Reduced Motor Nerve Conduction Velocity Research Articles

Length of affected nerve segment in ulnar neuropathies at the elbow

ObjectiveTo establish length of the affected nerve segment (LANS) in ulnar neuropathy at the elbow (UNE). MethodsIn a group of our previously reported UNE patients we identified 2-cm segments with reduced motor nerve conduction velocity (MNCV) on electrodiagnostic (EDx) studies and increased nerve cross-sectional areas (CSA) on ultrasonographic (US) studies. LANS was obtained by summation of these abnormal 2-cm segments separately for each approach. We also studied effect of selected independent parameters on LANS. ResultsAltogether we studied 189 patients (194 arms). Mean (SD) LANS determined in 171 arms with reduced ulnar MNCV was 4.15 (1.89) cm, and was similar (p = 0. 21) to LANS obtained in 147 arms with increased CSA 4.46 (2.29) cm. Longer LANS were found in right arms, clinically severe UNE, axonal UNE and UNE due to entrapment. The most commonly affected 6 cm segment included 89% of abnormal 2-cm segments, with 50% of included 2-cm segments being normal. By contrast, the whole 10 cm segment included all abnormal 2-cm segments, with 66% of included segments being normal. ConclusionsIn UNE both EDx and US studies revealed average LANS of around 4 cm. LANS was longer in more severe UNE. SignificanceLANS needs to be taken into account in discussion of the mechanisms of UNE and approach to EDx diagnosis of UNE, particularly length of the segment used in nerve conduction studies across the elbow.

P0267CLINICAL MANIFESTATIONS, PREVALENCE AND PREDICTORS OF PERIPHERAL NEUROPATHY IN NON DIABETIC CHRONIC KIDNEY DISEASE PATIENTS. A CROSS SECTIONAL STUDY FROM TERTIARY CARE CENTRE

Abstract Background and Aims There is a progressive increase in the prevalence of chronic kidney disease (CKD). The impairment of functions of kidney secondary to CKD leads to uraemia. Peripheral neuropathy is one of the common manifestations of uraemia. The present study focuses on the prevalence, clinical manifestations and predictors of peripheral neuropathy in patients with non-diabetic CKD. Method This was a cross sectional study conducted in the Department of General Medicine, Maharaja Krishna Chandra Gajapathi Medical College and Hospital, Berhampur, Odisha, India from October 2015 to October 2017. Patients with serum creatinine >2 mg/dl, estimated glomerular filtration rate <60 ml/min (calculated by using Modification of Diet in Renal Disease equation), kidney size < 8.5cm on ultrasound abdomen were included in the study and patients with age less than 18 years, patients with diabetes mellitus and other recognizable risk factors for peripheral neuropathy (Alcoholism, Drugs, Connective tissue disorders, Sarcoidosis, Vasculitis, Thyroid dysfunction, HIV, Hansen’s disease, Paraneoplastic disease etc.) and patients on dialysis were excluded. Peripheral neuropathy was assessed by both clinical methods and nerve conduction studies (NCS). Reduced motor nerve conduction velocity, delayed distal latency, fall in the amplitude of compound muscle action potential on Motor Nerve Conduction Study (MNCS) and delay in the peak latencies, reduced sensory nerve action potential on Sensory Nerve Conduction study (SNCS) were considered as evidence for peripheral neuropathy. From upper limb, median nerve and ulnar nerve were selected for MNCS and SNCS. From lower limb, common peroneal and posterior tibial nerves were selected for MNCS and sural nerve was selected for SNCS. Results Total 109 patients were included in the study and 75(68.8%) were proved to have peripheral neuropathy. Majority of the affected patients were in 40 to 50 years age group (n=24;32%). Forty four of 75 (58.6%) were males and 31(41.33%) were females. Patients with both sensory and motor neuropathy were 35(32.1%), 26(23.9%) were affected with only sensory neuropathy, while 14(12.8%) were affected with only motor neuropathy. Patients with clinical neuropathy (patients who have clinical symptoms and signs of neuropathy and also evidence on NCS) were 35(46.6%) and with subclinical neuropathy (only evident on NCS) were 40(53.3%).On univariate analysis, age (p-0.015), hypertension (p-0.031), duration of disease (p<0.0001), serum creatinine (p<0.0001), eGFR (p<0.0001), serum uric acid (p<0.0001), serum parathyroid (p<0.0001), serum phosphorus (p<0.0001), serum calcium (p-0.0003), serum magnesium (p-0.0002) and serum potassium (p-0.0028) were significantly correlated with peripheral neuropathy however on logistic regression analysis, sex [OR-0.058;95%CI(0.004-0.831)], serum parathyroid hormone [OR-1.032;95%CI(2.708-6043.5)], serum phosphorus[OR3.881;95%CI(1.114-13.524)], serum magnesium [OR-127.28;95%CI(0.901-1.113)] and duration of CKD[OR1.109;95%CI(1.005-1.224)] were shown to be independent predictors. Conclusion Peripheral neuropathy is one of the frequent complications of uremia. Subclinical presentation is most common. Serum parathyroid, serum phosphorus, serum magnesium and duration of disease are independent predictors of uremia induced peripheral neuropathy

