Nerve Compound Muscle Action Potential Research Articles

P89: Do higher proximal ulnar nerve compound muscle action potentials result from higher conduction velocities of axons mediating the second of its two negative peaks?

P89: Do higher proximal ulnar nerve compound muscle action potentials result from higher conduction velocities of axons mediating the second of its two negative peaks?

Factors Contributing to Postural Sway in Patients with Diabetes in an In-Hospital Education Program

Objective: We investigated the effect of polyneuropathy, nephropathy, and retinopathy on postural sway in patients with poorly controlled diabetes mellitus (DM) who were hospitalized for DM education. We also investigated the relationship between postural sway and hearing disturbances. Methods: We included 50 subjects who were hospitalized for the purpose of DM education. Mean age was 57.2 years, mean HbA_1c was 9.4%, and mean DM duration was 11.1 years. Renal function, retina condition, and nerve conduction were evaluated in relation to DM complications (nephropathy, retinopathy, and neuropathy). Static posturography was performed to assess DM-related postural sway. Nerve conduction studies were used to obtain information on the condition of peripheral nerves. Pure-tone audiometry was measured. Stepwise multiple linear regression was used to assess DM-related factors that affected postural sway. Results: Deterioration of median nerve compound muscle action potential (CMAP) amplitude, tibial nerve CMAP conduction velocity, and peroneal nerve CMAP latency were associated with deterioration of postural sway. Deterioration of hearing in the worse ear was also associated with postural sway. Conclusion: In patients with poorly controlled DM, postural sway was particularly associated with deterioration of motor nerve conduction study parameters represented by median nerve CMAP amplitude, tibial nerve CMAP conduction velocity, and peroneal nerve CMAP latency. A link between diabetic polyneuropathy, diabetes-related postural sway, and diabetes-related hearing loss was recognized.

Plasma total homocysteine is not associated with peripheral neuropathy in a groups Bangladeshi type 2 diabetic subjects

Aims: The present study was undertaken to explore the relationship of plasma homocysteine in the pathogenesis of neuropathy in diabetic patients.Subjects and Methods: Forty two type 2 diabetic patients [22 with neuropathy (DN group) and 20 without neuropathy (DNN group)], age range between 35-70 years had relatively controlled glycemia and duration of diabetes 7-15 years, were studied. Motor and sensory nerve conduction velocities and action potential amplitudes of peripheral nerves were determined by following standard protocol. HbA1c was estimated by modified HPLC (BIO-RAD Variant, USA). Serum C-peptide was measured by enzyme linked immunosorbentassay (ELISA), plasma total homocysteine by Fluorescent Polarization Immunoassay (FPIA). Results: Age, BMI and blood pressure of the study subjects were. Duration of diabetes between DN and DNN groups was comparable. DN group had significantly higher fasting glucose levels (9.8±3.8, mmol/l) compared to the DNN group (6.9±1.8, p=0.004). This trend was also reflected in the HbA1c level: 8.7± 2.1 vs 7.2±1.6 in DN group and DNN group respectively (p=0.009). The two diabetic groups had relatively higher absolute C-peptide level compared to the controls (p=ns). DN and DNN groups had significantly higher plasma homocysteine level compared to the Controls. But between the two diabetic groups no significant difference was observed. Ulnar and peroneal motor nerve conduction velocities and compound muscle action potentials in the diabetic neuropathy group significantly lower compared to diabetic counterpart and the controls. Ulnar and sural sensory nerve conduction velocities and action potentials were significantly lower in the diabetic neuropathy group compared to the diabetic counterpart and the controls. Plasma homocysteine did not show any correlation with nerve conduction velocities and action potential amplitudes.Conclusions: The data concluded that (i) Diabetic neuropathy may not be related to hyperhomocysteinemia in type 2 diabetic patients of Bangladeshi origin; (ii) Hyperglycemia, even at milder level, is related to neuronal dysfunction in these subjects; and (ii) Hyperinsulinemia don't seem to be prerequisite for neuropathy in these subjects. DOI: http://dx.doi.org/10.3329/bjms.v11i4.12607 Bangladesh Journal of Medical Science Vol. 11 No. 04 Oct’12

