Subclinical Neuropathy Research Articles

The Reliability and Reproducibility of Corneal Confocal Microscopy in Children

To assess the image and patient level interrater agreement and repeatability within 1 month for corneal nerve fiber length (CNFL) measured using in vivo corneal confocal microscopy (IVCCM) in children. Seventy-one subjects (mean [SD] age 14.3 [2.6] years, range 8-18 years; 44 with type 1 diabetes and 27 controls; 36 males and 35 females) were included. 547 images (∼6 images per subject) were analyzed manually by two independent and masked observers. One-month repeat visit images were analyzed by a single masked observer in 21 patients. Automated image analysis was then performed using a specialized computerized software (ACCMetrics). For CNFL, the ICC (95% CI) were 0.94 (0.93-0.95) for image-level, 0.86 (0.78-0.91) for patient-level, and 0.88 (0.72-0.95) for the 1-month repeat assessment, and the Bland-Altman plots showed minimal bias between observers. Although there was excellent agreement between manual and automated analysis according to an ICC 0.89 (0.82-0.93), the Bland-Altman plot showed a consistent bias with manual measurements providing higher readings. In vivo corneal confocal microscopy image analysis shows good reproducibility with excellent intraindividual and interindividual variability in pediatric subjects. Since the image-level reproducibility is stronger than the patient-level reproducibility, refinement of the method for image selection will likely further increase the robustness of this novel, rapid, and noninvasive approach to detect early neuropathy in children with diabetes. Further studies on the use of IVCCM to identify early subclinical neuropathy in children are indicated.

Neurophysiologic Evaluation of Children with Beta-Thalassemia Major

Neural pathway involvement is considered to be a neurological complication in Beta-thalassemia major (BTM). This study aimed to detect possible involvement of central and peripheral neural pathways in a group of neurologically asymptomatic patients with BTM. It was performed on 30 patients diagnosed as having BTM (group I), and 10 healthy children who were matched for age, sex, and height (group II). Serum ferritin, iron, glucose tolerance test, intelligence quotient (IQ) test, and electroencephalogram (EEG) were assessed in BTM patients. Electrophysiologic study was assessed in both groups. The mean age of the patients was 10.45 ± 2.88 years. They were 14 males and 16 females. The results of the present study showed that 66.7% of patients had subclinical sensory peripheral neuropathy. Twenty percent of the patients had abnormal somatosensory evoked potentials. Low average and slow learner total IQ score were found in 63.3% of the studied patients. These findings did not correlate with age, disease duration, serum iron, and ferritin. Twenty-three patients had mature EEG background activity, while seven patients had immature background activity. The EEG background maturity had significant correlation with age, duration of desferrioxamine therapy, and serum iron. There was no correlation between serum ferritin level, EEG, and electrophysiologic findings. Regular electrophysiologic monitoring and intellectual evaluation are recommended to detect relevant abnormalities and apply appropriate management.

Electrodiagnostic testing in diabetic neuropathy: Which limb?

Electrodiagnosis of subclinical diabetic neuropathies by nerve conduction studies remains challenging. The question arises about which nerves should be tested and what the best electrodiagnostic protocol to make an early diagnosis of diabetic neuropathies would be.On the basis of our findings and other evidence, which highlighted the remarkable prevalence of electrophysiological abnormalities in nerve conduction studies of the upper limbs, often in the presence of normal lower limb conduction parameters, we suggest that both ulnar and median nerves, in their motor and sensitive component, should be the two target nerves for electrodiagnostic protocols in diabetic neuropathies.

