Compound Motor Action Potential Amplitude Research Articles

Functional Recovery of Regenerating Motor Axons is Delayed in Mice Heterozygously Deficient for the Myelin Protein P0 Gene

Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated axons with only a borderline impairment in conduction and Rotor-Rod. Plantar muscle reinnervation occurred within 21days in all mice. Shortly after reinnervation the conduction of P0+/- regenerated axons was markedly slower than WT, however, this difference decayed with time. Nevertheless, after 1month, regenerated P0+/- axons had longer strength-duration time constant, larger threshold changes during hyperpolarizing electrotonus and longer relative refractory period. Their performance at Rotor-Rod remained also markedly impaired. In contrast, the number and diameter distribution of regenerating myelinated fibers became similar to regenerated WT. Our data suggest that in the presence of heterozygously P0 deficient Schwann cells, regenerating motor axons retain their ability to reinnervate their targets and remyelinate, though their functional recovery is delayed.

852 RESULTS OF USING A NEW TECHNOLOGY TO IMPROVE THE IDENTIFICATION AND PRESERVATION OF NERVE TISSUE DURING ROBOTIC ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY

You have accessJournal of UrologyTechnology & Instruments: Robotics: Benign & Malignant Disease (I)1 Apr 2013852 RESULTS OF USING A NEW TECHNOLOGY TO IMPROVE THE IDENTIFICATION AND PRESERVATION OF NERVE TISSUE DURING ROBOTIC ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY Ronald Kuhn and Ronald Kuhn Ronald KuhnRonald Kuhn North Little Rock, AR More articles by this author and Ronald KuhnRonald Kuhn North Little Rock, AR More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.420AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Efforts to improve continence after robotic assisted laparoscopic radical prostatectomy (RALRP) have focused on preserving periurethral and bladder neck tissue along with posterior reconstruction and anterior suspension. Many patients still have varying degrees of urinary incontinence. Literature has shown that nerves innervating the levator ani (LA) contribute to continence and anatomic landmarks are not accurate in determining their location. Inadvertent damage to these nerves may contribute to post RALRP incontinence. Intra-operative identification of nerve tissue using a stimulated EMG produces a waveform known as a compound motor action potential (CMAP) and is standard of care in brain, spine and facial surgery. The Author used a new technology that elicits and records CMAP's during RALRP and evaluated the ability to identify and preserve the nerves innervating the LA. METHODS 20 consecutive patients underwent RALRP using a posterior dissection without bias for stage, age, BMI, or commorbidites. After opening the endopelvic fascia and dividing the bladder neck, two 0.2mm diameter electrodes were passed through the anterior abdominal and placed into the LA bilaterally. A stimulatory signal was delivered through a daVinci bipolar instrument and CMAP's were recorded and used to identify the nerve to the LA during the procedure. 8 weeks post-op patients completed an EPIC score to measure urinary incontinence. RESULTS The nerves innervating the LA were identified in 100% of the cases as demonstrated by eliciting a CMAP that corresponded to known CMAP's from other motor nerves. The use of this technology added less than 2 minutes to procedure times. A correlation was seen between increasing CMAP amplitude and increasing proximity to the nerves. Additionally, EPIC scores at 8 weeks post RALRP revealed that improved post-operative continence was associated with a shorter intra-op CMAP latency. CONCLUSIONS Real-time intra operative monitoring of the otherwise invisible nerves that innervate the LA during RALRP is reproducible and efficient using this new technology. The information gained by using this technology correlates with proximity to the nerve and postoperative continence. Therefore, the use of this technology and the intra operative information it provides, accompanied by careful anatomic dissection demonstrates great promise in improving continence after RALRP. Further study is warranted in exploring how using this technology may improve postoperative continence following RALRP. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e350 Peer Review Report Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ronald Kuhn North Little Rock, AR More articles by this author Ronald Kuhn North Little Rock, AR More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Phrenic nerve conduction studies in patients with chronic obstructive pulmonary disease

The most common etiology of hypercapnic respiratory failure is chronic obstructive pulmonary disease (COPD). However, the differential diagnosis also includes neuromuscular disorders. We studied the specificity of reduced amplitude phrenic nerve compound motor action potential (CMAP) to diagnose neuromuscular disorders. A group of patients with advanced COPD were recruited prospectively and compared with controls. Phrenic nerve CMAPs were measured bilaterally using supraclavicular surface stimulation and bipolar recording (G1: 5 cm above the xiphoid; G2: 16 cm from G1). A group of 20 patients (15 men) and a group of 29 controls (15 men) were included. Phrenic nerve CMAPs of patients with COPD had significantly longer latency and higher amplitude. Our study demonstrates that patients with hypercapnic respiratory failure and reduced phrenic nerve CMAP amplitude most probably have a neuromuscular disorder affecting the diaphragm and not COPD or another lung disorder.

