Lower Motor Neuron Injury Research Articles

Novel Technologies to Address the Lower Motor Neuron Injury and Augment Reconstruction in Spinal Cord Injury.

Lower motor neuron (LMN) damage results in denervation of the associated muscle targets and is a significant yet under-appreciated component of spinal cord injury (SCI). Denervated muscle undergoes a progressive degeneration and fibro-fatty infiltration that eventually renders the muscle non-viable unless reinnervated within a limited time window. The distal nerve deprived of axons also undergoes degeneration and fibrosis making it less receptive to axons. In this review, we describe the LMN injury associated with SCI and its clinical consequences. The process of degeneration of the muscle and nerve is broken down into the primary components of the neuromuscular circuit and reviewed, including the nerve and Schwann cells, the neuromuscular junction, and the muscle. Finally, we discuss three promising strategies to reverse denervation atrophy. These include providing surrogate axons from local sources; introducing stem cell-derived spinal motor neurons into the nerve to provide the missing axons; and finally, instituting a training program of high-energy electrical stimulation to directly rehabilitate these muscles. Successful interventions for denervation atrophy would significantly expand reconstructive options for cervical SCI and could be transformative for the predominantly LMN injuries of the conus medullaris and cauda equina.

Nerve Transfer After Cervical Spinal Cord Injury: Who Has a “Time Sensitive” Injury Based on Electrodiagnostic Findings?

ObjectiveTo use the ulnar compound muscle action potential (CMAP) to abductor digiti minimi (ADM) to identify the proportion of individuals with cervical spinal cord injury (SCI) who have lower motor neuron (LMN) abnormalities involving the C8-T1 spinal nerve roots, within 3-6 months, and thus may influence the response to nerve transfer surgery. DesignRetrospective analysis of prospectively collected data. Data were analyzed from European Multicenter Study About SCI database. SettingMulti-center, academic hospitals. ParticipantsWe included 79 subjects (age=41.4±17.7, range:16-75; 59 men; N=79), who were classified as cervical level injuries 2 weeks after injury and who had manual muscle strength examinations that would warrant consideration for nerve transfer (C5≥4, C8<3). InterventionsNone. Main Outcome MeasuresThe ulnar nerve CMAP amplitude to ADM was used as a proxy measure for C8-T1 spinal segment health. CMAP amplitude was stratified into very abnormal (<1.0 mV), sub-normal (1.0-5.9 mV), and normal (>6.0 mV). Analysis took place at 3 (n=148 limbs) and 6 months (n=145 limbs). ResultsAt 3- and 6-month post-injury, 33.1% and 28.3% of limbs had very abnormal CMAP amplitudes, respectively, while in 54.1% and 51.7%, CMAPs were sub-normal. Median change in amplitude from 3 to 6 months was 0.0 mV for very abnormal and 1.0 mV for subnormal groups. A 3-month ulnar CMAP <1 mV had a positive predictive value of 0.73 (95% CI 0.69-0.76) and 0.78 (95% CI 0.75-0.80) for C8 and T1 muscle strength of 0 vs 1 or 2. ConclusionA high proportion of individuals have ulnar CMAPs below the lower limit of normal 3- and 6-month post cervical SCI and may also have intercurrent LMN injury. Failure to identify individuals with LMN denervation could result in a lost opportunity to improve hand function through timely nerve transfer surgeries.

Could tractography help in the diagnosis of motor neuron diseases\amyotrophic lateral sclerosis? A case report

Introduction: Amyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons, progressively degenerating them. This degeneration process has a complex and multifactorial etiology, culminating in the motor disability of the carriers. Case Report: The case report discusses a clinical suspicion of motor neuron disease (ALS) in the patient NVF, male, 72 years old, with a report of falls and paresis in the left distal crural third for two years. His condition evolved with the four limbs and trunk involvement, but it does not show bulbar involvement. In addition, atrophy, fasciculations, and paresis have been identified from lower motor neuron injury in all four limbs. Regarding the pyramidal pathway, only lively but symmetrical reflexes. Conclusion: In the last two decades, there have been significant advances in non-invasive imaging techniques, which allow the evaluation of brain structure, as is the case with tractography. Although this technique does not diagnose ALS, it can help early detection.