Neurophysiologic evaluation of peripheral nerve function in uremic Egyptian children

Information concerning clinical and sub-clinical peripheral neuropathy in uremic children is still scarce. We aimed to evaluate role of neurophysiologic testing for detection of peripheral nerve dysfunction in asymptomatic uremic Egyptian children. A cohort of 81 uremic children was enrolled from Pediatric Nephrology Unit in Mansoura University Children's Hospital. It comprised 39 cases on conservative therapy; conservative group (CG) (27 males and 12 females, with mean age 9.8 ± 3.3 years) and 42 cases under regular hemodialysis for at least 6 months; hemodialysis group (HG) (27 males and 15 females, with mean age 11.8 ± 1.6 years). A third group of twenty healthy children was taken as control (12 males, and eight females, with mean age 9.9 ± 2.4 years). Nerve conduction studies including motor and sensory functions were done successfully in most cases; data were analyzed using SPSS version 10.0. Different proportions of abnormal motor and sensory conduction studies were reported in both patients' groups with reference to pediatric ranges built-in Sierra II software. Comparing these observations to controls, motor peroneal and median conduction velocities as well as sensory ulnar conduction velocity were significantly delayed in HG (38.46 ± 4.49 vs. 48.33 ± 3.35 for peroneal, 50.68 ± 10.87 vs. 57.22 ± 7.13 for median and 32.82 ± 9.8 vs. 52.08 ± 20.12 for ulnar nerve). However, in CG antidromic sensory median conduction was the only significant abnormality detected (41.13 ± 9.63 vs. 53.89 ± 12.32). F wave latencies in CG were almost normal but in HG they were moderately affected compared to controls. We can conclude that sensory dysfunction could be early detected in asymptomatic uremic children by neurophysiologic testing. Further prospective studies should be warranted to evaluate sequential electrophysiological changes in response to hemodialysis.

Quantitative Sensory Testing at Baseline and During Cycle 1 Oxaliplatin Infusion Detects Subclinical Peripheral Neuropathy and Predicts Clinically Overt Chronic Neuropathy in Gastrointestinal Malignancies

PurposeOxaliplatin neurotoxicity has a spectrum of manifestations from an often reversible acute neurotoxicity to a more irreversible “stocking and glove” chronic neuropathy that is associated with high morbidity. Quantitative sensory testing (QST) is a noninvasive psychometric testing method that can potentially be used in the clinic setting to measure subclinical neurologic changes early on to identify patients that will experience chronic oxaliplatin-induced peripheral neuropathy at 1 year. Patients and MethodsThirty patients with gastrointestinal malignancies who were receiving oxaliplatin were recruited. QST and patient-reported outcomes were assessed at baseline; during infusion cycles 1, 2, 4, and 6; and at 1 year. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, chronic neuropathy scores were assessed at the 1-year time point. The variables at each time point were evaluated for prediction of 1-year chronic neuropathy scores. ResultsWe found that patients with preexisting subclinical neuropathy were more likely to experience grades 2 and 3 chronic neuropathy than were those who did not have this condition (heat detection threshold, Spearman correlation coefficient (rs) = 0.39; P = .037; pellet retrieval time, rs = 0.47; P = .024). Patients in whom thermal and cutaneous sensory deficits developed with cycle 1 infusion were also more likely to experience grades 2 and 3 neuropathy at 1 year (cold detection threshold, rs = 0.50; P = .007; heat detection threshold, rs = 0.39; P = .042; cutaneous detection threshold, rs = 0.42; P = .043). ConclusionQST provides a noninvasive, commercially available, and feasible clinical test to select patients, even before oxaliplatin treatment, who are likely to experience moderate to severe chronic peripheral neuropathy.

Clinical diagnosis of distal diabetic polyneuropathy using neurological examination scores: correlation with nerve conduction studies

