High-Resolution Ultrasonography for Detecting Peripheral Neuropathy in Leprosy: A Systematic Review and Meta-Analysis.

BackgroundLeprosy is an age-old chronic infectious disease with the majority of annual new case detections from South-East Asia. The disease manifestations coupled with the stigma attached to it often creates grave socioeconomic problems. Leprosy is curable and if detected and treated in the early stages can prevent disability. Ultrasonography provides information regarding location and degree of the nerve damage, nerve morphologic alterations, echo texture, fascicular pattern and vascularity. The aim of this study was to study the ultrasonographic features of neuropathy in leprosy with electrophysiologic correlation.ResultsA total of 34 histopathological proven cases of leprosy were included in this study, which was conducted for 1 year. High-resolution ultrasound (HRUS) of a total of 204 peripheral nerves in these 34 patients, including bilateral ulnar, median and common peroneal nerves, was performed. Cross-sectional areas, nerve diameters, nerve morphology and vascularity were noted and correlated with electrophysiologic study of these nerves. The results showed that all the patients having reduced motor or sensory function [decreased compound muscle action potential (CMAP), decreased compound nerve action potential (SNAP) and increased latency] in ulnar and common peroneal nerves were thickened on HRUS (100% in ulnar and common peroneal nerves) while 92% right median and 89% left median nerves with reduced motor or sensory function showed thickening on HRUS. Also, 5.8% ulnar nerves and 11.7% common peroneal nerves showed thickening on HRUS; however, sensory or motor conduction of these nerves was unaffected on nerve conduction study (NCS). So, a positive correlation was observed for nerve involvement as detected by ultrasonographic findings of nerve hypertrophy and the electrophysiologic study. The most common finding was focal or diffuse nerve thickening. Ulnar nerve was the most commonly thickened nerve in leprosy patients with the most common location of nerve thickening at medial epicondyle.ConclusionsUltrasound and electrophysiologic study of peripheral nerves in leprosy are complimentary to each other in diagnosing leprotic neuropathy.

To evaluate ultrasonographic (US) cross-sectional areas (CSAs) of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs) and between tunnel (T) and pre-tunnel (PT) ulnar CSAs (∆TPTs) in leprosy patients (LPs) and healthy volunteers (HVs). Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M) and common fibular (CF) nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p < 0.0001) at the PT (5.67/9.78 mm2) and T (6.50/10.94 mm2) points, as well as at the M (5.85/8.48 mm2) and CF (8.17/14.14 mm2) nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm2 and 68-85% for the PT point, 7.35 mm2 and 71-78% for the T point, 6.75 mm2 and 62-75% for the M nerve and 9.55 mm2 and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 80%) and ∆TPT had the highest specificity (> 90%). New sonographic peripheral nerve measurements (∆CSAs and ∆TPT) provide an important methodological improvement in the detection of leprosy neuropathy.

Background: Nerve examination in leprosy is subjective. There is a paucity of literature on objective methods to evaluate nerve involvement in Leprosy. Aims and Objectives: (1) To measure cross-sectional area (CSA) of nerves and identify echotexural changes in nerves in patients of leprosy by high-frequency ultrasonography (HFUS). (2) To compare HFUS findings in CSA and echotexture of nerves at baseline and after treatment. (3) To compare clinical grading and HFUS grading of nerves before and after treatment. Methods: Both newly diagnosed and treated patients of leprosy were included in the study. Nerve examination was done clinically and clinical grading of nerve thickening was done. Then, thickened nerves were subjected to HUFS to examine CSA (CSA) and echotextural changes. Nerves were also graded by HFUS grading. Parameters such as CSA, echotextural changes, and clinical and HFUS grading were compared before and after completion of treatment. Observations: Sixty-four leprosy patients were studied. Most of the patients in our study were in the third and fourth decade with a male preponderance and the mean age of presentation is 35.75 years. A total of 154 peripheral nerves were studied in 64 leprosy patients. Borderline tuberculoid leprosy (BTH) was the most common type of leprosy. The ulnar nerve was the most commonly imaged nerve followed by the greater auricular nerve. There was a statistically significant difference in CSA of nerves before and after treatment. Only 7 of 23 patients, who were found to have features of neuritis on USG, were clinically symptomatic. Three patients were diagnosed to have nerve abscesses. Conclusion: HFUS appears to be an objective, simple method to evaluate nerve involvement in leprosy. It is also useful to diagnose silent neuritis and nerve abscess. Limitations: All the peripheral nerves were not examined in healthy controls and leprosy patients.

