenic factors, e.g., nerve growth factor (NGF), leads to neuropathic pain. To further investigate this proposed mechanism, we have now studied more proximal thigh skin biopsies, to see if the same disproportion between increased vasculature and decreased nerve fibers generally differentiates painful DPN from painless DPN.MethodsA total of 28 subjects with type 2 diabetes (T2DM) and 13 healthy volunteers (HV) underwent detailed clinical and neurophysiological assessments, based on the neuropathy composite score of the lower limbs [NIS(LL)] plus 7 tests. T2DM subjects were subsequently divided into three groups: painful DPN (n = 15), painless DPN (n = 7), and no DPN (n = 6). All subjects underwent skin punch biopsy from the upper lateral thigh 20 cm below the anterior iliac spine.ResultsSkin biopsies showed decreased PGP 9.5-positive intraepidermal nerve fiber (IENF) density in both painful DPN (p < 0.0001) and painless DPN (p = 0.001). Vascular marker von Willebrand Factor (vWF) density was markedly increased in painful DPN vs. other groups, including painless DPN (p = 0.01). There was a resulting significant decrease in the ratio of intraepidermal nerve fiber density to vasculature and PGP9.5 to vWF, in painful DPN vs. painless DPN (p = 0.05). These results were similar in pattern to those observed in these HV and T2DM groups previously in distal calf biopsies; however, the increase in vWF was much higher and nerve fiber density much lower in the calf than thigh for painful DPN. Thigh skin vWF density was significantly correlated with several metabolic (waist/hip ratio, HbA1c), clinical (e.g., pain score), and neurophysiological measures.ConclusionThis study supports our proposal that increased dermal vasculature, and its disproportionate ratio to reduced nociceptors, may help differentiate painful DPN from painless DPN. This disproportion is greater in the distal calf than the proximal thigh skin; hence, neuropathic pain in DPN is length-dependent and first localized to the distal lower limbs, mainly feet.

A - 115 Cognitive Predictors of Phosphorylated Skin Nerve α-Synuclein Deposition in Patients with Suspected Synucleinopathy

Abstract Objective Synucleinopathies are a group of neurodegenerative diseases caused by abnormal α-Synuclein aggregates and characterized by motor, autonomic, and cognitive changes, including Parkinson’s disease, Lewy Body disease, and Multiple System Atrophy. Due to variability in presentation, clinical phenotyping is challenging for diagnosis and treatment planning. Phosphorylated α-Synuclein (P-syn) detected in nerve fibers using skin biopsy shows promise in clinical phenotyping of synucleinopathies. However, cognitive predictors of P-syn deposition in synucleinopathies have not been fully explored. This study aimed to examine the utility of cognitive testing in predicting P-syn deposition in a clinical sample. Method A chart review of 52 older adults (Mean age = 72.8 years) referred to an outpatient neurology clinic for a diagnostic dementia workup was conducted. Clinical variables were collected, including skin biopsy (Syn-One) and cognitive test scores (Short Test of Mental Status [STMS]). P-syn was detected in 22 patients (42%) and at 68%, 41%, and 55% of central (neck) and distal (thigh and calf) biopsy sites, respectively. Results Overall cognition (STMS Total) did not significantly differ between patients with (Mean = 30.5) and without (Mean = 29.6) P-syn (p = 0.51). Within the P-syn positive group, STMS Registration-Trials and Calculation scores significantly predicted distally deposited P-syn (F(1,18) = 7.54, p = 0.01). This relationship was more pronounced in the thigh compared to the calf biopsy sites. Conclusion STMS Registration-Trials (immediate recall) and Calculation scores were significantly related to distally deposited P-syn. These findings highlight the importance of how cognitive test performance can potentially impact clinical phenotyping in synucleinopathies. Future research will examine the relationship between cognition, clinical features, and other neurodegenerative disease biomarkers.

Application of the ankle pump method in a sitting position to evaluate calf perforating veins by color Doppler ultrasound