Functional Motor Recovery after Peripheral Nerve Repair with an Aligned Nanofiber Tubular Conduit in a Rat Model

Current synthetic tubular conduits are inferior to nerve autograft for the repair of segmental peripheral nerve injuries. We examined motor outcomes with the use of longitudinally aligned poly (L-lactide-co-caprolactone) nanofiber conduits for repair of nerve gap injury in a rat model. Ten-millimeter segments of sciatic nerve were resected in 44 Lewis rats. The gaps were either left unrepaired (n = 6), repaired with nerve autograft (n = 19), or repaired with conduit (n = 19). After 12 weeks, nerve conduction latency, compound muscle action potential amplitude, muscle force and muscle mass were measured. The numbers of axons and axon diameters both within the grafts and distally were determined. After 12 weeks, gastrocnemius isometric tetanic force and muscle mass for the conduit group reached 85 and 82% of autograft values, respectively. Nerve conduction and compound muscle action potential were not significantly different between these two groups, although the latter approached significance. There was no recovery in the unrepaired group. Muscle recovery for the animals treated with this aligned nanofiber conduit approached that of autograft, suggesting the importance of internal conduit structure for nerve repair.

Flexion myelopathy: Hirayama’s syndrome

Flexion-induced myelopathy is a rare differential diagnosis in unilateral, sometimes bilateral, juvenile upper limb muscular atrophies innervated by C7–Th1 spinal segments. We report a patient with Hirayama’s syndrome with special emphasis on the radiological findings. We report a 29-year-old German female patient who was admitted to our hospital for the presence of atrophy and weakness of the distal upper extremities. Family history was negative for neuromuscular disorders. Symptoms began insidiously and stabilized after several years. Neurologic examination showed a marked bilateral asymmetric atrophy of intrinsic hand and forearm muscles with sparing of all other muscles, including the bulbar ones. No pyramidal or sensory signs or bladder dysfunction were observed. Results of routine blood analysis including vitamin B12 and of CSF analysis were normal. Neurophysiologic examinations showed bilateral severe chronic neurogenic changes in C7–C8–Th1 myotomes, low ulnar nerve compound muscle action potentials, especially no signs of conduction block, and no somatosensory conduction abnormalities. F-wave analysis of the median and of the ulnar nerve, and somatosensory evoked potentials of the medial, ulnar and tibial nerves showed normal results (Figs. 1, 2 and 3). Routine MRI of the spinal column showed focal hyperintensities in the T2 weighted images in the anterior caudal segments of the cervical spinal cord. MRI in neck flexion revealed forward displacement of the posterior cervical dural sac and flattening of the cervical cord, which was pressed against vertebrae and discs. Axial taping reduced forward displacement. The Hirayama hypothesis (Hirayama et al. [5], original description as juvenile muscular atrophy of distal upper extremity) continues to explain best the disease pathogenesis: neck flexion causes tightening of the dura and intramedullary microcirculatory compromise with resultant nerve cell damage. The age-related factor can most likely be accounted for by a growth imbalance between the vertebral column and the cord/dural elements. Resolution of progression is associated with cessation of body growth, after which the symptoms plateau or modestly improve. Hence, spinal compression appears to be related to forward displacement of the posterior dura during neck flexion, and the overly tight dura results in microcirculatory compromise with damage to anterior horn cells [2, 4, 8]. Furthermore, Taylor and Byrnes [7] showed, that compression of any of the upper four segments of the cervical spinal cord, particularly by extramedullary agents, usually causes early symptoms and signs which suggest dysfunction of the lower part of the cervical enlargement. Wasting of the C8–Th1 innervated muscles of the upper limbs, associated with upper cervical compression, was first described by Oppenheim [6]. MRI in neck flexion is diagnostic in Hirayama’s syndrome. Forward displacement of the posterior dura during neck flexion obviously results in microcirculatory compromise with damage to anterior horn cells. The lower cervical segments are not necessarily the place of F. Weber (&) U. M. Mauer Department of Neurology, Military Hospital Ulm, Oberer Eselsberg 40, 89081 Ulm/Donau, Germany e-mail: Dr.Frank.Weber@t-online.de