Peripheral nerve involvement is a well-established feature of leprosy. However, it may go unnoticed by clinicians due to a decline in clinical examination skills. High-resolution ultrasonography (HRUS) offers the advantage of identifying subclinical nerve involvement at an earlier stage.This article aims to evaluate and compare the effectiveness of HRUS and clinical examination in detecting peripheral nerve involvement in leprosy, the correlation of sonological findings with clinical findings, and the calculation of sensitivity, specificity, and predictive values of HRUS taking clinical examination as the reference method.This cross-sectional observational study was conducted over 1.5 years involving 60 newly diagnosed leprosy patients. Clinical assessment and sonographic evaluation of five nerve pairs (ulnar, median, greater auricular, common peroneal, and posterior tibial) were done. Findings were recorded, analyzed, and compared.HRUS detected abnormalities in 111 of 600 (18.5%) of all nerves, surpassing the 90 of 600 (15%) nerves detected clinically. HRUS parameters demonstrated substantial agreement with clinical findings, with Cohen's kappa values of 0.740 for cross-sectional area, 0.246 for hypervascularity, and 0.166 for hypoechogenicity. The overall diagnostic performance of HRUS reported a sensitivity of 86.7%, specificity of 93.5%, and positive predictive value of 70.3% with a negative predictive value of 97.6%.This study highlights the critical role of HRUS in detecting and monitoring leprosy neuropathy, emphasizing its superiority over clinical examination in identifying both early and advanced nerve involvement.

P-NU003. Estimation of cross-sectional area reference values of nerves in the upper and lower extremities using ultrasonography in the Indian population

The purpose of the study was to assess the usefulness of high-resolution ultrasonography (HRU) in the evaluation of diabetic peripheral neuropathy (DPN). Thirty-seven adult diabetic patients with clinically diagnosed DPN and 45 healthy adult volunteers were included in the study. HRU of the right medial, ulnar, common peroneal, and posterior tibial nerves was done. The mean cross-sectional area (CSA) of the involved nerves was measured in the two groups at identical positions. The CSA was compared between the two groups, and Student t-test was applied to assess statistical significance. There was a significant increase in the CSA of the median, ulnar, common peroneal, and posterior tibial nerve in DPN patients as compared to healthy volunteers. Sonographic findings were compared with nerve conduction study (NCS) for all the nerves studied except common peroneal nerve (CPN), as the NCS of CPN is not routinely done. DPN was classified as mild or moderate to severe on the basis of latency and velocity assessed by NCS. The mean CSA in all the examined nerves was higher in moderate to severe DPN than the mild DPN, but this was not statistically significant except for ulnar nerve with a P value of < 0.0001. HRU demonstrates a morphological change in patients with DPN in the form of an increase in CSAs, which was statistically significant. HRU can objectively complement other diagnostic investigations such as NCS. High resolution ultrasonography of peripheral nerves has the potential to become the investigation of first choice for the evaluation of DPN.