ObjectiveWe investigated the feasibility and efficacy of assessing calf perforating veins (PVs) using the ankle pump in a sitting position (AP-sit) method by color Doppler ultrasound. MethodsWe performed a multicenter prospective clinical trial between November 2022 and October 2023. Eligible patients with chronic venous disease and healthy controls were enrolled. The calf PVs were assessed using three different methods: manual compression in a standing position, manual compression in a sitting position, and AP-sit method. The reflux durations and detection rate of incompetent PVs (IPVs) were compared among the three methods. The number and diameter of calf PVs and distribution of IPVs were analyzed. ResultsA total of 50 patients with chronic venous disease and 50 healthy controls were included. There were 173 calves analyzed, including 97 healthy calves and 76 calves with chronic venous disease. The number of PVs per calf was higher in the diseased calves (median, 7.0; interquartile range [IQR], 6.0-8.0) than in the healthy calves (median, 5.0; IQR, 3.0-6.0; P < .001). The diameter of IPVs (median, 2.3 mm; IQR, 2.0-3.1 mm) was larger than that of competent PVs (median, 1.4 mm; IQR, 1.2-1.7 mm). Most of the IPVs (78.8%) were located in the medial and posterior middle of the calf. The reflux duration induced by the AP-sit method was greater than that induced by the manual compression methods (P < .001). Although the AP-sit method had a higher detection rate (92.0%) of IPVs than the manual compression methods (71.7% and 74.3% for standing and sitting, respectively; P < .001), especially in the distal lower leg, the manual compression methods found IPVs not found using the AP-sit method. ConclusionsDiseased calves with chronic venous disease have more PVs than do healthy calves. IPVs are commonly larger than competent PVs, with most IPVs located in the medial and posterior middle of the calf. Most importantly, the AP-sit method provides a convenient and effective approach for assessing the calf PVs, especially those located in the distal calf, as an alternative or complementary method to traditional manual compression, which is valuable in the daily practice of sonographers.

Generation of a Predictive Clinical Model for Isolated Distal Deep Vein Thrombosis (ICMVT) Detection.

BACKGROUND Isolated distal deep vein thrombosis (ICMVT) increases the risk of pulmonary embolism. Although predictive models are available, their utility in predicting the risk is unknown. To develop a clinical prediction model for isolated distal calf muscle venous thrombosis, data from 462 patients were used to assess the independent risk variables for ICMVT. MATERIAL AND METHODS The area under curve (AUC) for Model A and Model B were calculated and other risk factors were based on age, pitting edema in the symptomatic leg, calf swelling with least 3 cm larger than the asymptomatic leg, recent bed rest for 3 days or more in the past 4 weeks, requiring general or major surgery with regional anesthesia, sex, and local tenderness distributed along the deep venous system as independent predictors of calf muscle venous thrombosis. Model A includes the risk variables for C-reactive protein and D-dimer. RESULTS The area under ROC curve for Model A training set was 0.924 (95% CI: 0.895-0.952), the area under ROC curve for Model B training set was 0.887 (95% CI: 0.852-0.922), and the AUC difference between the 2 models was statistically significant (P<0.001); the area under ROC curve for Model A obtained in the validation set was 0.902 (95% CI: 0.844-0.961), the area under ROC curve for Model B was 0.842 (95% CI: 0. 0.773-0.910), and the difference between the 2 models was statistically significant (P=0.012). CONCLUSIONS Predictive Model A better predicts isolated calf muscle venous thrombosis and is able to help clinicians rapidly and early diagnose ICMVT, displaying higher utility for missed diagnosis prevention and disease therapy.

Do Patients with Antiphospholipid Syndrome Have More Significant Venous Thromboembolic Clot Burden?: A Single-Center Retrospective Analysis

