Takotsubo-like Myocardial Dysfunction in a Patient with Botulism.

PubMed

Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki

2017-11-01

Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease.

Takotsubo-like Myocardial Dysfunction in a Patient with Botulism

PubMed Central

Tonomura, Shuichi; Kakehi, Yoshiaki; Sato, Masatoshi; Naito, Yuki; Shimizu, Hisao; Goto, Yasunobu; Takahashi, Nobuyuki

2017-01-01

Botulinum toxin A (BTXA) can disrupt the neuromuscular and autonomic functions. We herein report a case of autonomic system dysfunction that manifested as Takotsubo-like myocardial dysfunction in a patient with botulism. Takotsubo syndrome results in acute cardiac insufficiency, another fatal complication of botulism in addition to respiratory muscle paralysis, particularly in patients with cardiovascular disease. PMID:28924131

Physiology in Medicine: neuromuscular consequences of diabetic neuropathy

PubMed Central

Doherty, Timothy J.; Rice, Charles L.; Kimpinski, Kurt

2016-01-01

Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment. PMID:26989220

Physiology in Medicine: neuromuscular consequences of diabetic neuropathy.

PubMed

Allen, Matti D; Doherty, Timothy J; Rice, Charles L; Kimpinski, Kurt

2016-07-01

Diabetic polyneuropathy (DPN) refers to peripheral nerve dysfunction as a complication of diabetes mellitus. This condition is relatively common and is likely a result of vascular and/or metabolic disturbances related to diabetes. In the early or less severe stages of DPN it typically results in sensory impairments but can eventually lead to major dysfunction of the neuromuscular system. Some of these impairments may include muscle atrophy and weakness, slowing of muscle contraction, and loss of power and endurance. Combined with sensory deficits these changes in the motor system can contribute to decreased functional capacity, impaired mobility, altered gait, and increased fall risk. There is no pharmacological disease-modifying therapy available for DPN and the mainstay of treatment is linked to treating the diabetes itself and revolves around strict glycemic control. Exercise therapy (including aerobic, strength, or balance training-based exercise) appears to be a promising preventative and treatment strategy for patients with DPN and those at risk. The goal of this Physiology in Medicine article is to highlight important and overlooked dysfunction of the neuromuscular system as a result of DPN with an emphasis on the physiologic basis for that dysfunction. Additionally, we sought to provide information that clinicians can use when following patients with diabetes or DPN including support for the inclusion of exercise-based therapy as an effective, accessible, and inexpensive form of treatment. Copyright © 2016 the American Physiological Society.

Effects of Local Compression on Peroneal Nerve Function in Humans

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Botte, Michael J.; Swenson, Michael R.; Gelberman, Richard H.; Rhoades, Charles E.; Akeson, Wayne H.

1993-01-01

A new apparatus was developed to compress the anterior compartment selectively and reproducibly in humans. Thirty-five normal volunteers were studied to determine short-term thresholds of local tissue pressure that produce significant neuromuscular dysfunction. Local tissue fluid pressure adjacent to the deep peroneal nerve was elevated by the compression apparatus and continuously monitored for 2-3 h by the slit catheter technique. Elevation of tissue fluid pressure to within 35-40 mm Hg of diastolic blood pressure (approx. 40 mm Hg of in situ pressure in our subjects) elicited a consistent progression of neuromuscular deterioration including, in order, (a) gradual loss of sensation, as assessed by Semmes-Weinstein monofilaments, (b) subjective complaints, (c) reduced nerve conduction velocity, (d) decreased action potential amplitude of the extensor digitorum brevis muscle, and (e) motor weakness of muscles within the anterior compartment. Generally, higher intracompartment at pressures caused more rapid deterioration of neuromuscular function. In two subjects, when in situ compression levels were 0 and 30 mm Hg, normal neuromuscular function was maintained for 3 h. Threshold pressures for significant dysfunction were not always the same for each functional parameter studied, and the magnitudes of each functional deficit did not always correlate with compression level. This variable tolerance to elevated pressure emphasizes the need to monitor clinical signs and symptoms carefully in the diagnosis of compartment syndromes. The nature of the present studies was short term; longer term compression of myoneural tissues may result in dysfunction at lower pressure thresholds.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study.

PubMed

Duyff, R F; Van den Bosch, J; Laman, D M; van Loon, B J; Linssen, W H

2000-06-01

To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

Postoperative respiratory muscle dysfunction: pathophysiology and preventive strategies.

PubMed

Sasaki, Nobuo; Meyer, Matthew J; Eikermann, Matthias

2013-04-01

Postoperative pulmonary complications are responsible for significant increases in hospital cost as well as patient morbidity and mortality; respiratory muscle dysfunction represents a contributing factor. Upper airway dilator muscles functionally resist the upper airway collapsing forces created by the respiratory pump muscles. Standard perioperative medications (anesthetics, sedatives, opioids, and neuromuscular blocking agents), interventions (patient positioning, mechanical ventilation, and surgical trauma), and diseases (lung hyperinflation, obesity, and obstructive sleep apnea) have differential effects on the respiratory muscle subgroups. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. Such strategies include minimally invasive procedures rather than open surgery, early and optimal mobilizing of respiratory muscles while on mechanical ventilation, judicious use of respiratory depressant anesthetics and neuromuscular blocking agents, and noninvasive ventilation when possible.

Fatigue in neuromuscular disorders: focus on Guillain-Barré syndrome and Pompe disease.

PubMed

de Vries, J M; Hagemans, M L C; Bussmann, J B J; van der Ploeg, A T; van Doorn, P A

2010-03-01

Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain-Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain-Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated.

Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

PubMed

Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

2018-02-05

Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

PubMed Central

Duyff, R.; Van den Bosch, J.; Laman, D; van Loon, B.-J. P.; Linssen, W.

2000-01-01

OBJECTIVES—To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism.
METHODS—A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment.
RESULTS—In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6months).
CONCLUSIONS—Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

 PMID:10811699

Selected Articles on Feeding Children Who Have a Neuromuscular Disorder. TIES: Therapy in Educational Settings.

ERIC Educational Resources Information Center

Hall, Sandra; And Others

The manual contains articles about evaluating and addressing the feeding needs of children who have oral-motor dysfunctions. "Helpful Hints for Feeding Children with Oral-Motor Dysfunction" (Janet Wilson) offers 20 suggestions relating to such areas as positioning the child, monitoring food preferences, and attending to oral hygiene.…

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting.

PubMed

Tintignac, Lionel A; Brenner, Hans-Rudolf; Rüegg, Markus A

2015-07-01

The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia. Copyright © 2015 the American Physiological Society.

Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

PubMed

Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

2012-06-20

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

Neuromuscular transmission failure in myasthenia gravis: decrement of safety factor and susceptibility of extraocular muscles.

PubMed

Serra, Alessandro; Ruff, Robert L; Leigh, Richard John

2012-12-01

An appropriate density of acetylcholine receptors (AChRs) and Na(+) channels (NaChs) in the normal neuromuscular junction (NMJ) determines the magnitude of safety factor (SF) that guarantees fidelity of neuromuscular transmission. In myasthenia gravis (MG), an overall simplification of the postsynaptic folding secondary to NMJ destruction results in AChRs and NaChs depletion. Loss of AChRs and NaChs accounts, respectively, for 59% and 40% reduction of the SF at the endplate, which manifests as neuromuscular transmission failure. The extraocular muscles (EOM) have physiologically less developed postsynaptic folding, hence a lower baseline SF, which predisposes them to dysfunction in MG and development of fatigue during "high performance" eye movements, such as saccades. However, saccades in MG show stereotyped, conjugate initial components, similar to normal, which might reflect preserved neuromuscular transmission fidelity at the NMJ of the fast, pale global fibers, which have better developed postsynaptic folding than other extraocular fibers. © 2012 New York Academy of Sciences.

Effects of Neuromuscular Fatigue on Quadriceps Strength and Activation and Knee Biomechanics in Individuals Post-Anterior Cruciate Ligament Reconstruction and Healthy Adults.

PubMed

Thomas, Abbey C; Lepley, Lindsey K; Wojtys, Edward M; McLean, Scott G; Palmieri-Smith, Riann M

2015-12-01

Laboratory-based experiment using a pretest/posttest design. To determine the effects of neuromuscular fatigue on quadriceps strength and activation and sagittal and frontal plane knee biomechanics during dynamic landing following anterior cruciate ligament reconstruction (ACLR). Impaired quadriceps central activation occurs post-ACLR, likely altering lower extremity biomechanics. Neuromuscular fatigue similarly reduces volitional muscle activation and impairs neuromuscular control. Upon return to full activity post-ACLR, individuals likely concurrently experience quadriceps central activation deficits and neuromuscular fatigue, though the effects of fatigue on muscle strength and activation and biomechanics post-ACLR are unknown. Seventeen individuals 7 to 10 months post-ACLR and 16 controls participated. Quadriceps strength and central activation ratio were recorded prefatigue and postfatigue, which was induced via sets of double-leg squats. Knee biomechanics were recorded during a dynamic landing activity prefatigue and postfatigue. Both groups demonstrated smaller knee flexion (initial contact, P = .017; peak, P = .004) and abduction (initial contact, P = .005; peak, P = .009) angles postfatigue. The ACLR group had smaller peak knee flexion angles (P<.001) prefatigue and postfatigue than controls. Knee flexion moment was smaller in those post-ACLR than controls prefatigue (P<.001), but not postfatigue (P = .103). Controls had smaller knee flexion moments postfatigue (P = .001). Knee abduction moment was smaller in both groups postfatigue (P = .003). All participants demonstrated significantly lower strength (P<.001) and activation (P = .003) postfatigue. Impaired strength, central activation, and biomechanics were present postfatigue in both groups, suggesting that neuromuscular fatigue may increase noncontact ACL injury risk. However, these changes were not exaggerated in those post-ACLR, likely because they already demonstrated a stiff-legged landing strategy prefatigue.

Low-Load Resistance Training with Blood Flow Occlusion as a Countermeasure to Disuse Atrophy

NASA Technical Reports Server (NTRS)

Ploutz-Snyder, L. L.; Cook, S. B.

2009-01-01

Decreases in strength and neuromuscular function are observed following prolonged disuse. Exercise countermeasures to prevent muscle dysfunction during disuse typically involve high intensity resistance training. The purpose of the study is to evaluate the effectiveness of low-load resistance training with a blood flow occlusion to mitigate muscle loss and dysfunction during 30 days of unilateral lower limb suspension (ULLS).

42 CFR 410.100 - Included services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of techniques...

42 CFR 410.100 - Included services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of techniques...

42 CFR 410.100 - Included services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... function or dysfunction of the neuromuscular, musculoskeletal, cardiovascular and respiratory systems; and... create difficulties in communication. (e) Respiratory therapy services. (1) Respiratory therapy services... cardiopulmonary function. (2) Respiratory therapy services include the following: (i) Application of techniques...

Thyroid-related neurological disorders and complications in children.

PubMed

Nandi-Munshi, Debika; Taplin, Craig E

2015-04-01

Thyroid hormones exert critical roles throughout the body and play an important and permissive role in neuroendocrine, neurological, and neuromuscular function. We performed a PubMed search through June 2014 with search terms including "hypothyroidism," "hyperthyroidism," "neurological complications," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy." Relevant publications reviewed included case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials. The neurological outcomes of congenital hypothyroidism were reviewed, along with the clinical features of associated neuromuscular syndromes of both hypothyroidism and hyperthyroidism, including other autoimmune conditions. Evidence for, and pathophysiological controversies surrounding, Hashimoto encephalopathy was also reviewed. The establishment of widespread newborn screening programs has been highly successful in attenuating or preventing early and irreversible neurological harm resulting from congenital thyroid hormone deficiency, but some children continue to display neuromuscular, sensory, and cognitive defects in later life. Acquired disorders of thyroid function such as Hashimoto thyroiditis and Graves' disease are associated with a spectrum of central nervous system and/or neuromuscular dysfunction. However, considerable variation in clinical phenotype is described, and much of our knowledge of the role of thyroid disease in childhood neurological disorders is derived from adult case series. Early and aggressive normalization of thyroxine levels in newborn infants with congenital hypothyroidism is important in minimizing neurological sequelae, but maternal thyroid hormone sources are also critically important to the early developing brain. A spectrum of neurological disorders has been reported in older children with acquired thyroid disease, but the frequency with which these occur remains poorly defined in the literature, and much must be extrapolated from adult data. A high index of suspicion for acquired thyroid disease is paramount in the investigation of many neurological disorders of youth, as many reported sequelae of hypothyroidism and hyperthyroidism are reversible with appropriate endocrine management. Copyright © 2015 Elsevier Inc. All rights reserved.

Botulinum Neurotoxin Type A in Neurology: Update.

PubMed

Orsini, Marco; Leite, Marco Antonio Araujo; Chung, Tae Mo; Bocca, Wladimir; de Souza, Jano Alves; de Souza, Olivia Gameiro; Moreira, Rayele Priscila; Bastos, Victor Hugo; Teixeira, Silmar; Oliveira, Acary Bulle; Moraes, Bruno da Silva; Matta, André Palma; Jacinto, Luis Jorge

2015-09-24

This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy.

Botulinum Neurotoxin Type A in Neurology: Update

PubMed Central

Orsini, Marco; Leite, Marco Antonio Araujo; Chung, Tae Mo; Bocca, Wladimir; de Souza, Jano Alves; de Souza, Olivia Gameiro; Moreira, Rayele Priscila; Bastos, Victor Hugo; Teixeira, Silmar; Oliveira, Acary Bulle; Moraes, Bruno da Silva; Matta, André Palma; Jacinto, Luis Jorge

2015-01-01

This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy. PMID:26487928

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Acute disseminated encephalomyelitis in dengue viral infection.

PubMed

Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

2017-09-01

Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

ACUTE PHARMACOLOGICAL INHIBITION OF CHOLINESTERASE RESULTS IN MINIMAL NEUROMUSCULAR JITTER CHANGES.

EPA Science Inventory

Concern over the lack of available endpoints to assess peripheral nervous system dysfunction after pesticide exposure has led to the search for new laboratory models. Recently our lab adapted the in vivo clinical practice of stimulation single fiber electromyography (SFEMG) for u...

Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming

PubMed Central

Silva, Anjana; Hodgson, Wayne C.; Isbister, Geoffrey K.

2017-01-01

Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this. PMID:28422078

Forward head posture: its structural and functional influence on the stomatognathic system, a conceptual study.

PubMed

Gonzalez, H E; Manns, A

1996-01-01

An extensive conceptual analysis to establish the primary role a forward head posture plays in the appearance of some craniomandibular dysfunctions and internal derangements of the temporomandibular joints, associated to craniocervical postural disturbances. The analysis is based on findings contributed by scientific investigations in the field of dentofacial orthopedics and dysfunction. Special emphasis has been put on the influence of forward head posture on the craniofacial growth as it can determine a morphoskeletal and neuromuscular pattern leading to a dysfunctional condition. A correlation is established between Class II Occlusion, forward head posture, and craniomandibular dysfunction. The concept of craniocervical postural position is defined, as well as its close relation to the mandibular postural position.

Acute lower motor neuron tetraparesis.

PubMed

Añor, Sònia

2014-11-01

Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

A theoretical framework for understanding neuromuscular response to lower extremity joint injury.

PubMed

Pietrosimone, Brian G; McLeod, Michelle M; Lepley, Adam S

2012-01-01

Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes.

A Theoretical Framework for Understanding Neuromuscular Response to Lower Extremity Joint Injury

PubMed Central

Pietrosimone, Brian G.; McLeod, Michelle M.; Lepley, Adam S.

2012-01-01

Background: Neuromuscular alterations are common following lower extremity joint injury and often lead to decreased function and disability. These neuromuscular alterations manifest in inhibition or abnormal facilitation of the uninjured musculature surrounding an injured joint. Unfortunately, these neural alterations are poorly understood, which may affect clinical recognition and treatment of these injuries. Understanding how these neural alterations affect physical function may be important for proper clinical management of lower extremity joint injuries. Methods: Pertinent articles focusing on neuromuscular consequences and treatment of knee and ankle injuries were collected from peer-reviewed sources available on the Web of Science and Medline databases from 1975 through 2010. A theoretical model to illustrate potential relationships between neural alterations and clinical impairments was constructed from the current literature. Results: Lower extremity joint injury affects upstream cortical and spinal reflexive excitability pathways as well as downstream muscle function and overall physical performance. Treatment targeting the central nervous system provides an alternate means of treating joint injury that may be effective for patients with neuromuscular alterations. Conclusions: Disability is common following joint injury. There is mounting evidence that alterations in the central nervous system may relate to clinical changes in biomechanics that may predispose patients to further injury, and novel clinical interventions that target neural alterations may improve therapeutic outcomes. PMID:23016066

Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study.

PubMed

van den Engel-Hoek, Lenie; Erasmus, Corrie E; van Hulst, Karen C M; Arvedson, Joan C; de Groot, Imelda J M; de Swart, Bert J M

2014-05-01

To determine whether findings on videofluoroscopic swallow studies reveal different patterns of dysphagia between children with central and peripheral neurologic disorders, a retrospective study of 118 videofluoroscopic swallow studies was completed. There were 3 groups: cerebral palsy with only spastic features (n = 53), cerebral palsy with dyskinetic features (n = 34), and neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I-II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n = 10). Interpretation of the videofluoroscopic swallow studies was not blinded. The video fluoroscopic swallow study findings were compared dichotomously between the groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal residue after swallow. The underlying swallowing problem in neuromuscular disorder is muscle weakness whereas that in cerebral palsy is more complex, having to do with abnormal control of swallowing. This study serves as a first exploration on specific characteristics of swallowing in different neurologic conditions and will help clinicians anticipate what they might expect.

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

PubMed Central

Patel, Nimesh SA; Nandra, Kiran K; Brines, Michael; Collino, Massimo; Wong, WS Fred; Kapoor, Amar; Benetti, Elisa; Goh, Fera Y; Fantozzi, Roberto; Cerami, Anthony; Thiemermann, Christoph

2011-01-01

Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect—an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB. PMID:21607291

Influence of patterned electrical neuromuscular stimulation on quadriceps activation in individuals with knee joint injury.

PubMed

Glaviano, Neal R; Langston, William T; Hart, Joseph M; Saliba, Susan

2014-12-01

Neuromuscular Electrical Stimulation is a common intervention to address muscle weakness, however presents with many limitations such as fatigue, muscle damage, and patient discomfort that may influence its effectiveness. One novel form of electrical stimulation purported to improve neuromuscular re-education is Patterned Electrical Neuromuscular Stimulation (PENS), which is proposed to mimic muscle-firing patterns of healthy individuals. PENS provides patterned stimulating to the agonist muscle, antagonist muscle and then agonist muscle again in an effort to replicate firing patterns. The purpose of this study was to determine the effect of a single PENS treatment on knee extension torque and quadriceps activation in individuals with quadriceps inhibition. 18 subjects (10 males and 8 females: 24.2±3.4 years, 175.3±11.8cm, 81.8±12.4kg) with a history of knee injury/pain participated in this double-blinded randomized controlled laboratory trial. Participants demonstrated quadriceps inhibition with a central activation ratio of ≤90%. Maximal voluntary isometric contraction of the quadriceps and central activation ratio were measured before and after treatment. The treatment intervention was a 15-minute patterned electrical stimulation applied to the quadriceps and hamstring muscles with a strong motor contraction or a sham group, who received an identical set up as the PENS group, but received a 1mA subsensory stimulation. A 2×2 (group × time) ANCOVA was used to determine differences in maximal voluntary isometric contraction and central activation ratio between groups. The maximal voluntary isometric contraction was selected as a covariate due to baseline differences. There were no differences in change scores between pre- and post-intervention for maximal voluntary isometric contraction: (PENS: 0.09±0.32Nm/kg and Sham 0.15±0.18Nm/kg, p=0.713), or central activation ratio:(PENS: -1.22±6.06 and Sham: 1.48±3.7, p=0.270). A single Patterned Electrical Neuromuscular Stimulation treatment did not alter quadriceps central activation ratio or maximal voluntary isometric contraction. Unlike other types of muscle stimulation, PENS did not result in a reduction of quadriceps torque. Level III.

Genome Editing of Monogenic Neuromuscular Diseases: A Systematic Review.

PubMed

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N

2016-11-01

Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9-mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing-meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies.

Genome Editing of Monogenic Neuromuscular Diseases

PubMed Central

Long, Chengzu; Amoasii, Leonela; Bassel-Duby, Rhonda; Olson, Eric N.

2017-01-01

IMPORTANCE Muscle weakness, the most common symptom of neuromuscular disease, may result from muscle dysfunction or may be caused indirectly by neuronal and neuromuscular junction abnormalities. To date, more than 780 monogenic neuromuscular diseases, linked to 417 different genes, have been identified in humans. Genome-editing methods, especially the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 (CRISPR-associated protein 9) system, hold clinical potential for curing many monogenic disorders, including neuromuscular diseases such as Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1. OBJECTIVES To provide an overview of genome-editing approaches; to summarize published reports on the feasibility, efficacy, and safety of current genome-editing methods as they relate to the potential correction of monogenic neuromuscular diseases; and to highlight scientific and clinical opportunities and obstacles toward permanent correction of disease-causing mutations responsible for monogenic neuromuscular diseases by genome editing. EVIDENCE REVIEW PubMed and Google Scholar were searched for articles published from June 30, 1989, through June 9, 2016, using the following keywords: genome editing, CRISPR-Cas9, neuromuscular disease, Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, andmyotonic dystrophy type 1. The following sources were reviewed: 341 articles describing different approaches to edit mammalian genomes; 330 articles describing CRISPR-Cas9–mediated genome editing in cell culture lines (in vitro) and animal models (in vivo); 16 websites used to generate single-guide RNA; 4 websites for off-target effects; and 382 articles describing viral and nonviral delivery systems. Articles describing neuromuscular diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, amyotrophic lateral sclerosis, and myotonic dystrophy type 1, were also reviewed. FINDINGS Multiple proof-of-concept studies reveal the feasibility and efficacy of genome-editing–meditated correction of monogenic neuromuscular diseases in cultured cells and animal models. CONCLUSIONS AND RELEVANCE Genome editing is a rapidly evolving technology with enormous translational potential once efficacy, delivery, and safety issues are addressed. The clinical impact of this technology is that genome editing can permanently correct disease-causing mutations and circumvent the hurdles of traditional gene- and cell-based therapies. PMID:27668807

Restoration of Motor Defects Caused by Loss of Drosophila TDP-43 by Expression of the Voltage-Gated Calcium Channel, Cacophony, in Central Neurons.

PubMed

Lembke, Kayly M; Scudder, Charles; Morton, David B

2017-09-27

Defects in the RNA-binding protein, TDP-43, are known to cause a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. A variety of experimental systems have shown that neurons are sensitive to TDP-43 expression levels, yet the specific functional defects resulting from TDP-43 dysregulation have not been well described. Using the Drosophila TDP-43 ortholog TBPH, we previously showed that TBPH-null animals display locomotion defects as third instar larvae. Furthermore, loss of TBPH caused a reduction in cacophony , a Type II voltage-gated calcium channel, expression and that genetically restoring cacophony in motor neurons in TBPH mutant animals was sufficient to rescue the locomotion defects. In the present study, we examined the relative contributions of neuromuscular junction physiology and the motor program to the locomotion defects and identified subsets of neurons that require cacophony expression to rescue the defects. At the neuromuscular junction, we showed mEPP amplitudes and frequency require TBPH. Cacophony expression in motor neurons rescued mEPP frequency but not mEPP amplitude. We also showed that TBPH mutants displayed reduced motor neuron bursting and coordination during crawling and restoring cacophony selectively in two pairs of cells located in the brain, the AVM001b/2b neurons, also rescued the locomotion and motor defects, but not the defects in neuromuscular junction physiology. These results suggest that the behavioral defects associated with loss of TBPH throughout the nervous system can be associated with defects in a small number of genes in a limited number of central neurons, rather than peripheral defects. SIGNIFICANCE STATEMENT TDP-43 dysfunction is a common feature in neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal lobar dementia, and Alzheimer's disease. Loss- and gain-of-function models have shown that neurons are sensitive to TDP-43 expression levels, but the specific defects caused by TDP-43 loss of function have not been described in detail. A Drosophila loss-of-function model displays pronounced locomotion defects that can be reversed by restoring the expression levels of a voltage-gated calcium channel, cacophony. We show these defects can be rescued by expression of cacophony in motor neurons and by expression in two pairs of neurons in the brain. These data suggest that loss of TDP-43 can disrupt the central circuitry of the CNS, opening up identification of alternative therapeutic targets for TDP-43 proteinopathies. Copyright © 2017 the authors 0270-6474/17/379486-12$15.00/0.

A stem-cell based bioassay to critically assess the pathology of dysfunctional neuromuscular junctions.

PubMed

Chipman, Peter H; Zhang, Ying; Rafuse, Victor F

2014-01-01

Pluripotent stem cells can be directed to differentiate into motor neurons and assessed for functionality in vitro. An emerging application of this technique is to model genetically inherited diseases in differentiated motor neurons and to screen for new therapeutic targets. The neuromuscular junction (NMJ) is essential to the functionality of motor neurons and its dysfunction is a primary hallmark of motor neuron disease. However, mature NMJs that possess the functional and morphological characteristics of those formed in vivo have so far not been obtained in vitro. Here we describe the generation and analysis of mature NMJs formed between embryonic stem cell-derived motor neurons (ESCMNs) and primary myotubes. We compared the formation and maturation of NMJs generated by wild-type (NCAM+/+) ESCMNs to those generated by neural cell adhesion molecule null (NCAM-/-) ESCMNs in order to definitively test the sensitivity of this assay to identify synaptic pathology. We find that co-cultures using NCAM-/- ESCMNs replicate key in vivo NCAM-/- phenotypes and reveal that NCAM influences neuromuscular synaptogenesis by controlling the mode of synaptic vesicle endocytosis. Further, we could improve synapse formation and function in NCAM-/- co-cultures by chronic treatment with nifedipine, which blocks an immature synaptic vesicle recycling pathway. Together, our results demonstrate that this ESCMN/myofiber co-culture system is a highly sensitive bioassay for examining molecules postulated to regulate synaptic function and for screening therapeutics that will improve the function of compromised NMJs.

Selective disruption of acetylcholine synthesis in subsets of motor neurons: a new model of late-onset motor neuron disease.

PubMed

Lecomte, Marie-José; Bertolus, Chloé; Santamaria, Julie; Bauchet, Anne-Laure; Herbin, Marc; Saurini, Françoise; Misawa, Hidemi; Maisonobe, Thierry; Pradat, Pierre-François; Nosten-Bertrand, Marika; Mallet, Jacques; Berrard, Sylvie

2014-05-01

Motor neuron diseases are characterized by the selective chronic dysfunction of a subset of motor neurons and the subsequent impairment of neuromuscular function. To reproduce in the mouse these hallmarks of diseases affecting motor neurons, we generated a mouse line in which ~40% of motor neurons in the spinal cord and the brainstem become unable to sustain neuromuscular transmission. These mice were obtained by conditional knockout of the gene encoding choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine. The mutant mice are viable and spontaneously display abnormal phenotypes that worsen with age including hunched back, reduced lifespan, weight loss, as well as striking deficits in muscle strength and motor function. This slowly progressive neuromuscular dysfunction is accompanied by muscle fiber histopathological features characteristic of neurogenic diseases. Unexpectedly, most changes appeared with a 6-month delay relative to the onset of reduction in ChAT levels, suggesting that compensatory mechanisms preserve muscular function for several months and then are overwhelmed. Deterioration of mouse phenotype after ChAT gene disruption is a specific aging process reminiscent of human pathological situations, particularly among survivors of paralytic poliomyelitis. These mutant mice may represent an invaluable tool to determine the sequence of events that follow the loss of function of a motor neuron subset as the disease progresses, and to evaluate therapeutic strategies. They also offer the opportunity to explore fundamental issues of motor neuron biology. Copyright © 2014 Elsevier Inc. All rights reserved.

S-nitrosoglutathione reductase deficiency-induced S-nitrosylation results in neuromuscular dysfunction.

PubMed

Montagna, Costanza; Di Giacomo, Giuseppina; Rizza, Salvatore; Cardaci, Simone; Ferraro, Elisabetta; Grumati, Paolo; De Zio, Daniela; Maiani, Emiliano; Muscoli, Carolina; Lauro, Filomena; Ilari, Sara; Bernardini, Sergio; Cannata, Stefano; Gargioli, Cesare; Ciriolo, Maria R; Cecconi, Francesco; Bonaldo, Paolo; Filomeni, Giuseppe

2014-08-01

Nitric oxide (NO) production is implicated in muscle contraction, growth and atrophy, and in the onset of neuropathy. However, many aspects of the mechanism of action of NO are not yet clarified, mainly regarding its role in muscle wasting. Notably, whether NO production-associated neuromuscular atrophy depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a matter of debate. Here, we aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs. We demonstrate that, without any sign of protein nitration, young GSNOR-KO mice show neuromuscular atrophy due to loss of muscle mass, reduced fiber size, and neuropathic behavior. In particular, GSNOR-KO mice show a significant decrease in nerve axon number, with the myelin sheath appearing disorganized and reduced, leading to a dramatic development of a neuropathic phenotype. Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and myotubes, conditions that are reverted by N-acetylcysteine treatment. Nevertheless, although atrogene transcription is induced, and bulk autophagy activated, no removal of damaged mitochondria is observed. These events, alongside basal increase of apoptotic markers, contribute to persistence of a neuropathic and myopathic state. Our study provides the first evidence that GSNOR deficiency, which affects exclusively SNOs reduction without altering nitrotyrosine levels, results in a clinically relevant neuromuscular phenotype. These findings provide novel insights into the involvement of GSNOR and S-nitrosylation in neuromuscular atrophy and neuropathic pain that are associated with pathological states; for example, diabetes and cancer.

Functional capacity and muscular abnormalities in subclinical hypothyroidism.

PubMed

Reuters, Vaneska S; Teixeira, Patrícia de Fátima S; Vigário, Patrícia S; Almeida, Cloyra P; Buescu, Alexandre; Ferreira, Márcia M; de Castro, Carmen L N; Gold, Jaime; Vaisman, Mario

2009-10-01

Neuromuscular abnormalities and low exercise tolerance are frequently observed in overt hypothyroidism, but it remains controversial if they can also occur in subclinical hypothyroidism (sHT). The aim of this study is to evaluate neuromuscular symptoms, muscle strength, and exercise capacity in sHT, compared with healthy euthyroid individuals. A cross-sectional study was performed with 44 sHT and 24 euthyroid outpatients from a university hospital. Neuromuscular symptoms were questioned. Muscle strength was tested for neck, shoulder, arm, and hip muscle groups, using manual muscle testing (MMT). Quadriceps muscle strength was tested with a chair dynamometer and inspiratory muscle strength (IS) by a manuvacuometer. Functional capacity was estimated based on the peak of oxygen uptake (mL/kg/min), using the Bruce treadmill protocol. Cramps (54.8% versus 25.0%; P < 0.05), weakness (45.2% versus 12.6; P < 0.05), myalgia (47.6% versus 25.0%; P = 0.07), and altered MMT (30.8% versus 8.3%; P = 0.040) were more frequent in sHT. Quadriceps strength and IS were not impaired in sHT and the same was observed for functional capacity. IS was significantly lower in patients complaining of fatigue and weakness (P < 0.05) and tended to be lower in those with altered MMT (P = 0.090). Neuromuscular complaints and altered MMT were significantly more frequent in sHT than in controls, and IS was lower in patients with these abnormalities. Results suggest that altered muscle strength by MMT and the coexistence of neuromuscular complaints in patients with sHT may indicate neuromuscular dysfunction.

Effect of Artificial Gravity: Central Nervous System Neurochemical Studies

NASA Technical Reports Server (NTRS)

Fox, Robert A.; D'Amelio, Fernando; Eng, Lawrence F.

1997-01-01

The major objective of this project was to assess chemical and morphological modifications occurring in muscle receptors and the central nervous system of animals subjected to altered gravity (2 x Earth gravity produced by centrifugation and simulated micro gravity produced by hindlimb suspension). The underlying hypothesis for the studies was that afferent (sensory) information sent to the central nervous system by muscle receptors would be changed in conditions of altered gravity and that these changes, in turn, would instigate a process of adaptation involving altered chemical activity of neurons and glial cells of the projection areas of the cerebral cortex that are related to inputs from those muscle receptors (e.g., cells in the limb projection areas). The central objective of this research was to expand understanding of how chronic exposure to altered gravity, through effects on the vestibular system, influences neuromuscular systems that control posture and gait. The project used an approach in which molecular changes in the neuromuscular system were related to the development of effective motor control by characterizing neurochemical changes in sensory and motor systems and relating those changes to motor behavior as animals adapted to altered gravity. Thus, the objective was to identify changes in central and peripheral neuromuscular mechanisms that are associated with the re-establishment of motor control which is disrupted by chronic exposure to altered gravity.

Herpes Simplex Virus Type 1 Infects Enteric Neurons and Triggers Gut Dysfunction via Macrophage Recruitment.

PubMed

Brun, Paola; Qesari, Marsela; Marconi, Peggy C; Kotsafti, Andromachi; Porzionato, Andrea; Macchi, Veronica; Schwendener, Reto A; Scarpa, Marco; Giron, Maria C; Palù, Giorgio; Calistri, Arianna; Castagliuolo, Ignazio

2018-01-01

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets.

Neuromuscular Electrical Stimulation for Motor Restoration in Hemiplegia

PubMed Central

Knutson, Jayme S.; Fu, Michael J.; Sheffler, Lynne R.; Chae, John

2015-01-01

Synopsis This article reviews the most common therapeutic and neuroprosthetic applications of neuromuscular electrical stimulation (NMES) for upper and lower extremity stroke rehabilitation. Fundamental NMES principles and purposes in stroke rehabilitation are explained. NMES modalities used for upper and lower limb rehabilitation are described and efficacy studies are summarized. The evidence for peripheral and central mechanisms of action is also summarized. PMID:26522909

Anesthetic Considerations of Sporadic Inclusion Body Myositis in an Elderly Man With Orthopedic Trauma.

PubMed

Steck, Dominik T; Choi, Christine; Gollapudy, Suneeta; Pagel, Paul S

2016-04-01

Sporadic inclusion body myositis (IBM) is an inflammatory myopathy characterized by progressive asymmetric extremity weakness, oropharyngeal dysphagia, and the potential for exaggerated sensitivity to neuromuscular blockers and respiratory compromise. The authors describe their management of a patient with IBM undergoing urgent orthopedic surgery. An 81-year-old man with IBM suffered a left intertrochanteric femoral fracture after falling down stairs. His IBM caused progressive left proximal lower extremity, bilateral distal upper extremity weakness (left > right), and oropharyngeal dysphagia (solid food, pills). He denied dyspnea, exercise intolerance, and a history of aspiration. Because respiratory insufficiency resulting from diaphragmatic dysfunction and prolonged duration of action of neuromuscular blockers may occur in IBM, the authors avoided using a neuromuscular blocker. After applying cricoid pressure, anesthesia was induced using intravenous lidocaine, propofol, remifentanil followed by manual ventilation with inhaled sevoflurane in oxygen. Endotracheal intubation was accomplished without difficulty; anesthesia was then maintained using remifentanil and sevoflurane. The fracture was repaired with a trochanteric femoral nail. The patient was extubated without difficulty and made an uneventful recovery. In summary, there is a lack of consensus about the use of neuromuscular blockers in patients with IBM. The authors avoided these drugs and were able to easily secure the patient's airway and maintain adequate muscle relaxation using a balanced sevoflurane-remifentanil anesthetic. Clinical trials are necessary to define the pharmacology of neuromuscular blockers in patients with IBM and determine whether use of these drugs contributes to postoperative respiratory insufficiency in these vulnerable patients.

S-Nitrosoglutathione Reductase Deficiency-Induced S-Nitrosylation Results in Neuromuscular Dysfunction

PubMed Central

Montagna, Costanza; Di Giacomo, Giuseppina; Rizza, Salvatore; Cardaci, Simone; Ferraro, Elisabetta; Grumati, Paolo; De Zio, Daniela; Maiani, Emiliano; Muscoli, Carolina; Lauro, Filomena; Ilari, Sara; Bernardini, Sergio; Cannata, Stefano; Gargioli, Cesare; Ciriolo, Maria R.; Cecconi, Francesco; Bonaldo, Paolo

2014-01-01

Abstract Aims: Nitric oxide (NO) production is implicated in muscle contraction, growth and atrophy, and in the onset of neuropathy. However, many aspects of the mechanism of action of NO are not yet clarified, mainly regarding its role in muscle wasting. Notably, whether NO production-associated neuromuscular atrophy depends on tyrosine nitration or S-nitrosothiols (SNOs) formation is still a matter of debate. Here, we aim at assessing this issue by characterizing the neuromuscular phenotype of S-nitrosoglutathione reductase-null (GSNOR-KO) mice that maintain the capability to produce NO, but are unable to reduce SNOs. Results: We demonstrate that, without any sign of protein nitration, young GSNOR-KO mice show neuromuscular atrophy due to loss of muscle mass, reduced fiber size, and neuropathic behavior. In particular, GSNOR-KO mice show a significant decrease in nerve axon number, with the myelin sheath appearing disorganized and reduced, leading to a dramatic development of a neuropathic phenotype. Mitochondria appear fragmented and depolarized in GSNOR-KO myofibers and myotubes, conditions that are reverted by N-acetylcysteine treatment. Nevertheless, although atrogene transcription is induced, and bulk autophagy activated, no removal of damaged mitochondria is observed. These events, alongside basal increase of apoptotic markers, contribute to persistence of a neuropathic and myopathic state. Innovation: Our study provides the first evidence that GSNOR deficiency, which affects exclusively SNOs reduction without altering nitrotyrosine levels, results in a clinically relevant neuromuscular phenotype. Conclusion: These findings provide novel insights into the involvement of GSNOR and S-nitrosylation in neuromuscular atrophy and neuropathic pain that are associated with pathological states; for example, diabetes and cancer. Antioxid. Redox Signal. 21, 570–587. PMID:24684653

Endomicroscopy and electromyography of neuromuscular junctions in situ

PubMed Central

Brown, Rosalind; Dissanayake, Kosala N; Skehel, Paul A; Ribchester, Richard R

2014-01-01

Objective Electromyography (EMG) is used routinely to diagnose neuromuscular dysfunction in a wide range of peripheral neuropathies, myopathies, and neuromuscular degenerative diseases including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Definitive neurological diagnosis may also be indicated by the analysis of pathological neuromuscular innervation in motor-point biopsies. Our objective in this study was to preempt motor-point biopsy by combining live imaging with electrophysiological analysis of slow degeneration of neuromuscular junctions (NMJs) in vivo. Methods We combined conventional needle electromyography with fiber-optic confocal endomicroscopy (CEM), using an integrated hand-held, 1.5-mm-diameter probe. We utilized as a test bed, various axotomized muscles in the hind limbs of anaesthetized, double-homozygous thy1.2YFP16: WldS mice, which coexpress the Wallerian-degeneration Slow (WldS) protein and yellow fluorescent protein (YFP) in motor neurons. We also tested exogenous vital stains, including Alexa488-α-bungarotoxin; the styryl pyridinium dye 4-Di-2-Asp; and a GFP conjugate of botulinum toxin Type A heavy chain (GFP-HcBoNT/A). Results We show that an integrated EMG/CEM probe is effective in longitudinal evaluation of functional and morphological changes that take place over a 7-day period during axotomy-induced, slow neuromuscular synaptic degeneration. EMG amplitude declined in parallel with overt degeneration of motor nerve terminals. EMG/CEM was safe and effective when nerve terminals and motor endplates were selectively stained with vital dyes. Interpretation Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics. PMID:25540801

Neuromuscular Electrical Stimulation for Motor Restoration in Hemiplegia.

PubMed

Knutson, Jayme S; Fu, Michael J; Sheffler, Lynne R; Chae, John

2015-11-01

This article reviews the most common therapeutic and neuroprosthetic applications of neuromuscular electrical stimulation (NMES) for upper and lower extremity stroke rehabilitation. Fundamental NMES principles and purposes in stroke rehabilitation are explained. NMES modalities used for upper and lower limb rehabilitation are described, and efficacy studies are summarized. The evidence for peripheral and central mechanisms of action is also summarized. Copyright © 2015 Elsevier Inc. All rights reserved.

Myotonic dystrophytype 1 - report of non-24-h sleep-wake disorder with excessive daytime sleepiness.

PubMed

Filho, Lucio Huebra Pimentel; Gomes, Ana Carolina Dias; Gonçalves, Bruno; Tufik, Sergio; Coelho, Fernando Morgadinho

2018-05-15

Myotonic dystrophy (MD) is a neuromuscular disease with myotonia, progressive weakness, and involvement of CNS, heart, and gastrointestinal system. Excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (MD1) is related to sleep breathing diseases, restless leg syndrome, periodic limb movements during sleep and narcoleptic-like phenotype. However, authors highlight a central dysfunction of sleep regulation. We describe a 26-year-old, female, MD1 patient with EDS. Sleep diary/actigraphy evidenced two different circadian periods with values of 1442 and 1522 min. Agomelatine, 50 mg at night, was prescribed with improvement of the circadian rhythm and complaints of sleepiness. The identification of unanticipated causes of EDS, such as circadian rhythm disorders permits an appropriated treatment. As we know, it is the first relate of non-24-h sleep-wake disorder in patient with MD1. Sleep diary and actigraphy could be good options to investigate sleep-wake cycle disorder in patients with MD and EDS.

The mechanism of catalysis by type-II NADH:quinone oxidoreductases

PubMed Central

Blaza, James N.; Bridges, Hannah R.; Aragão, David; Dunn, Elyse A.; Heikal, Adam; Cook, Gregory M.; Nakatani, Yoshio; Hirst, Judy

2017-01-01

Type II NADH:quinone oxidoreductase (NDH-2) is central to the respiratory chains of many organisms. It is not present in mammals so may be exploited as an antimicrobial drug target or used as a substitute for dysfunctional respiratory complex I in neuromuscular disorders. NDH-2 is a single-subunit monotopic membrane protein with just a flavin cofactor, yet no consensus exists on its mechanism. Here, we use steady-state and pre-steady-state kinetics combined with mutagenesis and structural studies to determine the mechanism of NDH-2 from Caldalkalibacillus thermarum. We show that the two substrate reactions occur independently, at different sites, and regardless of the occupancy of the partner site. We conclude that the reaction pathway is determined stochastically, by the substrate/product concentrations and dissociation constants, and can follow either a ping-pong or ternary mechanism. This mechanistic versatility provides a unified explanation for all extant data and a new foundation for the development of therapeutic strategies. PMID:28067272

Using Rolling to Develop Neuromuscular Control and Coordination of the Core and Extremities of Athletes

PubMed Central

Voight, Michael L.; Cook, Gray; Gill, Lance

2009-01-01

Rolling is a movement pattern seldom used by physical therapists for assessment and intervention with adult clientele with normal neurologic function. Rolling, as an adult motor skill, combines the use of the upper extremities, core, and lower extremities in a coordinated manner to move from one posture to another. Rolling is accomplished from prone to supine and supine to prone, although the method by which it is performed varies among adults. Assessment of rolling for both the ability to complete the task and bilateral symmetry may be beneficial for use with athletes who perform rotationally-biased sports such as golf, throwing, tennis, and twisting sports such as dance, gymnastics, and figure skating. Additionally, when used as intervention techniques, the rolling patterns have the ability to affect dysfunction of the upper quarter, core, and lower quarter. By applying proprioceptive neuromuscular facilitation (PNF) principles, the therapist may assist patients and clients who are unable to complete a rolling pattern. Examples given in the article include distraction/elongation, compression, and manual contacts to facilitate proper rolling. The combined experience of the four authors is used to describe techniques for testing, assessment, and treatment of dysfunction, using case examples that incorporate rolling. The authors assert that therapeutic use of the developmental pattern of rolling with techniques derived from PNF is a hallmark in rehabilitation of patients with neurologic dysfunction, but can be creatively and effectively utilized in musculoskeletal rehabilitation. PMID:21509112

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2008-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Neuromuscular fatigue in racquet sports.

PubMed

Girard, Olivier; Millet, Grégoire P

2009-02-01

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Extraocular Muscles in Patients With Infantile Nystagmus

PubMed Central

Berg, Kathleen T.; Hunter, David G.; Bothun, Erick D.; Antunes-Foschini, Rosalia; McLoon, Linda K.

2013-01-01

Objective To test the hypothesis that the extraocular muscles (EOMs) of patients with infantile nystagmus have muscular and innervational adaptations that may have a role in the involuntary oscillations of the eyes. Methods Specimens of EOMs from 10 patients with infantile nystagmus and postmortem specimens from 10 control subjects were prepared for histologic examination. The following variables were quantified: mean myofiber cross-sectional area, myofiber central nucleation, myelinated nerve density, nerve fiber density, and neuromuscular junction density. Results In contrast to control EOMs, infantile nystagmus EOMs had significantly more centrally nucleated myofibers, consistent with cycles of degeneration and regeneration. The EOMs of patients with nystagmus also had a greater degree of heterogeneity in myofiber size than did those of controls, with no difference in mean myofiber cross-sectional area. Mean myelinated nerve density, nerve fiber density, and neuromuscular junction density were also significantly decreased in infantile nystagmus EOMs. Conclusions The EOMs of patients with infantile nystagmus displayed a distinct hypoinnervated phenotype. This represents the first quantification of changes in central nucleation and myofiber size heterogeneity, as well as decreased myelinated nerve, nerve fiber, and neuromuscular junction density. These results suggest that deficits in motor innervation are a potential basis for the primary loss of motor control. Clinical Relevance Improved understanding of the etiology of nystagmus may direct future diagnostic and treatment strategies. PMID:22411664

Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

PubMed Central

Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d’Amati, Giulia

2014-01-01

Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2−/−) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2−/− mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. PMID:24316510

Physiological and Functional Alterations after Spaceflight and Bed Rest.

PubMed

Mulavara, Ajitkumar P; Peters, Brian T; Miller, Chris A; Kofman, Igor S; Reschke, Millard F; Taylor, Laura C; Lawrence, Emily L; Wood, Scott J; Laurie, Steven S; Lee, Stuart M C; Buxton, Roxanne E; May-Phillips, Tiffany R; Stenger, Michael B; Ploutz-Snyder, Lori L; Ryder, Jeffrey W; Feiveson, Alan H; Bloomberg, Jacob J

2018-04-03

Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. A test battery comprised of 7 functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 days of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included Control and Exercise groups to examine the effects of exercise during bed rest. Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased heart rate to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function, however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. Bed rest data indicates that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the Exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular function, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.

Rapid reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery.

PubMed

Fujita, Ai; Ishibe, Natsuki; Yoshihara, Tatsuya; Ohashi, Jun; Makino, Hideichi; Ikeda, Mizuko; Setoguchi, Hidekazu

2014-06-01

Sugammadex rapidly reverses neuromuscular blockade (NMB) induced by rocuronium. NMB induced by rocuronium is prolonged in patients with liver dysfunction, because the drug is mainly excreted into the bile. However, the efficacy and safety of sugammadex in terms of reversing rocuronium-induced NMB in patients with liver dysfunction undergoing hepatic surgery have not been evaluated. This observational study investigated the efficacy and safety of sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Remifentanil/propofol anesthesia was administered to 31 patients: 15 patients in the control group, and 16 patients from a group with liver dysfunction. Rocuronium (0.6 mg/kg) was administered, followed by continuous infusion. The enrolled patients were then subdivided into two groups according to the dose of sugammadex. In the first group a single dose of sugammadex (2.0 mg/kg) was given at the reappearance of the second twitch (T2). In the second group a single dose of sugammadex (4.0 mg/kg) was given at the first twitch response if T2 did not reappear in 15 minutes after stopping rocuronium. The primary outcome was time from administration of sugammadex to recovery of a train-of-four ratio to 0.9. The dose of rocuronium required in the liver dysfunction group was lower than that in the control group (6.2 vs. 8.2 μg/kg/min, p = 0.002). The mean time from the administration of sugammadex to recovery of the train-of-four ratio to 0.9 was not significantly different between the liver dysfunction group and the control group (2.2 minutes vs. 2.0 minutes in the 2 mg/kg administration group, p = 0.44 and 1.9 minutes vs. 1.7 minutes in the 4 mg/kg administration group, p = 0.70, respectively). No evidence of recurarization was observed in any of the patients. Most of the adverse events were found to be mild and such events were not related to the use of sugammadex. None of the patients was eliminated from the study because of an adverse event. One patient died due to cholestatic liver cirrhosis because of repeated hepatic surgery. Sugammadex can rapidly reverse NMB after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Sugammadex was found to be safe and well tolerated. However, further studies of sugammadex under similar conditions should be conducted involving a large number of patients with liver dysfunction undergoing hepatic surgery. Copyright © 2014. Published by Elsevier B.V.

AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

ClinicalTrials.gov

2018-05-21

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Nervous System Diseases; Central Nervous System Diseases

DYNAMIC NEUROMUSCULAR STABILIZATION & SPORTS REHABILITATION

PubMed Central

Kobesova, Alena; Kolar, Pavel

2013-01-01

Dynamic neuromuscular (core) stability is necessary for optimal athletic performance and is not achieved purely by adequate strength of abdominals, spinal extensors, gluteals or any other musculature; rather, core stabilization is accomplished through precise coordination of these muscles and intra‐abdominal pressure regulation by the central nervous system. Understanding developmental kinesiology provides a framework to appreciate the regional interdependence and the inter‐linking of the skeleton, joints, musculature during movement and the importance of training both the dynamic and stabilizing function of muscles in the kinetic chain. The Dynamic Neuromuscular Stabilization (DNS) approach provides functional tools to assess and activate the intrinsic spinal stabilizers in order to optimize the movement system for both pre‐habilitation and rehabilitation of athletic injuries and performance. Level of Evidence: 5 PMID:23439921

Diaphragm Dysfunction in Critical Illness.

PubMed

Supinski, Gerald S; Morris, Peter E; Dhar, Sanjay; Callahan, Leigh Ann

2018-04-01

The diaphragm is the major muscle of inspiration, and its function is critical for optimal respiration. Diaphragmatic failure has long been recognized as a major contributor to death in a variety of systemic neuromuscular disorders. More recently, it is increasingly apparent that diaphragm dysfunction is present in a high percentage of critically ill patients and is associated with increased morbidity and mortality. In these patients, diaphragm weakness is thought to develop from disuse secondary to ventilator-induced diaphragm inactivity and as a consequence of the effects of systemic inflammation, including sepsis. This form of critical illness-acquired diaphragm dysfunction impairs the ability of the respiratory pump to compensate for an increased respiratory workload due to lung injury and fluid overload, leading to sustained respiratory failure and death. This review examines the presentation, causes, consequences, diagnosis, and treatment of disorders that result in acquired diaphragm dysfunction during critical illness. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Neuromuscular dysfunction in type 2 diabetes: underlying mechanisms and effect of resistance training.

