Motor Nerve Action Potentials Research Articles

Conduction slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies: Electrophysiology meets pathology.

Nerve conduction studies are usually the first diagnostic step in peripheral nerve disorders and their results are the basis for planning further investigations. However, there are some commonplaces in the interpretation of electrodiagnostic findings in peripheral neuropathies that, although useful in the everyday practice, may be misleading: (1) conduction block and abnormal temporal dispersion are distinctive features of acquired demyelinating disorders; (2) hereditary neuropathies are characterized by uniform slowing of conduction velocity; (3) axonal neuropathies are simply diagnosed by reduced amplitude of motor and sensory nerve action potentials with normal or slightly slow conduction velocity. In this review, we reappraise the occurrence of uniform and non-uniform conduction velocity slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies attempting, with a translational approach, a correlation between electrophysiological and pathological features as derived from sensory nerve biopsy in patients and animal models. Additionally, we provide some hints to navigate in this complex field.

Removal of schwannoma from the psoas muscle with intraoperative neurophysiological monitoring: A case report.

The incidence of a schwannoma within the psoas muscle is rare, and only a few cases have been reported. The surgical approach to removing schwannomas present in the psoas muscle is challenging because of its anatomical proximity to the lumbar plexus. A 31-year-old man experienced right lower back pain and anterolateral thigh numbness for 2 months. Magnetic resonance imaging of the patient's lumbar spine revealed a mass lesion, which was radiologically diagnosed as a well-demarcated schwannoma. The patient underwent surgery for excision of the schwannoma in the right psoas muscle at the second to fourth lumbar vertebrae levels. During surgery, intraoperative neurophysiological monitoring modalities, free-running and triggered electromyography and evoked potentials, from the target muscles were recorded. There was no neurotonic discharge corresponding to neuronal injury. Compound motor nerve action potential was detected in the triggered electromyography of muscles around the medial margin of the tumor. However, direct integration of the motor nerve was not observed in the intra-tumor region. We report that schwannoma removal in the psoas muscle, which is adjacent to the lumbar plexus, can be safely performed using intraoperative neurophysiological monitoring.

Characteristics of diabetic and non-diabetic carpal tunnel syndrome in terms of clinical, electrophysiological, and Sonographic features: a cross-sectional study

BackgroundAlthough diabetes is considered a major risk factor for carpal tunnel syndrome (CTS), the characteristics of diabetic CTS have not been fully understood.ObjectiveThis study is aimed at evaluation of the clinical, electrophysiological, and ultrasonographic findings of non-diabetic and diabetic CTS.MethodsThis retrospective, cross-sectional study included patients diagnosed with CTS. Patient age, sex, involved side, body mass index, clinical and electrophysiological findings, and median nerve cross-sectional area (CSA) were identified. Diabetes was identified through patient or guardian interviews, medical records, and medication history. Linear and binary logistic regression models were established to confirm the associations between the electrophysiological findings, median nerve CSA, and clinical outcomes. Covariates, such as age, sex, body mass index, diabetes, symptom duration, and thenar muscle weakness were adjusted.ResultsOut of the 920 hands, 126 and 794 belonged to the diabetic and non-diabetic CTS groups, respectively. The patients were significantly older in the diabetic CTS group (P < 0.001). The rate of thenar weakness in the diabetic CTS group was also significantly higher than that in the non-diabetic CTS group (P = 0.009). The diabetic CTS group had a more severe electrodiagnostic grade (P = 0.001). The prolonged onset latency of the compound motor nerve action potential (CMAP) and median nerve CSA were well associated with the degree of clinical symptoms. Increased median nerve CSA was significantly associated with prolonged CMAP onset latency (β = 0.64; P = 0.012), prolonged transcarpal latency (β = 0.95; P = 0.044), and decreased CMAP amplitude (β = -0.17; P = 0.002) in the non-diabetic CTS group.ConclusionDiabetic CTS had more profound electrophysiological abnormalities. Distal motor latency and median nerve CSA were not only associated with each other, but also with clinical symptoms. Further studies are needed to investigate the pathophysiological mechanisms underlying diabetic CTS.

Role of Fibrinogen in Type-2 Diabetes Mellitus with Diabetic Neuropathy and its Preliminary Mechanism.