The aim of this study was to diagnose diabetic sensorimotor polyneuropathy using neurological examination scores and to correlate the findings with nerve conduction studies (NCS). Thirty patients with type 2 diabetes were included in the study. Detection and grading of neuropathy were carried out based on the Diabetic Neuropathy Symptom (DNS) Score, modified Neuropathy Symptom Score (NSS), Diabetic Neuropathy Examination (DNE), and modified Neuropathy Disability Score (NDS). For the NCS, amplitudes, velocities, and latencies of seven nerves — that is, four motor (median, ulnar, tibial, and common peroneal) and three sensory (median, ulnar, and sural) nerves — were recorded. If the patient had two or more abnormal findings in any of these nerves, the patient was diagnosed as having peripheral sensorimotor neuropathy. Thereafter, the sensitivity, specificity, and diagnostic efficacy of each neurological score were recorded taking NCS as the gold standard. Diabetic sensorimotor polyneuropathy was diagnosed clinically and electrophysiologically in 17 patients (56.7%). However, there were nine cases (30%) of subclinical neuropathy. Neurological examination scores were significantly correlated with each other and with individual variables of NCS and the nerve conduction sum score. Taking the NCS as gold standard, DNS, modified NSS, DNE, and modified NDS had 65.4, 61.5, 30.8, and 61.5% sensitivity and 100, 75, 100, and 100% specificity, respectively. Their diagnostic efficacies were 70, 63.3, 40, and 66.7%, respectively. Neurological examination scores can detect and grade neuropathy in the majority of cases. However, NCS was accurate for detection of diabetic sensorimotor polyneuropathy, especially for the subclinical neuropathies.

Syndromic parkinsonism and dementia associated with OPA1 missense mutations

ObjectiveMounting evidence links neurodegenerative disorders such as Parkinson disease and Alzheimer disease with mitochondrial dysfunction, and recent emphasis has focused on mitochondrial dynamics and quality control. Mitochondrial dynamics and mtDNA maintenance is another link recently emerged, implicating mutations in the mitochondrial fusion genes OPA1 and MFN2 in the pathogenesis of multisystem syndromes characterized by neurodegeneration and accumulation of mtDNA multiple deletions in postmitotic tissues. Here, we report 2 Italian families affected by dominant chronic progressive external ophthalmoplegia (CPEO) complicated by parkinsonism and dementia.MethodsPatients were extensively studied by optical coherence tomography (OCT) to assess retinal nerve fibers, and underwent muscle and brain magnetic resonance spectroscopy (MRS), and muscle biopsy and fibroblasts were analyzed. Candidate genes were sequenced, and mtDNA was analyzed for rearrangements.ResultsAffected individuals displayed a slowly progressive syndrome characterized by CPEO, mitochondrial myopathy, sensorineural deafness, peripheral neuropathy, parkinsonism, and/or cognitive impairment, in most cases without visual complains, but with subclinical loss of retinal nerve fibers at OCT. Muscle biopsies showed cytochrome c oxidase‐negative fibers and mtDNA multiple deletions, and MRS displayed defective oxidative metabolism in muscle and brain. We found 2 heterozygous OPA1 missense mutations affecting highly conserved amino acid positions (p.G488R, p.A495V) in the guanosine triphosphatase domain, each segregating with affected individuals. Fibroblast studies showed a reduced amount of OPA1 protein with normal mRNA expression, fragmented mitochondria, impaired bioenergetics, increased autophagy and mitophagy.InterpretationThe association of CPEO and parkinsonism/dementia with subclinical optic neuropathy widens the phenotypic spectrum of OPA1 mutations, highlighting the association of defective mitochondrial dynamics, mtDNA multiple deletions, and altered mitophagy with parkinsonism. Ann Neurol 2015;78:21–38

Peripheral neuropathy electrophysiological screening in children with celiac disease.