PubMed

Orlando, Giorgio; Balducci, Stefano; Bazzucchi, Ilenia; Pugliese, Giuseppe; Sacchetti, Massimo

2016-01-01

Diabetic patients are at higher risk of developing physical disabilities than non-diabetic subjects. Physical disability appears to be related, at least in part, to muscle dysfunction. Several studies have reported reduced muscle strength and power under dynamic and static conditions in both the upper and lower limbs of patients with type 2 diabetes. Additional effects of diabetes include a reduction in muscle mass, quality, endurance and an alteration in muscle fibre composition, though the available data on these parameters are conflicting. The impact of diabetes on neuromuscular function has been related to the co-existence of long-term complications. Peripheral neuropathy has been shown to affect muscle by impairing motor nerve conduction. Also, vascular complications may contribute to the decline in muscle strength. However, muscle dysfunction occurs early in the course of diabetes and affects also the upper limbs, thus suggesting that it may develop independently of micro and macrovascular disease. A growing body of evidence indicates that hyperglycaemia may cause an alteration of the intrinsic properties of the muscle to generate force, via several mechanisms. Recently, resistance exercise has been shown to be an effective strategy to counteract the deterioration of muscular performance. High-intensity exercise seems to provide greater benefits than moderate-intensity training, whereas the effect of a power training is yet unknown. This article reviews the available literature on the impairment of muscle function induced by diabetes, the underlying mechanisms, and the effect of resistance training on this defect. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Magnesium replacement therapy.

PubMed

DiPalma, J R

1990-07-01

Magnesium is involved as a cofactor in many vital enzymatic reactions. It is also important in the maintenance of membrane electric potential. Diagnosis of magnesium disturbances must often be based on clinical judgment. Hypomagnesemia is frequently associated with hypokalemia and hypocalcemia; hypermagnesemia most often occurs in patients with acute or chronic renal failure. Hypomagnesemia presents as neuromuscular, central nervous system and cardiac abnormalities. Inadequate dietary intake of magnesium occurs in alcoholism, catabolic states and gastrointestinal diseases. Intravenous administration of magnesium can cause neuromuscular paralysis and cardiac arrhythmias.

Neurologic disorders of mineral metabolism and parathyroid disease.

PubMed

Agrawal, Lily; Habib, Zeina; Emanuele, Nicholas V

2014-01-01

Disorders of mineral metabolism may cause neurologic manifestations of the central and peripheral nervous systems. This is because plasma calcium stabilizes excitable membranes in the nerve and muscle tissue, magnesium is predominantly intracellular and is required for activation of many intracellular enzymes, and extracellular magnesium affects synaptic transmission. This chapter reviews abnormalities in electrolytes and minerals which can be associated with several neuromuscular symptoms including neuromuscular irritability, mental status changes, cardiac and smooth muscle changes, etc. © 2014 Elsevier B.V. All rights reserved.

Peripheral neuromuscular dysfunction and falls in an elderly cohort.

PubMed

Sorock, G S; Labiner, D M

1992-09-01

In a prospective study of 169 tenants of senior citizen housing in New Jersey in 1986-1987, the relations between tests of peripheral sensory and motor functions in the lower extremities and the rate of first falls were evaluated. The mean age of the cohort was 79.8 years. Fifty-seven persons fell at least once during the follow-up period (mean, 5.6 months). After adjustment for history of stroke, heart failure, emphysema, and use of a walker or cane, rate ratios for first falls were elevated in subjects with reduced toe joint position sense (rate ratio (RR) = 2.2) and sharp-dull discrimination (RR = 2.0), but to a lesser extent for reduced ankle strength (RR = 1.5). Presence of one or more of these three deficits was defined as a peripheral neuromuscular dysfunction and was associated with first falls after adjustment for multiple covariates (RR = 2.4, 95% confidence interval 1.3-4.5). Having two or all three sensory or motor deficits increased the rate of falling 3.9 times (95% confidence interval 2.1-7.0) compared with persons without these deficits. These data suggest that impaired sensory and motor function of the lower extremities plays an important role in falls in the elderly.

THE ROLE OF THE SCAPULA

PubMed Central

Voight, Michael L.

2013-01-01

Previously, the scapular musculature was often neglected in designing a rehabilitation protocol for the shoulder. In the past two decades a significant amount of research has been performed in order to help identify the role of the scapula in upper extremity function. Weakness of the scapular stabilizers and resultant altered biomechanics could result in: 1) abnormal stresses to the anterior capsular structures of the shoulder, 2) increased possibility of rotator cuff compression, and 3) decreased shoulder complex neuromuscular performance. This clinical commentary presents facts about the anatomy and biomechanics of the scapula and surrounding musculature, and describes the pathomechanics of scapular dysfunction. The focus is upon the assessment of dysfunction and retraining of the scapular musculature. Level of Evidence: 5 PMID:24175141

Influence of blood flow occlusion on the development of peripheral and central fatigue during small muscle mass handgrip exercise

PubMed Central

Broxterman, R M; Craig, J C; Smith, J R; Wilcox, S L; Jia, C; Warren, S; Barstow, T J

2015-01-01

Abstract The influence of the muscle metabolic milieu on peripheral and central fatigue is currently unclear. Moreover, the relationships between peripheral and central fatigue and the curvature constant (W ′) have not been investigated. Six men (age: 25 ± 4 years, body mass: 82 ± 10 kg, height: 179 ± 4 cm) completed four constant power handgrip tests to exhaustion under conditions of control exercise (Con), blood flow occlusion exercise (Occ), Con with 5 min post-exercise blood flow occlusion (Con + Occ), and Occ with 5 min post-exercise blood flow occlusion (Occ + Occ). Neuromuscular fatigue measurements and W ′ were obtained for each subject. Each trial resulted in significant peripheral and central fatigue. Significantly greater peripheral (79.7 ± 5.1% vs. 22.7 ± 6.0%) and central (42.6 ± 3.9% vs. 4.9 ± 2.0%) fatigue occurred for Occ than for Con. In addition, significantly greater peripheral (83.0 ± 4.2% vs. 69.0 ± 6.2%) and central (65.5 ± 14.6% vs. 18.6 ± 4.1%) fatigue occurred for Occ + Occ than for Con + Occ. W ′ was significantly related to the magnitude of global (r = 0.91) and peripheral (r = 0.83) fatigue. The current findings demonstrate that blood flow occlusion exacerbated the development of both peripheral and central fatigue and that post-exercise blood flow occlusion prevented the recovery of both peripheral and central fatigue. Moreover, the current findings suggest that W ′ may be determined by the magnitude of fatigue accrued during exercise. Key points Critical power represents an important threshold for neuromuscular fatigue development and may, therefore, dictate intensities for which exercise tolerance is determined by the magnitude of fatigue accrued. Peripheral fatigue appears to be constant across O2 delivery conditions for large muscle mass exercise, but this consistency is equivocal for smaller muscle mass exercise. We sought to determine the influence of blood flow occlusion during handgrip exercise on neuromuscular fatigue development and to examine the relationship between neuromuscular fatigue development and W ′. Blood flow occlusion influenced the development of both peripheral and central fatigue, thus providing further evidence that the magnitude of peripheral fatigue is not constant across O2 delivery conditions for small muscle mass exercise. W ′ appears to be related to the magnitude of fatigue accrued during exercise, which may explain the reported consistency of intramuscular metabolic perturbations and work performed for severe-intensity exercise. PMID:26104881

Sirt3 modulation may be beneficial in the treatment of ejaculation dysfunction.

PubMed

Mandava, Sree Harsha; Hellstrom, Wayne J G

2013-09-01

Disorders of ejaculation are the most common form of sexual dysfunction. The ejaculatory reflex consists of two phases: emission and expulsion. Premature ejaculation (PE) can arise from overactivity of the smooth muscles responsible for ejaculation. On the other side of the spectrum, delayed ejaculation occurs when an individual is unable to either reach orgasm within an adequate time frame or experiences no ejaculation. While premature ejaculation and to a lesser degree delayed ejaculation have been recognized for quite some time, no FDA approved treatment has been developed. Since both types of ejaculatory dysfunction have an underlying neuro-muscular component, this may be a target for future treatment strategies. We thereby hypothesize that modulation of the rhythmic contraction of the ejaculatory smooth muscles with either a Sirt3 activator or inhibitor may prove beneficial in treating either premature or delayed ejaculation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mitochondrial medicine for neurodegenerative diseases.

PubMed

Du, Heng; Yan, Shirley ShiDu

2010-05-01

Mitochondrial dysfunction has been reported in a wide array of neurological disorders ranging from neuromuscular to neurodegenerative diseases. Recent studies on neurodegenerative diseases have revealed that mitochondrial pathology is generally found in inherited or sporadic neurodegenerative diseases and is believed to be involved in the pathophysiological process of these diseases. Commonly seen types of mitochondrial dysfunction in neurodegenerative diseases include excessive free radical generation, lowered ATP production, mitochondrial permeability transition, mitochondrial DNA lesions, perturbed mitochondrial dynamics and apoptosis. Mitochondrial medicine as an emerging therapeutic strategy targeted to mitochondrial dysfunction in neurodegenerative diseases has been proven to be of value, though this area of research is still at in its early stage. In this article, we report on recent progress in the development of several mitochondrial therapies including antioxidants, blockade of mitochondrial permeability transition, and mitochondrial gene therapy as evidence that mitochondrial medicine has promise in the treatment of neurodegenerative diseases. 2010 Elsevier Ltd. All rights reserved.

Exchanging the minimal cell binding fragments of tetanus neurotoxin in botulinum neurotoxin A and B impacts their toxicity at the neuromuscular junction and central neurons.

PubMed

Höltje, Markus; Schulze, Sebastian; Strotmeier, Jasmin; Mahrhold, Stefan; Richter, Karin; Binz, Thomas; Bigalke, Hans; Ahnert-Hilger, Gudrun; Rummel, Andreas

2013-12-01

The modular four domain structure of clostridial neurotoxins supports the idea to reassemble individual domains from tetanus and botulinum neurotoxins to generate novel molecules with altered pharmacological properties. To treat disorders of the central nervous system drug transporter molecules based on catalytically inactive clostridial neurotoxins circumventing the passage of the blood-brain-barrier are desired. Such molecules can be produced based on the highly effective botulinum neurotoxin serotype A incorporating the retrograde axonal sorting property of tetanus neurotoxin which is supposed to be encoded within its C-terminal cell binding domain HC. The corresponding exchange of the tetanus neurotoxin HC-fragment in botulinum neurotoxin A yielded the novel hybrid molecule AATT which displayed decreased potency at the neuromuscular junction like tetanus neurotoxin but exerted equal activity in cortical neurons compared to botulinum neurotoxin A wild-type. Minimizing the tetanus neurotoxin cell binding domain to its N- or C-terminal half drastically reduced the potencies of AATA and AAAT in cortical neurons indicating that the structural motif mediating sorting of tetanus neurotoxin is predominantly encoded within the entire HC-fragment. However, the reciprocal exchange resulted in TTAA which showed a similar potency as tetanus neurotoxin at the neuromuscular junction indicating that the tetanus neurotoxin portion prevents a high potency as observed for botulinum neurotoxins. In conclusion, clostridial neurotoxin based inactivated drug transporter for targeting central neurons should contain the cell binding domain of tetanus neurotoxin to exert its tropism for the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

PubMed

Francio, Vinicius T; Boesch, Ron; Tunning, Michael

2015-03-01

Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

Miscellaneous neurologic or neuromuscular disorders in horses.

PubMed

Aleman, Monica

2011-12-01

NMD is an important cause of morbidity in horses. Signs of dysfunction could be variable depending on the specific area affected. NM disease can go unrecognized if a thorough evaluation is not performed in diseased horses. Electrodiagnostic testing is an area that has the potential to document and improve our understanding of NM disease yet is uncommonly performed. Keeping an open and observant mind will enhance our ability to search and find answers.

Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

PubMed Central

Hulse, Elspeth J.; Davies, James O. J.; Simpson, A. John; Sciuto, Alfred M.

2014-01-01

Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities. PMID:25419614

Current concepts in the pathophysiology, evaluation, and diagnosis of compartment syndrome

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Mubarak, S. J.

1998-01-01

This article reviews present knowledge of the pathophysiology and diagnosis of acute compartment syndromes. Recent results using compression of legs in normal volunteers provide objective data concerning local pressure thresholds for neuromuscular dysfunction in the anterior compartment. Results with this model indicate that a progression of neuromuscular deficits occurs when IMP increases to within 35 to 40 mm Hg of diastolic blood pressure. These findings provide useful information on the diagnosis and compression thresholds for acute compartment syndromes. Time factors are also important, however, and usually are incompletely known in most cases of acute compartment syndrome. Although the slit catheter is a very good technique for monitoring IMP during rest, these catheters and their associated extracorporeal transducer systems are not ideal. Recently developed miniature transducer-tipped catheters and, perhaps, future development of noninvasive techniques may provide accurate recordings of IMP in patients with acute compartment syndromes.

Development of a neuromuscular electrical stimulation protocol for sprint training.

PubMed

Russ, David W; Clark, Brian C; Krause, Jodi; Hagerman, Fredrick C

2012-09-01

Sprint training is associated with several beneficial adaptations in skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca(2+) release. Unfortunately, several patient populations (e.g., the elderly, those with cardiac dysfunction) that might derive great benefit from sprint exercise are unlikely to tolerate it. The purpose of this report was to describe the development of a tolerable neuromuscular electrical stimulation (NMES) protocol that induces skeletal muscle adaptations similar to those observed with sprint training. Our NMES protocol was modeled after a published sprint exercise protocol and used a novel electrode configuration and stimulation sequence to provide adequate training stimulus while maintaining subject tolerance. Nine young, healthy subjects (four men) began and completed the training protocol of the knee extensor muscles. All subjects completed the protocol, with ratings of discomfort far less than those reported in studies of traditional NMES. Training induced significant increases in SR Ca(2+) release and citrate synthase activity (~16% and 32%, respectively), but SR Ca(2+) uptake did not change. The percentage of myosin heavy chain IIx isoform was decreased significantly after training. At the whole muscle level, neither central activation nor maximum voluntary isometric contraction force were significantly altered, although isometric force did exhibit a trend toward an increase (~3%, P = 0.055). Surprisingly, the NMES training produced a significant increase in muscle cross-sectional area (~3%, P = 0.04). It seems that an appropriately designed NMES protocol can mimic many of the benefits of sprint exercise training, with a low overall time commitment and training volume. These findings suggest that NMES has the potential to bring the benefits of sprint exercise to individuals who are unable to tolerate traditional sprint training.

Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS

PubMed Central

Scarpa, Melania; Marchiori, Chiara; Sarasin, Gloria; Caputi, Valentina; Porzionato, Andrea; Giron, Maria Cecilia; Palù, Giorgio; Castagliuolo, Ignazio

2017-01-01

Background We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. Methods Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1β, IL-10 and IL-4. Results S. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100β protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins. Conclusions S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome. PMID:28732069

Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS.

PubMed

Brun, Paola; Scarpa, Melania; Marchiori, Chiara; Sarasin, Gloria; Caputi, Valentina; Porzionato, Andrea; Giron, Maria Cecilia; Palù, Giorgio; Castagliuolo, Ignazio

2017-01-01

We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1β, IL-10 and IL-4. S. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100β protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins. S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome.

Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges.

PubMed

Aboussouan, Loutfi S; Mireles-Cabodevila, Eduardo

2017-10-01

Normal sleep-related rapid eye movement sleep atonia, reduced lung volumes, reduced chemosensitivity, and impaired airway dilator activity become significant vulnerabilities in the setting of neuromuscular disease. In that context, the compounding effects of respiratory muscle weakness and disease-specific features that promote upper airway collapse or cause dilated cardiomyopathy contribute to various sleep-disordered breathing events. The reduction in lung volumes with neuromuscular disease is further compromised by sleep and the supine position, exaggerating the tendency for upper airway collapse and desaturation with sleep-disordered breathing events. The most commonly identified events are diaphragmatic/pseudo-central, due to a decrease in the rib cage contribution to the tidal volume during phasic rapid eye movement sleep. Obstructive and central sleep apneas are also common. Noninvasive ventilation can improve survival and quality of sleep but should be used with caution in the context of dilated cardiomyopathy or significant bulbar symptoms. Noninvasive ventilation can also trigger sleep-disordered breathing events, including ineffective triggering, autotriggering, central sleep apnea, and glottic closure, which compromise the potential benefits of the intervention by increasing arousals, reducing adherence, and impairing sleep architecture. Polysomnography plays an important diagnostic and therapeutic role by correctly categorizing sleep-disordered events, identifying sleep-disordered breathing triggered by noninvasive ventilation, and improving noninvasive ventilation settings. Optimal management may require dedicated hypoventilation protocols and a technical staff well versed in the identification and troubleshooting of respiratory events. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Quadriceps muscle function after exercise in men and women with a history of anterior cruciate ligament reconstruction.

PubMed

Kuenze, Christopher M; Hertel, Jay; Hart, Joseph M

2014-01-01

Sex differences in lower extremity neuromuscular function have been reported after anterior cruciate ligament reconstruction (ACLR). Research evidence supports different levels of fatigability in men and women and between patients with ACLR and healthy controls. The influence of sex on the response to continuous exercise in patients with ACLR is not clear. To compare quadriceps neuromuscular function after exercise between men and women with ACLR. Descriptive laboratory study. Laboratory. Twenty-six active volunteers (13 men [50%]: age = 24.1 ± 4.4 years, height = 179.1 ± 9.8 cm, mass = 80.1 ± 9.4 kg, months since surgery = 43.5 ± 37.0; 13 women [50%]: age = 24.2 ± 5.6 years, height = 163.0 ± 5.9 cm, mass = 62.3 ± 8.3 kg, months since surgery = 45.8 ± 42.7) with a history of unilateral primary ACLR at least 6 months earlier. Thirty minutes of continuous exercise comprising 5 separate 6-minute cycles, including 5 minutes of uphill walking and 1 minute of body-weight squatting and step-ups. Normalized knee-extension maximal voluntary isometric contraction torque, quadriceps superimposed-burst torque, and quadriceps central activation ratio before and after exercise. We performed separate 2 (sex: men, women) × 2 (time: preexercise, postexercise) repeated-measures analyses of variance for the 3 variables. Separate, independent-samples t tests were calculated to compare preexercise with postexercise change in all dependent variables between sexes. A significant group-by-time interaction was present for knee-extension torque (P = .04). The percentage reduction in knee-extension maximal voluntary isometric contraction torque (men = 1.94%, women = -10.32%; P = .02) and quadriceps central activation ratio (men = -1.45%, women = -8.69%; P = .03) experienced by men was less than that observed in women. In the presence of quadriceps dysfunction, female participants experienced greater-magnitude reductions in quadriceps function after 30 minutes of exercise than male participants. This indicates a reduced ability to absorb knee-joint loads, which may have significant implications for reinjury and joint osteoarthritis in women after ACLR.

Facilitatory effects of piracetam on excitability of motor nerve terminals and neuromuscular transmission.

PubMed

Hall, E D; Von Voigtlander, P F

1987-11-01

The possible in vivo facilitatory effects of the pyrrolidine acetamide no-otropic agent piracetam on neuromuscular transmission, were studied based upon reports of enhancement of central cholinergic function. Piracetam was shown to antagonize the lethal effects of the neuromuscular blocking agent hemicholinium-3 (HC-3), in female CF-1 mice when administered in a dose of 100 mg/kg (i.p.) simultaneously with HC-3. A 30 mg/kg (i.p.) dose of piracetam was ineffective by itself, although it potentiated the protective effects of choline (25 mg/kg i.p.). The analogs of piracetam, aniracetam, oxiracetam, pramiracetam and dupracetam also significantly antagonized the lethality of HC-3 at doses over a 30-300 mg/kg range. The acute facilitatory properties of piracetam on neuromuscular transmission were examined in more detail in vivo in the soleus nerve muscle preparation of the cat. A 100 mg/kg (i.v.) dose of piracetam, while having no effect on its own, significantly enhanced the ability of a 200 micrograms/kg (i.v.) dose of edrophonium to produce a potentiation of muscle contraction dependent on repetitive discharges in the soleus motor nerve terminals. In preparations in which the motor nerve terminals of the soleus were in a partially degenerated state as a result of section of the motor axons 48 hr earlier, piracetam acted to restore their sensitivity to edrophonium. Furthermore, in both normal and partially degenerated preparations, piracetam significantly decreased the neuromuscular blocking effects of a 150 micrograms/kg (i.v.) dose of d-tubocurarine. The mechanism of the neuromuscular facilitatory effects of piracetam on neuromuscular transmission is discussed in terms of an enhanced excitability of motor nerve terminals together with an action to increase the synthesis and/or release of acetylcholine.

Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis.

PubMed

Triadafilopoulos, George; Nguyen, Linda; Clarke, John O

2017-01-01

Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder. To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances. In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols. We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups. Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients.

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature

PubMed Central

Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-01-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K+ channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1V408A/+). Here, we investigated the neuromuscular transmission of Kv1.1V408A/+ ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve–muscle from Kv1.1+/+ and Kv1.1V408A/+ mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca2 + signals that occurred abnormally only in preparations dissected from Kv1.1V408A/+ mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca2 + homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K+ channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult. PMID:22609489

The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex.

PubMed

Langley, Ross J; McFadzean, Jillian; McCormack, Jon

2016-01-01

We describe a 2-day-old male infant who received rocuronium as part of general anesthesia for a tracheal esophageal fistula repair. Postoperatively, he had prolonged central and peripheral neuromuscular blockade despite cessation of the rocuronium infusion several hours previously. This case discusses the presumed central nervous system effects of rocuronium in a neonate and its effective reversal with sugammadex. © 2015 John Wiley & Sons Ltd.

Stimulated single fiber electromyography in the mouse: techniques and normative data

NASA Technical Reports Server (NTRS)

Gooch, C. L.; Mosier, D. R.

2001-01-01

As the number of new transgenic mouse models of human neuromuscular disease continues to increase, the development of sophisticated electrophysiologic techniques for assessing the peripheral nervous system in these models has become important. Neuromuscular junction (NMJ) dysfunction, in particular, is often not detectable by morphologic or other techniques. To enable sensitive testing of murine NMJ function, we developed and tested a method for stimulated single fiber electromyography (S-SFEMG) in the gastrocnemius muscles of anesthetized mice. Jitter was assessed by measuring the mean consecutive latency difference (MCD) of single fiber responses to sciatic nerve stimulation at 2 HZ. Mean MCD values in normothermic mice were in the range of 6-8 micros for different strains, with no MCD values exceeding 25 micros. Reduced core temperature (to 29 degrees--30 degrees C) resulted in increased jitter, whereas intubation and mechanical ventilation of mice did not alter these values. Intraperitoneal and intravenous injection of vecuronium, however, resulted in progressively increased jitter followed by blocking in continuously monitored fibers. These observations validate the utility of S-SFEMG in mice as an index of NMJ function under a variety of physiologic conditions, and suggest that a high safety factor for neuromuscular transmission exists at mouse NMJs. Copyright 2001 John Wiley & Sons, Inc.

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report

PubMed Central

Francio, Vinicius T.; Boesch, Ron; Tunning, Michael

2015-01-01

Objective: Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. Clinical features: A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Intervention and Outcome: Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient’s perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. Conclusion: PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option. PMID:25729084

Central Processing Dysfunctions in Children: A Review of Research.

ERIC Educational Resources Information Center

Chalfant, James C.; Scheffelin, Margaret A.

Research on central processing dysfunctions in children is reviewed in three major areas. The first, dysfunctions in the analysis of sensory information, includes auditory, visual, and haptic processing. The second, dysfunction in the synthesis of sensory information, covers multiple stimulus integration and short-term memory. The third area of…

Myotonic dystrophy type 1, daytime sleepiness and REM sleep dysregulation.

PubMed

Dauvilliers, Yves A; Laberge, Luc

2012-12-01

Myotonic dystrophy type 1 (DM1), or Steinert's disease, is the most common adult-onset form of muscular dystrophy. DM1 also constitutes the neuromuscular condition with the most significant sleep disorders including excessive daytime sleepiness (EDS), central and obstructive sleep apneas, restless legs syndrome (RLS), periodic leg movements in wake (PLMW) and periodic leg movements in sleep (PLMS) as well as nocturnal and diurnal rapid eye movement (REM) sleep dysregulation. EDS is the most frequent non-muscular complaint in DM1, being present in about 70-80% of patients. Different phenotypes of sleep-related problems may mimic several sleep disorders, including idiopathic hypersomnia, narcolepsy without cataplexy, sleep apnea syndrome, and periodic leg movement disorder. Subjective and objective daytime sleepiness may be associated with the degree of muscular impairment. However, available evidence suggests that DM1-related EDS is primarily caused by a central dysfunction of sleep regulation rather than by sleep fragmentation, sleep-related respiratory events or periodic leg movements. EDS also tends to persist despite successful treatment of sleep-disordered breathing in DM1 patients. As EDS clearly impacts on physical and social functioning of DM1 patients, studies are needed to identify the best appropriate tools to identify hypersomnia, and clarify the indications for polysomnography (PSG) and multiple sleep latency test (MSLT) in DM1. In addition, further structured trials of assisted nocturnal ventilation and randomized trials of central nervous system (CNS) stimulant drugs in large samples of DM1 patients are required to optimally treat patients affected by this progressive, incurable condition. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of inertial loading on wrist postural tremor in essential tremor.

PubMed

Héroux, M E; Pari, G; Norman, K E

2009-05-01

Determine the effect of inertial loading on the strength of motor unit entrainment and the synergistic/competitive interaction between central and mechanical reflex tremor components in subjects with essential tremor (ET). Twenty-three subjects with ET and 22 controls held their hand in an outstretched position while supporting sub-maximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Hand postural tremor and wrist extensor neuromuscular activity were recorded. Inertial loading resulted in a reduction in postural tremor in all ET subjects. The largest reduction in tremor amplitude occurred between 5% and 15% loads, which was associated with spectral separation of the mechanical reflex and central tremor components in a large number of ET subjects. Despite an increase in overall neuromuscular activity with inertial loading, EMG tremor spectral power did not increase with loading. The effect of inertial loading on postural tremor amplitude appears to be mediated in large part by its effect on the interaction between mechanical reflex and central tremor components. Also, ET is associated with a constant absolute level of motor unit entrainment. The amplitude of postural tremor is dependent on both central and peripheral factors, with proportionally greater motor unit entrainment occurring at low contraction intensities.

Heterogeneous neuromuscular activation within human rectus femoris muscle during pedaling.

PubMed

Watanabe, Kohei; Kouzaki, Motoki; Moritani, Toshio

2015-09-01

We investigated the effect of workload and the use of pedal straps on the spatial distribution of neuromuscular activation within the rectus femoris (RF) muscle during pedaling movements. Eleven healthy men performed submaximal pedaling exercises on an electrically braked ergometer at different workloads and with or without pedal straps. During these tasks, surface electromyograms (SEMGs) were recorded from the RF using 36 electrode pairs, and central locus activation (CLA) was calculated along the longitudinal line of the muscle. CLA moved markedly, indicating changes in spatial distribution of SEMG within the muscle, during a crank cycle under all conditions (P < 0.05). There were significant differences in CLA among different workloads and between those with and without pedal straps (P < 0.05). These results suggest that neuromuscular activation within the RF is regulated regionally by changes in workload and the use of pedal straps during pedaling. © 2014 Wiley Periodicals, Inc.

[Orthognathic surgery, master-piece of maxillo-facial surgery].

PubMed

Reychler, H

2001-01-01

Orthognathic surgery is this field of the maxillofacial surgery which aims to reposition the jaws or some segments of these jaws when masticatory dysfunctions are evident. This tridimensional repositioning in the craniofacial skeleton allows to restore the masticatory function by means of osteotomies, which must be followed either by preoperative simulated bony displacements or by callus bone distraction. Not only are the functional benefits evident on the dental, articular and neuromuscular levels, but also a facial esthetic harmony can almost be obtained.

Respiratory muscle dysfunction: a multicausal entity in the critically ill patient undergoing mechanical ventilation.

PubMed

Díaz, Magda C; Ospina-Tascón, Gustavo A; Salazar C, Blanca C

2014-02-01

Respiratory muscle dysfunction, particularly of the diaphragm, may play a key role in the pathophysiological mechanisms that lead to difficulty in weaning patients from mechanical ventilation. The limited mobility of critically ill patients, and of the diaphragm in particular when prolonged mechanical ventilation support is required, promotes the early onset of respiratory muscle dysfunction, but this can also be caused or exacerbated by other factors that are common in these patients, such as sepsis, malnutrition, advanced age, duration and type of ventilation, and use of certain medications, such as steroids and neuromuscular blocking agents. In this review we will study in depth this multicausal origin, in which a common mechanism is altered protein metabolism, according to the findings reported in various models. The understanding of this multicausality produced by the same pathophysiological mechanism could facilitate the management and monitoring of patients undergoing mechanical ventilation. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

Etiology and Recovery of Neuromuscular Fatigue following Competitive Soccer Match-Play

PubMed Central

Brownstein, Callum G.; Dent, Jack P.; Parker, Paul; Hicks, Kirsty M.; Howatson, Glyn; Goodall, Stuart; Thomas, Kevin

2017-01-01

Aim: Previous research into the etiology of neuromuscular fatigue following competitive soccer match-play has primarily focused on peripheral perturbations, with limited research assessing central nervous system function in the days post-match. The aim of the present study was to examine the contribution and time-course of recovery of central and peripheral factors toward neuromuscular fatigue following competitive soccer match-play. Methods: Sixteen male semi-professional soccer players completed a 90-min soccer match. Pre-, post- and at 24, 48, and 72 h participants completed a battery of neuromuscular, physical, and perceptual tests. Maximal voluntary contraction force (MVC) and twitch responses to electrical (femoral nerve) and transcranial magnetic stimulation (TMS) of the motor cortex during isometric knee-extension and at rest were measured to assess central nervous system (voluntary activation, VA) and muscle contractile (potentiated twitch force, Qtw, pot) function. Electromyography responses of the rectus femoris to single- and paired-pulse TMS were used to assess corticospinal excitability and short-interval intracortical inhibition (SICI), respectively. Fatigue and perceptions of muscle soreness were assessed via visual analog scales, and physical function was assessed through measures of jump (countermovement jump height and reactive strength index) and sprint performance. Results: Competitive match-play elicited significant post-match declines in MVC force (−14%, P < 0.001) that persisted for 48 h (−4%, P = 0.01), before recovering by 72 h post-exercise. VA (motor point stimulation) was reduced immediately post-match (−8%, P < 0.001), and remained depressed at 24 h (−5%, P = 0.01) before recovering by 48 h post-exercise. Qtw,pot was reduced post-match (−14%, P < 0.001), remained depressed at 24 h (−6%, P = 0.01), before recovering by 48 h post-exercise. No changes were evident in corticospinal excitability or SICI. Jump performance took 48 h to recover, while perceptions of fatigue persisted at 72 h. Conclusion: Competitive soccer match-play elicits substantial impairments in central nervous system and muscle function, requiring up to 48 h to resolve. The results of the study could have important implications for fixture scheduling, the optimal management of the training process, squad rotation during congested competitive schedules, and the implementation of appropriate recovery interventions. PMID:29118716

Experiences of living with myasthenia gravis: a qualitative study with Taiwanese people.

PubMed

Chen, Yu Tai; Shih, Fu Jin; Hayter, Mark; Hou, Chang Chiu; Yeh, Jiann Horng

2013-04-01

Myasthenia gravis (MG) is an auto-immune, neuromuscular disorder, which presents with symptoms of fluctuating muscle fatigue because of a dysfunction of the neuromuscular junction. This study explores the illness experience of patients with MG, their experiences of illness, its challenges, and their coping and support strategies. In-depth interviews were undertaken with nine participants with MG (six for a generalized type of MG, three for ocular type). Data were subjected to inductive content and thematic analysis. Four themes emerged from MG patients with associated subthemes. They were "perceptions of MG," "challenges of MG, "social support," and "adapting and adjusting to MG." The study reveals the way in which individuals respond to and cope with their diagnosis. The importance of social and peer support is a key factor as well as the development of psychological strategies to live with MG. The recognition that there was a need to recognize the role of Western medicine in controlling their disease was also an important finding.

Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning.

PubMed

Bird, Steven B; Krajacic, Predrag; Sawamoto, Keigo; Bunya, Naofumi; Loro, Emanuele; Khurana, Tejvir S

2016-06-01

Organophosphorus (OP) pesticide poisoning is a leading cause of morbidity and mortality in the developing world, affecting an estimated three million people annually. Much of the morbidity is directly related to muscle weakness, which develops 1-4 days after poisoning. This muscle weakness, termed the intermediate syndrome (IMS), leads to respiratory, bulbar, and proximal limb weakness and frequently necessitates the use of mechanical ventilation. While not entirely understood, the IMS is most likely due to persistently elevated acetylcholine (ACh), which activates nicotinic ACh receptors at the neuromuscular junction (NMJ). Thus, the NMJ is potentially a target-rich area for the development of new therapies for acute OP poisoning. In this manuscript, we discuss what is known about the IMS and studies investigating the use of nicotinic ACh receptor antagonists to prevent or mitigate NMJ dysfunction after acute OP poisoning. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction.

PubMed

Francis, Michael M; Evans, Susan P; Jensen, Michael; Madsen, David M; Mancuso, Joel; Norman, Kenneth R; Maricq, Andres Villu

2005-05-19

Nicotinic (cholinergic) neurotransmission plays a critical role in the vertebrate nervous system, underlies nicotine addiction, and nicotinic receptor dysfunction leads to neurological disorders. The C. elegans neuromuscular junction (NMJ) shares many characteristics with neuronal synapses, including multiple classes of postsynaptic currents. Here, we identify two genes required for the major excitatory current found at the C. elegans NMJ: acr-16, which encodes a nicotinic AChR subunit homologous to the vertebrate alpha7 subunit, and cam-1, which encodes a Ror receptor tyrosine kinase. acr-16 mutants lack fast cholinergic current at the NMJ and exhibit synthetic behavioral deficits with other known AChR mutants. In cam-1 mutants, ACR-16 is mislocalized and ACR-16-dependent currents are disrupted. The postsynaptic deficit in cam-1 mutants is accompanied by alterations in the distribution of cholinergic vesicles and associated synaptic proteins. We hypothesize that CAM-1 contributes to the localization or stabilization of postsynaptic ACR-16 receptors and presynaptic release sites.

Impacts of obesity and stress on neuromuscular fatigue development and associated heart rate variability.

PubMed

Mehta, R K

2015-02-01

Obesity and stress are independently associated with decrements in neuromuscular functions. The present study examined the interplay of obesity and stress on neuromuscular fatigue and associated heart rate variability (HRV). Forty-eight non-obese (18.5

Oxygen Administration Improves Survival but Worsens Cardiopulmonary Functions in Chlorine-exposed Rats.

PubMed

Okponyia, Obiefuna C; McGraw, Matthew D; Dysart, Marilyn M; Garlick, Rhonda B; Rioux, Jacqueline S; Murphy, Angela L; Roe, Gates B; White, Carl W; Veress, Livia A

2018-01-01

Chlorine is a highly reactive gas that can cause significant injury when inhaled. Unfortunately, its use as a chemical weapon has increased in recent years. Massive chlorine inhalation can cause death within 4 hours of exposure. Survivors usually require hospitalization after massive exposure. No countermeasures are available for massive chlorine exposure and supportive-care measures lack controlled trials. In this work, adult rats were exposed to chlorine gas (LD 58-67 ) in a whole-body exposure chamber, and given oxygen (0.8 Fi O 2 ) or air (0.21 Fi O 2 ) for 6 hours after baseline measurements were obtained. Oxygen saturation, vital signs, respiratory distress and neuromuscular scores, arterial blood gases, and hemodynamic measurements were obtained hourly. Massive chlorine inhalation caused severe acute respiratory failure, hypoxemia, decreased cardiac output, neuromuscular abnormalities (ataxia and hypotonia), and seizures resulting in early death. Oxygen improved survival to 6 hours (87% versus 42%) and prevented observed seizure-related deaths. However, oxygen administration worsened the severity of acute respiratory failure in chlorine-exposed rats compared with controls, with increased respiratory acidosis (pH 6.91 ± 0.04 versus 7.06 ± 0.01 at 2 h) and increased hypercapnia (180.0 ± 19.8 versus 103.2 ± 3.9 mm Hg at 2 h). In addition, oxygen did not improve neuromuscular abnormalities, cardiac output, or respiratory distress associated with chlorine exposure. Massive chlorine inhalation causes severe acute respiratory failure and multiorgan damage. Oxygen administration can improve short-term survival but appears to worsen respiratory failure, with no improvement in cardiac output or neuromuscular dysfunction. Oxygen should be used with caution after massive chlorine inhalation, and the need for early assisted ventilation should be assessed in victims.

Neuromuscular function of the quadriceps muscle during isometric maximal, submaximal and submaximal fatiguing voluntary contractions in knee osteoarthrosis patients

PubMed Central

Jacksteit, Robert; Jackszis, Mario; Feldhege, Frank; Weippert, Matthias; Mittelmeier, Wolfram; Bader, Rainer; Skripitz, Ralf; Behrens, Martin

2017-01-01

Introduction Knee osteoarthrosis (KOA) is commonly associated with a dysfunction of the quadriceps muscle which contributes to alterations in motor performance. The underlying neuromuscular mechanisms of muscle dysfunction are not fully understood. The main objective of this study was to analyze how KOA affects neuromuscular function of the quadriceps muscle during different contraction intensities. Materials and methods The following parameters were assessed in 20 patients and 20 healthy controls: (i) joint position sense, i.e. position control (mean absolute error, MAE) at 30° and 50° of knee flexion, (ii) simple reaction time task performance, (iii) isometric maximal voluntary torque (IMVT) and root mean square of the EMG signal (RMS-EMG), (iv) torque control, i.e. accuracy (MAE), absolute fluctuation (standard deviation, SD), relative fluctuation (coefficient of variation, CV) and periodicity (mean frequency, MNF) of the torque signal at 20%, 40% and 60% IMVT, (v) EMG-torque relationship at 20%, 40% and 60% IMVT and (vi) performance fatigability, i.e. time to task failure (TTF) at 40% IMVT. Results Compared to the control group, the KOA group displayed: (i) significantly higher MAE of the angle signal at 30° (99.3%; P = 0.027) and 50° (147.9%; P < 0.001), (ii) no significant differences in reaction time, (iii) significantly lower IMVT (-41.6%; P = 0.001) and tendentially lower RMS-EMG of the rectus femoris (-33.7%; P = 0.054), (iv) tendentially higher MAE of the torque signal at 20% IMVT (65.9%; P = 0.068), significantly lower SD of the torque signal at all three torque levels and greater MNF at 60% IMVT (44.8%; P = 0.018), (v) significantly increased RMS-EMG of the vastus lateralis at 20% (70.8%; P = 0.003) and 40% IMVT (33.3%; P = 0.034), significantly lower RMS-EMG of the biceps femoris at 20% (-63.6%; P = 0.044) and 40% IMVT (-41.3%; P = 0.028) and tendentially lower at 60% IMVT (-24.3%; P = 0.075) and (vi) significantly shorter TTF (-51.1%; P = 0.049). Conclusion KOA is not only associated with a deterioration of IMVT and neuromuscular activation, but also with an impaired position and torque control at submaximal torque levels, an altered EMG-torque relationship and a higher performance fatigability of the quadriceps muscle. It is recommended that the rehabilitation includes strengthening and fatiguing exercises at maximal and submaximal force levels. PMID:28505208

An anterior cruciate ligament injury does not affect the neuromuscular function of the non-injured leg except for dynamic balance and voluntary quadriceps activation.

PubMed

Zult, Tjerk; Gokeler, Alli; van Raay, Jos J A M; Brouwer, Reinoud W; Zijdewind, Inge; Hortobágyi, Tibor

2017-01-01

The function of the anterior cruciate ligament (ACL) patients' non-injured leg is relevant in light of the high incidence of secondary ACL injuries on the contralateral side. However, the non-injured leg's function has only been examined for a selected number of neuromuscular outcomes and often without appropriate control groups. We measured a broad array of neuromuscular functions between legs of ACL patients and compared outcomes to age, sex, and physical activity matched controls. Thirty-two ACL-deficient patients (208 ± 145 days post-injury) and active and less-active controls (N = 20 each) participated in the study. We measured single- and multi-joint neuromuscular function in both legs in each group and expressed the overall neuromuscular function in each leg by calculating a mean z-score across all neuromuscular measures. A group by leg MANOVA and ANOVA were performed to examine group and leg differences for the selected outcomes. After an ACL injury, duration (-4.3 h/week) and level (Tegner activity score of -3.9) of sports activity decreased and was comparable to less-active controls. ACL patients showed bilateral impairments in the star excursion balance test compared to both control groups (P ≤ 0.004) and for central activation ratio compared to active controls (P ≤ 0.002). There were between-leg differences within each group for maximal quadriceps and hamstring strength, voluntary quadriceps activation, star excursion balance test performance, and single-leg hop distance (all P < 0.05), but there were no significant differences in quadriceps force accuracy and variability, knee joint proprioception, and static balance. Overall neuromuscular function (mean z-score) did not differ between groups, but ACL patients' non-injured leg displayed better neuromuscular function than the injured leg (P < 0.05). Except for poorer dynamic balance and reduced quadriceps activation, ACL patients had no bilateral neuromuscular deficits despite reductions in physical activity after injury. Therapists can use the non-injured leg as a reference to assess the injured leg's function for tasks measured in the present study, excluding dynamic balance and quadriceps activation. Rehabilitation after an ACL injury should be mainly focused on the injured leg. III.

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units

PubMed Central

Sanchez, Gabriel N.; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L.; Schnitzer, Mark J.

2017-01-01

SUMMARY Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle’s contractile units. Despite the motor unit’s centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. PMID:26687220

In Vivo Imaging of Human Sarcomere Twitch Dynamics in Individual Motor Units.

PubMed

Sanchez, Gabriel N; Sinha, Supriyo; Liske, Holly; Chen, Xuefeng; Nguyen, Viet; Delp, Scott L; Schnitzer, Mark J

2015-12-16

Motor units comprise a pre-synaptic motor neuron and multiple post-synaptic muscle fibers. Many movement disorders disrupt motor unit contractile dynamics and the structure of sarcomeres, skeletal muscle's contractile units. Despite the motor unit's centrality to neuromuscular physiology, no extant technology can image sarcomere twitch dynamics in live humans. We created a wearable microscope equipped with a microendoscope for minimally invasive observation of sarcomere lengths and contractile dynamics in any major skeletal muscle. By electrically stimulating twitches via the microendoscope and visualizing the sarcomere displacements, we monitored single motor unit contractions in soleus and vastus lateralis muscles of healthy individuals. Control experiments verified that these evoked twitches involved neuromuscular transmission and faithfully reported muscle force generation. In post-stroke patients with spasticity of the biceps brachii, we found involuntary microscopic contractions and sarcomere length abnormalities. The wearable microscope facilitates exploration of many basic and disease-related neuromuscular phenomena never visualized before in live humans. Copyright © 2015 Elsevier Inc. All rights reserved.

[Design of an embedded stroke rehabilitation apparatus system based on Linux computer engineering].

PubMed

Zhuang, Pengfei; Tian, XueLong; Zhu, Lin

2014-04-01

A realizaton project of electrical stimulator aimed at motor dysfunction of stroke is proposed in this paper. Based on neurophysiological biofeedback, this system, using an ARM9 S3C2440 as the core processor, integrates collection and display of surface electromyography (sEMG) signal, as well as neuromuscular electrical stimulation (NMES) into one system. By embedding Linux system, the project is able to use Qt/Embedded as a graphical interface design tool to accomplish the design of stroke rehabilitation apparatus. Experiments showed that this system worked well.

Anesthetic management of an obstetric patient with MELAS syndrome: case report and literature review.

PubMed

Maurtua, M; Torres, A; Ibarra, V; DeBoer, G; Dolak, J

2008-10-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) is a mitochondrial disorder associated with neurologic, cardiac, neuromuscular, hepatic, metabolic and gastrointestinal dysfunction and potential anesthetic and obstetric complications. The case of a parturient with MELAS syndrome requiring labor analgesia is presented. A Medline literature search limited to the English language was undertaken to review cases of MELAS syndrome. Based on our experience and literature review, parturients with MELAS syndrome appear to benefit from neuraxial analgesia and anesthesia, which blunt excessive oxygen consumption and acidosis.

Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis

PubMed Central

Triadafilopoulos, George; Nguyen, Linda; Clarke, John O

2017-01-01

Background Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder. Aims To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances. Methods In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols. Results We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups. Conclusions Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients. PMID:29177065

Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

PubMed

Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

2012-09-01

Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or ischemic insult. Copyright © 2012 Elsevier Inc. All rights reserved.

Post-neonatal Tetanus in a PICU of a Developing Economy: Intensive Care Needs, Outcome and Predictors of Mortality.

PubMed

Angurana, Suresh Kumar; Jayashree, Muralidharan; Bansal, Arun; Singhi, Sunit; Nallasamy, Karthi

2018-02-01

To evaluate pediatric intensive care unit (PICU) needs, outcome and predictors of mortality in post-neonatal tetanus. Review of 30 consecutive post-neonatal tetanus cases aged 1 months to 12 years admitted to a PICU in north India over a period of 10 years (January 2006 to December 2015). Chronic suppurative otitis media was the commonest portal of entry. All received tetanus toxoid, human tetanus immunoglobulin (HTIG) and appropriate antibiotics; 7 (23.3%) received intrathecal HTIG. Common complications were respiratory failure, rhabdomyolysis, autonomic dysfunction, acute kidney injury and healthcare-associated infections. PICU needs were as follows: ventilation; benzodiazepine, morphine and magnesium sulfate infusion; neuromuscular blockers, inotropes, tracheostomy and renal replacement therapy. Mortality rate was 40%; severity Grade IIIb, autonomic dysfunction, use of vasoactive drugs and those who did not receive intrathecal HTIG were significantly associated with mortality. Post-neonatal tetanus is associated with high mortality, and PICU needs include management of spasms, autonomic dysfunction and complications and cardiorespiratory support. © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Effect of complement and its regulation on myasthenia gravis pathogenesis

PubMed Central

Kusner, Linda L; Kaminski, Henry J; Soltys, Jindrich

2015-01-01

Myasthenia gravis (MG) is primarily caused by antibodies directed towards the skeletal muscle acetylcholine receptor, leading to muscle weakness. Although these antibodies may induce compromise of neuromuscular transmission by blocking acetylcholine receptor function or antigenic modulation, the predominant mechanism of injury to the neuromuscular junction is complement-mediated lysis of the postsynaptic membrane. The vast majority of data to support the role of complement derives from experimentally acquired MG (EAMG). In this article, we review studies that demonstrate the central role of complement in EAMG and MG pathogenesis along with the emerging role of complement in T- and B-cell function, as well as the potential for complement inhibitor-based therapy to treat human MG. PMID:20477586

Neuronal Lipid Metabolism: Multiple Pathways Driving Functional Outcomes in Health and Disease

PubMed Central

Tracey, Timothy J.; Steyn, Frederik J.; Wolvetang, Ernst J.; Ngo, Shyuan T.

2018-01-01

Lipids are a fundamental class of organic molecules implicated in a wide range of biological processes related to their structural diversity, and based on this can be broadly classified into five categories; fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids and sphingolipids. Different lipid classes play major roles in neuronal cell populations; they can be used as energy substrates, act as building blocks for cellular structural machinery, serve as bioactive molecules, or a combination of each. In amyotrophic lateral sclerosis (ALS), dysfunctions in lipid metabolism and function have been identified as potential drivers of pathogenesis. In particular, aberrant lipid metabolism is proposed to underlie denervation of neuromuscular junctions, mitochondrial dysfunction, excitotoxicity, impaired neuronal transport, cytoskeletal defects, inflammation and reduced neurotransmitter release. Here we review current knowledge of the roles of lipid metabolism and function in the CNS and discuss how modulating these pathways may offer novel therapeutic options for treating ALS. PMID:29410613

A SMN-Dependent U12 Splicing Event Essential for Motor Circuit Function

PubMed Central

Lotti, Francesco; Imlach, Wendy L.; Saieva, Luciano; Beck, Erin S.; Hao, Le T.; Li, Darrick K.; Jiao, Wei; Mentis, George Z.; Beattie, Christine E.; McCabe, Brian D.; Pellizzoni, Livio

2012-01-01

SUMMARY Spinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency of the ubiquitous survival motor neuron (SMN) protein. To define the mechanisms of selective neuronal dysfunction in SMA, we investigated the role of SMN-dependent U12 splicing events in the regulation of motor circuit activity. We show that SMN deficiency perturbs splicing and decreases the expression of a subset of U12 intron-containing genes in mammalian cells and Drosophila larvae. Analysis of these SMN target genes identifies Stasimon as a novel protein required for motor circuit function. Restoration of Stasimon expression in the motor circuit corrects defects in neuromuscular junction transmission and muscle growth in Drosophila SMN mutants and aberrant motor neuron development in SMN-deficient zebrafish. These findings directly link defective splicing of critical neuronal genes induced by SMN deficiency to motor circuit dysfunction, establishing a molecular framework for the selective pathology of SMA. PMID:23063131

Transcriptomics of aged Drosophila motor neurons reveals a matrix metalloproteinase that impairs motor function.

PubMed

Azpurua, Jorge; Mahoney, Rebekah E; Eaton, Benjamin A

2018-04-01

The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner. Modulation of physiological aging also altered the rate of dMMP1 expression, validating dMMP1 expression as a bona fide aging biomarker for motor neurons. Temporally controlled overexpression of dMMP1 specifically in motor neurons was sufficient to induce deficits in climbing behavior and cause a decrease in neurotransmitter release at neuromuscular synapses. These deficits were reversible if the dMMP1 expression was shut off again immediately after the onset of motor dysfunction. Additionally, repression of dMMP1 enzymatic activity via overexpression of a tissue inhibitor of metalloproteinases delayed the onset of age-dependent motor dysfunction. MMPs are required for proper tissue architecture during development. Our results support the idea that matrix metalloproteinase 1 is acting as a downstream effector of antagonistic pleiotropy in motor neurons and is necessary for proper development, but deleterious when reactivated at an advanced age. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Slow transit constipation and lower urinary tract dysfunction.

PubMed

Queiroz Machado, V; Monteiro, A; Peçanha, A; Garcez da Fonseca, E

2015-12-01

Many theories have been proposed for the coexistence of constipation and lower urinary tract dysfunction (LUTD), such as bladder compression from a distended rectum and stimulation of sacral reflexes from a full rectum. In these cases, successful treatment of constipation should result in resolution of bladder symptoms. Some children have refractory constipation and others respond well to treatment, but once treatment is discontinued most children relapse back into their constipation. This may indicate the existence of a defect in colon motility, with a persistent peristalsis problem. The existence of a common neuromuscular disorder should be the base for both bladder and bowel dysfunction (BBD). To study colonic transit time (CTT) in children and adolescents with refractory constipation and lower urinary tract symptoms (LUTS). A total of 15 children (mean age 9.7 years) with refractory constipation and LUTS were evaluated with: standardized medical history; physical examination; bladder and bowel diaries; Bristol stool scale; Rome III criteria; Dysfunctional Voiding Scoring System (DVSS); ultrasound examination of the kidneys and urinary tract, and measurement of rectal diameter; urodynamic evaluation; and a CTT study using radiopaque markers. Urodynamic features were abnormal in 13 out of 15 children: 10 (66.7%) presented with detrusor overactivity (DO) and voiding dysfunction (VD), two (16.7%) had isolated DO, and one (8.3%) had a VD. The CTT study was abnormal in 12 out of 15 children: nine (60%) presented with slow transit constipation, three (20%) had outlet obstruction, and three (20%) had a normal CTT study. When comparing CTT and LUTD, nine (100%) children with slow transit constipation (STC) and three (50%) with no STC had DO (P = 0.04). Seven (77.8%) children with STC and three (50%) with no STC had VD (P = 0.29). The DVSS scores ranged from 6 to 21. The subgroup with STC had a DVSS score that was significantly higher than that of the subgroup with noF STC (Figure). The present study showed a high prevalence of STC in children and adolescents with refractory constipation and LUTS. This was in accordance with previous studies that have demonstrated a rate of 50-60% of STC in children with refractory constipation. In addition, DO was found to be associated with STC, which raises the chance for the existence of a common neuromuscular disorder to be the base for both bladder and bowel dysmotility. The limitation of this study was the number of participants. The present study demonstrated an association between DO and STC. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Exercise issues related to the neuromuscular function and adaptation to microgravity

NASA Technical Reports Server (NTRS)

Edgerton, Reggie

1989-01-01

Explored here is the question of whether astronauts can perform extravehicular activities effectively, efficiently, and productively. The loss of muscle mass, movement control, central nervous system function, muscle atrophy and fatigue, all consequent to weightlessness exposure, are discussed. The author recommends more research in these areas.