Diabetic peripheral neuropathy (DN) is the most common complication of type 2 diabetes mellitus (T2DM). This study aimed to explore the role of fibrinogen (FIB) in T2DM neuropathy and its preliminary mechanism. Ten male Sprague-Dawley rats were divided into a normal control group (NC group) and a T2DM neuropathy model group (DN group). The DN group was given a high-energy diet and streptozotocin, while the NC group was given a normal diet and a citric acid buffer. The expression levels of related proteins were analysed. Electrophysiology: Compared with the NC group, the conduction latency of the somatosensory-evoked potential and nerve conduction velocity was prolonged in the DN group, while the motor nerve action potential was decreased. As seen under a light microscope, the peripheral nerve fibres in the DN group were swollen, and the nerve fibres in the posterior funiculus of the spinal cord were loose or missing. Moreover, as seen under an electron microscope, the peripheral nerve demyelination of the DN group was severe, with microvascular blood coagulation, luminal stenosis, and collapse. Compared with the NC group, in the DN group, the expression of FIB was positively correlated with the expression of both ionised calcium-binding adaptor molecule-1 and glial fibrillary acidic protein. Compared with the NC group, in the DN group, the expression of platelet/endothelial cell adhesion molecule-1 and B-cell lymphoma 2 was negatively correlated. The increased concentration of FIB may be the cause of neuropathy, and its mechanism may be related to its promotion of inflammatory response, blood coagulation, and vascular stenosis.

Detection of C8/T1 radiculopathy by measuring the root motor conduction time

BackgroundRoot motor conduction time (RMCT) can noninvasively evaluate the status of the proximal root segment. However, its clinical application remains limited, and wider studies regarding its use are scarce. We aimed to investigate the association between C8/T1 level radiculopathy and RMCT.MethodsThis was a retrospective cross-sectional study. Subjects were extracted from a general hospital’s spine clinic database. A total of 48 C8/T1 root lesions from 37 patients were included, and 48 C8/T1 root levels from control subjects were matched for age, sex, and height. RMCT was measured in the abductor pollicis brevis muscle and the assessment of any delays owing to C8/T1 radiculopathy.ResultsThe RMCT of the C8/T1 radiculopathy group was 1.7 ± 0.6 ms, which was significantly longer than that in the control group (1.2 ± 0.8 ms; p = 0.001). The delayed RMCT was independently associated with radiculopathy (adjusted odds ratio, 1.15; 95% confidence interval, 1.06–1.27; p = 0.011) after adjusting for the peripheral motor conduction time, amplitude of median compound motor nerve action potential, and shortest F-wave latency. The area under the Receiver Operating Characteristic curve for diagnosing C8/T1 radiculopathy using RMCT was 0.72 (0.61–0.82). The RMCT was significantly correlated with symptom duration (coefficient = 0.58; p < 0.001) but was not associated with the degree of arm pain.ConclusionOur findings illustrate the clinical applicability of the RMCT by demonstrating its utility in diagnosing radiculopathy at certain spinal levels.

The Muscle Cuff Regenerative Peripheral Nerve Interface for the Amplification of Intact Peripheral Nerve Signals.

Robotic exoskeletons have gained recent acclaim within the field of rehabilitative medicine as a promising modality for functional restoration for those individuals with extremity weakness. However, their use remains largely confined to research institutions, frequently operating as a means of static extremity support as motor detection methods remain unreliable. Peripheral nerve interfaces have arisen as a potential solution to this shortcoming; however, due to their inherently small amplitudes, these signals can be difficult to differentiate from background noise, lowering their overall motor detection accuracy. As current interfaces rely on abiotic materials, inherent material breakdown can occur alongside foreign body tissue reaction over time, further impacting their accuracy. The Muscle Cuff Regenerative Peripheral Nerve Interface (MC-RPNI) was designed to overcome these noted complications. Consisting of a segment of free muscle graft secured circumferentially to an intact peripheral nerve, the construct regenerates and becomes reinnervated by the contained nerve over time. In rats, this construct has demonstrated the ability to amplify a peripheral nerve's motor efferent action potentials up to 100 times the normal value through the generation of compound muscle action potentials (CMAPs). This signal amplification facilitates high accuracy detection of motor intent, potentially enabling reliable utilization of exoskeleton devices.