Peripheral Nerve Regeneration Is Independent From Schwann Cell p75NTR Expression.

Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75NTR has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury. However, most studies base this conclusion on results obtained from complete p75NTR knockout mouse models and cannot dissect the specific role of p75NTR expressed by Schwann cells. In this present study, a conditional knockout model selectively deleting p75NTR expression in Schwann cells was generated, where p75NTR expression is replaced with that of an mCherry reporter. Silencing of Schwann cell p75NTR expression was confirmed in the sciatic nerve in vivo and in vitro, without altering axonal expression of p75NTR. No difference in sciatic nerve myelination during development or following sciatic nerve crush injury was observed, as determined by quantification of both myelinated and unmyelinated nerve fiber densities, myelinated axonal diameter and myelin thickness. However, the absence of Schwann cell p75NTR reduced motor nerve conduction velocity after crush injury. Our data indicate that the absence of Schwann cell p75NTR expression in vivo is not critical for axonal regrowth or remyelination following sciatic nerve crush injury, but does play a key role in functional recovery. Overall, this represents the first step in redefining the role of p75NTR in the peripheral nervous system, suggesting that the Schwann cell-axon unit functions as a syncytium, with the previous published involvement of p75NTR in remyelination most likely depending on axonal/neuronal p75NTR and/or mutual glial-axonal interactions.

HbA1C Variability Is Strongly Associated With the Severity of Peripheral Neuropathy in Patients With Type 2 Diabetes.

Variability in HbA1c is associated with a higher risk of cardiovascular disease and microvascular complications in patients with type 2 diabetes. The present study evaluated the severity of somatic nerve dysfunction at different stages of chronic glycemic impairment, and its correlation with different cardio-metabolic parameters. The study was conducted on 223 patients with type 2 diabetes. We calculated the intrapersonal mean, standard deviation (SD), and coefficient of variation of HbA1c for each patient using all measurements obtained for 3 years prior to the study. Patients were divided into quartiles according to the SD of HbA1c, and we constructed composite scores of nerve conduction as the severity of peripheral neuropathy. Linear regression analysis was performed to evaluate the influence of independent variables on mean composite scores. Those with higher SD-HbA1c had a higher body mass index, mean and index HbA1c, triglyceride and uric acid level, urinary albumin excretion and albumin-creatinine ratio, proportion of insulin therapy, and prevalence of hypertension as the underlying diseases, but lower estimate glomerular filtration rate (eGFR). In addition, those with higher SD-HbA1c showed lower amplitudes and reduced motor nerve conduction velocity in tested nerves, and lower sensory nerve conduction velocity in the sural nerve. Furthermore, those with higher SD-HbA1c had higher composite scores of low extremities. Multiple linear regression analysis revealed that diabetes duration, SD-HbA1c, and eGFR were independently associated with mean composite scores. Based on our results, HbA1c variability plus chronic glycemic impairment is strongly associated with the severity of peripheral neuropathy in patients with type 2 diabetes. Aggressively control blood glucose to an acceptable range and avoid blood glucose fluctuations by individualized treatment to prevent further nerve damage.