Background: Antiphospholipid syndrome (APS) is a prothrombotic condition defined by arterial or venous thrombotic events and/or obstetrical morbidity in the presence of persistently positive antiphospholipid antibodies (aPL). Venous thromboembolic disease (VTE), comprised mostly of deep vein thrombosis (DVT) and pulmonary embolism (PE), is the initial presenting clinical manifestation in approximately 35% of APS diagnoses. VTE is a heterogenous disease and can present with varying degrees of clot burden. Lower extremity DVT can present with thrombus in the iliofemoral, femoropopliteal, and/or distal calf veins; pulmonary embolism can present with thrombus in the main pulmonary arteries, lobar branches, segmental, and/or subsegmental branches. In both DVT and PE, more proximal clot burden portends higher morbidity and mortality. While VTE is a commonly encountered clinical presentation, the decision regarding whom to test for APS is often challenging. Current guidelines recommend that clinicians consider testing for APS in patients with unexplained venous or arterial thrombotic events, especially young patients, or when a patient has one or more specific adverse outcomes related to pregnancy. To date, no data exist to suggest that patients with APS are more likely to present with more extensive venous thromboembolic clot burden as compared to patients without APS. Purpose: To assess clot burden in patients with a co-diagnosis of VTE and APS in comparison to patients with VTE without APS to determine if clot burden should be considered when deciding whom to test for APS. Methods: This retrospective cohort study included adult patients with a history of VTE who had also been tested for APS within a multihospital academic healthcare system from December 1, 2019 through January 31, 2022. All patients in the study had a history of VTE and were considered to be positive for APS if they had persistently positive aPL and/or lupus anticoagulant in accordance with the revised Sapporo APS Classification Criteria. Patients were excluded if they had confounding provoking risk factors for thrombosis. Patients were stratified as APS and non-APS. Significant clot burden was defined as PE involving the main and/or lobar pulmonary arteries or DVT involving the iliofemoral veins. Assessment of clot burden was performed by review of radiology reports of the sentinel clotting event.Patients were further stratified based on age, BMI, insurance status, severity of APS (triple-positive APS versus non-triple-positive APS), and type of APS (primary versus secondary). Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Chi square test was used to compare percentages and t-test was used to compare means. Univariate and multivariate regression models were used to analyze the predictors of significant clot burden. Results: We identified 748 patients with a history of VTE who had also been tested for APS. The study population was comprised of 53.1% females with a median age of 59 (IQR 46-69). A majority of the patients were Caucasian (85%). APS was detected in 75 (10%) patients. Significant clot burden was present in 29 (38.7%) APS patients and 269 (40.0%) non-APS patients (OR 0.95, 95% CI 0.58-1.56; P = 0.85). On univariate analysis, age (OR 1.01, 95% CI 1.00-1.02; P = 0.02) and being uninsured (OR 9.2, 95% CI 1.10-76.10; P = 0.04) were associated with more significant clot burden. No predictors for significant clot burden were found on multivariable analysis. Triple positive APS (OR 0.83, 95% CI 0.16-4.21; P = 0.82) and primary APS (OR 0.72, 95% CI 0.15-3.45; P = 0.68) were not associated with more significant clot burden. Conclusions: In this retrospective cohort of 748 patients with a history of VTE, the presence of antiphospholipid syndrome was not associated with more significant VTE clot burden as compared to non-APS patients. Based on these data, VTE clot burden may not be a reliable predictor for the presence of APS. Study limitations include selection bias, retrospective design, and lack of precise volumetric measurement of blood clots.

Sonographic imaging and assessment of the sural nerve

AbstractThe sural nerve is a sensory nerve which innervates the posterolateral distal calf and lateral foot. It can be demonstrated using high resolution ultrasound and travels near the small saphenous vein throughout most of its course. There are variations in its origin and relative position through the posterior distal calf, lateral ankle, and foot. To allow this nerve and any potential pathology or injury to be sonographically demonstrated, a good understanding of the sonographic relative anatomy, course, and common anatomical variations, as well as the sonographic normal appearances throughout need to be appreciated and these are reviewed in this paper.

CPC01 A puzzling panniculitis

Abstract A 51-year-old White woman was seen by dermatology services for a 3-day history of a painful subcutaneous nodule affecting her right distal calf, which was on a background of recurrent erythema nodosum diagnosed in childhood and an admission 6 months prior secondary to neutrophilic panniculitis affecting the right groin. The patient had sustained a traumatic injury to the leg following a fall. She was treated with oral antibiotics for a presumed infected haematoma. As her pain increased, she presented to the emergency department 3 weeks after the fall. On examination, a tender erythematous subcutaneous lesion with central sloughing was noted. She was tachycardic and hypotensive on presentation. Her C-reactive protein was elevated (172 mg L−1), and leucocytosis (15 × 109 cells L−1), with associated neutrophilia and anaemia (9.0 g dL−1), was noted on complete blood count review. Two days later, despite treatment with intravenous (IV) benzylpenicillin, flucloxacillin, clindamycin and topical clobetasol propionate, the lesion enlarged rapidly. Dermatology was consulted. Viral screens, including HIV, herpes simplex virus, Epstein–Barr virus, cytomegalovirus, and hepatitis B and C, were all negative. Serum protein electrophoresis and serum angiotensin-converting enzyme were within normal limits. Her α-1 antitrypsin level was elevated (3.16 g L−1; reference interval 1.1–2.1 g L−1). Her admission was complicated by sepsis, which required escalation of IV antibiotics to meropenem, vancomycin and clindamycin. Punch biopsy revealed epidermal necrosis and ulceration with extensive neutrophilic dermatosis and dermal abscess formation. The inflammation was seen to extend into the subcutis. Findings were reported as consistent with neutrophilic panniculitis. Colchicine was commenced based on ongoing sepsis and anaemia secondary to acute-on-chronic inflammation. Over 2 weeks, the lesion rapidly enlarged, prompting the introduction of oral corticosteroids (0.5 mg kg−1). Adalimumab and doxycycline were further introduced to reduce steroid requirements. Outpatient echocardiogram and colonoscopy revealed no pathology. Reduced levels of α-1 antitrypsin were noted on two occasions (0.89 g L−1 and 0.91 g L−1), coinciding with normal inflammatory markers following her acute illness. To date, no α-1 antitrypsin genetic abnormality has been detected. Panniculitis can be a rare and life-threatening manifestation of α-1 antitrypsin deficiency. Patients presenting with systemic inflammatory response syndrome and panniculitis have a reportedly high mortality risk. No hepatic or respiratory manifestation of α-1 antitrypsin deficiency was seen in this case, highlighting the importance of considering α-1 antitrypsin deficiency in the assessment of panniculitis and rechecking α-1 antitrypsin in this context as it is an acute-phase reactant.