Venomous snake bites, scorpions, and spiders.

PubMed

Kularatne, S A M; Senanayake, Nimal

2014-01-01

Neurologic dysfunction due to natural neurotoxins is an important, but neglected, public health hazard in many parts of the world, particularly in the tropics. These toxins are produced by or found among a variety of live forms that include venomous snakes, arthropods such as scorpions, spiders, centipedes, stinging insects (Hymenoptera), ticks, certain poisonous fish, shellfish, crabs, cone shells, skin secretions of dart-poison frogs, and bacterial poisons such as botulinum toxin. These toxins commonly act on neuromuscular transmission at the neuromuscular junction where acetylcholine is the neurotransmitter, but in certain situations the toxins interfere with neurotransmitters such as GABA, noradrenaline, adrenaline, dopamine, and γ-aminobutyrate. Of the toxins, α-toxins and κ-toxins (e.g., Chinese krait, Bungarus multicinctus) act on the postsynaptic membrane, blocking the receptors, whilst β-toxin (e.g., common krait, B. caeruleus) acts on the presynaptic membrane, causing impairment of acetylcholine release. Conversely, dendrotoxins of the African mamba enhance acetylcholine release. The toxins of scorpions and spiders commonly interfere with voltage-gated ion channels. Clinically, the cardinal manifestation is muscle paralysis. In severe cases respiratory paralysis could be fatal. Effective antivenoms are the mainstay of treatment of envenoming, but their lack of availability is the major concern in the regions of the globe where they are desperately needed. Interestingly, some toxins have proved to be valuable pharmaceutical agents, while some others are widely exploited to study neuromuscular physiology and pathology. © 2014 Elsevier B.V. All rights reserved.

Effect of pyridostigmine on in vivo and in vitro respiratory muscle of mdx mice.

PubMed

Amancio, Gabriela de Cássia Sousa; Grabe-Guimarães, Andrea; Haikel, Dridi; Moreau, Johan; Barcellos, Neila Marcia Silva; Lacampagne, Alain; Matecki, Stefan; Cazorla, Olivier

2017-09-01

The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs. Copyright © 2017. Published by Elsevier B.V.

Neuromuscular dysfunction that may predict ACL injury risk: a case report.

PubMed

Saunders, Natalie; McLean, Scott G; Fox, Aaron S; Otago, Leonie

2014-06-01

This case report examined the neuromuscular function of a competitive female netball player six days prior to an incident where she sustained an acute anterior cruciate ligament injury during normal sports activity. Electromyography was used to examine activation onsets of four lower limb muscles (rectus femoris, biceps femoris, medial hamstrings and gluteus medius) relative to initial contact (IC) during netball-specific landings of varying complexity. The results of the injured participant were compared to the remaining participants in the study (n=8), and the injured participant's injured limb was compared to the contralateral limb. The injured participant was the only player to record delayed pre-injury muscle onsets after IC for all muscles tested in the injured limb, while her non-injured limb was comparable to the other participants tested. Furthermore, delayed muscle onset after IC occurred more frequently as landing complexity increased. This case report suggests that delayed muscle activity onset after IC during landing may be an important risk factor for ACL injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Presynaptic Disorders: Lambert-Eaton Myasthenic Syndrome and Botulism.

PubMed

Gable, Karissa L; Massey, Janice M

2015-08-01

Lambert-Eaton myasthenic syndrome (LEMS) and botulism are acquired presynaptic nerve terminal disorders of the neuromuscular junction. Lambert-Eaton myasthenic syndrome is an idiopathic or paraneoplastic autoimmune syndrome in which autoantibodies of the P/Q-type voltage-gated calcium channel play a role in decreasing the release of acetylcholine, resulting in clinical symptoms of skeletal muscle weakness, diminished reflexes, and autonomic symptoms. Paraneoplastic LEMS is most often associated with small cell lung cancer. Diagnosis is confirmed by positive serologic testing and electrophysiological studies, which display characteristic features of low compound muscle action potentials, a decrement at 3Hz repetitive nerve stimulation, and facilitation with exercise or high-frequency repetitive stimulation. Treatment involves cancer monitoring and treatment, 3,4-diaminopyridine, immunosuppressive medications, and acetylcholinesterase inhibitors. Botulism is another presynaptic disorder of neuromuscular transmission. Clinical features classically involve cranial and bulbar palsies followed by descending weakness of the limbs, respiratory failure, and autonomic dysfunction. Electrodiagnostic testing is important in the evaluation and diagnosis. Treatment is supportive, and administration of antitoxin is beneficial in selected cases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles

PubMed Central

Liu, An-Tang; Liu, Ben-Li; Lu, Li-Xuan; Chen, Gang; Yu, Da-Zhi; Zhu, Lie; Guo, Rong; Dang, Rui-Shan; Jiang, Hua

2014-01-01

The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm2), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm2). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18–0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the ‘design’ of their functional capability. In addition to improving our understanding of muscle anatomy and function, elucidation of forearm neuromuscular compartments architecture may ultimately provide information useful for selection of muscle subdivisions used in tendon transfer. PMID:24836406

Outcomes and complications of S2 alar iliac fixation technique in patients with neuromuscular scoliosis: experience in a third level pediatric hospital.

PubMed

Montero, Carlos Segundo; Meneses, David Alberto; Alvarado, Fernando; Godoy, Wilmer; Rosero, Diana Isabel; Ruiz, Jose Manuel

2017-12-01

Multiple techniques are utilized for distal fixation in patients with neuromuscular scoliosis. Although there is evidence of benefit with S2 alar iliac (S2AI) fixation, this remains controversial. The objective of this study is to evaluate the radiological outcomes and complications associated with this surgical technique in a pediatric population. An observational retrospective case series study was performed. All pediatric patients between January 2011 and February 2014 diagnosed with neuromuscular scoliosis associated with pelvic obliquity, which required surgery with fixation unto S2AI, were included. Clinical, radiological findings, and adverse events were presented with measures of central tendency. Comparison of deformity correction was carried out using a non-parametric analysis for related samples (Wilcoxon signed-rank test). Significance was set at P<0.05. A total of 31 patients diagnosed with neuromuscular scoliosis that met inclusion criteria were analyzed. The leading cause of neuromuscular scoliosis in 23 (74.2%) patients was spastic cerebral palsy (CP). The correction of pelvic obliquity in the immediate postoperative period was of 76%, which is statistically significant. The extent of correction that patients maintained at the end of the follow-up was analyzed, and it was found that there were no significant differences in this magnitude, compared with the immediate postoperative pelvic obliquity. The mean follow-up time was 9±7 months. Regarding postoperative adverse events, occurred in 64.5% of patients, the most common outcome was pneumonia (14.8%). The overall rate of complications related to instrumentation was low (1.9%), which corresponds to one patient with an intra-articular screw in the left hip that required repositioning. S2AI fixation for the treatment of neuromuscular scoliosis is a safe alternative, in which the onset of adverse events is related to the comorbidities of patients instead of the surgical procedure itself. An approximate correction of 76% of pelvic obliquity is maintained during the follow-up.

Isaacs' syndrome in a patient with dermatomyositis: case report and review of the literature.

PubMed

Lertnawapan, Ratchaya; Kulkantrakorn, Kongkiat

2017-08-01

This is a case report of Isaacs' syndrome in dermatomyositis. The patient presented with proximal muscle weakness, rash, elevated muscle enzyme, myopathic electromyograph and typical muscle biopsy. Ultimately he developed typical symptoms of Isaacs' syndrome which is an autoimmune channelopathy from voltage gated potassium channel antibody (anti-VGKC) leading to dysfunction of axonal discharge at neuromuscular junctions. It shares some similar characteristics with dermatomyositis such as autoimmunity, its association with malignancy and the response to treatment. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Botulinum toxin in myotonia congenita: it does not help against rigidity and pain.

PubMed

Dressler, Dirk; Adib Saberi, Fereshte

2014-05-01

Botulinum toxin (BT) is a potent local muscle relaxant with analgetic properties. Myotonia congenita (MC) is a genetic disorder producing muscle rigidity and pain. BT injected into the trapezius produced mild paresis, but no effect on rigidity and pain. There were no signs of systemic effects. Lack of BT efficacy on MC rigidity confirms its origin from muscle membrane dysfunction rather than from inappropriate neuromuscular activation. Lack of BT efficacy on pain could be caused by lack of anti-rigidity effect. It could also be due to separate non-muscular pain mechanisms unresponsive to BT.

Reliability of a Test Battery Designed for Quickly and Safely Assessing Diverse Indices of Neuromuscular Function

NASA Technical Reports Server (NTRS)

Spiering, Barry A.; Lee, Stuart M. C.; Mulavara, Ajitkumar P.; Bentley, Jason, R.; Buxton, Roxanne E.; Lawrence, Emily L.; Sinka, Joseph; Guilliams, Mark E.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

2010-01-01

Spaceflight affects nearly every physiological system. Spaceflight-induced alterations in physiological function translate to decrements in functional performance. Purpose: To develop a test battery for quickly and safely assessing diverse indices of neuromuscular performance. I. Quickly: Battery of tests can be completed in approx.30-40 min. II. Safely: a) No eccentric muscle actions or impact forces. b) Tests present little challenge to postural stability. III. Diverse indices: a) Strength: Excellent reliability (ICC = 0.99) b) Central activation: Very good reliability (ICC = 0.87) c) Power: Excellent reliability (ICC = 0.99) d) Endurance: Total work has excellent reliability (ICC = 0.99) e) Force steadiness: Poor reliability (ICC = 0.20 - 0.60) National

Sugammadex, a Neuromuscular Blockade Reversal Agent, Causes Neuronal Apoptosis in Primary Cultures

PubMed Central

Palanca, José M.; Aguirre-Rueda, Diana; Granell, Manuel V.; Aldasoro, Martin; Garcia, Alma; Iradi, Antonio; Obrador, Elena; Mauricio, Maria Dolores; Vila, Jose; Gil-Bisquert, Anna; Valles, Soraya L.

2013-01-01

Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system). Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types. PMID:23983586

Republished: Symptomatic reflux disease: the present, the past and the future

PubMed Central

Boeckxstaens, Guy; El-Serag, Hashem B; Smout, André J P M; Kahrilas, Peter J

2015-01-01

The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future. PMID:25583739

Symptomatic reflux disease: the present, the past and the future

PubMed Central

Boeckxstaens, Guy; El-Serag, Hashem B; Smout, André J P M; Kahrilas, Peter J

2014-01-01

The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future. PMID:24607936

Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase

PubMed Central

Puzzo, Francesco; Colella, Pasqualina; Biferi, Maria G.; Bali, Deeksha; Paulk, Nicole K.; Vidal, Patrice; Collaud, Fanny; Simon-Sola, Marcelo; Charles, Severine; Hardet, Romain; Leborgne, Christian; Meliani, Amine; Cohen-Tannoudji, Mathilde; Astord, Stephanie; Gjata, Bernard; Sellier, Pauline; van Wittenberghe, Laetitia; Vignaud, Alban; Boisgerault, Florence; Barkats, Martine; Laforet, Pascal; Kay, Mark A.; Koeberl, Dwight D.; Ronzitti, Giuseppe; Mingozzi, Federico

2018-01-01

Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics analysis and protein engineering, we developed transgenes encoding GAA that could be expressed and secreted by hepatocytes. Then, we used adeno-associated virus (AAV) vectors optimized for hepatic expression to deliver the GAA transgenes to Gaa knockout (Gaa−/−) mice, a model of Pompe disease. Therapeutic gene transfer to the liver rescued glycogen accumulation in muscle and the central nervous system, and ameliorated cardiac hypertrophy as well as muscle and respiratory dysfunction in the Gaa−/− mice; mouse survival was also increased. Secretable GAA showed improved therapeutic efficacy and lower immunogenicity compared to nonengineered GAA. Scale-up to nonhuman primates, and modeling of GAA expression in primary human hepatocytes using hepatotropic AAV vectors, demonstrated the therapeutic potential of AAV vector–mediated liver expression of secretable GAA for treating pathological glycogen accumulation in multiple tissues in Pompe disease. PMID:29187643

Effects of Short- and Long-Duration Space Flight on Neuromuscular Function

NASA Technical Reports Server (NTRS)

Buxton, Roxanne E.; Spiering, Barry A.; Ryder, Jeffrey W.; Ploutz-Snyder, Lori L.; Bloomberg, Jacob J.

2010-01-01

The Functional Task Tests (FTT) is an interdisciplinary study designed to correlate the changes in functional tasks (such as emergency egress, ladder climbing, and hatch opening) with changes in neuromuscular, cardiovascular, and sensorimotor function. One aspect of the FTT, the neuromuscular function test, is used to investigate the neuromuscular component underlying changes in the ability of astronauts to perform functional tasks (representative of critical mission tasks) safely and quickly after flight. PURPOSE: To describe neuromuscular function after short- and long-duration space flight. METHODS: To date, 5 crewmembers on short-duration (10- to 15-day) missions and 3 on long-duration missions have participated. Crewmembers were assessed 30 days before flight, on landing day (short-duration subjects only) and 1, 6, and 30 days after landing. The interpolated twitch technique, which utilizes a combination of maximal voluntary contractions and electrically evoked contractions, was used to assess the maximal voluntary isometric force (MIF) and central activation capacity of the knee extensors. Leg-press and bench-press devices were used to assess MIF and maximal dynamic power of the lower and upper body respectively. Specifically, power was measured during concentric-only ballistic throws of the leg-press sled and bench-press bar loaded to 40% and 30% of MIF respectively. RESULTS: Data are currently being collected from both Shuttle and ISS crewmembers. Emerging data indicate that measures of knee extensor muscle function are decreased with long-duration flight. DISCUSSION: The relationships between flight duration, neural drive, and muscle performance are of particular interest. Ongoing research will add to the current sample size and will focus on defining changes in muscle performance measures after long-duration space flight.

[CLINICAL STUDIES ON EFFECT OF ARTHROSCOPIC INTERCONDYLAR FOSSA ANGIOPLASTY ON ABILITY OF NEUROMUSCULAR CONTROL IN ELDERLY PATIENTS WITH KNEE OSTEOARTHRITIS].

PubMed

Huang, Jingmin; Wang, Haijiao; Wu, Jiang; Li, Dongchao; Li, Yuhong

2015-08-01

To study the effect of arthroscopic intercondylar fossa angioplasty on the ability of neuromuscular control of the knee joint in elderly patients with knee osteoarthritis (KOA). Between June 2012 and March 2013, 20 elderly patients with KOA and in accordance with inclusion and exclusion criteria underwent arthroscopic intercondylar fossa angioplasty (operation group), and 20 healthy elderly people served as control group. There was no significant difference in age, height, weight, and body mass index between 2 groups (P > 0.05). The proprioception capability (using passive regeneration test at measurement angles of 15, 30, and 60°) and quadriceps mobilization [including maximum voluntary contraction (MVC), central activation ratio (CAR), and activation deficit (AD)] were measured to avaluate the neuromuscular control of the knee; the Lysholm score was used to evaluate knee function. The above indexes were measured to assess the knee neuromuscular control and recovery of joint function in patients of operation group at 3, 6, and 9 months after operation. Compared with the control group, MVC, CAR, and Lysholm scores were significantly decreased, and the AD and passive knee angle difference were significantly increased in operation group (P < 0.05) before operation. With the time after operation, the Lysholm score, CAR, and MVC increased gradually, and the AD and the passive knee angle difference decreased gradually. There was no significant difference in the indexes between 2 groups at 9 months after operation (P > 0.05). Arthroscopic intercondylar fossa angioplasty can relieve ACL pressure, abrasion, and impact, which will recover the ability of neuromuscular control, increase proprioception and quadriceps mobilization capacity, and improve the joint function.

Metabotropic GABAB receptors mediate GABA inhibition of acetylcholine release in the rat neuromuscular junction.

PubMed

Malomouzh, Artem I; Petrov, Konstantin A; Nurullin, Leniz F; Nikolsky, Evgeny E

2015-12-01

Gamma-aminobutyric acid (GABA) is an amino acid which acts as a neurotransmitter in the central nervous system. Here, we studied the effects of GABA on non-quantal, spontaneous, and evoked quantal acetylcholine (ACh) release from motor nerve endings. We found that while the application of 10 μM of GABA had no effect on spontaneous quantal ACh release, as detected by the frequency of miniature endplate potentials, GABA reduced the non-quantal ACh release by 57%, as determined by the H-effect value. Finally, the evoked quantal ACh release, estimated by calculating the quantal content of full-sized endplate potentials (EPPs), was reduced by 34%. GABA's inhibitory effect remained unchanged after pre-incubation with picrotoxin, an ionotropic GABAA receptor blocker, but was attenuated following application of the GABAB receptor blocker CGP 55845, which itself had no effect on ACh release. An inhibitor of phospholipase C, U73122, completely prevented the GABA-induced decrease in ACh release. Immunofluorescence demonstrated the presence of both subunits of the GABAB receptor (GABAB R1 and GABAB R2) in the neuromuscular junction. These findings suggest that metabotropic GABAB receptors are expressed in the mammalian neuromuscular synapse and their activation results in a phospholipase C-mediated reduction in the intensity of non-quantal and evoked quantal ACh release. We investigated the effect of gamma-aminobutyric acid (GABA) on neuromuscular transmission. GABA reduced the non-quantal and evoked quantal release of acetylcholine. These effects are mediated by GABAB receptors and are implemented via phospholipase C (PLC) activation. Our findings suggest that in the mammalian neuromuscular synapse, metabotropic GABAB receptors are expressed and their activation results in a reduction in the intensity of acetylcholine release. © 2015 International Society for Neurochemistry.

Cardiorespiratory and neuromuscular deconditioning in fatigued and non-fatigued breast cancer survivors.

PubMed

Neil, Sarah E; Klika, Riggs J; Garland, S Jayne; McKenzie, Donald C; Campbell, Kristin L

2013-03-01

Fatigue is one of the most commonly reported side effects during treatment for breast cancer and can persist following treatment completion. Cancer-related fatigue after treatment is multifactorial in nature, and one hypothesized mechanism is cardiorespiratory and neuromuscular deconditioning. The purpose of this study was to compare cardiorespiratory and neuromuscular function in breast cancer survivors who had completed treatment and met the specified criteria for cancer-related fatigue and a control group of breast cancer survivors without fatigue. Participants in the fatigue (n = 16) and control group (n = 11) performed a maximal exercise test on a cycle ergometer for determination of peak power, power at lactate threshold, and VO(2) peak. Neuromuscular fatigue was induced with a sustained submaximal contraction of the right quadriceps. Central fatigue (failure of voluntary activation) was evaluated using twitch interpolation, and peripheral fatigue was measured with an electrically evoked twitch. Power at lactate threshold was lower in the fatigue group (p = 0.05). There were no differences between groups for power at lactate threshold as percentage of peak power (p = 0.10) or absolute or relative VO(2) peak (p = 0.08 and 0.33, respectively). When adjusted for age, the fatigue group had a lower power at lactate threshold (p = 0.02) and absolute VO(2) peak (p = 0.03). There were no differences between groups in change in any neuromuscular parameters after the muscle-fatiguing protocol. Findings support the hypothesis that cardiorespiratory deconditioning may play a role in the development and persistence of cancer-related fatigue following treatment. Future research into the use of exercise training to reduce cardiorespiratory deconditioning as a treatment for cancer-related fatigue is warranted to confirm these preliminary findings.

Mitochondrial Disorders of DNA Polymerase γ Dysfunction

PubMed Central

Zhang, Linsheng; Chan, Sherine S. L.; Wolff, Daynna J.

2011-01-01

Context Primary mitochondrial dysfunction is one of the most common causes of inherited disorders predominantly involving the neuromuscular system. Advances in the molecular study of mitochondrial DNA have changed our vision and our approach to primary mitochondrial disorders. Many of the mitochondrial disorders are caused by mutations in nuclear genes and are inherited in an autosomal recessive pattern. Among the autosomal inherited mitochondrial disorders, those related to DNA polymerase γ dysfunction are the most common and the best studied. Understanding the molecular mechanisms and being familiar with the recent advances in laboratory diagnosis of this group of mitochondrial disorders are essential for pathologists to interpret abnormal histopathology and laboratory results and to suggest further studies for a definitive diagnosis. Objectives To help pathologists better understand the common clinical syndromes originating from mutations in DNA polymerase γ and its associated proteins and use the stepwise approach of clinical, laboratory, and pathologic diagnosis of these syndromes. Data Sources Review of pertinent published literature and relevant Internet databases. Conclusions Mitochondrial disorders are now better recognized with the development of molecular tests for clinical diagnosis. A cooperative effort among primary physicians, diagnostic pathologists, geneticists, and molecular biologists with expertise in mitochondrial disorders is required to reach a definitive diagnosis. PMID:21732785

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

PubMed

van den Noort, J C; Bar-On, L; Aertbeliën, E; Bonikowski, M; Braendvik, S M; Broström, E W; Buizer, A I; Burridge, J H; van Campenhout, A; Dan, B; Fleuren, J F; Grunt, S; Heinen, F; Horemans, H L; Jansen, C; Kranzl, A; Krautwurst, B K; van der Krogt, M; Lerma Lara, S; Lidbeck, C M; Lin, J-P; Martinez, I; Meskers, C; Metaxiotis, D; Molenaers, G; Patikas, D A; Rémy-Néris, O; Roeleveld, K; Shortland, A P; Sikkens, J; Sloot, L; Vermeulen, R J; Wimmer, C; Schröder, A S; Schless, S; Becher, J G; Desloovere, K; Harlaar, J

2017-07-01

To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena. © 2017 EAN.

Screening and Assessment of Young Children.

ERIC Educational Resources Information Center

Friedlander, Bernard Z.

Most language development hazards in infancy and early childhood fall into the categories of auditory impairment, central integrative dysfunction, inadequate environmental support, and peripheral expressive impairment. Existing knowledge and techniques are inadequate to meet the screening and assessment problems of central integrative dysfunction,…

Central Auditory Nervous System Dysfunction in Echolalic Autistic Individuals.

ERIC Educational Resources Information Center

Wetherby, Amy Miller; And Others

1981-01-01

The results showed that all the Ss had normal hearing on the monaural speech tests; however, there was indication of central auditory nervous system dysfunction in the language dominant hemisphere, inferred from the dichotic tests, for those Ss displaying echolalia. (Author)

Increased Force Variability Is Associated with Altered Modulation of the Motorneuron Pool Activity in Autism Spectrum Disorder (ASD).

PubMed

Wang, Zheng; Kwon, Minhyuk; Mohanty, Suman; Schmitt, Lauren M; White, Stormi P; Christou, Evangelos A; Mosconi, Matthew W

2017-03-25

Force control deficits have been repeatedly documented in autism spectrum disorder (ASD). They are associated with worse social and daily living skill impairments in patients suggesting that developing a more mechanistic understanding of the central and peripheral processes that cause them may help guide the development of treatments that improve multiple outcomes in ASD. The neuromuscular mechanisms underlying force control deficits are not yet understood. Seventeen individuals with ASD and 14 matched healthy controls completed an isometric index finger abduction test at 60% of their maximum voluntary contraction (MVC) during recording of the first dorsal interosseous (FDI) muscle to determine the neuromuscular processes associated with sustained force variability. Central modulation of the motorneuron pool activation of the FDI muscle was evaluated at delta (0-4 Hz), alpha (4-10 Hz), beta (10-35 Hz) and gamma (35-60 Hz) frequency bands. ASD patients showed greater force variability than controls when attempting to maintain a constant force. Relative to controls, patients also showed increased central modulation of the motorneuron pool at beta and gamma bands. For controls, reduced force variability was associated with reduced delta frequency modulation of the motorneuron pool activity of the FDI muscle and increased modulation at beta and gamma bands. In contrast, delta, beta, and gamma frequency oscillations were not associated with force variability in ASD. These findings suggest that alterations of central mechanisms that control motorneuron pool firing may underlie the common and often impairing symptoms of ASD.

Botulinum Toxin Induces Muscle Paralysis and Inhibits Bone Regeneration in Zebrafish

PubMed Central

Recidoro, Anthony M.; Roof, Amanda C.; Schmitt, Michael; Worton, Leah E.; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J.; Srinivasan, Sundar; Moon, Randall T.; Gardiner, Edith M.; Kaminsky, Werner; Bain, Steven D.; Allan, Christopher H.; Gross, Ted S.; Kwon, Ronald Y.

2016-01-01

Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (e.g., development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study we developed a model of BTx-induced muscle paralysis in adult zebrafish, and examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders. PMID:24806738

Deficits in Endogenous Adenosine Formation by Ecto-5′-Nucleotidase/CD73 Impair Neuromuscular Transmission and Immune Competence in Experimental Autoimmune Myasthenia Gravis

PubMed Central

Cristina Costa, Ana; Guerra-Gomes, Sónia; Ferreirinha, Fátima; Magalhães-Cardoso, Maria Teresa; Correia-de-Sá, Paulo

2015-01-01

AMP dephosphorylation via ecto-5′-nucleotidase/CD73 is the rate limiting step to generate extracellular adenosine (ADO) from released adenine nucleotides. ADO, via A2A receptors (A2ARs), is a potent modulator of neuromuscular and immunological responses. The pivotal role of ecto-5′-nucleotidase/CD73, in controlling extracellular ADO formation, prompted us to investigate its role in a rat model of experimental autoimmune myasthenia gravis (EAMG). Results show that CD4+CD25+FoxP3+ regulatory T cells express lower amounts of ecto-5′-nucleotidase/CD73 as compared to controls. Reduction of endogenous ADO formation might explain why proliferation of CD4+ T cells failed upon blocking A2A receptors activation with ZM241385 or adenosine deaminase in EAMG animals. Deficits in ADO also contribute to neuromuscular transmission failure in EAMG rats. Rehabilitation of A2AR-mediated immune suppression and facilitation of transmitter release were observed by incubating the cells with the nucleoside precursor, AMP. These findings, together with the characteristic increase in serum adenosine deaminase activity of MG patients, strengthen our hypothesis that the adenosinergic pathway may be dysfunctional in EAMG. Given that endogenous ADO formation is balanced by ecto-5′-nucleotidase/CD73 activity and that A2ARs exert a dual role to restore use-dependent neurocompetence and immune suppression in myasthenics, we hypothesize that stimulation of the two mechanisms may have therapeutic potential in MG. PMID:25691808

Current Concepts in Ejaculatory Dysfunction

PubMed Central

Wolters, Jeffrey P; Hellstrom, Wayne J. G

2006-01-01

Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the α1-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality. PMID:17215997

Temperature-induced changes in neuromuscular function: central and peripheral mechanisms.

PubMed

Goodman, D; Hancock, P A; Runnings, D W; Brown, S L

1984-10-01

Three series of experimental tests were conducted on subjects under both elevated and depressed thermal conditions. Tripartite series consisted of whole-body immersion excepting the head, whole-body immersion excepting the head and response limb, and immersion of the discrete-response limb. Measures of physiological and behavioural responses were made at sequential .4 degrees C changes during whole-body immersions and approximately 5 degrees C changes of water temperature during the immersion of a limb only. Results suggested that velocity of nerve conduction decreased with thermal depression. Premotor, motor, simple, and choice reaction times varied differentially as a function of the hot and cold conditions. Implications of these differential effects on neuromuscular function are examined with respect to person-machine performance in artificially induced or naturally occurring extremes of ambient temperature.

The CNDR: collaborating to translate new therapies for Canadians.

PubMed

Korngut, Lawrence; Campbell, Craig; Johnston, Megan; Benstead, Timothy; Genge, Angela; Mackenzie, Alex; McCormick, Anna; Biggar, Douglas; Bourque, Pierre; Briemberg, Hannah; O'Connell, Colleen; Dojeiji, Suzan; Dooley, Joseph; Grant, Ian; Hogan, Gillian; Johnston, Wendy; Kalra, Sanjay; Katzberg, Hans D; Mah, Jean K; McAdam, Laura; McMillan, Hugh J; Melanson, Michel; Selby, Kathryn; Shoesmith, Christen; Smith, Garth; Venance, Shannon L; Wee, Joy

2013-09-01

Patient registries represent an important method of organizing "real world" patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry. We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR). The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 "index disease" patients. Another 618 "non-index" patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. "Index disease" patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS. The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

[Clinical use of neurostimulation].

PubMed

Schmidt, R A; Tanagho, E A

1990-07-01

Our experience is broad-based and covers a number of difficult conditions that urologists deal with regularly. In patients who have been followed for several years, consistency of stimulation response has been observed. Even after use of the stimulator for several months or years, symptoms often return as soon as the stimulation ceases in cases of a malfunction or electrode movement. Neurostimulation, however, is no panacea. Patients with specific muscular dysfunction, determined urodynamically, must be carefully selected. They must also be willing to cooperate actively in their care. Test stimulation of the sacral nerves has provided invaluable insight into the neuromuscular responses mediated by the S2-4 nerves and has thus helped identify dysfunction that is specifically associated with each of these nerves. It has also helped discern differences between the integrity of pelvic muscles and the capability of the patient to use these muscles. This information allows the urologist to focus on a specific muscular dysfunction and to re-educate the patient to use the pelvic musculature properly or, failing this, to use neurostimulation via an implant to modulate the dysfunction. There must be a strong commitment on the part of the physician. No two patients are alike. Attention to patients' symptoms, the pattern of muscle dysfunction found in the pelvis, the responses to test stimulation, the urodynamic findings with and without stimulation, and the underlying anxieties of patients, which can contribute to symptoms, are all important considerations. Neurostimulation is an exciting and fascinating addition to the urologist's armamentarium. Most important, urologists are now able to test the functional integrity of the pelvic musculature and specifically identify weakness and dysfunction. Therapy can now be based on an assessment of the functional capabilities of the nervous system involved in micturition control.

Properties of slow- and fast-twitch muscle fibres in a mouse model of amyotrophic lateral sclerosis.

PubMed

Atkin, Julie D; Scott, Rachel L; West, Jan M; Lopes, Elizabeth; Quah, Alvin K J; Cheema, Surindar S

2005-05-01

This investigation was undertaken to determine if there are altered histological, pathological and contractile properties in presymptomatic or endstage diseased muscle fibres from representative slow-twitch and fast-twitch muscles of SOD1 G93A mice in comparison to wildtype mice. In presymptomatic SOD1 G93A mice, there was no detectable peripheral dysfunction, providing evidence that muscle pathology is secondary to motor neuronal dysfunction. At disease endstage however, single muscle fibre contractile analysis demonstrated that fast-twitch muscle fibres and neuromuscular junctions are preferentially affected by amyotrophic lateral sclerosis-induced denervation, being unable to produce the same levels of force when activated by calcium as muscle fibres from their age-matched controls. The levels of transgenic SOD1 expression, aggregation state and activity were also examined in these muscles but there no was no preference for muscle fibre type. Hence, there is no simple correlation between SOD1 protein expression/activity, and muscle fibre type vulnerability in SOD1 G93A mice.

Motor Neuron Rescue in Spinal Muscular Atrophy Mice Demonstrates That Sensory-Motor Defects Are a Consequence, Not a Cause, of Motor Neuron Dysfunction

PubMed Central

Gogliotti, Rocky G.; Quinlan, Katharina A.; Barlow, Courtenay B.; Heier, Christopher R.; Heckman, C. J.

2012-01-01

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN rescue also corrects hyperexcitability in SMA motor neurons and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 d, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction. PMID:22423102

Tissue fluid pressures - From basic research tools to clinical applications

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Akeson, Wayne H.; Mubarak, Scott J.; Owen, Charles A.; Gershuni, David H.

1989-01-01

This paper describes clinical applications of two basic research tools developed and refined in the past 20 years: the wick catheter (for measuring tissue fluid pressure) and the colloid osmometer (for measuring osmotic pressure). Applications of the osmometer include estimations of the reduced osmotic pressure of sickle-cell hemoglobin with deoxygenation, and of reduced swelling pressure of human nucleus pulposus with hydration or upon action of certain enzymes. Clinical uses of the wick-catheter technique include an improvement of diagnosis and treatment of acute and chronic compartment syndromes, the elucidation of the tissue pressure thresholds for neuromuscular dysfunction, and the development of a better tourniquet for orthopedics.

Minimally invasive surgery for esophageal achalasia.

PubMed

Chen, Huan-Wen; Du, Ming

2016-07-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow's relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia.

Minimally invasive surgery for esophageal achalasia

PubMed Central

Chen, Huan-Wen

2016-01-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow’s relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia. PMID:27499977

Adducin at the Neuromuscular Junction in Amyotrophic Lateral Sclerosis: Hanging on for Dear Life

PubMed Central

Krieger, Charles; Wang, Simon Ji Hau; Yoo, Soo Hyun; Harden, Nicholas

2016-01-01

The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts. By controlling the levels of synaptic proteins, adducin can de-stabilize synaptic contacts. Interestingly, elevated levels of phosphorylated adducin have been reported in ALS patients and in a mouse model of the disease. Adducin is regulated by phosphorylation through protein kinase C (PKC), some isoforms of which exhibit Ca2+-dependence, raising the possibility that changes in intracellular Ca2+ might alter PKC activation and secondarily influence adducin phosphorylation. Furthermore, adducin has interactions with the alpha subunit of the Na+/K+-ATPase. Thus, the phosphorylation of adducin may secondarily influence synaptic stability at the NMJ and so influence pre- and post-synaptic integrity at the NMJ in ALS. PMID:26858605

Hypoxic ischemic encephalopathy in a case of intranuclear rod myopathy without any prenatal sentinel event.

PubMed

Kawase, Koya; Nishino, Ichizo; Sugimoto, Mari; Kouwaki, Masanori; Koyama, Norihisa; Yokochi, Kenji

2015-02-01

Intranuclear rod myopathy (IRM), a variant of nemaline myopathy, is characterized by the presence of nemaline bodies in myonuclei. We report a case of IRM presenting with hypoxic ischemic encephalopathy (HIE). There were no prenatal complications caused by fetal brain injury. Although no nemaline bodies were observed in the cytoplasm, intranuclear rods were observed in some fibers under light and electron microscopy. Molecular analysis identified a heterozygous variant, c.449C>T (p.Thr150Ile), in ACTA1. On magnetic resonance imaging at 9days of age, injuries to the basal ganglia, thalamus, and brainstem consistent with perinatal HIE were seen. Respiratory insufficiency at birth was strongly suspected to be the cause of HIE. Our case highlights that a patient with a congenital neuromuscular disorder who presents with severe respiratory dysfunction requiring substantial resuscitative efforts at birth can be complicated by HIE without any prenatal sentinel event. Prenatal detection of neuromuscular disorders, careful management of delivery, and neonatal resuscitation and adequate respiratory management are important in preventing irreversible brain injury in these patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Outcomes and complications of S2 alar iliac fixation technique in patients with neuromuscular scoliosis: experience in a third level pediatric hospital

PubMed Central

Montero, Carlos Segundo; Meneses, David Alberto; Alvarado, Fernando; Godoy, Wilmer; Ruiz, Jose Manuel

2017-01-01

Background Multiple techniques are utilized for distal fixation in patients with neuromuscular scoliosis. Although there is evidence of benefit with S2 alar iliac (S2AI) fixation, this remains controversial. The objective of this study is to evaluate the radiological outcomes and complications associated with this surgical technique in a pediatric population. Methods An observational retrospective case series study was performed. All pediatric patients between January 2011 and February 2014 diagnosed with neuromuscular scoliosis associated with pelvic obliquity, which required surgery with fixation unto S2AI, were included. Clinical, radiological findings, and adverse events were presented with measures of central tendency. Comparison of deformity correction was carried out using a non-parametric analysis for related samples (Wilcoxon signed-rank test). Significance was set at P<0.05. Results A total of 31 patients diagnosed with neuromuscular scoliosis that met inclusion criteria were analyzed. The leading cause of neuromuscular scoliosis in 23 (74.2%) patients was spastic cerebral palsy (CP). The correction of pelvic obliquity in the immediate postoperative period was of 76%, which is statistically significant. The extent of correction that patients maintained at the end of the follow-up was analyzed, and it was found that there were no significant differences in this magnitude, compared with the immediate postoperative pelvic obliquity. The mean follow-up time was 9±7 months. Regarding postoperative adverse events, occurred in 64.5% of patients, the most common outcome was pneumonia (14.8%). The overall rate of complications related to instrumentation was low (1.9%), which corresponds to one patient with an intra-articular screw in the left hip that required repositioning. Conclusions S2AI fixation for the treatment of neuromuscular scoliosis is a safe alternative, in which the onset of adverse events is related to the comorbidities of patients instead of the surgical procedure itself. An approximate correction of 76% of pelvic obliquity is maintained during the follow-up. PMID:29354726

The fusimotor and reafferent origin of the sense of force and weight

PubMed Central

Luu, Billy L; Day, Brian L; Cole, Jonathan D; Fitzpatrick, Richard C

2011-01-01

Abstract Signals associated with the command the brain sends to muscles are thought to create the sensation of heaviness when we lift an object. Thus, as a muscle is weakened by fatigue or partial paralysis (neuromuscular blockade), the increase in the motor command needed to lift a weight is thought to explain the increasing subjective heaviness of the lifted object. With different fatiguing contractions we approximately halved the force output of the thumb flexor muscles, which were then used to lift an object. For two deafferented subjects the perceived heaviness of the lifted object approximately doubled, in keeping with the central-signal theory. However, for normal subjects this resulted in objects feeling the same or lighter, inconsistent with the central-signal theory but consistent with the expected effects of the conditioning contractions on the sensitivity of peripheral receptors. In separate experiments we subjected the forearm muscles to complete paralysis with a non-depolarising neuromuscular blocking agent and then allowed them to recover to approximately half-force output. This also resulted in objects feeling lighter when lifted by the semi-paralysed thumb, even though the motor command to the motoneurons must have been greater. This is readily explained by reduced lift-related reafference caused by the prolonged paralysis of muscle spindle intrafusal fibres. We conclude that peripheral signals, including a major contribution from muscle spindles, normally give rise to the sense of exerted force. In concept, however, reafference from peripheral receptors may also be considered a centrally generated signal that traverses efferent and then afferent pathways to feed perceptual centres rather than one confined entirely to the central nervous system. These results therefore challenge the distinction between central- and peripheral-based perception, and the concept that muscle spindles provide only information about limb position and movement. PMID:21521756

The glutamate dehydrogenase GENE of Drosophila melanogaster: molecular analysis and expression.

PubMed

Papadopoulou, D; Louis, C

2000-09-01

Glutamate dehydrogenase is an enzyme that, in addition to its role in the energy metabolism in mitochondria, is involved in neuromuscular transmission. Here we present the structure and sequence of the Gdh gene of Drosophila melanogaster, as well as the analysis of its spatial and temporal pattern of expression. Unlike all other organisms analyzed so far, two forms of the enzyme, differing by the inclusion of 13 extra amino acids, are found in the fruitfly. We show the presence of Gdh mRNA in several tissues of the developing embryo, including the central nervous system, muscles and the alimentary tract. Moreover, we detect the localization of the Gdh protein in specific areas of the muscles, a fact that is consistent both with an involvement in energy metabolism and the role of glutamate as the major neuromuscular transmitter in Drosophila.

Increased Force Variability Is Associated with Altered Modulation of the Motorneuron Pool Activity in Autism Spectrum Disorder (ASD)

PubMed Central

Wang, Zheng; Kwon, MinHyuk; Mohanty, Suman; Schmitt, Lauren M.; White, Stormi P.; Christou, Evangelos A.; Mosconi, Matthew W.

2017-01-01

Force control deficits have been repeatedly documented in autism spectrum disorder (ASD). They are associated with worse social and daily living skill impairments in patients suggesting that developing a more mechanistic understanding of the central and peripheral processes that cause them may help guide the development of treatments that improve multiple outcomes in ASD. The neuromuscular mechanisms underlying force control deficits are not yet understood. Seventeen individuals with ASD and 14 matched healthy controls completed an isometric index finger abduction test at 60% of their maximum voluntary contraction (MVC) during recording of the first dorsal interosseous (FDI) muscle to determine the neuromuscular processes associated with sustained force variability. Central modulation of the motorneuron pool activation of the FDI muscle was evaluated at delta (0–4 Hz), alpha (4–10 Hz), beta (10–35 Hz) and gamma (35–60 Hz) frequency bands. ASD patients showed greater force variability than controls when attempting to maintain a constant force. Relative to controls, patients also showed increased central modulation of the motorneuron pool at beta and gamma bands. For controls, reduced force variability was associated with reduced delta frequency modulation of the motorneuron pool activity of the FDI muscle and increased modulation at beta and gamma bands. In contrast, delta, beta, and gamma frequency oscillations were not associated with force variability in ASD. These findings suggest that alterations of central mechanisms that control motorneuron pool firing may underlie the common and often impairing symptoms of ASD. PMID:28346344

An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease.

PubMed

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P N Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N A; Janssens, Wim; Polkey, Micheal I; Roca, Josep; Saey, Didier; Schols, Annemie M W J; Spruit, Martijn A; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D

2014-05-01

Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

PubMed Central

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P. N. Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R.; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N. A.; Janssens, Wim; Polkey, Micheal I.; Roca, Josep; Saey, Didier; Schols, Annemie M. W. J.; Spruit, Martijn A.; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D.

2014-01-01

Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. Results: We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Conclusions: Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed. PMID:24787074

Molecular, anatomical, and biochemical events associated with neurodegeneration in mice with Niemann-Pick type C disease.

PubMed

Li, Hao; Repa, Joyce J; Valasek, Mark A; Beltroy, Eduardo P; Turley, Stephen D; German, Dwight C; Dietschy, John M

2005-04-01

In Niemann-Pick type C (NPC) disease, cholesterol associated with either apoE or apoB100 is taken up by cells in all tissues, including the central nervous system, through clathrin-coated pits and becomes trapped in late endosomes and lysosomes. This study defines the functional, biochemical, and molecular events that ensue as nerve cell death occurs. In mice homozygous for a mutation in NPC1, neuromuscular dysfunction begins at 5 weeks and death occurs at 13 weeks of age. Cholesterol accumulates in every tissue in the body. Purkinje cell loss in the cerebellum begins at 3 to 4 weeks of age and is nearly complete by 11 weeks. This neurodegeneration in the cerebellum is associated with increases in the levels of mRNA for caspase 1, caspase 3, NPC2, LipA, apoE, apoD, glial fibrillary acidic protein, and tumor necrosis factor-alpha, but not for most target genes of the LXR nuclear receptors. The level for apoER2 is significantly reduced. These studies show there is a compensatory increase in NPC2 and LipA in an attempt to overcome the physiological defect caused by the mutation. Nevertheless, neurodegeneration proceeds utilizing apoptosis with activation of glial cells, increased apoE and apoD synthesis, and increased cholesterol turnover across the CNS.

Hemodialysis Tunneled Catheter Noninfectious Complications

PubMed Central

Miller, Lisa M.; MacRae, Jennifer M.; Kiaii, Mercedeh; Clark, Edward; Dipchand, Christine; Kappel, Joanne; Lok, Charmaine; Luscombe, Rick; Moist, Louise; Oliver, Matthew; Pike, Pamela; Hiremath, Swapnil

2016-01-01

Noninfectious hemodialysis catheter complications include catheter dysfunction, catheter-related thrombus, and central vein stenosis. The definitions, causes, and treatment strategies for catheter dysfunction are reviewed below. Catheter-related thrombus is a less common but serious complication of catheters, requiring catheter removal and systemic anticoagulation. In addition, the risk factors, clinical manifestation, and treatment options for central vein stenosis are outlined. PMID:28270922

Assessment of the paraspinal muscles of subjects presenting an idiopathic scoliosis: an EMG pilot study

PubMed Central

Gaudreault, Nathaly; Arsenault, A Bertrand; Larivière, Christian; DeSerres, Sophie J; Rivard, Charles-Hilaire

2005-01-01

Background It is known that the back muscles of scoliotic subjects present abnormalities in their fiber type composition. Some researchers have hypothesized that abnormal fiber composition can lead to paraspinal muscle dysfunction such as poor neuromuscular efficiency and muscle fatigue. EMG parameters were used to evaluate these impairments. The purpose of the present study was to examine the clinical potential of different EMG parameters such as amplitude (RMS) and median frequency (MF) of the power spectrum in order to assess the back muscles of patients presenting idiopathic scoliosis in terms of their neuromuscular efficiency and their muscular fatigue. Methods L5/S1 moments during isometric efforts in extension were measured in six subjects with idiopathic scoliosis and ten healthy controls. The subjects performed three 7 s ramp contractions ranging from 0 to 100% maximum voluntary contraction (MVC) and one 30 s sustained contraction at 75% MVC. Surface EMG activity was recorded bilaterally from the paraspinal muscles at L5, L3, L1 and T10. The slope of the EMG RMS/force (neuromuscular efficiency) and MF/force (muscle composition) relationships were computed during the ramp contractions while the slope of the EMG RMS/time and MF/time relationships (muscle fatigue) were computed during the sustained contraction. Comparisons were performed between the two groups and between the left and right sides for the EMG parameters. Results No significant group or side differences between the slopes of the different measures used were found at the level of the apex (around T10) of the major curve of the spine. However, a significant side difference was seen at a lower level (L3, p = 0.01) for the MF/time parameter. Conclusion The EMG parameters used in this study could not discriminate between the back muscles of scoliotic subjects and those of control subject regarding fiber type composition, neuromuscular efficiency and muscle fatigue at the level of the apex. The results of this pilot study indicate that compensatory strategies are potentially seen at lower level of the spine with these EMG parameters. PMID:15760468

Central obesity is an independent predictor of erectile dysfunction in older men.

PubMed

Riedner, Charles Edison; Rhoden, Ernani Luis; Ribeiro, Eduardo Porto; Fuchs, Sandra Costa

2006-10-01

There is a growing body of evidence in the literature correlating erectile dysfunction to obesity. We investigated the correlation of different anthropometric indexes of central obesity to erectile dysfunction. A cross-sectional study was performed including 256 consecutive men 40 years old or older. All men completed the International Index of Erectile Function, and were evaluated routinely with a clinical history, physical examination and blood analysis for fasting serum glucose, lipid profile and serum testosterone. Anthropometric measures included body mass index, waist circumference, sagittal abdominal diameter, maximal abdominal circumference, and waist-hip, waist-thigh, waist-height, sagittal abdominal diameter-thigh and sagittal abdominal diameter-height indexes. In men 40 to 60 years old the different anthropometric indexes of central obesity were not correlated with the presence of erectile dysfunction (p > 0.05). Men older than 60 years (41%, range 61 to 81) demonstrated an association among erectile dysfunction and waist-hip index (p = 0.04), waist-thigh index (p = 0.02), sagittal abdominal diameter (p = 0.03), sagittal abdominal diameter-height index (p = 0.02) and maximal abdominal circumference (p = 0.04). After logistic regression analysis an independent effect on the presence of erectile dysfunction was observed for waist-hip index (OR 8.56, 95% CI 1.44-50.73), sagittal abdominal diameter (OR 7.87, 95% CI 1.24-49.75), sagittal abdominal diameter-height index (OR 14.21, 95% CI 1.11-182.32), maximum abdominal circumference (OR 11.72, 95% CI 1.73-79.18) and waist circumference (OR 19.37, 95% CI 1.15-326.55). This study suggests that central obesity, assessed by several anthropometric indicators, is associated to the presence of erectile dysfunction in men older than 60 years. Sagittal abdominal diameter, sagittal abdominal diameter-height index, maximum abdominal circumference, waist circumference and waist-hip index were useful indicators to predict the presence of erectile dysfunction.

Rhombencephalitis associated with Dengue fever.

PubMed

Verma, Rajesh; Bharti, Kavita; Mehta, Mannan; Bansod, Amrit

2016-05-01

Dengue infection is gradually disseminating throughout the world in alarming proportions. It is a arbovirus infection,transmitted by aedes mosquitoes. It is a multi-systemic disorder associated with varied neurological complications. There is increased trend of development of neurological complications in dengue fever. The neurological complications arising due to dengue infection can be categorized into central and neuromuscular complications. The central nervous system disorders reported with dengue fever are encephalopathy,encephalitis and myelitis.Here we report a case of rhombencephalitis associated with dengue fever. The literature does not mention rhombencephalitis occurring with dengue illness. Copyright © 2016 Elsevier B.V. All rights reserved.

Peripheral Distribution of Thrombus Does Not Affect Outcomes After Surgical Pulmonary Embolectomy.

PubMed

Pasrija, Chetan; Shah, Aakash; George, Praveen; Mohammed, Isa; Brigante, Francis A; Ghoreishi, Mehrdad; Jeudy, Jean; Taylor, Bradley S; Gammie, James S; Griffith, Bartley P; Kon, Zachary N

2018-04-04

Thrombus located distal to the main or primary pulmonary arteries has been previously viewed as a relative contraindication to surgical pulmonary embolectomy. We compared outcomes for surgical pulmonary embolectomy for submassive and massive pulmonary embolism (PE) in patients with central versus peripheral thrombus burden. All consecutive patients (2011-2016) undergoing surgical pulmonary embolectomy at a single center were retrospectively reviewed. Based on computed tomographic angiography of each patient, central PE was defined as any thrombus originating within the lateral pericardial borders (main or right/left pulmonary arteries). Peripheral PE was defined as thrombus exclusively beyond the lateral pericardial borders, involving the lobar pulmonary arteries or distal. The primary outcome was in-hospital and 90-day survival. 70 patients were identified: 52 (74%) with central PE and 18 (26%) with peripheral PE. Preoperative vital signs and right ventricular dysfunction were similar between the two groups. Compared to the central PE cohort, operative time was significantly longer in the peripheral PE group (191 vs. 210 minutes, p<0.005)). Median right ventricular dysfunction decreased from moderate dysfunction preoperatively to no dysfunction at discharge in both groups. Overall 90-day survival was 94%, with 100% survival in patients with submassive PE in both cohorts. This single center experience demonstrates excellent overall outcomes for surgical pulmonary embolectomy with resolution of right ventricular dysfunction, and comparable morbidity and mortality for central and peripheral PE. In an experienced center and when physiologically warranted, surgical pulmonary embolectomy for peripheral distribution of thrombus is both technically feasible and effective. Copyright © 2018. Published by Elsevier Inc.

Load-dependent regulation of neuromuscular system

NASA Technical Reports Server (NTRS)

Ohira, Yoshinobu; Kawano, Fuminori; Stevens, James L.; Wang, Xiao D.; Ishihara, Akihiko

2004-01-01

Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.