Ulnar Nerve Latency at Above-Elbow Stimulation

The purpose of this study was to obtain the latency norms of ulnar nerve stimulating at 10 cm above the elbow as a complementary test of the segmental conduction velocity criteria used in the American Association of Electrodiagnostic Medicine guideline for ulnar neuropathy at the elbow (UNE). This is a cross-sectional study of 100 subjects recruited to the electrodiagnostic laboratory of an academic medical center and a retrospective analysis of 14 symptomatic patients diagnosed with UNE using the American Association of Electrodiagnostic Medicine practice guideline. Sensory nerve action potential and compound muscle action potential were recorded at the fifth finger and abductor digiti minimi muscle, respectively, with 10-cm above-elbow stimulation and with elbow flexion at 90 degrees. The latency values of ulnar nerve, together with the participant's anthropometric data, were measured and correlated. Afterward, these values were compared with latency values from 14 patients with UNE. Sensory peak and motor onset latency at 10-cm above-elbow stimulation showed mean ± SD values of 8.3 ± 0.7 and 8.0 ± 0.7 msecs, respectively. Latencies were highly correlated with finger-to-arm length (r = 0.87 for sensory and 0.84 for motor). The cutoff values (twice the standard deviation plus the mean) for "abnormal" are 9.7 and 9.4 msecs for sensory and motor latencies, respectively. Applying the motor cutoff value (9.4 msecs) for abnormal, 12 of 14 symptomatic UNE cases were categorized as abnormal, with a sensitivity of 86%. All 14 patients with UNE showed latencies beyond the upper limit of 95% confidence interval of predicted value based on finger-to-arm length. This study provides latency norms of ulnar sensory and motor nerves simulating at 10 cm above the elbow. It can be used as a complementary tool to assess the validity of segmental conduction velocity criteria in the electrodiagnosis of UNE.

Treatment guidelines for Guillain-Barré Syndrome

Guillain–Barre syndrome (GBS) is an acute onset, usually monophasic immune-mediated disorder of the peripheral nervous system. The term GBS is often considered to be synonymous with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), but with the increasing recognition of variants over the past few decades, the number of diseases that fall under the rubric GBS have grown to include axonal variants and more restricted variants, such as Miller Fisher syndrome (MFS) [Table 1].[1] Table 1 Guillain–Barre syndrome—clinical variants Epidemiology The reported incidence rates for GBS are 1–2 per 100,000 population.[2–4] The lifetime likelihood of any individual acquiring GBS is 1:1000.[5] The subtypes of GBS have different incidence rates in different parts of the world. In Europe and North America AIDP is dominant contributing to 90% of the cases. In contrast in China and Japan AMAN being the most common subtype.[6,7] The picture is intermediate when we look at other population. In Indian series the incidence of AIDP and AMAN are virtually equal although AMAN is more common in younger patients.[8] There seems to be a slight preponderance of AIDP in studies by Gupta et al[9] and by Meena et al (unpublished data from NIMS, Hyderabad). Available Indian literature indicates a peak incidence between June–July and Sept–October.[10] In western countries, GBS is common in the 5th decade,[11] but in India it occurs more commonly at a younger age.[10,12] GBS is equally common in men and women and can occur at any age. There is a male preponderance among the hospitalized population.[10,12]

Effect of Ipsilateral C7 Nerve Root Transfer on Restoration of Rat Upper Trunk Muscle and Nerve Function After Brachial Plexus Root Avulsion