Electrophysiological, biochemical and ultrastructural effects of radiotherapy on normal rat sciatic nerve

Purpose: The aim of the present study was to evaluate the electrophysiological, biochemical and ultrastructural changes on the rat sciatic nerve after radiotherapy.Material and Methods: Thirty male Wistar albino rats were divided into three groups as: Control group (n = 10), Group I: 3 months after radiotherapy (n = 10), and Group II: 6 months after radiotherapy (n = 10). Groups I and II were irradiated with a 60Co gamma source. A dose of 20 Gy in 10 fractions was applied to Groups I and II. Compound motor action potentials (CMAP) were recorded in all groups. Superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) levels were measured in the sciatic nerve of rats using the biochemical methods. Ultrastructural changes were determined by electron microscopy.Results: In Groups I and II, the amplitude of CMAP was significantly lower and the latency was significantly higher than that of the control group. There were no significant differences between Groups I and II regarding the CMAP amplitude and latency. The MDA levels were significantly increased, whereas the SOD and CAT activities were significantly decreased in experimental groups when compared with the control group. However, there were no significant changes in these parameters between Groups I and II. Degeneration in myelinated nerve fibers was observed ultrastructurally only in the experimental groups. Significant changes were observed between the control group and experimental groups in terms of ultrastructural myelin grading score and axonal damage score. No significant differences were found between Groups I and II.Conclusions: These findings indicated that the dose of 20 Gy in 10 fractions radiotherapy caused neuropathic damages in normal rat sciatic nerve 3 and 6 months after irradiation.

DYSMETABOLIC NEUROPATHY IN CHILDREN WITH DIABETES TYPE I

Neuropathy is the most frequent symptomatic complication of diabetes. Diabetic polyneuropathy (DPN) is the most common variety of neuropathy, which represents chronic symmetrical sensorimotor polyneuropathy. (DPN) typically begins as a generalized asymptomatic dysfunction of peripheral nerve fibers, which may be revealed by electromyography. However, nerve conduction study (NCS) is a sensitive method for early detecting of peripheral neuropathy. We have performed NCS in 69 children with poorly compensated diabetes type I aged 7-18 y. Study protocol included testing of peripheral motor and sensory nerve conduction velocities (NCVs) and compound motor and sensory nerve action potential amplitudes. We revealed subclinical abnormalities, which were symmetric, suggestive of DPN and reflecting disorders of predominantly motor, rather than sensory nerves. In addition, nerve conduction abnormalities were correlated with high HbA1c level, patient age and disease (diabetes) duration. Poor metabolic control was the most important contributor to abnormal electrophysiological parameters.

Long-term follow-up of spinal and bulbar muscular atrophy in Taiwan

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy disease, is a rare neurodegenerative disorder presenting with insidious onset of weakness in bulbar and limb muscles. Information regarding long-term clinical and functional progression has been limited, especially for the Taiwanese population. The purpose of the study aimed to investigate early diagnosis and long-term prognosis of SBMA. We retrospectively analyzed 21 genetically confirmed SBMA patients who visited our hospital between 1993 and 2010, focusing on clinical symptoms, nerve conduction studies, and functional disability. We also analyzed the relationship between length of cytosine-adenine-guanine (CAG) repeats and age of disease onset. Weakness developed at a mean age of 39±7 years (mean±standard deviation). The length of CAG repeats and age at onset of weakness showed inverse (but nonsignificant) correlation. The most common symptoms at initial presentation were hand tremor (86%), limb weakness (86%), and perioral fasciculation (76%). Creatine kinase (CK) was elevated in 17 out of 18 patients. Initial nerve conduction studies showed statistical difference from normal controls, especially decreased amplitudes of compound motor action potential (CMAP) and sensory nerve action potential (SNAP). Functional disability showed very slow progression, with only three patients becoming wheelchair-dependent during follow-up at a median age of 72 years. Patients with SBMA may present with a myriad of symptoms, including limbs weakness, tremor, muscle atrophy, and perioral fasciculations. Elevated serum CK and decreased CMAP and SNAP amplitudes were supportive laboratory findings of SBMA. Disease progression was gradual, and most patients remained functionally independent many years after the onset of weakness.

