Small Nerve Research Articles

Assessing Corneal Confocal Microscopy and Other Small Fiber Measures in Diabetic Polyneuropathy.

Damage to small nerve fibers is common in diabetic polyneuropathy (DPN), and the diagnosis of DPN relies on subjective symptoms and signs in a combination with objective confirmatory tests, typically electrophysiology or intraepidermal nerve fiber density (IENFD) from skin biopsy. Corneal confocal microscopy (CCM) has been introduced as a tool to detect DPN. However, it is unclear if CCM can reliably be used to diagnose DPN and how the technique compares with other commonly used measures of small fiber damage, such as IENFD, cold detection threshold (CDT), and warm detection threshold (WDT). Therefore, we assessed and compared the use of CCM, IENFD, CDT, and WDT in the diagnosis of DPN in patients with type 2 diabetes. In this cohort study, the participants underwent detailed neurologic examination, electrophysiology, quantification of IENFD, CCM, and quantitative sensory testing. Definition of DPN was made in accordance with the Toronto criteria for diabetic neuropathy (without relying on IENFD and thermal thresholds). A total of 214 patients with at least probable DPN, 63 patients without DPN, and 97 controls without diabetes were included. Patients with DPN had lower CCM measures (corneal nerve fiber length [CNFL], nerve fiber density, and branch density), IENFD, CDT, and WDT compared with patients without DPN (p ≤ 0.001, <0.001, 0.002, p < 0.001, p = 0.003, and <0.005, respectively), whereas there was no difference between controls and patients with diabetes without DPN. All 3 CCM measures showed a very low diagnostic sensitivity with CNFL showing the highest (14.4% [95% CI 9.8-18.4]) and a specificity of 95.7% (88.0-99.1). In comparison, the sensitivity of abnormal CDT and/or WDT was 30.5% (24.4-37.0) with a specificity of 84.9% (74.6-92.2). The sensitivity of abnormal IENFD was highest among all measures with a value of 51.1% (43.7-58.5) and a specificity of 90% (79.5-96.2). CCM measures did not correlate with IENFD, CDT/WDT, or neuropathy severity in the group of patients with DPN. CCM measures showed the lowest sensitivity compared with other small fiber measures in the diagnosis of DPN. This indicates that CCM is not a sensitive method to detect DPN in recently diagnosed type 2 diabetes. This study provides Class III evidence that CCM measures aid in the detection of DPN in recently diagnosed type 2 diabetics but with a low sensitivity when compared with other small fiber measures.

Integrative miRNA-mRNA profiling of human epidermis: unique signature of SCN9A painful neuropathy.

Personalized management of neuropathic pain is an unmet clinical need due to heterogeneity of the underlying aetiologies, incompletely understood pathophysiological mechanisms and limited efficacy of existing treatments. Recent studies on microRNA in pain preclinical models have begun to yield insights into pain-related mechanisms, identifying nociception-related species differences and pinpointing potential drug candidates. With the aim of bridging the translational gap towards the clinic, we generated a human pain-related integrative miRNA and mRNA molecular profile of the epidermis, the tissue hosting small nerve fibres, in a deeply phenotyped cohort of patients with sodium channel-related painful neuropathy not responding to currently available therapies. We identified four miRNAs strongly discriminating patients from healthy individuals, confirming their effect on differentially expressed gene targets driving peripheral sensory transduction, transmission, modulation and post-transcriptional modifications, with strong effects on gene targets including NEDD4. We identified a complex epidermal miRNA-mRNA network based on tissue-specific experimental data suggesting a cross-talk between epidermal cells and axons in neuropathy pain. Using immunofluorescence assay and confocal microscopy, we observed that Nav1.7 signal intensity in keratinocytes strongly inversely correlated with NEDD4 expression that was downregulated by miR-30 family, suggesting post-transcriptional fine tuning of pain-related protein expression. Our targeted molecular profiling advances the understanding of specific neuropathic pain fine signatures and may accelerate process towards personalized medicine in patients with neuropathic pain.

Application of microdialysis combined with UHPLC-QTOF/MS to screen for endogenous metabolites in aquatic organisms as biomarkers of exposure to an emerging contaminant, triclosan.