Nerve Transfer To Restore Pinch And Grasp For Patients With Tetraplegia

<h3>Research Objectives</h3> To evaluate the efficacy of supinator to anterior interosseous (AIN) transfers for pinch and grasp reconstruction in patients with tetraplegia. Popularization of nerve transfers has increased reconstructive options available to patients with tetraplegia. Outcomes of supinator to posterior interosseous nerve transfers in this patient population have been documented, as well as a variety of other options for restoration of AIN function. However, outcomes of supinator to AIN transfers reconstruction have not been published. <h3>Design</h3> A retrospective review of all patients who received supinator to AIN transfers at our institution with at least one year follow-up was performed. <h3>Setting</h3> This study was performed at a tertiary referral center. <h3>Participants</h3> Ten patients were identified, and four were excluded for inadequate follow-up time. Data for the remaining six patients (seven limbs) was reviewed. <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Charts were reviewed for pre- and post-operative physical exam findings, intraoperative response to nerve stimulation, and complications. The physical exams included Medical Research Council (MRC) manual muscle testing of relevant muscle groups. An MRC grade of 3 or higher was considered a successful outcome. <h3>Results</h3> Of the six patients (seven limbs), six had successful outcomes with MRC grade 3-4 flexor digitorum profundus and/or flexor pollicis longus function. One patient had weaker return of pinch compared to grasp. One patient reported decreased sensation to light touch at the tip of the thumb after surgery. No other donor site deficits or complications were noted. <h3>Conclusions</h3> Six of seven limbs in this cohort regained AIN function. However, one patient did not have any recovery 12 months after surgery. That patient's AIN was within the zone of injury (i.e. lower motor neuron injury), corroborated by the lack of response to stimulation intraoperatively; however, time to surgery was within an appropriate window. These findings suggest that supinator to AIN transfer is a viable option for restoration of pinch and grasp function in patients with spinal cord injury. <h3>Author(s) Disclosures</h3> None.

Urological Management of the Spinal Cord-Injured Patient: Suggestions for Improving Intermittent Catheterization and Reflex Voiding

Spinal cord injury can either be complete with no neural communication across the injury level or incomplete with limited communication. Similarly, motor neuron injuries above the sacral spinal cord are classified as upper motor neuron injuries, while those inside the sacral cord are classified as lower motor neuron injuries. Specifically, we provide recommendations regarding the urological management of complete upper motor neuron spinal cord injuries; however, we also make limited comments related to other injuries. The individual with a complete upper motor neuron injury may encounter five lower urinary tract conditions: first, neurogenic detrusor overactivity causing urinary incontinence; second, neurogenic detrusor underactivity resulting in high post-void residual volumes; third, detrusor sphincter dyssynergia, which is contraction of striated and/or smooth muscle urethral sphincters during detrusor contractions; fourth, urinary tract infection; and fifth, autonomic dysreflexia during detrusor contractions, which produces high blood pressure as well as smooth muscle detrusor sphincter dyssynergia. Intermittent catheterization is the recommended urinary management method because it addresses the five lower urinary tract conditions and has good long-term outcomes. This method uses periodic catheterizations to drain the bladder, but also needs bladder inhibitory interventions to prevent urinary incontinence between catheterizations. Primary limitations associated with this management method include difficulties with the multiple catheterizations, side effects of bladder inhibitory medications, and urinary tract infections. Three suggestions to address these concerns include the use of low-friction catheters, wireless, genital-nerve neuromodulation for bladder inhibition, and consideration of urine egress into the urethra as a risk factor for UTI as well as egress treatment. The second management method is reflex voiding. This program uses external condoms for urine collection in males and diapers for females. Suprapubic tapping is used to promote bladder contractions. This method is not recommended because it has high rates of medical complications. In particular, it is associated with high detrusor pressure, which can lead to ureteral reflux and kidney pathology. Botulinum toxin injection into the urethral striated sphincter can manage detrusor sphincter dyssynergia, reduce voiding pressures, and risks to the kidney. We suggest a modified method for botulinum toxin injections as well as five additional methods to improve reflex voiding outcomes. Finally, the use of intermittent catheterization and reflex voiding for individuals with incomplete spinal injuries, lower motor neuron injuries and multiple scleroses are briefly discussed.