The involvement of the peripheral nervous system in children with celiac disease is particularly rare. The aim of this study was to assess the need for neurophysiological testing in celiac disease patients without neurological symptoms in order to detect early subclinical neuropathy and its possible correlations with clinical and demographic characteristics. Two hundred and twenty consecutive children with celiac disease were screened for neurological symptoms and signs, and those without symptoms or signs were included. Also, patients with comorbidities associated with peripheral neuropathy or a history of neurological disease were excluded. The remaining 167 asymptomatic patients as well as 100 control cases were tested electro-physiologically for peripheral nervous system diseases. Motor nerve conduction studies, including F-waves, were performed for the median, ulnar, peroneal, and tibial nerves, and sensory nerve conduction studies were performed for the median, ulnar, and sural nerves with H reflex of the soleus muscle unilaterally. All studies were carried out using surface recording electrodes. Normative values established in our laboratory were used. Evidence for subclinical neuropathy was not determined with electrophysiological studies in any of the participants. In this highly selective celiac disease group without any signs, symptoms as well as the predisposing factors for polyneuropathy, we did not determine any cases with neuropathy. With these results we can conclude that in asymptomatic cases with celiac disease electrophysiological studies are not necessary. However, larger studies with the electrophysiological studies performed at different stages of disease at follow-ups are warranted.

The effect of transient, moderate dietary phosphorus deprivation on phosphorus metabolism, muscle content of different phosphorus-containing compounds, and muscle function in dairy cows

Hypophosphatemia is a common finding in periparturient and anorectic cattle. Although the clinical relevance of hypophosphatemia in cattle is uncertain, it has been empirically associated with persistent recumbency, specifically in periparturient dairy cows. The objective of the present study was to determine if transient dietary phosphorus (P) deprivation over a course of 5 wk, by feeding an approximately 40% P-deficient ration to lactating dairy cows, would result in altered muscle function or muscle P metabolism severe enough to present a risk for animal health and well-being. In addition, we wanted to determine the association between the plasma phosphate concentration ([Pi]) and muscle tissue P content to assess to what extent intracellular P deprivation of muscle cells could be extrapolated from subnormal plasma [Pi]. Ten healthy multiparous, mid-lactating dairy cows received a ration with a P content of 0.18% over a period of 5 wk. Following the P-deprivation phase, the same ration supplemented with P to obtain a dietary P content of 0.43% was fed for 2 wk. Blood and urine samples were collected regularly and muscle biopsies were obtained repeatedly to determine the P content in muscle tissue. Function of skeletal and heart muscles was evaluated by electrocardiography and electromyography conducted repeatedly throughout the study. Feeding the P-deficient ration resulted in the rapid development of marked hypophosphatemia. The lowest plasma [Pi] were measured after 9 d of P depletion and were, on average, 60% below predepletion values. Plasma [Pi] increased thereafter, despite ongoing dietary P depletion. None of the animals developed clinical signs commonly associated with hypophosphatemia or any other health issues. Urine analysis revealed increasing renal calcium, pyridinoline, and hydroxypyridinoline excretion with ongoing P deprivation. Biochemical muscle tissue analysis showed that dietary P depletion and hypophosphatemia were not associated with a decline in muscle tissue P content. Electromyographic examination revealed increased occurrence of pathological spontaneous activity in striated muscles after 2 wk of dietary P depletion in several cows, which could be suggestive of neuromuscular membrane instability. No effect on heart muscle activity was identified electrocardiographically. These results suggest that counter-regulatory mechanisms were sufficient to maintain normal muscle tissue P content during transient and moderate P deprivation. Muscle function was not grossly affected, although the increased occurrence of pathological spontaneous activity suggests that subclinical neuropathy or myopathy, or both, may have occurred with ongoing P deprivation. The results presented here indicate that plasma [Pi] is unsuitable for assessing muscle tissue P content in cattle.

Do cancer patients present with subclinical peripheral neuropathy prior to initiating neurotoxic chemotherapy?

9631 Background: Chemotherapy-induced peripheral neuropathy (CIPN), is a common dose-limiting toxicity which may compromise patient survival, leaving many with chronic pain, disability and a negati...