Study of the Transcutaneous Auricular Vagus Nerve Stimulation May Advance Outcome in Chronic Pediatric Inflammatory Diseases

The recent insight that the immune system is innervated has initiated a search for neural reflex circuits suitable for therapeutic targeting in human inflammatory diseases. The inflammatory reflex, signaling along the vagus system to maintain immune system homeostasis, is the best characterized such circuit. Proinflammatory molecules, extracellularly released during infectious or sterile injury, are sensed by afferent vagal nerves that transmit this information to the nucleus of tractus solitarius in the brainstem. The afferent signals generate efferent action potentials that travel from the brainstem via efferent vagal nerves to the spleen and other organs. This culminates in T cell release of acetylcholine, which interacts with α7 nicotinic acetylcholine receptors on immunocompetent cells to inhibit proinflammatory cytokine release. These mobile anti-inflammatory T lymphocytes thus operate both inside and outside compartments innervated by the vagus system. Therapeutic proof-of-concept anti-inflammatory studies following surgical implantation of electrical vagus nerve stimulators were first conducted in rheumatoid arthritis and Crohn´s disease. Long term use of these devices was uneventful, while the initial surgical procedure caused adverse effects in some patients. The auricular branch of the vagus nerve reaches superficial parts in the concha and tragus in both ears, enabling transcutaneous electrical auricular vagus nerve stimulation (taVNS) as a safer therapeutic alternative. Invasive VNS and taVNS activate similar parts of the central nervous system indicated by functional imaging methods. Pilot taVNS studies in patients with inflammatory diseases have so far been conducted to treat rheumatoid arthritis, osteoarthritis, lupus, pediatric inflammatory bowel diseases, and pediatric nephrotic syndromes.

The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis.

The neuromuscular junction (NMJ) is a highly specialized synapse between a motor neuron nerve terminal and its muscle fiber that are responsible for converting electrical impulses generated by the motor neuron into electrical activity in the muscle fibers. On arrival of the motor nerve action potential, calcium enters the presynaptic terminal, which leads to the release of the neurotransmitter acetylcholine (ACh). ACh crosses the synaptic gap and binds to ACh receptors (AChRs) tightly clustered on the surface of the muscle fiber; this leads to the endplate potential which initiates the muscle action potential that results in muscle contraction. This is a simplified version of the events in neuromuscular transmission that take place within milliseconds, and are dependent on a tiny but highly structured NMJ. Much of this review is devoted to describing in more detail the development, maturation, maintenance and regeneration of the NMJ, but first we describe briefly the most important molecules involved and the conditions that affect their numbers and function. Most important clinically worldwide, are myasthenia gravis (MG), the Lambert-Eaton myasthenic syndrome (LEMS) and congenital myasthenic syndromes (CMS), each of which causes specific molecular defects. In addition, we mention the neurotoxins from bacteria, snakes and many other species that interfere with neuromuscular transmission and cause potentially fatal diseases, but have also provided useful probes for investigating neuromuscular transmission. There are also changes in NMJ structure and function in motor neuron disease, spinal muscle atrophy and sarcopenia that are likely to be secondary but might provide treatment targets. The NMJ is one of the best studied and most disease-prone synapses in the nervous system and it is amenable to in vivo and ex vivo investigation and to systemic therapies that can help restore normal function.

Overexpression of Neuregulin-1 (NRG-1) Gene Contributes to Surgical Repair of Brachial Plexus Injury After Contralateral C7 Nerve Root Transfer in Rats.

BackgroundSurgeons usually transfer the contralateral C7 to the median nerve on the injured side via a nerve graft to recover sensation and movement in a paralyzed hand. The purpose of our study was to determine whether NRG-1 affects the recovery of nerve function in brachial plexus injury after contralateral C7 nerve root transfer in a rat model.Material/MethodsAn injury model of left brachial plexus and contralateral C7 nerve root transfer was established. Four weeks after the operation, NRG-1 expression was examined by reverse transcription quantitative polymerase chain reaction and Western blot analysis. The diameter rate differences of the healthy limb and affected limb were estimated. The postoperative mass of the left latissimus dorsi, triceps, extensor carpi radialis brevis, and musculus extensor digitorum were examined. The number of nerve fibers and typical area of the affected side were assessed. Postoperative left motor nerve conduction velocity (MNCV) and motor nerve action potential (MNAP) were tested by use of a biological information recording and collecting system.ResultsEukaryotic expression plasmid of pcDNA4/myc/A-NRG-1 was successfully constructed, and NRG-1 was overexpressed. Compared with the model group, the NRG-1 group had a lower rate of differences of the limbs; higher mass of left latissimus dorsi, triceps, extensor carpi radialis brevis, and musculus extensor digitorum; more nerve fibers and larger typical area in the affected side, left MNCV, and MNAP; and wider CSA of the left triceps.ConclusionsThese results demonstrated that NRG-1 can promote recovery of nerve function in brachial plexus injury after contralateral C7 nerve root transfer in rats.

Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

The Relationship between Nerve Conduction Study and Clinical Grading of Carpal Tunnel Syndrome.

Carpal Tunnel Syndrome (CTS) is the most common nerve entrapment. Subjective sensory symptoms are common place in patients with CTS, but sometimes they are not supported by objective findings in the neurological examination. Electrodiagnostic (EDx) studies are a valid and reliable means of confirming the diagnosis. The amplitudes along with the conduction velocities of the sensory nerve action potential and motor nerve action potential reflect the functional state of axons, and are useful parameters and complement the clinical grading in the assessment of severity of CTS. To conduct median nerve sensory and motor conduction studies on patients with carpal tunnel syndrome and correlate the relationship between nerve conduction study parameters and the clinical severity grading. Based on clinical assessment, the study patients were divided into 03 groups with mild CTS, moderate CTS and severe CTS respectively as per Mackinnson's classification. Median and ulnar nerve conduction studies were performed on bilateral upper limbs of 50 patients with symptoms of CTS and 50 age and sex matched healthy control subjects. The relationship between the clinical severity grade and various nerve conduction study parameters were correlated. In this prospective case control study, 50 patients with symptoms consistent with CTS and 50 age and sex matched healthy control subjects were examined over a 10 month period. A total of 30 patients had unilateral CTS (right upper limb in 19 and left upper limb in 11) and 20 patients had bilateral CTS. Female to male ratio was 3.54 to 1. Age ranged from 25 to 81 years. The mean age at presentation was 49.68±11.7 years. Tingling paresthesias of hand and first three fingers were the most frequent symptoms 48 (98%). Tinel's and Phalen's sign were positive in 36 (72%) and 44 (88%) patients respectively. The mean duration of symptoms at presentation was 52.68±99.81 weeks. 16 patients (32%) had mild CTS, 25 (50%) had moderate CTS and 9 (18%) had severe CTS clinically. Prolongation of motor latency, latency difference between median and ulnar amplitudes, motor and sensory nerve conduction velocities, sensory latency between median and ulnar nerves, sensory nerve conduction velocities showed significant changes in comparison with controls. Among them sensory latency difference between median and ulnar nerves and sensory nerve conduction velocities are the most sensitive and specific for diagnosing CTS. In this study, there was a graded deterioration of electrophysiological parameters along with the clinical severity grades, thus reiterating the fact that NCS provide additional, independent objective evidence in the diagnosis and severity assessment of CTS. The sensory conductions were more sensitive than motor conductions in assessing CTS.

Results after simple decompression of the ulnar nerve in cubital tunnel syndrome.

Cubital tunnel syndrome represents the second most common compression neuropathy of the upper limb. For more than four decades there has been a controversy about the best surgical treatment modality for cubital tunnel syndrome. In this study the results of 28 patients with simple ulnar nerve decompression are presented. Data analyses refers to clinical examination, personal interview, DASH-questionnaire, and electrophysiological measurements, which were assessed pre- and postoperatively.28 patients (15 females, 13 males) were included in this study. The average age at time of surgery was 47.78 years (31.68–73.10 years). The period from onset of symptoms to surgery ranged from 2 to 24 months (mean 6 months). The mean follow-up was 2.11 years (0.91–4.16 years).Postoperatively there was a significant decrease in DASH score from 52.6 points to 13.3 points (p<0.001). Also the electrophysiological findings improved significantly: motor nerve conduction velocity increased from 36.0 m/s to 44.4 m/s (p=0.008) and the motor nerve action potential reached 5,470 mV compared to 3,665 mV preoperatively (p=0.018). A significant increase of grip strength from 59% (in comparison to the healthy hand) to 80% was observed (p=0.002). Pain was indicated by means of a visual analog scale from 0 to 100. Preoperatively the median level of pain was 29 and postoperatively it was 0 (p=0.001). The decrease of the two-point-discrimination of the three ulnar finger nerves was also highly significant (p<0.001) from 11.3 mm to 5.0 mm. Significant postoperative improvement was also observed in the clinical examination concerning muscle atrophy (p=0.002), clawing (p=0.008), paresthesia (p=0.004), the sign of Froment (p=0.004), the sign of Hoffmann-Tinel (p=0.021), and clumsiness (p=0.002).Overall nearly 90% of all patients were satisfied with the result of the operation. In 96.4% of all cases, surgery improved the symptoms and in one patient (3.6%) the success was noted as “poor” because the symptoms remained unchanged. In 35.7% the success was graded as “moderate”, in 10.7% as “good” and in 50.0% as “very good”.