Is peripheral neuron degeneration involved in multiple system atrophy? A clinical and electrophysiological study

Lower motor neuron lesions are not among the characteristic features of multiple system atrophy (MSA), although electromyography (EMG) and autopsy studies revealed peripheral neuron abnormalities in some cases of MSA.The aim of the study was to evaluate subclinical involvement of the peripheral neuron in MSA using EMG and electroneurography (ENG). Material48 patients with clinically probable MSA (mean age 60.6years; 67% males) were included in the study and divided into subgroups, with predominant cerebellar (MSA-C) and parkinsonian signs (MSA-P). MethodsENG in ulnar, peroneal and sural nerves and EMG of the first interosseus dorsal and tibial anterior muscles were performed. ResultsAbnormal ENG in one nerve was recorded in 20.8% of patients, and in two nerves in another 20.8% of patients. The most frequent and significant findings were decreased compound motor action potential amplitudes in the ulnar nerve in the overall MSA group as well as in the MSA-P type as compared to controls. Abnormalities suggesting reinnervation was observed in 43 of 96 examined muscles (44.7%). In individual cases, neurogenic features were recorded in one muscle in 31.2% of patients and in two muscles in 29.1% of patients. ConclusionsSubclinical axonopathy in MSA is not frequent and is more pronounced in MSA with predominant parkinsonian signs. In MSA, neurogenic EMG abnormalities in muscles are more frequent than peripheral nerve lesions and as evidenced by increased motor unit potential amplitudes, could be considered a sign of anterior horn cell involvement and a hallmark of the “continuum” of neurodegeneration in MSA.

A Prospective, Randomized Controlled Trial of Valproic Acid in Ambulant Adults with SMA: The VALIANT Trial (S25.002)

Objective: To report the results of a randomized, double-blind, placebo-controlled trial of valproic acid (VPA) in ambulatory adults with spinal muscular atrophy (SMA). Background Much evidence suggests that VPA, a histone deacetylase inhibitor, might benefit patients with SMA by modulating SMN2 splicing to increase production of full-length SMN transcript from SMN2 . Five open-label human trials of VPA in SMA showed a benefit in strength and function. Design/Methods: This was a prospective, randomized, double blind, 12 month study in SMA adults over 18 years old. After two baseline assessments, subjects were randomized to VPA or placebo and then crossed over to the other group at six months. Patients were evaluated at 3, 6, and 12 months. Primary outcome was the six-month strength change by maximum voluntary isometric contraction testing. Secondary outcomes included adverse events and changes in ulnar compound motor action potential amplitude and motor unit number estimation, strength by handheld dynamometry, 6 minute walk test, pulmonary function, functional rating scale (SMAFRS), and quality of life assessment. Results: Thirty-three subjects (20 M, 13 F; mean age 37.1) were enrolled; 16 patients were initially on VPA and 17 on placebo. Three patients did not complete the study; two due to adverse events not related to VPA and one withdrew. There were no significant adverse events. There was no significant change in the primary or secondary outcome after six months of treatment. Conclusions: VPA at doses used in this study did not improve strength or function in ambulatory SMA adults, and is compatible with earlier published negative CARNI-VAL studies in SMA children. The Project Cure-SMA group is currently analyzing data from open label studies in infants with Type 1 that should provide additional important information on VPA and its effect on biomarkers. Supported by: This study was entirely funded by FSMA through the Project Cure Investigators Network, and NIH CCTS funding at Ohio State. Disclosure: Dr. Elsheikh has nothing to disclose. Dr. Kolb has nothing to disclose. Dr. King has nothing to disclose. Dr. Chelnick has nothing to disclose. Dr. Scott has nothing to disclose. Dr. LaSalle has nothing to disclose. Dr. Krosschell has nothing to disclose. Dr. Reyna has nothing to disclose. Dr. Swoboda has received research support from BioMarin Pharmaceuticals and Orphamed, Dr. Kissel has nothing to disclose.