Central Nervous System Tumors in Children.

Central Nervous System Tumors in Children.

Can the electrically stimulated manual muscle test differentiate upper from lower motor neuron injury in persons with acute SCI?

ABSTRACT Objective To determine if the motor response on the stimulated manual muscle test (SMMT) in muscles with a grade 0 motor score on the manual muscle test (MMT) can differentiate lower motor neuron (LMN) from upper motor neuron (UMN) injury based on the presence of spontaneous activity (SA) with needle EMG. Design Prospective Study. Participants/Methods Twenty-one subjects with acute traumatic cervical SCI. Methods An upper extremity International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) evaluation was completed on all subjects. A needle EMG and an electrically stimulated manual muscle test (SMMT) were completed on all key upper extremity muscles with a MMT motor score of zero. Results The MMT, SMMT and Needle EMG were done on 77 muscles. The SMMT motor score was 0 on 10 muscles and >1 on 67 muscles. The needle EMG identified spontaneous activity (SA) in 55/77 muscles. Seventy percent (7/10) of the muscles with MMT and SMMT motor score of zero demonstrated SA on EMG. Seventy-two percent (48/67) of the muscles with MMT motor score = 0 and SMMT motor score ≥1 demonstrated SA on EMG. Conclusion In our study, 70% of the muscles with a SMMT motor response of zero and 72% of the muscles with a SMMT motor response greater than or equal to one demonstrated SA on EMG. The use of the SMMT as a clinical measure to differentiate LMN from UMN integrity may be limited when applied.

Using electrodiagnostics to define injury patterns amenable to nerve transfer surgery in tetraplegia: an illustrative case report

Spinal cord injury is a devastating condition affecting a person's independence and quality of life. Nerve transfers are increasingly used to restore critical upper extremity function. Electrodiagnostic studies guide operative planning but the implications for clinical outcomes is not well defined. This case study delineates how clinical examination and electrodiagnostics can define the varying patterns of neuronal injury to guide timing and strategy for optimal outcomes in nerve transfers. We discuss a 20-year-old man with a C6-7 spinal cord injury (SCI). We illustrate how history, physical examination, and electrodiagnostic studies predicted patterns of upper and lower motor neuron injury, confirmed intraoperatively via direct nerve stimulation. We undertook brachialis nerve transfer to the median fascicles supplying flexor digitorum superficialis and anterior interosseous nerve (to restore digit flexion), and supinator nerve transfer to posterior interosseous nerve (to restore digit extension). Preoperative electrodiagnostics of the right upper extremity demonstrated a pure upper motor neuron injury to median innervated muscles, and mixed upper and lower motor neuron injury to radial innervated muscles. These findings were confirmed via intraoperative direct neuromuscular stimulation. The preoperative studies provided important information regarding the anatomic basis and time sensitivity of the proposed nerve transfers. At 2 years post operatively the reconstructed digit flexion and extension resulted in improved hand function and independence. Upper and lower motor neuron injuries can coexist in individuals with SCI. This example provides proof-of-concept that preoperative electrodiagnostic studies predict LMN injury, and surgery can achieve positive outcomes if completed soon after SCI.

The sacral exam-what is needed to best care for our patients?

