Assessment of neuropathy subtypes in type 1 diabetes.

INTRODUCTION: Diabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage-SFN, LFN, and MFN-in T1DM-associated DPN, both with and without pain. RESEARCH DESIGN AND METHODS: In this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests). RESULTS: MFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern. CONCLUSIONS: DPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.

Carpal Tunnel Syndrome: Rapid Evidence Review.

Carpal tunnel syndrome (CTS) is caused by compression of the median nerve as it travels through the carpal tunnel. Patients commonly experience pain, paresthesia, and, less often, weakness in the distribution of the median nerve. Provocative maneuvers, such as the Phalen test and Tinel sign, have varying sensitivity and specificity for the diagnosis of CTS. Thenar atrophy is a late finding and highly specific for CTS. Although patients with a classic presentation of CTS do not need additional testing for diagnosis, electrodiagnostic studies can confirm the diagnosis in atypical cases, exclude other causes, and gauge severity for surgical prognosis. An abnormal nerve conduction study is useful for ruling in CTS, but a normal test does not necessarily exclude it. Over-the-counter analgesics, such as nonsteroidal anti-inflammatory drugs and acetaminophen, have not shown benefit for CTS. Patients with mild to moderate CTS initially may be offered nonsurgical treatments, such as splinting or local corticosteroid injections. Night-only splinting is as effective as continuous wear. A neutral wrist splint may be more effective than an extension splint. In patients with recent onset of CTS, corticosteroid injections provide slightly greater improvement of symptoms compared with splinting at 6 weeks, with similar outcomes at 6 months. Patients with severe CTS, including objective weakness or sensory deficits, should be offered surgical decompression. Endoscopic and open carpal tunnel release techniques are equally effective.

Development and Progression of Polyneuropathy Over 5 Years in Patients With Type 2 Diabetes.

BACKGROUND AND OBJECTIVES: There is a need for knowledge regarding the natural course of diabetic polyneuropathy (DPN), a complication in type 2 diabetes (T2D). The aim of this study was to examine the development of DPN over time. METHODS: Patients with newly diagnosed T2D, recruited from a national cohort, and controls without diabetes of similar age and sex, underwent sensory phenotyping in 2016-2018. The Toronto consensus criteria were used to classify patients into possible, probable, and confirmed DPN. For this 5-year, observational, follow-up, cohort study, all participants were invited to a reexamination combining bedside sensory examination, quantitative sensory testing (QST), nerve conduction studies (NCSs), and skin biopsies measuring intraepidermal nerve fiber density (IENFD) in order to compare phenotypic and diagnostic changes over time. RESULTS: Of the baseline 389 patients and 97 controls, 184 patients (median [interquartile range] diabetes duration 5.9 [4.1-7.4] years, mean hemoglobin A1c [HbA1c] 51 ± 11 mmol/mol at baseline) and 43 controls completed follow-up (46.9%). Confirmed DPN was present in 35.8% and 50.3%, probable DPN in 27.2% and 14.6%, possible DPN in 17.2% and 16.6%, and no DPN in 15.2% and 17.9% at baseline and follow-up, respectively. The estimated prevalence (95% CI) of confirmed DPN was 33.5% (24.9-42.1) compared with 22.7% (17.5-28.0) at baseline. During the follow-up period, 43.9% of patients with probable DPN developed confirmed DPN. Progression of neuropathy occurred in 16.5% and 24.7% and regression in 5.9% and 18.6% of patients based on NCS and IENFD, respectively. Progression based on NCS and/or IENFD was associated with higher baseline waist circumference and triglycerides, and regression with lower baseline HbA1c. Patients with at least probable DPN at baseline but neither patients without DPN nor controls developed increased spread of hyposensitivity, more hyposensitivity on QST and lower NCS z-scores at follow-up, and worsening of nerve parameters at follow-up correlated with higher baseline triglycerides. DISCUSSION: In patients with well-regulated T2D, the proportion of patients with confirmed DPN increased over 5 years driven by progression from probable DPN. A large proportion of patients progressed, and a smaller proportion regressed on nerve parameters. Higher triglycerides correlated with this progression and may constitute a risk factor.

Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Electroneuromyography comparison between pre-elderly adult females with and without MS; the potential role of a mind-body therapy in improving neurophysiological profile of MS during pandemic.