The effects of ipsilateral cervical nerve root transfer on the restoration of the rat upper trunk muscle and nerve brachial plexus root avulsion were studied. After simulated root avulsion of the upper trunk brachial plexus, 120 rats were randomly divided into 4 groups: (A) ipsilateral C7 root transfer group; (B) Oberlin group; (C) phrenic nerve group; and (D) no axillary nerve restoration group. At 3, 6, and 12 weeks postoperatively, Ochiai score, Barth feet overreaching test, Terzis grooming test, and indices of neurotization were determined in 10 rats from each group. Twelve weeks postoperatively, nearly all the behavioral, neuroelectrophysiological, and histological outcomes of the axillary nerve and deltoid muscle and some of the indices of musculocutaneous nerve and biceps brachii function in the ipsilateral C7 group were superior to those in the other 3 groups. No significant difference was found between the ipsilateral C7 group and the other 3 groups in recovery rate of wet biceps muscle weight. No significant difference was found between the ipsilateral C7 group and the Oberlin group in the recovery of the axillary nerve compound muscle action potential and biceps brachii cell size. No significant difference was found between the ipsilateral C7 group and the phrenic nerve and no axillary nerve restoration groups in amplitude recovery rate of musculocutaneous nerve compound muscle action potential. No significant difference was found between the ipsilateral C7 and the Oberlin groups in the early recovery of musculocutaneous nerve compound muscle action potential, but recovery was significantly better in the ipsilateral C7 group at 12 weeks. Ipsilateral C7 root transfer can improve the quality of restoration of muscle and nerve function in the rat upper trunk after brachial plexus root avulsion.

Sequential neuroradiological and neurophysiological studies in a Japanese girl with merosin-deficient congenital muscular dystrophy

We describe the early manifestation and sequential assessment of the central and peripheral nervous system in a Japanese girl with merosin-deficient congenital muscular dystrophy. She showed severe hypotonia (‘‘floppy infant”) and suffered mild respiratory failure postnatally. Serum creatine kinase was elevated to 11,487 IU/L. The muscle biopsy showed dystrophic changes with negative expression of merosin (laminin α2), thereby confirming merosin-deficient congenital muscular dystrophy. Her motor milestones were severely delayed, but she could sit without support at the age of 3 years. After 3 years, her motor ability deteriorated and by the age of 5 years, she could not sit and control her neck. Magnetic resonance imaging (MRI) at 2 months of age revealed patterns that were appropriate for her age. At 1 year of age, the T2 weighted images showed diffuse high signal intensities throughout the centrum semiovale, and periventricular and subcortical white matter of the frontal and occipital lobes, while the U fibers, the corpus callosum and the internal capsule were spared. At the age of 7 years, these white matter abnormalities decreased. MR spectroscopy (MRS) revealed normal values of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr metabolite ratios as well as slightly increased myoinositol (mI)/Cr metabolite ratios. Neurophysiological motor nerve conduction velocity (MCV) and compound muscle action potential (CMAP) of the median nerve were in the normal range at the age of 2 months. After the child reached 1 year of age, the MCV and CMAP lagged behind those of healthy controlled children. The sensory nerve conduction velocity of the median nerve demonstrated a mild delay at the age of 15 months. It improved to normal range at the age of 6 years but decreased at 7 years of age . These sequential findings suggest not only that muscular degeneration and dysmyelination had occurred but also that various other factors, including demyelination and the vasogenic system, may influence the pathology of MDC1A.

Optimal Placement of Recording Electrodes for Quantifying Facial Nerve Compound Muscle Action Potential

To analyze optimal placement of recording-needle electrodes surrounding the eye and lip for facial nerve monitoring by identifying the maximum compound muscle action potential (CMAP) recorded by electrode pairs of different spatial configurations. Prospective clinical trial. Ambulatory surgery at a tertiary care center. Thirty adults undergoing chronic ear surgery such as tympanoplasty, mastoidectomy, ossicular chain reconstruction, stapedectomy, and cochlear implantation. Facial nerve monitoring. Suprathreshold (threshold + 0.2 V) CMAP responses are recorded from referential paired needle electrodes placed into orbicularis oculi (1.5-cm spacing; n = 15) and orbicularis oris (1.0-cm spacing; n = 15) muscles. Optimal recording electrode placement is inferred by identifying the maximum evoked CMAP amplitude. For the eye, placement of electrodes by the orbital rim and into the upper eyelid is significantly better (Friedman test; p < 0.01) than the other 2 configurations. For the lip, placement of electrodes into the oral commissure and either the upper or lower lip is satisfactory because there is no statistically significant difference among the configurations (Friedman test; p > 0.2). Recording electrode placement configurations that capture the largest CMAP responses are recommended as standard operating procedure for intraoperative facial nerve monitoring.