P188. Gender-dependent differences in a cohort of Charcot-Marie-tooth (CMT) patients

Charcot-Marie-Tooth (CMT)-disease is the most common form of hereditary neuropathy and affects approximately 1 in 2500 people. It is inherited in an autosomal-dominant, -recessive or X-linked fashion (Gess et al., 2013). Mutations in >80 genes are known to cause CMT (CeGat). An effective treatment is not available yet. In this project, we aimed to test gender-dependent differences in CMT severity. Data from the German CMT patient registry (Friedrich-Baur-Institut) and our neuromuscular outpatient clinic were evaluated. 103 patients from Muenster (74.6%) with a genetically proven CMT were included. CMT1A built the largest sub-group with 67% (69 patients). The gender distribution was slightly unequal, with a surplus of women (41; 59.4%). The overall mean age was 47.4years (SD 13.3; men: 50.4/SD 15.5; women: 44.2/ SD 11.2). The examination consisted of patient history, muscle force testing (MRC grades divided into MRC⩾4 and ⩽3; foot dorsal extension dynamometry), nerve conduction studies (mNCV, CMAP, sNCV, SNAP) and CMT Neuropathy Scores (CMTNS and CMTNS-2). In a statistic analysis we assessed whether the CMTNS/CMTNS-2, muscle force, nerve conduction studies and foot operations differed in men and women and if they were dependent age. Men's mean CMTNS (18.2/SD 5.8) and CMTNS-2 (16.5/SD 5.6) were both higher than women's (16.4/SD 3.9 and 15.0/SD 4.1) within our patients. This difference was shown to be not significant ( p =0.249 and p =0.376). In a multivariate analysis with gender and age as covariates, gender showed to have no influence on both Neuropathy Scores ( p =0.527 for CMTNS, p =0.854 for CMTNS-2). However, age showed a highly significant influence on CMTNS and a trend on CMTNS-2 ( p =0.008 for n =59; p =0.085 for n =36). We could show that muscle force was not dependent of age or foot operations, but of gender. Regarding muscle force grades in the lower limb, statistically significant differences depending on gender could be found. The significance levels were p =0.029/0.006 (right/left) for dorsal extension and p =0.078/0.030 for plantar flexion of the foot. In the upper limbs, no difference with respect to gender could be detected. Within the small group of patients for whom we obtained these measurements ( n =27) no significant differences with respect to gender ( p =0.132 right, p =0.067 left) or age could be found. Examining the values for sensory/ motor nerve conduction velocities and nerve action potentials of the ulnar nerve on the non-dominant hand, we could not find any significant differences between men and women. SNAP showed a trend though ( p =0.087). Besides, we could show that age was negatively correlated to the values for CMAP ( p =0.003). Regarding foot operations, the relation of operated to non-operated patients was almost identical in both sexes. Taken together, this preliminary analysis of our ongoing study showed no significant difference in CMTNS scores, but significantly worse muscle force grades of the lower limbs in men compared to women, independent of age and foot surgery. Hence, there is the possibility that men with CMT1A lose their muscle strength (in the lower limbs) faster than women do.

Spinocerebellar Ataxia Type 7: A Neurodegenerative Disorder with Peripheral Neuropathy

Background: Autosomal dominant spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative disorders that typically show peripheral neuropathy. SCA7 is one of the rarest forms of SCA (<1/100,000 individuals). However, the disease shows a prevalence of ∼800/100,000 inhabitants in certain regions of Mexico. This low global prevalence may explain, at least in part, the isolated anecdotal and limited clinical data regarding peripheral neuropathy in SCA7 patients. Aim: To assess sensory and motor peripheral nerve action potentials in an SCA7 patients group and in healthy volunteers, and subsequently correlate the electrophysiological findings with clinical and genetic features. Materials and Methods: We enrolled in our study, 13 symptomatic SCA7 patients with a confirmed molecular and clinical diagnosis, and 19 healthy volunteers as the control group. Nerve conduction studies were carried out using standard electromyography recording methods. The sensory and motor latency, amplitude and conduction velocity were recorded in both experimental groups and analyzed using the Student's t-test. Results: SCA7 patients showed a significant prolongation of sensory nerve conduction latencies, as well as a decrease in sensory amplitudes. Decreases in motor amplitudes and peroneal conduction velocity were also observed. Finally, we found an association between CAG repeats and the severity of cerebellar and non-cerebellar symptoms with electrophysiological signs of demyelinization. Discussion: Our results reveal the existence of a critical sensorimotor peripheral neuropathy in SCA7 patients. Moreover, we show that using sensitive electrophysiological tools to evaluate nerve conduction can improve the diagnosis and design of therapeutic options based on pharmacological and rehabilitative strategies. Conclusion: These findings demonstrate that SCA7 is a disease that globally affects the peripheral nervous system.