Sacral reflexes are important to allow the SCI practitioner to gain information about the state of the sacral spinal cord segments. The presence of the bulbocavernosus and/or the anal wink reflex indicate an intact spinal reflex arc and reflex conal autonomic function (as part of the upper motor neuron syndrome); their absence defines a lower motor neuron syndrome. The assessment of sacral reflexes helps predict the type of bladder, bowel and sexual functions and the related therapeutic interventions. We suggest adding the sacral component of the International Standards for the Assessment of Autonomic Function after SCI (ISAFSCI) to the International Standards for the Neurologic Classification of Spinal Cord Injury (ISNCSCI) examination so there can be a detailed description of these important functions. As an alternative, the performance of sacral reflexes should be routinely required as part of the neurologic examination after SCI. Whether the sacral motor neuron system is classified as upper or lower motor neuron injury is also quite useful and as such should be present in the ISCNSCI.

Imaging Predictors for Significant Lower Motor Neuron Injury in Traumatic Cervical Spinal Cord Injury

Abstract INTRODUCTION Traumatic spinal cord injury (SCI) results in loss of both white and grey matter in the spinal cord and adjacent to the site of impact. Loss of gray matter within the injured area leads to lower motor neuron (LMN) injury, due to direct destruction of the alpha motor neurons and associated axonal loss within the adjacent peripheral nerves. The extent of gray matter loss can be discrete, or it can extend multiple levels from the site of impact. Since these changes can become irreversible within a year after injury, early identification of significant LMN injury in patients with traumatic SCI allows them to benefit from available reconstructive surgeries before the window for reinnervation closes. METHODS In this single-center retrospective study the charts of 21 previously healthy individuals aged 15 to 50 yr who suffered traumatic SCI with AIS C4-C8 A-D classification and hand functional impairment, without concomitant peripheral nerve or brachial plexus injury, were reviewed. Magnetic resonance (MR) images of cervical spine, obtained within 6 wk from the injury, were reviewed to identify structural imaging characteristics that correspond to gray matter destruction. Severity of LMN injury predicted by imaging findings was compared with the results of compound muscle action potential (CMAP), motor unit potential (MUP), intraoperative stimulation, and Medical Research Council (MRC) grading of the major muscle groups of the upper extremity. RESULTS The extent of LMN injury as determined by electrophysiological evaluations and intraoperative stimulation could be predicted with some degree of specificity by the preoperative imaging findings. CONCLUSION In this study, simple imaging biomarkers indicate the extent of LMN injury in patients with traumatic SCI. By noting the extent of soft tissue damage within the injured metamere of the spinal cord, the degree of lower motor neuron injury can be anticipated and thus appropriate triage performed.

Clarifying the Diagnosis of Acute Flaccid Myelitis

Acute flaccid myelitis is a serious condition primarily affecting children. It attacks spinal cord gray matter, resulting in lower motor neuron injury and flaccid weakness in the extremities. Although the specific cause of most cases is unknown, viruses, toxins, and genetic disorders have been implicated. Preventing the spread of viral infections is crucial to preventing the spread of this potentially disabling disease. If acute flaccid myelitis is suspected, nurse practitioners must act quickly with the assistance of local or state health departments in collaboration with the Centers for Disease Control and Prevention to implement evidence-based interventions for the patient.

The Effect of Electrically Induced Cycling and Nutritional Counseling on Cardiometabolic Health in Upper and Lower Motor Neuron Chronic Spinal Cord Injury: Dual Case Report.