Functional Electrical Stimulation and Spinal Cord Injury

PubMed Central

Ho, Chester H.; Triolo, Ronald J.; Elias, Anastasia L.; Kilgore, Kevin L.; DiMarco, Anthony F.; Bogie, Kath; Vette, Albert H.; Audu, Musa; Kobetic, Rudi; Chang, Sarah R.; Chan, K. Ming; Dukelow, Sean; Bourbeau, Dennis J.; Brose, Steven W.; Gustafson, Kenneth J.; Kiss, Zelma; Mushahwar, Vivian K.

2015-01-01

Synopsis Spinal cord injuries (SCI) can disrupt communications between the brain and the body, leading to a loss of control over otherwise intact neuromuscular systems. The use of electrical stimulation (ES) of the central and peripheral nervous system can take advantage of these intact neuromuscular systems to provide therapeutic exercise options, to allow functional restoration, and even to manage or prevent many medical complications following SCI. The use of ES for the restoration of upper extremity, lower extremity and truncal functions can make many activities of daily living a potential reality for individuals with SCI. Restoring bladder and respiratory functions and preventing pressure ulcers may significantly decrease the morbidity and mortality following SCI. Many of the ES devices are already commercially available and should be considered by all SCI clinicians routinely as part of the lifelong rehabilitation care plan for all eligible individuals with SCI. PMID:25064792

[Neuromuscular electric stimulation therapy in otorhinolaryngology].

PubMed

Miller, S; Kühn, D; Jungheim, M; Schwemmle, C; Ptok, M

2014-02-01

Animal experiments have shown that after specific nerve traumatization, neuromuscular electrostimulation (NMES) can promote nerve regeneration and reduce synkinesia without negatively interfering with normal regeneration processes. NMES is used routinely in physical rehabilitation medicine. This systematic literature search in the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the DAHTA database, the Health Technology Assessment Database and MEDLINE or PubMed considered studies on the use of NMES in otorhinolaryngology that have been published in German or English. The search identified 180 studies. These were evaluated and relevant studies were included in the further evaluation. In the fields of otorhinolaryngology and phoniatry/paediatric audiology, clinical studies investigating the effects of NMES on facial and laryngeal paresis, as well as dysphonia and dysphagia have been carried out. The evidence collected to date is encouraging; particularly for the treatment of certain forms of dysphagia and laryngeal paresis.

Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls

PubMed Central

Leininger, Elizabeth C.; Kelley, Darcy B.

2013-01-01

Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated  Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors. PMID:23407829

Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls.

PubMed

Leininger, Elizabeth C; Kelley, Darcy B

2013-04-07

Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors.

Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze.

PubMed

Emamghoreishi, Masoumeh; Khasaki, Mohammad; Aazam, Maryam Fath

2005-01-15

The clinical applications of benzodiazepines as anxiolytics are limited by their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Among medicinal plants, Coriandrum sativum L. has been recommended for relief of anxiety and insomnia in Iranian folk medicine. Nevertheless, no pharmacological studies have thus far evaluated its effects on central nervous system. Therefore, the aim of this study was to examine if the aqueous extract of Coriandrum sativum seed has anxiolytic effect in mice. Additionally, its effect on spontaneous activity and neuromuscular coordination were evaluated. The anxiolytic effect of aqueous extract (10, 25, 50, 100 mg/kg, i.p.) was examined in male albino mice using elevated plus-maze as an animal model of anxiety. The effects of the extract on spontaneous activity and neuromuscular coordination were assessed using Animex Activity Meter and rotarod, respectively. In the elevated plus-maze, aqueous extract at 100 mg/kg showed an anxiolytic effect by increasing the time spent on open arms and the percentage of open arm entries, compared to control group. Aqueous extract at 50, 100 and 500 mg/kg significantly reduced spontaneous activity and neuromuscular coordination, compared to control group. These results suggest that the aqueous extract of Coriandrum sativum seed has anxiolytic effect and may have potential sedative and muscle relaxant effects.

Clinical features and ryanodine receptor type 1 gene mutation analysis in a Chinese family with central core disease.

PubMed

Chang, Xingzhi; Jin, Yiwen; Zhao, Haijuan; Huang, Qionghui; Wang, Jingmin; Yuan, Yun; Han, Ying; Qin, Jiong

2013-03-01

Central core disease is a rare inherited neuromuscular disorder caused by mutations in ryanodine receptor type 1 gene. The clinical phenotype of the disease is highly variable. We report a Chinese pedigree with central core disease confirmed by the gene sequencing. All 3 patients in the family presented with mild proximal limb weakness. The serum level of creatine kinase was normal, and electromyography suggested myogenic changes. The histologic analysis of muscle biopsy showed identical central core lesions in almost all of the muscle fibers in the index case. Exon 90-106 in the C-terminal domain of the ryanodine receptor type 1 gene was amplified using polymerase chain reaction. One heterozygous missense mutation G14678A (Arg4893Gln) in exon 102 was identified in all 3 patients. This is the first report of a familial case of central core disease confirmed by molecular study in mainland China.

The effects of neuromuscular electrical stimulation at different frequencies on the activations of deep abdominal stabilizing muscles.

PubMed

Cho, Hee Kyung; Jung, Gil Su; Kim, Eun Hyuk; Cho, Yun Woo; Kim, Sang Woo; Ahn, Sang Ho

2016-01-01

Low back pain is associated with transversus abdominis (TrA) dysfunction. Recently, it was proposed that Neuromuscular Electrical Stimulation (NMES) could be used to stimulate deep abdominal muscle contractions and improve lumbopelvic stability. The purpose of this study was to determine the optimal stimulation frequency required during NMES for the activation of deep abdominal muscles. Twenty healthy volunteers between the ages of 24 and 32 were included. The portable research-stimulator was applied using a 10 second contraction time, and a 10 second resting time at 20 Hz, 50 Hz, and 80 Hz. Changes in muscle thicknesses were determined for the TrA, obliquus internus (OI), and obliquus externus (OE) by real time ultrasound imaging. Significant thickness increases in the TrA, OI, and OE were observed during NMES versus the resting state (p < 0.05). Of the frequencies examined, 50 Hz NMES produced the greatest increase in TrA thickness (1.33 fold as compared with 1.22 fold at 20 Hz and 1.21 fold at 80 Hz) (p < 0.05). Our results indicate that NMES can preferentially stimulate contractions in deep abdominal stabilizing muscles. Most importantly, 50 Hz NMES produced greater muscle thickness increases than 20 or 80 Hz.

Prevalence and determinants of erectile dysfunction among diabetic patients attending in hospitals of central and northwestern zone of Tigray, northern Ethiopia: a cross-sectional study.

PubMed

Seid, Awole; Gerensea, Hadgu; Tarko, Shambel; Zenebe, Yosef; Mezemir, Rahel

2017-03-15

The prevalence of erectile dysfunction among diabetic men varies between 35-90%. Although erectile dysfunction is widespread among men with diabetes, the condition often remains undiagnosed and demands appropriate assessment and prompt treatment. Erectile dysfunction can affect all aspects of a patient's life including physical, emotional, social, sexual, and relationships. The main aim of this study is to determine the prevalence and determinants of erectile dysfunction among diabetic patients attending hospitals in the Central and Northwest zone of Tigray, Ethiopia. A hospital based cross-sectional study was conducted on 249 male diabetic patients attending five hospitals in the Central and Northwestern Zone of Tigray, Ethiopia using systematic random sampling. The data was collected from January 1 - February 30, 2016 and was entered and analyzed using SPSS version 20. Correlation and multivariate logistic regression was employed to test associations between independent and outcome variables. The mean age of study participants was 43.39 years and the mean duration of diabetes diagnosis was 6.22 years. The overall prevalence of erectile dysfunction was 69.9%, with 32.9% suffering from mild, 31.7% moderate, and 5.2% severe erectile dysfunction. Multivariate logistic regression revealed that erective dysfunction was significantly predicted by old age (Adjusted Odds Ratio [AOR] =15.013, CI:3.212-70.166), longer duration of diabetes (AOR = 3.77, CI:1.291-11.051), and lower monthly income (AOR = 0.285, CI:0.132-0.615). No association was found with body mass index, co-morbidity, glycemic control, and alcohol consumption. The prevalence of erective dysfunction in this study population was very high. Age, income, and duration of diabetes were the independent predictors of erectile dysfunction. Nearly all of the patients in the sample (97%) had not been screened or treated for erectile dysfunction. Assessment and management of erectile dysfunction in the diabetic clinic should be part of routine medical care during follow-up visits with diabetic patients. Healthcare providers should put an emphasis on screening and treating older patients and those who had a diabetes diagnosis for a longer duration.

Metabolite profile of a mouse model of Charcot–Marie–Tooth type 2D neuropathy: implications for disease mechanisms and interventions

PubMed Central

Bais, Preeti; Beebe, Kirk; Morelli, Kathryn H.; Currie, Meagan E.; Norberg, Sara N.; Evsikov, Alexei V.; Miers, Kathy E.; Seburn, Kevin L.; Guergueltcheva, Velina; Kremensky, Ivo; Jordanova, Albena; Bult, Carol J.

2016-01-01

ABSTRACT Charcot–Marie–Tooth disease encompasses a genetically heterogeneous class of heritable polyneuropathies that result in axonal degeneration in the peripheral nervous system. Charcot–Marie–Tooth type 2D neuropathy (CMT2D) is caused by dominant mutations in glycyl tRNA synthetase (GARS). Mutations in the mouse Gars gene result in a genetically and phenotypically valid animal model of CMT2D. How mutations in GARS lead to peripheral neuropathy remains controversial. To identify putative disease mechanisms, we compared metabolites isolated from the spinal cord of Gars mutant mice and their littermate controls. A profile of altered metabolites that distinguish the affected and unaffected tissue was determined. Ascorbic acid was decreased fourfold in the spinal cord of CMT2D mice, but was not altered in serum. Carnitine and its derivatives were also significantly reduced in spinal cord tissue of mutant mice, whereas glycine was elevated. Dietary supplementation with acetyl-L-carnitine improved gross motor performance of CMT2D mice, but neither acetyl-L-carnitine nor glycine supplementation altered the parameters directly assessing neuropathy. Other metabolite changes suggestive of liver and kidney dysfunction in the CMT2D mice were validated using clinical blood chemistry. These effects were not secondary to the neuromuscular phenotype, as determined by comparison with another, genetically unrelated mouse strain with similar neuromuscular dysfunction. However, these changes do not seem to be causative or consistent metabolites of CMT2D, because they were not observed in a second mouse Gars allele or in serum samples from CMT2D patients. Therefore, the metabolite ‘fingerprint’ we have identified for CMT2D improves our understanding of cellular biochemical changes associated with GARS mutations, but identification of efficacious treatment strategies and elucidation of the disease mechanism will require additional studies. PMID:27288508

No Neuromuscular Side-Effects of Scopolamine in Sensorimotor Control and Force-Generating Capacity Among Parabolic Fliers

NASA Astrophysics Data System (ADS)

Ritzmann, Ramona; Freyler, Kathrin; Krause, Anne; Gollhofer, Albert

2016-10-01

Scopolamine is used to counteract motion sickness in parabolic flight (PF) experiments. Although the drug's anticholinergic properties effectively impede vomiting, recent studies document other sensory side-effects in the central nervous system that may considerably influence sensorimotor performance. This study aimed to quantify such effects in order to determine if they are of methodological and operational significance for sensorimotor control. Ten subjects of a PF campaign received a weight-sex-based dose of a subcutaneous scopolamine injection. Sensorimotor performance was recorded before medication, 20min, 2h and 4h after injection in four space-relevant paradigms: balance control in one-leg stance with eyes open (protocol 1) and closed as well as force-generating capacity in countermovement jumps and hops (protocol 2). Postural sway, forces and joint angles were recorded. Neuromuscular control was assessed by electromyography and peripheral nerve stimulation; H-reflexes and M-waves were used to monitor spinal excitability of the Ia afferent reflex circuitry and maximal motor output. (1) H-reflex amplitudes, latencies and functional reflexes remained unchanged after scopolamine injection. (2) M-waves, neuromuscular activation intensities and antagonistic muscle coordination did not change with scopolamine administration. (3) Balance performance and force-generating capacity were not impeded by scopolamine. We found no evidence for changes in sensorimotor control in response to scopolamine injection. Sensory processing of daily relevant reflexes, spinal excitability, maximal motor output and performance parameters were not sensitive to the medication. We conclude that scopolamine administration can be used to counteract motion sickness in PF without methodological and operational concerns or interference regarding sensorimotor skills associated with neuromuscular control.

Neuromuscular Functions on Experimental Acute Methanol Intoxication.

PubMed

Moral, Ali Reşat; Çankayalı, İlkin; Sergin, Demet; Boyacılar, Özden

2015-10-01

The incidence of accidental or suicidal ingestion of methyl alcohol is high and methyl alcohol intoxication has high mortality. Methyl alcohol intoxication causes severe neurological sequelae and appears to be a significant problem. Methyl alcohol causes acute metabolic acidosis, optic neuropathy leading to permanent blindness, respiratory failure, circulatory failure and death. It is metabolised in the liver, and its metabolite formic acid has direct toxic effects, causing oxidative stress, mitochondrial damage and increased lipid peroxidation associated with the mechanism of neurotoxicity. Methanol is known to cause acute toxicity of the central nervous system; however, the effects on peripheral neuromuscular transmission are unknown. In our study, we aimed to investigate the electrophysiological effects of experimentally induced acute methanol intoxication on neuromuscular transmission in the early period (first 24 h). After approval by the Animal Experiment Ethics Committee of Ege University, the study was carried out on 10 Wistar rats, each weighing about 200 g. During electrophysiological recordings and orogastric tube insertion, the rats were anaesthetised using intra-peritoneal (IP) injection of ketamine 100 mg kg(-1) and IP injection of xylazine 10 mg kg(-1). The rats were given 3 g kg(-1) methyl alcohol by the orogastric tube. Electrophysiological measurements from the gastrocnemius muscle were compared with baseline. Latency measurements before and 24 h after methanol injection were 0.81±0.11 ms and 0.76±0.12 ms, respectively. CMAP amplitude measurements before and 24 h after methanol injection were 9.85±0.98 mV and 9.99±0.40 mV, respectively. CMAP duration measurements before and 24 h after methanol injection were 9.86±0.03 ms and 9.86±0.045 ms, respectively. It was concluded that experimental methanol intoxication in the acute phase (first 24 h) did not affect neuromuscular function.

Muscle atrophy, voluntary activation disturbances, and low serum concentrations of IGF-1 and IGFBP-3 are associated with weakness in people with chronic stroke.

PubMed

Silva-Couto, Marcela de Abreu; Prado-Medeiros, Christiane Lanatovitz; Oliveira, Ana Beatriz; Alcântara, Carolina Carmona; Guimarães, Araci Teixeira; Salvini, Tania de Fatima; Mattioli, Rosana; de Russo, Thiago Luiz

2014-07-01

The muscle weakness that is exhibited poststroke is due to a multifactorial etiology involving the central nervous system and skeletal muscle changes. Insulinlike growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been described as biomarkers of neuromuscular performance in many conditions. However, no information about these biomarkers is available for people with chronic hemiparesis. The purpose of this study was to investigate possible factors involved in muscle weakness, such as IGF-1 and IGFBP-3 serum concentrations, muscle volume, and neuromuscular performance of the knee flexors and extensors, in people with chronic hemiparesis poststroke. This was a cross-sectional study. A cross-sectional study was performed on 14 individuals poststroke who were paired with healthy controls. Mobility, function, balance, and quality of life were recorded as outcome measures. Knee flexor and extensor muscle volumes and neuromuscular performance were measured using nuclear magnetic resonance imaging, dynamometry, and electromyography. The serum concentrations of IGF-1 and IGFBP-3 were quantified by enzyme-linked immunosorbent assay (ELISA). The hemiparetic group had low serum concentrations of IGF-1 (25%) and IGFBP-3 (40%); reduced muscle volume in the vastus medialis (32%), vastus intermedius (29%), biceps femoris (16%), and semitendinosus and semimembranosus (12%) muscles; reduced peak torque, power, and work of the knee flexors and extensors; and altered agonist and antagonist muscle activation compared with controls. Low serum concentrations of IGF-1 and IGFBP-3, deficits in neuromuscular performance, selective muscle atrophy, and decreased agonist muscle activation were found in the group with chronic hemiparesis poststroke. Both hemorrhagic and ischemic stroke were considered, and the data reflect a chronic poststroke population with good function. © 2014 American Physical Therapy Association.

The Association between Central Adiposity and Autonomic Dysfunction in Obesity

PubMed Central

Fidan-Yaylali, Güzin; Yaylali, Yalin Tolga; Erdogan, Çağdaş; Can, Beray; Senol, Hande; Gedik-Topçu, Bengi; Topsakal, Senay

2016-01-01

Objective To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. Subjects and Methods The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. Results The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = −0.32; WC-HRR2: r = −0.31; WC-HRR3: r = −0.26; WC-HRR4: r = −0.23; WC-HRR5: r = −0.21; age-HRR2: r = −0.32; age-HRR3: r = −0.28; age-HRR4: r = −0.41; age-HRR5: r = −0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. Conclusion In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery. PMID:27194294

Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction.

PubMed

Arshad, Q; Roberts, R E; Ahmad, H; Lobo, R; Patel, M; Ham, T; Sharp, D J; Seemungal, B M

2017-04-01

We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted. We report the results of a retrospective analysis of both the comprehensive clinical and vestibular laboratory testing of 20 consecutive THI patients with prominent and persisting vestibular symptoms still present at least 6months post THI. Individual THI patients typically had multiple vestibular diagnoses and unique to this group of vestibular patients, often displayed both peripheral and central vestibular dysfunction. Despite expert neuro-otological management, at two years 20% of patients still had persisting vestibular symptoms. In summary, chronic vestibular dysfunction in THI could relate to: (i) the presence of multiple vestibular diagnoses, increasing the risk of 'missed' vestibular diagnoses leading to persisting symptoms; (ii) the impact of brain trauma which may impair brain plasticity mediated repair mechanisms. Apart from alerting physicians to the potential for multiple vestibular diagnoses in THI, future work to identify the specific deficits in brain function mediating poor recovery from post-THI vestibular dysfunction could provide the rationale for developing new therapy for head injury patients whose vestibular symptoms are resistant to treatment. Copyright © 2017. Published by Elsevier B.V.

Development and Maturation of the Neuromuscular Junciton in Cell Culture Under Conditions of Simulated Zero-gravity

NASA Technical Reports Server (NTRS)

Gruener, R.

1985-01-01

Alterations in gravitational conditions which alter the normal development and interactions of nerve and muscle cells grown in culture is examined. Clinostat conditions, similating Og, which produce changes in cell morphology and growth patterns is studied. Data show that rotation of cocultures of nerve and muscle cells results in morphologic changes which are predicted to significantly alter the functional interactions between the elements of a prototypic synapse. It is further predicted that similar alterations may occur in central synapses which may therefore affect the development of the central nervous system when subjected to altered gravitational conditions.

Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005.

PubMed

Higgins, Michael A; Rossmeisl, John H; Panciera, David L

2006-01-01

With the exception of myxedema coma, central nervous system signs are rare in hypothyroid dogs. Central vestibular dysfunction is a possible and reversible manifestation of hypothyroidism. Medical records of dogs with vestibular dysfunction and hypothyroidism were reviewed. Of 113 records identified, 10 dogs with at least 2 concurrent clinical neurologic abnormalities localizable to the central vestibular system were included. Retrospective, descriptive study. Median age at diagnosis was 7 years (range, 5-10 years). All dogs were referred for progressive neurologic disease. Lesions were localized to the myelencephalic region in 5 dogs and to the vestibulocerebellum in 5 dogs. Two dogs had evidence of multifocal intracranial disease. Non-neurologic physical abnormalities suggestive of hypothyroidism were absent in 7 of 10 dogs. Hypercholesterolemia was the only consistent clinicopathologic abnormality detected, and was present in 7 of 10 dogs. All dogs had total thyroxine (TT4) and free thyroxine (fT4) concentrations below reference ranges, and 9 of 10 had increased TSH concentrations. Intracranial imaging studies were normal in 5 of 8 dogs, and identified lesions consistent with infarctions in 3 of 8 dogs. Albuminocytologic dissociation was detected in 5 of 6 CSF analyses. Brainstem auditory-evoked responses disclosed prolonged wave V latencies in 3 of 4 dogs tested. No other causes of central vestibular dysfunction were identified during other diagnostic investigations. The median time from initiation of treatment to clinical improvement was 4 days. Vestibular signs resolved in 9 of 10 dogs within 4 weeks. Although the pathogenesis in dogs without evidence of infarction is unknown, central vestibular dysfunction appears to be a rare but reversible neurologic sequelae of hypothyroidism.

Study on the effectiveness of the kinetic method in patients with rheumatic diseases and temporomandibular joint dysfunction.

PubMed

Havriş, Maria Daniela; Ancuţa, Codrina; Iordache, Cristina; Chirieac, Rodica Marieta

2012-01-01

Selecting the appropriate treatment decision is essential for achieving optimal results in the management of algo-dysfunctional syndrome of the temporo-mandibular joint (TMJD). The study aims to decide on the most effective (symptomatic control, preserved motility) kinetic program in patients with TMJ involvement. prospective observational study on 83 consecutive patients with rheumatic diseases and TMJ dysfunction. Clinical assessment (pain, noises, muscle spasm, range of motion, ROM) was performed at baseline and after 3 months of specific kinetic rehabilitation program. Change in clinical parameters and TM3 index was reported, p<0.05. over 45% TMJ involvement at baseline as defined by TMJ index (mean value of 13.56) and only 36.66% at 3 months (p<0.05). Significant improvement in pain (presence, severity) was demonstrated at 3 moths (p<0.05): 18.05% spontaneous pain, 75.9% provoked pain, with 12.11% respectively 2.41% decreased in nocturnal respectively diurnal pain. Significant decrease (p<0.05) in joint noises at movements: 27.71% when opening and 12.04% when closing the mouth, 8.43 at protrusion and 3.61% at retraction, while 18% at the side movements. Complex accurate kinetic reeducation is mandatory for achieving correct posture (head, neck and trunk), normal mastication, swallowing and respiration, as well as correction of neuromuscular imbalances in patients with TMJD secondary to rheumatic disorders.

[Post-polio syndrome. Part I. The "legacy" of forgotten disease, challenges for professionals and polio survivors].

PubMed

Matyja, Ewa

2012-01-01

The outcome of paralytic polio was believed to be a stable neurological state. Now, it is established that polio has an additional, slowly progressive phase, called post-polio syndrome (PPS) that develops 30-40 years after the acute poliomyelitis in 25-80% of paralytic and about 40% of nonparalytic polio survivors. The clinical symptoms are nonspecific and usually include muscle weakness, fatigue and muscle or joint pain. Some patients suffer from muscular atrophy, respiratory insufficiency, dysphagia, sleep disturbances or cold intolerance. The etiopathogenesis of PPS is unclear and many factors, such as dysfunction of the surviving motor units, aging, defects of neuromuscular transmission, persistence of viral infection and immunological mechanisms, are considered.

Autonomic dysfunction in pediatric patients with headache: migraine versus tension-type headache.

PubMed

Rabner, Jonathan; Caruso, Alessandra; Zurakowski, David; Lazdowsky, Lori; LeBel, Alyssa

2016-12-01

To examine symptoms indicating central nervous system (CNS) autonomic dysfunction in pediatric patients with migraine and tension-type headache. A retrospective chart review assessed six symptoms (i.e. constipation, insomnia, dizziness, blurry vision, abnormal blood pressure, and cold and clammy palms and soles) indicating central nervous system (CNS) autonomic dysfunction in 231 patients, ages 5-18 years, diagnosed with migraine, tension-type headache (TTH), or Idiopathic Scoliosis (IS). Higher frequencies of "insomnia," "dizziness," and "cold and clammy palms and soles" were found for both migraine and TTH patients compared to the IS control group (P < 0.001). Frequencies of all six symptoms were greater in TTH than migraine patients with "cold and clammy palms and soles" reaching significance (P < 0.001). The need for prospective research investigating autonomic dysfunction in pediatric headache patients is discussed.

Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

PubMed

Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

2017-08-24

Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

Exercise training improves the defective centrally mediated erectile responses in rats with type I diabetes.

PubMed

Zheng, Hong; Mayhan, William G; Patel, Kaushik P

2011-11-01

Erectile dysfunction is a serious and common complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for the penile erection. The goal of the present study was to determine the impact of exercise training (ExT) on the centrally mediated erectile dysfunction in streptozotocin (STZ)-induced type I diabetic (T1D) rats. Male Sprague-Dawley rats were injected with STZ to induce diabetes mellitus. Three weeks after STZ or vehicle injections, rats were assigned to either ExT (treadmill running for 3-4 weeks) or sedentary groups to produce four experimental groups: control + sedentary, T1D + sedentary, control + ExT, and T1D + ExT. After 3-4 weeks ExT, central N-methyl-D-aspartic acid (NMDA) or sodium nitroprusside (SNP)-induced penile erectile responses were measured. Neuronal nitric oxide synthase (nNOS) expression in the paraventricular nucleus (PVN) of the hypothalamus was measured by using histochemistry, real time polymerase chain reaction (PCR) and Western blot approaches. In rats with T1D, ExT significantly improved the blunted erectile response, and the intracavernous pressure changes to NMDA (50 ng) microinjection within the PVN (T1D + ExT: 3.0 ± 0.6 penile erection/rat; T1D + sedentary: 0.5 ± 0.3 penile erection/rat within 20 minutes, P < 0.05). ExT improved erectile dysfunction induced by central administration of exogenous nitric oxide (NO) donor, SNP in T1D rats. Other behavior responses including yawning and stretching, induced by central NMDA and SNP microinjection were also significantly increased in T1D rats after ExT. Furthermore, we found that ExT restored the nNOS mRNA and protein expression in the PVN in T1D rats. These results suggest that ExT may have beneficial effects on the erectile dysfunction in diabetes through improvement of NO bioavailability within the PVN. Thus, ExT may be used as therapeutic modality to up-regulate nNOS within the PVN and improve the central component of the erectile dysfunction in diabetes mellitus. © 2011 International Society for Sexual Medicine.

[Change in laryngeal vibratory mechanism: a physiological entity].

PubMed

Roubeau, B; Chevrie-Muller, C; Arabia, C; Arragon, C

1993-01-01

The purpose of this paper is to examine the change of laryngeal vibratory mechanism in 10 males and 9 females trained and untrained singers. The electroglottographic (E.G.G.) data analysis demonstrated strong evidence to support the view that such event could be considered as a whole physiological entity. In fact findings clearly indicated biomechanical, neuromuscular and central levels in the control of the laryngeal vibration involved in the change of mechanism.

Power-duration relationship: Physiology, fatigue, and the limits of human performance.

PubMed

Burnley, Mark; Jones, Andrew M

2018-02-01

The duration that exercise can be maintained decreases as the power requirements increase. In this review, we describe the power-duration (PD) relationship across the full range of attainable power outputs in humans. We show that a remarkably small range of power outputs is sustainable (power outputs below the critical power, CP). We also show that the origin of neuromuscular fatigue differs considerably depending on the exercise intensity domain in which exercise is performed. In the moderate domain (below the lactate threshold, LT), fatigue develops slowly and is predominantly of central origin (residing in the central nervous system). In the heavy domain (above LT but below CP), both central and peripheral (muscle) fatigue are observed. In this domain, fatigue is frequently correlated with the depletion of muscle glycogen. Severe-intensity exercise (above the CP) is associated with progressive derangements of muscle metabolic homeostasis and consequent peripheral fatigue. To counter these effects, muscle activity increases progressively, as does pulmonary oxygen uptake ([Formula: see text]), with task failure being associated with the attainment of [Formula: see text] max. Although the loss of homeostasis and thus fatigue develop more rapidly the higher the power output is above CP, the metabolic disturbance and the degree of peripheral fatigue reach similar values at task failure. We provide evidence that the failure to continue severe-intensity exercise is a physiological phenomenon involving multiple interacting mechanisms which indicate a mismatch between neuromuscular power demand and instantaneous power supply. Valid integrative models of fatigue must account for the PD relationship and its physiological basis.

Sleep disorders associated with primary mitochondrial diseases.

PubMed

Ramezani, Ryan J; Stacpoole, Peter W

2014-11-15

Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

Neuromuscular Fatigue during Prolonged Exercise in Hypoxia.

PubMed

Jubeau, Marc; Rupp, Thomas; Temesi, John; Perrey, Stéphane; Wuyam, Bernard; Millet, Guillaume Y; Verges, Samuel

2017-03-01

Prolonged cycling exercise performance in normoxia is limited because of both peripheral and central neuromuscular impairments. It has been reported that cerebral perturbations are greater during short-duration exercise in hypoxia compared with normoxia. The purpose of this study was to test the hypothesis that central deficits are accentuated in hypoxia compared with normoxia during prolonged (three bouts of 80 min separated by 25 min) whole-body exercise at the same relative intensity. Ten subjects performed two sessions consisting of three 80-min cycling bouts at 45% of their relative maximal aerobic power in normoxia and hypoxia (FiO2 = 0.12). Before exercise and after each bout, maximal voluntary force, voluntary activation assessed with nerve stimulation and transcranial magnetic stimulation, corticospinal excitability (motor evoked potential), intracortical inhibition (cortical silent period), and electrical (M-wave) and contractile (twitch and doublet peak forces) properties of the knee extensors were measured. Prefrontal and motor cortical oxygenation was also recorded during each cycling bout in both conditions. A significant but similar force reduction (≈-22%) was observed at the end of exercise in normoxia and hypoxia. The modifications of voluntary activation assessed with transcranial magnetic stimulation and nerve stimulation, motor evoked potential, cortical silent period, and M-wave were also similar in both conditions. However, cerebral oxygenation was reduced in hypoxia compared with normoxia. These findings show that when performed at the same relative low intensity, prolonged exercise does not induce greater supraspinal fatigue in hypoxia compared with normoxia. Despite lower absolute exercise intensities in hypoxia, reduced brain O2 availability might contribute to similar amounts of central fatigue compared with normoxia.

Tissue inhibitor of metalloproteinase-2(TIMP-2)-deficient mice display motor deficits.

PubMed

Jaworski, Diane M; Soloway, Paul; Caterina, John; Falls, William A

2006-01-01

The degradation of the extracellular matrix is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Matrix components of the basement membrane play critical roles in the development and maintenance of the neuromuscular junction (NMJ), yet almost nothing is known about the regulation of MMP and TIMP expression in either the pre- or postsynaptic compartments. Here, we demonstrate that TIMP-2 is expressed by both spinal motor neurons and skeletal muscle. To determine whether motor function is altered in the absence of TIMP-2, motor behavior was assessed using a battery of tests (e.g., RotaRod, balance beam, hindlimb extension, grip strength, loaded grid, and gait analysis). TIMP-2(-/-) mice fall off the RotaRod significantly faster than wild-type littermates. In addition, hindlimb extension is reduced and gait is both splayed and lengthened in TIMP-2(-/-) mice. Motor dysfunction is more pronounced during early postnatal development. A preliminary analysis revealed NMJ alterations in TIMP-2(-/-) mice. Juvenile TIMP-2(-/-) mice have increased nerve branching and acetylcholine receptor expression. Adult TIMP-2(-/-) endplates are enlarged and more complex. This suggests a role for TIMP-2 in NMJ sculpting during development. In contrast to the increased NMJ nerve branching, cerebellar Purkinje cells have decreased neurite outgrowth. Thus, the TIMP-2(-/-) motor phenotype is likely due to both peripheral and central defects. The tissue specificity of the nerve branching phenotype suggests the involvement of different MMPs and/or extracellular matrix molecules underlying the TIMP-2(-/-) motor phenotype.

Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy.

PubMed

Sahashi, Kentaro; Katsuno, Masahisa; Hung, Gene; Adachi, Hiroaki; Kondo, Naohide; Nakatsuji, Hideaki; Tohnai, Genki; Iida, Madoka; Bennett, C Frank; Sobue, Gen

2015-11-01

Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

PubMed

Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

2017-07-01

The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

PubMed

Iwasaki, Hajime; Sasakawa, Tomoki; Takahoko, Kenichi; Takagi, Shunichi; Nakatsuka, Hideki; Suzuki, Takahiro; Iwasaki, Hiroshi

2016-06-01

We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

The Dysfunctions of Bureaucratic Structure.

ERIC Educational Resources Information Center

Duttweiler, Patricia Cloud

1988-01-01

Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

Elite Female Basketball Players' Body-Weight Neuromuscular Training and Performance on the Y-Balance Test

PubMed Central

Benis, Roberto; Bonato, Matteo; Torre, Antonio La

2016-01-01

Context: Neuromuscular training enhances unconscious motor responses by stimulating both the afferent signals and central mechanisms responsible for dynamic joint control. Dynamic joint-control training is a vital component of injury-prevention programs. Objective: To investigate the effects of body-weight neuromuscular training on Y-Balance Test (YBT) performance and postural control in female basketball players. Design: Randomized controlled clinical trial. Setting: Basketball practice sessions. Patients or Other Participants: A total of 28 healthy elite female basketball players were randomly assigned to an experimental (n = 14) or a control group (n = 14). Intervention(s): Before their regular practice sessions, the experimental group warmed up with body-weight neuromuscular exercises and the control group with standard tactical-technical exercises twice weekly for 8 weeks. Main Outcome Measure(s): Anterior-, posteromedial-, and posterolateral-reach and composite YBT scores were measured before and after 8 weeks of training. Results: Improvement over baseline scores was noted in the posteromedial (right = 86.5 ± 4.5 cm versus 89.6 ± 2.2 cm, +3.5%, P = .049; left = 85.5 ± 4.3 cm versus 90.2 ± 2.7 cm, +5.5%, P = .038)- and posterolateral (right = 90.7 ± 3.6 cm versus 94.0 ± 2.7 cm, +3.6%, P = .016; left = 90.9 ± 3.5 cm versus 94.2 ± 2.6 cm, +3.6%, P = .011)-reach directions and in the composite YBT scores (right = 88.6% ± 3.2% versus 94.0% ± 1.8%, +5.4%, P = .0004; left = 89.2% ± 3.2% versus 94.5% ± 3.0%, +5.8%, P = .001) of the experimental group. No differences in anterior reach were detected in either group. Differences were noted in postintervention scores for posteromedial reach (right = 89.6 ± 2.2 cm versus 84.3 ± 4.4 cm, +4.1%, P = .005; left = 94.2 ± 2.6 cm versus 84.8 ± 4.4 cm, +10%, P = .003) and composite scores (right = 94.0% ± 1.8% versus 87.3% ± 2.0%, +7.1%, P = .003; left = 94.8% ± 3.0% versus 87.9% ± 3.4%, +7.3%, P < .0001) between the experimental and control groups. Conclusions: Body-weight neuromuscular training improved postural control and lower limb stability in female basketball players as assessed with the YBT. Incorporating neuromuscular training into the workout routines for basketball players may enhance joint awareness and reduce the risk of lower extremity injury. PMID:27824252

Elite Female Basketball Players' Body-Weight Neuromuscular Training and Performance on the Y-Balance Test.

PubMed

Benis, Roberto; Bonato, Matteo; La Torre, Antonio La

2016-09-01

Neuromuscular training enhances unconscious motor responses by stimulating both the afferent signals and central mechanisms responsible for dynamic joint control. Dynamic joint-control training is a vital component of injury-prevention programs. To investigate the effects of body-weight neuromuscular training on Y-Balance Test (YBT) performance and postural control in female basketball players. Randomized controlled clinical trial. Basketball practice sessions. A total of 28 healthy elite female basketball players were randomly assigned to an experimental (n = 14) or a control group (n = 14). Before their regular practice sessions, the experimental group warmed up with body-weight neuromuscular exercises and the control group with standard tactical-technical exercises twice weekly for 8 weeks. Anterior-, posteromedial-, and posterolateral-reach and composite YBT scores were measured before and after 8 weeks of training. Improvement over baseline scores was noted in the posteromedial (right = 86.5 ± 4.5 cm versus 89.6 ± 2.2 cm, +3.5%, P = .049; left = 85.5 ± 4.3 cm versus 90.2 ± 2.7 cm, +5.5%, P = .038)- and posterolateral (right = 90.7 ± 3.6 cm versus 94.0 ± 2.7 cm, +3.6%, P = .016; left = 90.9 ± 3.5 cm versus 94.2 ± 2.6 cm, +3.6%, P = .011)-reach directions and in the composite YBT scores (right = 88.6% ± 3.2% versus 94.0% ± 1.8%, +5.4%, P = .0004; left = 89.2% ± 3.2% versus 94.5% ± 3.0%, +5.8%, P = .001) of the experimental group. No differences in anterior reach were detected in either group. Differences were noted in postintervention scores for posteromedial reach (right = 89.6 ± 2.2 cm versus 84.3 ± 4.4 cm, +4.1%, P = .005; left = 94.2 ± 2.6 cm versus 84.8 ± 4.4 cm, +10%, P = .003) and composite scores (right = 94.0% ± 1.8% versus 87.3% ± 2.0%, +7.1%, P = .003; left = 94.8% ± 3.0% versus 87.9% ± 3.4%, +7.3%, P < .0001) between the experimental and control groups. Body-weight neuromuscular training improved postural control and lower limb stability in female basketball players as assessed with the YBT. Incorporating neuromuscular training into the workout routines for basketball players may enhance joint awareness and reduce the risk of lower extremity injury.

Pericyte function in the physiological central nervous system.

PubMed

Muramatsu, Rieko; Yamashita, Toshihide

2014-01-01

Damage to the central nervous system (CNS) leads to disruption of the vascular network, causing vascular dysfunction. Vascular dysfunction is the major event in the pathogenesis of CNS diseases and is closely associated with the severity of neuronal dysfunction. The suppression of vascular dysfunction has been considered a promising avenue to limit damage to the CNS, leading to efforts to clarify the cellular and molecular basis of vascular homeostasis maintenance. A reduction of trophic support and oxygen delivery due to circulatory insufficiency has long been regarded as a major cause of vascular damage. Moreover, recent studies provide a new perspective on the importance of the structural stability of blood vessels in CNS diseases. This updated article discusses emerging information on the key role of vascular integrity in CNS diseases, specially focusing on pericyte function. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice

PubMed Central

Kwon, Deborah Y.; Motley, William W.; Fischbeck, Kenneth H.; Burnett, Barrington G.

2011-01-01

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by reduced levels of the survival motor neuron (SMN) protein. Here we show that the proteasome inhibitor, bortezomib, increases SMN in cultured cells and in peripheral tissues of SMA model mice. Bortezomib-treated animals had improved motor function, which was associated with reduced spinal cord and muscle pathology and improved neuromuscular junction size, but no change in survival. Combining bortezomib with the histone deacetylase inhibitor trichostatin A (TSA) resulted in a synergistic increase in SMN protein levels in mouse tissue and extended survival of SMA mice more than TSA alone. Our results demonstrate that a combined regimen of drugs that decrease SMN protein degradation and increase SMN gene transcription synergistically increases SMN levels and improves the lifespan of SMA model mice. Moreover, this study indicates that while increasing SMN levels in the central nervous system may help extend survival, peripheral tissues can also be targeted to improve the SMA disease phenotype. PMID:21693563

Being the lifeline: the parent experience of caring for a child with neuromuscular disease on home mechanical ventilation.

PubMed

Mah, Jean K; Thannhauser, Jennifer E; McNeil, Deborah A; Dewey, Deborah

2008-12-01

We describe the experience of parents caring for children with neuromuscular disease (NMD) on home mechanical ventilation (HMV). Data was obtained from semi-structured interviews and analyzed using a phenomenological framework. Fifteen families including 19 parents of children with DMD (n=3), SMA (n=5), and other NMD (n=7) participated. The central theme of these parents' experience was being the "lifeline" for their child's life and quality of life. The families' lives changed significantly with the decision to place their child on HMV; over time, these changes became part of their new "normal". Despite becoming expert caregivers, the parents experienced a recurrent sense of loss and uncertainty. Those who perceived insufficient support felt the weight of responsibility as sole care providers for their child with NMD. Beyond recognizing the parents as experts, more support by health care professionals, their extended family, and their community are needed to enable parents to fulfill their vital role.

Efficiently Assessing Negative Cognition in Depression: An Item Response Theory Analysis of the Dysfunctional Attitude Scale

ERIC Educational Resources Information Center

Beevers, Christopher G.; Strong, David R.; Meyer, Bjorn; Pilkonis, Paul A.; Miller, Ivan R.

2007-01-01

Despite a central role for dysfunctional attitudes in cognitive theories of depression and the widespread use of the Dysfunctional Attitude Scale, form A (DAS-A; A. Weissman, 1979), the psychometric development of the DAS-A has been relatively limited. The authors used nonparametric item response theory methods to examine the DAS-A items and…

21 CFR 882.5810 - External functional neuromuscular stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional neuromuscular...

21 CFR 882.5810 - External functional neuromuscular stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false External functional neuromuscular stimulator. 882.5810 Section 882.5810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... External functional neuromuscular stimulator. (a) Identification. An external functional neuromuscular...

Dilysine motifs in exon 2b of SMN protein mediate binding to the COPI vesicle protein α-COP and neurite outgrowth in a cell culture model of spinal muscular atrophy.

PubMed

Custer, Sara K; Todd, Adrian G; Singh, Natalia N; Androphy, Elliot J

2013-10-15

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder that stems from low levels of survival of motor neuron (SMN) protein. The processes that cause motor neurons and muscle cells to become dysfunctional are incompletely understood. We are interested in neuromuscular homeostasis and the stresses put upon that system by loss of SMN. We recently reported that α-COP, a member of the coatomer complex of coat protein I (COPI) vesicles, is an SMN-binding partner, implicating this protein complex in normal SMN function. To investigate the functional significance of the interaction between α-COP and SMN, we constructed an inducible NSC-34 cell culture system to model the consequences of SMN depletion and find that depletion of SMN protein results in shortened neurites. Heterologous expression of human SMN, and interestingly over-expression of α-COP, restores normal neurite length and morphology. Mutagenesis of the canonical COPI dilysine motifs in exon 2b results in failure to bind to α-COP and abrogates the ability of human SMN to restore neurite outgrowth in SMN-depleted motor neuron-like NSC-34 cells. We conclude that the interaction between SMN and α-COP serves an important function in the growth and maintenance of motor neuron processes and may play a significant role in the pathogenesis of SMA.

Involvement of the P2X7 purinergic receptor in colonic motor dysfunction associated with bowel inflammation in rats.

PubMed

Antonioli, Luca; Giron, Maria Cecilia; Colucci, Rocchina; Pellegrini, Carolina; Sacco, Deborah; Caputi, Valentina; Orso, Genny; Tuccori, Marco; Scarpignato, Carmelo; Blandizzi, Corrado; Fornai, Matteo

2014-01-01

Recent evidence indicates an involvement of P2X7 purinergic receptor (P2X7R) in the fine tuning of immune functions, as well as in driving enteric neuron apoptosis under intestinal inflammation. However, the participation of this receptor in the regulation of enteric neuromuscular functions remains undetermined. This study was aimed at investigating the role of P2X7Rs in the control of colonic motility in experimental colitis. Colitis was induced in rats by 2,4-dinitrobenzenesulfonic acid. P2X7R distribution was examined by immunofluorescence analysis. The effects of A804598 (selective P2X7R antagonist) and BzATP (P2X7R agonist) were tested on contractions of longitudinal smooth muscle evoked by electrical stimulation or by carbachol in the presence of tetrodotoxin. P2X7Rs were predominantly located in myenteric neurons, but, in the presence of colitis, their expression increased in the neuromuscular layer. In normal preparations, A804598 elicited a negligible increase in electrically induced contractions, while a significant enhancement was recorded in inflamed tissues. In the presence of Nω-propyl-L-arginine (NPA, neuronal nitric oxide synthase inhibitor) the A804598 effects were lost. P2X7R stimulation with BzATP did not significantly affect electrical-induced contractions in normal colon, while a marked reduction was recorded under inflammation. The inhibitory effect of BzATP was antagonized by A804598, and it was also markedly blunted by NPA. Both P2X7R ligands did not affect carbachol-induced contractions. The purinergic system contributes to functional neuromuscular changes associated with bowel inflammation via P2X7Rs, which modulate the activity of excitatory cholinergic nerves through a facilitatory control on inhibitory nitrergic pathways.

Stimulation of Central A1 Adenosine Receptors Suppresses Seizure and Neuropathology in a Soman Nerve Agent Seizure Rat Model

DTIC Science & Technology

2014-05-22

acetylcholinesterase (AChE), the enzyme responsible for hydrolyzing the neurotransmitter acetylcholine (ACh) in the cholinergic synapses and neuromuscular...1992; Fosbraey et al., 1990; Lallement et al., 1991; O’Donnell et al., 2010, 2011; Wade et al., 1987). Many potential inhibitory compounds and drugs...2005). Despite such cardiovascular effects, van Helden et al. (1998) recognized adenosine’s potential as a CWNA countermeas- ure. In their early

Need for tissue plasminogen activator for central venous catheter dysfunction is significantly associated with thrombosis in pediatric cancer patients.

PubMed

MacLean, Jessica; MacDonald, Tamara; Digout, Carol; Smith, Nadine; Rigby, Krista; Kulkarni, Ketan

2018-06-01

Central venous catheter (CVC) dysfunction is a common complication among pediatric cancer patients. Tissue plasminogen activator (tPA) is administered to resolve CVC dysfunction. The present study was designed to determine risk factors associated with requirement of tPA for CVC dysfunction and to assess the clinical impact of CVC dysfunction in terms of CVC loss and venous thrombotic events (VTE). Case records of all pediatric patients with cancer from the Maritimes, Canada were reviewed following ethics approval. Data regarding demographics, clinical diagnosis, CVC dysfunction, characteristics of CVCs, and VTE were pooled from multiple data sources. Seven hundred and forty-one patients required ≥1 CVC. 26.3% of patients required tPA for ≥1 episodes of CVC dysfunction. Requirement of one or more doses of tPA for episodes of CVC dysfunction increased the odds of VTE by two times (95% confidence interval, 1.1-3.6). Patients that required ≥1 doses of tPA required significantly more CVCs (2.05 ± 1.29 per individual patient, 55% of the patients needed >1 CVCs) as compared to the remainder (1.52 ± 0.95 per individual patient, 32% needed >1 CVCs) (P = 0.0001). Multivariate analysis revealed age > 10 years, diagnosis of sarcoma, and tunneled line were independently associated with tPA requirement. We determined independent risk factors associated with requirement of tPA for CVC dysfunction. Requirement of tPA for CVC dysfunction was associated with significantly increased risk of VTE and requirement of more CVCs. These observations can assist in identification of patients at increased risk of CVC dysfunction and inform approaches to reduce CVC loss and VTE. © 2018 Wiley Periodicals, Inc.

Learning Disability Assessed through Audiologic and Physiologic Measures: A Case Study.

ERIC Educational Resources Information Center

Greenblatt, Edward R.; And Others

1983-01-01

The report describes a child with central auditory dysfunction, the first reported case where brain-stem dysfunction on audiologic tests were associated with specific electrophysiologic changes in the brain-stem auditory-evoked responses. (Author/CL)

Synaptic dysfunction and altered excitability in C9ORF72 ALS/FTD.

PubMed

Starr, Alexander; Sattler, Rita

2018-08-15

Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis. The most common shared genetic mutation in ALS/FTD is a hexanucleuotide repeat expansion within intron 1 of C9ORF72 (C9). Three potentially overlapping, putative toxic mechanisms have been proposed: loss of function due to haploinsufficient expression of the C9ORF72 mRNA, gain of function of the repeat RNA aggregates, or RNA foci, and repeat-associated non-ATG-initiated translation (RAN) of the repeat RNA into toxic dipeptide repeats (DPRs). Regardless of the causative mechanism, disease symptoms are ultimately caused by a failure of neurotransmission in three regions: the brain, the spinal cord, and the neuromuscular junction. Here, we review C9 ALS/FTD-associated synaptic dysfunction and aberrant neuronal excitability in these three key regions, focusing on changes in morphology and synapse formation, excitability, and excitotoxicity in patients, animal models, and in vitro models. We compare these deficits to those seen in other forms of ALS and FTD in search of shared pathways, and discuss the potential targeting of synaptic dysfunctions for therapeutic intervention in ALS and FTD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

21 CFR 882.5860 - Implanted neuromuscular stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted neuromuscular stimulator. 882.5860... neuromuscular stimulator. (a) Identification. An implanted neuromuscular stimulator is a device that provides electrical stimulation to a patient's peroneal or femoral nerve to cause muscles in the leg to contract, thus...

Central cholinergic dysfunction could be associated with oropharyngeal dysphagia in early Parkinson's disease.

PubMed

Lee, Kyung Duck; Koo, Jung Hoi; Song, Sun Hong; Jo, Kwang Deog; Lee, Moon Kyu; Jang, Wooyoung

2015-11-01

Dysphagia is an important issue in the prognosis of Parkinson's disease (PD). Although several studies have reported that oropharyngeal dysphagia may be associated with cognitive dysfunction, the exact relationship between cortical function and swallowing function in PD patients is unclear. Therefore, we investigated the association between an electrophysiological marker of central cholinergic function, which reflected cognitive function, and swallowing function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the enrolled patients into two groups: PD with dysphagia and PD without dysphagia. The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of the dysphagia. To assess central cholinergic dysfunction, short latency afferent inhibition (SAI) was evaluated. We analyzed the relationship between central cholinergic dysfunction and oropharyngeal dysphagia and investigated the characteristics of the dysphagia. The SAI values were significantly different between the two groups. The comparison of each VFSS component between the PD with dysphagia group and the PD without dysphagia group showed statistical significance for most of the oral phase components and for a single pharyngeal phase component. The total score on the VDS was higher in the PD with dysphagia group than in the PD without dysphagia group. The Mini-Mental State Examination and SAI values showed significant correlations with the total score of the oral phase components. According to binary logistic regression analysis, SAI value independently contributed to the presence of dysphagia in PD patients. Our findings suggest that cholinergic dysfunction is associated with dysphagia in early PD and that an abnormal SAI value is a good biomarker for predicting the risk of dysphagia in PD patients.

Fascia: A missing link in our understanding of the pathology of fibromyalgia.

PubMed

Liptan, Ginevra L

2010-01-01

Significant evidence exists for central sensitization in fibromyalgia, however the cause of this process in fibromyalgia-and how it relates to other known abnormalities in fibromyalgia-remains unclear. Central sensitization occurs when persistent nociceptive input leads to increased excitability in the dorsal horn neurons of the spinal cord. In this hyperexcited state, spinal cord neurons produce an enhanced responsiveness to noxious stimulation, and even to formerly innocuous stimulation. No definite evidence of muscle pathology in fibromyalgia has been found. However, there is some evidence for dysfunction of the intramuscular connective tissue, or fascia, in fibromyalgia. This paper proposes that inflammation of the fascia is the source of peripheral nociceptive input that leads to central sensitization in fibromyalgia. The fascial dysfunction is proposed to be due to inadequate growth hormone production and HPA axis dysfunction in fibromyalgia. Fascia is richly innervated, and the major cell of the fascia, the fibroblast, has been shown to secrete pro-inflammatory cytokines, particularly IL-6, in response to strain. Recent biopsy studies using immuno-histochemical staining techniques have found increased levels of collagen and inflammatory mediators in the connective tissue surrounding the muscle cells in fibromyalgia patients. The inflammation of the fascia is similar to that described in conditions such as plantar fasciitis and lateral epicondylitis, and may be better described as a dysfunctional healing response. This may explain why NSAIDs and oral steroids have not been found effective in fibromyalgia. Inflammation and dysfunction of the fascia may lead to central sensitization in fibromyalgia. If this hypothesis is confirmed, it could significantly expand treatment options to include manual therapies directed at the fascia such as Rolfing and myofascial release, and direct further research on the peripheral pathology in fibromyalgia to the fascia.