PD05-02 SMALL FIBER POLYNEUROPATHY AS A THERAPEUTIC TARGET FOR PATIENTS WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME

You have accessJournal of UrologyCME1 Apr 2023PD05-02 SMALL FIBER POLYNEUROPATHY AS A THERAPEUTIC TARGET FOR PATIENTS WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME Wyatt Whitman, Maxwell Sandberg, Dylan Wolff, Raymond Xu, Tyler Overholt, Robert Evans, Catherine Matthews, Gopal Badlani, and Stephen Walker Wyatt WhitmanWyatt Whitman More articles by this author , Maxwell SandbergMaxwell Sandberg More articles by this author , Dylan WolffDylan Wolff More articles by this author , Raymond XuRaymond Xu More articles by this author , Tyler OverholtTyler Overholt More articles by this author , Robert EvansRobert Evans More articles by this author , Catherine MatthewsCatherine Matthews More articles by this author , Gopal BadlaniGopal Badlani More articles by this author , and Stephen WalkerStephen Walker More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003229.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In addition to a variety of co-occurring urological and non-urological symptoms and syndromes, we have found that ∼30% of patients with a diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS) also have small fiber polyneuropathy (SFPN). The objective of this study was to determine the association between SFPN and co-occurring symptoms and syndromes in IC/BPS patients. METHODS: Skin biopsies were taken from the distal calf of IC/BPS patients who were undergoing therapeutic hydrodistension (HOD). SFPN status (+ or -) was determined by counting intraepidermal nerve fibers (IENF) in a stained section from the biopsy and comparing the IENF density to normative reference values. Patient characteristics such as anesthetic bladder capacity (BC), Hunner lesion (HL) status, and glomerulations were determined at the time of hydrodistension under direct cystoscopy. Patient demographics, co-occurring medical conditions, and symptomatology was obtained via patient reports and review of medical records. To test for an association of SFPN+ with demographic and clinical characteristics, an optimized logistic regression model was created using variables with p<0.1 on univariable analysis and/or those with an established clinical relevance. Standard logistic regression diagnostics were utilized to ensure the model fit to the data RESULTS: Between October 2019 and April 2022 153 participants were enrolled (134F;19M). Mean age was 50.32 (±15.32). Overall, one third (50/153) were SFPN+. There was a statistically significant difference in the adjusted odds ratios (OR, [95% CI]) between the SFPN+ and SFPN- groups for chronic fatigue syndrome (3.054, [1.22, 7.68]) and diabetes mellitus (4.185, [1.471, 11.90]). CONCLUSIONS: SFPN is common in patients with IC/BPS and is significantly associated with concomitant diagnoses of chronic fatigue syndrome and diabetes mellitus. These findings suggest that for a large subset of IC/BPS patients that have a systemic pain disorder, SFPN may provide an important new therapeutic target. Source of Funding: R01 DK124599 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e148 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wyatt Whitman More articles by this author Maxwell Sandberg More articles by this author Dylan Wolff More articles by this author Raymond Xu More articles by this author Tyler Overholt More articles by this author Robert Evans More articles by this author Catherine Matthews More articles by this author Gopal Badlani More articles by this author Stephen Walker More articles by this author Expand All Advertisement PDF downloadLoading ...

Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration.

Current oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e., "disease modification." We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy. 50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment. At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p = 0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (p = 0.02), and correlated with reduction in SF-MPQ overall pain score (p = 0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibers (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p = 0.0002) and NPDPN Q+SOC (p = 0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibers (SENF) were observed with GAP43 (marker of regenerating nerve fibers) only in PDPN Q+SOC (p = 0.003) and NPDPN Q+SOC (p = 0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (p = 0.0008) and GAP43 (p = 0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibers persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p = 0.006). Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers.