Body size and the neural control of movement

Summary Nervous systems, muscles, and motor organs (biomechanics) generate movement cooperatively and should therefore change coordinately as body size changes. Proving this hypothesis requires a description of the nervous system, muscle, and biomechanics of individual species and comparison of these properties across a collection of species spanning a large size range. Obtaining these data in even one species is daunting, and we are far from reaching a general theory of how nervous system, muscle, and biomechanics depend on body size. Sufficient cross-species data nonetheless exist to identify some consequences of body size on the neural control of movement, which form the focus of this Primer: for example, locomotor cycle period depends on leg length; large animals should devote more neural resources to hazard avoidance and stride correction; the importance of gravity and momentum increases, and of passive muscle properties decreases, with limb size; and the medium in which movements occur affects these size dependencies. These considerations suggest that, in applying biological data to robotic design, proper ‘size' should be maintained across all levels (i.e., if small-animal neural mechanisms are used, so should small-animal muscle and biomechanical properties).

Clinical analysis and outcomes of amyotrophic lateral sclerosis with demyelinating polyneuropathy

Abnormalities of both motor and sensory nerve action potentials, similar to those found in demyelinating polyneuropathy, may occur in patients with amyotrophic lateral sclerosis (ALS). We analyzed the clinical features of unusual ALS patients with demyelinating polyneuropathy (DPN) to delineate the characteristics and outcomes of this rare condition. We reviewed three ALS patients with DPN who were confirmed to meet the electrophysiological nerve conduction criteria for DPN among 157 patients with ALS. At the initial neurological examination, one patient had both subjective sensory symptoms and abnormal results of sensory examinations, and one patient had sensory symptoms. Motor weakness of the limbs was present in all patients, and fasciculation was present in two patients. Anti-GalNAc-GD1a IgG antibodies were evident in one. Sural nerve biopsy showed a moderate, marginal reduction in myelin thickness, and teased fiber analysis revealed segmental demyelination and remyelination, but axonal degeneration was found in one patient. The mean interval from disease onset to respiratory failure or death in our three patients and seven previously documented ALS patients with DPN was 43.1 ± 18.7 months. Our findings suggest that survival in ALS with DPN is similar to that in classic ALS.

Experimental Study on Mechanical Vibration Massage for Treatment of Brachial Plexus Injury in Rats

To investigate the curative effect of the self-made mechanical vibration massage instrument for treatment of brachial plexus injury in rats and to explore its mechanism. Brachial plexus injury models were made in 144 Wistar rats and one week after natural healing of the wound, they were randomly divided into 3 groups, mechanical vibration treatment group (MV group), nerve growth factor treatment group (NGF group) and model group, 48 rats in each group. Then again, the each group was randomly divided into 4 subgroups, 7-day group, 14-day group, 21-day group and 28-day group, 12 rats in each subgroup. The MV group were treated by mechanical vibration at acupoints on three-yang and three-yin channels of the hand with the mechanical vibration massage instrument; The NGF group were treated with injection of NGF into musculus pectoralis major on the affected side; And the model group were normally fed with no treatment. After treatment for 7, 14, 21 and 28 days, the diameter of both forelimbs were measured, the electrophysiological examination on the brachial plexus in vitro and the ultrastructure observation with electron microscope on the affected side were carried out, the motor nerve conduction velocity (MNCV) and motor nerve action potential (MNAP) of the brachial plexus on the affected side, NGF content of submaxillary gland as well as muscular Na+, K(+)-ATPase activity were determined respectively. The different rates of the forelimb diameter in the MV group and the NGV group on the 14th d, 21st d and 28th d were better than those in the model group (P < 0.05 or P < 0.001), and in the MV group were better than those in the NGF group on the 21st d and the 28th d (P < 0.05). MNCV in the MV group and the NGV group on the 21st d and 28th d was better than that in the model group (P < 0.05 or P < 0.001), and in the MV group was better than that in the NGF group on the 28th d (P < 0.05). MNAP in the MV group and the NGV group on the 14th d, 21st d and 28th d was better than that in the model group (P < 0.05 or P < 0.001), and in the MV group was better than that in the NGF group on the 21st d and 28th d (P < 0.05). The NGF mean gray index of submaxillary gland in the model group was higher than that in the MV group and the NGF group on the 7th d (P < 0.05); in the NGF group and the model group was higher than that in the MV group on the 14th d (P < 0.05); and in the NGF group and the MV group was higher than that in the model group on the 21st d and 28th d (P < 0.05). Na+, K(+)-ATPase activity in the model group and the MV group was higher than that in the NGF group (P < 0.05) on the 14th d, and in the MV group was higher than that in the model group on the 28th d (P < 0.05). As compared with the NGF group and the model group, mechanical vibration treatment can effectively accelerate repair of injured brachial plexus, slow down atrophy of skeletal muscle, and promote secretion of NGF in submaxillary gland.