The detection of emerging contaminants (ECs) and understanding their ecotoxicity has brought new challenges to water pollution control. Triclosan (TCS), as an emerging contaminant, is a commonly used antibacterial agent widely present in the environment. Microdialysis (MD), as a sampling technique, can overcome some of the deficiencies of traditional approaches to sampling, using sources such as blood, urine, tissue, and target organs, in terms of invasiveness, time from collection to analysis, and possible changes during sample preparation. In this study, we coupled MD with analysis using UHPLC-QTOF/MS to identify the endogenous metabolites in the liver as biomarkers of the exposure of living crucian carp to TCS. The identified biomarkers were then quantified using UHPLC-MS/MS to continuously monitor the effect of TCS on endogenous metabolites in the liver of living crucian carp, which contributes to a better understanding of the toxicological effect of TCS. The experimental results demonstrated that TCS exposure interfered with the metabolic pathways of amino acids (L-isoleucine and L-histidine), purines (xanthine and hypoxanthine), and small nerve molecules (acetylcholine and choline).

Microphthalmia, aphakia and agenesis of the optic chiasm and tract in a wild fox squirrel (Sciurusniger)

We describe gross and histopathological features of multiple ocular and neuro-ophthalmic abnormalities in a fox squirrel (Sciurus niger). Ophthalmic findings included severe bilateral microphthalmos, with the right eye more affected than the left. Histopathology confirmed severe microphthalmia, aphakia, disorganized retinal tissue and small optic nerves, as well as agenesis of the optic chiasm and optic tract. This combination of neuro-ophthalmic abnormalities has not been previously described in wild animals.

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC.

The test–retest reliability of large and small fiber nerve excitability testing with threshold tracking

ObjectiveStandard nerve excitability testing (NET) predominantly assesses Aα- and Aβ-fiber function, but a method examining small afferents would be of great interest in pain studies. Here, we examined the properties of a novel perception threshold tracking (PTT) method that preferentially activates Aδ-fibers using weak currents delivered by a novel multipin electrode and compared its reliability with NET. MethodsEighteen healthy subjects (mean age:34.06 ± 2.0) were examined three times with motor and sensory NET and PTT in morning and afternoon sessions on the same day (intra-day reliability) and after a week (inter-day reliability). NET was performed on the median nerve, while PTT stimuli were delivered through a multipin electrode located on the forearm. During PTT, subjects indicated stimulus perception via a button press and the intensity of the current was automatically increased or decreased accordingly by Qtrac software. This allowed changes in the perception threshold to be tracked during strength-duration time constant (SDTC) and threshold electrotonus protocols. ResultsThe coefficient of variation (CoV) and interclass coefficient of variation (ICC) showed good–excellent reliability for most NET parameters. PTT showed poor reliability for both SDTC and threshold electrotonus parameters. There was a significant correlation between large (sensory NET) and small (PTT) fiber SDTC when all sessions were pooled (r = 0.29, p = 0.03). ConclusionsThreshold tracking technique can be applied directly to small fibers via a psychophysical readout, but with the current technique, the reliability is poor. SignificanceFurther studies are needed to examine whether Aβ-fiber SDTC may be a surrogate biomarker for peripheral nociceptive signalling.

Propagation of neuronal signals in intact and injured peripheral nerves: The role of nonlinear diffusion of transmembrane potential

We present results of a computational study of the influence of nonlinear diffusion on propagation of electrical excitation generated in normal and injured peripheral nerves (PN) using a one-dimensional Fitzhugh-Nagumo (FN) model. Changes in action potential duration (APD) and repolarization intervals (RI) were observed based upon modification of the FN model. Namely, the model has been altered by adding an additional power function type nonlinear diffusion term which accounted for substantial intra-extracellular charge balance changes developing during action potential formation in small peripheral nerves. It was found that changes in magnitude of nonlinear diffusion coefficient result in oscillations of APD and RI in both normal and injured PNs with partially reduced conductivity. It was also found that these oscillations in injured PNs had markedly higher amplitudes dependent on the PN's length as well as on the width of its injured part. Results of our study may be useful in improving of monitoring of peripheral nerve growth and adjusting propagation of excitation to enhance impaired connectivity in injured peripheral nerves.