Introduction:Various therapies have been utilized to improve cardiometabolic health after spinal cord injury (SCI), including Functional Electrical Stimulation (FES) cycling. Typically, FES is used in SCI cases resulting from Upper Motor Neuron Injury (UMN-SCI). However, it has been reported that FES may improve muscle torque and functional mobility in individuals with Lower Motor Neuron Injuries (LMN-SCI) but potential effects on cardiometabolic health have not been studied before. Thus, this study examined the cardiometabolic health response to FES cycling combined with nutritional counseling in two individuals with chronic SCI; one person with LMN-SCI and one with UMN-SCI.Case Presentation:Body composition, vascular stiffness, and glucose deposition were assessed before and after participation in the FES cycling and nutritional counseling program. Despite the decrease in body mass in the case of LMN-SCI but not UMN-SCI, the fat mass-to-lean mass ratio in the lower limbs and trunk increased +4% and +8% respectively, in the former and decreased −10% and −8% respectively in the latter. Both subjects decreased markers of central vascular stiffness (AIx@75, reflection magnitude) as well as blood glucose and HbA1c levels, however, the changes were greater in the case of UMN-SCI.Discussion:This dual case study provides only a partial support for the use of FES cycling alone or in combination with nutritional counseling for improving cardio metabolic health in LMN-SCI, however modest decreases in glucose and vascular stiffness warrant further investigations.

A Comparison of Robotic Walking Therapy and Conventional Walking Therapy in Individuals With Upper Versus Lower Motor Neuron Lesions: A Randomized Controlled Trial

ObjectiveTo compare a walking reeducation program with robotic locomotor training plus overground therapy (LKOGT) to conventional overground training (OGT) in individuals with incomplete upper motor neuron (UMN) or lower motor neuron (LMN) injuries having either traumatic or nontraumatic nonprogressive etiology. DesignRandomized open controlled trial with blind evaluation by an independent observer. SettingAn inpatient spinal cord injury rehabilitation center. ParticipantsA total of 88 adults within 6 months of spinal cord injury onset (group A, 44 with UMN injury, and group B, 44 with LMN injury) were graded on the American Spinal Injury Association Impairment Scale as C or D. Each of these groups was then randomly allocated to conditions 1 or 2. InterventionsCondition 1: Subgroups A1 and B1 were treated with LKOGT for 60 minutes. Condition 2: Subgroups A2 and B2 received 60 minutes of conventional OGT 5 days per week for 8 weeks. Subjects with UMN and LMN were randomized into 2 training groups. Main Outcome MeasuresTen-meter walk test and 6-minute walk test (6MWT). Walking Index for Spinal Cord Injury II, lower extremity motor score (LEMS), and the FIM-Locomotor were secondary outcome measures. ResultsBy using the LKOGT program compared with OGT, we found significant differences in the 6MWT for groups A1 and B1. LKOGT also provided higher scores than did OGT in secondary outcomes such as the LEMS and the FIM-Locomotor. ConclusionsRobotic-assisted step training yielded better results in the 6MWT and the LEMS in patients with UMN and LMN.

Occurrence of eye movement disorders in motor neuron disease

The diagnosis of amyotrophic lateral sclerosis (ALS) relies on symptoms and signs related to upper and lower motor neuron injury. Preservation of normal ocular motor movements is an important criterion for making this diagnosis as oculomotility pathways are classically spared in ALS. However, some authors report eye disturbances resulting from nuclear and supranuclear ophthalmoplegia in autopsy-proven ALS. Here, we report a case in which eye movement disorders were an early sign associated with a bulbar-onset ALS. The association of progressive ophthalmoplegia, dysexecutive syndrome and automatico-voluntary dissociation of eyelid occlusion suggested a 'progressive supranuclear palsy variant' of ALS caused by a disturbance in the descending frontal projections, even though morphological imaging was normal. Motor neuron disease with eye movement disorders must not be considered as a distinct clinical entity and must not exclude a diagnosis of ALS.

Muscle, tendons, and bone: structural changes during denervation and FES treatment

