Neuropathy Symptom Profile Research Articles

Assessing the effectiveness of Toronto clinical neuropathy score in diagnosing diabetic peripheral neuropathy – A descriptive comparative study

Background: There has been an increasing prevalence of diabetes worldwide. Diabetic peripheral neuropathy is the most common complication of type I and II diabetes. Peripheral neuropathy is a damage occurring in the nerves due to prolonged higher levels of blood sugar and diabetes. There are various screening tests such as vibration perception threshold (VPT), neuropathy symptom profile, michigan neuropathy screening instrument, neuropathy disability score, and Michigan diabetic neuropathy score. VPT accounts for an easy and accurate identification of diabetic patients, who are at risk, including patients, with early neuropathic deficits. Toronto clinical neuropathy score (TCNS) has been validated as a score for monitoring and diagnosing diabetic peripheral neuropathy. Aims and Objectives: This study was done to estimate the sensitivity, evaluate specificity, and determine the positive predictive value and negative predictive value of TCNS scoring in diabetic peripheral neuropathy patients considering VPT as the gold standard. Materials and Methods: In this study, VPT and TCNS were determined in 100 type 2 diabetic subjects with signs and symptoms of peripheral neuropathy. Results: In this study, it was estimated that TCNS is a reliable measure of distal poly neuropathy with a sensitivity of 95.83%, 100% specificity, positive predictive value of 100%, and negative predictive value of 50%. Conclusion: From our study, it was found that TCNS is a sensitive indicator of definite clinical neuropathy.

The Peripheral Neuropathy Prevalence and Characteristics Are Comparable in People with Obesity and Long-Duration Type1 Diabetes.

IntroductionPeripheral neuropathy is reported in obesity even in the absence of hyperglycaemia.ObjectiveTo compare the prevalence and characterise the phenotype of peripheral neuropathy in people living with obesity (OB) and long-duration type 1 diabetes (T1D).Patients and MethodsWe performed a prospective cross-sectional study of 130 participants including healthy volunteers (HV) (n = 28), people with T1D (n = 51), and OB (BMI 30–50 kg/m2) (n = 51). Participants underwent assessment of neuropathic symptoms (Neuropathy Symptom Profile, NSP), neurological deficits (Neuropathy Disability Score, NDS), vibration perception threshold (VPT) and evaluation of sural nerve conduction velocity and amplitude.ResultsPeripheral neuropathy was present in 43.1% of people with T1D (age 49.9 ± 12.9 years; duration of diabetes 23.4 ± 13.5 years) and 33.3% of OB (age 48.2 ± 10.8 years). VPT for high risk of neuropathic foot ulceration (VPT ≥ 25 V) was present in 31.4% of T1D and 19.6% of OB. Participants living with OB were heavier (BMI 42.9 ± 3.5 kg/m2) and had greater centripetal adiposity with an increased body fat percentage (FM%) (P < 0.001) and waist circumference (WC) (P < 0.001) compared to T1D. The OB group had a higher NDS (P < 0.001), VAS for pain (P < 0.001), NSP (P < 0.001), VPT (P < 0.001) and reduced sural nerve conduction velocity (P < 0.001) and amplitude (P < 0.001) compared to HV, but these parameters were comparable in T1D. VPT was positively associated with increased WC (P = 0.011), FM% (P = 0.001) and HbA1c (P < 0.001) after adjusting for age (R2 = 0.547). Subgroup analysis of respiratory quotient (RQ) measured in the OB group did not correlate with VPT (P = 0.788), nerve conduction velocity (P = 0.743) or amplitude (P = 0.677).ConclusionThe characteristics of peripheral neuropathy were comparable between normoglycaemic people living with obesity and people with long-duration T1D, suggesting that metabolic factors linked to obesity play a pivotal role in the development of peripheral neuropathy. Further studies are needed to investigate the mechanistic link between visceral adiposity and neuropathy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02208-z.