Long-term results of peripheral nerve repair: A comparison of nerve anastomosis with ethyl-cyanoacrylate and epineural sutures

Event Abstract Back to Event Long-term results of peripheral nerve repair: A comparison of nerve anastomosis with ethyl-cyanoacrylate and epineural sutures Thomas Landegren1* 1 Karolinska Institutet, Department of Clinical Science and Education, Sweden There is a need for complementary surgical techniques which offers rapid and reliable primary repair of transected nerves. Anastomosis of a nerve with synthetic adhesive following a lesion has previously been shown to indicate recovery to an extent comparable to that of conventional techniques. The aim of this study was to quantify the morphological and functional recovery and evaluate the selectivity of muscle reinnervation after transection and repair of rat sciatic nerve, and compare epineural sutures with a synthetic ethyl-cyanoacrylate tissue adhesive. Six month after repair, when reinnervation had well been completed the tibial branch to the lateral gastrocnemius muscle and the caudal sural cutaneous nerve were examined with electrophysiological measurements of motor and sensory conduction velocity, motor nerve action potentials, and quantitative histological examinations. Furthermore, cholera toxin B technique of retrograde axonal tracing was used to evaluate the morphology, the number and the three-dimensional location of a-motoneurons in L5 spinal cord, innervating the lateral gastrocnemius muscle and the results were put in relation to the recorded wet weight of the muscle. There was functional reinnervation of motor and sensory nerves in both groups, as shown by equivalent recovery of motor and sensory conduction velocities, and motor nerve action potentials. Histological examination showed no significant difference in the mean diameter, fibre density or the number of regenerated myelinated motor and sensory axons distal to the repair site between the two groups. Moreover, independent of repair method, the redistribution of the motoneuron pool were markedly disorganized, had increased apparently in number, and were scattered throughout a larger volume of the spinal cord grey matter with a decrease in the synaptic coverage compared to controls. A reduction in muscle weight was observed as well. Differences compared to controls were statistically significant. We conclude that anastomosis of the nerve with ethyl-cyanoacrylate adhesive supports morphological and functional recovery comparable to that of conventional epineural sutures after a unilateral lesion of the sciatic nerve in adult rats. Keywords: cyanoacrylate, motoneuron, Nerve repair, peripheral nerve, Regeneration, retrograde tracing, spinal misdirection, synthetic adhesive Conference: Karolinska Institutet 200 years anniversary Symposium on Traumatic Injuries in the Nervous System, Stockholm, Sweden, 15 Sep - 16 Sep, 2010. Presentation Type: Presentation Topic: Traumatic Injuries in the Nervous System Citation: Landegren T (2010). Long-term results of peripheral nerve repair: A comparison of nerve anastomosis with ethyl-cyanoacrylate and epineural sutures. Front. Neurol. Conference Abstract: Karolinska Institutet 200 years anniversary Symposium on Traumatic Injuries in the Nervous System. doi: 10.3389/conf.fneur.2010.56.00011 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 07 Sep 2010; Published Online: 21 Sep 2010. * Correspondence: Dr. Thomas Landegren, Karolinska Institutet, Department of Clinical Science and Education, Stockholm, Sweden, Thomas.landegren@ki.se Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Thomas Landegren Google Thomas Landegren Google Scholar Thomas Landegren PubMed Thomas Landegren Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Excitability properties of motor axons in the maturing mouse