<title/>Objectives: This paper describes a novel approach to determine structural changes in bone, muscle, and tendons using medical imaging, finite element models, and processing techniques to evaluate and quantify: (1) progression of atrophy in permanently lower motor neuron (LMN) denervated human muscles, and tendons; (2) their recovery as induced by functional electrical stimulation (FES); and (3) changes in bone mineral density and bone strength as effect of FES treatment.Methods: Briefly, we used three-dimensional reconstruction of muscle belly, tendons, and bone images to study the structural changes occurring in these tissues in paralysed subjects after complete lumbar-ischiadic spinal cord injury (SCI). These subjects were recruited through the European project RISE, an endeavour designed to establish a novel clinical rehabilitation method for patients who have permanent and non-recoverable muscle LMN denervation in the lower extremities. This paper describes the use of segmentation techniques to study muscles, tendons, and bone in several states: healthy, LMN denervated-degenerated but not stimulated, and LMN denervated-stimulated. Here, we have used medical images to develop three-dimensional models and advanced imaging, including computational tools to display tissue density. Different tissues are visualized associating proper Hounsfield intervals defined experimentally to fat, connective tissue, and muscle. Finite element techniques are used to calculate Young’s modulus on the patella bone and to analyse correlation between muscle contraction and bone strength changes.Results: These analyses show restoration of muscular structures, tendons, and bone after FES as well as decline of the same tissues when treatment is not performed. This study suggests also a correlation between muscle growth due to FES treatment and increase in density and strength in patella bone.Conclusion: Segmentation techniques and finite element analysis allow the study of the structural changes of human skeletal muscle, tendons, and bone in SCI patient with LMN injury and to monitor effects and changes in tissue composition due to FES treatment. This work demonstrates improved bone strength in the patella through the FES treatment applied on the quadriceps femur.

Sildenafil efficacy in erectile dysfunction secondary to spinal cord injury depends on the level of cord injuries

To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile dysfunction (ED) secondary to upper motor neuron (UMN) and lower motor neuron (LMN) spinal cord injury (SCI). After taking consents 105 patients suffering from ED were enrolled in this prospective study. Seventy-two patients had signs and symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed (UMN and LMN) spinal cord injuries. The patients took 50-100 mg sildenafil or placebo tablet at least 45 min before sexual intercourse. Based on a IIEF questionnaire, success in achieving erection adequate for sexual intercourse was compared between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries. In patients with UMN disease, sildenafil was effective in 82% of patients and its efficacy was statistically higher than placebo (82 vs. 25%, p < 0.05). Twenty-eight per cent of patients with non-UMN disease had a favourable response to sildenafil that was not statistically different from placebo. Sildenafil seems more effective in the treatment of neurogenic ED secondary to UMN spinal cord injury compared with that secondary to LMN injury. Actually, its efficacy on LMN injuries does not seem different from placebo and administration of this treatment may not be effective in spinal cord injury which has caused LMN symptoms.

Facial paralysis: A critical review of accepted explanation

Historically, paralysis of facial muscles has been divided into "upper motor neuron injury" and "lower motor neuron injury". Patients who experience a stroke in the cortex or internal capsule have UMN injury and cannot purse their lips or smile on command. They are, however, able to wrinkle their forehead, raise their eyebrows, and completely close their eyes. Patients with LMN injury, in addition to the aforementioned impairments cannot raise their eyebrows. The classical explanations for these clinical findings are that the upper facial muscles receive bilateral innervation from the cerebral cortex and the lower facial muscles receive only unilateral innervation from the contralateral cerebral cortex. However, a review of the basic science literature indicates that commonly accepted explanations and the pattern of cortical projections are not consistent with anatomical studies. Studies in monkeys demonstrate that both the upper facial nucleus and the lower facial nucleus receive bilateral cortical projections. As well, there is no direct anatomical evidence in human beings that the facial nucleus (upper or lower) receives any innervation from the cortex.

Electrophysiological signs of changes in motor units after ischaemic stroke

Objective To study changes in motor units on the hemiparetic side, and the relationship between these changes and time after stroke onset and hemiparetic severity. Methods Neurography and concentric needle EMG were performed, and hemiparetic side mean and extreme parameter values were compared with the unaffected side mean and extreme parameter values using non-parametric tests. Results The mean M wave amplitude was significantly lower, while the spontaneous activity and the mean number of motor unit potential (MUAP) phases and turns were significantly higher on the hemiparetic side. The outliers above maximum for MUAP duration and amplitude on the hemiparetic side were significantly higher than those on the unaffected side. Correlations were found between the hemiparetic side parameter values and time after stroke onset and hemiparetic severity. Conclusions Axonal or neuronal lesion occurs and collateral reinnervation starts in the acute phase after stroke, while enlarged motor units are found in the chronic state. These changes correlate with hemiparetic severity. Significance This work confirms the controversial concept about lower motor neuron injury with stroke, and provides some information about its time course.