The role of abnormalities of lipoproteins and HDL functionality in small fibre dysfunction in people with severe obesity

Obesity and associated dyslipidemia may contribute to increased cardiovascular disease. Obesity has also been associated with neuropathy. We have investigated presence of peripheral nerve damage in patients with severe obesity without type 2 diabetes and the status of metabolic syndrome and lipoprotein abnormalities. 47participants with severe obesity and 30 age-matched healthy controls underwent detailed phenotyping of neuropathy and an assessment of lipoproteins and HDL-functionality. Participants with severe obesity had a higher neuropathy symptom profile, lower sural and peroneal nerve amplitudes, abnormal thermal thresholds, heart rate variability with deep breathing and corneal nerve parameters compared to healthy controls. Circulating apolipoprotein A1 (P = 0.009), HDL cholesterol (HDL-C) (P < 0.0001), cholesterol efflux (P = 0.002) and paroxonase-1 (PON-1) activity (P < 0.0001) were lower, and serum amyloid A (SAA) (P < 0.0001) was higher in participants with obesity compared to controls. Obese participants with small nerve fibre damage had higher serum triglycerides (P = 0.02), lower PON-1 activity (P = 0.002) and higher prevalence of metabolic syndrome (58% vs. 23%, P = 0.02) compared to those without. However, HDL-C (P = 0.8), cholesterol efflux (P = 0.08), apoA1 (P = 0.8) and SAA (P = 0.8) did not differ significantly between obese participants with and without small nerve fibre damage. Small nerve fibre damage occurs in people with severe obesity. Patients with obesity have deranged lipoproteins and compromised HDL functionality compared to controls. Obese patients with evidence of small nerve fibre damage, compared to those without, had significantly higher serum triglycerides, lower PON-1 activity and a higher prevalence of metabolic syndrome.

No evidence of improvement in neuropathy after renal transplantation in patients with end stage kidney disease.

To assess the impact of renal transplantation on peripheral nerve damage in patients with chronic kidney disease (CKD). Fifteen patients with CKD (eGFR <15 mL/min/1.73 m2 ) underwent longitudinal assessment after renal transplantation (age: 56.88 ± 2.53 years, eGFR: 46.82 ± 4.86) and were compared with 15 age-matched controls (age: 58.25 ± 2.18 years, eGFR: 86.0 ± 2.0). The neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration perception threshold (VPT), cold and warm sensation threshold (CST and WST), cold and heat induced pain (CIP and HIP), deep breathing heart rate variability (DB-HRV), nerve conduction studies and corneal confocal microscopy (CCM) to quantify small nerve fibre pathology, were undertaken within 1-month of renal transplantation (baseline) and at 6, 12 and 24 months of follow up. There was no significant difference in NSP (P=.1), NDS (P=.3), VPT (P=.6), CST (P=.2), CIP (P=.08), HIP (P=.1), DB-HRV (P=.9) and sural (P=.4) and peroneal (P=.1) nerve amplitude between patients with CKD and controls at baseline. However, sural (P=.04), peroneal (P=.002) and tibial (P=.007) nerve conduction velocity and tibial nerve amplitude (P=.03) were significantly lower, WST (P=.02) was significantly higher and corneal nerve fibre density (P=.004) was significantly lower in patients with CKD compared with controls. There was no significant change in NSP, NDS, quantitative sensory testing, DB-HRV, nerve conduction or CCM parameters 24 months after renal transplantation. There is evidence of small and large fibre neuropathy in patients with CKD, but no change up to 24 months after successful renal transplantation.

Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity.

Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm2) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm2) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm2) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04). Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy

Accurately quantifying the progression of diabetic peripheral neuropathy is key to identify individuals who will progress to foot ulceration and to power clinical intervention trials. We have undertaken detailed neuropathy phenotyping to assess the longitudinal utility of different measures of neuropathy in patients with diabetes. Nineteen patients with diabetes (age 52.5 ± 14.7 years, duration of diabetes 26.0 ± 13.8 years) and 19 healthy controls underwent assessment of symptoms and signs of neuropathy, quantitative sensory testing, autonomic nerve function, neurophysiology, intra-epidermal nerve fibre density (IENFD) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). Mean follow-up was 6.5 years. Glycated haemoglobin (p = 0.04), low-density lipoprotein-cholesterol (LDL-C) (p = 0.0009) and urinary albumin creatinine ratio (p < 0.0001) improved. Neuropathy symptom profile (p = 0.03), neuropathy disability score (p = 0.04), vibration perception threshold (p = 0.02), cold perception threshold (p = 0.006), CNFD (p = 0.03), CNBD (p < 0.0001), CNFL (p < 0.0001), IENFD (p = 0.04), sural (p = 0.02) and peroneal motor nerve conduction velocity (p = 0.03) deteriorated significantly. Change (∆) in CNFL correlated with ∆CPT (p = 0.006) and ∆Expiration/Inspiration ratio (p = 0.002) and ∆IENFD correlated with ∆CNFD (p = 0.005), ∆CNBD (p = 0.02) and ∆CNFL (p = 0.01). This study shows worsening of diabetic neuropathy across a range of neuropathy measures, especially CCM, despite an improvement in HbA1c and LDL-C. It further supports the utility of CCM as a rapid, non-invasive surrogate measure of diabetic neuropathy.

Improvements in Diabetic Neuropathy and Nephropathy After Bariatric Surgery: a Prospective Cohort Study

PurposeThere are limited data on the impact of bariatric surgery on microvascular complications of type 2 diabetes (T2D), particularly diabetic neuropathy. We assessed microvascular complications (especially neuropathy) in obese patients with T2D before and 12 months after bariatric surgery.Materials and MethodsThis was a prospective observational cohort study. Measurements of neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration (VPT), cold (CPT) and warm (WPT) perception thresholds, nerve conduction studies (NCS) and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL); urinary albumin/creatinine ratio (uACR), estimated glomerular filtration rate (eGFRcyst-creat) and retinal grading were taken.ResultsTwenty-six (62% female; median age 52 years) obese patients with T2D were recruited. Body mass index (BMI) (47.2 to 34.5 kg/m2; p < 0.001) decreased post-operatively. There were improvements in CNFD (27.1 to 29.2/mm2; p = 0.005), CNBD (63.4 to 77.8/mm2; p = 0.008), CNFL (20.0 to 20.2/mm2; p = 0.001), NSP (3 to 0/38; p < 0.001) and eGFRcyst-creat (128 to 120 ml/min; p = 0.015) post-bariatric surgery. Changes in (Δ) triglycerides were independently associated with ΔCNFL (β = − 0.53; p = 0.024) and Δsystolic blood pressure (β = 0.62;p = 0.017), and %excess BMI loss (β = − 0.004; p = 0.018) were associated with ΔeGFRcyst-creat. There was no significant change in NDS, VPT, CPT, WPT, NCS, uACR or retinopathy status. Glomerular hyperfiltration resolved in 42% of the 12 patients with this condition pre-operatively.ConclusionBariatric surgery results in improvements in small nerve fibres and glomerular hyperfiltration in obese people with T2D, which were associated with weight loss, triglycerides and systolic blood pressure, but with no change in retinopathy or uACR at 12 months.

Early nerve fibre regeneration in individuals with type 1 diabetes after simultaneous pancreas and kidney transplantation

Aims/hypothesisThe study aimed to assess the impact on neuropathy of simultaneous pancreas and kidney transplantation (SPK) in individuals with type 1 diabetes.MethodsThis longitudinal observational study examined neuropathic symptoms, deficits, quantitative sensory testing, neurophysiology, corneal confocal microscopy and skin biopsy results in 32 healthy (non-diabetic) control participants, 29 individuals with type 1 diabetes and severe diabetic peripheral neuropathy [DPN] and 36 individuals with type 1 diabetes after SPK.ResultsFollowing SPK, HbA1c, eGFR, triacylglycerols and HDL improved significantly (all p < 0.05). Compared with the DPN group, which remained unchanged over the 36 month study period, corneal confocal microscopy assessments improved over 36 months following SPK, with increasing corneal nerve fibre density of 5/mm2 (95% CI 1.8, 8.2; p = 0.003) and corneal nerve fibre length of 3.2 mm/mm2 (95% CI 0.9, 5.5; p = 0.006). The Neuropathy Symptom Profile and peroneal nerve conduction velocity also improved significantly by 36 months compared with DPN (2.5; 95% CI 0.7, 4.3; p = 0.008 and 4.7 m/s; 95% CI 2.2, 7.4; p = 0.0004, respectively), but with a temporal delay compared with the corneal confocal microscopy assessments. Intraepidermal nerve fibre density did not change following SPK; however, mean dendritic length improved significantly at 12 (p = 0.020) and 36 (p = 0.019) months. In contrast, there were no changes in the Neuropathy Disability Score, quantitative sensory testing or cardiac autonomic function assessments. Except for a small decrease in corneal nerve fibre density in the healthy control group, there were no changes in any other neuropathy measure in the healthy control or DPN groups over 36 months.Conclusions/interpretationSPK is associated with early and maintained small nerve fibre regeneration in the cornea and skin, followed by an improvement in neuropathic symptoms and peroneal nerve conduction velocity.