Failure of lower motor neuron radial outgrowth precedes retrograde degeneration in a feline model of spinal muscular atrophy

Feline spinal muscular atrophy (SMA) is a fully penetrant, autosomal recessive lower motor neuron disease in domestic cats that clinically resembles human SMA Type III. A whole genome linkage scan identified a ∼140-kb deletion that abrogates expression of LIX1, a novel SMA candidate gene of unknown function. To characterize the progression of feline SMA, we assessed pathological changes in muscle and spinal cord from 3 days of age to beyond onset of clinical signs. Electromyographic (EMG) analysis indicating denervation occurred between 10 and 12 weeks, with the first neurological signs occurring at the same time. Compound motor action potential (CMAP) amplitudes were significantly reduced in the soleus and extensor carpi radialis muscles at 8-11 weeks. Quadriceps femoris muscle fibers from affected cats appeared smaller at 10 weeks; by 12 weeks atrophic fibers were more prevalent than in age-matched controls. In affected cats, significant loss of L5 ventral root axons was observed at 12 weeks. By 21 weeks of age, affected cats had 40% fewer L5 motor axons than normal. There was no significant difference in total L5 soma number, even at 21 weeks; thus degeneration begins distal to the cell body and proceeds retrogradely. Morphometric analysis of L5 ventral roots and horns revealed that 4 weeks prior to axon loss, motor axons in affected cats failed to undergo radial enlargement, suggesting a role for the putative disease gene LIX1 in radial growth of axons.

Behavioral, electrophysiological, and histopathological characterization of a severe murine chronic demyelinating polyneuritis model

The objective of this study was to define the behavioral, electrophysiological, and morphological characteristics of spontaneous autoimmune peripheral polyneuropathy (SAPP) in female B7-2 deficient non-obese diabetic (NOD) mice. A cohort of 77 female B7-2 deficient and 31 wild-type control NOD mice were studied from 18 to 40 weeks of age. At pre-defined time points, the dorsal caudal tail and sciatic motor nerve conduction studies (MNCS) were performed. Sciatic nerves were harvested for morphological evaluation. SAPP mice showed slowly progressive severe weakness in hind and forelimbs without significant recovery after 30 weeks of age. MNCS showed progressive reduction in mean compound motor action potential amplitudes and conduction velocities, and increase in mean total waveform duration from 24 to 27 weeks of age, peaking between 32 and 35 weeks of age. Toluidine blue-stained, semi-thin plastic-embedded sections demonstrated focal demyelination associated with mononuclear cell infiltration early in the disease course, with progressively diffuse demyelination and axonal loss associated with more intense mononuclear infiltration at peak severity. Immunohistochemistry confirmed macrophage-predominant inflammation. This study verifies SAPP as a progressive, unremitting chronic inflammatory demyelinating polyneuropathy with axonal loss.

Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial spasm: a nerve conduction study

Botulinum toxin type-A is currently thought to be effective and safe for hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the neuromuscular junction induces depression of orbicularis oculi muscle compound motor action potential (CMAP). The aim of our study was to evaluate at what extent end-plate functional recovery is possible even in botulinum toxin treatments lasting up to 15 years. We examined 81 outpatients with primary HFS (mean treatment duration = 7.2 ± 4.2 years) who underwent neurophysiologic study, once clinical effect of the previous treatment had vanished. The mean CMAP amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and area of response 2 (R2) of treated orbicularis oculi muscle were measured in comparison to the controlateral side. Mean amplitude of the above mentioned parameters was slightly lower (about 20%; p < 0.001) in the treated side at the end of the follow-up period (4.7 ± 1.7 months). The CMAP amplitude reduction weakly correlated with the interval from last treatment, while other neurophysiologic parameters did not change due to treatment duration or total toxin amount. Our study demonstrates that botulinum toxin affects compound motor action potential and blink-reflex responses for at least 4-5 months in HFS patients. The residual block is slight and does not increase with repeated injections after several years of treatment. Our study, beside confirming the long-term efficacy of botulinum toxin treatment for HFS, provides neurophysiologic evidence that therapeutic effect may be obtained without hindering the regenerative potential of the nerve-muscle complex.