Immunohistochemical staining for nerve fibers in normal tissues with frozen sections: Structure and Function Relationship

Small nerve fibers are difficult to immunostain with routinely formalin-fixed and paraffin- embedded sections. Normal tissues except central nervous system are not densely innervated compared to densely distributed lymphatic and blood vessels and nerve fibers are not properly preserved in the routinely formalin-fixed and paraffin-embedded tissues. Nerve density technique with skin punch biopsy is an established method using 50 µm tissue sections, which are initially preserved in fixative. The fixed tissues are frozen sectioned and floating tissue sections are immunostained for nerve fiber markers. We had developed an alternative method using unfixed frozen sections mounted on glass slides. We had previously used this frozen section method for lymphatic and blood vessel immunohistochemistry and extended to nerve fiber immunostaining using neurofilament and CD56 as nerve fiber markers. Immunostained tissues with frozen sections were compared to formalin-fixed and paraffin-embedded colon and kidney sections. The normal tissues from rhesus monkey included heart, intestines, diaphragm, pancreas, spleen, kidney, thyroid, urinary bladder and others. Frozen section immunostained sections clearly depicted much more fine nerve fibers especially using CD56 as a nerve marker than with paraffin-embedded tissues. This technique is more labor-intensive but provides more precise distribution of fine nerve fibers than with routinely paraffin-embedded tissues. This immunostaining with frozen sections validated usefulness to depict more detailed nerve distribution and will shed light on normal histology and histopathology.

The severity of corneal nerve loss differentiates motor subtypes in patients with Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.

Central Sensitization and Small-fiber Neuropathy Are Associated in Patients With Fibromyalgia

To study the prevalence of small-fiber neuropathy (SFN) in a large cohort of patients with fibromyalgia (FM) and to better characterize the subset of patients with both FM and SFN. This 1-year, retrospective, observational cohort study included 265 patients with FM. They all performed electrochemical skin conductance (ESC) using the Sudoscan device, 1 of the simplest and most reliable technique to assess the distal autonomic nerve fibers. They completed 4 self-assessment questionnaires: (1) the Central Sensitization Inventory (CSI), (2) the Neuropathic Pain Symptom Inventory (NPSI), and (3) the Hospital Anxiety and Depression Scale (HADS), the Fibromyalgia Impact Questionnaire (FIQ). Fifty-three patients (20%) had reduced ESC values. These patients had higher CSI and HADS scores, and a larger intake of analgesic drugs compared with patients with no ESC abnormalities. Central sensitization, which was extreme in 69% of the patients (CSI score ≥60), was 1 of the main determinants of ESC abnormalities and was associated with a higher NPSI score, even though these 2 factors were not correlated. Over the past 10 years, studies have shown that a significant proportion of patients with FM have signs of small nerve fiber impairment. The possible involvement of SFN, in the occurrence and presentation of clinical symptoms in FM patients, remains however unclear. This is the first study that showed an association between central sensitization and both small nerve fiber impairment and neuropathic pain features in FM patients, rather than a direct association between SFN and neuropathic pain.

Assessment of Hearing and Vestibular Functions in a Post-COVID-19 Patient: A Clinical Case Study

SARS-CoV-2 infection may cause such complications as post-COVID-19 syndrome, which includes chronic fatigue, myalgia, arthralgia, as well as a variety of neurological manifestations, e.g., neuropathy of small fibers, hearing and vestibular dysfunction, and cognitive impairment. This clinical case describes a 41-year-old patient suffering from post-COVID-19 syndrome and chronic fatigue syndrome. A detailed examination was performed, including an in-depth study of peripheral and central hearing and vestibular functions, as well as small nerve fibers length and density in the skin and cornea of the eye. Contrary to expectations, no peripheral nervous system dysfunction was detected, despite the presence of dizziness and gait instability in the patient. Hearing tests (gap detection test and dichotic test) showed central auditory processing disorders. The evaluated lesion in the processing of temporal and verbal auditory information can be a significant factor contributing to additional overload of the neural activity and leading to chronic fatigue when performing daily activities in patients with CFS and post-COVID-19 complications.

Biomarkers in small fiber neuropathy

Small fiber neuropathy (SFN) is a relatively common, but largely understudied neurological syndrome which has affected the lives of many globally. The common symptoms of SFN include pain, dysesthesia, and autonomic dysfunction, which are caused by damage to small nerve fibers. Due to its heterogeneous nature, SFN causes a multitude of symptoms which makes the disease and its subtypes difficult to diagnose. Furthermore, as the pathophysiology of SFN remains largely enigmatic, no cause is found in around 50% of the cases and these are classified as idiopathic SFN (iSFN). The difficult task of diagnosing SFN, and the even more elusive feat of hunting for the underlying etiology, demands accurate, precise, preferably noninvasive, and affordable tools, or a combination of them. Accordingly, appropriate biomarkers for SFN are needed to stratify patients and develop cause-centered treatments in addition to symptomatic treatments. As peripheral axons grow and repair, identifying underlying causes of SFN and intervening early may spur axonal regeneration in young patients, which can greatly improve their symptoms and improve quality of life. This narrative review aims to objectively highlight functional, histological, and molecular biomarkers to aid clinicians in discerning the diagnostic tests they should use to diagnose, confirm and determine the etiology of SFN. The strengths and limitations of each potential biomarker will be discussed. Clearer diagnostic criteria, guidelines, and work-up for SFN are required for clinicians to better identify the disease in patients presenting with non-specific symptoms.

Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers-Danlos syndromes.

Ehlers-Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype is the hypermobile type. In addition to symptoms of small fibre neuropathy (SFN) due to damage to the small peripheral nerve fibres, with degeneration of the distal nerve endings, autonomic disorders such as postural tachycardia syndrome (PoTS) are frequently reported features in patients with hypermobile Ehlers-Danlos syndrome (hEDS). To date, the underlying pathophysiological mechanisms are still not completely understood. To better understand pathophysiological mechanisms of small fiber neuropathy and autonomic neuropathy in hypermobile Ehlers-Danlos Syndromes. We prospectively investigated 31 patients with hEDS compared to 31 healthy controls by using skin biopsy, quantitative sensory testing, tilt-table testing, the painDetect, Small Fibre Neuropathy Screening List and the COMPASS-31 (Composite Autonomic Symptom Score 31) questionnaire. Nineteen (61%) patients with hEDS were diagnosed with SFN, and 10 (32%) fulfilled the criteria for PoTS. Patients with hEDS had significantly higher heart rates than controls. According to quantitative sensory testing, these patients had generalized thermal and tactile hypesthesia. Skin biopsy revealed significantly reduced intraepithelial nerve fibre density proximally (thigh) and distally (lower leg) in patients compared to controls. This was consistent with various complaints of pain and sensory disturbances in both the proximal and distal body regions. These results confirm histologically proven SFN as a common feature in patients with hEDS, revealing a generalized distribution of nerve fibre loss. Regarding the frequently reported autonomic and neuropathic dysfunctions, the findings support SFN as an important, but not the only, underlying pathomechanism.

Subcategorization of Perineural Invasion and Its Impact on Survival in Patients with Oral Squamous Cell Carcinoma.

Perineural invasion (PNI) is recognizedas apoor prognostic factor in oral squamous cell carcinoma (OSCC). However, the prognostic significance offurther histologic subcategorization of PNI is inconclusive. In this study,we determined the prognostic relevance of histologic subcategories of PNI and their correlation with the presence of other clinical and pathological parameters METHODS: This is a retrospective studyof 207 homogeneously treated OSCC patientswith histologically documented PNI from a single center.Univariate and multivariate survival outcomes, namely, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) of patients with various subcategories of PNI,namely-number of foci, size of the involved nerve, extratumoral or intratumoral extent, and intraneural or perineural location-were determined. Within the histologic subcategories of PNI, tongue primary and presence of lymph node metastasis correlated significantly with the number of nerves involved with PNI. Larger size of involved nerve correlated with advanced tumor stage. Number of foci, extent, and location of PNI werenot prognostically significantexcept size of the involved nerve which showed an inverse correlation with disease outcome as involvement of larger nerves displayed better outcomes in terms of DFS and LRFS but not of OS on multivariate analysis. Addition of adjuvant chemotherapy to radiotherapy emerged as a significant predictor of improved LRFS, DFS, and OS. Histologic subcategorization of PNI did not have prognostic relevance in our study. Involvement of even small nerves was associated with poor prognosis. Addition of chemoradiation was seen to improve prognosis.

Longitudinal Median Nerve Ultrasound Changes in Individuals With Spinal Cord Injury and an Age- and Sex-Matched Nondisabled Cohort.