INTRODUCTION: Imaginary exercises seem to be useful therapeutic approaches to modulate neuromuscular functions due to two main reasons: first, this training would not greatly increase body temperature, and secondly, it can positively affect brain-muscle pathways-which are both primary factors should be considered in rehabilitation programs for patients with multiple sclerosis (MS). METHOD: 32 pre-elderly adult females with relapsing-remitting MS (n = 16 - age M (SD): 56.75 (5.07)) and without MS (n = 16 - age M (SD): 56.56 (4.35)) voluntarily recruited. First, they were assigned into two groups: MS patients and healthy controls, to investigate baseline between-group comparison. Then, MS patients were randomly divided into two groups of eight each, designated as experimental and control groups. Recording the nerve conduction velocity (NCV) of tibial nerve and integrated electromyographic muscle activation (IEMG) of gastrocnemius muscle was conducted twice, before and after a six-week mind-body exercise therapy to evaluate its effectiveness on improving neuromuscular function. RESULTS: The results showed significant difference in both tibial NCV (P < 0.001) and IEMG (P = 0.001) variables between non-MS group and MS group. Furthermore, there was a significant main effect of intervention (P = 0.05) and time (P < 0.001) on IEMG in the MS group, while there was no significant effect of intervention (P = 0.18) and time (P = 0.23) on NCV (p = 0.89). CONCLUSION: Neuromuscular dysfunction were apparent in MS patients, and a mind-body therapy of imagery isometric training was found to be useful on improving the neurological deficit in women with MS. TRIAL REGISTRATION NUMBER: UMIN000046935.

A case control study of the relationship between persistent serum creatine kinase elevation and polyneuropathy.

Creatine kinase (CK) has been associated with neuropathy, but the mechanisms are uncertain. We hypothesized that peripheral nerve function is impaired in subjects with persistent CK elevation (hyperCKemia) compared to age- and sex matched controls in a general population. The participants were recruited from the population based Tromsø study in Norway. Neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG) in subjects with persistent hyperCKemia (n = 113; 51 men, 62 women) and controls (n = 128; 61 men, 67 women) were performed. The hyperCKemia group had higher NIS score than the controls (p = 0.050). NCS of the tibial nerve showed decreased compound motor action potential amplitude (p < 0.001), decreased motor conduction velocity (p < 0.001) and increased F-wave latency (p = 0.044). Also, reduced sensory amplitudes of the median, ulnar, and sural nerves were found. EMG showed significantly increased average motor unit potential amplitude in all examined muscles. CK correlated positively with glycated hemoglobin and non-fasting glucose in the hyperCKemia group, although not when controlled for covariates. The length dependent polyneuropathy demonstrated in the hyperCKemia group is unexplained, but CK leakage and involvement of glucose metabolism are speculated on.

Corpus Callosum-Mediated Interhemispheric Interactions in Cervical Spondylotic Myelopathy.

PURPOSE: The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation. METHODS: Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined. RESULTS: In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls ( p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls ( p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs ( p > 0.05 for all) bilaterally. CONCLUSIONS: Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.

[To determine the value of iMAX, a new electrodiagnostic method, and its application in the evaluation of peripheral motor nerve excitability].

Objective: To test the new method of iMAX (the minimum stimulus current that elicits the maximum compound muscle action potential amplitude) electrodiagnosis, verify the feasibility of this method in evaluating the excitability of peripheral motor axons, and preliminarily explore the clinical application value. Methods: This study was a cross-sectional study. A total of 50 healthy subjects were recruited from the outpatient department of Peking University Third Hospital from June 2022 to March 2023, including 25 males and 25 females, aged 25-68 (48±8) years. Eleven patients with Charcot-Marie-Pain-1A (CMT1A), 7 males and 4 females, aged 19-55 (41±13) years and 21 patients with diabetic peripheral neuropathy (DPN), 10 males and 11 females, aged 28-79 (53±16) years were enrolled in this study. iMAX of bilateral median nerves, ulnar nerves and peroneal nerves were detected in all patients. Repeatable motor responses with minimum motor threshold and amplitude of at least 0.1 mV and the minimum stimulus current intensity, at which the maximum compound muscle action potential amplitude is elicited, were measured respectively [1 mA increment is called (iUP) and, 0.1 mA adjustment is called (iMAX)].Comparison of the parameters: the parameters of threshold, iUP and iMAX were compared among different age groups, genders and sides, body mass index(BMI) values and detection time , as well as between CMT1A patients, DPN patients and healthy subjects. Results: In healthy subjects, the threshold, iUP value and iMAX value were (1.8±0.7) mA, (4.4±1.2) mA, and (4.2±1.3) mA respectively; ulnar nerve (3.1±1.6) mA, (6.8±3.2) mA, (6.4±3.2) mA; peroneal nerve (3.7±2.0) mA, (7.8±2.8) mA, (7.4±2.9) mA. There were statistically significant differences in threshold, iUP value and iMAX value among different age groups (all P<0.001).With the increase of age, there was a trend of increasing threshold, iUP, and iMAX values in different nerves, and the differences are statistically significant (all P<0.001). There were no significant differences in gender, side and detection time threshold, iUP value and iMAX value (all P>0.05). The parameters of healthy subjects with high BMI value were higher than those of healthy subjects with low BMI value(all P<0.05). Compared with the healthy subjects, the parameters of 11 CMT1A patients were significantly increased (all P<0.05), and the parameters of 21 DPN patients were slightly increased (P<0.05). Conclusion: The new iMAX method reflects the excitability of motor axons and early axonal dysfunction, which is an important supplement to the traditional nerve conduction, and can be used to monitor motor axon excitability disorders.