An unusual cause of thenar hypertrophy and carpal tunnel syndrome

Carpal tunnel syndrome (CTS) is characterized by classic symptoms of paresthesias in the median distribution and weakness that is sometimes accompanied by thenar atrophy. We describe an unusual case presenting with thenar hypertrophy. A 52 year-old, right-handed man presented with 10 years of intermittent paresthesias in the left median nerve distribution and difficulty snapping the fingers. Driving and typing worsened his symptoms. His examination revealed increased thenar bulk without focal masses (Fig. 1A). A Tinel sign was present. Sensory exam did not elicit significant abnormalities. Mild thenar weakness was noted. Electrodiagnostic studies revealed prolonged distal motor latency (7.9 ms), decreased compound motor action potential amplitude compared to the right (left 5.1 mV, right 9.2 mV) and absent left median sensory nerve action potential. Ulnar studies and F-wave latencies were normal. Needle EMG of abductor pollicis brevis showed increased insertional activity, 1+ fibrillation potentials, 2+ positive sharp waves, 3+ fasciculation potentials, increased motor unit potential (MUP) amplitude, reduced MUP recruitment and increased firing rate. Studies were consistent with left focal median neuropathy at the wrist. Figure 1 A) Thenar eminence in the symptomatic left hand is appreciably larger compared to the right. B) MR axial T1 weighted non-fat saturated image reveals linear strands of hyperintense fat (arrow) infiltrating the thenar muscles. C) MR axial fat saturated ... To further elucidate the etiology of thenar hypertrophy, MRI of the hand and wrist was performed to assess structural detail. MRI revealed linear strands of fat infiltrating thenar muscles (Fig. 1B), which was different from diffuse fibrofatty change associated with advanced muscle atrophy. There was globular enlargement of the median nerve with linear cable-like appearance of the nerve fascicles with surrounding fat. The enlargement measured 1.2 × 1.6 centimeters and was consistent with lipofibromatous hamartoma (LFH) (Fig. 1C). He underwent decompression of the nerve. Nerve enlargement and swelling was noted at the time surgery but fibrofatty change was not appreciated because of intact epineurium. Three months post-operatively, paresthesias improved. However, imaging revealed no change in the size of the median nerve mass (Fig. 1D). This case is instructive because thenar hypertrophy led to imaging, which revealed LFH. Thenar hypertrophy could result from either pseudohypertrophy or true hypertrophy related to spontaneous activity, increased work of remaining fibers, and fiber stretching 2, 3. Chronic denervation and spontaneous activity on needle EMG raises the possibility of true thenar hypertrophy. The focal, band-like pattern of fatty infiltration in thenar muscles suggests extension of LFH. If the fatty replacement were due to severe muscle atrophy, then significant clinical weakness and diffuse fibrofatty change should be present. To our knowledge, we describe the first case of thenar pseudohypertrophy likely due to extension of median nerve LFH. Besides LFH, localized hypertrophic neuropathy has been reported in hereditary sensory motor neuropathy type 1, Refsum syndrome and diabetic neuropathy 4. However, a “cable-like” appearance of the median nerve is pathognomonic for LFH and arguably nullifies the need for biopsy 5. Additionally, LFH have a predilection for the median nerve 6. The etiology of LFH is unknown. There are many proposed mechanisms including a post-traumatic reactive process, congenital and association with neurofibromatosis 7. Surgical treatment of the tumor is debated. Mass excision can lead to sensory deficits 6. In our case, an initial conservative decompression procedure resulted in improvement in sensory symptoms. LFH of the median nerve should be considered for patients who present with CTS and clinical thenar pseudohypertrophy.