Peripheral Nerve Involvement at First Diagnosis of Multiple Sclerosis: A Prospective MR Neurography Study.

The aim of this study was to assess peripheral nerve involvement in patients with multiple sclerosis (MS) at first clinical presentation using quantitative magnetic resonance (MR) neurography in correlation with clinical, laboratory, electrophysiological, and central nervous MR imaging data. In this prospective monocentric study, 30 patients first diagnosed with MS according to the McDonald criteria (19 women; mean age, 32.4 ± 8.8 years) and 30 age- and sex-matched healthy volunteers were examined with high-resolution 3 T MR neurography using a dual-echo T2-relaxometry sequence covering the tibial and peroneal nerves from proximal thigh to distal calf. Magnetic resonance biomarkers of T2 relaxation time (T2 app ), proton spin density (PSD), and nerve cross-sectional area (CSA) were correlated with clinical symptoms, intrathecal immunoglobulin (Ig) synthesis, nerve conduction study, and lesion load on brain and spine MR imaging. The diagnostic accuracy of MR biomarkers was assessed using receiver-operating characteristic curves. Diffuse nerve changes were detected along the tibial and peroneal nerves in MS patients, who showed decreased PSD ( P < 0.001), increased T2 app ( P < 0.001), and smaller tibial nerve CSA ( P < 0.001) compared with healthy subjects. Tibial PSD was identified as best parameter separating patients from controls (area under the curve = 0.876). Intrathecal IgG and IgM synthesis correlated with PSD values ( r = -0.44, P = 0.016, and r = -0.42, P = 0.022). Contrast-enhancement of brain or spine lesions was related to larger tibial and peroneal CSA ( P < 0.001, P = 0.033). Abnormal electrophysiology correlated with higher tibial and peroneal T2 app ( P < 0.001 and P = 0.033), lower tibial and peroneal PSD ( P = 0.018 and P = 0.002), and smaller peroneal CSA ( P < 0.001). Quantitative MR neurography reveals peripheral nerve changes in patients with initial diagnosis of MS. Correlation of imaging findings with intrathecal immunoglobulin synthesis may indicate a primary coaffection of the peripheral nervous system in MS.

Cross-sectional area reference values for high-resolution ultrasonography of the lower extremity nerves in healthy Korean adults.

The cross-sectional area (CSA) reference values of the lower extremity nerves in Asians have been rarely reported. For this study, 107 sex- and age-matched, healthy subjects with a mean age of 46 years (range, 24–75 years) were recruited. All subjects underwent standardized nerve conduction studies of the upper and lower extremities. The CSA was measured unilaterally at 12 sites in the lower extremity nerves, including the femoral, lateral femoral cutaneous, sciatic, common peroneal, superficial peroneal, deep peroneal, tibial, and sural nerves. The CSA significantly correlated with height, weight, and body mass index. The CSA was significantly larger in males than females at most nerves except for the lateral femoral cutaneous, common peroneal (fibular head), and superficial peroneal nerves (distal calf). There was no statistically significant difference between the age groups except for the tibial nerve (ankle). The results of this study provide CSA reference values for the lower extremity nerves including small branches and the values can be useful in the ultrasonographic investigation of various peripheral neuropathies in East Asian populations.

Effects of wearable resistance load placement on neuromuscular activity and stride kinematics: A preliminary study.

Wearable resistance (WR) training is a modality that allows athletes to perform loaded sport-specific movements to develop force and power outputs. The acute responses by which WR works is still relatively unknown, and the effects of WR load and location of the load has not yet been examined. To investigate the acute neuromuscular and stride characteristic responses to different wearable resistance (WR) loads and placements on the calf muscles during high-speed running. Ten well-trained subjects completed a workout of ten sets of three 10s runs at 18km.h-1 (20s of rest between runs and one min between sets). Five conditions were tested: (1) unloaded control, (2) bilateral 0.75 vs. 1.5% body mass (BM) loading on the distal posterior calf, (3) bilateral proximal vs. distal loading of 1.5% BM positioned posteriorly, (4) bilateral anterior vs. posterior loading of 1.5% BM positioned distally, (5) unilateral loading of 1.5% BM on the distal posterior calf. Data were collected using Electromyography (EMG) and back-mounted GPS-embedded accelerometers. Magnitude of differences of within athlete and between muscle comparisons were calculated using effect sizes (ES) ± 90% confidence limits (CL). No substantial differences in accelerometry data were observed between any of the loaded conditions and the control. EMG activity was lower for proximal loading compared to the control for the gluteus maximus (ES±90%CL; -0.72±0.41), vastus lateralis (-0.89±0.47) and vastus medialis (VM) (-0.97±0.46). Anterior loading induced substantially lower EMG activity for the semitendinosus (-0.70±0.48) and VM (-0.64±0.39) muscles compared with the control. EMG activity of the VM (-0.73±0.46) muscle was also substantially lower for posterior loading compared to the control. Unilateral loading induced no substantial differences in EMG activity between the loaded and unloaded legs. This preliminary study has provided a rationale for the performance of further investigations into the effects of WR lower limb loading on stride characteristics and EMG activity from a chronic standpoint using a larger population.