Sensory neuropathy in young people with type 1 diabetes: a systematic review

Peripheral sensory neuropathy and its risk factors are well-described in adults with type 1 diabetes (T1D). While clinically evident neuropathy is rare in young people with T1D, we and others have shown that subclinical peripheral neuropathy is common [1]. However, the prevalence of sensory neuropathies may be underestimated, due to a lack of established testing guidelines. We performed a systematic review of the epidemiology of peripheral sensory neuropathy, and diagnostic accuracy of tools used for its assessment, in young people with T1D. We searched Medline and Embase from Jan 1985 to Mar 2014. Inclusion criteria were studies in young people with diabetes duration > 1 year which tested for sensory neuropathy using nerve conduction velocity (NCV), temperature perception threshold (TPT), vibration perception threshold (VPT) and/or clinical examination. We identified 26 eligible studies, involving 5527 young people with T1D. Only 7/26 (27%) studies were of good methodological quality (Newcastle Ottowa Scale score > 7). Clinical examination yielded a wide variation in the rates of sensory neuropathy, with pooled prevalence of 15% (95% CI 13 to 17). Abnormal VPT was more common, with pooled prevalence 33% (30 to 36), as was TPT, with pooled prevalence 32% (26 to 39). The prevalence of abnormal NCV was similar 36% (33 to 39). Overall, the pooled prevalence of sensory neuropathy, using any test, was 26% (24 to 27). We calculated sensitivity and specificity of the different diagnostic tests that were used in the included studies, in comparison with neuropathies detected by ‘gold standard’ nerve NCV testing. The sensitivity of VPT ranged from 29-62%, and specificity from 65-100%. Sensitivity of TPT was 19% and specificity was 65% (one study). The sensitivity of clinical examination ranged from 0-100% and specificity from 81-100%. In conclusion, there is marked variation in reported prevalence rates of sensory neuropathy, due to lack of consensus on its definition, classification of abnormal results, and testing methodology. Clinical examination demonstrates the lowest sensitivity for detection of sensory neuropathy in young people with T1D.

Detecting Subclinical Diabetic Cardiac Autonomic Neuropathy by Analyzing Ventricular Repolarization Dynamics.

In this study, a linear parametric modeling technique was applied to model ventricular repolarization (VR) dynamics. Three features were selected from the surface ECG recordings to investigate the changes in VR dynamics in healthy and cardiac autonomic neuropathy (CAN) participants with diabetes including heart rate variability (calculated from RR intervals), repolarization variability (calculated from QT intervals), and respiration [calculated by ECG-derived respiration (EDR)]. Surface ECGs were recorded in a supine resting position from 80 age-matched participants (40 with no cardiac autonomic neuropathy (NCAN) and 40 with CAN). In the CAN group, 25 participants had early/subclinical CAN (ECAN) and 15 participants were identified with definite/clinical CAN (DCAN). Detecting subclinical CAN is crucial for designing an effective treatment plan to prevent further cardiovascular complications. For CAN diagnosis, VR dynamics was analyzed using linear parametric autoregressive bivariate (ARXAR) and trivariate (ARXXAR) models, which were estimated using 250 beats of derived QT, RR, and EDR time series extracted from the first 5 min of the recorded ECG signal. Results showed that the EDR-based models gave a significantly higher fitting value (p < 0.0001) than models without EDR, which indicates that QT-RR dynamics is better explained by respiratory-information-based models. Moreover, the QT-RR-EDR model fitting values gradually decreased from the NCAN group to ECAN and DCAN groups, which indicate a decoupling of QT from RR and the respiration signal with the increase in severity of CAN. In this study, only the EDR-based model significantly distinguished ECAN and DCAN groups from the NCAN group (p < 0.05) with large effect sizes (Cohen's d > 0.75) showing the effectiveness of this modeling technique in detecting subclinical CAN. In conclusion, the EDR-based trivariate QT-RR-EDR model was found to be better in detecting the presence and severity of CAN than the bivariate QT-RR model. This finding also establishes the importance of adding respiratory information for analyzing the gradual deterioration of normal VR dynamics in pathological conditions, such as diabetic CAN.