Endoneurial microvascular pathology in feline diabetic neuropathy

Endoneurial capillaries in nerve biopsies from 12 adult diabetic cats with varying degrees of neurological dysfunction were examined for evidence of microvascular pathology and compared to nerves obtained at necropsy from 7 adult non-diabetic cats without clinical evidence of neurological dysfunction. As reported previously [Mizisin, A.P., Nelson, R.W., Sturges, B.K., Vernau, K.M., LeCouteur, R.A., Williams, D.C., Burgers, M.L., Shelton, G.D., 2007. Comparable myelinated nerve pathology in feline and human diabetes mellitus. Acta Neuropathol. 113, 431–442.], the diabetic cats had elevated glycosylated hemoglobin and serum fructosamine levels, decreased motor nerve conduction velocity and compound muscle action potential (CMAP) amplitude, and markedly decreased myelinated nerve fiber densities. Compared to non-diabetic cats, there was a non-significant 26% increase in capillary density and a significant ( P < 0.009) 45% increase in capillary size in diabetic cats. Capillary luminal size was also significantly ( P < 0.001) increased, while an index of vasoconstriction was significantly decreased ( P < 0.001) in diabetic cats compared to non-diabetic controls. No differences in endothelial cell size, endothelial cell number or pericyte size were detected between non-diabetic and diabetic cats. In diabetic cats, basement membrane thickening, seen as a reduplication of the basal lamina, was significantly ( P < 0.0002) increased by 73% compared to non-diabetic controls. Regression analysis of either myelinated nerve fiber density or CMAP amplitude against basement membrane size demonstrated a negative correlation with significant slopes ( P < 0.03 and P < 0.04, respectively). These data demonstrate that myelinated nerve fiber injury in feline diabetic neuropathy is associated with microvascular pathology and that some of these changes parallel those documented in experimental rodent and human diabetic neuropathy.

Mechanism of post-stroke reflex sympathetic dystrophy:study with needle electromyography

To explore the mechanism of post-stroke reflex sympathetic dystrophy (RSD) patients electromyographic abnormality and confirm its clinical value. Fifty patients with first-onset stroke, aged 33 - 78, including 30 with RSD and 20 without RSD, underwent needle electromyography (EMG) to test the nerve conduction velocity (NCV) and sensory nerve conduction velocity (SCV) of bilateral median nerves, and the number and position of spontaneous EMG activity of bilateral short abductor muscles of thumb and abductor muscles little finger. The median nerve compound muscle action potential (CMAP) amplitude of the affected upper extremities of the RSD group was 8.6 mV +/- 2.9 mV, significantly lower than that of the non-RSD group (13.2 mV +/- 4.6 mV, P < 0.01). The incidence of spontaneous electrical potential of the RSD group was 100%; significantly higher than hat of the non-RSD group (65%, P < 0.001). The quantity of spontaneous EMG activity on the short abductor muscles of thumb and abductor muscles little finger was increased in the RSD group (P < 0.01). The motor nerve conduction velocity and electrophysiological presentation of sensory nerve of these 2 groups were all normal and without significant differences between them. Partial axonal degeneration occurs on the distal motor never fibers of the affected upper extremity of the RSD patients, which may be related to subsequent peripheral nerve injury after central nerve system impairment.

Vincristine-induced neuropathy in rat: electrophysiological and histological study