To assess the natural history for development of carpal tunnel syndrome (CTS) in persons with acute spinal cord injury (SCI) at 1 year postdischarge from initial rehabilitation and to assess baseline median nerve (MN) cross-sectional area (CSA) above/below 10 mm2 correlates with any longitudinal changes in quantitative ultrasound (US) of the MN. A prospective cohort study of persons with acute SCI evaluated for CTS using quantitative US and compared to a group without SCI (non-SCI). Academic medical center. N=69 total (N=34 SCI, N=35 non-SCI). The average age in both groups was 28 and the SCI group included 30 males and 2 females and the non-SCI group included 30 males and 3 females. Not applicable. The primary outcome was the change in quantitative US parameters of the MN, including CSA and grayscale, from baseline to 1-year follow-up in those with SCI and those without SCI. CTS symptomatology and physical exam sum score and US measures for dominant and nondominant arms were considered secondary outcomes. The SCI had darker nerves at baseline (P=.036, nondominant), greater CTS symptoms at follow-up (P≤.036, bilateral), and no differences in all change scores (all P≥.056). Individuals with smaller nerves at baseline had larger increases in nerve size (P=.029, nondominant) vs those with larger nerves. Change in CTS symptoms CSA (nondominant) and nerve echogenicity (dominant) were inversely associated with their respective baseline values (all P≤.045). We observed few differences between the SCI group and the non-SCI control group and between those with smaller vs larger MN. In general, MN pathology changes (CTS symptoms and US variables) over 1 year were more common in the nondominant arm and appear to be a function of MN pathology at enrollment. Individuals with SCI may experience increased CTS symptoms as soon as 1 year after injury.

Sympathetic skin response, cutaneous silent period and nociceptive flexion reflex in Fabry disease

Background &amp; Objective: Fabry disease is one of the well-known causes of the small fiber neuropathy. This study aims to explore small and large nerve fiber functions in patients with Fabry disease without using any extra equipment in a standard neurophysiology laboratory. Methods: Patients with Fabry disease at our tertiary center were invited to the electrophysiology laboratory. Routine nerve conduction studies (NCS), sympathetic skin response (SSR), cutaneous silent period (CSP) and nociceptive flexion reflex (NFR) tests were performed. The same protocol was applied to matched healthy subjects. Results: Nineteen patients and 19 healthy controls were included. Carpal tunnel syndrome was diagnosed in 3 patients (15.9%). Palmar and plantar SSRs could not be obtained in 4 and 9 patients, respectively. Abnormal CSP responses in the upper and lower extremities were recorded in 2 and 7 patients, respectively. The NFR response was abnormal in 8 patients. In total, at least one of the SSR, CSP or NFR was abnormal in 73.7% of patients. Conclusions: The study showed that combining SSR, CSP and NFR tests along with NCS could help to determine any abnormality in small and large fiber functions in most patients. The overall sensitivity of all tests was approximately 70% compared with the clinical diagnosis of small fiber neuropathy. This study is unique in that it explored a combination of NCS, SSR, CSP and NFR tests in Fabry disease.

Continuous glucose monitoring reveals a novel association between duration and severity of hypoglycemia, and small nerve fiber injury in patients with diabetes.

Continuous glucose monitoring (CGM) has revealed that glycemic variability and low time in range are associated with albuminuria and retinopathy. We have investigated the relationship between glucose metrics derived from CGM and a highly sensitive measure of neuropathy using corneal confocal microscopy in participants with type 1 and type 2 diabetes. A total of 40 participants with diabetes and 28 healthy controls underwent quantification of corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and inferior whorl length (IWL) and those with diabetes underwent CGM for four consecutive days. CNBD was significantly lower in patients with high glycemic variability (GV) compared to low GV (median (range) (25.0 (19.0-37.5) vs 38.6 (29.2-46.9); P = 0.007); in patients who spent >4% compared to <4% time in level 1 hypoglycemia (54-69 mg/dL) (25.0 (22.9-37.5) vs 37.5 (29.2-46.9); P = 0.045) and in patients who spent >1% compared to <1% time in level 2 hypoglycemia (<54 mg/dL) (25.0 (19.8-41.7) vs 35.4 (28.1-44.8); P = 0.04). Duration in level 1 hypoglycemia correlated with CNBD (r = -0.342, P = 0.031). Duration in level 1 (181-250 mg/dL) and level 2 (>250 mg/dL) hyperglycemia did not correlate with CNFD (P > 0.05), CNBD (P > 0.05), CNFL (P > 0.05) or IWL (P > 0.05). Greater GV and duration in hypoglycemia, rather than hyperglycemia, are associated with nerve fiber loss in diabetes.

Pronator Quadratus: A Preferable Recipient for Targeted Muscle Reinnervation of Neuromas in the Hand.