Trigeminal nerve electrophysiological assessment in sickle cell anemia: correlation with disease severity and radiological findings

The aim of our study was to assess, electrophysiologically, the possibility of associated subclinical trigeminal neuropathy in sickle cell anemia (SCA) patients and correlate the results with disease severity and findings of computerized tomography. Fifty patients with SCA were included; 20 of these patients had clinical unilateral trigeminal neuropathy (group II), whereas the others were asymptomatic (group I). Forty matched healthy individuals served as a control group. Trigeminal evoked potential (TEP) and inferior alveolar nerve (IAN) conduction studies were carried out for all patients and controls. Findings were correlated with the frequency of vaso-occlusive crisis, mental foramen (MF), and mandibular canal (MC) dimensions as measured by computerized tomography. There were highly significantly longer N13, 19, and 20 latencies and reduced N13-P19 amplitude in patient groups in comparison with the controls (P<0.001). There were delayed P19 latency, IAN latency, reduced IAN amplitude (P<0.05), and conduction velocity (P<0.001) in SCA patients with trigeminal neuropathy versus those without trigeminal neuropathy, and also in asymptomatic patients versus controls. The vaso-occlusive crisis frequency in group II was correlated positively with all TEP waves’ latencies and IAN latency and correlated negatively with IAN amplitude, conduction velocity, and N13/P19 amplitude. MF and MC dimensions were significantly reduced in group II in comparison with the controls (P<0.05). MF height and MC diameter were correlated negatively with ipsilateral P19 latency. Subclinical trigeminal neuropathy may be associated with SCA. The trigeminal nerve could be affected along its peripheral or the central pathway. Central affection may occur as a result of lesions in its nuclei or at the somatosensory cortex. Electrophysiological assessment is recommended in SCA patients to diagnose trigeminal neuropathy and detect the level of its affection. This will provide new insights into its prevention and treatment.

Upper extremity subclinical autonomic and peripheral neuropathy in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune, multiorgan disease that affects connective tissues of many organs or systems, including the nervous system, where it affects the autonomic, the peripheral, and the central nervous system. The aim of this study was to investigate the association of subclinical autonomic and peripheral neuropathy with SLE and to correlate neurophysiological parameters with clinical and laboratory data. Fifty-six SLE patients were included in this study. In addition, thirty age-matched and sex-matched healthy participants served as a control group. Exclusion criteria included patients having symptoms or signs indicating autonomic dysfunction or peripheral neuropathy. Also, endocrinal, toxic, compression, and traumatic neuropathies were excluded. Patients were assessed clinically and by laboratory investigations. Neurophysiological assessment included sympathetic skin response of the median nerve including latency and amplitude. In addition, nerve conduction study of both median and ulnar nerves was performed including motor distal latency, amplitude, nerve conduction velocity, and distal sensory latency. Pure sensory abnormality was detected in one patient, whereas pure motor neuropathy was found in 19 patients. Mixed sensory–motor abnormalities were detected in two patients. Sympathetic skin response was not elicited in 13 patients, whereas latency and amplitude abnormalities were detected in 11/43 and 9/43 patients, respectively. Sympathetic and axonal neuropathy was not correlated with the disease duration or the disease activity. The pattern of neuropathy in SLE is mainly axonal. Also, the sympathetic nervous system is affected in lupus patients with a rate of up to 40% of the cases.

Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin.

The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats.

Electrophysiologic vestibular evaluation in type 2 diabetic and prediabetic patients: Air conduction ocular and cervical vestibular evoked myogenic potentials

Objective: Chronically increased blood glucose levels may affect the vestibular system by damaging cells and neural structures in diabetes mellitus (DM). We aimed to search the effects of neurovascular degeneration on the vestibular system in type 2 DM and prediabetic patients by using air-conducted ocular (oVEMP) and cervical (cVEMP) vestibular evoked myogenic potentials. Design: Prospective study. Study sample: Thirty diabetic, 30 prediabetic patients, and 31 age- and sex-matched controls having no peripheral or central vestibular disease, were enrolled. All participants were evaluated by audiovestibular tests, oVEMP, and cVEMP. Results: In the diabetic group, mean values of both oVEMP and cVEMP p1, n1 latencies were significantly longer compared to the prediabetic group and the control group, whereas latencies were similar in prediabetic and the control groups. Bilateral neural dysfunction was recognized in both tests and lateralization was not seen in VEMP asymmetric ratios. In the diabetic group, prevalence of pathological p1 and n1 latencies in oVEMP were 30.4% and 37.5%, whereas they were 53.7%, 59.3% in cVEMP, respectively. p1 latencies of cVEMP and oVEMP were positively correlated with HbA1c and fasting plasma glucose level in the diabetic group. Conclusion: Subclinical vestibular neuropathy can be a newly defined diabetes-related complication.