Influence of low level laser therapy versus pulsed electromagnetic field on diabetic peripheral neuropathy

Abstract Background: Peripheral neuropathy is a common complaint of diabetes, leading to pain and reduced motor nerve conduction velocity. Clinical symptoms of peripheral neuropathy are present in approximately 25% of

Muscle spindle alterations precede onset of sensorimotor deficits in Charcot–Marie–Tooth type 2E

Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-LE396K ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-LE396K mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered. Progression from presymptomatic to symptomatic included a 50% loss of large diameter sensory axons within the fifth lumbar dorsal root of hNF-LE396K mice. Owing to proprioceptive deficits and loss of large diameter sensory axons, we analyzed muscle spindle morphology in presymptomatic and symptomatic hNF-LE396K and hNF-L control mice. Muscle spindle cross-sectional area and volume were reduced in all hNF-LE396K mice analyzed, suggesting that alterations in muscle spindle morphology occurred prior to the onset of typical CMT pathology. These data suggested that CMT2E pathology initiated in the muscle spindles altering the proprioceptive sensory system. Early sensory pathology in CMT2E could provide a unifying hypothesis for the convergence of pathology observed in CMT.

A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy.

Adiponectin, markers of subclinical inflammation and nerve conduction in individuals with recently diagnosed type 1 and type 2 diabetes.

Subclinical inflammation has been implicated in the development of diabetic sensorimotor polyneuropathy (DSPN), but studies using electrophysiological assessment as outcomes are scarce. Therefore, we aimed to investigate associations of biomarkers reflecting different aspects of subclinical inflammation with motor and sensory nerve conduction velocity (NCV) in individuals with diabetes. Motor and sensory NCV was assessed in individuals with recently diagnosed type 2 (n=352) or type 1 diabetes (n=161) from the baseline cohort of the observational German Diabetes Study. NCV sum scores were calculated for median, ulnar and peroneal motor as well as median, ulnar and sural sensory nerves. Associations between inflammation-related biomarkers, DSPN and NCV sum scores were estimated using multiple regression models. In type 2 diabetes, high serum interleukin (IL)-6 was associated with the presence of DSPN and reduced motor NCV. Moreover, higher levels of high-molecular weight (HMW) adiponectin, total adiponectin and their ratio were associated with prevalent DSPN and both diminished motor and sensory NCV, whereas no consistent associations were observed for C-reactive protein, IL18, soluble intercellular adhesion molecule-1 and E-selectin. In type 1 diabetes, only HMW and total adiponectin showed positive associations with motor NCV. Our results point to a link between IL6 and both DSPN and slowed motor NCV in recently diagnosed type 2 diabetes. The reverse associations between adiponectin and NCV in type 1 and type 2 diabetes are intriguing, and further studies should explore whether they may reflect differences in the pathogenesis of DSPN in both diabetes types.

Electrodiagnostic studies in presumptive primary hypothyroidism and polyneuropathy in dogs with reevaluation during hormone replacement therapy.

BackgroundPeripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated polyneuropathy in dogs are very limited and usually lack a reevaluation after hormone replacement therapy. The objective of this study was to perform a detailed, retrospective analysis of electromyographic (EMG), motor nerve conduction velocity (MNCV), F-wave and brainstem auditory evoked response (BAER) findings in 24 dogs with presumptive primary hypothyroidism and polyneuropathy with a comparison of the results before and after initiation of levothyroxine treatment with the assessment of the clinical outcome.ResultsThe results obtained from hypothyroid dogs showed a significant reduction in MNCV at a proximal–distal and middle–distal stimulation, decreased amplitudes of compound muscle action potentials (CMAP), an increased CMAP duration and a prolonged distal latency prior to treatment. Fifty percent of the dogs had an increased F-wave latency. A normal BAER recording was found in 78 % of the hypothyroid patients without vestibular impairment. Bilaterally increased peak V latencies and increased interpeak I–V latencies were found in the remaining individuals. Dogs with concurrent vestibular impairment had ipsilaterally increased peak latencies with normal interpeak latencies and decreased amplitudes of wave I and II. A comparison of the findings before and after 2 months of treatment revealed a decrease in the pathological activity on EMG, an improvement of proximal, middle and distal CMAP amplitudes and an increase in the proximal–distal conduction velocity in all dogs. F-wave latency improved in 38 % of dogs. The BAER reexamination revealed a persistent prolongation of peak I, II, III and V latencies and decreased wave I amplitude on the affected side in all dogs manifesting vestibular signs. Conversely, in dogs without vestibular signs, the peak V and interpeak I–V latencies decreased to normal values after a given time of the treatment.ConclusionsThe results indicate a demyelinating and axonal pattern of polyneuropathy in dogs with suspected hypothyroidism. Most of the patients without vestibular signs showed neither peripheral nor central auditory pathway impairment, concurrent to the generalized neuropathy. The follow-up examination showed a very good clinical outcome and only partial improvement in electrophysiological assessment.