Neuromuscular adaptations predict functional disability independently of clinical pain and psychological factors in patients with chronic non-specific low back pain.

PubMed

Dubois, Jean-Daniel; Abboud, Jacques; St-Pierre, Charles; Piché, Mathieu; Descarreaux, Martin

2014-08-01

Patients with chronic low back pain exhibit characteristics such as clinical pain, psychological symptoms and neuromuscular adaptations. The purpose of this study was to determine the independent contribution of clinical pain, psychological factors and neuromuscular adaptations to disability in patients with chronic low back pain. Clinical pain intensity, pain catastrophizing, fear-avoidance beliefs, anxiety, neuromuscular adaptations to chronic pain and neuromuscular responses to experimental pain were assessed in 52 patients with chronic low back pain. Lumbar muscle electromyographic activity was assessed during a flexion-extension task (flexion relaxation phenomenon) to assess both chronic neuromuscular adaptations and neuromuscular responses to experimental pain during the task. Multiple regressions showed that independent predictors of disability included neuromuscular adaptations to chronic pain (β=0.25, p=0.006, sr(2)=0.06), neuromuscular responses to experimental pain (β=-0.24, p=0.011, sr(2)=0.05), clinical pain intensity (β=0.28, p=0.002, sr(2)=0.08) and psychological factors (β=0.58, p<0.001, sr(2)=0.32). Together, these predictors accounted for 65% of variance in disability (R(2)=0.65 p<0.001). The current investigation revealed that neuromuscular adaptations are independent from clinical pain intensity and psychological factors, and contribute to inter-individual differences in patients' disability. This suggests that disability, in chronic low back pain patients, is determined by a combination of factors, including clinical pain, psychological factors and neuromuscular adaptations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of myasthenia gravis using electrooculography signals.

PubMed

Liang, T; Boulos, M I; Murray, B J; Krishnan, S; Katzberg, H; Umapathy, K

2016-08-01

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting from skeletal muscle weakness and fatigue. An early common symptom is fatigable weakness of the extrinsic ocular muscles; if symptoms remain confined to the ocular muscles after a few years, this is classified as ocular myasthenia gravis (OMG). Diagnosis of MG when there are mild, isolated ocular symptoms can be difficult, and currently available diagnostic techniques are insensitive, non-specific or technically cumbersome. In addition, there are no accurate biomarkers to follow severity of ocular dysfunction in MG over time. Single-fiber electromyography (SFEMG) and repetitive nerve stimulation (RNS) offers a way of detecting and measuring ocular muscle dysfunction in MG, however, challenges of these methods include a poor signal to noise ratio in quantifying eye muscle weakness especially in mild cases. This paper presents one of the attempts to use the electric potentials from the eyes or electrooculography (EOG) signals but obtained from three different forms of sleep testing to differentiate MG patients from age- and gender-matched controls. We analyzed 8 MG patients and 8 control patients and demonstrated a difference in the average eye movements detected between the groups. A classification accuracy as high as 68.8% was achieved using a linear discriminant analysis based classifier.

Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models

PubMed Central

O'Hern, Patrick J; do Carmo G. Gonçalves, Inês; Brecht, Johanna; López Soto, Eduardo Javier; Simon, Jonah; Chapkis, Natalie; Lipscombe, Diane; Kye, Min Jeong; Hart, Anne C

2017-01-01

Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals. We determined that miR-2 regulates expression of the C. elegans M2 muscarinic receptor (m2R) ortholog, GAR-2. GAR-2 loss ameliorated smn-1(lf) and mel-46(lf) synaptic defects. In an SMA mouse model, m2R levels were increased and pharmacological inhibition of m2R rescued MN process defects. Collectively, these results suggest decreased SMN leads to defective microRNA function via MEL-46 misregulation, followed by increased m2R expression, and neuronal dysfunction in SMA. DOI: http://dx.doi.org/10.7554/eLife.20752.001 PMID:28463115

Central-Approach Surgical Repair of Coarctation of the Aorta with a Back-up Left Ventricular Assist Device for an Infant Presenting with Severe Left Ventricular Dysfunction.

PubMed

Kim, Tae Hoon; Shin, Yu Rim; Kim, Young Sam; Kim, Do Jung; Kim, Hyohyun; Shin, Hong Ju; Htut, Aung Thein; Park, Han Ki

2015-12-01

A two-month-old infant presented with coarctation of the aorta, severe left ventricular dysfunction, and moderate to severe mitral regurgitation. Through median sternotomy, the aortic arch was repaired under cardiopulmonary bypass and regional cerebral perfusion. The patient was postoperatively supported with a left ventricular assist device for five days. Left ventricular function gradually improved, eventually recovering with the concomitant regression of mitral regurgitation. Prompt surgical repair of coarctation of the aorta is indicated for patients with severe left ventricular dysfunction. A central approach for surgical repair with a back-up left ventricular assist device is a safe and effective treatment strategy for these patients.

Anterior Knee Pain in Children and Adolescents: Overview and Management.

PubMed

Slotkin, Steven; Thome, Andrew; Ricketts, Cassandra; Georgiadis, Andrew; Cruz, Aristides I; Seeley, Mark

2018-05-01

Anterior knee pain (AKP) is a common presenting complaint for pediatricians and orthopaedic surgeons and is often seen in young athletes. AKP is multifactorial and has a broad differential diagnosis. The growth changes, biomechanics, and anatomy around the knee add to the complexity of diagnosis and treatment of AKP. Common causes of AKP include Osgood-Schlatter's disease, patellar tendinitis, and patellofemoral instability. In the diagnosis of AKP, it is important to rule out serious and morbid causes of pain, including infection and tumor. It is crucial to complete a detailed history and physical examination and obtain appropriate imaging studies. In general, the majority of patients will respond to nonoperative measures targeted to correct neuromuscular control and kinetic chain dysfunction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Quantification of Dihydroxyacetone Phosphate (DHAP) in Human Red Blood Cells by HPLC-TripleTOF 5600™ Mass Spectrometer.

PubMed

Deng, Shuang; Scott, David; Myers, Douglas; Garg, Uttam

2016-01-01

Triosephosphate isomerase (TPI) is a glycolytic enzyme which catalyzes the interconversion between glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). TPI deficiency results in accumulation of DHAP in human red blood cells and other tissues. The disease is characterized by congenital hemolytic anemia, and progressive neuromuscular dysfunction. The laboratory diagnosis is generally made by measurement of TPI activity in RBCs. Measurement of DHAP can be useful in further confirmation and follow-up of the disease. We developed HPLC/TOF-MS method for quantitation of DHAP in RBCs. The method involves simple protein precipitation, reverse phase C8 column chromatography, ion pairing with tributylamine, and long run time of 50 min to separate the two isomers (G3P and DHAP).

Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

PubMed

Rana, P; Sripathy, G; Varshney, A; Kumar, P; Devi, M Memita; Marwaha, R K; Tripathi, R P; Khushu, S

2012-02-01

Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

Effect of the Fatigue Induced by a 110-km Ultramarathon on Tibial Impact Acceleration and Lower Leg Kinematics

PubMed Central

Giandolini, Marlene; Gimenez, Philippe; Temesi, John; Arnal, Pierrick J.; Martin, Vincent; Rupp, Thomas; Morin, Jean-Benoit; Samozino, Pierre; Millet, Guillaume Y.

2016-01-01

Ultramarathon runners are exposed to a high number of impact shocks and to severe neuromuscular fatigue. Runners may manage mechanical stress and muscle fatigue by changing their running kinematics. Our purposes were to study (i) the effects of a 110-km mountain ultramarathon (MUM) on tibial shock acceleration and lower limb kinematics, and (ii) whether kinematic changes are modulated according to the severity of neuromuscular fatigue. Twenty-three runners participated in the study. Pre- and post-MUM, neuromuscular tests were performed to assess knee extensor (KE) and plantar flexor (PF) central and peripheral fatigue, and a treadmill running bouts was completed during which step frequency, peak acceleration, median frequency and impact frequency content were measured from tibial acceleration, as well as foot-to-treadmill, tibia-to-treadmill, and ankle flexion angles at initial contact, and ankle range of motion using video analysis. Large neuromuscular fatigue, including peripheral changes and deficits in voluntary activation, was observed in KE and PF. MVC decrements of ~35% for KE and of ~28% for PF were noted. Among biomechanical variables, step frequency increased by ~2.7% and the ankle range of motion decreased by ~4.1% post-MUM. Runners adopting a non rearfoot strike pre-MUM adopted a less plantarflexed foot strike pattern post-MUM while those adopting a rearfoot strike pre-MUM tended to adopt a less dorsiflexed foot strike pattern post-MUM. Positive correlations were observed between percent changes in peripheral PF fatigue and the ankle range of motion. Peripheral PF fatigue was also significantly correlated to both percent changes in step frequency and the ankle angle at contact. This study suggests that in a fatigued state, ultratrail runners use compensatory/protective adjustments leading to a flatter foot landing and this is done in a fatigue dose-dependent manner. This strategy may aim at minimizing the overall load applied to the musculoskeletal system, including impact shock and muscle stretch. PMID:27031830

Acute and chronic neuromuscular adaptations to local vibration training.

PubMed

Souron, Robin; Besson, Thibault; Millet, Guillaume Y; Lapole, Thomas

2017-10-01

Vibratory stimuli are thought to have the potential to promote neural and/or muscular (re)conditioning. This has been well described for whole-body vibration (WBV), which is commonly used as a training method to improve strength and/or functional abilities. Yet, this technique may present some limitations, especially in clinical settings where patients are unable to maintain an active position during the vibration exposure. Thus, a local vibration (LV) technique, which consists of applying portable vibrators directly over the tendon or muscle belly without active contribution from the participant, may present an alternative to WBV. The purpose of this narrative review is (1) to provide a comprehensive overview of the literature related to the acute and chronic neuromuscular changes associated with LV, and (2) to show that LV training may be an innovative and efficient alternative method to the 'classic' training programs, including in the context of muscle deconditioning prevention or rehabilitation. An acute LV application (one bout of 20-60 min) may be considered as a significant neuromuscular workload, as demonstrated by an impairment of force generating capacity and LV-induced neural changes. Accordingly, it has been reported that a training period of LV is efficient in improving muscular performance over a wide range of training (duration, number of session) and vibration (frequency, amplitude, site of application) parameters. The functional improvements are principally triggered by adaptations within the central nervous system. A model illustrating the current research on LV-induced adaptations is provided.

Neuromuscular fatigue following constant versus variable-intensity endurance cycling in triathletes.

PubMed

Lepers, R; Theurel, J; Hausswirth, C; Bernard, T

2008-07-01

The aim of this study was to determine whether or not variable power cycling produced greater neuromuscular fatigue of knee extensor muscles than constant power cycling at the same mean power output. Eight male triathletes (age: 33+/-5 years, mass: 74+/-4 kg, VO2max: 62+/-5 mL kg(-1) min(-1), maximal aerobic power: 392+/-17 W) performed two 30 min trials on a cycle ergometer in a random order. Cycling exercise was performed either at a constant power output (CP) corresponding to 75% of the maximal aerobic power (MAP) or a variable power output (VP) with alternating +/-15%, +/-5%, and +/-10% of 75% MAP approximately every 5 min. Maximal voluntary contraction (MVC) torque, maximal voluntary activation level and excitation-contraction coupling process of knee extensor muscles were evaluated before and immediately after the exercise using the technique of electrically evoked contractions (single and paired stimulations). Oxygen uptake, ventilation and heart rate were also measured at regular intervals during the exercise. Averaged metabolic variables were not significantly different between the two conditions. Similarly, reductions in MVC torque (approximately -11%, P<0.05) after cycling were not different (P>0.05) between CP and VP trials. The magnitude of central and peripheral fatigue was also similar at the end of the two cycling exercises. It is concluded that, following 30 min of endurance cycling, semi-elite triathletes experienced no additional neuromuscular fatigue by varying power (from +/-5% to 15%) compared with a protocol that involved a constant power.

Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury

DTIC Science & Technology

2010-09-01

adrenal insufficiency, hypopituitarism, hypothyroidism , growth- hormone deficiency and posterior pituitary dysfunction [53, 54, 56-60]. Growth...central hypothyroidism which can result in fatigue, apathy, decreased strength and cognitive dysfunction, symptoms commonly observed in PTSD [54

Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

PubMed

Sabharwal, Rasna; Chapleau, Mark W

2014-04-01

New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of LV dysfunction and higher mortality in Sgcd-/- mice. Treatment of Sgcd-/- mice with the angiotensin type 1 receptor blocker losartan for 8-9 weeks, beginning at 3 weeks of age, decreased fibrosis and oxidative stress in skeletal muscle, increased locomotor activity and prevented autonomic dysfunction. Chronic infusion of the counter-regulatory peptide angiotensin-(1-7) resulted in similar protection. We conclude that activation of the renin-angiotensin system, at a young age, contributes to skeletal muscle and autonomic dysfunction in muscular dystrophy. We speculate that the latter is mediated via abnormal sensory nerve and/or cytokine signalling from dystrophic skeletal muscle to the brain and contributes to age-related LV dysfunction, dilated cardiomyopathy, arrhythmias and premature death. Therefore, correcting the early autonomic dysregulation and renin-angiotensin system activation may provide a novel therapeutic approach in muscular dystrophy.

Physical examination of dizziness in athletes after a concussion: A descriptive study.

PubMed

Reneker, Jennifer C; Cheruvu, Vinay K; Yang, Jingzhen; James, Mark A; Cook, Chad E

2018-04-01

Dizziness is commonly reported after concussion. With the forces experienced at the time of the injury, several anatomical locations may have been altered, causing dizziness. Describe an objective examination and the types of impairment/dysfunction implicated by the results of clinical examination tests in subjects with dizziness after a concussion. Cross-Sectional. Athletes between ages 10-23 were enrolled with a diagnosis of concussion. An examination was completed to identify areas potentially contributing to dizziness, including tests of oculomotor control, the vestibular system, neuromotor control, and musculoskeletal components of the cervical spine. Descriptive analyses were completed to define the anatomical areas/types of dysfunction identified by positive findings of the examination tests. All (n = 41; 100%) subjects had examination findings consistent with central dysfunction. Of these, 36 (97.8%) had oculomotor control deficits; 29 (70.7%) demonstrated motion sensitivity; and 6 (15%) had central vestibular deficits. Nineteen (46.3%) had peripheral dysfunction, including 18 (43.9%) with unilateral hypofunction, and 2 (4.9%) with Benign Paroxysmal Positional Vertigo. Thirty-four (82.9%) had cervical dysfunction, with 11 (26.8%) presenting with cervicogenic dizziness, and 31 (75.6%) with altered neuromotor control. Functional injury to centrally-mediated pathways, specifically oculomotor control, and afferent and efferent pathways in the cervical spine are commonly identified through clinical examination tests in individuals with a complaint of dizziness post-concussion. According to results presented here, a high majority (90%) of the participants demonstrated dizziness that appeared to be multifactorial in nature and was not attributable to one main type of dysfunction. The common pathways between the systems make it difficult to isolate only one anatomical area as a contributor to dizziness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Review of the pathophysiological aspects involved in urological disease associated with metabolic syndrome.

PubMed

Sáenz Medina, J; Carballido Rodríguez, J

2016-06-01

Metabolic syndrome is a constellation of disorders that includes insulin resistance, central obesity, arterial hypertension and hyperlipidaemia. These disorders can have implications for the genitourinary apparatus. To conduct a review on the pathophysiological aspects that explain the relationship between metabolic syndrome and sexual dysfunction, lower urinary tract syndrome, prostate cancer and stone disease. We performed a qualitative, narrative literature review through a literature search on PubMed of articles published between 1997 and 2015, using the terms pathophysiology, metabolic syndrome, endothelial dysfunction, lipotoxicity, mitochondrial dysfunction, kidney stones, hypogonadism, erectile dysfunction, lower urinary tract syndrome and prostate cancer. Metabolic syndrome constitutes an established complex of symptoms, defined as the presence of insulin resistance, central obesity, hypertension and hyperlipidaemia. Endothelial dysfunction secondary to lipotoxicity generates an inflammatory state, which involves renal cell metabolism, vascularisation of the pelvis and androgen production. These facts explain the relationship between metabolic syndrome, nephrolithiasis, lower urinary tract syndrome, hypogonadism and erectile dysfunction in men. Strategies such as proper diet, regular exercise, insulin treatment, testosterone-replacement therapy, therapy with antioxidants and free-radical inhibitors and urological treatments classically used for lower urinary tract syndrome have shown promising results in this syndrome. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Hepatic dysfunction.

PubMed

McCord, Kelly W; Webb, Craig B

2011-07-01

This article reviews the common pathophysiology that constitutes hepatic dysfunction, regardless of the inciting cause. The systemic consequences of liver failure and the impact of this condition on other organ systems are highlighted. The diagnostic tests available for determining the cause and extent of liver dysfunction are outlined, treatment strategies aimed at supporting hepatic health and recovery are discussed, and prognosis is briefly covered. The article emphasizes the fact that because of the central role of the liver in maintaining normal systemic homeostasis, hepatic dysfunction cannot be effectively addressed as an isolated entity. Copyright © 2011 Elsevier Inc. All rights reserved.

In Vivo Magnetic Stimulation of Rat Sciatic Nerve With Centimeter- and Millimeter-Scale Solenoid Coils.

PubMed

Kagan, Zachary B; RamRakhyani, Anil Kumar; Lazzi, Gianluca; Normann, Richard A; Warren, David J

2016-11-01

Previous reports of magnetic stimulation of the peripheral nervous system (PNS) used various coil geometries, all with outer diameters larger than 35 mm, and stimulation energies in the 50 J range to evoke neural excitation. Recent reports of central nervous system (CNS) activation used sub-mm-scale solenoid coils with mJ energy levels. The goal of this study was to translate the lower energy levels from the CNS to the PNS via using smaller coils placed in closer proximity to the neural tissue. Such a performance improvement would advance the state of the art of magnetic stimulation and provide a path towards new neuroprosthetic devices. Primarily, we investigated the range of coil outer diameters from 25 mm down to 5 mm to better understand the dependence of coil diameter on energy required for PNS activation. Nine cm- and mm-scale copper solenoid coils, with various resistances, inductances, inner and outer diameters, and heights were compared by quantizing neuromuscular responses to magnetic stimulation via capacitive discharge excitation of rat sciatic nerves in vivo. Additionally, the effects of stimulus duration and coil position were investigated. As opposed to prior work, this study compares a subset of stimulation parameters in an intact nerve preparation, and shows that magnetic stimulation with coils that abut the nerve is a reliable, effective method of neuromuscular stimulation. Although we observed different energies required for neuromuscular activation depending on the coil and excitation parameters used, for the experimental configuration, devices, and stimulus waveform shapes presented in this manuscript, no systematic dependence of PNS activation on coil diameter was found, even for the mm-scale coils investigated herein. However, there was a clear relationship between discharge circuit capacitance and energy required to evoke a neuromuscular response. Coils approximately 12 mm in outer diameter and larger consistently evoked responses, whereas coils 5 mm in outer diameter did not. Furthermore, we observed meaningful neuromuscular excitation when stimulating with energies as low as 20 J. Although this is an improvement over prior work, it is still orders of magnitude greater than the energy required for conventional electrical stimulation, suggesting that these devices are presently not suitable for use in an application requiring continued pulsed stimulation. Nevertheless, these devices are suitable for basic research and as clinical tools that infrequently stimulate, such as in diagnostic applications.

Neuromuscular responses differ between slip-induced falls and recoveries in older adults

PubMed Central

Pai, Yi-Chung (Clive); Bhatt, Tanvi; Ting, Lena H.

2016-01-01

How does the robust control of walking and balance break down during a fall? Here, as a first step in identifying the neuromuscular determinants of falls, we tested the hypothesis that falls and recoveries are characterized by differences in neuromuscular responses. Using muscle synergy analysis, conventional onset latencies, and peak activity, we identified differences in muscle coordination between older adults who fell and those who recovered from a laboratory-induced slip. We found that subjects who fell recruited fewer muscle synergies than those who recovered, suggesting a smaller motor repertoire. During slip trials, compared with subjects who recovered, subjects who fell had delayed knee flexor and extensor onset times in the leading/slip leg, as well as different muscle synergy structure involving those muscles. Therefore, the ability to coordinate muscle activity around the knee in a timely manner may be critical to avoiding falls from slips. Unique to subjects who fell during slip trials were greater bilateral (interlimb) muscle activation and the recruitment of a muscle synergy with excessive coactivation. These differences in muscle coordination between subjects who fell and those who recovered could not be explained by differences in gait-related variables at slip onset (i.e., initial motion state) or variations in slip difficulty, suggesting that differences in muscle coordination may reflect differences in neural control of movement rather than biomechanical constraints imposed by perturbation or initial walking mechanics. These results are the first step in determining the causation of falls from the perspective of muscle coordination. They suggest that there may be a neuromuscular basis for falls that could provide new insights into treatment and prevention. Further research comparing the muscle coordination and mechanics of falls and recoveries within subjects is necessary to establish the neuromuscular causation of falls. NEW & NOTEWORTHY A central question relevant to the prevention of falls is: How does the robust control of walking and balance break down during a fall? Previous work has focused on muscle coordination during successful balance recoveries or the kinematics and kinetics of falls. Here, for the first time, we identified differences in the spatial and temporal coordination of muscles among older adults who fell and those who recovered from an unexpected slip. PMID:27832608

Neuromuscular responses differ between slip-induced falls and recoveries in older adults.

PubMed

Sawers, Andrew; Pai, Yi-Chung Clive; Bhatt, Tanvi; Ting, Lena H

2017-02-01

How does the robust control of walking and balance break down during a fall? Here, as a first step in identifying the neuromuscular determinants of falls, we tested the hypothesis that falls and recoveries are characterized by differences in neuromuscular responses. Using muscle synergy analysis, conventional onset latencies, and peak activity, we identified differences in muscle coordination between older adults who fell and those who recovered from a laboratory-induced slip. We found that subjects who fell recruited fewer muscle synergies than those who recovered, suggesting a smaller motor repertoire. During slip trials, compared with subjects who recovered, subjects who fell had delayed knee flexor and extensor onset times in the leading/slip leg, as well as different muscle synergy structure involving those muscles. Therefore, the ability to coordinate muscle activity around the knee in a timely manner may be critical to avoiding falls from slips. Unique to subjects who fell during slip trials were greater bilateral (interlimb) muscle activation and the recruitment of a muscle synergy with excessive coactivation. These differences in muscle coordination between subjects who fell and those who recovered could not be explained by differences in gait-related variables at slip onset (i.e., initial motion state) or variations in slip difficulty, suggesting that differences in muscle coordination may reflect differences in neural control of movement rather than biomechanical constraints imposed by perturbation or initial walking mechanics. These results are the first step in determining the causation of falls from the perspective of muscle coordination. They suggest that there may be a neuromuscular basis for falls that could provide new insights into treatment and prevention. Further research comparing the muscle coordination and mechanics of falls and recoveries within subjects is necessary to establish the neuromuscular causation of falls. A central question relevant to the prevention of falls is: How does the robust control of walking and balance break down during a fall? Previous work has focused on muscle coordination during successful balance recoveries or the kinematics and kinetics of falls. Here, for the first time, we identified differences in the spatial and temporal coordination of muscles among older adults who fell and those who recovered from an unexpected slip. Copyright © 2017 the American Physiological Society.

Auditory system dysfunction in Alzheimer disease and its prodromal states: A review.

PubMed

Swords, Gabriel M; Nguyen, Lydia T; Mudar, Raksha A; Llano, Daniel A

2018-07-01

Recent findings suggest that both peripheral and central auditory system dysfunction occur in the prodromal stages of Alzheimer Disease (AD), and therefore may represent early indicators of the disease. In addition, loss of auditory function itself leads to communication difficulties, social isolation and poor quality of life for both patients with AD and their caregivers. Developing a greater understanding of auditory dysfunction in early AD may shed light on the mechanisms of disease progression and carry diagnostic and therapeutic importance. Herein, we review the literature on hearing abilities in AD and its prodromal stages investigated through methods such as pure-tone audiometry, dichotic listening tasks, and evoked response potentials. We propose that screening for peripheral and central auditory dysfunction in at-risk populations is a low-cost and effective means to identify early AD pathology and provides an entry point for therapeutic interventions that enhance the quality of life of AD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

The effects of neuromuscular training on knee joint motor control during sidecutting in female elite soccer and handball players.

PubMed

Zebis, Mette K; Bencke, Jesper; Andersen, Lars L; Døssing, Simon; Alkjaer, Tine; Magnusson, S Peter; Kjaer, Michael; Aagaard, Per

2008-07-01

The project aimed to implement neuromuscular training during a full soccer and handball league season and to experimentally analyze the neuromuscular adaptation mechanisms elicited by this training during a standardized sidecutting maneuver known to be associated with non-contact anterior cruciate ligament (ACL) injury. The players were tested before and after 1 season without implementation of the prophylactic training and subsequently before and after a full season with the implementation of prophylactic training. A total of 12 female elite soccer players and 8 female elite team handball players aged 26 +/- 3 years at the start of the study. The subjects participated in a specific neuromuscular training program previously shown to reduce non-contact ACL injury. Neuromuscular activity at the knee joint, joint angles at the hip and knee, and ground reaction forces were recorded during a sidecutting maneuver. Neuromuscular activity in the prelanding phase was obtained 10 and 50 ms before foot strike on a force plate and at 10 and 50 ms after foot strike on a force plate. Neuromuscular training markedly increased before activity and landing activity electromyography (EMG) of the semitendinosus (P < 0.05), while quadriceps EMG activity remained unchanged. Neuromuscular training increased EMG activity for the medial hamstring muscles, thereby decreasing the risk of dynamic valgus. This observed neuromuscular adaptation during sidecutting could potentially reduce the risk for non-contact ACL injury.

Effects of nitric oxide on neuromuscular properties of developing zebrafish embryos.

PubMed

Jay, Michael; Bradley, Sophie; McDearmid, Jonathan Robert

2014-01-01

Nitric oxide is a bioactive signalling molecule that is known to affect a wide range of neurodevelopmental processes. However, its functional relevance to neuromuscular development is not fully understood. Here we have examined developmental roles of nitric oxide during formation and maturation of neuromuscular contacts in zebrafish. Using histochemical approaches we show that elevating nitric oxide levels reduces the number of neuromuscular synapses within the axial swimming muscles whilst inhibition of nitric oxide biosynthesis has the opposite effect. We further show that nitric oxide signalling does not change synapse density, suggesting that the observed effects are a consequence of previously reported changes in motor axon branch formation. Moreover, we have used in vivo patch clamp electrophysiology to examine the effects of nitric oxide on physiological maturation of zebrafish neuromuscular junctions. We show that developmental exposure to nitric oxide affects the kinetics of spontaneous miniature end plate currents and impacts the neuromuscular drive for locomotion. Taken together, our findings implicate nitrergic signalling in the regulation of zebrafish neuromuscular development and locomotor maturation.

Impact of neuromuscular electrical stimulation on functional capacity of patients with chronic kidney disease on hemodialysis.

PubMed

Roxo, Renata Spósito; Xavier, Vivian Bertoni; Miorin, Luiz Antônio; Magalhães, Andrea Olivares; Sens, Yvoty Alves Dos Santos; Alves, Vera Lúcia Dos Santos

2016-01-01

Literature shows that patients undergoing hemodialysis present poor physical conditioning and low tolerance to exercise. They may also suffer from respiratory dysfunctions. The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation on pulmonary function and functional capacity of patients with chronic kidney disease on hemodialysis. Forty adult patients with chronic kidney disease on hemodialysis were prospectively studied and randomized into two groups (control n = 20 and treatment n = 20). The treatment group underwent bilateral femoral quadriceps muscles electrical stimulation for 30 minutes during hemodialysis, three times per week, for two months. The patients were evaluated by pulmonary function test, maximum respiratory pressures, maximum one-repetition test, and six-minute walk test (6MWT), before and after the treatment protocol. The treatment group presented increased maximum inspiratory (MIP) (p = 0.02) and expiratory pressures (MEP) (p < 0.0001), muscular strength in maximum one-repetition test (p < 0.001), and distance covered in the 6MWT (p = 0.03), and decreased systolic blood pressure (p < 0.001) and respiratory frequency (p < 0.001) when compared with the control group. Electrical neuromuscular stimulation had a positive impact on pulmonary function and functional capacity, leading to better physical performance in patients on hemodialysis. Pacientes submetidos à hemodiálise apresentam baixo condicionamento físico além de serem acometidos por disfunções respiratórias. Objetivamos avaliar os efeitos da estimulação elétrica neuromuscular na função pulmonar e capacidade funcional de pacientes com doença renal crônica em hemodiálise. 40 adultos com doença renal crônica em hemodiálise foram estudados prospectivamente e randomizados em dois grupos (controle n = 20 e tratamento n = 20). O grupo tratamento realizou protocolo com estimulação elétrica neuromuscular em quadríceps femoral por 30 minutos durante a hemodiálise, três vezes por semana, durante dois meses. Todos pacientes realizaram espirometria, pressões respiratórias máximas, teste de uma repetição máxima e teste da caminhada dos seis minutos (TC6), antes e após o período de acompanhamento. O grupo tratamento apresentou aumento da pressão inspiratória máxima com p = 0,02 na comparação entre grupos e p < 0,001 para a pressão máxima expiratória. O teste de uma repetição máxima e a distância percorrida no TC6 apresentaram-se maiores após o protocolo no grupo de tratamento com p < 0,001 e 0,03 respectivamente. Houve diminuição da pressão arterial sistólica (p < 0,001) e frequência respiratória (p < 0,001) após a estimulação elétrica quando comparado ao grupo controle. A estimulação elétrica neuromuscular teve impacto positivo sobre a função pulmonar e a capacidade funcional levando ao melhor desempenho físico em pacientes em hemodiálise.

Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial.

PubMed

de Souza, Camila M; Tardelli, Maria A; Tedesco, Helio; Garcia, Natalia N; Caparros, Mario P; Alvarez-Gomez, Jose A; de Oliveira Junior, Itamar S

2015-10-01

Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. A prospective clinical trial. Two university hospitals, from 1 October 2011 to 31 January 2012. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) <30 ml min] and 20 control patients (ClCr >90 ml min). Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5.6 ± 3.6 min) compared with the control group (2.7 ± 1.3 min, P = 0.003). No adverse events or evidence of recurrence of neuromuscular block were observed. In patients with renal failure, sugammadex (4 mg kg) effectively and safely reversed profound rocuronium induced neuromuscular block, but the recovery was slower than healthy patients. Clinicaltrials.gov identifier NCT01785758.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

PubMed

Murray, Michael J; DeBlock, Heidi; Erstad, Brian; Gray, Anthony; Jacobi, Judi; Jordan, Che; McGee, William; McManus, Claire; Meade, Maureen; Nix, Sean; Patterson, Andrew; Sands, M Karen; Pino, Richard; Tescher, Ann; Arbour, Richard; Rochwerg, Bram; Murray, Catherine Friederich; Mehta, Sangeeta

2016-11-01

To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Chronic effect of different types of stretching on ankle dorsiflexion range of motion: Systematic review and meta-analysis.

PubMed

Medeiros, Diulian Muniz; Martini, Tamara Fenner

2018-03-01

The calf muscles are one of the muscle groups that have the most need for adequate flexibility since they are deeply related to normal lower limb function. When the goal is to increase flexibility, the most commonly used technique is stretching. However, it remains unknown which stretching technique and parameters are the most effective to increase flexibility. Hence, the aim of the current review was to investigate the influence of chronic stretching on ankle dorsiflexion range of motion (DFROM) of healthy individuals. The search strategy included MEDLINE, PEDro, Cochrane CENTRAL, LILACS, and manual search from inception to February 2017. Randomized and controlled clinical trials that have analyzed the influence of chronic stretching on DFROM were included. On the other hand, studies with special populations (children, and people with any dysfunction/disease), and articles with no control group were excluded. Twenty studies were included out of 493 identified. The meta-analysis was performed according to the stretching technique used in the study. The results show that static stretching (5.17°; 95% CI: 4.39-5.95; I 2 : 0%) and proprioceptive neuromuscular facilitation (4.32°; 95% CI: 1.59-7.04; I 2 : 46%) are effective in increasing DFROM. Ballistic stretching did not show positive results to increase DFROM (3.77°; 95% CI: -0.03 to 7.56; I 2 : 46%). In conclusion, chronic stretching is an effective way of improving ankle mobility in healthy individuals, especially when it contains a static component. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rehabilitation of syndesmotic (high) ankle sprains.

PubMed

Williams, Glenn N; Allen, Eric J

2010-11-01

High ankle sprains are common in athletes who play contact sports. Most high ankle sprains are treated nonsurgically with a rehabilitation program. All years of PUBMED, Cochrane Database of Systematic Reviews, CINAHL PLUS, SPORTDiscuss, Google Scholar, and Web of Science were searched to August 2010, cross-referencing existing publications. Keywords included syndesmosis ankle sprain or high ankle sprain and the following terms: rehabilitation, treatment, cryotherapy, braces, orthosis, therapeutic modalities, joint mobilization, massage, pain, pain medications, TENS (ie, transcutaneous electric nerve stimulation), acupuncture, aquatic therapy, strength, neuromuscular training, perturbation training, and outcomes. Level of evidence, 5. A 3-phase rehabilitation program is described. The acute phase is directed at protecting the joint while minimizing pain, inflammation, muscle weakness, and loss of motion. Most patients are treated with some form of immobilization and have weightbearing restrictions. A range of therapeutic modalities are used to minimize pain and inflammation. Gentle mobilization and resistance exercises are used to gain mobility and maintain muscle size and strength. The subacute phase is directed at normalizing range of motion, strength, and function in activities of daily living. Progressive mobilization and strengthening are hallmarks of this phase. Neuromuscular training is begun and becomes the central component of rehabilitation. The advanced training phase focuses on preparing the patient for return to sports participation. Perturbation of support surfaces, agility drills, plyometrics, and sport-specific training are central components of this phase. The rehabilitation guidelines discussed may assist clinicians in managing syndesmotic ankle sprains.

Central and peripheral fatigue in knee and elbow extensor muscles after a long-distance cross-country ski race.

PubMed

Boccia, G; Dardanello, D; Zoppirolli, C; Bortolan, L; Cescon, C; Schneebeli, A; Vernillo, G; Schena, F; Rainoldi, A; Pellegrini, B

2017-09-01

Although elbow extensors (EE) have a great role in cross-country skiing (XC) propulsion, previous studies on neuromuscular fatigue in long-distance XC have investigated only knee extensor (KE) muscles. In order to investigate the origin and effects of fatigue induced by long-distance XC race, 16 well-trained XC skiers were tested before and after a 56-km classical technique race. Maximal voluntary isometric contraction (MVC) and rate of force development (RFD) were measured for both KE and EE. Furthermore, electrically evoked double twitch during MVC and at rest were measured. MVC decreased more in KE (-13%) than in EE (-6%, P = 0.016), whereas the peak RFD decreased only in EE (-26%, P = 0.02) but not in KE. The two muscles showed similar decrease in voluntary activation (KE -5.0%, EE -4.8%, P = 0.61) and of double twitch amplitude (KE -5%, EE -6%, P = 0.44). A long-distance XC race differently affected the neuromuscular function of lower and upper limbs muscles. Specifically, although the strength loss was greater for lower limbs, the capacity to produce force in short time was more affected in the upper limbs. Nevertheless, both KE and EE showed central and peripheral fatigue, suggesting that the origins of the strength impairments were multifactorial for the two muscles. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density: A study in 417 older women.

PubMed

Belavý, Daniel L; Armbrecht, Gabriele; Blenk, Tilo; Bock, Oliver; Börst, Hendrikje; Kocakaya, Emine; Luhn, Franziska; Rantalainen, Timo; Rawer, Rainer; Tomasius, Frederike; Willnecker, Johannes; Felsenberg, Dieter

2016-02-01

We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD. Copyright © 2015 Elsevier Inc. All rights reserved.

Caspase 6 has a protective role in SOD1(G93A) transgenic mice.

PubMed

Hogg, Marion C; Mitchem, Mollie R; König, Hans-Georg; Prehn, Jochen H M

2016-06-01

In amyotrophic lateral sclerosis (ALS), it has been suggested that the process of neurodegeneration starts at the neuromuscular junction and is propagated back along axons towards motor neurons. Caspase-dependent pathways are well established as a cause of motor neuron death, and recent work in other disease models indicated a role for caspase 6 in axonal degeneration. Therefore we hypothesised that caspase 6 may be involved in motor neuron death in ALS. To investigate the role of caspase 6 in ALS we profiled protein levels of caspase-6 throughout disease progression in the ALS mouse model SOD1(G93A); this did not reveal differences in caspase 6 levels during disease. To investigate the role of caspase 6 further we generated a colony with SOD1(G93A) transgenic mice lacking caspase 6. Analysis of the transgenic SOD1(G93A); Casp6(-/-) revealed an exacerbated phenotype with motor dysfunction occurring earlier and a significantly shortened lifespan when compared to transgenic SOD1(G93A); Casp6(+/+) mice. Immunofluorescence analysis of the neuromuscular junction revealed no obvious difference between caspase 6(+/+) and caspase 6(-/-) in non-transgenic mice, while the SOD1(G93A) transgenic mice showed severe degeneration compared to non-transgenic mice in both genotypes. Our data indicate that caspase-6 does not exacerbate ALS pathogenesis, but may have a protective role. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of innovative virtual reality game and EMG biofeedback on neuromotor control in cerebral palsy.

PubMed

Yoo, Ji Won; Lee, Dong Ryul; Sim, Yon Ju; You, Joshua H; Kim, Cheol J

2014-01-01

Sensorimotor control dysfunction or dyskinesia is a hallmark of neuromuscular impairment in children with cerebral palsy (CP), and is often implicated in reaching and grasping deficiencies due to a neuromuscular imbalance between the triceps and biceps. To mitigate such muscle imbalances, an innovative electromyography (EMG)-virtual reality (VR) biofeedback system were designed to provide accurate information about muscle activation and motivation. However, the clinical efficacy of this approach has not yet been determined in children with CP. The purpose of this study was to investigate the effectiveness of a combined EMG biofeedback and VR (EMG-VR biofeedback) intervention system to improve muscle imbalance between triceps and biceps during reaching movements in children with spastic CP. Raw EMG signals were recorded at a sampling rate of 1,000 Hz, band-pass filtered between 20-450 Hz, and notch-filtered at 60 Hz during elbow flexion and extension movements. EMG data were then processed using MyoResearch Master Edition 1.08 XP software. All participants underwent both interventions consisting of the EMG-VR biofeedback combination and EMG biofeedback alone. EMG analysis resulted in improved muscle activation in the underactive triceps while decreasing overactive or hypertonic biceps in the EMG-VR biofeedback compared with EMG biofeedback. The muscle imbalance ratio between the triceps and biceps was consistently improved. The present study is the first clinical trial to provide evidence for the additive benefits of VR intervention for enhancing the upper limb function of children with spastic CP.

The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock

PubMed Central

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-01-01

Abstract Introduction: Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. Methods and analysis: It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect. PMID:29419665

Impaired Inhibitory Force Feedback in Fixed Dystonia.

PubMed

Mugge, Winfred; Schouten, Alfred C; van Hilten, Jacobus J; van der Helm, Frans C T

2016-04-01

Complex regional pain syndrome (CRPS) is a multifactorial disorder associated with an aberrant host response to tissue injury. About 25% of CRPS patients suffer poorly understood involuntary sustained muscle contractions associated with dysfunctional reflexes that result in abnormal postures (fixed dystonia). A recent modeling study simulated fixed dystonia (FD) caused by aberrant force feedback. The current study aims to validate this hypothesis by experimentally recording the modulation of reflexive force feedback in patients with FD. CRPS patients with and without FD, patients with FD but without CRPS, as well as healthy controls participated in the experiment. Three task instructions and three perturbation characteristics were used to evoke a wide range of responses to force perturbations. During position tasks ("maintain posture"), healthy subjects as well as patients resisted the perturbations, becoming more stiff than when being relaxed (i.e., the relax task). Healthy subjects and CRPS patients without FD were both more compliant during force tasks ("maintain force") than during relax tasks, meaning they actively gave way to the imposed forces. Remarkably, the patients with FD failed to do so. A neuromuscular model was fitted to the experimental data to separate the distinct contributions of position, velocity and force feedback, as well as co-contraction to the motor behavior. The neuromuscular modeling indicated that inhibitory force feedback is deregulated in patients with FD, for both CRPS and non-CRPS patients. From previously published simulation results and the present experimental study, it is concluded that aberrant force feedback plays a role in fixed dystonia.

Are corticosteroids useful in all degrees of severity and rapid recovery of Bell's palsy?

PubMed

Ferreira, Margarida; Firmino, Machado J; Marques, Elisa A; Santos, Paula C; Duarte, José A

2016-07-01

Conclusions The results provide preliminary evidence that corticosteroids were not effective in all grades of dysfunction and for achieving a rapid remission in the early phase of BP, highlighting the need to define standard and rigorous criteria to prescribe corticosteroids in these patients. Objectives The main aim of this study was to investigate whether the use of corticosteroids better associated than paralleled with neuromuscular training (C + FNT) is more effective than facial neuromuscular training (FNT) applied alone, in terms of recovery degree and facial symmetry during the early phase of Bell's palsy (BP). Patients and methods A prospective single-blinded study involved 73 patients: the C + FNT group (n = 42; median age = 37.5 years) and FNT group (n = 31; median age = 49.0 years). Patients were assessed before and 6 weeks after treatment by House-Brackmann (HB-FGS) and Sunnybrook Facial Grading System (SB-FGS). Results Recovery degree and facial symmetry improved significantly in both groups (p < 0.001), without differences between groups (p > 0.05). However, the C + FNT group displayed better outcomes for cheek (p = 0.004) and mouth (p = 0.022) resting symmetry at SB-FGS, instead of compared to the FNT group. The corticosteroids had no significant effect on all recovery degrees (p = 0.992) and rapid remission (p = 0.952). Multiple linear regression analysis showed that the type of intervention was not a significant predictor for recovery degree (p = 0.917).

Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

PubMed

Sloan, Paul A; Rasul, Mazhar

2002-01-01

We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

Chronic perineal pain: current pathophysiological aspects, diagnostic approaches and treatment.

PubMed

Andromanakos, Nikolaos P; Kouraklis, Grigorios; Alkiviadis, Kostakis

2011-01-01

Chronic perineal pain is the anorectal and perineal pain without underlying organic disease, anorectal or endopelvic, which has been excluded by careful physical examination, radiological and endoscopic investigations. A variety of neuromuscular disorders of the pelvic floor lead to the different pathological conditions such as anorectal incontinence, urinary incontinence and constipation of obstructed defecation, sexual dysfunction and pain syndromes. The most common functional disorders of the pelvic floor muscles, accompanied by perineal pain are levator ani syndrome, proctalgia fugax, myofascial syndrome and coccygodynia. In the diagnosis of these syndromes, contributing to a thorough history, physical examination, selected specialized investigations and the exclusion of organic disease with proctalgia is carried out. Accurate diagnosis of the syndromes helps in choosing an appropriate treatment and in avoiding unnecessary and ineffective surgical procedures, which often are performed in an attempt to alleviate the patient's symptoms.

Neurological Complications in a Polynesian Traveler with Dengue.

PubMed

Doi, Maegan Lm; Tatsuno, Sydney Y; Singh, Gurdev; Tatsuno, Eric M; Mau, Marjorie M

2017-10-01

In recent times, there has been an increased focus on mosquito-borne Flaviviruses, in particular dengue and Zika. With the reappearance of dengue in Hawai'i and the mainland United States (US), clinicians should be aware of both the common presentations of dengue, as well as other less common complications associated with the disease. Dengue can result in neurologic disorders such as encephalopathy, encephalitis, immune-mediated syndromes, neuromuscular dysfunction, and neuro-ophthalmologic disorders. We present an interesting case of dengue that initially presented with classic symptoms (arthropathy, biphasic fever, and rash) and subsequently developed into a neurologic movement disorder with muscle tightening and twitching of the face, chest, and extremities. We review and update the epidemiology, biology, the clinical presentations including the neurologic complications associated with dengue, as well as their management and areas of future study in this field.

Musculoskeletal disorders (MSDs) and dental practice Part 2. Risk factors for dentistry, magnitude of the problem, prevention, and dental ergonomics.

PubMed

Yamalik, Nermin

2007-02-01

As a consequence of occupational stresses placed on their bodies, oral health care providers (OHP) are vulnerable to musculoskeletal disorders (MSDs). Muscular imbalance, neuromuscular inhibition, and pain and dysfunction may frequently be observed among OHP. Repeated unnatural, deviated or inadequate working postures, forceful hand movements, inadequate equipment or workplace designs and inappropriate work patterns are likely to be the particular risk factors. However, WMSDs are not an avoidable part of OHPs' professional lives. Paying the necessary attention to occupational and individual risk factors, prevalence, symptoms and consequences of WMSDs, and implementing the recommended health and safety measures can enable a long and healthy career. This review essentially aims to provide background information for OHP regarding the magnitude of the problem, particular risk factors and the available recommendations for prevention.

Respiratory chain deficiency in aged spinal motor neurons☆

PubMed Central

Rygiel, Karolina A.; Grady, John P.; Turnbull, Doug M.

2014-01-01

Sarcopenia, muscle wasting, and strength decline with age, is an important cause of loss of mobility in the elderly individuals. The underlying mechanisms are uncertain but likely to involve defects of motor nerve, neuromuscular junction, and muscle. Loss of motor neurons with age and subsequent denervation of skeletal muscle has been recognized as one of the contributing factors. This study investigated aspects of mitochondrial biology in spinal motor neurons from elderly subjects. We found that protein components of complex I of mitochondrial respiratory chain were reduced or absent in a proportion of aged motor neurons–a phenomenon not observed in fetal tissue. Further investigation showed that complex I-deficient cells had reduced mitochondrial DNA content and smaller soma size. We propose that mitochondrial dysfunction in these motor neurons could lead to the cell loss and ultimately denervation of muscle fibers. PMID:24684792

Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction.

PubMed

Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

2015-12-01

[Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period.

Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction

PubMed Central

Shim, Jae-Kwang; Choi, Ho-Suk; Shin, Jun-Ho

2015-01-01

[Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period. PMID:26834316

Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

PubMed

Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

2015-12-10

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.

Beyond the Joint: The Role of Central Nervous System Reorganizations in Chronic Musculoskeletal Disorders.

PubMed

Roy, Jean-Sébastien; Bouyer, Laurent J; Langevin, Pierre; Mercier, Catherine

2017-11-01

To a large extent, management of musculoskeletal disorders has traditionally focused on structural dysfunctions found within the musculoskeletal system, mainly around the affected joint. While a structural-dysfunction approach may be effective for musculoskeletal conditions in some populations, especially in acute presentations, its effectiveness remains limited in patients with recurrent or chronic musculoskeletal pain. Numerous studies have shown that the human central nervous system can undergo plastic reorganizations following musculoskeletal disorders; however, they can be maladaptive and contribute to altered joint control and chronic pain. In this Viewpoint, the authors argue that to improve rehabilitation outcomes in patients with chronic musculoskeletal pain, a global view of the disorder that incorporates both central (neural) and peripheral (joint-level) changes is needed. The authors also discuss the challenge of evaluating and rehabilitating central changes and the need for large, high-level studies to evaluate approaches incorporating central and peripheral changes and emerging therapies. J Orthop Sports Phys Ther 2017;47(11):817-821. doi:10.2519/jospt.2017.0608.

Neuromuscular Impairment Following Backpack Load Carriage

PubMed Central

Blacker, Sam D.; Fallowfield, Joanne L.; Bilzon, James L.J.; Willems, Mark E.T.

Load Carriage using backpacks is an occupational task and can be a recreational pursuit. The aim of this study was to investigate the mechanisms responsible for changes in neuromuscular function of the m. quadriceps femoris following load carriage. The physiological responses of 10 male participants to voluntary and electrically stimulated isometric contractions were measured before and immediately after two hours of treadmill walking at 6.5 km•h −1 during level walking with no load [LW], and level walking with load carriage (25 kg backpack) [LC]. Maximal voluntary contraction force decreased by 15 ± 11 % following LC (p=0.006), with no change following LW (p=0.292). Voluntary activation decreased after LW and LC (p=0.033) with no difference between conditions (p=0.405). Doublet contraction time decreased after both LW and LC (p=0.002), with no difference between conditions (p=0.232). There were no other changes in electrically invoked doublet parameters in either condition. The 20:50 Hz ratio did not change following LW (p=0.864) but decreased from 0.88 ± 0.04 to 0.84 ± 0.04 after LC (p=0.011) indicating reduced Ca2+ release from the sarcoplasmic reticulum during excitation contraction coupling. In conclusion, two hours of load carriage carrying a 25 kg back pack caused neuromuscular impairment through a decrease in voluntary activation (i.e. central drive) and fatigue or damage to the peripheral muscle, including impairment of the excitation contraction coupling process. This may reduce physical performance and increase the risk of musculoskeletal injury. PMID:24146709

A current approach to heart failure in Duchenne muscular dystrophy.

PubMed

D'Amario, Domenico; Amodeo, Antonio; Adorisio, Rachele; Tiziano, Francesco Danilo; Leone, Antonio Maria; Perri, Gianluigi; Bruno, Piergiorgio; Massetti, Massimo; Ferlini, Alessandra; Pane, Marika; Niccoli, Giampaolo; Porto, Italo; D'Angelo, Gianluca A; Borovac, Josip Anđelo; Mercuri, Eugenio; Crea, Filippo

2017-11-01

Duchenne muscular dystrophy (DMD) is a genetic, progressive neuromuscular condition that is marked by the long-term muscle deterioration with significant implications of pulmonary and cardiac dysfunction. As such, end-stage heart failure (HF) in DMD is increasingly becoming the main cause of death in this population. The early detection of cardiomyopathy is often challenging, due to a long subclinical phase of ventricular dysfunction and difficulties in assessment of cardiovascular symptomatology in these patients who usually loose ambulation during the early adolescence. However, an early diagnosis of cardiovascular disease in patients with DMD is decisive since it allows a timely initiation of cardioprotective therapies that can mitigate HF symptoms and delay detrimental heart muscle remodelling. Echocardiography and ECG are standardly used for screening and detection of cardiovascular abnormalities in these patients, although these tools are not always adequate to detect an early, clinically asymptomatic phases of disease progression. In this regard, cardiovascular magnetic resonance (CMR) with late gadolinium enhancement is emerging as a promising method for the detection of early cardiac involvement in patients with DMD. The early detection of cardiac dysfunction allows the therapeutic institution of various classes of drugs such as corticosteroids, beta-blockers, ACE inhibitors, antimineralocorticoid diuretics and novel pharmacological and surgical solutions in the multimodal and multidisciplinary care for this group of patients. This review will focus on these challenges and available options for HF in patients with DMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

PubMed

Yamada, Yuka; Kawakami, Michiyuki; Wada, Ayako; Otsuka, Tomoyoshi; Muraoka, Kaori; Liu, Meigen

2018-06-01

Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p < 0.001). In the BMD group, total VDS score significantly correlated with Swinyard stage (r = 0.78, p < 0.001), but not with age or lung function. Patients with BMD have swallowing problems similar to those observed in patients with DMD when matched according to physical functional status. These patients should be evaluated and followed-up for the duration of their disease. Implications for rehabiliation Dysphagia is one of the most critical problems in patients with progressive neuromuscular disease but dysphagia in patients with Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

Bladder, bowel, and sexual dysfunction in Parkinson's disease.