Introduction: Leprosy primarily affects the peripheral nerves and subsequently spreads to the skin and its appendages. The aim of this study was to correlate clinical patterns of nerve abnormalities of ulnar and common peroneal nerves of leprosy patients with ultrasonography (USG) and findings of nerve conduction studies (NCS).&#x0D; Methods: 180 ulnar nerves (UN) and 180 common peroneal nerves (CPN) of 90 patients with leprosy were assessed clinically. Cross sectional area (CSA) of nerves was measured by ultrasonography. Motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were measured in NCS.&#x0D; Results: The correlation of clinical palpation and ultrasound measures were significant; r= 0.378 (p&lt;0.01) in UN and r= 0.158 (p&lt;0.01) in CPN. There was a significant correlation between clinical findings and NCS; MNCV of UN r= -0.44 (p&lt;0.01), SNCV of UN r= -0.575 (p&lt;0.01) and MNCV of CPN r= -0.254 (p&lt;0.01). The correlation of maximum CSA and NCS was statistically significant in UN; MNCV r= -0.276 (p&lt;0.01) and SNCV r = -0.412 (p&lt;0.01).&#x0D; Conclusion: In leprosy patients, a significant positive correlation exists between clinical detection, ultrasound measures of nerve enlargement and slowing of MNCV and SNCV of UN and CPNs. In our study, USG was done using 4 - 11MHz linear transducer, which is available at any low resource setting. Therefore, ultrasonography without high resolution can be used to detect nerve enlargement in leprosy.

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), primarily effecting nerve and skin. Ultrasonography (USG) in the diagnosis of nerve involvement in leprosy is still in a preliminary stage, but it can be used to identify the early changes in the nerves. Aims: To assess the role of USG in identifying nerve involvement across the spectrum of leprosy. Methods: Thirty newly diagnosed, untreated cases of leprosy were recruited and classified into paucibacillary (PB) and multibacillary (MB) on basis of histopathology findings on skin biopsy. USG of ulnar nerve (UN), median nerve (MN), lateral popliteal nerve (LPN) and posterior tibial nerve (PTN) was done to identify the changes across the disease spectrum. Results: Thirty patients (16 multibacillary, MB and 14 paucibacillary, PB) with a mean age of 28.83 ± 18.57 years, M:F of 2:1 were studied. The nerves were significantly enlarged in USG examination in the MB group as compared to PB group for UN, MN, LPN and PTN (P = 0.004, 0.018, 0.019 and 0.020 respectively). 41 nerves that were not thickened clinically were found to be enlarged on USG (UN 3, MN 21, LPN 6 and PTN 11). Conclusion: USG can be a useful tool for identifying early nerve changes, as compared to clinical examination, as USG is more sensitive. Hence it may help to identify nerve involvement in an early stage and initiate treatment before any severe damage occurs.

Detection of subclinical neuropathy can aid in triage, timely intervention and dedicated care to reduce disease progression and morbidity. High resolution sonography has emerged as a promising technique for evaluation of peripheral nerves. The aim of the present study was to assess the utility of high resolution sonography in screening diabetic patients for subclinical neuropathy. A total of 70 adult patients with type 2 diabetes mellitus and 30 controls were enrolled; those with clinical features of neuropathy constituted the diabetic polyneuropathy group and those without symptoms/normal nerve conduction the non-diabetic polyneuropathy group. After institutional ethical committee approval and informed consent, high resolution sonography was performed by two musculoskeletal radiologists. Nerves studied were median (elbow and wrist), ulnar (cubital tunnel and Guyon's canal), common peroneal (fibular head) and posterior tibial nerve (medial malleolus).The size (cross sectional area), shape, echogenicity and morphology of nerve were assessed and compared between the groups. The mean cross sectional area of all nerves was significantly higher both in diabetic polyneuropathy and non-diabetic polyneuropathy group compared to controls (p value < .001). Common peroneal nerve cross sectional area of 4.5 mm2 had the highest sensitivity (93%) and specificity (86%) for detecting nerve changes in the non-diabetic polyneuropathy group. The nerves were more rounded, hypoechoic and had an altered morphology in both study groups. Presence of sonographic nerve changes in asymptomatic diabetics depicted that morphological alterations in nerves precede clinical symptoms. High resolution sonography detected nerve changes with a good accuracy, and thus, can be a potential screening tool for detection of subclinical diabetic polyneuropathy.