Peripheral sensory-motor neuropathy is one of the most frequent side effects of vincristine (VCR) administration, which often limits its usefulness in the treatment of a wide range of neoplastic diseases. The purpose of this work is to study VCR neurotoxicity in experimental animals from clinical, electrophysiological, and histological points of view. Sixty-five rats were used as a control group and 31 rats were divided into two groups and given VCR in two different regimens: the fixed-dose group (0.2 mg/kg) and the increasing-dose group (0.1 mg/kg, by an increment of 0.05 mg/kg/week). VCR was given intraperitoneally once weekly for five consecutive weeks. Electrophysiological examinations of the control and both treated groups were performed and included measurements of nerve conduction velocity and action potential (AP) amplitude of sciatic and tail nerves weekly during the period of treatment and 14 weeks after discontinuation of treatment. Histological sections of sciatic nerves were examined after the appearance of early electrophysiological changes, at the end of the 5th, and 19th weeks of the study (14 weeks after discontinuation of treatment). With the progress of the treatment, an increasing number of rats showing signs of neurological deficits were observed. During the first 5 weeks of this study, electrophysiological testing showed a nonsignificant difference in the conduction velocities of sciatic and tail nerves between the control and the treated groups, whereas a significant decrease in the amplitude of the sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) of the tested nerves was recorded. The reduction in the AP amplitude was associated with histological changes characterized by axonal degeneration with relative demyelination. Fourteen weeks after discontinuation of treatment, a significant increment in the SNAP and CMAP amplitudes of both sciatic and tail nerves was noticed. While the CMAP amplitude of the distal segment of the tail showed nonsignificant increment, lesser number of fibers with axonal and/or myelin lesions were found. The clinical, electrophysiological, and histological results suggest that VCR induces peripheral sensorimotor neuropathy of axonal type more prominent in the fixed- than the increasing-dose group. The discontinuation of VCR permitted the improvement of the electrophysiological and histological changes. The rat can be used as an animal model for studying VCR neurotoxicity. However, further studies on larger number of animals are required to evaluate the type of nerve fiber involvement and the site of damage.

Influence of Blood Lead Concentration on the Nerve Conduction Velocity in Patients with End-Stage Renal Disease

Diseases of the peripheral nervous system are the most prevalent in patients with end-stage renal disease (ESRD). Although increased blood levels of lead in ESRD have been reported, the role of lead remains to be elucidated. The purpose of this study was to determine the connection of blood lead concentration with peripheral nerve conduction velocity. One hundred ninety-eight healthy subjects (control group) and 68 patients with ESRD undergoing hemodialysis (ESRD group) were enrolled. Nerve conduction was measured within two hours after hemodialysis. Orthodromic sensory nerve action potentials and compound muscle action potentials were recorded on the median, ulnar, and radial nerves. Hemoglobin-corrected blood lead was significantly higher in ESRD patients than in controls (9.1±2.8 µg/dL vs. 5.9±2.3 µg/dL, p<0.001). 32.4% of 68 ESRD patients with diabetes mellitus were significantly related to poorer motor and sensory nerve conduction velocity (p<0.001). However, blood lead was not a significant predictor of the nerve conduction velocity (p>0.05). Our result suggested that even though the blood lead levels were high in ESRD, they were not associated with the decline of peripheral nerve function. Diabetes mellitus is a primary independent risk of neuropathy in ESRD patients.

Neurophysiological study of peripheral neuropathy after high-dose Paclitaxel: lack of neuroprotective effect of amifostine.

To determine if there is a beneficial effect of amifostine in preventing or reducing the neuropathy induced by high-dose paclitaxel. Breast cancer patients receiving high-dose infusional paclitaxel (725 mg/m(2)/24 h) in combination with doxorubicin (165 mg/m(2)/96 h) and cyclophosphamide (100 mg/kg/2 h; ACT) were studied on two autologous peripheral blood stem cell transplant protocols, one with and one without amifostine (740 mg/m(2) administered over 10 min before and 12 h after initiation of the paclitaxel infusion). Patients were evaluated before ACT and 20-40 days later with neurological examination, a composite peripheral neuropathy score, peroneal and sural nerve conduction studies, and quantitative sensory testing. There was no significant difference in paclitaxel maximum concentration, systemic clearance, or area under the curve determinations. Narcotic requirement as well as recovery of hematopoietic counts were also similar in subjects with or without amifostine. After ACT was administered, there was a decrease in peroneal nerve compound muscle action potential amplitude and sural nerve sensory action potential amplitude, as well as an increase in vibratory and cold detection thresholds. Clinical composite peripheral neuropathy scores were similar despite amifostine treatment; and logarithm to the base 2 ratios post/pre ACT showed no significant effect of amifostine on peroneal nerve compound muscle action potential, sural nerve sensory action potential, vibratory detection thresholds, or cold detection thresholds. All subjects had acroparesthesias and lost their ankle deep-tendon reflexes after administration of ACT. Single high-dose paclitaxel produces predictable clinical and neurophysiological changes so that patients receiving high-dose therapy are ideal subjects to test the effectiveness of neuroprotective agents. Amifostine was ineffective in preventing or reducing the neurotoxicity of high-dose paclitaxel.