A rare cause of ulnar nerve entrapment at the elbow area illustrated by six cases: The anconeus epitrochlearis muscle

Ulnar nerve entrapment is the second most common compressive neuropathy after carpal tunnel syndrome. The accessory anconeus epitrochlearis muscle – present in 4% to 34% of the general population – is a known, but rare cause of ulnar nerve entrapment at the elbow. The aim of this article was to expand our knowledge about this condition based on six cases that we encountered at our hospital between 2011 and 2015. Every patient had a typical clinical presentation: hypoesthesia or sensory deficit in the fourth and fifth fingers; potential intrinsics atrophy of the fourth intermetacarpal space; loss of strength and difficulty with fifth finger abduction. Although it can be useful to have the patient undergo ultrasonography or MRI to aid in the diagnosis, only electromyography (EMG) was performed in our patients. EMG revealed clear compression in the ulnar groove, with conduction block and a large drop in nerve conduction velocity. Treatment typically consists of conservative treatment first (splint, analgesics). Surgical treatment should be considered when conservative treatment has failed or the patient presents severe neurological deficits. In all of our patients, the ulnar nerve was surgically released but not transposed. Five of the six patients had completely recovered after 0.5 to 4years follow-up. Ulnar nerve entrapment at the elbow by the anconeus epitrochlearis muscle is not common, but it must not be ignored. Only ultrasonography, MRI or, preferably, surgical exploration can establish the diagnosis. EMG findings such as reduced motor nerve conduction velocity in a short segment of the ulnar nerve provides evidence of anconeus epitrochlearis-induced neuropathy.

Coexistence of Charcot‐Marie‐Tooth disease type 1A and anti‐MAG neuropathy

At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate.

Effects of electroacupuncture on muscle state and electrophysiological changes in rabbits with lumbar nerve root compression

To observe the effects of electroacupuncture on force-displacement value (FDV) of muscle state and electrophysiology of the muscle in rabbits with lumbar nerve root compression. Thirty New Zealand white rabbits were randomly divided into a control, a model, an electro-acupuncture acupoints (EAA), a medication, and an electro-acupuncture un-acupoints (EAU) group. All rabbits except those in the control group were subject to modeling (surgical lumbar nerve root compression). The control group was sham-operated without nerve root compression. The EAA group received electro-acupuncture at bilateral Shenshu (BL23) and Dachangshu (BL25) that were located 1.5 cun lateral to the posterior midline on the lower border of the spinous process of the 2nd and 4th lumbar vertebra, respectively. The EA was 15 mm deep and the frequency was 2 Hz. Each session lasted for 20 min per day for a total of 14 times. The medication group was treated with Loxoprofen sodium by gastrogavage at 4 mg/kg per day for 14 days. The EAU group received electro-acupuncture identical to the EAA group with regard to the treatment frequency and duration except a different acupoint at the tip of rabbit tail. Muscle states were determined by measuring FDVs of the bilateral biceps femoris using the Myotonometer® fast muscle state detector. Meanwhile, the prolonged and non-prolonged insertion potentials were measured by electromyography before and after modeling and after treatment. Latency, amplitude (Amp) of evoked potential, motor nerve conduction velocity (MNCV) were also determined after treatment. (1) After modeling, FDVs of right side activation (RSA, P=0.003) and right side relaxation (RSR) in the model group (P=0.000) were significantly decreased in comparison to the control group. The number of rabbits with non-prolonged insertion potentials in the model group was also significantly decreased (P=0.015) in comparison to the control group. (2) After treatment, FDVs of RSR were significantly increased in the EAA (P=0.000) and medication groups (P=0.018) in comparison to the model group. The increase in FDVs of RSR in the EAA group was significantly higher than that in EAU (P=0.000) and medication groups (P=0.002). MNCV in the model group was reduced compared with the control group (P=0.000). The reduction in MNCV after modeling was reversed in the EAA group (P=0.000) and medication group (P=0.008) after treatment and the increases were significant in both treatment groups in comparison to the model group. The EAA group had a greater MNCV recovery than the medication group (P=0.022). Electro-acupuncture could improve the rehabilitation and regeneration of FDVs and the electrophysiology index of the muscle with nerve control impairment.