Background: Electrophysiological tests such as nerve conduction study (NCS) are regarded as the gold standard in identifying peripheral neuropathies. Aims: The study aimed to evaluate the diagnostic performance of screening clinical tests used in the field setting in detecting nerve involvement in newly diagnosed multibacillary (MB) leprosy and to assess their agreement with NCS. Methodology: This cross-sectional study enrolled 40 newly diagnosed MB leprosy patients (age: 40.4 ± 12.9 years, 75% male, 45% Grade 2 disability) during 2022–23. Clinical assessments, including monofilament (MF) test, voluntary muscle testing (VMT) and nerve palpation (NP), were done. The Neuropack S1 EMG measuring equipment was used for NCS. Results: There was a significant difference in the proportion of patients with nerve function impairment by clinical tests and by NCS (motor: 30% vs. 65%; sensory: 50% vs. 73%; P &lt; 0.05 for both). Using the NCS as the gold standard, the MF test for the ulnar, median and sural nerves showed fair specificity (96%, 92% and 100%, respectively) but poor sensitivity (60%, 58% and 60%, respectively), which was also true for VMT in testing the ulnar, median and peroneal nerves (specificity: 100%, 97% and 100%, respectively; sensitivity: 32%, 37% and 5%, respectively). NP for the ulnar, median, tibial and peroneal nerves showed variable specificity (48%, 100%, 79% and 69%, respectively) and sensitivity (79%, 24%, 67% and 71%, respectively). The agreement between various clinical tests and NCS findings was moderate to weak. Conclusion: Clinical tests in the field setting have limited sensitivity and may fail to detect early nerve involvement in leprosy. The incorporation of NCS as a diagnostic tool enhances the detection of nerve impairment.

This study was conducted to evaluate the ability of sonography to visualize the ulnar nerve at Guyon's canal and the common peroneal nerve dorsal to the fibular head and to test for correlations between nerve measurements and subject characteristics. We used a 5-12-MHz linear-array transducer in sonographic evaluation of 15 healthy adult volunteers. We evaluated the correlations between nerve diameters and surface areas and subject body mass index and height. We also tested for differences between nerve measurements in women and men and between nerve measurements from the left and right sides of the body. Both nerves were visualized in all subjects. Subject height correlated significantly with the anteroposterior diameter of the right ulnar nerve. Body mass index correlated significantly with the surface area of both ulnar nerves, with the anteroposterior diameter of both ulnar nerves, with the transverse diameter of the left ulnar nerve, and with the transverse diameter of the right common peroneal nerve. There was a statistically significant difference in anteroposterior diameter of the left ulnar and left common peroneal nerves between women and men. There were no significant differences between left- and right-side measurements for the combined data from the entire group of subjects. A 5-12-MHz linear-array transducer readily allows for visualization of the ulnar nerve at Guyon's canal and the common peroneal nerve dorsal to the fibular head.

Diagnosis and monitoring of nerve function impairment (NFI) presents an ongoing challenge in global leprosy control. This was a prospective, observational study in leprosy patients receiving treatment with cutaneous and neurological examinations done every 3 months for 1 year. High-resolution ultrasonography and color Doppler (HRUS-CD) was performed in all patients at baseline, completion of treatment, and anytime during the study period if a patient had deterioration of nerve function noted clinically. All peripheral nerves were assessed, and parameters studied were cross-sectional area (CSA), length of thickening, endoneural flow signals (ENFS), and distortion in fascicular symmetry. Of 54 treatment-naive leprosy patients, loss of sensation was noted in 37 (68.5%), paresthesia in 20 (37.0%), and neuropathic pain in 7 (12.9%) at baseline presentation. At end of treatment of leprosy, maximum improvement in NFI across all clinical criteria was seen in ulnar and radial nerves (P <0.05). The number of impairments on HRUS-CD decreased consistently, significantly for ulnar (P = 0.009 right ulnar, P = 0.012 left ulnar) and right radial (P = 0.025) nerves, and significant improvements in CSA and ENFS were seen across multiple nerves, which correlated with improvement in NFI as well. Abnormal HRUS-CD findings in the target nerves were significantly associated with multibacillary cases (odds ratio [OR]: 4.33; 95% CI: 0.62-30.31), those in reaction (OR: 9.42; 95% CI: 1.51-58.66), and those older than 40 years (OR: 3.14; 95% CI: 0.49-19.93). This study provides objective evidence of improvement in NFI with anti-leprosy treatment, supporting integration of HRUS-CD imaging in monitoring nerve involvement in leprosy.