Double entrapment neuropathy of the ulnar nerve at the elbow and the wrist : double crush syndrome?

BACKGROUND: Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. METHODS: The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. RESULTS: In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. CONCLUSION: Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.

Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.

Study on the relationship between peripheral nerve fiber types and levodopa usage in Parkinson's disease.

Background and purpose:

The aim of this study is to comprehensively determine the types of affected fibers in Parkinson’s disease (PD) patients by employing nerve conduction studies (NCS), sympathetic skin response (SSR) examinations, and current perception threshold (CPT) testing and to analyze the correlation between levodopa use and nerve involvement.

This retrospective study included 36 clinically diagnosed PD patients who were recruited between January 2018 and April 2019. All patients underwent NCS, SSR testing, and CPT sensory examinations. Additionally, the PD patients were assessed for disease staging using the Hoehn and Yahr (H-Y) scale. 

Fifteen patients were included in the tremor-dominant subtype, ten patients in the rigid-dominant subtype, and eleven patients in the mixed subtype. Eleven patients were using levodopa, while twenty-five patients had never used any anti-Parkinson’s medication. Ten patients (28%) showed abnormal sympathetic skin responses (SSR). The CPT examination revealed sensory abnormalities in twenty-four patients (67%), with eighteen patients (75%) experiencing sensory hypersensitivity and six patients (25%) experiencing sensory hypoesthesia. Twelve patients (33%) had normal CPT results. Among the patients with abnormal CPT findings, seven cases (29%) involved large myelinated fiber damage, twenty-two cases (92%) involved small myelinated fiber damage, and nineteen cases (79%) involved unmyelinated fiber damage. The rate of sensory abnormalities was 64% (7/11) in the levodopa group and 68% (17/25) in the non-levodopa group, with no statistically significant difference between the two groups. 

The incidence of abnormal CPT findings in PD patients was higher than that of abnormal SSR responses, suggesting that nerve fiber damage primarily affects small fiber nerves (SFN).

Utility of single fibre electromyography (SFEMG)and motor unit number estimation technique (MUNE) in the diagnosis and differentiation of polyneuropathies of different aetiology.

OBJECTIVE: To determine whether single fibre electromyography and motor unit number index can distinguish between axonal and myelin lesions in polyneuropathies. METHODS: This case-control study was conducted at the Department of Medical Physiology, School of Medicine, University of Duhok, Iraq, and the Neurophysiology Department, Hawler Teaching Hospital, Erbil, Iraq, from January 2021 to March 2022. Group A had patients diagnosed with polyneuropathy regardless of the aetiology, while group B had age-matched healthy controls. Both groups were subjected to single fibre electromyography and motor unit number index as well as conventional nerve conduction study and concentric needle electromyography. Data was analysed using SPSS 26. RESULTS: Of the 140 subjects, 60(43%) were patients in group A; 40(67%) males and 20(33%) females with mean age 55.3±7.2 years. There were 80(57%) controls in group B; 43(54%) females and 37(46%) males with mean age 53.81±7.15. Group A had significantly higher single fibre electromyography jitter, and mean consecutive difference (MCD) values than group B (p<0.05). Group A patients with axonal polyneuropathy had a higher mean jitter (MCD) value (36.476.7ms) than those with demyelinating polyneuropathy (23.262.31 ms) (P <0.05). Patients in group A had a motor unit number index value with a significantly lower mean value (p<0.05) when compared to the controls. Axonal polyneuropathy patients had a lower MUNIX value (99.612.8) than demyelinating polyneuropathy patients (149.845.7) (P< 0.05). CONCLUSIONS: Single fibre electromyography and motor unit number index could help differentiate between the pathophysiology of axonal and demyelinating polyneuropathy.