Non-invasive excitability tests have been developed to appraise axonal membrane properties in peripheral nerves and are contributing to our understanding of neuropathies and neuronopathies. These techniques have been adapted to in vivo and in vitro rat models, but little data are available on mice, although mice provide more transgenic models of neurological disorders. This study was therefore undertaken to assess the suitability of mice to model human nerve excitability measurements and to document changes during maturation. Female mice, aged 4-19 weeks, were recorded under isoflurane anesthesia. Electrical stimuli were applied via surface electrodes to the caudal motor nerve and compound muscle action potentials (CMAPs) recorded from the tail with needle electrodes. Then, the sciatic nerve was stimulated above the ankle and CMAPs recorded from plantar muscles. The method was only minimally invasive, enabling the same animal to be tested up to eight times at weekly intervals. As in human studies, the multiple excitability program recorded stimulus-response, strength-duration, and current-threshold relationships; threshold electrotonus; and recovery cycle. The response waveforms were qualitatively similar to those from human axons. This resemblance was closer for the caudal nerve, which also showed more marked changes with age. Early hyperpolarizing electrotonus fell sharply from weeks 4 to 13 (p < 0.0001), while a progressive increase in superexcitability occurred throughout the period studied (p < 0.001). We conclude that multiple measures of nerve excitability can be performed reliably in mice in vivo, preferentially on the tail, and are suitable for longitudinal studies, but age matching is critical for younger animals.

Peripheral Neuropathy (PN) in Multiple Myeloma (MM) Responder Patients during Maintenance Therapy with Low-Intermittent Doses of Thalidomide (TAL).

Novel agents for MM treatment such as TAL, bortezomib and lenalidomide while offering higher rates of response and CR have lead to new side-effects, in particular peripheral neuropathy that is dose limiting in more than 40% of patients. We have investigated the toxicity and the effectivness of low doses of TAL as maintenance treatment in MM in order to minimize this harmful side-effect.METHODS: From October 1999, 54 pts (20 males/34 females) with advanced/relapsed MM (IgG-K 28; IgG-λ 11; IgA-K 8; IgA-λ 4; λ 2; K 1) were treated with TAL at 100 mg/day; if well tolerated, the dose could be increased to a maximum of 400 mg/day. 2 pts stopped treatment and weren't valuables for response. 11 pts (20%) progressed and 5 (9%) reached only a stable disease/minimal response. 27 pts (50%) responded to treatment with 22 (81%) PR (> 50% of reduction of MC) and 5 (9%) CR. Somnolence and stypsis were seen in all pts but were reversible and treated with symptomatic drugs. In 17 pts (11 F, 6 M, median age 70 yrs) we observed a symptomatic neuropathy and we decided to reduce dosage at 100 mg dayly only for 10 days at month as MT. All other causes of neuropathies were excluded. We prospectively performed longitudinal neurological and nerve conduction study before and during TAL treatment every 3 months. Nerve conduction studies included recording of sensory and motor nerve action potential from surale, radial, ulnar, common peroneal and tibial nerves. We considered -p SNAP and Cmap amplitude for each nerve. Electromyography examination was performed in distal muscles of the limbs including denervation potentials and pattern of activation.RESULTS: In 2 out of 17 we found a mild distal sensory-motor neuropathy before TAL treatment. One referred paresthesia in the 8 months before the diagnosis of MM; the other one was asymptomatic and the diagnosis of neuropathy was made on the basis of clinical and electrophysiological data. The 2 pts with PN before TAL treatment showed a mild clinical and electrophysiological progression of the disease after 6 months of therapy. The first clinical symptoms were painful paresthesias and numbness in all pts. At neurological examination we found a symmetric distal polyneuropathy of sensory type with major evidence at lower limbs. Hypopallestesia and hyporeflexia at lower limbs were detected in all pts; in 3 there was areflexia of achillei reflexes. In 2 pts we found hyperesthesia a stock and gloves distribution. No pts showed motor deficits or cranial nerves impairments. In 12 out of 17 pts an axonal sensory-motor neuropathy was found; in 3 pts a pure sensitive neuropathy, more evident at lower limbs, was detected. In the subsequent 58 months follow-up evaluation, no progression of clinical and electrophysiological findings was demonstrated in the 17 pts. Two of them, however, had to discontinue TAL therapy for severe painful paresthesias. After a median of 8 months' follow-up, 10/17 pts are alive (2–58 months) and in remission (2 CR and 8 PR); 5 pts showed a disease progression after a median therapy of 5 months (2–23 months) and two pts, who had achieved a PR, had to stop therapy because of severe neurotoxicity after 8 months of treatment (5–12 months).CONCLUSIONS: The incidence of TAL neuropathy is high and problematic, but the lower cumulative doses of this schedule appear to be less toxic and manageble also mainteining a high rate of response (58%).