Quantitative sensory testing in type 1 diabetic patients with painful and painless diabetic neuropathy

The mechanism underlying the development of painful diabetic neuropathy (DN) is unknown. The aim of this study was to compare quantitative sensory testing (QST) characteristics of patients with painful and painless DN and to correlate QST measures with DN pain. Fifty type 1 diabetic patients with DN (30 with painful DN and 20 with painless DN) and 32 age-matched non-diabetic controls were included in this study. For all patients and controls, a detailed assessment of DN was performed which comprised McGill visual analogue scale (McGill VAS) for pain, neuropathy symptom profile and neuropathy disability score (NDS), quantitative sensory testing in form of cold, warm and vibration perception thresholds, nerve conduction studies (NCS), deep-breathing hear rate variability and Neuropad staining scores. Measures of QST, NCS and DB-HRV were correlated with McGill VAS for pain. There were no significant differences in cold, warm and vibration perception thresholds, NCS, DB-HRV and Neuropad scores between patients with painful and painless DN. Cold (r=-0.57, P=0.005), warm (r=0.47, P=0.026) and DB-HRV (r=0.50, P=0.023), however, correlated significantly with McGill VAS scores of pain. In conclusion, Quantitative sensory testing is a helpful tool to identify small nerve fibres damage of DN, correlates with pain intensity but cannot differentiate between painful and painless DN. Both central and peripheral neural injury could be implicated in the genesis of DN pain.

Where Is the Core of the Volcano? The Undetermined Origin of Primary Restless Legs Syndrome

ABSTRACTAn association between small fiber neuropathy and primary Restless Legs Syndrome (RLS) is suggested since both of them share common characteristics. Our aim was to investigate the existence of autonomic neuropathy on the basis of autonomic tests. The patients and the age-matched controls were evaluated with Neuropathy Symptom Profile and Autonomic Symptom Profile, nerve conduction studies (NCS), and autonomic tests. Patients suffered from neuropathic and autonomic complaints obviously. There was no significant difference for NCS, heart rate variability tests, and sympathetic skin responses (SSRs) among patients and controls. Since both the NCSs and the autonomic tests were within normal, the complaints were considered to be the consequences of the problem in sensory integration due to the dysfunction of the caudal diencephalic A11 group, rather than a neuropathic process. The cardiac autonomic imbalance possibly emerges as a consequence of arousal periods prior to or during the Periodic Leg Movements (PLM) episodes during sleep, but not due to autonomic neuropathy.

Neuropathy Symptom Profile in health, motor neuron disease, diabetic neuropathy, and amyloidosis.

We developed a true-or-false questionnaire with several hundred questions about symptoms encountered in peripheral neuropathy, to be scored by optical reader and computer. Responses were grouped into scales called "Neuropathy," "Weakness," "Sensory," "Autonomic," and subsets of these. Profiles in health were estimated for each scale based on responses from 300 healthy subjects 15 to 65 years old. The sensitivity and specificity of the scales were tested in patients with motor neuron disease, amyloidosis, or diabetes, with or without neuropathy. The questionnaire was useful in detecting neuropathy and staging severity, and in recognizing patterns that may have diagnostic implications.