Patterns of Infra-Popliteal Arterial Disease

Introduction The growth of the diabetic population and the increased prevalence of peripheral arterial disease (PAD) below the knee has created an increased demand for duplex ultrasound (DUS) evaluation of the infra-popliteal arteries. The purpose of this study is to show how DUS can be used to identify the patterns of infra-popliteal arterial occlusive disease. Methods: We performed infra-popliteal duplex ultrasound scans on 100 consecutive patients (199 limbs) with suspected PAD. Peak systolic velocity (PSV) was obtained from the anterior tibial artery (ATA) and posterior tibial artery (PTA) at the distal, mid, and proximal calf levels. The acceleration time (AT) was measured in the distal ATA and PTA segments. Results: The PTA was the infra-popliteal artery that was most often totally occluded (21% of limbs). Segmental PTA occlusions occurred predominantly in the proximal and distal segments. The ATA was totally occluded in 8% of limbs, with segmental occlusions located predominantly in the mid segment. We also confirmed that proximal PAD prolongs distal infra-popliteal artery AT and reduces distal PSV. Conclusion: These data add to our understanding of the patterns of infra-popliteal arterial disease and should be of interest to sonographers who perform DUS of the lower extremity arteries.

Diameter-reflux relationship of the saphenous vein in the C0-C3 patients of chronic venous disease.

To evaluate the relationship between the saphenous vein's diameter and reflux and determine the cut point of the saphenous vein's diameter that indicates lack of reflux. A retrospective cohort study conducted in 807 limbs underwent the venous ultrasound for 36months. The saphenous vein's diameter in the reflux and non-reflux groups was evaluated. The receiver operating characteristics (ROC) curve was constructed to determine the saphenous vein's diameter that maximizes the summation of sensitivity and specificity for saphenous vein reflux in C0-C3 patients. The reflux group had a significantly greater diameter than a non-reflux group at four great saphenous vein (GSV) levels and two small saphenous vein (SSV) levels (p-value < 0.001). The venous reflux correlated significantly with GSV diameter at all four GSV levels and two SSV levels (p-value <0.001). The ROC area of the diameter at four GSV levels ranges from 0.59 to 0.69. The optimal cut-off diameter for GSV reflux is 3.8mm at the proximal thigh, 2.8mm at the distal thigh, 3.2mm at the proximal calf, and 2.5mm at the distal calf. The ROC area of the diameter at two SSV levels ranges from 0.66 to 0.67. The optimal cut-off diameter for SSV reflux is 2.5mm at the proximal calf and 2.3mm at the distal calf. The saphenous vein's diameter has been proved to be significantly correlated with the presence of reflux in duplex ultrasound in all lower limbs' levels. Unfortunately, the study's cut point diameter is considered poor accuracy and is not an accurate measurement to use as the screening test for the presence of reflux.

PD01-10 SMALL FIBER POLYNEUROPATHY: A NEXUS LINKING CO-OCCURRING PAIN SYNDROMES IN WOMEN WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME?