Muscle pathology without severe nerve pathology in a new mouse model of Charcot–Marie–Tooth disease type 2E

Mutations in neurofilament light (NF-L) have been linked to Charcot-Marie-Tooth disease type 2E (CMT2E) in humans. To provide insight into disease pathogenesis, we developed a novel line of CMT2E mice that constitutively express human NF-L (hNF-L) with a glutamic acid to lysine mutation at position 397 (hNF-L(E397K)). This new line of mice developed signs consistent with CMT2E patients. Disease signs were first observed at 4 months in hNF-L(E397K) mice, and consisted of aberrant hind limb posture, digit deformities, reduced voluntary locomotor activity, reduced motor nerve conduction velocities (MNCVs) and muscle atrophy. Reduced voluntary locomotor activity and muscle pathology occurred without significant denervation, and hNF-L(E397K) mice showed relatively mild signs of nerve pathology. Nerve pathology in hNF-L(E397K) mice was characterized by ectopic accumulations of phosphorylated NFs in motor neuron cell bodies as early as 1 month. Moreover, NF organization was altered in motor and sensory roots, with small motor axons being most affected. Peak axonal diameter was reduced for small motor axons prior to and after the onset of overt phenotypes, whereas large motor axons were affected only after onset, which correlated with reduced MNCVs. Additionally, there was a small reduction in the number of sensory axons in symptomatic hNF-L(E397K) mice. hNF-L(E397K) mice are a novel line of CMT2E mice that recapitulate many of the overt phenotypes observed in CMT2E patients and hNF-L(P22S) mice. The cellular pathology observed in hNF-L(E397K) mice differed from that recently reported in hNF-L(P22S) mice, suggesting that overt CMT2E phenotypes may arise through different cellular mechanisms.

Effects of 1-bromopropane on neurological and hematological changes of female exposed workers

To investigate the health effects of 1-bromopropane (1-BP) on female exposed workers. Four 1-BP manufacturing plants were investigated. Workers were interviewed with questionnaire and examined with neurobehavioral core test battery, nerve conduction velocity tests of nervus tibialis and nervus suralis, vibration sensation test, hematological and biochemical tests. Ambient 1-BP concentration was measured with detection tube, and time-weighed average levels of individual workers were estimated with passive samplers. 1-BP concentration in the plants ranged from 0 to 402.40 mg/m3 (Geomean 32.19 mg/m3). Time-weighted average exposure levels (TWA-8 h) ranged from 0.35 to 535.19 mg/m3 (Geomean 14.08 mg/m3). Compared with the control group, 1-BP exposed workers showed reduced motor nerve conduction velocity [(44.8 +/- 8.7) m/s] and sensory nerve conduction velocity [(45.5 +/- 4.9) m/s], prolonged distal latency [(7.5 +/- 2.1) ms], reduced toe vibration perception, and altered neurobehavior parameters(POMS vigor, tension, anxiety, confusion) significantly (P < 0.05). As to hematological and biochemical indicators, the exposed workers showed decreased white blood cell count [(5.6 +/- 2.17) x 10(3)/microl], red blood cell count [(3.9 +/- 0.4) x 10(6)/microl], hemoglobin [(121.1 +/- 14.5) g/L] and creatine kinase [(82.0 +/- 27.5) IU/L] (P < 0.05), and increased serum total protein (8.0 +/- 0.5 g/dl), lactate dehydrogenase [(335.2 +/- 356.6) IU/L], thyroid-stimulating hormone [(3.6 +/- 2.3) microIU/ml] and follicle-stimulating hormone levels (18.7 +/- 24.4 mIU/ml) (P < 0.05). 1-BP exposure may affect peripheral nerves and central nervous system, and lead to abnormal hematological and biomedical indicators.