PubMed

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called "pelvic organ" dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and "prokinetic" drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life.

Bladder, Bowel, and Sexual Dysfunction in Parkinson's Disease

PubMed Central

Sakakibara, Ryuji; Kishi, Masahiko; Ogawa, Emina; Tateno, Fuyuki; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori

2011-01-01

Bladder dysfunction (urinary urgency/frequency), bowel dysfunction (constipation), and sexual dysfunction (erectile dysfunction) (also called “pelvic organ” dysfunctions) are common nonmotor disorders in Parkinson's disease (PD). In contrast to motor disorders, pelvic organ autonomic dysfunctions are often nonresponsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine-basal ganglia circuit, which normally suppresses the micturition reflex. By contrast, peripheral myenteric pathology causing slowed colonic transit (loss of rectal contractions) and central pathology causing weak strain and paradoxical anal sphincter contraction on defecation (PSD, also called as anismus) are responsible for the bowel dysfunction. In addition, hypothalamic dysfunction is mostly responsible for the sexual dysfunction (decrease in libido and erection) in PD, via altered dopamine-oxytocin pathways, which normally promote libido and erection. The pathophysiology of the pelvic organ dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. Dietary fibers, laxatives, and “prokinetic” drugs such as serotonergic agonists are used to treat bowel dysfunction in PD. Phosphodiesterase inhibitors are used to treat sexual dysfunction in PD. These treatments might be beneficial in maximizing the patients' quality of life. PMID:21918729

The effect of pelvic floor muscle training alone or in combination with electrostimulation in the treatment of sexual dysfunction in women with multiple sclerosis.

PubMed

Lúcio, A C; D'Ancona, C A L; Lopes, M H B M; Perissinotto, M C; Damasceno, B P

2014-11-01

Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD. © The Author(s), 2014.

Intrinsic neuromodulation: altering neuronal circuits from within.

PubMed

Katz, P S; Frost, W N

1996-02-01

There are two sources of neuromodulation for neuronal circuits: extrinsic inputs and intrinsic components of the circuits themselves. Extrinsic neuromodulation is known to be pervasive in nervous systems, but intrinsic neuromodulation is less recognized, despite the fact that it has now been demonstrated in sensory and neuromuscular circuits and in central pattern generators. By its nature, intrinsic neuromodulation produces local changes in neuronal computation, whereas extrinsic neuromodulation can cause global changes, often affecting many circuits simultaneously. Studies in a number of systems are defining the different properties of these two forms of neuromodulation.

Preparing for the unexpected: special considerations and complications after sugammadex administration.

PubMed

Iwasaki, Hajime; Renew, J Ross; Kunisawa, Takayuki; Brull, Sorin J

2017-10-17

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

Distribution of serine/threonine kinase SAD-B in mouse peripheral nerve synapse.

PubMed

Hagiwara, Akari; Harada, Kenu; Hida, Yamato; Kitajima, Isao; Ohtsuka, Toshihisa

2011-05-11

The serine/threonine kinase SAD regulates neural functions such as axon/dendrite polarization and neurotransmitter release. In the vertebrate central nervous system, SAD-B, a homolog of Caenorhabditis elegans SAD-1, is associated with synaptic vesicles and the active zone cytomatrix in nerve terminals. However, the distribution of SAD-B in the peripheral nervous system remains elusive. Here, we show that SAD-B is specifically localized to neuromuscular junctions. Although the active zone protein bassoon showed a punctated signal indicating its localization to motor end plates, SAD-B shows relatively diffuse localization indicating its association with both the active zone and synaptic vesicles. Therefore, SAD kinase may regulate neurotransmitter release from motor end plates in a similar manner to its regulation of neurotransmitter release in the central nervous system.

Sex differences in the effects of androgens acting in the central nervous system on metabolism

PubMed Central

Morford, Jamie; Mauvais-Jarvis, Franck

2016-01-01

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner. We compare the organizational actions of testosterone, which program the hypothalamic control of metabolic homeostasis during development, and the activational actions of testosterone, which affect metabolic function after puberty. We also discuss how the metabolic effect of testosterone is centrally mediated via the androgen receptor. PMID:28179813

[Impact of a quality assurance program on the use of neuromuscular monitoring and reversal of muscle relaxants].

PubMed

Motamed, C; Bourgain, J-L

2009-04-01

As part of a quality assurance in the anaesthesia department, this study was designed to enhance the rate of neuromuscular blockade monitoring for patients receiving muscle relaxant during anaesthesia. After approval of our local ethical committee, we assessed 200 computerized anaesthesia records in which neuromuscular relaxants were used. The following data were collected: demographic characteristics, durations of anaesthesia and surgery, use of neuromuscular monitoring, reversal agents and the quality of neuromuscular monitoring. The results were discussed with all anaesthesia providers of the department and an internal guideline was elaborated with the endpoint that all patients having muscle relaxants should have quantitative neuromuscular monitoring. Six months later, another assessment of 200 consecutive records collected the same data to check the efficiency of the elaborated guideline. The monitoring rate was of 67% at the first assessment and increased to 94% (p<0.05). The reversal rate was at 48% in the first assessment and was stable at the second assessment (50%). The rate of patients not monitored and not reversed decreased from 5 to 2% (p<0.05). This study shows that as part of a quality assurance program systematic quantitative monitoring of neuromuscular blockade can be significantly increased.

Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects.

PubMed

Yuan, Chun-Su

2007-06-01

To review the mechanisms of action of methylnaltrexone and its effects on opioid bowel dysfunction, as well as its effects on other opioid-induced adverse effects (ADEs), and its potential roles in clinical practice. A literature search using the MEDLINE and Cochrane Collaboration databases for articles published between 1966 and March 2007 was performed. Additional data sources were obtained from manual searches of recent journal articles, book chapters, and monographs. An updated literature search showed no additional publications. Abstracts and original preclinical and clinical research reports published in the English language were identified for review. Review articles, commentaries, and news reports of this compound were excluded. Literature related to opioids, opioid receptors, opioid antagonists, methylnaltrexone, opioid-induced bowel dysfunction, constipation, nausea, and vomiting was evaluated and selected based on consideration of the support shown for the proof of concept, mechanistic findings, and timeliness. Fifty-eight original articles from preclinical studies and clinical trials using methylnaltrexone were identified. Pharmacologic action, benefits, and ADEs of methylnaltrexone were reviewed, with a focus on its effects on bowel dysfunction after opioids. Emphases were placed on its receptor binding activities and therapeutically relevant sites of action (peripheral vs central), in which peripheral opioid receptors in the body contribute to physiological and drug-induced effects. Morphine and related opioids are associated with a number of limiting ADEs, including opioid-induced bowel dysfunction. Methylnaltrexone, a quaternary derivative of naltrexone, blocks peripheral effects of opioids while sparing central analgesic effects. It is currently under late-stage clinical investigation for the treatment of opioid-induced constipation in patients with advanced illness. Reported results showed the drug to be generally well-tolerated. The rapid reversal of constipation is very encouraging. Hastening postoperative discharge may also be possible. Methylnaltrexone has the potential to prevent or treat opioid-induced peripherally mediated ADEs on bowel dysfunction without interfering with central analgesia. The study of methylnaltrexone leads to a greater understanding of the mechanisms of action of opioid pharmacology.

Management of Cardiac Involvement in NeuroMuscular Diseases: Review

PubMed Central

Bouhouch, Rachida; Elhouari, Tarik; Oukerraj, Latifa; Fellat, Ibtissam; Zarzur, Jamila; Bennani, Rajaa; Arharbi, Mhamed

2008-01-01

Neuromuscular Diseases are a heterogeneous molecular, clinical and prognosis group. Progress has been achieved in the understanding and classification of these diseases. Cardiac involvement in neuromuscular diseases namely conduction disorders, ventricular dilatation and dilated cardiomyopathy with its impact on prognosis, is often dissociated from the peripheral myopathy. Therefore, close surveillance is mandatory in the affected patients. In this context, preventive therapy (beta-blockers and angiotensin converting enzyme inhibitors) has been recently recommended in the most common Neuromuscular Diseases, Duchenne Muscular Dystrophy and Myotonic Dystrophy. PMID:19337361

Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency.

PubMed

Thomsen, J L; Nielsen, C V; Palmqvist, D F; Gätke, M R

2015-07-01

Patients with butyrylcholinesterase (BChE) deficiency can experience prolonged paralysis after receiving suxamethonium or mivacurium. We hypothesized that patients suspected of BChE deficiency had a higher risk of being awakened while paralysed and having respiratory complications if neuromuscular monitoring was not applied before awakening. We retrospectively included patients referred to the Danish Cholinesterase Research Unit between 2004 and 2012 on suspicion of BChE deficiency. We collected data on genotype, BChE activity, neuromuscular blocking agents administered, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation <90%, assisted ventilation, reintubation of the trachea, and pulmonary aspiration. Patients were classified as prematurely awakened if anaesthesia had been terminated while the patient was still paralysed. We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored and monitored patients, respectively (P<0.001, Fisher's exact test). In 11 of the monitored patients, the results of neuromuscular monitoring were interpreted as equipment failure or were disregarded. Respiratory complications occurred in 19 (25%) and five (10%) of the unmonitored and monitored patients, respectively (P=0.06). Patients with BChE deficiency are at higher risk of being awakened while paralysed if neuromuscular monitoring is not applied or used; neuromuscular monitoring is recommended whenever a neuromuscular blocking agent is administered. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Recommendations on the use of deep neuromuscular blockade by anaesthesiologists and surgeons. AQUILES (Anestesia QUIrúrgica para Lograr Eficiencia y Seguridad) Consensus.

PubMed

Errando-Oyonarte, C L; Moreno-Sanz, C; Vila-Caral, P; Ruiz de Adana-Belbel, J C; Vázquez-Alonso, E; Ramírez-Rodríguez, J M; Veiga-Ruiz, G; Guasch-Arévalo, E; Lora-Tamayo D'Ocón, J I

2017-02-01

Neuromuscular blockade enables airway management, ventilation and surgical procedures. However there is no national consensus on its routine clinical use. The objective was to establish the degree of agreement among anaesthesiologists and general surgeons on the clinical use of neuromuscular blockade in order to make recommendations to improve its use during surgical procedures. Multidisciplinary consensus study in Spain. Anaesthesiologists experts in neuromuscular blockade management (n=65) and general surgeons (n=36) were included. Delphi methodology was selected. A survey with 17 final questions developed by a dedicated scientific committee was designed. The experts answered the successive questions in two waves. The survey included questions on: type of surgery, type of patient, benefits/harm during and after surgery, impact of objective neuromuscular monitoring and use of reversal drugs, viability of a multidisciplinary and efficient approach to the whole surgical procedure, focussing on the level of neuromuscular blockade. Five recommendations were agreed: 1) deep neuromuscular blockade is very appropriate for abdominal surgery (degree of agreement 94.1%), 2) and in obese patients (76.2%); 3) deep neuromuscular blockade maintenance until end of surgery might be beneficial in terms of clinical aspects, such as as immobility or better surgical access (86.1 to 72.3%); 4) quantitative monitoring and reversal drugs availability is recommended (89.1%); finally 5) anaesthesiologists/surgeons joint protocols are recommended. Collaboration among anaesthesiologists and surgeons has enabled some general recommendations to be established on deep neuromuscular blockade use during abdominal surgery. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

The immediate effect of neuromuscular joint facilitation on the rotation of the tibia during walking.

PubMed

Li, Desheng; Huang, Qiuchen; Huo, Ming; Hiiragi, Yukinobu; Maruyama, Hitoshi

2017-01-01

[Purpose] The aim of this study was to investigate the change in tibial rotation during walking among young adults after neuromuscular joint facilitation therapy. [Subjects and Methods] The subjects were twelve healthy young people (6 males, 6 females). A neuromuscular joint facilitation intervention and nonintervention were performed. The interventions were performed one after the other, separated by a 1-week interval. The order of the interventions was completely randomized. The rotation of the tibia during walking was evaluated before and after treatment. [Results] The neuromuscular joint facilitation group demonstrated increased lateral rotation of the tibia in the overall gait cycle and stance phase, and decreased medial rotation of the tibia in the overall gait cycle, stance phase, and swing phase after the neuromuscular joint facilitation intervention. In the control group, there were no significant differences. [Conclusion] These results suggest neuromuscular joint facilitation intervention has an immediate effect on the rotational function of the knee.

Discovery, development, and clinical application of sugammadex sodium, a selective relaxant binding agent

PubMed Central

Welliver, Mark; McDonough, John; Kalynych, Nicholas; Redfern, Robert

2008-01-01

Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits. PMID:19920893

An exploratory study of physical activity and perceived barriers to exercise in ambulant people with neuromuscular disease compared with unaffected controls.

PubMed

Phillips, Margaret; Flemming, Nicola; Tsintzas, Kostas

2009-08-01

To determine activity patterns and perceived barriers to exercise in ambulant people with neuromuscular disease compared with ambulatory controls. Prospective controlled parallel group design. Outpatient clinic and community. Thirteen ambulatory people with neuromuscular disease and 18 ambulatory controls. Heart rates were recorded during sedentary activity and treadmill walking at various speeds to indicate activity threshold (flex heart rate), followed by ambulatory heart rate monitoring over two weekdays and one weekend day. The EPIC-Norfolk Physical Activity Questionnaire-2 and Barriers to Physical Activity and Disability Survey were completed. Participants with neuromuscular disease were less active than controls as estimated by both the EPIC-Norfolk Physical Activity Questionnaire-2, P<0.004, and the flex heart rate method, P<0.05. The number of perceived barriers was greater in the neuromuscular group, a mean of 7 (SD 4.2) barriers, compared with mean 3 (SD 2.1) barriers for controls, P<0.05. Specific barriers differed, with the barriers of 'pain', 'lack of energy' and 'exercise is too difficult' showing the greatest discrepancy and being higher in the neuromuscular disease group. Physical activity, as determined by two different methods, was less and barriers to exercise greater in people with neuromuscular disease compared with healthy controls. Specific barriers were different in the two groups. This information could assist in the design of achievable and effective exercise programmes for people with neuromuscular disease.

The Broader Cognitive Phenotype of Autism in Parents: How Specific Is the Tendency for Local Processing and Executive Dysfunction?

ERIC Educational Resources Information Center

Bolte, Sven; Poustka, Fritz

2006-01-01

Background: The objective of this study was to investigate the tendency for local processing style ("weak central coherence") and executive dysfunction in parents of subjects with an autism spectrum disorder (ASD) compared with parents of individuals with early onset schizophrenia (EOS) and mental retardation (MR). Method: Sixty-two…

Neuromuscular Blockade and Reversal Agents: A Primer for Postanesthesia Nurses.

ERIC Educational Resources Information Center

Pesci, Barbara R.

1986-01-01

Presents a comprehensive review of neuromuscular blocking agents, reversal agents used in anesthesia, and factors affecting reversal. It is aimed at nurses who provide care to patients recovering from anesthesia. It discusses the neuromuscular transmission system, depolarizing muscle relaxants, nondepolarizing blocking agents, and criteria for…

Central pattern generation involved in oral and respiratory control for feeding in the term infant

PubMed Central

Barlow, Steven M.

2009-01-01

Purpose of review Drinking and eating are essential skills for survival and benefit from the coordination of several pattern generating networks and their musculoskeletal effectors to achieve safe swallows. Oral-pharyngo-esophageal motility develops during infancy and early childhood, and is influenced by various factors, including neuromuscular maturation, dietary and postural habits, arousal state, ongoing illnesses, congenital anomalies, and the effects of medical or surgical interventions. Gastroesophageal reflux is frequent in neonates and infants, and its role in neonatal morbidity including dysphagia, chronic lung disease, or apparent life-threatening events is not well understood. This review highlights recent studies aimed at understanding the development of oral feeding skills, and cross-system interactions among the brainstem, spinal, and cerebral networks involved in feeding. Recent Findings Functional linkages between suck-swallow and swallow-respiration manifest transitional forms during late gestation through the first year of life which can be delayed or modified by sensory experience and/or disease processes. Relevant central pattern generator (CPG) networks and their neuromuscular targets attain functional status at different rates, which ultimately influences cross-system CPG interactions. Entrainment of trigeminal primary afferents accelerates pattern genesis for the suck CPG and transition-to-oral feed in the RDS preterm infant. Summary The genesis of within-system CPG control for rate and amplitude scaling matures differentially for suck, mastication, swallow, and respiration. Cross-system interactions among these CPGs represent targets of opportunity for new interventions which optimize experience-dependent mechanisms to promote safe swallows among newborn and pediatric patients. PMID:19417662

Tempol Supplementation Restores Diaphragm Force and Metabolic Enzyme Activities in mdx Mice

PubMed Central

Burns, David P.; Ali, Izza; Rieux, Clement; Healy, James; Jasionek, Greg; O’Halloran, Ken D.

2017-01-01

Duchenne muscular dystrophy (DMD) is characterized by striated muscle weakness, cardiomyopathy, and respiratory failure. Since oxidative stress is recognized as a secondary pathology in DMD, the efficacy of antioxidant intervention, using the superoxide scavenger tempol, was examined on functional and biochemical status of dystrophin-deficient diaphragm muscle. Diaphragm muscle function was assessed, ex vivo, in adult male wild-type and dystrophin-deficient mdx mice, with and without a 14-day antioxidant intervention. The enzymatic activities of muscle citrate synthase, phosphofructokinase, and lactate dehydrogenase were assessed using spectrophotometric assays. Dystrophic diaphragm displayed mechanical dysfunction and altered biochemical status. Chronic tempol supplementation in the drinking water increased diaphragm functional capacity and citrate synthase and lactate dehydrogenase enzymatic activities, restoring all values to wild-type levels. Chronic supplementation with tempol recovers force-generating capacity and metabolic enzyme activity in mdx diaphragm. These findings may have relevance in the search for therapeutic strategies in neuromuscular disease. PMID:29210997

[Hereditary motor and sensory Lom-neuropathy--first Hungarian case report].

PubMed

Szabó, Antal; Siska, Eva; Molnár, Mária Judit

2007-01-20

Hereditary motor and sensory neuropathy-Lom is an autosomal recessive disorder of the peripheral nervous system, which occurs only in the european Roma population. The symptoms start in the first decade with slowly progressive gait disturbance, weakness and wasting of distal upper extremity muscles, joint deformities and hearing loss develop later in the second and third decades. This disorder is caused by a homozygous missense mutation of the NDRG1 gene, located in the 8q24 region. The Schwann cell dysfunction is most probably caused by altered lipid metabolism as a consequence of the NDRG1 mutation. Molecular genetic testing can be a first diagnostic step among roma individuals showing a Lom neuropathy phenotype, making evaluation of such patients and also genetic counselling faster and easier. Screening for hereditary neuromuscular disorders in this genetically isolated community may become an important public health issue in the near future.

Paraneoplastic Lambert-Eaton syndrome in a patient with disseminated metastatic cancer.

PubMed

Arellano-Aguilar, Gregorio; Núñez-Mojica, Erik Santiago; Gutiérrez-Velazco, José Luis; Domínguez-Carrillo, Luis Gerardo

2018-01-01

Neurological paraneoplastic syndromes are rare, occur in 0.01% of all cancer patients; like part of them, the Lambert-Eaton syndrome is an autoimmune presynaptic disorder of neuromuscular transmission characterized by muscle weakness and neurovegetative dysfunction, and often associated with small cell lung cancer. A 72 years old female with a family history of lung cancer and leukemia, with 7 months of dry cough and 3 months with waist and pelvic muscle weakness, oropharyngeal dysphagia, dry mouth, chronic constipation and weight loss of 10 kg. Physical examination: patient prostrated; clinical muscle examination: pelvic muscles waist -3/5 and -4/5 the rest; diminished reflexes. Laboratory normal parathormone and hypercalcemia. With electrophysiological study and positive anti-voltage-gated calcium channel antibodies, confirming Lambert-Eaton syndrome and imaging studies with neoplastic condition in brain, liver and kidney, with unspecified primary origin. Copyright: © 2018 Permanyer.

[Rhabdomyolysis in a Bipolar Adolescent. Analysis of Associated Factors].

PubMed

Restrepo, Diana; Montoya, Pablo; Giraldo, Laura; Gaviria, Génesis; Mejía, Catalina

2015-01-01

To describe a case of rhabdomyolysis associated with the use of quetiapine and lamotrigine in an adolescent treated for bipolar disorder. Description of the clinical case, analysis of the associated factors and a non-systematic review of the relevant literature. An 18 year old male, with bipolar disorder and treated pharmacologically with quetiapine and lamotrigine, after two weeks of physical activity presents with rhabdomyolysis. Quetiapine and exercise have been associated with rhabdomyolysis. The mediator mechanism of this association has not been found, although it has been established that there is neuromuscular dysfunction and an increase in sarcomere permeability. This clinical case allowed the complex interaction between antipsychotic agents and increased physical activity to be observed in a psychiatric adolescent patient, as well as the appearance of a potentially lethal medical complication. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Tubocurarine and pancuronium: a pharmacokinetic view.

PubMed

Shanks, C A; Somogyi, A A; Ramzan, M I; Triggs, E J

1980-02-01

This review is an attempt to bring together the pharmacokinetic data on d-tubocurarine and pancuronium with clinical observations on relaxant dosage and effect. The modelling techniques used here represent an oversimplification of the relationships between relaxant plasma concentration and response as they do not predict either the time of onset of paralysis or its peak intensity. However, they do enable calculation of a bolus dose of relaxant required to achieve a particular intensity of paralysis for the average patient once pseudo-distribution equilibrium has been achieved. This has been further extended to predict the cumulation of the relaxants with subsequent dosage in average patients. Suggested regimens incorporating bolus and infusion doses of the relaxants to achieve continuous neuromuscular blockade have been calculated also. Averaged pharmacokinetic parameters derived from patients with renal or hepatic dysfunction have been used to predict the likely duration and intensities of paralysis for the relaxants.

Determinants of respiratory pump function in patients with cystic fibrosis.

PubMed

Dassios, Theodore

2015-01-01

Respiratory failure constitutes the major cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Respiratory failure could either be due to lung parenchyma damage or to insufficiency of the respiratory pump which consists of the respiratory muscles, the rib cage and the neuromuscular transmission pathways. Airway obstruction, hyperinflation and malnutrition have been historically recognised as the major determinants of respiratory pump dysfunction in CF. Recent research has identified chronic infection, genetic predisposition, dietary and pharmaceutical interventions as possible additional determinants of this impairment. Furthermore, new methodological approaches in assessing respiratory pump function have led to a better understanding of the pathogenesis of respiratory pump failure in CF. Finally, respiratory muscle function could be partially preserved in CF patients with structured interventions such as aerobic exercise, inspiratory muscle training and non-invasive ventilation and CF patients could consequently be relatively protected from respiratory fatigue and respiratory failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

TEACHING NEUROMUSCULAR RELAXATION.

ERIC Educational Resources Information Center

NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

Neuromuscular Control and Coordination during Cycling

ERIC Educational Resources Information Center

Li, Li

2004-01-01

The neuromuscular control aspect of cycling has been investigated through the effects of modifying posture and cadence. These studies show that changing posture has a more profound influence on neuromuscular coordination than does changing slope. Most of the changes with standing posture occur late in the downstroke: increased ankle and knee joint…

Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

NASA Technical Reports Server (NTRS)

Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

2002-01-01

The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

Effects of napping on neuromuscular fatigue in myasthenia gravis.

PubMed

Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D

2013-11-01

The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.

Effects of pivoting neuromuscular training on pivoting control and proprioception.

PubMed

Lee, Song Joo; Ren, Yupeng; Chang, Alison H; Geiger, François; Zhang, Li-Qun

2014-07-01

Pivoting neuromuscular control and proprioceptive acuity may play an important role in anterior cruciate ligament injuries. The goal of this study was to investigate whether pivoting off-axis intensity adjustable neuromuscular control training (POINT) could improve pivoting neuromuscular control, proprioceptive acuity, and functional performance. Among 41 subjects, 21 subjects participated in 18 sessions of POINT (three sessions per week for 6 wk), and 20 subjects served as controls who did their regular workout. Both groups received pre-, mid-, and postintervention evaluations. Propensity score analysis with multivariable regression adjustment was used to investigate the effect of training on pivoting neuromuscular control (pivoting instability, leg pivoting stiffness, maximum internal, and external pivoting angles), proprioceptive acuity, and functional performance in both groups. Compared with the control group, the training group significantly improved pivoting neuromuscular control as reduced pivoting instability, reduced maximum internal and external pivoting angles, increased leg pivoting stiffness, and decreased entropy of time to peak EMG in the gluteus maximus and lateral gastrocnemius under pivoting perturbations. Furthermore, the training group enhanced weight-bearing proprioceptive acuity and improved the single leg hop distance. Improvement of pivoting neuromuscular control in functional weight-bearing activities and task performances after POINT may help develop lower limb injury prevention and rehabilitation methods to reduce anterior cruciate ligament and other musculoskeletal injuries associated with pivoting sports.

Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint injury.

PubMed

Tenforde, Adam S; Shull, Pete B; Fredericson, Michael

2012-05-01

Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces applied to a joint that cause injury and degenerative changes. An estimated 12% of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be attributed to a post-traumatic cause. Neuromuscular prehabilitation is the process of improving neuromuscular function to prevent development of PTOA after an initial traumatic joint injury. Prehabilitation strategies include restoration of normative movement patterns that have been altered as the result of traumatic injury, along with neuromuscular exercises and gait retraining to prevent the development of OA after an injury occurs. A review of the current literature shows that no studies have been performed to evaluate methods of neuromuscular prehabilitation to prevent PTOA after a joint injury. Instead, current research has focused on management strategies after knee injuries, the value of exercise in the management of OA, and neuromuscular exercises after total knee arthroplasty. Recent work in gait retraining that alters knee joint loading holds promise for preventing the development of PTOA after joint trauma. Future research should evaluate methods of neuromuscular prehabilitation strategies in relationship to the outcome of PTOA after joint injury. Copyright © 2012 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Neuromuscular response amplitude to mechanical stimulation using large-array surface electromyography in participants with and without chronic low back pain.

PubMed

Pagé, Isabelle; Nougarou, François; Descarreaux, Martin

2016-04-01

The present study aimed to compare the neuromuscular response under various mechanical stimulations of the lumbar spine in participants with and without chronic low back pain (cLBP). Four mechanical stimulations, characterized by forces ranging from 75 to 225N, were delivered using a servo-controlled linear actuator motor to the L3 spinous process of 25 healthy participants and 26 participants with cLBP. Lumbar neuromuscular responses were recorded using 64-electrodes large surface electromyography arrays. Between-group differences in the dose-response relationship (neuromuscular response amplitude according to each force level) were assessed using mixed model ANOVAs. No differences between groups were shown (all p values>.05). A significant linear relationship was observed between forces and neuromuscular response amplitudes (p<.001) indicating an increase in response amplitudes with increasing stimulation force. Responses were observed throughout the lumbar region with highest response amplitudes in the vicinity of the contacted vertebra. The neuromuscular response amplitude triggered by localized lumbar mechanical stimulations does not differ between participants with and without cLBP. Moreover, even though stimulations were delivered at specific spinal segment, a neuromuscular response, although rapidly decreasing, was observed in areas distant from the contact site. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Pivoting Neuromuscular Training on Pivoting Control and Proprioception

PubMed Central

Lee, Song Joo; Ren, Yupeng; Chang, Alison H.; Geiger, François; Zhang, Li-Qun

2014-01-01

Purpose Pivoting neuromuscular control and proprioceptive acuity may play an important role in ACL injuries. The goal of this study was to investigate whether pivoting neuromuscular training on an offaxis elliptical trainer (POINT) could improve pivoting neuromuscular control, proprioceptive acuity, and functional performance. Methods Among 41 subjects, 21 subjects participated in 18 sessions of POINT (3 sessions/week for 6 weeks), and 20 subjects served as controls who did their regular workout. Both groups received pre-, mid-, and post-intervention evaluations. Propensity score analysis with multivariable regression adjustment was used to investigate the effect of training on pivoting neuromuscular control (pivoting instability, leg pivoting stiffness, maximum internal and external pivoting angles), proprioceptive acuity, and functional performance in both groups. Results Compared to the control group, the training group significantly improved pivoting neuromuscular control as reduced pivoting instability, reduced maximum internal and external pivoting angles, increased leg pivoting stiffness, and decreased entropy of time to peak EMG in the gluteus maximus and lateral gastrocnemius under pivoting perturbations. Furthermore, the training group enhanced weight-bearing proprioceptive acuity and improved the single leg hop distance. Conclusion Improvement of pivoting neuromuscular control in functional weight-bearing activities and task performances following POINT may help develop lower limb injury prevention and rehabilitation methods to reduce ACL and other musculoskeletal injuries associated with pivoting sports. PMID:24389517

Physiological and neurophysiological determinants of postcancer fatigue: design of a randomized controlled trial

PubMed Central

2012-01-01

Background Postcancer fatigue is a frequently occurring, severe, and invalidating problem, impairing quality of life. Although it is possible to effectively treat postcancer fatigue with cognitive behaviour therapy, the nature of the underlying (neuro)physiology of postcancer fatigue remains unclear. Physiological aspects of fatigue include peripheral fatigue, originating in muscle or the neuromuscular junction; central fatigue, originating in nerves, spinal cord, and brain; and physical deconditioning, resulting from a decreased cardiopulmonary function. Studies on physiological aspects of postcancer fatigue mainly concentrate on deconditioning. Peripheral and central fatigue and brain morphology and function have been studied for patients with fatigue in the context of chronic fatigue syndrome and neuromuscular diseases and show several characteristic differences with healthy controls. Methods/design Fifty seven severely fatigued and 21 non-fatigued cancer survivors will be recruited from the Radboud University Nijmegen Medical Centre. Participants should have completed treatment of a malignant, solid tumour minimal one year earlier and should have no evidence of disease recurrence. Severely fatigued patients are randomly assigned to either the intervention condition (cognitive behaviour therapy) or the waiting list condition (start cognitive behaviour therapy after 6 months). All participants are assessed at baseline and the severely fatigued patients also after 6 months follow-up (at the end of cognitive behaviour therapy or waiting list). Primary outcome measures are fatigue severity, central and peripheral fatigue, brain morphology and function, and physical condition and activity. Discussion This study will be the first randomized controlled trial that characterizes (neuro)physiological factors of fatigue in disease-free cancer survivors and evaluates to which extent these factors can be influenced by cognitive behaviour therapy. The results of this study are not only essential for a theoretical understanding of this invalidating condition, but also for providing an objective biological marker for fatigue that could support the diagnosis and follow-up of treatment. Trial registration The study is registered at http://ClinicalTrials.gov (NCT01096641). PMID:22708881

Centrally Mediated Erectile Dysfunction in Rats with Type 1 Diabetes: Role of Angiotensin II and Superoxide

PubMed Central

Zheng, Hong; Liu, Xuefei; Patel, Kaushik P.

2015-01-01

Introduction Erectile dysfunction is a serious complication of diabetes mellitus. Apart from the peripheral actions, central mechanisms are also responsible for penile erection. Aim To determine the contribution of angiotensin (ANG) II in the dysfunction of central N-methyl-D-aspartic acid (NMDA)-nitric oxide (NO)-induced erectile responses in streptozotocin-induced type 1 diabetic (T1D) rats. Methods Three weeks after streptozotocin injections, rats were randomly treated with the angiotensin-converting enzyme inhibitor-enalapril, or the ANG II type 1 receptor blocker, losartan, or the superoxide dismutase mimetic, tempol or vehicle via chronic intracerebroventricular infusion by osmotic mini-pump for 2 weeks. Main Outcome Measure Central NMDA receptor stimulation or the administration of the NO donor, sodium nitroprusside (SNP)-induced penile erectile responses and concurrent behavioral responses were monitored in conscious rats. Results Two weeks of enalapril, losartan or tempol treatment significantly improved the erectile responses to central microinjection of both NMDA and SNP in the paraventricular nucleus (PVN) of conscious T1D rats (NMDA responses – T1D+enalapril: 1.7 ± 0.6, T1D+losartan: 2.0 ± 0.3, T1D+tempol: 2.0 ± 0.6 vs. T1D+vehicle: 0.6 ± 0.3 penile erections/rat in the first 20 min, P < 0.05; SNP responses – T1D+enalapril: 0.9 ± 0.3, T1D+losartan: 1.3 ± 0.3, T1D+tempol: 1.4 ± 0.4 vs. T1D+vehicle: 0.4 ± 0.2 penile erections/rat in the first 20 min, P < 0.05). Concurrent behavioral responses including yawning and stretching, induced by central NMDA and SNP microinjections were also significantly increased in T1D rats after enalapril, losartan or tempol treatments. Neuronal NO synthase expression within the PVN was also significantly increased and superoxide production was reduced in T1D rats after these treatments. Conclusions These data strongly support the contention that enhanced ANG II mechanism/s within the PVN of T1D rats contributes to the dysfunction of central NMDA-induced erectile responses in T1D rats via stimulation of superoxide. PMID:23841890

Phlebitis as a consequence of peripheral intravenous administration of cisatracurium besylate in critically ill patients.

PubMed

Meeder, Annelijn M; van der Steen, Marijke S; Rozendaal, Annemieke; van Zanten, Arthur R H

2016-10-03

This case report series describes 3 cases of cisatracurium besylate associated phlebitis after an infusion period of 14-20 hours. No similar cases have been reported in the literature. Association of phlebitis with another neuromuscular blocking agent, atracurium, has been described in the literature. The acidity of atracurium is thought to be the main cause. It is recommended that atracurium is administered only via central venous catheters when indicated to infuse over prolonged periods of time due to the acidity. Cisatracurium is a stereoisomer of atracurium and as such has the same molecular weight. Although cisatracurium also has a similar acidity as atracurium, a recommendation concerning infusion via a central venous catheter is lacking. We suggest prolonged administration of cisatracurium besylate only via centrally placed venous catheters or if not possible to careful monitor relevant peripheral intravenous sites to diminish the risks of phlebitis and associated complications or other cutaneous reactions. 2016 BMJ Publishing Group Ltd.

Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice.

PubMed

Yano, Michiko; Minegishi, Yoshihiko; Sugita, Satoshi; Ota, Noriyasu

2017-10-15

Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The effects of physical therapy with neuromuscular electrical stimulation in patients with septic shock: Study protocol for a randomized cross-over design.

PubMed

Lago, Alessandra Fabiane; de Oliveira, Anamaria Siriani; de Souza, Hugo Celso Dutra; da Silva, João Santana; Basile-Filho, Anibal; Gastaldi, Ada Clarice

2018-02-01

Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect.

A novel externally applied neuromuscular stimulator for the treatment of stress urinary incontinence in women--€”a pilot study.

PubMed

Maher, Ruth M; Caulfield, Brian

2013-01-01

€‚ Neuromuscular electrical stimulation (NMES) is commonly used to treat lower urinary tract dysfunctions. This study evaluated the efficacy of a novel externally applied stimulator in the treatment of stress urinary incontinence (SUI). €‚ Nine women were included in this study. Provocative tests included a cough and jumping jack test assessed via pad weight. Ultrasound (US) imaging assessed pelvic floor muscle (PFM) contraction. A bladder filling protocol allowed for delineation of the bladder from the pelvic floor and standardized volume. External electrodes were used during 30 €ƒmin, at least four times per week treatment protocol at home for eight weeks. Participants were blinded to US and were not instructed regarding pelvic floor contractions. €‚ At week 1, participants could perform PFM contractions verified with US. More importantly, an 87.43% decrease in leakage was noted. At week 8, participants reported a 97.71% decrease in leakage (p= 0.0001). Changes noted in Incontinence Impact Questionnaire and Modified Oxford scores were significant (p= 0.0001 and p= 0.0001). €‚ NMES is frequently used to promote muscle strength and coordination. Studies have shown NMES to be effective in decreasing symptoms associated with SUI; however, few, if any, have used it as a primary treatment modality. The novel device in this study was shown to be effective in improving muscle strength, reducing or ablating the symptoms associated with SUI, and in eliciting PFM contractions. The device is noninvasive and can be used as a home treatment. © 2012 International Neuromodulation Society.

Activity of periscapular muscles and its correlation with external oblique during push-up: Does scapular dyskinesis change the electromyographic response?

PubMed

de Araújo, Rodrigo Cappatode; Pirauá, André Luiz Torres; Beltrão, Natália Barros; Pitangui, Ana Carolina Rodarti

2018-03-01

Scapular dyskinesis is the term used to describe changes in the positioning or movement of the scapula. Such dysfunction is associated with changes in the activation of the scapular muscles. However, the influence of the axial muscles on the scapular muscles activity of subjects with scapular dyskinesis is unknown. This study aimed to compare the electromyography (EMG) activity of periscapular muscles and its correlation with the external oblique muscle during the execution of push-up performed in different surfaces, in volunteers with and without scapular dyskinesis. Thirty-six men, divided in two groups (control and dyskinesis), performed push-up on stable and unstable surface. The EMG activity of serratus anterior (SA_5th and SA_7th fibers), upper (UT) and lower (LT) trapezius, external oblique (EO) was recorded during execution of each task condition. Statistical analyzes were performed using two way ANOVA repeated measures and Pearson correlation. It was observed effect of interaction between factors, being evidenced increased activity of UT, SA_7th and OE for the control group and decreased activity of SA_5th, SA_7th and EO for dyskinesis group during execution of push-up on unstable surface. In both groups positive correlations (r > 0.47) were observed between EMG activity of SA and EO. In the exercises tested, there seems to be an anatomical and functional relationship between the SA and EO muscles. The use of the unstable surface promotes increased neuromuscular demand, but the neuromuscular strategies appear to differ between groups.

Induced formation and maturation of acetylcholine receptor clusters in a defined 3D bio-artificial muscle.

PubMed

Wang, Lin; Shansky, Janet; Vandenburgh, Herman

2013-12-01

Dysfunction of the neuromuscular junction is involved in a wide range of muscular diseases. The development of neuromuscular junction through which skeletal muscle is innervated requires the functional modulation of acetylcholine receptor (AchR) clustering on myofibers. However, studies on AchR clustering in vitro are mostly done on monolayer muscle cell culture, which lacks a three-dimensional (3D) structure, a prominent limitation of the two-dimensional (2D) system. To enable a better understanding on the structure-function correlation underlying skeletal muscle innervation, a muscle system with a well-defined geometry mimicking the in vivo muscular setting is needed. Here, we report a 3D bio-artificial muscle (BAM) bioengineered from green fluorescent protein-transduced C3H murine myoblasts as a novel in vitro tissue-based model for muscle innervation studies. Our cell biological and molecular analysis showed that this BAM is structurally similar to in vivo muscle tissue and can reach the perinatal differentiation stage, higher than does 2D culture. Effective clustering and morphological maturation of AchRs on BAMs induced by agrin and laminin indicate the functional activity and plasticity of this BAM system toward innervation. Taken together, our results show that the BAM provides a favorable 3D environment that at least partially recapitulates real physiological skeletal muscle with regard to innervation. With a convenience of fabrication and manipulation, this 3D in vitro system offers a novel model for studying mechanisms underlying skeletal muscle innervation and testing therapeutic strategies for relevant nervous and muscular diseases.

Is non-invasive neuromuscular electrical stimulation effective in severe chronic neurogenic dysphagia? Reporton a post-traumatic brain injury patient.

PubMed

Calabrò, Rocco Salvatore; Nibali, Valeria Conti; Naro, Antonino; Floridia, Daniela; Pizzimenti, Maria; Salmeri, Lucia; Salviera, Carlo; Bramanti, Placido

2016-01-01

Neurogenic dysphagia is a difficulty in swallowing induced by nervous system disease. It often causes serious complications, which are preventable if dysphagia is properly managed. There is growing debate concerning the usefulness of non-invasive neuromuscular electrical stimulation (NMES) in treating swallowing dysfunction. Aim of this study was to assess the effectiveness of Vitalstim© device, and to investigate the neurophysiological mechanisms underlying functional recovery. A 34-year-old man, affected by severe chronic dysphagia following traumatic brain injury, underwent two different intensive rehabilitation trainings, including either conventional rehabilitation alone or coupled to Vitalstim training. We evaluated patient swallowing function in two separate sessions (i.e. before and after the two trainings) by means of ad hoc swallowing function scales and electrophysiological parameters (rapid paired associative stimulation). The overall Vitalstim program was articulated in 6 weekly sessions for 6 weeks. The patient did not report any side-effect either during or following both the intensive rehabilitation trainings. We observed an important improvement in swallowing function only after Vitalstim training. In fact, the patient was eventually able to safely eat even solid food. This is the first report objectively suggesting (by means of rPAS) a correlation between the brain neuroplastic changes induced by Vitalstim and the swallowing function improvement. It is hypothesizable that Vitalstim may have targeted cortical (and maybe subcortical) brain areas that are recruited during the highly coordinated function of swallowing, and it may have thus potentiated the well-known neuroplastic changes induced by repetitive and intensive swallowing exercises, probably thanks to metaplasticity phenomena.

Synaptic defects associated with s-inclusion body myositis are prevented by copper.

PubMed

Aldunate, R; Minniti, A N; Rebolledo, D; Inestrosa, N C

2012-08-01

Sporadic-inclusion body myositis (s-IBM) is the most common skeletal muscle disorder to afflict the elderly, and is clinically characterized by skeletal muscle degeneration. Its progressive course leads to muscle weakness and wasting, resulting in severe disability. The exact pathogenesis of this disease is unknown and no effective treatment has yet been found. An intriguing aspect of s-IBM is that it shares several molecular abnormalities with Alzheimer's disease, including the accumulation of amyloid-β-peptide (Aβ). Both disorders affect homeostasis of the cytotoxic fragment Aβ(1-42) during aging, but they are clinically distinct diseases. The use of animals that mimic some characteristics of a disease has become important in the search to elucidate the molecular mechanisms underlying the pathogenesis. With the aim of analyzing Aβ-induced pathology and evaluating the consequences of modulating Aβ aggregation, we used Caenorhabditis elegans that express the Aβ human peptide in muscle cells as a model of s-IBM. Previous studies indicate that copper treatment increases the number and size of amyloid deposits in muscle cells, and is able to ameliorate the motility impairments in Aβ transgenic C. elegans. Our recent studies show that neuromuscular synaptic transmission is defective in animals that express the Aβ-peptide and suggest a specific defect at the nicotine acetylcholine receptors level. Biochemical analyses show that copper treatment increases the number of amyloid deposits but decreases Aβ-oligomers. Copper treatment improves motility, synaptic structure and function. Our results suggest that Aβ-oligomers are the toxic Aβ species that trigger neuromuscular junction dysfunction.

Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

PubMed

Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

2016-06-01

Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. © 2016 International Society for Neurochemistry.

Compliance With Neuromuscular Training and Anterior Cruciate Ligament Injury Risk Reduction in Female Athletes: A Meta-Analysis

PubMed Central

Sugimoto, Dai; Myer, Gregory D.; Bush, Heather M.; Klugman, Maddie F.; McKeon, Jennifer M. Medina; Hewett, Timothy E.

2012-01-01

Context No consensus exists about the influence of compliance with neuromuscular training programs on reduction of the risk of anterior cruciate ligament (ACL) injury. Objective To systematically review and synthesize the published literature to determine if compliance with neuromuscular training is associated with reduced incidence of ACL injury in young female athletes. Data Sources We searched PubMed, SPORTDiscus, CINAHL, and MEDLINE for articles published from 1995 to 2010 using the key words anterior cruciate ligament prevention, ACL prevention, knee prevention, prospective knee prevention, neuromuscular training, and neuromuscular intervention. Study Selection Criteria for inclusion required that (1) the number of ACL injuries was reported, (2) a neuromuscular training program was used, (3) females were included as participants, (4) the study design was prospective and controlled, and (5) compliance data for the neuromuscular training program were provided. Data Extraction Extracted data included the number of ACL injuries, total number of participants per group, observation time period, number of participants who completed each session, number of sessions completed by an entire team, and number of total sessions. Attendance was calculated as the number of participants who completed each session converted into a percentage of the total number of participants. Intervention completion was calculated as the number of sessions completed by an entire team converted into a percentage of the total number of training sessions. These data were used to calculate an overall rate of compliance. Data Synthesis Six of 205 identified studies were included. Incidence rates of ACL injury were lower in studies with high rates of compliance with neuromuscular training than in studies with low compliance rates (incidence rate ratio = 0.27 [95% confidence interval = 0.07, 0.80]). Tertile analysis indicated rates of ACL injury incidence were lower in studies with high compliance rates than in studies with moderate and low compliance rates (incidence rate ratio = 0.18 [95% confidence interval = 0.02, 0.77]). Conclusions A potential inverse dose-response relationship exists between compliance with neuromuscular training and incidence of ACL injury. Attending and completing recommended neuromuscular sessions appears to be an important factor for preventing ACL injuries. PMID:23182020

Unusual cause of central aortic prosthetic regurgitation during transcatheter replacement.

PubMed

López-Mínguez, José Ramón; Millán-Núñez, Victoria; González-Fernández, Reyes; Nogales-Asensio, Juan Manuel; Fuentes-Cañamero, María Eugenia; Merchán-Herrera, Antonio

2016-04-01

Transcatheter aortic valve replacement (TAVR) is an increasingly common procedure for the treatment of aortic stenosis in elderly patients with comorbidities that prevent the use of standard surgery. It has been shown that implantation without aortic regurgitation is related to lower mortality. Mild paravalvular regurgitation is inevitable in some cases due to calcification of the aortic annulus and its usually somewhat elliptical shape. Central regurgitation is less common, but has been associated with valve overdilatation in cases in which reduction of paravalvular regurgitation was attempted after the initial inflation. However, there are no reported cases of central prosthetic aortic regurgitation due to acute LV dysfunction. We report a case in which central aortic regurgitation occurred due to transient ventricular dysfunction secondary to occlusion of the right coronary artery by an embolus. The regurgitation disappeared after thrombus aspiration and normal ventricular function was immediately recovered. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Etomidate evokes synaptic vesicle exocytosis without increasing miniature endplate potentials frequency at the mice neuromuscular junction.

PubMed

Valadão, Priscila Aparecida Costa; Naves, Lígia Araújo; Gomez, Renato Santiago; Guatimosim, Cristina

2013-11-01

Etomidate is an intravenous anesthetic used during anesthesia induction. This agent induces spontaneous movements, especially myoclonus after its administration suggesting a putative primary effect at the central nervous system or the periphery. Therefore, the aim of this study was to investigate the presynaptic and postsynaptic effects of etomidate at the mouse neuromuscular junction (NMJ). Diaphragm nerve muscle preparations were isolated and stained with the styryl dye FM1-43, a fluorescent tool that tracks synaptic vesicles exo-endocytosis that are key steps for neurotransmission. We observed that etomidate induced synaptic vesicle exocytosis in a dose-dependent fashion, an effect that was independent of voltage-gated Na(+) channels. By contrast, etomidate-evoked exocytosis was dependent on extracellular Ca(2+) because its effect was abolished in Ca(2+)-free medium and also inhibited by omega-Agatoxin IVA (30 and 200nM) suggesting the participation of P/Q-subtype Ca(2+) channels. Interestingly, even though etomidate induced synaptic vesicle exocytosis, we did not observe any significant difference in the frequency and amplitude of miniature end-plate potentials (MEPPs) in the presence of the anesthetic. We therefore investigated whether etomidate could act on nicotinic acetylcholine receptors labeled with α-bungarotoxin-Alexa 594 and we observed less fluorescence in preparations exposed to the anesthetic. In conclusion, our results suggest that etomidate exerts a presynaptic effect at the NMJ inducing synaptic vesicle exocytosis, likely through the activation of P-subtype voltage gated Ca(2+) channels without interfering with MEPPs frequency. The present data contribute to a better understanding about the effect of etomidate at the neuromuscular synapse and may help to explain some clinical effects of this agent. Copyright © 2013 Elsevier Ltd. All rights reserved.

The assessment of neuromuscular fatigue during 120 min of simulated soccer exercise.

PubMed

Goodall, Stuart; Thomas, Kevin; Harper, Liam David; Hunter, Robert; Parker, Paul; Stevenson, Emma; West, Daniel; Russell, Mark; Howatson, Glyn

2017-04-01

This investigation examined the development of neuromuscular fatigue during a simulated soccer match incorporating a period of extra time (ET) and the reliability of these responses on repeated test occasions. Ten male amateur football players completed a 120 min soccer match simulation (SMS). Before, at half time (HT), full time (FT), and following a period of ET, twitch responses to supramaximal femoral nerve and transcranial magnetic stimulation (TMS) were obtained from the knee-extensors to measure neuromuscular fatigue. Within 7 days of the first SMS, a second 120 min SMS was performed by eight of the original ten participants to assess the reliability of the fatigue response. At HT, FT, and ET, reductions in maximal voluntary force (MVC; -11, -20 and -27%, respectively, P ≤ 0.01), potentiated twitch force (-15, -23 and -23%, respectively, P < 0.05), voluntary activation (FT, -15 and ET, -18%, P ≤ 0.01), and voluntary activation measured with TMS (-11, -15 and -17%, respectively, P ≤ 0.01) were evident. The fatigue response was robust across both trials; the change in MVC at each time point demonstrated a good level of reliability (CV range 6-11%; ICC 2,1 0.83-0.94), whilst the responses identified with motor nerve stimulation showed a moderate level of reliability (CV range 5-18%; ICC 2,1 0.63-0.89) and the data obtained with motor cortex stimulation showed an excellent level of reliability (CV range 3-6%; ICC 2,1 0.90-0.98). Simulated soccer exercise induces a significant level of fatigue, which is consistent on repeat tests, and involves both central and peripheral mechanisms.

LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner

PubMed Central

Ohkawara, Bisei; Cabrera-Serrano, Macarena; Nakata, Tomohiko; Milone, Margherita; Asai, Nobuyuki; Ito, Kenyu; Ito, Mikako; Masuda, Akio; Ito, Yasutomo; Engel, Andrew G.; Ohno, Kinji

2014-01-01

Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Using Sanger and exome sequencing in a CMS patient, we identified two heteroallelic mutations, p.Glu1233Lys and p.Arg1277His, in LRP4 coding for the postsynaptic low-density lipoprotein receptor-related protein 4. LRP4, expressed on the surface of the postsynaptic membrane of the neuromuscular junction, is a receptor for neurally secreted agrin, and LRP4 bound by agrin activates MuSK. Activated MuSK in concert with Dok-7 stimulates rapsyn to concentrate and anchor AChR on the postsynaptic membrane and interacts with other proteins implicated in the assembly and maintenance of the neuromuscular junction. LRP4 also functions as an inhibitor of Wnt/beta-catenin signaling. The identified mutations in LRP4 are located at the edge of its 3rd beta-propeller domain and decrease binding affinity of LRP4 for both MuSK and agrin. Mutations in the LRP4 3rd beta-propeller domain were previously reported to impair Wnt signaling and cause bone diseases including Cenani–Lenz syndactyly syndrome and sclerosteosis-2. By analyzing naturally occurring and artificially introduced mutations in the LRP4 3rd beta-propeller domain, we show that the edge of the domain regulates the MuSK signaling whereas its central cavity governs Wnt signaling. We conclude that LRP4 is a new CMS disease gene and that the 3rd beta propeller domain of LRP4 mediates the two signaling pathways in a position-specific manner. PMID:24234652

Factors that affect the onset of action of non-depolarizing neuromuscular blocking agents

PubMed Central

Kim, Yong Byum; Sung, Tae-Yun

2017-01-01

Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs. PMID:29046769

Hypoventilation improvement in an adult non-invasively ventilated patient with Rapid-onset Obesity with Hypothalamic Dysfunction Hypoventilation and Autonomic Dysregulation (ROHHAD).