The role of electrodiagnosis in focal neuropathies.

Electrodiagnostic (EDX) testing plays an important role in confirming a mononeuropathy, localizing the site of nerve injury, defining the pathophysiology, and assessing the severity and prognosis. The combination of nerve conduction studies (NCS) and needle electromyography findings provides the necessary information to fully assess a nerve. The pattern of NCS abnormalities reflects the underlying pathophysiology, with focal slowing or conduction block in neuropraxic injuries and reduced amplitudes in axonotmetic injuries. Needle electromyography findings, including spontaneous activity and voluntary motor unit potential changes, complement the NCS findings and further characterize chronicity and degree of axon loss and reinnervation. EDX is used as an objective marker to follow the progression of a mononeuropathy over time.

Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes.

OBJECTIVE: The objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. METHODS: In 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. RESULTS: RF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

Slow touch and ultrafast pain fibres: Revisiting peripheral nerve classification.

One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aß afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axons molecular expression and electrophysiological response properties.

Longitudinal follow-up and prognostic factors in nitrous oxide-induced neuropathy.

BACKGROUND AND AIM: Recreational use of nitrous oxide (N2O) has been associated with the development of severe nitrous oxide-induced neuropathy (N2On). Follow-up of these patients poses challenges, and their clinical progression remains largely unknown. The identification of prognostic factors is made difficult by the lack of standardized longitudinal assessments in most studies. The objective was to document the course of neuropathy through systematic follow-up assessments in N2On patients to identify prognostic factors for persistent disability after 6 months. METHODS: We gathered demographic, clinical, biological, and electrophysiological data from N2On patients hospitalized in the Referral center in Marseille, both at baseline and during a standardized follow-up assessment at 6 months. RESULTS: We retrospectively included 26 N2On patients (mean age 22.6 ± 4.4). Significant improvements were observed in all main clinical scores including Rankin, ONLS, and MRC testing (p < .01). Electrophysiological studies (EDX) revealed a predominantly motor neuropathy with marked reduction in CMAP in the lower limbs at baseline, and no significant improvement in motor parameters (p = .543). Rankin score at 6 months correlated with the initial weekly N2O consumption (r = .43, p = .03) and the CMAP sum score in the lower limbs at the first EDX (r = -.47, p = .02). Patients with and without myelitis showed similar Rankin and ONLS score after 6 months. INTERPRETATION: The clinical course generally improved favorably at 6 months with notable amelioration in the primary disability scores, sensory deficits, and ataxia. However, distal motor impairment associated with peripheral neuropathy persisted, with distal axonal loss emerging as the main prognostic factor for long-term disability in these young patients.

Muscle excitability testing.

Conventional electrophysiological methods, i.e. nerve conduction studies and electromyography are suitable methods for the diagnosis of neuromuscular disorders, however, they provide limited information about muscle fibre membrane properties and underlying disease mechanisms. Muscle excitability testing is a technique that provides in vivo information about muscle fibre membrane properties such as membrane potential and ion channel function. Since the 1960s, various methodologies have been suggested to examine muscle membrane properties but technical difficulties have limited its use. In 2009, an automated, fast and simple application, the so-called multi-fibre muscle velocity recovery cycles (MVRC) has accelerated the use of muscle excitability testing. Later, frequency ramp and repetitive stimulation protocols have been developed. Though this method has been used mainly in research for revealing disease mechanisms across a broad range of neuromuscular disorders, it may have additional diagnostic uses; value has been shown particularly in muscle channelopathies. This review will provide a description of the state-of-the art of methodological and clinical studies for muscle excitability testing.

Nerve cross-sectional area in advanced uremic neuropathy: A nerve ultrasound pilot study.