Compound Motor Action Potential Interexaminer Variability in Photoguided Placement of the Recording Electrodes

Interpretation of neurographic data in follow-up studies of patients with neuromuscular disease is sometimes challenging because of the expected variability in repeated tests. In this study, we explored whether the interexaminer variability of the compound motor action potential (CMAP) amplitude is reduced if the examiner is guided by the previously taken photographs of the position of the recording electrodes. The CMAPs were recorded from 20 subjects by unilateral distal stimulation of the median, ulnar, peroneal, and tibial nerve by 4 different technicians. All the subjects were examined on 2 occasions (∼1 week apart). On the first occasion, the technicians recorded the CMAP values according to routine protocols. On the second occasion, the technicians had additional guidance from photographs displaying the recording electrode positions from the first study. The CMAP coefficient of variation (CoV) was calculated for each nerve examined by the four technicians. Differences in CoV between the two types of tests (i.e., with or without photographs) were evaluated. When the examiners were guided by the photographs during electrode application, the CMAP CoV for the tibial innervated abductor hallucis (AH) muscle was reduced (P = 0.02) from 18.5% to 13%. There were, however, no significant reductions in CoV for the abductor pollicis brevis (APB, P = 0.23, median nerve), abductor digiti minimi (P = 0.37, ulnar nerve), or extensor digitorum brevis (EDB, P = 0.15, peroneal nerve) muscles. Photographic documentation of the CMAP recording electrodes seems to have a limited overall effect on interexaminer variability in a subsequent study.

Neuropathy in type 1 diabetic renal transplanted patients

This study was undertaken to study the changes in neuropathy in type 1 diabetic patients with end-stage renal disease (ESRD) after renal transplantation. From April 2007 to June 2010, 30 renal transplanted patients with type 1 diabetes mellitus (RT) and 30 type 1 diabetic patients with ESRD were enrolled in this study. Electroneurodiagnostic tests of peroneal, sural, ulnar, and median nerves were performed. Nerve conduction velocity (NCV), compound motor action potentials (CMAPs), and sensory nerve action potentials (SNAPs) were analyzed at 6, 12, and 18 months after renal transplantation. The NCV improved in the RT group in 18 months of the follow-up period (P <0.01 versus baseline). This parameter worsened significantly in the control group throughout the study period (P = 0.03), but in the cross-sectional analysis between the groups, we could not find any remarkable differences (P = 0.07). Both SNAP and CMAP amplitudes improved in the RT (SNAP Sural = 0.04, SNAP Median = 0.01 and CAMP Peroneal = 0.03, CAMP Ulnar = 0.02) but worsened in the control group (SNAP Sural < 0.001, SAP Median < 0.01 and CAMP Peroneal < 0.01, CAMP Ulnar < 0.01). Comparison of both groups did not show any significant statistical changes. Electroneurodiagnostic values improved after renal transplantation in type 1 diabetic patients with ESRD, but cross-sectional analysis did not reveal statistically significant differences between the studied groups.

Evaluation of in Vivo Rotator Cuff Muscle Function After Acute and Chronic Detachment of the Supraspinatus Tendon

Surgical repair of large chronic rotator cuff tears can be technically demanding because it requires manipulation of a muscle-tendon unit that is scarred, retracted, and stiffer than normal, all of which contribute to increased tension at the repair site. The purpose of the present study was to characterize the in vivo rotator cuff muscle-tendon unit function after acute and chronic injury at surgically relevant preload tensions. Sixty-two Sprague-Dawley rats were divided into a healthy, uninjured (control) group (n = 22), an acute injury group (n = 20), and a chronic injury group (n = 20) and underwent in vivo muscle force testing and electromyographic testing of the supraspinatus muscle-tendon unit at various preload tensions. Preload tension affected the maximum supraspinatus muscle contractile force in all groups (p < 0.05). At the peak tension required to repair an acute tear, there was a 28% to 30% reduction in maximum tetanic contraction amplitude in all groups (p < 0.05). At the peak tension required to repair a chronic tear, there was a 40% to 53% reduction in maximal tetanic contraction amplitude in all groups (p < 0.05). The uninjured (control) group showed increased muscle endurance (p < 0.05) in comparison with the acute injury and chronic injury groups at all preload tensions. The chronic injury group showed reduced compound motor action potential amplitude (p < 0.05). Both the acute and chronic injury groups demonstrated functional impairment related to increasing preload tensions. Higher repair tensions, associated with the chronic injury setting, resulted in greater functional impairment. The present study also demonstrates an association between increased time from rotator cuff tendon injury and impaired in vivo rotator cuff muscle electromyographic findings.