Targeted muscle reinnervation (TMR) has emerged as a useful solution to the problem of painful neuromas and is increasingly being applied in many clinical circumstances. Relatively little has been written about TMR for painful neuromas of the hand, and what has been written describes use of the intrinsic muscles as recipients for the nerve transfer. Except in cases of amputation, intrinsic muscle sacrifice carries morbidity. Furthermore, TMR to intrinsic muscles will place the nerve coaptation in areas subject to pressure with loading of the palm. For these reasons, the pronator quadratus may be a preferable target muscle when performing TMR for painful neuromas of the hand. In this report, we describe the rationale for its use and demonstrate the surgical technique and outcomes with case examples.

Updates on the Diagnosis and Treatment of Peripheral Autonomic Neuropathies.

Autonomic neuropathies are a complex group of disorders and result in diverse clinical manifestations that affect the cardiovascular, gastrointestinal, urogenital, and sudomotor systems. We focus this review on the diagnosis and treatment of peripheral autonomic neuropathies. We summarize the diagnostic tools and current treatment options that will help the clinician care for individuals with peripheral autonomic neuropathies. Autonomic neuropathies occur often in conjunction with somatic neuropathies but they can also occur in isolation. The autonomic reflex screen is a validated tool to assess sympathetic postganglionic sudomotor, cardiovascular sympathetic noradrenergic, and cardiac parasympathetic (i.e., cardiovagal) function. Initial laboratory evaluation for autonomic neuropathies includes fasting glucose or oral glucose tolerance test, thyroid function tests, kidney function tests, vitamin-B12, serum, and urine protein electrophoresis with immunofixation. Other laboratory tests should be guided by the clinical context. Reduced intraepidermal nerve density on skin biopsy is a finding, not a diagnosis. Skin biopsy can be helpful in selected individuals for the diagnosis of disorders affecting small nerve fibers; however, we strongly discourage the use of skin biopsy without clinical-physiological correlation. Ambulatory blood pressure monitoring may lead to early identification of patients with cardiovascular autonomic neuropathy in the primary care setting. Disease-modifying therapies should be used when available in combination with nonpharmacological management and symptomatic pharmacologic therapies. Autonomic function testing can guide the therapeutic decisions and document improvement with treatment. A systematic approach guided by the autonomic history and standardized autonomic function testing may help clinicians when identifying and/or counseling patients with autonomic neuropathies. Treatment should be individualized and disease-modifying therapies should be used when available.

Carotid atherosclerosis: An independent risk factor for small fiber nerve dysfunction in patients with type 2 diabetes mellitus.

To explore whether carotid atherosclerosis is an independent risk factor for small fiber nerve dysfunction in type 2 diabetes mellitus patients. A total of 247 type 2 diabetes patients from Nanjing Drum Tower Hospital received carotid ultrasonography and quantitative sensory testing, including cold and warm detection thresholds, and some patients received cold and heat pain detection thresholds, respectively. According to the results of quantitative sensory testing, patients were divided into normal small fiber nerve function (NSF)and small fiber nerve dysfunction (SFD) group. Meanwhile, patients were divided into the non-carotid atherosclerosis group, carotid intimal thickening, unilateral carotid atherosclerosis and bilateral carotid atherosclerosis group. The correlation between carotid ultrasonography with quantitative sensory testing parameters was analyzed by SPSS 26.0. First, the incidence rate of SFD increased significantly in patients with carotid atherosclerosis (72.2%, P < 0.001) especially in bilateral carotid atherosclerosis (81.7%, P < 0.001). Second, compared with the NS group, the carotid intima-media thickness in SFD was thicker (P=0.018) and the size of atherosclerotic plaque was larger (P < 0.001). In addition, the cold detection threshold decreased (P < 0.001), whereas the warm detection threshold (P < 0.001) and heat pain detection threshold (P < 0.001) increased as aggravation of carotid atherosclerosis. In the correlation analysis, the size of atherosclerotic plaque presented a positive correlation with the warm detection threshold (r=0.476, P < 0.001) and heat pain detection threshold (r=0.213, P < 0.001), but presented a negative correlation with the cold detection threshold (r=-0.239, P < 0.01). Furthermore, carotid atherosclerosis (odds ratio 2.326, P=0.017), especially bilateral carotid atherosclerosis (odds ratio 5.042, P=0.001), was an independent risk factor for SFD (P < 0.05). Carotid atherosclerosis was significantly associated with quantitative sensory testing and found to be an independent risk factor for small fiber nerve dysfunction in type 2 diabetes patients.