Sonographic Evaluation of the Peripheral Nerve in Diabetic Patients

Early detection of nerve dysfunction is important to provide appropriate care for patients with diabetic polyneuropathy. The aim of this study was to assess the echo intensity of the peripheral nerve and to evaluate the relationship between nerve conduction study results and sonographic findings in patients with type 2 diabetes mellitus. Thirty patients with type 2 diabetes (mean +/- SD, 59.8 +/- 10.2 years) and 32 healthy volunteers (mean, 53.7 +/- 13.9 years) were enrolled in this study. The cross-sectional area (CSA) and echo intensity of the peripheral nerve were evaluated at the carpal tunnel and proximal to the wrist (wrist) of the median nerve and in the tibial nerve at the ankle. There was a significant increase in the CSA and hypoechoic area of the nerve in diabetic patients compared with controls (wrist, 7.1 +/- 2.0 mm(2), 62.3% +/- 3.0%; ankle, 8.9 +/- 2.8 mm(2), 57.6% +/- 3.9%; and wrist, 9.8 +/- 3.7 mm(2), 72.3% +/- 6.6%; ankle, 15.0 +/- 6.1 mm(2), 61.4% +/- 5.3% in controls and diabetic patients, respectively; P < .05). Cross-sectional areas were negatively correlated with reduced motor nerve conduction velocity and delayed latency. These results suggest that sonographic examinations are useful for the diagnosis of diabetic neuropathy.

Targeted Inactivation of a Developmentally Regulated Neural Plectin Isoform (Plectin 1c) in Mice Leads to Reduced Motor Nerve Conduction Velocity

Cytolinker proteins stabilize cells mechanically, regulate cytoskeleton dynamics, and provide scaffolds for signaling molecules. For plectin, the prototype of these proteins, an unusual diversity of isoforms has been reported, which show distinct expression patterns, subcellular localizations, and functions. Plectin has been shown to have important functions in skin and muscle, but little is known about its role in neural cells. To address this issue, we generated two knock-out mouse lines, one which was selectively lacking plectin 1c (P1c), the major isoform expressed in neural cells, and another in which plectin was conditionally deleted in neuronal precursor cells. Using isoform-specific antibodies, we found P1c to be expressed late in development and to associate with postsynaptic dendrites of central nervous system neurons, motorneurons of spinal cord, sciatic nerve axons, and Schwann cells. Motor nerve conduction velocity was found significantly reduced in sciatic nerve from P1c-deficient as well as from conditional knock-out mice. This defect was traceable to an increased number of motor nerve fibers with small cross-sectional areas; the thicknesses of axons and of myelin sheaths were unaffected. This is the first report demonstrating an important role of plectin in a major nerve function.

The role of folate deficiency in electrophysiological neuropathy of experimental hepatoma of the rats.

Experimental hepatoma of the rats was induced by chronic administration of 3'-methyl-dimethylamino-azobenzene. The folate level of the hepatoma-bearing rats tended to be low as compared with that of normal controls, and the co-existence of folate deficiency and reduced motor nerve conduction velocity of the dorsal nerve trunks appeared not uncommon. The hepatoma-bearing rats revealed the disturbance of serine to glycine conversion in serum, and folate administration to them prevented electrophysiological neuropathy along with normalization of serine to glycine conversion. Therefore, the reduced motor nerve conduction velocity could be at least in part the result of a metabolic impairment due to folate deficiency.