Anti-neurofilament antibodies in neuropathy with monoclonal gammopathy of undetermined significance produce experimental motor nerve conduction block.

Elevated levels of serum antibodies to neurofilament proteins have been associated with a variety of neurological diseases, including autoimmune disorders such as neuropathy with monoclonal gammopathy of undetermined significance (MGUS). The pathological significance of anti-neurofilament antibodies in sera of affected patients, however, remains unclear. In this study, we report our findings of polyclonal antibodies in sera from 4 of 16 IgG MGUS neuropathy patients that react strongly on immunoblot with a high molecular weight neurofilament protein (NFH). The effect of anti-NFH polyclonal antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-NFH antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly attenuated proximal-evoked motor nerve compound muscle action potential (CMAP) amplitudes in a complement-dependent manner. In contrast, ankle-evoked CMAP amplitudes were unaffected by intraneural injection of sera containing anti-NFH antibody. Anti-NFH serum-injected nerves showed changes in both axon caliber (shrinkage) and myelin ultrastructure (vesiculation and ovoid formation), suggestive of intramyelinic edema. Preincubation of sera containing anti-NFH antibody with purified NFH protein abolished immunoreactivity to NFH protein and neutralized the serum-mediated toxicity. The data suggest that anti-NFH polyclonal antibodies occurring in sera of some patients with IgG MGUS neuropathy may elicit peripheral nerve conduction block independent of the patients' IgG paraprotein. Anti-neural polyclonal antibodies in sera of IgG MGUS neuropathy patients may have a greater pathological significance than previously anticipated.

X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiologic study.

To relate X-linked Charcot-Marie-Tooth disease (CMTX) phenotypes to gender and type of neuropathy by the study of a large series of CMTX patients with proven Cx32 point mutations. CMTX is an X-linked form of Charcot-Marie-Tooth disease, caused by mutations in the connexin 32 gene. Males are usually more severely affected and have slower nerve conduction velocities than females. Forty-eight patients from 10 families with Cx32 mutations were examined clinically and electrophysiologically. Mutations were characterized in index cases by automatic sequencing and detected in at-risk individuals by polymerase chain reaction (PCR)-restriction or single strand conformation polymorphism (SSCP) analysis. Two patients from different families had light and electron microscopy examination of a sural nerve biopsy. Males (n = 21) were more severely affected than females (n = 27), although six of the females were severely disabled. In the majority of males, the median motor nerve conduction velocity (MNCV) was between 30 and 40 m/s, whereas in females it ranged from 30 to normal values. Two children with mutation, a 6-year-old boy and a 7-year-old girl, were normal clinically and electrophysiologically. In most patients, the amplitude of motor nerve compound muscle action potentials (CMAP) was reduced in all nerves tested. MNCV was reduced as a function of the degree of axonal loss. A significant correlation was found between the decrease in CMAP amplitude and MNCV in the median, ulnar, and peroneal nerves. Sural nerve biopsies in one patient with a missense and one with a nonsense mutation both showed axonal neuropathy. Electrophysiologic and histologic findings support primary axonal neuropathy in CMTX with Cx32 mutations. Clinical and electrophysiologic data in males with different missense mutations in the of Cx32 gene differed significantly. Furthermore, males with a nonsense mutation (Arg22Stop) had earlier onset and a more severe phenotype than males with missense mutations.