Isolated bulbar phenotype of amyotrophic lateral sclerosis

Typical bulbar-onset ALS generally portends a poor prognosis. To determine whether a relatively isolated bulbar phenotype (IBP) may have a better prognosis, patients with bulbar onset presentations were prospectively assessed, with IBP defined by an absence of limb progression over an initial six-month period. Clinical features and neurophysiological characteristics were compared. From a cohort of 300 consecutive referrals, 32 patients with bulbar onset disease (21 females, 11 males) were identified and compared to 23 age-matched control subjects. In total, patients were followed for 54 months. Twelve patients were identified with IBP (nine female, three male) and 20 had more typical bulbar ALS (12 female, eight male). Clinically, IBP was characterized by greater female predominance and upper motor neuron bulbar involvement. Compound motor action potential amplitudes were preserved in IBP compared to bulbar ALS (IBP, 7.1 mV; bulbar ALS, 4.2 mV, p <0.05), as was the neurophysiological index (IBP, 1.2; bulbar ALS 0.5, p <0.05). Furthermore, short interval intracortical inhibition was normal in IBP and reduced in typical bulbar ALS. In conclusion, patients with IBP were typically female with prominent upper motor neuron bulbar features and had normal cortical excitability. Biomarkers of cortical excitability may prove useful for further classifying ALS.

Severe phenotypes of paralysis periodica paramyotonia are associated with the Met1592Val mutation in the voltage-gated sodium channel gene ( SCN4A) in a Chinese family

Paralysis periodica paramyotonia (PPP) is caused by mutation of the adult skeletal muscle sodium channel gene’s alpha (α)-subunit (SCN4A). Here, we report four generations of a Chinese family affected by a remarkably severe form of PPP with progressive myopathy. Routine electromyograms (EMG) showed myotonic discharge and after a long exercise test, compound motor action potential amplitudes were markedly decreased by 40–55%. Muscle biopsy revealed obvious vacuolar changes. Moreover, genetic analysis revealed the Met1592Val mutation in the α-subunit, SCN4A. The patients showed a striking clinical and electrophysiological improvement during treatment with acetazolamide. Thus, our findings showed that mutation of Met1592Val in the SCN4A gene is associated with aggressive development of PPP characterized by severe vacuolar myopathy.

West Nile virus neuroinvasive disease presenting with acute flaccid paralysis and bilateral sensorineural hearing loss

West Nile virus (WNV), is an emerging virus [1]. Most human infections are subclinical or manifest as a mild febrile illness, while fewer than 1% develop a neuroinvasive disease (WNND), including meningitis, encephalitis, and/or an acute flaccid paralysis (AFP) [2–4]. We describe a case of sensorineural hearing loss (SNHL) secondary to WNV infection. A 55 year-old previously healthy and normoacousic man, was admitted (in September 2010) for bilateral hearing loss and leg weakness. He complained, about 2 weeks before, of malaise, fever, generalized fatigue, and diffuse myalgias, initially attributed to a flu-like syndrome. After a few days he noted a mild weakness in both of his legs evolving over a week into a flaccid paraparesis. At the same time, he also developed a sudden bilateral hearing loss. He was afebrile, with stable vital signs. Routine and immunological laboratory data were within the normal range. Neurologic examination was remarkable for a flaccid areflexic paraparesis, weakness being more pronounced in the right leg and proximally (3/5 strength in the right leg, 4/5 strength in the left leg), with flexor plantar responses. No cranial nerve involvement, vestibular, cerebellar, brainstem or meningeal signs were noted. MRI of the brain and whole spine was normal without meningeal, parenchymal or ventral nerve root enhancement. Audiological tests, including the Weber and Rinne tuning fork tests, pure tone and speech audiometry, tympanic admittance, auditory evoked potentials (ABRs) and a screening test for acoustic emissions (OAEs), demonstrated a bilateral, down-sloping SNHL—mild on the left side, severe on the right—with normal acoustic admittance, and impaired OAEs, which were absent in the right ear. Weber test was lateralized to the left side, and the Rinne test was not significant. ABR with click at maximum output level (125 dB SPL) was not evocable by stimulating the right ear and normal for the left ear after latencies correction for the hearing threshold elevation. On the whole, the data were compatible with a bilateral asymmetric cochlear damage. Electrodiagnostic studies showed normal sensory and motor nerve conductions, and moderate decrease of compound motor action potential amplitudes. Late responses were normal. Concentric needle electromyography showed active denervation with a neurogenic recruitment pattern in all four limbs, with a clear predominance in legs. The findings fulfilled the diagnostic criteria for WNV AFP [4, 5]. Neurophysiological examination of cranial nerves and brainstem reflexes studies gave normal results. Since the symptoms began during a work-related stay in Romania where a WNV infection outbreak was occurring [6, 7], we considered the above infection in the differential diagnosis. Serum IgM and low-avidity IgG WNV-specific antibodies were detected (titre:1:1,600; 1:51,200, respectively). The presence of IgMand low avidity IgG WNV-specific I. Casetta (&) E. Cesnik Section of Neurology, Department of Medical and Neurological Sciences of Communication and Behaviour, University of Ferrara, Corso della Giovecca 203, 44121 Ferrara, Italy e-mail: cti@unife.it