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD01)1 Sep 2021PD01-10 SMALL FIBER POLYNEUROPATHY: A NEXUS LINKING CO-OCCURRING PAIN SYNDROMES IN WOMEN WITH INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME? Raymond Xu, Tyler Overholt, Catherine A. Matthews, Robert Evans, Gopal Badlani, Christine Ahn, Trang Simon, and Stephen J. Walker Raymond XuRaymond Xu More articles by this author , Tyler OverholtTyler Overholt More articles by this author , Catherine A. MatthewsCatherine A. Matthews More articles by this author , Robert EvansRobert Evans More articles by this author , Gopal BadlaniGopal Badlani More articles by this author , Christine AhnChristine Ahn More articles by this author , Trang SimonTrang Simon More articles by this author , and Stephen J. WalkerStephen J. Walker More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001965.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often have one or more co-occurring chronic pain syndromes (e.g., chronic pelvic pain (CPP), fibromyalgia (FM), and/or vulvodynia (VD)). The objective of this study was to explore the role of small fiber polyneuropathy (SFPN) as a potential nexus between IC/BPS and chronic pain syndromes. METHODS: Fifty-one women with IC/BPS undergoing therapeutic hydrodistention (HOD) provided a skin biopsy from the distal calf. Processed biopsy tissue was stained with protein gene product (PGP) 9.5, a marker for intraepidermal nerve fibers (IENF), and SFPN (+/-) status was determined by comparing linear IENF density (fibers/mm2; Figure 1) with normative reference values. Co-occurring chronic pain syndrome status (e.g., CPP, FM, and VD) was determined from patient report. RESULTS: Approximately one quarter (13/51; 25.49%) of the women in this cohort were SFPN+. Average age (years) of SFPN+ patients was 40.92 versus 48.73 for patients without SFPN (SFPN-). Among SFPN+ patients, co-occurring widespread pain syndromes were 76.92% (10/13), 46.15% (6/13), and 38.46% (5/13) for chronic pelvic pain (CPP), fibromyalgia (FM), and vulvodynia (VD), respectively. Among the SFPN- patient group, 42.10% (16/38), 36.84% (14/38), and 15.79% (6/38) reported CPP, FM, VD, respectively (Table 1). CONCLUSIONS: Contrary to normative reference range values that show IENF density decreases with age, the SFPN+ patients were, on average, almost 8 years younger than their SFPN- counterparts. SFPN+ women with IC/BPS reported a higher prevalence of chronic pelvic pain, fibromyalgia, and vulvodynia. There was high concordance between SFPN and co-occurrence of CPP (∼77%), suggesting a possible etiological role of SFPN in this generalized pain descriptor. Further studies to determine the mechanisms by which SFPN may contribute to chronic pain syndromes in women with IC/BPS are warranted. Source of Funding: 1R01DK124599-01 (Walker, PI) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e34-e35 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Raymond Xu More articles by this author Tyler Overholt More articles by this author Catherine A. Matthews More articles by this author Robert Evans More articles by this author Gopal Badlani More articles by this author Christine Ahn More articles by this author Trang Simon More articles by this author Stephen J. Walker More articles by this author Expand All Advertisement Loading ...

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration.

Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application.Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment.Results: Participants showed significant decrease in spontaneous pain (mean NPRS: −1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (−1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001).Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019).Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.

In Vivo Matrigel Plug Assay as a Potent Method to Investigate Specific Individual Contribution of Angiogenesis to Blood Flow Recovery in Mice.

Neovascularization restores blood flow recovery after ischemia in peripheral arterial disease. The main two components of neovascularization are angiogenesis and arteriogenesis. Both of these processes contribute to functional improvements of blood flow after occlusion. However, discriminating between the specific contribution of each process is difficult. A frequently used model for investigating neovascularization is the murine hind limb ischemia model (HLI). With this model, it is difficult to determine the role of angiogenesis, because usually the timing for the sacrifice of the mice is chosen to be optimal for the analysis of arteriogenesis. More importantly, the occurring angiogenesis in the distal calf muscles is probably affected by the proximally occurring arteriogenesis. Therefore, to understand and subsequently intervene in the process of angiogenesis, a model is needed which investigates angiogenesis without the influence of arteriogenesis. In this study we evaluated the in vivo Matrigel plug assay in genetic deficient mice to investigate angiogenesis. Mice deficient for interferon regulatory factor (IRF)3, IRF7, RadioProtective 105 (RP105), Chemokine CC receptor CCR7, and p300/CBP-associated factor (PCAF) underwent the in vivo Matrigel model. Histological analysis of the Matrigel plugs showed an increased angiogenesis in mice deficient of IRF3, IRF7, and RP105, and a decreased angiogenesis in PCAF deficient mice. Our results also suggest an involvement of CCR7 in angiogenesis. Comparing our results with results of the HLI model found in the literature suggests that the in vivo Matrigel plug assay is superior in evaluating the angiogenic response after ischemia.

Clinical and Neuroimaging Features in Charcot-Marie-Tooth Patients with GNB4 Mutations.