Charcot-Marie-Tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases

A clinical and electrophysiological study was performed in 119 Type 1A Charcot-Marie-Tooth disease (CMT1A) patients with proven 17p11.2 duplication. Onset of the first functional manifestations was in the first decade in 50% of cases and before the age of 20 years in 70% of cases. The predominant clinical signs were muscle weakness and wasting in the lower limbs. None of the patients was normal on clinical examination and all presented at least pes cavus or ankle jerk areflexia. Motor nerve conduction velocity (MNCV) was uniformly reduced in all nerves, and was < or = 33 m/s in the median nerve for all patients. Sensory potentials were abnormal in all cases, even where there was no clinical sensory loss. Needle electromyography recruitment was reduced in distal muscles for all patients. MNCV slowing was fully consistent with the presence of duplication even in clinically asymptomatic individuals or in children, confirming the complete electrophysiological penetrance of 17p11.2 duplication and making median nerve MNCV a reliable tool for screening affected at-risk individuals. Functional disability was mild. Ninety-six percent of patients were autonomous; 25% were asymptomatic and diagnosed by systematic family investigation especially on the basis of median nerve MNCV reduction. Early age at onset and greatly reduced median nerve MNCV were predictive of a more severe disease course; the earlier the onset the more reduced the median nerve MNCV and the higher the functional disability tended to be after an equivalent disease duration. Cross-sectional analysis of neurological deficit, functional deficit and MNCV according to disease duration showed that, regardless of age at onset, CMT1A disease with 17p11.2 duplication is a clinically progressive disorder. Neurological deficit and functional disability increased, whereas median nerve MNCV and compound muscle action potential (CMAP) amplitude did not change with disease course. Intrafamilial phenotype variation between parents and children and between siblings was studied in large families. Functional disability and neurological deficit differed widely and the highest range of median nerve MNCV within a family reached 23 m/s. Clinical and electrophysiological data were compared with those of CMT1B patients with peripheral myelin P0 protein point mutation. CMT1A patients were found to be more severely affected with more prolonged distal motor latency and more reduced CMAP amplitude, whereas MNCV did not significantly differ, indicating that peripheral myelin P0 protein point mutation is not always associated with a severe phenotype. The same genetic defect (17p11.2 duplication) results in variable expression within the phenotype, even in siblings with variations in age at onset, clinical severity and MNCV slowing. This phenotypic variation could be due to additional genetic factors related to peripheral myelin protein 22 expression as well as to other endogenous or environmental factors.

Predominant involvement of motor fibres in patients with critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) is a recognized cause of muscle weakness and failure of weaning from a ventilator. In order to characterize the features of CIP, we have examined 28 consecutive surgical patients with severe sepsis using bedside electrophysiology. Of the 28 patients (median APACHE II score 31), 20 developed moderate to severe CIP, as shown by the presence of moderate to severe denervation activity on resting EMG. The median nerve compound muscle action potential (CMAP) amplitudes were reduced to 3.24 (SEM 0.48) mV, while sensory nerve action potential (SNAP) amplitudes obtained from the same nerve were normal (13.1 (1.9) microV). In approximately 50% of these patients, the reduction in CMAP exceeded 50% of the lower limit of normal. Similar results were obtained from stimulation of the ulnar nerve. We conclude that CIP is a major complication in patients with severe sepsis and prolonged artificial ventilation. It predominantly involves motor fibres and thus markedly interferes with weaning from the ventilator.

Fatigue-induced changes in group IV muscle afferent activity: differences between high- and low-frequency electrically induced fatigues

Recordings of group IV afferent activity of tibialis anterior muscle were performed in paralysed rabbits during runs of electrically induced fatigue produced by direct muscle stimulation at a high (100 Hz, high-frequency fatigue HFF) or a low rate (10 Hz, low-frequency fatigue LFF). In addition to analysis of afferent nerve action potentials, muscle force and compound muscle action potentials (M waves) elicited by direct muscle stimulation with single shocks were recorded. Changes in M wave configuration were used as an index of the altered propagation of membrane potentials and the associated efflux of potassium from muscle fibers. The data show that increased group IV afferent activity occurred during LFF as well as HFF trials and developed parallel with force failure. Enhanced afferent activity was significantly higher during LFF (maximal Δf impulses=249±35%) than HFF (147±45%). No correlation was obtained between the responses of group IV afferents to LFF or to pressure exerted on tibialis anterior muscle. On the other hand, decreased M wave amplitude was minimal with LFF while it was pronounced with HFF. Close correlations were found between fatigue-induced activation of group IV afferents and decreases in force or M wave amplitude, but their strength was significantly higher with LFF compared to HFF. Thus, electrically induced fatigue activates group IV muscle afferents with a prominent effect of low-frequency stimulation. The mechanism of muscle afferent stimulation does not seem to be due to the sole increase in extracellular potassium concentration, but also by the efflux of muscle metabolites, present during fatiguing contractions at low rate of stimulation.