Tests of Respiratory Muscle Strength In Neonates

After completing this article, readers should be able to: 1. Describe the underlying cause of respiratory failure in about 50% of preterm infants who require intubation and mechanical ventilation. 2. Compare compliance characteristics of the chest wall in infants, older children, and adults. 3. List some of the conditions seen in neonates that can adversely affect respiratory muscle function. 4. List noninvasive tests for assessing respiratory muscle strength in neonates. Chest wall mechanics of neonates and infants play an essential role in ventilation that frequently is underappreciated. Dysfunction of the respiratory muscles can cause both a disease process and an inability of the patient to compensate for it. As an example, respiratory muscle failure may be the underlying cause in about 50% of preterm infants who have ventilatory failure. (1) In this article, we detail the current understanding of the physiology of the respiratory muscles in neonates and discuss a number of tests designed to assess their function. Mechanically, the respiratory system can be thought of as being composed of two components. The first includes the respiratory muscles, the rib cage, and the anterior abdominal wall, which together make up the “pump,” whose function is to move air in and out of the lungs. The second includes the airways and lung parenchyma through which gas exchange occurs and can be referred to as the “load” on which the pump must act. For ventilation to occur, the respiratory pump must overcome both the frictional (eg, airway resistance) and tissue elastic forces (eg, lung and chest wall compliance) that create the load. The balance between the capabilities of the pump and the magnitude of the load can influence whether respiratory “success” or “failure” occurs. The chest wall, which contains muscles and skeletal structures, undergoes dramatic maturational changes over the first several years of life. In addition …

Resistance to d-Tubocurarine in Lower Motor Neuron Injury Is Related to Increased Acetylcholine Receptors at the Neuromuscular Junction

The hypothesis that lower motor neuron injury, with its associated proliferation of acetylcholine receptors (AChR), induces resistance to the neuromuscular effects of d-tubocurarine (dTC) was tested in the rat. The left gastrocnemius was denervated by a 75-80% lesion of the sciatic nerve. The effective dose for 95% twitch depression (ED95) was studied in the denervated gastrocnemius and compared to the contralateral undenervated and sham-injured (control) gastrocnemius muscles approximately 2 weeks after injury. The AChR number was quantitated by the specific ligand 125I-alpha-bungarotoxin (125I-alpha-BT). Plasma dTC concentrations, measured by high-performance liquid chromatography (HPLC), were correlated to twitch tension during spontaneous recovery from neuromuscular blockade in the denervated animal. The ED95 (mean +/- SE) of dTC for the denervated leg was significantly (P less than 0.05) higher (0.26 +/- 0.06 mg.kg-1) than contralateral (0.16 +/- 0.03) and sham-operated left (0.13 +/- 0.03) legs. The twitch tension recovered to 50% of control twitch height at significantly (P less than 0.05) higher plasma dTC concentrations in the denervated (0.78 micrograms.ml-1) compared to contralateral (0.24 micrograms.ml-1) limb. The AChR number was significantly increased in the denervated limb (1041 +/- 96 fmol.mg protein-1) compared to contralateral right (109 +/- 4) and control left limb (113 +/- 11). There was a significant (P less than 0.05) positive correlation (R2 = 0.73) between ED95 and AChR number; that is, 73% of the variability in ED95 could be explained by changes in AChR. This study, therefore, confirms the hypothesis that proliferation of AChR after nerve denervation results in resistance to the neuromuscular effects of dTC.(ABSTRACT TRUNCATED AT 250 WORDS)