BACKGROUND AND PURPOSE: Uremic neuropathy (UN) is a disabling neuropathy in end-stage kidney disease (ESKD) affecting the majority of patients receiving long-term hemodialysis (HD). One previous nerve ultrasound study reported an increased cross-sectional area (CSA) of the median nerve in moderate UN, while another study found enlarged sural nerves in small-fiber polyneuropathy associated with ESKD. The present cohort study aims to analyze bilateral CSA of multiple nerves in UN. METHODS: Ten nondiabetic ESKD patients with UN on HD for at least 2 years and 10 healthy age-matched controls underwent bilateral ultrasound examinations with CSA measurements in 13 arm and leg nerve sites. Nerve conduction studies (NCS) and the total neuropathy score (TNS) were recorded. Pearson's coefficient and the Mann-Whitney U-test were used to analyze correlations and compare groups. RESULTS: ESKD patients presented advanced neuropathic symptoms (mean TNS 15.9). NCS showed significantly reduced motor and sensory amplitudes in the UN group compared to the control group, and a slightly reduced nerve CSA was observed in 5 of 13 nerve sites (p < .05); the other nerve sites were not enlarged. Sural nerve CSA (p < .05) and sensory amplitude (p < .01) were negatively correlated with the TNS. CONCLUSIONS: Nerve enlargement was not observed in the present study in advanced UN. A reduced nerve CSA observed in the sural nerve suggests an axonal loss associated with long-term HD in ESKD. During clinical workup of an acute disease of the peripheral nervous system in ESKD patients, nerve enlargement might be attributable to other causes than chronic UN.

Oral and topical analgesia in pediatric electrodiagnostic studies.

INTRODUCTION/AIMS: Electrodiagnostic examinations, such as nerve conduction studies (NCS) and needle electromyography (EMG), are perceived as painful by children and their parents/guardians. Methods to reduce peri-procedural pain improve compliance and have neurocognitive and neuropsychiatric benefits. This study aimed to assess the efficacy of combined oral and topical analgesics (COTA), oral analgesics (OA), and placebo in reducing pain during NCS/EMG in children. METHODS: We performed a double-blind, randomized, placebo-controlled trial on children presenting to our neurophysiology lab. Patients were stratified into two age groups (6M-6Y and 7Y-18Y) and randomized into three arms: COTA, OA, and placebo. Pain scores post-NCS/EMG were assessed using the Modified Behavioral Pain Scale (MBPS) and Faces Pain Scale-Revised (FPS-R). RESULTS: One hundred thirteen participants were enrolled. A comparison of participants from both age groups combined revealed no significant differences in guardian FPS-R scores across all arms for NCS and EMG. A significant difference in the distribution of post-NCS FPS-R score severities in children aged 7Y-18Y was noted between OA and placebo (p = .007). EMG was more painful than NCS across all arms (p < .05). In children aged 6M-6Y undergoing at least 10 muscle samplings during EMG, those receiving COTA had significantly lower pain scores (p = .014). DISCUSSION: This study reveals the complexity of pediatric pain perception during NCS/EMG and highlights that other methods to reduce experienced pain are required. Our findings suggest that procedural characteristics, such as number of muscles sampled, may influence the effectiveness of analgesia and serve as a foundation for future research aimed at optimizing pain management strategies.

Exploring pathogenic pathways in carpal tunnel syndrome: sterile inflammation and oxidative stress.

OBJECTIVES: The main objective of the current study was to find the association between oxidative stress, inflammatory markers, and electrophysiological profile with symptom severity in patients of carpal tunnel syndrome (CTS). METHODS: Thirty-two carpal tunnel syndrome patients and 32 controls were included in the study. Boston CTS questionnaire along with plasma oxidative stress markers including superoxide dismutase, malondialdehyde, and nitric oxide and inflammatory markers including IL-6 and TNF-α were compared with the electrophysiological parameters derived from nerve conduction studies. Statistical significance of the levels between groups was calculated using unpaired-t test after checking for normality with D'Agostino & Pearson omnibus normality test. RESULTS: We found that the median nerve conduction velocity was prolonged, amplitude was decreased, while the levels of oxidative stress markers like malondialdehyde (MDA), superoxidase dismutase (SOD), and nitric oxide (NO) were increased in CTS patients compared to controls. Inflammatory markers like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also increased in CTS patients. We found that plasma SOD and TNF-α correlated well with the median motor amplitude. There was no other significant correlation between oxidative stress markers and inflammatory markers with nerve conduction studies or disease severity. Patients with mild disease also showed lesser levels of SOD, NO, IL-6, and TNF-α markers than patients with severe disease. CONCLUSIONS: CTS is probably a disease of sterile inflammation and disbalance of oxidative stress, with higher inflammatory and oxidative stress markers pointing to a more severe disease.