Diabetic neuropathies.

This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy. Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain.

Subclinical peripheral neuropathy in patients with multiple myeloma before chemotherapy is correlated with decreased fingertip innervation density.

The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy. QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy. Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold. Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density.

Peripheral neuropathy: detection with diffusion-tensor imaging.

To investigate the ability of diffusion-tensor imaging (DTI) and T2 to help detect the mildest nerve lesion conceivable, that is, subclinical ulnar neuropathy at the elbow. This prospective study was approved by the institutional ethics board. Written informed consent was obtained from all participants. Magnetic resonance neurography was performed at 3.0 T by using proton density- and T2-weighted relaxometry and DTI on elbows in 30 healthy subjects without clinical evidence of neuropathy. Quantitative analysis of ulnar nerve T2 and fractional anisotropy (FA) was performed, and T2 and FA values were correlated to electrical nerve conduction velocities (NCVs) with Pearson correlation analysis. Additional qualitative assessment of T2-weighted and FA images was performed by two readers, and sensitivity and specificity were calculated. Ten of the 30 subjects (33%) had NCV slowing across the elbow segment. Compared with subjects without NCV slowing, subjects with slowing had decreased FA values (0.51 ± 0.09 vs 0.41 ± 0.07, respectively; P = .006) and increased T2 values (64.2 msec ± 10.9 vs 76.2 msec ± 13.7, respectively; P = .01) in the proximal ulnar sulcus. FA values showed a significant correlation (P = .01) with NCV slowing over the sulcus as an electrophysiologic indicator of myelin sheath damage. Qualitative assessment of FA maps and T2-weighted images helped identify subjects with conduction slowing with a sensitivity of 80% and 55%, respectively, and a specificity of 83% and 63%. FA maps can accurately depict even mild peripheral neuropathy and perform better than the current standard of reference, T2-weighted images. DTI may therefore add diagnostic value as a highly sensitive technique for the detection of peripheral neuropathy.

Characterization of somatosensory profiles in patients with Crohn's disease.

Crohn's disease (CD) is a painful chronic inflammatory bowel disease. It primarily affects terminal ileum, but the involvement of large and small intestines or extraintestinal manifestations is very common. CD may go along with neurogenic inflammation, mediated by substance P and CGRP, which are also key players in pain transmission. This may in turn contribute to hyperalgesia and altered somatosensory function in CD. One hundred and three (103) patients with CD and 80 healthy volunteers were enrolled. Patient characteristics and disease history were documented. We used quantitative sensory testing (QST) to investigate the somatosensory profile in patients and volunteers. We also calculated z-scores for the QST results of the patients with CD based on the data of our control group. A 2-step cluster analysis, using all QST data, was performed to find subgroups within patients and volunteers. Thresholds of warm detection, mechanical pain, and vibration detection did significantly differ between patients with CD and volunteers. Z-scores indicated a general trend of sensory loss in CD patients with a significant relationship between patients with a sensory loss for cold and warm detection. In the hyposensitive cluster of the CD cohort, patients were more frequently male, had a higher incidence of extraintestinal manifestations, and suffered longer from CD. Our findings are consistent with the presence of a subclinical small fiber neuropathy. The group of CD patients with pronounced neuropathy findings were predominantly males, had a higher incidence of extraintestinal manifestations, and tended to have a longer history of disease duration.