Diaphragmatic electromyography during cryoballoon ablation: a novel concept in the prevention of phrenic nerve palsy

Hemidiaphragmatic paralysis is the most frequent complication associated with cryoballoon ablation for atrial fibrillation. To date, no preventive strategy has proved effective. We sought to assess the feasibility of diaphragmatic electromyography during cryoballoon ablation, explore the relationship between altered signals and phrenic nerve palsy, and define characteristic changes that herald hemidiaphragmatic paralysis. Cryoballoon ablation was performed in the right superior pulmonary vein or superior vena cava in 16 mongrel dogs weighing 37.7 ± 2.4 kg, at sites determined by phrenic nerve capture. During ablation, the phrenic nerve was paced at 60 bpm from the superior vena cava while recording diaphragmatic compound motor action potentials (CMAPs) by esophageal decapolar catheters. Diaphragmatic excursion was monitored by fluoroscopy and abdominal palpation. Before ablation, the CMAP amplitude was 592 (interquartile range 504, 566) μV, initial latency 21.5 ± 4.2 ms, peak latency 64.7 ± 21.1 ms, and duration 101.7 ± 13.3 ms. Hemidiaphragmatic paralysis was obtained in all dogs 62 ± 34 seconds into the cryoapplication. The CMAP amplitude decreased exponentially, with no patterned changes in latencies and duration. Discriminatory analyses by receiver-operating curve characteristics identified a 30% reduction in CMAP amplitude as the most predictive cutoff value for hemidiaphragmatic paralysis (c-statistic 0.965; P<.0001). This criterion presaged diaphragmatic paralysis, as detected by abdominal palpation, by 31 ± 23 seconds. Diaphragmatic electromyographic signals could be reliably recorded during cryoballoon ablation. An exponential decrease in CMAP amplitude precedes diaphragmatic paralysis, with a 30% reduction yielding the best discriminatory potential. A promising safety margin was detected, which merits prospective validation.

P7-15 The effect of chronic intermittent hypoxia in ALS mice model

Patients were diagnosed with IBP if there was no limb progression over six months. Patient demographics, clinical features and neurophysiological biomarkers, including cortical excitability using paired pulse, threshold tracking, transcranial magnetic stimulation, were recorded. IBP patients were compared to more typical bulbar-ALS patients. Results: From a cohort of 250 consecutive referrals, 32 patients with bulbar onset disease (11 males, 21 females, age 64.1±9.0 years) were identified. Twelve patients had IBP (3 male, 9 female, age 61.1±8.2 years) and twenty had bulbar-ALS (8 males, 12 females, age 65.9±9.3 years). IBP was characterized by female predominance and predominantly upper motor neuron bulbar features. In contrast, patients with bulbar-ALS had more prominent lower motor neuron bulbar features. The compound motor action potential amplitude was preserved in patients with IBP compared to patients with bulbar-ALS (7.1mV compared to 4.2mV, P< 0.05) as was the neurophysiological index (1.22 compared to 0.45, P< 0.05). Furthermore, cortical excitability was normal in patients with IBP and abnormal in patients with bulbar-ALS. Conclusions: Patients with IBP were predominantly female with prominent upper motor neuron bulbar features. Neurophysiologically, IBP patients had no evidence of peripheral lower motor neuron dysfunction and had normal cortical excitability. Neurophysiological biomarkers such as SICI may prove useful for patient diagnosis, selection and monitoring in clinical trials.