Objective To investigate the characteristics of giant F-waves in patients with amyotrophic lateral sclerosis (ALS) and the relationship between giant F-waves and disease phenotype. Methods Motor nerve conduction study and F-waves were performed to the median, ulnar, tibial and peroneal nerves of 55 patients with ALS and 52 healthy volunteers. A series of 100 electrical stimuli were employed to obtain F-waves. The following F-wave variables were estimated: frequency of giant F-waves, frequency of patients with giant F-waves, the relationship between giant F-waves and lower motor neuron dysfunction, the relationship between giant F-waves and upper motor neuron dysfunction, the relationship between giant F-waves and disease duration, the relationship between giant F-waves and disease severity, and the relationship between giant F-waves and disease progression rate (DPR). Results The frequencies of giant F-waves (ALS: median nerve 0.00(0.00)%, ulnar nerve 0.00(1.02)%, tibial nerve 0.00(0.00)%, peroneal nerve 0.00(0.00)%. Normal controls: median nerve 0.00(0.00)%, Z=-2.360, P=0.018; ulnar nerve 0.00(0.00)%, Z=-3.997, P<0.01; tibial nerve 0.00(0.00)%, Z=-3.006, P=0.003; peroneal nerve 0.00(0.00)%, Z=-3.006, P=0.003) and the frequencies of patients with giant F-waves (ALS: median nerve 13/55, 23.6%, ulnar nerve 26/55, 47.2%, tibial nerve 18/55, 32.7%, peroneal nerve 16/55, 29.1%. Normal controls: median nerve 4/52, 7.7%, χ2=0.024, P=0.024; ulnar nerve 7/52, 13.5%, χ2=14.326, P<0.01; tibial nerve 6/52, 11.5%, χ2=6.897, P=0.009; peroneal nerve 6/52, 11.5%, χ2=5.042, P=0.025) in the median nerve, ulnar nerve, tibial nerve and peroneal nerve were significantly increased compared with those of the normal controls. No significant differences were found in the frequencies of upper motor neuron dysfunction between nerves with giant F-waves and nerves without giant F-waves in the median nerves, ulnar nerves, tibial nerves and peroneal nerves of ALS patients. The compound muscle action potential amplitude of nerves with giant F-waves was significantly higher than those of nerves without giant F-waves in the median nerves (11.20(5.80) mV vs 5.90(8.50) mV, t=2.883, P=0.004)and tibial nerves ((13.20±4.61) mV vs (10.69±4.76) mV, t=-2.222, P=0.028)of the ALS patients. No significant correlation was detected between the frequency of giant F-waves and disease duration or ALS functional rating scale in the ALS patients, while the frequency of giant F-waves correlated inversely with the DPR(r=-0.287, P=0.034). No significant differences were detected in disease duration between ALS patients with giant F-waves and those without giant F-waves. Compared with those in ALS patients without giant F-waves, the revised ALS Functional Rating Scale score (37.00(3.00) vs 42.00(4.75), Z=3.197, P=0.001) was more, the DPR (0.50(0.35)vs 0.90(0.43), Z=-3.033, P=0.002) was slower in ALS patients with giant F-waves. Conclusions The giant F-waves were significantly increased in the ALS patients than those in the healthy volunteers and were distributed asymmetrically between the left and right sides. These electrophysiological characteristics of ALS patients fitted well with progressive loss of anterior horn cells, and indicated differential involvement of different spinal motoneuron pools in the ALS patients. No correlations were found between the frequency of giant F-waves and disease duration. The appearance of giant F-waves may indicate loss of spinal motoneuron early in the disease course, and may suggest that the degree of reinnervation and functional compensation are relatively good after motoneuron loss. Key words: Amyotrophic lateral sclerosis; Neural conduction; F-wave