Daily inhibition of postprandial hyperglycaemia with JTT‐608, a novel oral antidiabetic agent, ameliorates pancreatic function in neonatally streptozotocin‐treated rats

Chronic glycaemic control, in particular, the control of postprandial hyperglycaemia, is essential for preventing the development of diabetic complications. We therefore evaluated the chronic treatment effect of a new antidiabetic agent, JTT-608 [trans-4-(methylcyclohexyl)-4-oxobutyric acid], in neonatally streptozotocin-treated rats. The rats were maintained with liquid meal three times a day and treated orally with JTT-608 10 min before each meal for 12 weeks. Haemoglobin A1C (HbA1C) and fasting blood glucose levels were measured at 4-week intervals, and effects of JTT-608 on pancreatic function and diabetic complications were examined after dosing period. The postprandial hyperglycaemia was suppressed by JTT-608 administration, and both HbA1C levels and fasting blood glucose levels were reduced during the experimental period. After the treatment period of 12 weeks, JTT-608 further improved the early insulin secretion and the impaired glucose tolerance after meal loading in the diabetic rats. Also, pathological examination revealed that JTT-608 reduced the incidence of the decrease in immunoreactivity of insulin. In examination of other diabetic complications, JTT-608 ameliorated the reduced motor nerve conduction velocities observed in diabetic rats and inhibited the incidence of cataracts with diabetes. We conclude that a newly developed antidiabetic agent, JTT-608, improves the pancreatic function and prevents the development of diabetic complications by inhibition of daily postprandial hyperglycaemia and could be useful for the treatment of diabetic subjects with impaired insulin secretion.

Antidiabetic effect of chronic administration of JTT-608, a new hypoglycemic agent, in diabetic Goto–Kakizaki rats

We investigated the chronic effect of a new antidiabetic agent, trans-4-(methylcyclohexyl)-4-oxobutyric acid (JTT-608), in Goto–Kakizaki rats, a genetic model of non-obese type II diabetes mellitus. The rats were fed a liquid meal, three times a day, for 12 weeks. The rats were treated orally with JTT-608 (10–100 mg/kg) 10 min before each meal. Fasting blood glucose, triglyceride and hemoglobin A1c levels were reduced by JTT-608 at all dose levels during the experimental period. Blood glucagon-like peptide-1 level with 100 mg/kg JTT-608 increased at the end of the treatment period. JTT-608 (30–100 mg/kg) reduced urinary protein levels after administration for 5–12 weeks. In Goto–Kakizaki rats showing slight diabetic renal lesions, pathological examination revealed that JTT-608 reduced the incidence of vacuolation in renal tubules. JTT-608 (30–100 mg/kg) ameliorated the reduced motor nerve conduction velocities observed in the Goto–Kakizaki rats after administration for 12 weeks. We conclude that chronic administration of JTT-608 produces good blood glucose control and gradually arrests the development of diabetic neuropathy and nephropathy.

Transgenic mice overexpressing aldose reductase in Schwann cells show more severe nerve conduction velocity deficit and oxidative stress under hyperglycemic stress

To further understand the role of aldose reductase (AR) in the etiology of diabetic neuropathy, we generated transgenic mice that overexpress AR specifically in the Schwann cells under the control of the rat myelin protein zero (P 0) promoter. One of the transgenic mouse lines, which has overexpression of AR mRNA in the Schwann cell only and higher AR activity in the sciatic nerve, was used to examine the relationship between increased AR activity and motor nerve conduction velocity (MNCV) deficit under diabetic and galactosemic conditions. Under these conditions, nontransgenic mice showed a slight reduction in MNCV compared to those of controls. However, transgenic mice exhibited a significantly greater reduction in MNCV under these conditions, particularly under galactosemic condition, indicating that a Schwann cell-specific increase in aldose reductase activity is sufficient to produce the phenotype. Interestingly, under galactosemic condition where the difference in MNCV deficit between transgenic and nontransgenic mice was most pronounced, there was no significant difference in accumulated galactitol levels in the sciatic nerve between these mice. These results indicate that increase in AR activity leads to greater reduction of MNCV under galactosemic and diabetic conditions, but galactitol and sorbitol levels may not be good indicators of the severity of neuropathy. On the other hand, the level of reduced glutathione (GSH) in the sciatic nerve was found to be correlated with the severity of MNCV deficit under the diabetic condition. Diabetic AR transgenic mice showed significant reduction of GSH in their sciatic nerve, whereas the diabetic nontransgenic mice showed no reduction in GSH level compared to the nondiabetic control, suggesting that AR is a key contributor to oxidative stress under diabetic condition.