Charcot–Marie–Tooth disease (CMT) is the most common inherited peripheral neuropathy. Mutations in the GNB4 gene cause dominant intermediate CMT type F (CMTDIF). The aim of this study is to investigate phenotypic heterogeneities and characteristics of CMT patients with GNB4 mutations. We enrolled 1143 Korean CMT families and excluded 344 families with a PMP22 duplication. We further analyzed the 799 remaining families to find their GNB4 mutations using whole-exome sequencing (WES). We identified two mutations (p.Gly77Arg and p.Lys89Glu) in three families, among which a heterozygous p.Gly77Arg mutation was novel. In addition, a significant uncertain variant (p.Thr177Asn) was observed in one family. The frequency of the GNB4 mutation in the Korean population is 0.38% in PMP22 duplication-negative families. All three families showed de novo mutation. Electrophysiological findings regarding the p.Lys89Glu mutation showed that the motor nerve conduction velocity (MNCV) of the median nerve was markedly reduced, indicating demyelinating neuropathy, and sural nerve biopsy revealed severe loss of myelinated axons with onion bulb formation. Lower extremity Magnetic Resonance Imaging (MRI) demonstrated relatively more severe intramuscular fat infiltrations in demyelinating type (p.Lys89Glu mutation) patients compared to intermediate type (p.Gly77Arg mutation) patients. The anterolateral and superficial posterior compartment muscles of the distal calf were preferentially affected in demyelinating type patients. Therefore, it seems that the investigated GNB4 mutations do cause not only the known intermediate type but also demyelinating-type neuropathy. We first presented three Korean families with GNB4 mutations and found phenotypic heterogeneities of both intermediate and demyelinating neuropathy. We suggest that those findings are useful for the differential diagnosis of CMT patients with unknown GNB4 variants.

Electrodes’ Configuration Influences the Agreement Between Surface EMG and B-Mode Ultrasound Detection of Motor Unit Fasciculation

Muscle fasciculations, resulting from the spontaneous activation of motor neurons, may be associated with neurological disorders, and are often assessed with intramuscular electromyography (EMG). Recently, however, both ultrasound (US) imaging and multichannel surface EMG have been shown to be more sensitive to fasciculations. In this study we combined these two techniques to compare their detection sensitivity to fasciculations occurring in different muscle regions and to investigate the effect of EMG electrodes' configuration on their agreement. Monopolar surface EMGs were collected from medial gastrocnemius and soleus with an array of 32 electrodes (10 mm Inter-Electrode Distance, IED) simultaneously with b-mode US images detected alongside either proximal, central or distal electrodes groups. Fasciculation potentials (FP) were identified from single differential EMGs with 10 mm (SD1), 20 mm (SD2) and 30 mm (SD3) IEDs, and fasciculation events (FE) from US image sequences. The number, location, and size of FEs and FPs in 10 healthy participants were analyzed. Overall, the two techniques showed similar sensitivities to muscle fasciculations. US was equally sensitive to FE occurring in the proximal and distal calf regions, while the number of FP revealed by EMG increased significantly with the IED and was larger distally, where the depth of FE decreased. The agreement between the two techniques was relatively low, with a percentage of fasciculation classified as common ranging from 22% for the smallest IED to 68% for the largest IED. The relevant number of events uniquely detected by the two techniques is discussed in terms of different spatial sensitivities of EMG and US, which suggest that a combination of US-EMG is likely to maximise the sensitivity to muscle fasciculations.

Not Just a Dog Bite: Unmasking Underlying Chronic Venous Insufficiency

An 81-year-old man sustained a dog bite to his right lateral calf. Despite antibiotics, the patient continued to have leg swelling, severe itching, and a chronic wound. He was evaluated at the Wound Center, at which time a diagnosis of chronic venous insufficiency was made, and a venous reflux examination was recommended. The patient was scanned using Intersocietal Accreditation Commission Vascular Testing venous reflux protocol. Imaging was directed to the area of concern at the lateral calf. A 1.1-mm vein branch off the proximal calf great saphenous vein (GSV) was identified under the itching/trauma area with venous reflux identified. Venous reflux examination findings identified significant venous reflux from the right saphenofemoral junction through the distal calf GSV and vein branches. An elective right GSV endothermal venous ablation and stab phlebectomy were performed. The patient returned per protocol on postoperative day 2. He reported no pain and complete resolution of itching. Physical examination demonstrated marked improvement in the excoriated area. Surveillance duplex revealed no evidence of an endovenous heat-induced thrombosis. Venous stasis dermatitis occurs when there is inflammation of the skin caused by chronic venous insufficiency. In the early stages, symptoms include swelling at the ankles, hyperpigmentation, dryness, and itching. The development of stasis dermatitis can be precipitated by trauma, thereby unmasking underlying chronic venous insufficiency. Stasis dermatitis in this patient resolved because we treated the cause: chronic venous insufficiency.