Introduction: There is a high prevalence of leprosy in certain areas of our country. The main problem with leprosy is the prevalence of disability in untreated patients. Aims: To know the clinical profile of leprosy patients and to find out the risk factors for disabilities. Methods: A retrospective study of 10 years was conducted from April 2003 to March 2014 was conduced. Results: There were 137 MB (75.6%) and 44 PB (24.4%) cases. There were 35 (19.33%) MB patients with disability and 5 (2.76%) PB patients with disability. There were 5 cases (2.7%) with childhood leprosy. The percentage of defaulters was 9 (4.97%). The Patients were grade II disability were 19.4% and patients with grade I disability were 2.8%. Regarding the nerve involvement in leprosy, ulnar nerve was most commonly involved in 45 (24.86%) patients, lateral popliteal nerve in 20 (11.04%) patients, posterior tibial nerve in 15 (8.28%) patients and median nerve was involved in 12 (6.62%) patients. Conclusions: The multibacillary patients are more susceptible to neuritis as compared to the paucibacillary patients. The occurence of neuritis is a significant risk factor for disabilities in leprosy. Early diagnosis and treatment is important to reduce the load of infection.

Objective: The study aimed to investigate whether sample sizes of F-wave study differed according to different nerves, different F-wave parameters, and amyotrophic lateral sclerosis(ALS) patients or healthy subjects. Methods: The F-waves in the median, ulnar, tibial, and deep peroneal nerves of 55 amyotrophic lateral sclerosis (ALS) patients and 52 healthy subjects were studied to assess the effect of sample size on the accuracy of measurements of the following F-wave parameters: F-wave minimum latency, maximum latency, mean latency, F-wave persistence, F-wave chronodispersion, mean and maximum F-wave amplitude. A hundred stimuli were used in F-wave study. The values obtained from 100 stimuli were considered "true" values and were compared with the corresponding values from smaller samples of 20, 40, 60 and 80 stimuli. F-wave parameters obtained from different sample sizes were compared between the ALS patients and the normal controls. Results: Significant differences were not detected with samples above 60 stimuli for chronodispersion in all four nerves in normal participants. Significant differences were not detected with samples above 40 stimuli for maximum F-wave amplitude in median, ulnar and tibial nerves in normal participants. When comparing ALS patients and normal controls, significant differences were detected in the maximum (median nerve, Z=-3.560, P<0.01; ulnar nerve, t=5.019, P<0.01; tibial nerve, Z=-2.475, P<0.05; peroneal nerve, Z=-2.088, P<0.05)and mean F-wave latency (median nerve, Z=-3.243, P<0.01; ulnar nerve, t=3.876, P<0.01; tibial nerve, Z=-2.206, P<0.05; peroneal nerve, Z=-2.205, P<0.05)in all four nerves, F-wave chronodispersion (Z=-3.152, P<0.01)in the ulnar nerve, F-wave persistence in the median (Z=6.139, P<0.01)and ulnar nerves(Z=5.350, P<0.01), mean F-wave amplitude in the tibial nerve(t=2.981, P<0.01), maximum F-wave amplitude in the ulnar (Z=-2.134, P<0.05)and tibial nerves (t=2.746, P<0.01)with 20 stimuli; for chronodispersion in tibial nerve (t=2.551, P<0.05)100 stimuli, for chronodispersion in peroneal nerve (Z=-2.086, P<0.05)80 stimuli, for F-wave persistence in tibial nerve (Z=2.119, P<0.05) 60 stimuli, for mean F-wave amplitude in ulnar (Z=-2.552, P<0.05)and peroneal nerve (Z=-2.228, P<0.05)40 stimuli, for maximum F-wave amplitude in peroneal nerve (t=2.693, P<0.01)60 stimuli were necessary to detect differences. Conclusions: Sample sizes of F-wave study differed according to different nerves, different F-wave parameters , and ALS patients or healthy subjects.