PubMed

Graziani, Alessandro; Casalini, Pierpaolo; Mirici-Cappa, Federica; Pezzi, Giuseppe; Giuseppe Stefanini, Francesco

2016-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare disease of unknown etiology, characterized by rapid-onset obesity in young children, hypoventilation, hypothalamic and autonomic dysfunction. Patients between the ages of 2 and 4 present with hyperphagia and weight gain, followed by neuro-hormonal dysfunction and central hypoventilation months or years later. Cardiac arrest may represent the fatal complication of alveolar hypoventilation and early mechanical ventilation is essential for the patient's life. In this paper, we describe a 22-year-old patient with ROHHAD syndrome who had an acute respiratory failure during nocturnal non-invasive ventilation (NIV).

Effects of antihypertensive agents on sexual function.

PubMed

Weiss, R J

1991-12-01

Patient compliance with antihypertensive therapy can be improved by minimizing drug-induced sexual dysfunction. Impotence, decreased libido, impaired ejaculation and gynecomastia are potential side effects, depending on the agent prescribed. Centrally acting antihypertensive agents such as methyldopa and clonidine, nonselective beta-adrenergic blockers and potassium-sparing diuretics are the drugs most often associated with sexual dysfunction. Thiazide diuretics cause impotence but may otherwise play a minimal role in sexual dysfunction. Alpha-adrenergic blockers, angiotensin converting enzyme inhibitors and calcium channel blockers have little adverse effect on sexual function. It is important to obtain an adequate history before and after initiating therapy. If sexual dysfunction develops in a patient, a different class of medication can be tried.

Clinical review: Long-term noninvasive ventilation

PubMed Central

Robert, Dominique; Argaud, Laurent

2007-01-01

Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive. PMID:17419882

Exogenous ciliary neurotrophic factor (CNTF) reduces synaptic depression during repetitive stimulation.

PubMed

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Priego, Mercedes; Obis, Teresa; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

2012-09-01

It has been shown that ciliary neurotrophic factor (CNTF) has trophic and maintenance effects on several types of peripheral and central neurons, glia, and cells outside the nervous system. Both CNTF and its receptor, CNTF-Rα, are expressed in the muscle. We use confocal immunocytochemistry to show that the trophic cytokine and its receptor are present in the pre- and post-synaptic sites of the neuromuscular junctions (NMJs). Applied CNTF (7.5-200 ng/ml, 60 min-3 h) does not acutely affect spontaneous potentials (size or frequency) or quantal content of the evoked acetylcholine release from post-natal (in weak or strong axonal inputs on dually innervated end plates or in the most mature singly innervated synapses at P6) or adult (P30) NMJ of Levator auris longus muscle of the mice. However, CNTF reduces roughly 50% the depression produced by repetitive stimulation (40 Hz, 2 min) on the adult NMJs. Our findings indicate that, unlike neurotrophins, exogenous CNTF does not acutely modulate transmitter release locally at the mammalian neuromuscular synapse but can protect mature end plates from activity-induced synaptic depression. © 2012 Peripheral Nerve Society.

Anticipatory Postural Activity During Long-Duration Space Flight

NASA Technical Reports Server (NTRS)

Layne, C. S.; Mulavara, A. P.; McDonald, P. V.; Pruett, C. J.; Koslovskaya, B.; Bloomberg, J. J.

1999-01-01

Somatosensory input has been used to modify motor output in many contexts. During space flight, the use of the lower limb musculature is much less than during activities in 1g. Consequently the neuromuscular activity of the legs is also reduced during space flight. This decrease in muscle activity contributes to muscle atrophy. Furthermore, adaptations to weightlessness contribute to posture and locomotion problems upon the return to Earth. Providing techniques to counter the negative effects of weightlessness on the neuromuscular system is an important goal, particularly during a long-duration mission. Previous work by our group has shown that lower limb neuromuscular activation that normally precedes arm movements in 1g is absent or greatly reduced during similar movements made while freefloating. However, preliminary evidence indicates that applying pressure to the feet results in enhanced neuromuscular activation during rapid arm movements performed while freefloating. This finding suggests that sensory input can be used to "drive" the motor system to increase neuromuscular functioning throughout a mission. The purpose of this investigation was to quantify the increase in neuromuscular activation resulting from the application of pressure to the feet.

A role for long-chain acyl-CoA synthetase-4 (ACSL4) in diet-induced phospholipid remodeling and obesity-associated adipocyte dysfunction

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: Regulation of fatty acid (FA) metabolism is central to adipocyte dysfunction during diet-induced obesity (DIO). Long-chain acyl-CoA synthetase-4 (ACSL4) has been hypothesized to modulate the metabolic fates of polyunsaturated FA (PUFA), including arachidonic acid (AA), but the in vivo act...

Effect of central and ovarian endocrine disturbances on the female genital tract--clinical signs and symptoms.

PubMed

Sillem, M; Rabe, T; Runnebaum, B

1997-01-01

Disorders of the female genital tract caused by endocrine disturbances commonly lead to two presenting complaints: dysfunctional uterine bleeding and infertility. In oestrogen deficiency, sequelae of vaginal atrophy may also be present. The common pathogenic "turntable" of these clinical signs is an impaired ovarian function, for which primary (i.e. intraovarian) and secondary (i.e. resulting from dysfunctions of other endocrine systems) causes are known. Primary ovarian failure can be the result of gonadal dysgenesis or premature menopause. Secondary ovarian dysfunction may be caused by hypothalamic-pituitary dysregulation, hyperprolactinaemia, thyroid disorders, and hyperandrogenaemia, which often also has an intraovarian component. For clinical considerations, several severities of ovarian dysfunction can be distinguished, ranging from corpus luteum insufficiency which is only relevant for the selection of infertility treatment to the complete absence of ovarian steroidogenesis leading to severe long term sequelae of the skeletal, cardiovascular and probably central nervous systems. Diagnosis and differential diagnosis are made by clinical examination, vaginal ultrasound, hormone assays, curettage and laparoscopy. Rarely, additional techniques like magnetic resonance imaging of the pituitary or the adrenals, or sequential catheterization of the inferior vena cava are needed.

Neuromuscular complications of immune checkpoint inhibitor therapy.

PubMed

Kolb, Noah A; Trevino, Christopher R; Waheed, Waqar; Sobhani, Fatemeh; Landry, Kara K; Thomas, Alissa A; Hehir, Mike

2018-01-17

Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune system to fight cancer. ICPIs improve overall cancer survival, however, the unbridling of the immune system may induce a variety of immune-related adverse events. Neuromuscular immune complications are rare but they can be severe. Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular adverse events but a variety of others including inflammatory myopathy are reported. The pathophysiologic mechanism of these autoimmune disorders may differ from that of non-ICPI-related immune diseases. Accordingly, while the optimal treatment for ICPI-related neuromuscular disorders generally follows a traditional paradigm, there are important novel considerations in selecting appropriate immunosuppressive therapy. This review presents 2 new cases, a summary of neuromuscular ICPI complications, and an approach to the diagnosis and treatment of these disorders. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

The Relationship Between Sexual Function and Quality of Sleep in Caregiving Mothers of Sons with Duchenne Muscular Dystrophy

PubMed Central

Nozoe, Karen T; Hachul, Helena; Hirotsu, Camila; Polesel, Daniel N; Moreira, Gustavo A; Tufik, Sergio; Andersen, Monica L

2014-01-01

Introduction The task of the caregiver, especially a caregiving mother of a son with a chronic and fatal disease, may interfere with their quality of sleep, sexuality, and some hormone levels. Aim The aim of this study was to evaluate the sexual function and the quality of sleep of caregiving mothers of sons with Duchenne muscular dystrophy (DMD). Methods We evaluated 20 caregiving mothers of sons with DMD and 20 caregiving mothers of sons without any neuromuscular or chronic disease. All of them voluntarily responded to the evaluating questionnaires about their sexuality and their quality of sleep, and gave blood samples to evaluate their hormonal levels. Main Outcome Measures All mothers were evaluated using the questionnaire of Female Sexual Function Index (FSFI) and the Pittsburgh questionnaire (PSQI). The blood samples were tested to determine serum levels of testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, progesterone, adrenocorticotropic hormone, and cortisol. Results Caregiving mothers of sons with DMD had significantly lower scores in the FSFI questionnaire, suggesting a higher risk for sexual dysfunction. The PSQI demonstrated that these caregiving mothers present increased sleep latency, reduced sleep efficiency, daytime dysfunction, and poor sleep quality. Blood tests showed a rise in cortisol levels, which correlated with the compromised sexuality and quality of sleep. Conclusions This study indicates that caregiving mothers of sons with DMD show major risk for sexual dysfunction and a reduction in their quality of sleep mediated in part by the hormonal changes related to stress. Nozoe KT, Hachul H, Hirotsu C, Polesel DN, Moreira GA, Tufik S, and Andersen ML. The relationship between sexual function and quality of sleep in caregiving mothers of sons with Duchenne muscular dystrophy. Sex Med 2014;2:133–140. PMID:25356310

A literature review of studies using qualitative research to explore chronic neuromuscular disease.

PubMed

LaDonna, Kori A

2011-06-01

Although most neuromuscular disease research articles reflect traditional quantitative approaches, qualitative methods are becoming more prevalent in the neuromuscular literature. Arguably, qualitative research provides rich data that may be used to generate patient-centered outcome measures or influence current standards of care. The purpose of this article is to explore the qualitative literature pertaining to individuals and families living with chronic neuromuscular disease in order to suggest implications for practice. Fifty-six qualitative articles addressing seven research themes including Illness Experience; Work, Recreation, and Services; Assisted Ventilation; Caregiving; Genetics; Communication and Information Seeking; and Palliative Care were identified.

Neuromuscular adaptations to training, injury and passive interventions: implications for running economy.

PubMed

Bonacci, Jason; Chapman, Andrew; Blanch, Peter; Vicenzino, Bill

2009-01-01

Performance in endurance sports such as running, cycling and triathlon has long been investigated from a physiological perspective. A strong relationship between running economy and distance running performance is well established in the literature. From this established base, improvements in running economy have traditionally been achieved through endurance training. More recently, research has demonstrated short-term resistance and plyometric training has resulted in enhanced running economy. This improvement in running economy has been hypothesized to be a result of enhanced neuromuscular characteristics such as improved muscle power development and more efficient use of stored elastic energy during running. Changes in indirect measures of neuromuscular control (i.e. stance phase contact times, maximal forward jumps) have been used to support this hypothesis. These results suggest that neuromuscular adaptations in response to training (i.e. neuromuscular learning effects) are an important contributor to enhancements in running economy. However, there is no direct evidence to suggest that these adaptations translate into more efficient muscle recruitment patterns during running. Optimization of training and run performance may be facilitated through direct investigation of muscle recruitment patterns before and after training interventions. There is emerging evidence that demonstrates neuromuscular adaptations during running and cycling vary with training status. Highly trained runners and cyclists display more refined patterns of muscle recruitment than their novice counterparts. In contrast, interference with motor learning and neuromuscular adaptation may occur as a result of ongoing multidiscipline training (e.g. triathlon). In the sport of triathlon, impairments in running economy are frequently observed after cycling. This impairment is related mainly to physiological stress, but an alteration in lower limb muscle coordination during running after cycling has also been observed. Muscle activity during running after cycling has yet to be fully investigated, and to date, the effect of alterations in muscle coordination on running economy is largely unknown. Stretching, which is another mode of training, may induce acute neuromuscular effects but does not appear to alter running economy. There are also factors other than training structure that may influence running economy and neuromuscular adaptations. For example, passive interventions such as shoes and in-shoe orthoses, as well as the presence of musculoskeletal injury, may be considered important modulators of neuromuscular control and run performance. Alterations in muscle activity and running economy have been reported with different shoes and in-shoe orthoses; however, these changes appear to be subject-specific and non-systematic. Musculoskeletal injury has been associated with modifications in lower limb neuromuscular control, which may persist well after an athlete has returned to activity. The influence of changes in neuromuscular control as a result of injury on running economy has yet to be examined thoroughly, and should be considered in future experimental design and training analysis.

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

PubMed Central

Toledo, Camilo; Andrade, David C.; Lucero, Claudia; Arce‐Alvarez, Alexis; Díaz, Hugo S.; Aliaga, Valentín; Schultz, Harold D.; Marcus, Noah J.; Manríquez, Mónica; Faúndez, Marcelo

2017-01-01

Key points Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho‐vagal imbalance.Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre‐sympathetic regions of the brainstem.Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho‐vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF. Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho‐vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague‐Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho‐vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h−1), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HFHRV)] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h−1). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HFHRV, normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h−1) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl−1). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF. PMID:28181258

Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care

ClinicalTrials.gov

2018-04-02

Adenovirus; Anesthesia; Anxiety; Anxiolysis; Autism; Autistic Disorder; Bacterial Meningitis; Bacterial Septicemia; Benzodiazepine; Bipolar Disorder; Bone and Joint Infections; Central Nervous System Infections; Convulsions; Cytomegalovirus Retinitis; Early-onset Schizophrenia Spectrum Disorders; Epilepsy; General Anesthesia; Gynecologic Infections; Herpes Simplex Virus; Infantile Hemangioma; Infection; Inflammation; Inflammatory Conditions; Intra-abdominal Infections; Lower Respiratory Tract Infections; Migraines; Pain; Pneumonia; Schizophrenia; Sedation; Seizures; Skeletal Muscle Spasms; Skin and Skin-structure Infections; Thromboprophylaxis; Thrombosis; Treatment-resistant Schizophrenia; Urinary Tract Infections; Withdrawal; Sepsis; Gram-negative Infection; Bradycardia; Cardiac Arrest; Cardiac Arrhythmia; Staphylococcal Infections; Nosocomial Pneumonia; Neuromuscular Blockade; Methicillin Resistant Staphylococcus Aureus; Endocarditis; Neutropenia; Headache

Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives.

PubMed

Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

2018-01-01

The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed.

Profile of sugammadex for reversal of neuromuscular blockade in the elderly: current perspectives

PubMed Central

Carron, Michele; Bertoncello, Francesco; Ieppariello, Giovanna

2018-01-01

The number of elderly patients is increasing worldwide. This will have a significant impact on the practice of anesthesia in future decades. Anesthesiologists must provide care for an increasing number of elderly patients, who have an elevated risk of perioperative morbidity and mortality. Complications related to postoperative residual neuromuscular blockade, such as muscle weakness, airway obstruction, hypoxemia, atelectasis, pneumonia, and acute respiratory failure, are more frequent in older than in younger patients. Therefore, neuromuscular blockade in the elderly should be carefully monitored and completely reversed before awakening patients at the end of anesthesia. Acetylcholinesterase inhibitors are traditionally used for reversal of neuromuscular blockade. Although the risk of residual neuromuscular blockade is reduced by reversal with neostigmine, it continues to complicate the postoperative course. Sugammadex represents an innovative approach to reversal of neuromuscular blockade induced by aminosteroid neuromuscular-blocking agents, particularly rocuronium, with useful applications in clinical practice. However, aging is associated with certain changes in the pharmacokinetics of sugammadex, and to date there has been no thorough evaluation of the use of sugammadex in elderly patients. The aim of this review was to perform an analysis of the use of sugammadex in older adults based on the current literature. Major issues surrounding the physiologic and pharmacologic effects of aging in elderly patients and how these may impact the routine use of sugammadex in elderly patients are discussed. PMID:29317806

Evaluation of neuromuscular activity in patients with obstructive sleep apnea using chin surface electromyography of polysomnography.

PubMed

Yin, Guo-ping; Ye, Jing-ying; Han, De-min; Wang, Xiao-yi; Zhang, Yu-huan; Li, Yan-ru

2013-01-01

It is believed that defects in upper airway neuromuscular control play a role in sleep apnea pathogenesis. Currently, there is no simple and non-invasive method for evaluating neuromuscular activity for the purpose of screening in patients with obstructive sleep apnea. This study was designed to assess the validity of chin surface electromyography of routine polysomnography in evaluating the neuromuscular activity of obstructive sleep apnea subjects and probe the neuromuscular contribution in the pathogenesis of the condition. The chin surface electromyography of routine polysomnography during normal breathing and obstructive apnea were quantified in 36 male patients with obstructive sleep apnea. The change of chin surface electromyography from normal breathing to obstructive apnea was expressed as the percent compensated electromyography value, where the percent compensated electromyography value = (normal breath surface electromyography - apnea surface electromyography)/normal breath surface electromyography, and the percent compensated electromyography values among subjects were compared. The relationship between sleep apnea related parameters and the percent compensated electromyography value was examined. The percent compensated electromyography value of the subjects varied from 1% to 90% and had a significant positive correlation with apnea hypopnea index (R(2) = 0.382, P < 0.001). Recording and analyzing chin surface electromyography by routine polysomnography is a valid way of screening the neuromuscular activity in patients with obstructive sleep apnea. The neuromuscular contribution is different among subjects with obstructive sleep apnea.

Rationale and Clinical Techniques for Anterior Cruciate Ligament Injury Prevention Among Female Athletes

PubMed Central

Myer, Gregory D; Ford, Kevin R; Hewett, Timothy E

2004-01-01

Objective: To present the rationale and detailed techniques for the application of exercises targeted to prevent anterior cruciate ligament (ACL) injury in high-risk female athletes. Background: Female athletes have a 4- to 6-fold increased risk for ACL injury compared with their male counterparts playing at similar levels in the same sports. The increased ACL injury risk coupled with greater sports participation by young women over the last 30 years (9-fold increase in high school and 5-fold increase in collegiate sports) has generated public awareness and fueled several sex-related mechanistic and interventional investigations. These investigations provide the groundwork for the development of neuromuscular training aimed at targeting identified neuromuscular imbalances to decrease ACL injury risk. Description: After the onset of puberty, female athletes may not have a neuromuscular spurt to match their similar, rapid increase in growth and development. The lack of a natural neuromuscular adaptation may facilitate the development of neuromuscular imbalances that increase the risk for ACL injury. Dynamic neuromuscular analysis training provides the methodologic approach for identifying high-risk individuals and the basis of using interventions targeted to their specific needs. Clinical Advantages: Dynamic neuromuscular training applied to the high-risk population may decrease ACL injury risk and help more female athletes enjoy the benefits of sports participation without the long-term disabilities associated with injury. PMID:15592608

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study

PubMed Central

Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

2017-01-01

Background Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. Objective The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff’s use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. Methods In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff’s knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. Results The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. Conclusions With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists’ use of neuromuscular monitoring. Trial Registration Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x) PMID:28986337

Corrective Neuromuscular Approach to the Treatment of Iliotibial Band Friction Syndrome: A Case Report

PubMed Central

Pettitt, Robert; Dolski, Angela

2000-01-01

Objective: To describe the evaluation and treatment process for inappropriate functional patterns of neuromuscular activity within the scope of an iliotibial band friction syndrome protocol. Background: Runners with iliotibial band friction syndrome are frequently fitted with orthotic devices to restrict excessive midfoot or rearfoot, or both, motions during the stance phase. These devices may fail to yield favorable results when underlying neuromuscular factors are associated with functional iliotibial band tightening. Differential Diagnosis: Distal biceps femoris tendinitis, popliteal tendinitis, lateral meniscus lesion. Treatment: The athlete's physical examination revealed several patterns of inappropriate neuromuscular activity attributed partly to the prolonged daily wear of beach-type sandals. Modifications of casual footwear and a temporary reduction in training volume were recommended initially to prevent exacerbation of the athlete's condition. Stretching, massage, and soft tissue mobilization were administered in accordance with the athlete's specific needs. The protocol included progressions of nonweightbearing and weightbearing therapeutic exercises. Neuromuscular electric stimulation was incorporated into the protocol to re-educate the role of the first ray within the stance phase of the athlete's walking gait. Uniqueness: Upon stationary examination, this athlete presented with normal lumbar and lower extremity postures. Gait analysis, however, revealed inappropriate dorsiflexion of the great toe during ambulation. Further, the athlete's performances on a series of tests to assess neuromuscular function were substandard. This athlete's response to previous treatment and unique physical findings required a corrective neuromuscular approach that deviates from iliotibial band friction syndrome protocols advocating the use of orthotics. Conclusions: While the role of any single treatment in the athlete's recovery remains unknown, it seems that a corrective neuromuscular approach in the management of iliotibial band friction syndrome represents a viable alternative to orthotic intervention. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5. PMID:16558617

Knee joint biomechanics and neuromuscular control during gait before and after total knee arthroplasty are sex-specific.

PubMed

Astephen Wilson, Janie L; Dunbar, Michael J; Hubley-Kozey, Cheryl L

2015-01-01

The future of total knee arthroplasty (TKA) surgery will involve planning that incorporates more patient-specific characteristics. Despite known biological, morphological, and functional differences between men and women, there has been little investigation into knee joint biomechanical and neuromuscular differences between men and women with osteoarthritis, and none that have examined sex-specific biomechanical and neuromuscular responses to TKA surgery. The objective of this study was to examine sex-associated differences in knee kinematics, kinetics and neuromuscular patterns during gait before and after TKA. Fifty-two patients with end-stage knee OA (28 women, 24 men) underwent gait and neuromuscular analysis within the week prior to and one year after surgery. A number of sex-specific differences were identified which suggest a different manifestation of end-stage knee OA between the sexes. Copyright © 2014 Elsevier Inc. All rights reserved.

The potential of disease management for neuromuscular hereditary disorders.

PubMed

Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

2009-01-01

Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

The role of proprioception and neuromuscular stability in carpal instabilities.

PubMed

Hagert, E; Lluch, A; Rein, S

2016-01-01

Carpal stability has traditionally been defined as dependent on the articular congruity of joint surfaces, the static stability maintained by intact ligaments, and the dynamic stability caused by muscle contractions resulting in a compression of joint surfaces. In the past decade, a fourth factor in carpal stability has been proposed, involving the neuromuscular and proprioceptive control of joints. The proprioception of the wrist originates from afferent signals elicited by sensory end organs (mechanoreceptors) in ligaments and joint capsules that elicit spinal reflexes for immediate joint stability, as well as higher order neuromuscular influx to the cerebellum and sensorimotor cortices for planning and executing joint control. The aim of this review is to provide an understanding of the role of proprioception and neuromuscular control in carpal instabilities by delineating the sensory innervation and the neuromuscular control of the carpus, as well as descriptions of clinical applications of proprioception in carpal instabilities. © The Author(s) 2015.

Effects of neuromuscular joint facilitation on bridging exercises with respect to deep muscle changes.

PubMed

Zhou, Bin; Huang, QiuChen; Zheng, Tao; Huo, Ming; Maruyama, Hitoshi

2015-05-01

[Purpose] This study examined the effects of neuromuscular joint facilitation on bridging exercises by assessing the cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis. [Subjects] Twelve healthy men. [Methods] Four exercises were evaluated: (a) supine resting, (b) bridging resistance exercise involving posterior pelvic tilting, (c) bridging resistance exercise involving anterior pelvic tilting, and (d) bridging resistance exercise involving neuromuscular joint facilitation. The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were measured during each exercise. [Results] The cross-sectional area of the multifidus muscle and thickness of the musculus transversus abdominis were significantly greater in the neuromuscular joint facilitation group than the others. [Conclusion] Neuromuscular joint facilitation intervention improves the function of deep muscles such as the multifidus muscle and musculus transversus abdominis. Therefore, it can be recommended for application in clinical treatments such as that for back pain.

Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke.

PubMed

Byeon, Haewon; Koh, Hyeung Woo

2016-06-01

[Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study's findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia.

Comparison of treatment effect of neuromuscular electrical stimulation and thermal-tactile stimulation on patients with sub-acute dysphagia caused by stroke

PubMed Central

Byeon, Haewon; Koh, Hyeung Woo

2016-01-01

[Purpose] The effectiveness of neuromuscular electrical stimulation in the rehabilitation of swallowing remains controversial. This study compared the effectiveness of neuromuscular electrical stimulation and thermal tactile oral stimulation, a traditional swallowing recovery treatment, in patients with sub-acute dysphagia caused by stroke. [Subjects and Methods] Subjects of the present study were 55 patients diagnosed with dysphagia caused by stroke. This study had a nonequivalent control group pretest-posttest design. [Results] Analysis of pre-post values of videofluoroscopic studies of the neuromuscular electrical stimulation and thermal tactile oral stimulation groups using a paired t-test showed no significant difference between the two groups despite both having decreased mean values of the videofluoroscopic studies after treatment. [Conclusion] This study’s findings show that both neuromuscular electrical stimulation and thermal tactile oral stimulation significantly enhanced the swallowing function of patients with sub-acute dysphagia. PMID:27390421

Neurologic manifestations of chronic methamphetamine abuse

PubMed Central

Rusyniak, Daniel E.

2011-01-01

Summary Chronic methamphetamine abuse has devastating effects on the central nervous system. The degree to which addicts will tolerate the dysfunction in the way they think, feel, move, and even look, is a powerful testimony to the addictive properties of this drug. While the mechanisms behind these disorders are complex, at their heart they involve the recurring increase in the concentrations of central monoamines with subsequent dysfunction in dopaminergic neurotransmission. The mainstay of treatment for the problems associated with chronic methamphetamine abuse is abstinence. However, by recognizing the manifestations of chronic abuse, clinicians will be better able to help their patients get treatment for their addiction and to deal with the neurologic complications related to chronic abuse. PMID:21803215

Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update.

PubMed

Khan, Mohammad; Nishi, Shamima Easmin; Hassan, Siti Nazihahasma; Islam, Md Asiful; Gan, Siew Hua

2017-01-01

Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome.

Trigeminal Neuralgia, Glossopharyngeal Neuralgia, and Myofascial Pain Dysfunction Syndrome: An Update

PubMed Central

Nishi, Shamima Easmin; Hassan, Siti Nazihahasma

2017-01-01

Neuropathic pain is a common phenomenon that affects millions of people worldwide. Maxillofacial structures consist of various tissues that receive frequent stimulation during food digestion. The unique functions (masticatory process and facial expression) of the maxillofacial structure require the exquisite organization of both the peripheral and central nervous systems. Neuralgia is painful paroxysmal disorder of the head-neck region characterized by some commonly shared features such as the unilateral pain, transience and recurrence of attacks, and superficial and shock-like pain at a trigger point. These types of pain can be experienced after nerve injury or as a part of diseases that affect peripheral and central nerve function, or they can be psychological. Since the trigeminal and glossopharyngeal nerves innervate the oral structure, trigeminal and glossopharyngeal neuralgia are the most common syndromes following myofascial pain dysfunction syndrome. Nevertheless, misdiagnoses are common. The aim of this review is to discuss the currently available diagnostic procedures and treatment options for trigeminal neuralgia, glossopharyngeal neuralgia, and myofascial pain dysfunction syndrome. PMID:28827979

Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction.

PubMed

Nath, Samir R; Yu, Zhigang; Gipson, Theresa A; Marsh, Gregory B; Yoshidome, Eriko; Robins, Diane M; Todi, Sokol V; Housman, David E; Lieberman, Andrew P

2018-05-29

Skeletal muscle has emerged as a critical, disease-relevant target tissue in spinal and bulbar muscular atrophy, a degenerative disorder of the neuromuscular system caused by a CAG/polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. Here, we used RNA-Seq to identify pathways that are disrupted in diseased muscle using AR113Q knock-in mice. This analysis unexpectedly identified significantly diminished expression of numerous ubiquitin-proteasome pathway genes in AR113Q muscle, encoding approximately 30% of proteasome subunits and 20% of E2 ubiquitin conjugases. These changes were age-, hormone- and glutamine length-dependent and arose due to a toxic gain-of-function conferred by the mutation. Moreover, altered gene expression was associated with decreased level of the proteasome transcription factor NRF1 and its activator DDI2 and resulted in diminished proteasome activity. Ubiquitinated ADRM1 was detected in AR113Q muscle, indicating the occurrence of stalled proteasomes in mutant mice. Finally, diminished expression of Drosophila orthologues of NRF1 or ADRM1 promoted the accumulation of polyQ AR protein and increased toxicity. Collectively, these data indicate that AR113Q muscle develops progressive proteasome dysfunction that leads to the impairment of quality control and the accumulation of polyQ AR protein, key features that contribute to the age-dependent onset and progression of this disorder.

Effect of sugammadex versus neostigmine/atropine combination on postoperative cognitive dysfunction after elective surgery.

PubMed

Batistaki, C; Riga, M; Zafeiropoulou, F; Lyrakos, G; Kostopanagiotou, G; Matsota, P

2017-09-01

This study aimed to assess the effects of sugammadex and neostigmine/atropine on postoperative cognitive dysfunction (POCD) in adult patients after elective surgery. A randomised, double-blind controlled trial was carried out on 160 American Society of Anesthesiologists physical status I to III patients who were >40 years. The Mini-Mental State Evaluation, clock-drawing test and the Isaacs Set test were used to assess cognitive function at three timepoints: 1) preoperatively, 2) one hour postoperatively, and 3) at discharge. The anaesthetic protocol was the same for all patients, except for the neuromuscular block reversal, which was administered by random allocation using either sugammadex or neostigmine/atropine after the reappearance of T2 in the train-of-four sequence. POCD was defined as a decline ≥1 standard deviation in ≥2 cognitive tests. The incidence of POCD was similar in both groups at one hour postoperatively and at discharge (28% and 10%, in the neostigmine group, 23% and 5.4% in the sugammadex group, P =0.55 and 0.27 respectively). In relation to individual tests, a significant decline of clock-drawing test in the neostigmine group was observed at one hour postoperatively and at discharge. For the Isaacs Set test, a greater decline was found in the sugammadex group. These findings suggest that there are no clinically important differences in the incidence of POCD after neostigmine or sugammadex administration.

Neural Excitability and Joint Laxity in Chronic Ankle Instability, Coper, and Control Groups.

PubMed

Bowker, Samantha; Terada, Masafumi; Thomas, Abbey C; Pietrosimone, Brian G; Hiller, Claire E; Gribble, Phillip A

2016-04-01

Neuromuscular and mechanical deficiencies are commonly studied in participants with chronic ankle instability (CAI). Few investigators have attempted to comprehensively consider sensorimotor and mechanical differences among people with CAI, copers who did not present with prolonged dysfunctions after an initial ankle sprain, and a healthy control group. To determine if differences exist in spinal reflex excitability and ankle laxity among participants with CAI, copers, and healthy controls. Case-control study. Research laboratory. Thirty-seven participants with CAI, 30 participants categorized as copers, and 26 healthy control participants. We assessed spinal reflex excitability of the soleus using the Hoffmann reflex protocol. Participants' ankle laxity was measured with an instrumented ankle arthrometer. The maximum Hoffmann reflex : maximal muscle response ratio was calculated. Ankle laxity was measured as the total displacement in the anterior-posterior directions (mm) and total rotation in the inversion and eversion directions (°). Spinal reflex excitability was diminished in participants with CAI compared with copers and control participants (P = .01). No differences were observed among any of the groups for ankle laxity. Changes in the spinal reflex excitability of the soleus that likely affect ankle stability were seen only in the CAI group, yet no mechanical differences were noted across the groups. These findings support the importance of finding effective ways to increase spinal reflex excitability for the purpose of treating neural excitability dysfunction in patients with CAI.

Subjective and clinical assessment criteria suggestive for five clinical patterns discernible in nonspecific neck pain patients. A Delphi-survey of clinical experts.

PubMed

Dewitte, Vincent; Peersman, Wim; Danneels, Lieven; Bouche, Katie; Roets, Arne; Cagnie, Barbara

2016-12-01

Nonspecific neck pain patients form a heterogeneous group with different musculoskeletal impairments. Classifying nonspecific neck pain patients into subgroups based on clinical characteristics might lead to more comprehensive diagnoses and can guide effective management. To establish consensus among a group of experts regarding the clinical criteria suggestive of a clinical dominance of 'articular', 'myofascial', 'neural', 'central' and 'sensorimotor control' dysfunction patterns distinguishable in patients with nonspecific neck pain. Delphi study. A focus group with 10 academic experts was organized to elaborate on the different dysfunction patterns discernible in neck pain patients. Consecutively, a 3-round online Delphi-survey was designed to obtain consensual symptoms and physical examination findings for the 5 distinct dysfunction patterns resulting from the focus group. A total of 21 musculoskeletal physical therapists from Belgium and the Netherlands experienced in assessing and treating neck pain patients completed the 3-round Delphi-survey. Respectively, 33 (response rate, 100.0%), 27 (81.8%) and 21 (63.6%) respondents replied to rounds 1, 2 and 3. Eighteen 'articular', 16 'myofascial', 20 'neural', 18 'central' and 10 'sensorimotor control' clinical indicators reached a predefined ≥80% consensus level. These indicators suggestive of a clinical dominance of 'articular', 'myofascial', 'neural', 'central', and 'sensorimotor control' dysfunction patterns may help clinicians to assess and diagnose patients with nonspecific neck pain. Future validity testing is needed to determine how these criteria may help to improve the outcome of physical therapy interventions in nonspecific neck pain patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent achievements in restorative neurology: Progressive neuromuscular diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

1986-01-01

This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies.

[Mechanisms of the therapeutic effect of bemitil in neuromuscular diseases].

PubMed

Lobzin, V S; Saĭkova, L A; Chukhlovina, M L; Pustozerov, V G

1991-01-01

Studies into the mechanism of the therapeutic action of bemitil were carried out in 21 patients with neuromuscular diseases. Measurements of lipid peroxidation and permeability of the erythrocytic membranes demonstrated the drug to influence carbohydrate and lipid metabolism, lipid peroxidation, and permeability of the cellular membranes. It is recommended that bemitil be used for the treatment of neuromuscular diseases.

Correspondence and challenges as neurologists to Kumamoto Earthquakes in 2016.

PubMed

Nakajima, Makoto; Nakane, Nozomi; Takamatsu, Kotaro; Yamashita, Satoshi; Nakane, Shunya; Yamashita, Taro; Ando, Yukio

2016-12-28

Kumamoto Earthquakes in 2016 severely affected medical circumstances and condition of each patient with neuro-muscular diseases, in addition to having destroyed life circumstances of local residence. Number of neuro-muscular disease patients admitted to the Department of Neurology, Kumamoto University, the only university hospital in the prefecture, increased approximately twice compared to usual years. Most of the related facilities were able to admit emergency patients with neuro-muscular diseases although the hospital buildings were damaged in various degrees. A number of issues remained unsolved as to emergency contact system, securement of emergency beds for severe neuro-muscular diseases, and information system for these patients.

Effects of neuromuscular electrostimulation in patients with heart failure admitted to ward.

PubMed

de Araújo, Carlos José Soares; Gonçalves, Fernanda Souza; Bittencourt, Hugo Souza; dos Santos, Noélia Gonçalves; Mecca Junior, Sérgio Vitor; Neves, Júlio Leal Bandeira; Fernandes, André Maurício Souza; Aras Junior, Roque; dos Reis, Francisco José Farias Borges; Guimarães, Armênio Costa; Rodrigues Junior, Erenaldo de Souza; Carvalho, Vitor Oliveira

2012-11-15

Neuromuscular electrostimulation has become a promising issue in cardiovascular rehabilitation. However there are few articles published in the literature regarding neuromuscular electrostimulation in patients with heart failure during hospital stay. This is a randomized controlled pilot trial that aimed to investigate the effect of neuromuscular electrostimulation in the walked distance by the six-minute walking test in 30 patients admitted to ward for heart failure treatment in a tertiary cardiology hospital. Patients in the intervention group performed a conventional rehabilitation and neuromuscular electrostimulation. Patients underwent 60 minutes of electrostimulation (wave frequency was 20 Hz, pulse duration of 20 us) two times a day for consecutive days until hospital discharge. The walked distance in the six-minute walking test improved 75% in the electrostimulation group (from 379.7 ± 43.5 to 372.9 ± 46.9 meters to controls and from 372.9 ± 62.4 to 500 ± 68 meters to electrostimulation, p<0.001). On the other hand, the walked distance in the control group did not change. The neuromuscular electrostimulation group showed greater improvement in the walked distance in the six-minute walking test in patients admitted to ward for compensation of heart failure.

Gender differences in offaxis neuromuscular control during stepping under a slippery condition.

PubMed

Lee, Song Joo; Ren, Yupeng; Geiger, François; Zhang, Li-Qun

2013-11-01

Females are at greater risks of musculoskeletal injuries than are males, which may be related to decreased neuromuscular control in axial and/or frontal planes, offaxis neuromuscular control. The objective of this study was to investigate gender differences in offaxis neuromuscular control during stepping under a slippery condition. Forty-three healthy subjects (21 males and 22 females) performed different stepping tasks under a slippery condition, namely, free pivoting task (FPT) to control axial plane pivoting, free sliding task (FST) to control frontal plane sliding, and free pivoting and sliding task (FPST) to control axial pivoting, and frontal sliding on a custom-made offaxis elliptical trainer. Compared to males, females showed significantly higher pivoting instability, higher max internal and external pivoting angles, higher mean max medial and lateral sliding distance, and higher entropy of time to peak EMG in the medial and lateral gastrocnemius muscles during the FPST and higher entropy of time to peak EMG in the lateral gastrocnemius muscle during the FPT and FST. The findings may help us understand potential injury risk factors associated with gender differences, and provide a basis for developing targeted neuromuscular training to improve offaxis neuromuscular control, and reduce musculoskeletal injuries associated with excessive offaxis loadings.

A discrete event simulation model of clinical and operating room efficiency outcomes of sugammadex versus neostigmine for neuromuscular block reversal in Canada.

PubMed

Insinga, Ralph P; Joyal, Cédric; Goyette, Alexandra; Galarneau, André

2016-11-16

The objective of this analysis is to explore potential impact on operating room (OR) efficiency and incidence of residual neuromuscular blockade (RNMB) with use of sugammadex (Bridion™, Merck & Co., Inc., Kenilworth, NJ USA) versus neostigmine for neuromuscular block reversal in Canada. A discrete event simulation (DES) model was developed to compare ORs using either neostigmine or sugammadex for NMB reversal over one month. Selected inputs included OR procedure and turnover times, hospital policies for paid staff overtime and procedural cancellations due to OR time over-run, and reductions in RNMB and associated complications with sugammadex use. Trials show sugammadex's impact on OR time and RNMB varies by whether full neuromuscular recovery (train-of-four ratio ≥0.9) is verified prior to extubation in the OR. Scenarios were therefore evaluated reflecting varied assumptions for neuromuscular reversal practices. With use of moderate neuromuscular block, when full neuromuscular recovery is verified prior to extubation (93 procedures performed with sugammadex, 91 with neostigmine), use of sugammadex versus neostigmine avoided 2.4 procedural cancellations due to OR time over-run and 33.5 h of paid staff overtime, while saving an average of 62 min per OR day. No difference was observed between comparators for these endpoints in the scenario when full neuromuscular recovery was not verified prior to extubation, however, per procedure risk of RNMB at extubation was reduced from 60% to 4% (reflecting 51 cases prevented), with associated reductions in risks of hypoxemia (12 cases avoided) and upper airway obstruction (23 cases avoided). Sugammadex impact in reversing deep neuromuscular block was evaluated in an exploratory analysis. When it was hypothetically assumed that 30 min of OR time were saved per procedure, the number of paid hours of staff over-time dropped from 84.1 to 32.0, with a 93% reduction in the per patient risk of residual blockade. In clinical practice within Canada, for the majority of patients currently managed with moderate neuromuscular block, the principal impact of substituting sugammadex for neostigmine is likely to be a reduction in the risk of residual blockade and associated complications. For patients maintained at a deep level of block to the end of the procedure, sugammadex is likely to both enhance OR efficiency and reduce residual block complications.

Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.

PubMed

Tokuyama, Minami A; Xu, Cindy; Fisher, Rebecca E; Wilson-Rawls, Jeanne; Kusumi, Kenro; Newbern, Jason M

2018-01-15

Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response. Copyright © 2017 Elsevier Inc. All rights reserved.

Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a retrospectıve study.

PubMed

Ozmete, Ozlem; Bali, Cagla; Cok, Oya Yalcin; Turk, Hatice Evren Eker; Ozyilkan, Nesrın Bozdogan; Civi, Soner; Aribogan, Anıs

2016-12-01

To evaluate the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in infant patients. Retrospective observational study. University teaching hospital. Twenty-six infants (2-12 months of age; 3-11 kg) with an American Society of Anesthesiologists classification I, II, or III who were scheduled to undergo neurosurgical procedures were included in the study. Anesthesia was induced with 5 mg/kg thiopental, 1 μg/kg fentanyl and 0.6 mg/kg rocuronium. Sevoflurane was administered to all patients after intubation. The neuromuscular block was monitored with acceleromyography using train-of-four (TOF) stimuli. Patients received additional doses of rocuronium to maintain a deep block during surgery. If profound neuromuscular block (TOF, 0) persisted at the end of the surgery, 3mg/kg sugammadex was administered. The demographic data, surgeries, and anesthetic agents were recorded. The time from sugammadex administration to recovery of neuromuscular function (TOF ratio, >0.9) and complications during and after extubation were also recorded. Twenty-six infants who had a deep neuromuscular block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in infant surgical patients for reversal of deep neuromuscular block induced by rocuronium. Copyright © 2016 Elsevier Inc. All rights reserved.

Corticospinal excitability is associated with hypocapnia but not changes in cerebral blood flow

PubMed Central

Hartley, Geoffrey L.; Watson, Cody L.; Ainslie, Philip N.; Tokuno, Craig D.; Greenway, Matthew J.; Gabriel, David A.; O'Leary, Deborah D.

2016-01-01

Key points Reductions in cerebral blood flow (CBF) may be implicated in the development of neuromuscular fatigue; however, the contribution from hypocapnic‐induced reductions (i.e. P ETC O2) in CBF versus reductions in CBF per se has yet to be isolated.We assessed neuromuscular function while using indomethacin to selectively reduce CBF without changes in P ETC O2 and controlled hyperventilation‐induced hypocapnia to reduce both CBF and P ETC O2.Increased corticospinal excitability appears to be exclusive to reductions in P ETC O2 but not reductions in CBF, whereas sub‐optimal voluntary output from the motor cortex is moderately associated with decreased CBF independent of changes in P ETC O2.These findings suggest that changes in CBF and P ETC O2 have distinct roles in modulating neuromuscular function. Abstract Although reductions in cerebral blood flow (CBF) may be involved in central fatigue, the contribution from hypocapnia‐induced reductions in CBF versus reductions in CBF per se has not been isolated. This study examined whether reduced arterial PCO2 (P aC O2), independent of concomitant reductions in CBF, impairs neuromuscular function. Neuromuscular function, as indicated by motor‐evoked potentials (MEPs), maximal M‐wave (M max) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in ten males (29 ± 10 years) during three separate conditions: (1) cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg kg−1) to selectively reduce CBF by 28.8 ± 10.3% (estimated using transcranial Doppler ultrasound) without changes in end‐tidal PCO2 (P ETC O2); (2) controlled iso‐oxic hyperventilation‐induced reductions in P aC O2 (Hypocapnia), P ETC O2  = 30.1 ± 4.5 mmHg with related reductions in CBF (21.7 ± 6.3%); and (3) isocapnic hyperventilation (Isocapnia) to examine the potential direct influence of hyperventilation‐mediated activation of respiratory control centres on CBF and changes in neuromuscular function. Change in MEP amplitude (%M max) from baseline was greater in Hypocapnia tha in Isocapnia (11.7 ± 9.8%, 95% confidence interval (CI) [2.6, 20.7], P = 0.01) and Indomethacin (13.3 ± 11.3%, 95% CI [2.8, 23.7], P = 0.01) with a large Cohen's effect size (d ≥ 1.17). Although not statistically significant, cVA was reduced with a moderate effect size in Indomethacin (d = 0.7) and Hypocapnia (d = 0.9) compared to Isocapnia. In summary, increased corticospinal excitability – as reflected by larger MEP amplitude – appears to be exclusive to reduced P aC O2, but not reductions in CBF per se. Sub‐optimal voluntary output from the motor cortex is moderately associated with decreased CBF, independent of reduced P aC O2. PMID:26836470

Are Females More Resistant to Extreme Neuromuscular Fatigue?

PubMed

Temesi, John; Arnal, Pierrick J; Rupp, Thomas; Féasson, Léonard; Cartier, Régine; Gergelé, Laurent; Verges, Samuel; Martin, Vincent; Millet, Guillaume Y

2015-07-01

Despite interest in the possibility of females outperforming males in ultraendurance sporting events, little is known about the sex differences in fatigue during prolonged locomotor exercise. This study investigated possible sex differences in central and peripheral fatigue in the knee extensors and plantar flexors resulting from a 110-km ultra-trail-running race. Neuromuscular function of the knee extensors and plantar flexors was evaluated via transcranial magnetic stimulation (TMS) and electrical nerve stimulation before and after an ultra-trail-running race in 20 experienced ultraendurance trail runners (10 females and 10 males matched by percent of the winning time by sex) during maximal and submaximal voluntary contractions and in relaxed muscle. Maximal voluntary knee extensor torque decreased more in males than in females (-38% vs -29%, P = 0.006) although the reduction in plantar flexor torque was similar between sexes (-26% vs -31%). Evoked mechanical plantar flexor responses decreased more in males than in females (-23% vs -8% for potentiated twitch amplitude, P = 0.010), indicating greater plantar flexor peripheral fatigue in males. Maximal voluntary activation assessed by TMS and electrical nerve stimulation decreased similarly in both sexes for both muscle groups. Indices of knee extensor peripheral fatigue and corticospinal excitability and inhibition changes were also similar for both sexes. Females exhibited less peripheral fatigue in the plantar flexors than males did after a 110-km ultra-trail-running race and males demonstrated a greater decrease in maximal force loss in the knee extensors. There were no differences in the magnitude of central fatigue for either muscle group or TMS-induced outcomes. The lower level of fatigue in the knee extensors and peripheral fatigue in the plantar flexors could partly explain the reports of better performance in females in extreme duration running races as race distance increases.

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

PubMed

Wang, Haicui; Salter, Claire G; Refai, Osama; Hardy, Holly; Barwick, Katy E S; Akpulat, Ugur; Kvarnung, Malin; Chioza, Barry A; Harlalka, Gaurav; Taylan, Fulya; Sejersen, Thomas; Wright, Jane; Zimmerman, Holly H; Karakaya, Mert; Stüve, Burkhardt; Weis, Joachim; Schara, Ulrike; Russell, Mark A; Abdul-Rahman, Omar A; Chilton, John; Blakely, Randy D; Baple, Emma L; Cirak, Sebahattin; Crosby, Andrew H

2017-11-01

The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to a more severe spectrum with infantile lethality (p.Val112Glu). Cells transfected with mutant transporter construct revealed a virtually complete loss of transport activity that was paralleled by a reduction in transporter cell surface expression. Consistent with these findings, studies to determine the impact of gene mutations on the trafficking of the Caenorhabditis elegans choline transporter orthologue revealed deficits in transporter export to axons and nerve terminals. These findings contrast with our previous findings in autosomal dominant distal hereditary motor neuropathy of a dominant-negative frameshift mutation at the C-terminus of choline transporter that was associated with significantly reduced, but not completely abrogated choline transporter function. Together our findings define divergent neuropathological outcomes arising from different classes of choline transporter mutation with distinct disease processes and modes of inheritance. These findings underscore the essential role played by the choline transporter in sustaining acetylcholine neurotransmission at both central and neuromuscular synapses, with important implications for treatment and drug selection. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Central oculomotor disturbances and nystagmus: a window into the brainstem and cerebellum.

PubMed

Strupp, Michael; Hüfner, Katharina; Sandmann, Ruth; Zwergal, Andreas; Dieterich, Marianne; Jahn, Klaus; Brandt, Thomas

2011-03-01

Oculomotor disturbances and nystagmus are seen in many diseases of the nervous system, the vestibular apparatus, and the eyes, as well as in toxic and metabolic disorders. They often indicate a specific underlying cause. The key to diagnosis is systematic clinical examination of the patient's eye movements. This review deals mainly with central oculomotor disturbances, i.e., those involving smooth pursuit, saccades, gaze-holding, and central types of nystagmus. We searched the current literature for relevant publications on the diagnosis and treatment of oculomotor disturbances and nystagmus, and discuss them selectively in this review along with the German Neurological Society's guidelines on the topic. A detailed knowledge of the anatomy and physiology of eye movements usually enables the physician to localize the disturbance to a specific area in the brainstem or cerebellum. The examination of eye movements is an even more sensitive method than magnetic resonance imaging for the diagnosis of acute vestibular syndromes and for the differentiation of peripheral from central lesions. For example, isolated dysfunction of horizontal saccades is due to a pontine lesion, while isolated dysfunction of vertical saccades is due to a midbrain lesion. Generalized gaze-evoked nystagmus (GEN) has multiple causes; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. Internuclear ophthalmoplegia involves a constellation of findings, the most prominent of which is impaired adduction to the side of the causative lesion in the ipsilateral medial longitudinal fasciculus. The most common pathological types of central nystagmus are downbeat and upbeat nystagmus (DBN, UBN). DBN is generally due to cerebellar dysfunction, e.g., because of a neurodegenerative disease. This short review focuses on the clinical characteristics, pathophysiology and current treatment of oculomotor disorders and nystagmus.

Diagnostic support for selected neuromuscular diseases using answer-pattern recognition and data mining techniques: a proof of concept multicenter prospective trial.

PubMed

Grigull, Lorenz; Lechner, Werner; Petri, Susanne; Kollewe, Katja; Dengler, Reinhard; Mehmecke, Sandra; Schumacher, Ulrike; Lücke, Thomas; Schneider-Gold, Christiane; Köhler, Cornelia; Güttsches, Anne-Katrin; Kortum, Xiaowei; Klawonn, Frank

2016-03-08

Diagnosis of neuromuscular diseases in primary care is often challenging. Rare diseases such as Pompe disease are easily overlooked by the general practitioner. We therefore aimed to develop a diagnostic support tool using patient-oriented questions and combined data mining algorithms recognizing answer patterns in individuals with selected neuromuscular diseases. A multicenter prospective study for the proof of concept was conducted thereafter. First, 16 interviews with patients were conducted focusing on their pre-diagnostic observations and experiences. From these interviews, we developed a questionnaire with 46 items. Then, patients with diagnosed neuromuscular diseases as well as patients without such a disease answered the questionnaire to establish a database for data mining. For proof of concept, initially only six diagnoses were chosen (myotonic dystrophy and myotonia (MdMy), Pompe disease (MP), amyotrophic lateral sclerosis (ALS), polyneuropathy (PNP), spinal muscular atrophy (SMA), other neuromuscular diseases, and no neuromuscular disease (NND). A prospective study was performed to validate the automated malleable system, which included six different classification methods combined in a fusion algorithm proposing a final diagnosis. Finally, new diagnoses were incorporated into the system. In total, questionnaires from 210 individuals were used to train the system. 89.5 % correct diagnoses were achieved during cross-validation. The sensitivity of the system was 93-97 % for individuals with MP, with MdMy and without neuromuscular diseases, but only 69 % in SMA and 81 % in ALS patients. In the prospective trial, 57/64 (89 %) diagnoses were predicted correctly by the computerized system. All questions, or rather all answers, increased the diagnostic accuracy of the system, with the best results reached by the fusion of different classifier methods. Receiver operating curve (ROC) and p-value analyses confirmed the results. A questionnaire-based diagnostic support tool using data mining methods exhibited good results in predicting selected neuromuscular diseases. Due to the variety of neuromuscular diseases, additional studies are required to measure beneficial effects in the clinical setting.

Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep.

PubMed

Randerath, Winfried; Verbraecken, Johan; Andreas, Stefan; Arzt, Michael; Bloch, Konrad E; Brack, Thomas; Buyse, Bertien; De Backer, Wilfried; Eckert, Danny Joel; Grote, Ludger; Hagmeyer, Lars; Hedner, Jan; Jennum, Poul; La Rovere, Maria Teresa; Miltz, Carla; McNicholas, Walter T; Montserrat, Josep; Naughton, Matthew; Pepin, Jean-Louis; Pevernagie, Dirk; Sanner, Bernd; Testelmans, Dries; Tonia, Thomy; Vrijsen, Bart; Wijkstra, Peter; Levy, Patrick

2017-01-01

The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a "marker" of disease severity or a "mediator" of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation. Copyright ©ERS 2017.

Improving Neuromuscular Monitoring and Reducing Residual Neuromuscular Blockade With E-Learning: Protocol for the Multicenter Interrupted Time Series INVERT Study.

PubMed

Thomsen, Jakob Louis Demant; Mathiesen, Ole; Hägi-Pedersen, Daniel; Skovgaard, Lene Theil; Østergaard, Doris; Engbaek, Jens; Gätke, Mona Ring

2017-10-06

Muscle relaxants facilitate endotracheal intubation under general anesthesia and improve surgical conditions. Residual neuromuscular blockade occurs when the patient is still partially paralyzed when awakened after surgery. The condition is associated with subjective discomfort and an increased risk of respiratory complications. Use of an objective neuromuscular monitoring device may prevent residual block. Despite this, many anesthetists refrain from using the device. Efforts to increase the use of objective monitoring are time consuming and require the presence of expert personnel. A neuromuscular monitoring e-learning module might support consistent use of neuromuscular monitoring devices. The aim of the study is to assess the effect of a neuromuscular monitoring e-learning module on anesthesia staff's use of objective neuromuscular monitoring and the incidence of residual neuromuscular blockade in surgical patients at 6 Danish teaching hospitals. In this interrupted time series study, we are collecting data repeatedly, in consecutive 3-week periods, before and after the intervention, and we will analyze the effect using segmented regression analysis. Anesthesia departments in the Zealand Region of Denmark are included, and data from all patients receiving a muscle relaxant are collected from the anesthesia information management system MetaVision. We will assess the effect of the module on all levels of potential effect: staff's knowledge and skills, patient care practice, and patient outcomes. The primary outcome is use of neuromuscular monitoring in patients according to the type of muscle relaxant received. Secondary outcomes include last recorded train-of-four value, administration of reversal agents, and time to discharge from the postanesthesia care unit as well as a multiple-choice test to assess knowledge. The e-learning module was developed based on a needs assessment process, including focus group interviews, surveys, and expert opinions. The e-learning module was implemented in 6 anesthesia departments on 21 November 2016. Currently, we are collecting postintervention data. The final dataset will include data from more than 10,000 anesthesia procedures. We expect to publish the results in late 2017 or early 2018. With a dataset consisting of thousands of general anesthesia procedures, the INVERT study will assess whether an e-learning module can increase anesthetists' use of neuromuscular monitoring. Clinicaltrials.gov NCT02925143; https://clinicaltrials.gov/ct2/show/NCT02925143 (Archived by WebCite® at http://www.webcitation.org/6s50iTV2x). ©Jakob Louis Demant Thomsen, Ole Mathiesen, Daniel Hägi-Pedersen, Lene Theil Skovgaard, Doris Østergaard, Jens Engbaek, Mona Ring Gätke. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 06.10.2017.

Space, Time, and Dyslexia: Central Nervous System Factors in Reading Disability.

ERIC Educational Resources Information Center

Krippner, Stanley

Developmental and post-traumatic dyslexia are discussed in terms of a dysfunction of the central nervous system resulting in reading disabilities. The relationship of reading to other language functions is considered, with emphasis on the temporal aspects of speech and reading. An interdisciplinary approach is held necessary for the diagnosis of…

The epidemiology of neuromuscular disorders: Age at onset and gender in the Netherlands.

PubMed

Deenen, Johanna C W; van Doorn, Pieter A; Faber, Catharina G; van der Kooi, Anneke J; Kuks, Jan B M; Notermans, Nicolette C; Visser, Leo H; Horlings, Corinne G C; Verschuuren, Jan J G M; Verbeek, André L M; van Engelen, Baziel G M

2016-07-01

Based on approximately eight years of data collection with the nationwide Computer Registry of All Myopathies and Polyneuropathies (CRAMP) in the Netherlands, recent epidemiologic information for thirty neuromuscular disorders is presented. This overview includes age and gender data for a number of neuromuscular disorders that are either relatively frequently seen in the neuromuscular clinic, or have a particular phenotype. Since 2004, over 20,000 individuals with a neuromuscular disorder were registered in CRAMP; 56% men and 44% women. The number per diagnosis varied from nine persons with Emery-Dreifuss muscular dystrophy to 2057 persons with amyotrophic lateral sclerosis. Proportions of men ranged from 38% with post-polio syndrome to 68% with progressive spinal muscular atrophy, excluding X-chromosome linked disorders. Inclusion body myositis showed the highest median age at diagnosis of 70 years. These data may be helpful in the diagnostic process in clinical practice and trial readiness. Copyright © 2016 Elsevier B.V. All rights reserved.

The relative frequency of common neuromuscular diagnoses in a reference center.

PubMed

Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

2017-11-01

The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. To report the relative frequency of common neuromuscular diagnoses in a reference center. A 17-year chart review of patients with suspicion of myopathy. Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

Diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view.

PubMed

Engel, W King

2015-04-01

Ageing of the neuromuscular system in elderhood ingravescently contributes to slowness, weakness, falling and death, often accompanied by numbness and pain. This article is to put in perspective examples from a half-century of personal and team neuromuscular histochemical-pathological and clinical-pathological research, including a number of lucky and instructive accomplishments identifying new treatments and new diseases. A major focus currently is on some important, still enigmatic, aspects of the ageing neuromuscular system. It is also includes some of the newest references of others on various closely-related aspects of this ageing system. The article may help guide others in their molecular-based endeavors to identify paths leading to discovering new treatments and new pathogenic aspects. These are certainly needed - our ageing and unsteady constituents are steadily increasing. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy

PubMed Central

Kim, Ji Eun; Chun, Hea Rim

2017-01-01

Abstract Introduction: Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. Clinical features: An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. Conclusion: A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD. PMID:28353578

Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with duchenne muscular dystrophy: A case Report.

PubMed

Kim, Ji Eun; Chun, Hea Rim

2017-03-01

Anesthetic management of patients with Duchenne muscular dystrophy (DMD) is complicated because these patients are more sensitive to nondepolarizing neuromuscular blocking agents (NMBAs) and are vulnerable to postoperative complications, such as postoperative residual curarization and respiratory failure. Sugammadex is a new reversal agent for aminosteroidal NMBAs, but its safety in children is controversial. An 11-year-old boy with DMD underwent general anesthesia for a percutaneous nephrolithotomy. We used rocuronium bromide and sugammadex to reverse the deep neuromuscular block. Reversal of neuromuscular block was done 15 minutes after administration of 2 mg/kg of sugammadex. The patient's recovery from anesthesia was uneventful, and he was discharged to the postoperative recovery ward. A delayed recovery was achieved, but no adverse events were observed, such as recurarization or hypersensitivity to sugammadex. We report safe use of 2 mg/kg of sugammadex to reverse a deep neuromuscular block in a child with DMD.

A computer-controlled, closed-loop infusion system for infusing muscle relaxants: its use during motor-evoked potential monitoring.

PubMed

Stinson, L W; Murray, M J; Jones, K A; Assef, S J; Burke, M J; Behrens, T L; Lennon, R L

1994-02-01

A microcomputer-controlled closed-loop infusion system (MCCLIS) has been developed that provides stable intraoperative levels of partial neuromuscular blockade. Complete neuromuscular blockade interferes with intraoperative motor-evoked potential (MEP) monitoring used for patients undergoing surgical procedures that place them at risk for spinal cord ischemia. Nine patients were studied during which the MCCLIS maintained stable levels of partial neuromuscular blockade and allowed transcranial magnetic motor-evoked potential (TcM-MEP) monitoring during thoracoabdominal aortic aneurysmectomy. The use of TcM-MEP for monitoring intraoperative spinal cord function was balanced against surgical considerations for muscle relaxation with 80% to 90% neuromuscular blockade fulfilling each requirement. Intraoperative adjustment of partial neuromuscular blockade to facilitate TcM-MEP monitoring was also possible with the MCCLIS. The MCCLIS should allow for further investigation into the sensitivity, specificity, and predictability of TcM-MEP monitoring for any patient at risk for intraoperative spinal cord ischemia including those undergoing thoracoabdominal aortic aneurysmectomy.

An Integrated Approach to Change the Outcome Part II: Targeted Neuromuscular Training Techniques to Reduce Identified ACL Injury Risk Factors

PubMed Central

Myer, Gregory D.; Ford, Kevin R.; Brent, Jensen L.; Hewett, Timothy E.

2014-01-01

Prior reports indicate that female athletes who demonstrate high knee abduction moments (KAMs) during landing are more responsive to neuromuscular training designed to reduce KAM. Identification of female athletes who demonstrate high KAM, which accurately identifies those at risk for noncontact anterior cruciate ligament (ACL) injury, may be ideal for targeted neuromuscular training. Specific neuromuscular training targeted to the underlying biomechanical components that increase KAM may provide the most efficient and effective training strategy to reduce noncontact ACL injury risk. The purpose of the current commentary is to provide an integrative approach to identify and target mechanistic underpinnings to increased ACL injury in female athletes. Specific neuromuscular training techniques will be presented that address individual algorithm components related to high knee load landing patterns. If these integrated techniques are employed on a widespread basis, prevention strategies for noncontact ACL injury among young female athletes may prove both more effective and efficient. PMID:22580980

Effect of the Masako maneuver and neuromuscular electrical stimulation on the improvement of swallowing function in patients with dysphagia caused by stroke

PubMed Central

Byeon, Haewon

2016-01-01

[Purpose] The aim of this study was to compare improvements in swallowing function by the intervention of the Masako maneuver and neuromuscular electrical stimulation in patients with dysphagia caused by stroke. [Subjects and Methods] The Masako maneuver (n=23) and neuromuscular electrical stimulation (n=24) were conducted in 47 patients with dysphagia caused by stroke over a period of 4 weeks. Swallowing recovery was recorded using the functional dysphagia scale based on videofluoroscopic studies. [Results] Mean functional dysphagia scale values for the Masako maneuver and neuromuscular electrical stimulation groups decreased after the treatments. However, the pre-post functional dysphagia scale values showed no statistically significant differences between the groups. [Conclusion] The Masako maneuver and neuromuscular electrical stimulation each showed significant effects on the improvement of swallowing function for the patients with dysphagia caused by stroke, but no significant difference was observed between the two treatment methods. PMID:27512266

Swallowing and Secretion Management in Neuromuscular Disease.

PubMed

Britton, Deanna; Karam, Chafic; Schindler, Joshua S

2018-06-01

Neuromuscular disease frequently leads to dysphagia and difficulty managing secretions. Dysphagia may lead to medical complications, such as malnutrition, dehydration, aspiration pneumonia, and other pulmonary complications, as well as social isolation and reduced overall quality of life. This review provides an overview of dysphagia associated with neuromuscular disease in adults, along with a concise review of swallowing assessment and intervention options. Copyright © 2018 Elsevier Inc. All rights reserved.

Lumbopelvic flexibility modulates neuromuscular responses during trunk flexion-extension.

PubMed

Sánchez-Zuriaga, Daniel; Artacho-Pérez, Carla; Biviá-Roig, Gemma

2016-06-01

Various stimuli such as the flexibility of lumbopelvic structures influence the neuromuscular responses of the trunk musculature, leading to different load sharing strategies and reflex muscle responses from the afferents of lumbopelvic mechanoreceptors. This link between flexibility and neuromuscular response has been poorly studied. The aim of this study was to investigate the relationship between lumbopelvic flexibility and neuromuscular responses of the erector spinae, hamstring and abdominal muscles during trunk flexion-extension. Lumbopelvic movement patterns were measured in 29 healthy women, who were separated into two groups according to their flexibility during trunk flexion-extension. The electromyographic responses of erector spinae, rectus abdominis and biceps femoris were also recorded. Subjects with greater lumbar flexibility had significantly less pelvic flexibility and vice versa. Subjects with greater pelvic flexibility had a higher rate of relaxation and lower levels of hamstring activation during maximal trunk flexion. The neuromuscular response patterns of the hamstrings seem partially modulated by pelvic flexibility. Not so with the lumbar erector spinae and lumbar flexibility, despite the assertions of some previous studies. The results of this study improve our knowledge of the relationships between trunk joint flexibility and neuromuscular responses, a relationship which may play a role in low back pain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.

PubMed

Camacho, A; Esteban, J; Paradas, C

A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Do changes in neuromuscular activation contribute to the knee extensor angle-torque relationship?

PubMed

Lanza, Marcel B; Balshaw, Thomas G; Folland, Jonathan P

2017-08-01

What is the central question of the study? Do changes in neuromuscular activation contribute to the knee extensor angle-torque relationship? What is the main finding and its importance? Both agonist (quadriceps) and antagonist coactivation (hamstrings) differed with knee joint angle during maximal isometric knee extensions and thus both are likely to contribute to the angle-torque relationship. Specifically, two independent measurement techniques showed quadriceps activation to be lower at more extended positions. These effects might influence the capacity for neural changes in response to training and rehabilitation at different knee joint angles. The influence of joint angle on knee extensor neuromuscular activation is unclear, owing in part to the diversity of surface electromyography (sEMG) and/or interpolated twitch technique (ITT) methods used. The aim of the study was to compare neuromuscular activation, using rigorous contemporary sEMG and ITT procedures, during isometric maximal voluntary contractions (iMVCs) of the quadriceps femoris at different knee joint angles and examine whether activation contributes to the angle-torque relationship. Sixteen healthy active men completed two familiarization sessions and two experimental sessions of isometric knee extension and knee flexion contractions. The experimental sessions included the following at each of four joint angles (25, 50, 80 and 106 deg): iMVCs (with and without superimposed evoked doublets); submaximal contractions with superimposed doublets; and evoked twitch and doublet contractions whilst voluntarily passive, and knee flexion iMVC at the same knee joint positions. The absolute quadriceps femoris EMG was normalized to the peak-to-peak amplitude of an evoked maximal M-wave, and the doublet-voluntary torque relationship was used to calculate activation with the ITT. Agonist activation, assessed with both normalized EMG and the ITT, was reduced at the more extended compared with the more flexed positions (25 and 50 versus 80 and 106 deg; P ≤ 0.016), whereas antagonist coactivation was greatest in the most flexed compared with the extended positions (106 versus 25 and 50 deg; P ≤ 0.02). In conclusion, both agonist and antagonist activation differed with knee joint angle during knee extension iMVCs, and thus both are likely to contribute to the knee extensor angle-torque relationship. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures

PubMed Central

Knierim, Ellen; Hirata, Hiromi; Wolf, Nicole I.; Morales-Gonzalez, Susanne; Schottmann, Gudrun; Tanaka, Yu; Rudnik-Schöneborn, Sabine; Orgeur, Mickael; Zerres, Klaus; Vogt, Stefanie; van Riesen, Anne; Gill, Esther; Seifert, Franziska; Zwirner, Angelika; Kirschner, Janbernd; Goebel, Hans Hilmar; Hübner, Christoph; Stricker, Sigmar; Meierhofer, David; Stenzel, Werner; Schuelke, Markus

2016-01-01

Transcriptional signal cointegrators associate with transcription factors or nuclear receptors and coregulate tissue-specific gene transcription. We report on recessive loss-of-function mutations in two genes (TRIP4 and ASCC1) that encode subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex. We used autozygosity mapping and whole-exome sequencing to search for pathogenic mutations in four families. Affected individuals presented with prenatal-onset spinal muscular atrophy (SMA), multiple congenital contractures (arthrogryposis multiplex congenita), respiratory distress, and congenital bone fractures. We identified homozygous and compound-heterozygous nonsense and frameshift TRIP4 and ASCC1 mutations that led to a truncation or the entire absence of the respective proteins and cosegregated with the disease phenotype. Trip4 and Ascc1 have identical expression patterns in 17.5-day-old mouse embryos with high expression levels in the spinal cord, brain, paraspinal ganglia, thyroid, and submandibular glands. Antisense morpholino-mediated knockdown of either trip4 or ascc1 in zebrafish disrupted the highly patterned and coordinated process of α-motoneuron outgrowth and formation of myotomes and neuromuscular junctions and led to a swimming defect in the larvae. Immunoprecipitation of the ASC-1 complex consistently copurified cysteine and glycine rich protein 1 (CSRP1), a transcriptional cofactor, which is known to be involved in spinal cord regeneration upon injury in adult zebrafish. ASCC1 mutant fibroblasts downregulated genes associated with neurogenesis, neuronal migration, and pathfinding (SERPINF1, DAB1, SEMA3D, SEMA3A), as well as with bone development (TNFRSF11B, RASSF2, STC1). Our findings indicate that the dysfunction of a transcriptional coactivator complex can result in a clinical syndrome affecting the neuromuscular system. PMID:26924529

The Role of Neuromuscular Changes in Aging and Knee Osteoarthritis on Dynamic Postural Control

PubMed Central

Takacs, Judit; Carpenter, Mark G.; Garland, S. Jayne; Hunt, Michael A.

2013-01-01

Knee osteoarthritis (OA) is a chronic joint condition, with 30% of those over the age of 75 exhibiting severe radiographic disease. Nearly 50% of those with knee OA have experienced a fall in the past year. Falls are a considerable public health concern, with a high risk of serious injury and a significant socioeconomic impact. The ability to defend against a fall relies on adequate dynamic postural control, and alterations in dynamic postural control are seen with normal aging. Neuromuscular changes associated with aging may be responsible for some of these alterations in dynamic postural control. Even greater neuromuscular deficits, which may impact dynamic postural control and the ability to defend against a fall, are seen in people with knee OA. There is little evidence to date on how knee OA affects the ability to respond to and defend against falls and the neuromuscular changes that contribute to balance deficits. As a result, this review will: summarize the key characteristics of postural responses to an external perturbation, highlight the changes in dynamic postural control seen with normal aging, review the neuromuscular changes associated with aging that have known and possible effects on dynamic postural control, and summarize the neuromuscular changes and balance problems in knee OA. Future research to better understand the role of neuromuscular changes in knee OA and their effect on dynamic postural control will be suggested. Such an understanding is critical to the successful creation and implementation of fall prevention and treatment programs, in order to reduce the excessive risk of falling in knee OA. PMID:23696951

Robotic assessment of neuromuscular characteristics using musculoskeletal models: A pilot study.

PubMed

Jayaneththi, V R; Viloria, J; Wiedemann, L G; Jarrett, C; McDaid, A J

2017-07-01

Non-invasive neuromuscular characterization aims to provide greater insight into the effectiveness of existing and emerging rehabilitation therapies by quantifying neuromuscular characteristics relating to force production, muscle viscoelasticity and voluntary neural activation. In this paper, we propose a novel approach to evaluate neuromuscular characteristics, such as muscle fiber stiffness and viscosity, by combining robotic and HD-sEMG measurements with computational musculoskeletal modeling. This pilot study investigates the efficacy of this approach on a healthy population and provides new insight on potential limitations of conventional musculoskeletal models for this application. Subject-specific neuromuscular characteristics of the biceps and triceps brachii were evaluated using robot-measured kinetics, kinematics and EMG activity as inputs to a musculoskeletal model. Repeatability experiments in five participants revealed large variability within each subjects evaluated characteristics, with almost all experiencing variation greater than 50% of full scale when repeating the same task. The use of robotics and HD-sEMG, in conjunction with musculoskeletal modeling, to quantify neuromuscular characteristics has been explored. Despite the ability to predict joint kinematics with relatively high accuracy, parameter characterization was inconsistent i.e. many parameter combinations gave rise to minimal kinematic error. The proposed technique is a novel approach for in vivo neuromuscular characterization and is a step towards the realization of objective in-home robot-assisted rehabilitation. Importantly, the results have confirmed the technical (robot and HD-sEMG) feasibility while highlighting the need to develop new musculoskeletal models and optimization techniques capable of achieving consistent results across a range of dynamic tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of routine reversal of neuromuscular blockade on adequacy of recurrent laryngeal nerve stimulation during thyroid surgery.

PubMed

Marshall, S D; Boden, E; Serpell, J

2015-07-01

Testing of the integrity of the recurrent laryngeal nerve during thyroid surgery has become routine practice for many surgeons to aid dissection and minimise the chance of inadvertent nerve injury. We hypothesised that routine reversal of an intermediate-acting, non-depolarising neuromuscular blocking agent would improve conditions for stimulation of the recurrent laryngeal nerve. We conducted a single-centre, randomised, double-blind placebo-controlled trial of patients undergoing thyroid surgery by the same surgeon. After randomisation, the participants received either neostigmine 2.5 mg with glycopyrrolate 0.4 mg or placebo, at 30 minutes after induction of anaesthesia and administration of 0.4 mg/kg of atracurium. The primary outcome was the subjective assessment by the surgeon as to whether the neuromuscular function was adequate for stimulation of the recurrent laryngeal nerve using a neuromuscular integrity monitor (NIM). Time to NIM stimulation was 44.6 minutes in the placebo group and 41.4 minutes in the intervention group (P=0.268). Of the 21 patients who received the neuromuscular blockade reversal, 20 (95.2%) had adequate surgical conditions for NIM stimulation, compared to 9 out of 18 patients (50%) in the placebo group (P=0.002). Three of the ten patients (30%) with inadequate reversal showed no evidence of residual blockade assessed peripherally. The routine reversal of neuromuscular blockade at 30 minutes post induction appears to result in adequate surgical conditions for safe stimulation of the recurrent laryngeal nerve. Return of neuromuscular function at a peripheral site does not guarantee adequate laryngeal muscle function for use of the NIM.

VAChT overexpression increases acetylcholine at the synaptic cleft and accelerates aging of neuromuscular junctions.

PubMed

Sugita, Satoshi; Fleming, Leland L; Wood, Caleb; Vaughan, Sydney K; Gomes, Matheus P S M; Camargo, Wallace; Naves, Ligia A; Prado, Vania F; Prado, Marco A M; Guatimosim, Cristina; Valdez, Gregorio

2016-01-01

Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). Chat-ChR2-EYFP (VAChT Hyp ) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1 G93A ), and Chat-IRES-Cre and tdTomato transgenic mice were used in this study. NMJs, muscle fibers, and α-motor neurons' somata and their axons were examined using a light microscope. Transcripts for select genes in muscles and spinal cords were assessed using real-time quantitative PCR. Motor function tests were carried out using an inverted wire mesh and a rotarod. Electrophysiological recordings were collected to examine miniature endplate potentials (MEPP) in muscles. We show that VAChT is elevated in the spinal cord and at NMJs of VAChT Hyp mice. We also show that the amplitude of MEPPs is significantly higher in VAChT Hyp muscles, indicating that more ACh is loaded into synaptic vesicles and released into the synaptic cleft at NMJs of VAChT Hyp mice compared to control mice. While the development of NMJs was not affected in VAChT Hyp mice, NMJs prematurely acquired age-related structural alterations in adult VAChT Hyp mice. These structural changes at NMJs were accompanied by motor deficits in VAChT Hyp mice. However, cellular features of muscle fibers and levels of molecules with critical functions at the NMJ and in muscle fibers were largely unchanged in VAChT Hyp mice. In the SOD1 G93A mouse model for ALS, increasing synaptic ACh accelerated degeneration of NMJs caused motor deficits and resulted in premature death specifically in male mice. The data presented in this manuscript demonstrate that increasing levels of ACh at the synaptic cleft promote degeneration of adult NMJs, contributing to age- and disease-related motor deficits. We thus propose that maintaining normal cholinergic signaling in muscles will slow degeneration of NMJs and attenuate loss of motor function caused by aging and neuromuscular diseases.

The impact of neuromuscular electrical stimulation on recovery after intensive, muscle damaging, maximal speed training in professional team sports players.

PubMed

Taylor, Tom; West, Daniel J; Howatson, Glyn; Jones, Chris; Bracken, Richard M; Love, Thomas D; Cook, Christian J; Swift, Eamon; Baker, Julien S; Kilduff, Liam P

2015-05-01

During congested fixture periods in team sports, limited recovery time and increased travel hinder the implementation of many recovery strategies; thus alternative methods are required. We examined the impact of a neuromuscular electrical stimulation device on 24-h recovery from an intensive training session in professional players. Twenty-eight professional rugby and football academy players completed this randomised and counter-balanced study, on 2 occasions, separated by 7 days. After baseline perceived soreness, blood (lactate and creatine kinase) and saliva (testosterone and cortisol) samples were collected, players completed a standardised warm-up and baseline countermovement jumps (jump height). Players then completed 60 m × 50 m maximal sprints, with 5 min recovery between efforts. After completing the sprint session, players wore a neuromuscular electrical stimulation device or remained in normal attire (CON) for 8 h. All measures were repeated immediately, 2 and 24-h post-sprint. Player jump height was reduced from baseline at all time points under both conditions; however, at 24-h neuromuscular electrical stimulation was significantly more recovered (mean±SD; neuromuscular electrical stimulation -3.2±3.2 vs. CON -7.2±3.7%; P<0.001). Creatine kinase concentrations increased at all time points under both conditions, but at 24-h was lower under neuromuscular electrical stimulation (P<0.001). At 24-h, perceived soreness was significantly lower under neuromuscular electrical stimulation, when compared to CON (P=0.02). There was no effect of condition on blood lactate, or saliva testosterone and cortisol responses (P>0.05). Neuromuscular electrical stimulation improves recovery from intensive training in professional team sports players. This strategy offers an easily applied recovery strategy which may have particular application during sleep and travel. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Survey of how different groups of veterinarians manage the use of neuromuscular blocking agents in anesthetized dogs.

PubMed

Martin-Flores, Manuel; Sakai, Daniel M; Campoy, Luis; Gleed, Robin D

2018-03-23

To analyze practice habits associated with the use, reversal and monitoring of nondepolarizing neuromuscular blocking agents (NMBAs) in dogs by different groups of veterinarians. Online anonymous survey to veterinarians. Data from 390 answered surveys. A questionnaire was sent to e-mail list servers of the American College of Veterinary Anesthesia and Analgesia (ACVAA-list), Sociedad Española de Anestesia y Analgesia Veterinaria (SEEAV-list), Colégio Brasileiro de Anestesiologia Veterinária (Brazilian College of Veterinary Anesthesiology; CBAV-list) and American College of Veterinary Ophthalmologists (ACVO-list) to elicit information regarding use of NMBAs and reversal agents, monitoring techniques, criteria for redosing, reversing and assessing adequacy of recovery of neuromuscular function. Binomial logistic regression was used to test for association between responses and group of veterinarians in selected questions. Veterinarians of the ACVO-list use NMBAs on a higher fraction of their caseload than other groups (all p < 0.0001). Subjective assessment (observation) of spontaneous movement, including spontaneous breathing, is the most common method for assessing neuromuscular function (43% of pooled responses); 18% of participants always reverse NMBAs, whereas 16% never reverse them. Restoration of neuromuscular function is assessed subjectively by 35% of respondents. Residual neuromuscular block is the most common concern regarding the use of NMBAs for all groups of veterinarians. Side effects of reversal agents (anticholinesterases) were of least concern for all groups. While most veterinarians are concerned about residual neuromuscular block, relatively few steps are implemented to reduce the risks of this complication, such as routine use of quantitative neuromuscular monitoring or routine reversal of NMBAs. These results suggest a limitation in transferring information among groups of veterinarians, or in implementing techniques suggested by scientific research. Copyright © 2018 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue.

PubMed

Kogelnik, Andreas M; Loomis, Kristin; Hoegh-Petersen, Mette; Rosso, Fernando; Hischier, Courtney; Montoya, Jose G

2006-12-01

Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression. We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir. Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study. Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients. These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide

PubMed Central

Rane, Shruti; McReynolds, Lisa J.; Steppan, Diana A.; Chen, Allen R.; Paz-Priel, Ido

2016-01-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. PMID:27313069

The effect of rolling massage on the excitability of the corticospinal pathway.

PubMed

Aboodarda, Saied J; Greene, Rebecca M; Philpott, Devin T; Jaswal, Ramandeep S; Millet, Guillaume Y; Behm, David G

2018-04-01

The aim of the present study was to investigate the alterations of corticospinal excitability (motor evoked potential, MEP) and inhibition (silent period, SP) following rolling massage of the quadriceps muscles. Transcranial magnetic and femoral nerve electrical stimuli were used to elicit MEPs and compound muscle action potential (Mmax) in the vastus lateralis and vastus medialis muscles prior to and following either (i) 4 sets of 90-s rolling massage (ROLLING) or (ii) rest (CONTROL). One series of neuromuscular evaluations, performed after each set of ROLLING or CONTROL, included 3 MEPs and 1 Mmax elicited every 4 s during 15-s submaximal contractions at 10% (experiment 1, n = 16) and 50% (experiment 2, n = 10) of maximal voluntary knee extensions (MVC). The MEP/Mmax ratio and electromyographic activity recorded from vastus lateralis at 10% MVC demonstrated significantly lower values during ROLLING than CONTROL (P < 0.05). The ROLLING did not elicit any significant changes in muscle excitability (Mmax area) and duration of transcranial magnetic stimulation-induced SP recorded from any muscle or level of contraction (P > 0.05). The findings suggest that rolling massage can modulate the central excitability of the circuitries innervating the knee extensors; however, the observed effects are dependent on the background contraction intensity during which the neuromuscular measurements are recorded.

Computational models and motor learning paradigms: Could they provide insights for neuroplasticity after stroke? An overview.

PubMed

Kiper, Pawel; Szczudlik, Andrzej; Venneri, Annalena; Stozek, Joanna; Luque-Moreno, Carlos; Opara, Jozef; Baba, Alfonc; Agostini, Michela; Turolla, Andrea

2016-10-15

Computational approaches for modelling the central nervous system (CNS) aim to develop theories on processes occurring in the brain that allow the transformation of all information needed for the execution of motor acts. Computational models have been proposed in several fields, to interpret not only the CNS functioning, but also its efferent behaviour. Computational model theories can provide insights into neuromuscular and brain function allowing us to reach a deeper understanding of neuroplasticity. Neuroplasticity is the process occurring in the CNS that is able to permanently change both structure and function due to interaction with the external environment. To understand such a complex process several paradigms related to motor learning and computational modeling have been put forward. These paradigms have been explained through several internal model concepts, and supported by neurophysiological and neuroimaging studies. Therefore, it has been possible to make theories about the basis of different learning paradigms according to known computational models. Here we review the computational models and motor learning paradigms used to describe the CNS and neuromuscular functions, as well as their role in the recovery process. These theories have the potential to provide a way to rigorously explain all the potential of CNS learning, providing a basis for future clinical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuromuscular control and rehabilitation of the unstable ankle

PubMed Central

Hung, You-jou

2015-01-01

Lateral ankle sprain is a common orthopedic injury with a very high recurrence rate in athletes. After decades of research, it is still unclear what contributes to the high recurrence rate of ankle sprain, and what is the most effective intervention to reduce the incident of initial and recurrent injuries. In addition, clinicians often implement balance training as part of the rehabilitation protocol in hopes of enhancing the neuromuscular control and proprioception of the ankle joint. However, there is no consensus on whether the neuromuscular control and proprioception are compromised in unstable ankles. To reduce the prevalence of ankle sprains, the effectiveness of engaging balance training to enhance the neuromuscular control and proprioception of the ankle joint is also questionable. PMID:26085985

Is the relationship between increased knee muscle strength and improved physical function following exercise dependent on baseline physical function status?

PubMed

Hall, Michelle; Hinman, Rana S; van der Esch, Martin; van der Leeden, Marike; Kasza, Jessica; Wrigley, Tim V; Metcalf, Ben R; Dobson, Fiona; Bennell, Kim L

2017-12-08

Clinical guidelines recommend knee muscle strengthening exercises to improve physical function. However, the amount of knee muscle strength increase needed for clinically relevant improvements in physical function is unclear. Understanding how much increase in knee muscle strength is associated with improved physical function could assist clinicians in providing appropriate strength gain targets for their patients in order to optimise outcomes from exercise. The aim of this study was to investigate whether an increase in knee muscle strength is associated with improved self-reported physical function following exercise; and whether the relationship differs according to physical function status at baseline. Data from 100 participants with medial knee osteoarthritis enrolled in a 12-week randomised controlled trial comparing neuromuscular exercise to quadriceps strengthening exercise were pooled. Participants were categorised as having mild, moderate or severe physical dysfunction at baseline using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Associations between 12-week changes in physical function (dependent variable) and peak isometric knee extensor and flexor strength (independent variables) were evaluated with and without accounting for baseline physical function status and covariates using linear regression models. In covariate-adjusted models without accounting for baseline physical function, every 1-unit (Nm/kg) increase in knee extensor strength was associated with physical function improvement of 17 WOMAC units (95% confidence interval (CI) -29 to -5). When accounting for baseline severity of physical function, every 1-unit increase in knee extensor strength was associated with physical function improvement of 24 WOMAC units (95% CI -42 to -7) in participants with severe physical dysfunction. There were no associations between change in strength and change in physical function in participants with mild or moderate physical dysfunction at baseline. The association between change in knee flexor strength and change in physical function was not significant, irrespective of baseline function status. In patients with severe physical dysfunction, an increase in knee extensor strength and improved physical function were associated. ANZCTR 12610000660088 . Registered 12 August 2010.

[Effects of diabetes and obesity on the higher brain functions in rodents].

PubMed

Asato, Megumi; Ikeda, Hiroko; Kamei, Junzo

2012-11-01

Metabolic disorders, such as diabetes and obesity, have been indicated to disturb the function of the central nervous system (CNS) as well as several peripheral organs. Clinically, it is well recognized that the prevalence of anxiety and depression is higher in diabetic and obesity patients than in the general population. We have recently indicated that streptozotocin-induced diabetic and diet-induced obesity mice have enhanced fear memory and higher anxiety-like behavior in several tests such as the conditioned fear, tail-suspension, hole-board and elevated open-platform tests. The changes in fear memory and anxiety-like behavior of diabetic and obese mice are due to the dysfunction of central glutamatergic and monoaminergic systems, which is mediated by the changes of intracellular signaling. These results suggest that metabolic disorders strongly affect the function of the CNS and disturb the higher brain functions. These dysfunctions of the CNS in diabetes and obesity are involved in the increased prevalence of anxiety disorders and depression. Normalization of these dysfunctions in the CNS will be a new attractive target to treat the metabolic disorders and their complications.

Erectile dysfunction and central obesity: an Italian perspective

PubMed Central

Corona, Giovanni; Rastrelli, Giulia; Filippi, Sandra; Vignozzi, Linda; Mannucci, Edoardo; Maggi, Mario

2014-01-01

Erectile dysfunction (ED) is a frequent complication of obesity. The aim of this review is to critically analyze the framework of obesity and ED, dissecting the connections between the two pathological entities. Current clinical evidence shows that obesity, and in particular central obesity, is associated with both arteriogenic ED and reduced testosterone (T) levels. It is conceivable that obesity-associated hypogonadism and increased cardiovascular risk might partially justify the higher prevalence of ED in overweight and obese individuals. Conversely, the psychological disturbances related to obesity do not seem to play a major role in the pathogenesis of obesity-related ED. However, both clinical and preclinical data show that the association between ED and visceral fat accumulation is independent from known obesity-associated comorbidities. Therefore, how visceral fat could impair penile microcirculation still remains unknown. This point is particularly relevant since central obesity in ED subjects categorizes individuals at high cardiovascular risk, especially in the youngest ones. The presence of ED in obese subjects might help healthcare professionals in convincing them to initiate a virtuous cycle, where the correction of sexual dysfunction will be the reward for improved lifestyle behavior. Unsatisfying sexual activity represents a meaningful, straightforward motivation for consulting healthcare professionals, who, in turn, should take advantage of the opportunity to encourage obese patients to treat, besides ED, the underlying unfavorable conditions, thus not only restoring erectile function, but also overall health. PMID:24713832

Cardiac Dysautonomia in Huntington's Disease.

PubMed

Abildtrup, Mads; Shattock, Michael

2013-01-01

Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

Erectile dysfunction and central obesity: an Italian perspective.

PubMed

Corona, Giovanni; Rastrelli, Giulia; Filippi, Sandra; Vignozzi, Linda; Mannucci, Edoardo; Maggi, Mario

2014-01-01

Erectile dysfunction (ED) is a frequent complication of obesity. The aim of this review is to critically analyze the framework of obesity and ED, dissecting the connections between the two pathological entities. Current clinical evidence shows that obesity, and in particular central obesity, is associated with both arteriogenic ED and reduced testosterone (T) levels. It is conceivable that obesity-associated hypogonadism and increased cardiovascular risk might partially justify the higher prevalence of ED in overweight and obese individuals. Conversely, the psychological disturbances related to obesity do not seem to play a major role in the pathogenesis of obesity-related ED. However, both clinical and preclinical data show that the association between ED and visceral fat accumulation is independent from known obesity-associated comorbidities. Therefore, how visceral fat could impair penile microcirculation still remains unknown. This point is particularly relevant since central obesity in ED subjects categorizes individuals at high cardiovascular risk, especially in the youngest ones. The presence of ED in obese subjects might help healthcare professionals in convincing them to initiate a virtuous cycle, where the correction of sexual dysfunction will be the reward for improved lifestyle behavior. Unsatisfying sexual activity represents a meaningful, straightforward motivation for consulting healthcare professionals, who, in turn, should take advantage of the opportunity to encourage obese patients to treat, besides ED, the underlying unfavorable conditions, thus not only restoring erectile function, but also overall health.

Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies

PubMed Central

Romigi, A.; Albanese, M.; Liguori, C.; Placidi, F.; Marciani, M. G.; Massa, R.

2013-01-01

Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterized by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified, myotonic dystrophy type 1 (DM1 or Steinert's Disease) and myotonic dystrophy type 2 (DM2). Myotonic dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in DM1 are common and include sleep-disordered breathing (SDB), periodic limb movements (PLMS), central hypersomnia, and REM sleep dysregulation (high REM density and narcoleptic-like phenotype). Interestingly, drowsiness in DM1 seems to be due to a central dysfunction of sleep-wake regulation more than SDB. To date, little is known regarding the occurrence of sleep disorders in DM2. SDB (obstructive and central apnoea), REM sleep without atonia, and restless legs syndrome have been described. Further polysomnographic, controlled studies are strongly needed, particularly in DM2, in order to clarify the role of sleep disorders in the myotonic dystrophies. PMID:26316996

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report

PubMed Central

2011-01-01

Background Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. Methods The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: [1] Cumberland Ankle Instability Tool (CAIT) scores, [2] Star Excursion Balance Test (SEBT) reach distances, [3] ankle joint plantar flexion during drop landing and drop vertical jumping, and [4] ground reaction forces (GRFs) during walking. Results CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. Conclusions The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors. PMID:21658224

A comparison between the blocking actions of 2-(4-phenylpiperidino) cyclohexanol (AH 5183) and its N-methyl quaternary analogue (AH 5954)

PubMed Central

Marshall, I. G.

1970-01-01

1. The neuromuscular blocking activities of AH 5183 (2-(4-phenylpiperidino) cyclohexanol) and its N-methyl quaternary analogue (AH 5954) were compared in rapidly stimulated nerve-skeletal muscle preparations of the rat, chicken and cat. 2. The evidence indicated that in isolated preparations the neuromuscular block produced by both AH 5183 and AH 5954 was primarily pre-junctional in origin. That produced by AH 5954 was readily reversible either by washing the tissue or by reducing the stimulation frequency, whereas that produced by AH 5183 was difficult to reverse in these ways. 3. Low doses of AH 5954 sensitized the rat hemidiaphragm preparation to the neuromuscular blocking action of choline. The neuromuscular block produced by choline was reversible by tetraethylammonium but not by neostigmine. This suggested that the blocking action of choline is at least partly pre-junctional in nature. 4. In anaesthetized cats AH 5954 possessed a biphasic neuromuscular blocking action. The initial phase was rapid in onset, suggestive of a post-junctional action, whereas the second phase was prolonged and reversible by choline, suggestive of a prejunctional inhibitory action on the choline transport mechanism. AH 5183 produced no initial blocking action and was irreversible by choline. 5. Both AH 5183 and AH 5954 possessed local anaesthetic and α-adrenoceptor blocking actions. These actions and the neuromuscular blocking action were affected to different degrees by quaternization, suggesting that the three main actions of the two drugs are independent. 6. It was concluded that AH 5954 and AH 5183 act at different pre-junctional sites at the neuromuscular junction, AH 5954 acting extraneuronally by inhibiting choline transport and AH 5183 intraneuronally at the level of the synaptic vesicle membrane. PMID:4395087

Neuromuscular control and ankle instability.

PubMed

Gutierrez, Gregory M; Kaminski, Thomas W; Douex, Al T

2009-04-01

Lateral ankle sprains (LAS) are common injuries in athletics and daily activity. Although most are resolved with conservative treatment, others develop chronic ankle instability (AI)-a condition associated with persistent pain, weakness, and instability-both mechanical (such as ligamentous laxity) and functional (neuromuscular impairment with or without mechanical laxity). The predominant theory in AI is one of articular deafferentation from the injury, affecting closed-loop (feedback/reflexive) neuromuscular control, but recent research has called that theory into question. A considerable amount of attention has been directed toward understanding the underlying causes of this pathology; however, little is known concerning the neuromuscular mechanisms behind the development of AI. The purpose of this review is to summarize the available literature on neuromuscular control in uninjured individuals and individuals with AI. Based on available research and reasonable speculation, it seems that open-loop (feedforward/anticipatory) neuromuscular control may be more important for the maintenance of dynamic joint stability than closed-loop control systems that rely primarily on proprioception. Therefore, incorporating perturbation activities into patient rehabilitation schemes may be of some benefit in enhancing these open-loop control mechanisms. Despite the amount of research conducted in this area, analysis of individuals with AI during dynamic conditions is limited. Future work should aim to evaluate dynamic perturbations in individuals with AI, as well as subjects who have a history of at least one LAS and never experienced recurrent symptoms. These potential findings may help elucidate some compensatory mechanisms, or more appropriate neuromuscular control strategies after an LAS event, thus laying the groundwork for future intervention studies that can attempt to reduce the incidence and severity of acute and chronic lateral ankle injury.

Full-movement neuromuscular electrical stimulation improves plantar flexor spasticity and ankle active dorsiflexion in stroke patients: a randomized controlled study.

PubMed

Wang, Yong-Hui; Meng, Fei; Zhang, Yang; Xu, Mao-Yu; Yue, Shou-Wei

2016-06-01

To investigate whether full-movement neuromuscular electrical stimulation, which can generate full range of movement, reduces spasticity and/or improves motor function more effectively than control, sensory threshold-neuromuscular electrical stimulation, and motor threshold-neuromuscular electrical stimulation in sub-acute stroke patients. A randomized, single-blind, controlled study. Physical therapy room and functional assessment room. A total of 72 adult patients with sub-acute post-stroke hemiplegia and plantar flexor spasticity. Patients received 30-minute sessions of neuromuscular electrical stimulation on the motor points of the extensor hallucis and digitorum longus twice a day, five days per week for four weeks. Composite Spasticity Scale, Ankle Active Dorsiflexion Score, and walking time in the Timed Up and Go Test were assessed at pretreatment, posttreatment, and at two-week follow-up. After four weeks of treatment, when comparing interclass pretreatment and posttreatment, only the full-movement neuromuscular electrical stimulation group had a significant reduction in the Composite Spasticity Scale (mean % reduction = 19.91(4.96)%, F = 3.878, p < 0.05) and improvement in the Ankle Active Dorsiflexion Score (mean scores = 3.29(0.91), F = 3.140, p < 0.05). Furthermore, these improvements were maintained two weeks after the treatment ended. However, there were no significant differences in the walking time after four weeks of treatment among the four groups (F = 1.861, p > 0.05). Full-movement neuromuscular electrical stimulation with a stimulus intensity capable of generating full movement can significantly reduce plantar flexor spasticity and improve ankle active dorsiflexion, but cannot decrease walking time in the Timed Up and Go Test in sub-acute stroke patients. © The Author(s) 2015.

Effect of a 6-week dynamic neuromuscular training programme on ankle joint function: A Case report.

PubMed

O'Driscoll, Jeremiah; Kerin, Fearghal; Delahunt, Eamonn

2011-06-09

Ankle joint sprain and the subsequent development of chronic ankle instability (CAI) are commonly encountered by clinicians involved in the treatment and rehabilitation of musculoskeletal injuries. It has recently been advocated that ankle joint post-sprain rehabilitation protocols should incorporate dynamic neuromuscular training to enhance ankle joint sensorimotor capabilities. To date no studies have reported on the effects of dynamic neuromuscular training on ankle joint positioning during landing from a jump, which has been reported as one of the primary injury mechanisms for ankle joint sprain. This case report details the effects of a 6-week dynamic neuromuscular training programme on ankle joint function in an athlete with CAI. The athlete took part in a progressive 6-week dynamic neuromuscular training programme which incorporated postural stability, strengthening, plyometric, and speed/agility drills. The outcome measures chosen to assess for interventional efficacy were: 1 Cumberland Ankle Instability Tool (CAIT) scores, 2 Star Excursion Balance Test (SEBT) reach distances, 3 ankle joint plantar flexion during drop landing and drop vertical jumping, and 4 ground reaction forces (GRFs) during walking. CAIT and SEBT scores improved following participation in the programme. The angle of ankle joint plantar flexion decreased at the point of initial contact during the drop landing and drop vertical jumping tasks, indicating that the ankle joint was in a less vulnerable position upon landing following participation in the programme. Furthermore, GRFs were reduced whilst walking post-intervention. The 6-week dynamic neuromuscular training programme improved parameters of ankle joint sensorimotor control in an athlete with CAI. Further research is now required in a larger cohort of subjects to determine the effects of neuromuscular training on ankle joint injury risk factors.

A systematic review and meta-analysis of lower limb neuromuscular alterations associated with knee osteoarthritis during level walking.

PubMed

Mills, Kathryn; Hunt, Michael A; Leigh, Ryan; Ferber, Reed

2013-08-01

Neuromuscular alterations are increasingly reported in individuals with knee osteoarthritis (KOA) during level walking. We aimed to determine which neuromuscular alterations are consistent in KOA individuals and how these may be influenced by osteoarthritis severity, varus alignment and/or joint laxity. Electronic databases were searched up to July 2012. Cross-sectional observational studies comparing lower-limb neuromuscular activity in individuals with KOA, healthy controls or with different KOA cohorts were included. Two reviewers assessed methodological quality. Effect sizes were used to quantify the magnitude of observed differences. Where studies were homogenous, effect sizes were pooled using a fixed-effects model. Fourteen studies examining neuromuscular alterations in indices of co-contraction, muscle amplitude and muscle activity duration were included. Data pooling revealed that moderate KOA individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64 [0.3 to 0.97]) and moderately increased rectus femoris (ES 0.73 [0.23 to 1.22]), vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to 1.7]) mean amplitude. Non-pooled data indicated prolonged activity of these muscles. Increased medial knee neuromuscular activity was prevalent for those exhibiting varus alignment and medial knee joint laxity. Interpretation Individuals with KOA exhibited increased co-contraction, amplitude and duration of lateral knee muscles regardless of disease severity, limb alignment or medial joint laxity. Individuals with severe disease, varus alignment and medial joint laxity demonstrate up-regulation of medial knee muscles. Future research investigating the efficacy of neuromuscular rehabilitation programs should consider the effect of simultaneous up-regulation of medial and lateral knee muscles on disease progression. © 2013.

Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study.

PubMed

Pavoni, V; Gianesello, L; De Scisciolo, G; Provvedi, E; Horton, D; Barbagli, R; Conti, P; Conti, R; Giunta, F

2012-05-01

Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium-induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124±9.6, 143±163, 151±207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109±13.8, 124±0.6, and 135±14.1 sec. Times to TOF ratio 0.9 were 114±75 and 186±105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade.

Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

PubMed

Martinot, Amanda J; Abbink, Peter; Afacan, Onur; Prohl, Anna K; Bronson, Roderick; Hecht, Jonathan L; Borducchi, Erica N; Larocca, Rafael A; Peterson, Rebecca L; Rinaldi, William; Ferguson, Melissa; Didier, Peter J; Weiss, Deborah; Lewis, Mark G; De La Barrera, Rafael A; Yang, Edward; Warfield, Simon K; Barouch, Dan H

2018-05-17

The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

PubMed

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-05-28

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy

PubMed Central

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S.; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-01-01

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1. PMID:26018658

Robotics, assistive technology, and occupational therapy management to improve upper limb function in pediatric neuromuscular diseases.

PubMed

Rahman, Tariq; Basante, Joseph; Alexander, Michael

2012-08-01

This article presents an overview of occupational therapy assessments and treatment options for individuals with neuromuscular disabilities, with a particular focus on children with neuromuscular disorders. The discussion includes descriptions of standard treatments, commercial adaptive equipment, and homemade adaptive solutions. The state of the art in therapeutic and assistive robots and orthoses for the upper and lower extremity is also provided. Copyright © 2012. Published by Elsevier Inc.

Neuromuscular Coordination Deficit Persists 12 Months after ACL Reconstruction But Can Be Modulated by 6 Weeks of Kettlebell Training: A Case Study in Women's Elite Soccer

PubMed Central

Andersen, Christoffer H.; Bencke, Jesper; Ørntoft, Christina; Linnebjerg, Connie; Hölmich, Per

2017-01-01

The aim of the present single-case study was to investigate the effect of 6 weeks' kettlebell training on the neuromuscular risk profile for ACL injury in a high-risk athlete returning to sport after ACL reconstruction. A female elite soccer player (age 21 years) with no previous history of ACL injury went through neuromuscular screening as measured by EMG preactivity of vastus lateralis and semitendinosus during a standardized sidecutting maneuver. Subsequently, the player experienced a noncontact ACL injury. The player was screened again following postreconstruction rehabilitation, then underwent 6-week kettlebell training, and was subsequently screened again at 6-week follow-up. Prior to and after postreconstruction rehabilitation the player demonstrated a neuromuscular profile during sidecutting known to increase the risk for noncontact ACL injury, that is, reduced EMG preactivity for semitendinosus and elevated EMG preactivity for vastus lateralis. Subsequently, the 6-week kettlebell training increased semitendinosus muscle preactivity during sidecutting by 38 percentage points to a level equivalent to a neuromuscular low-risk profile. An ACL rehabilitated female athlete with a high-risk neuromuscular profile changed to low-risk in response to 6 weeks of kettlebell training. Thus, short-term kettlebell exercise with documented high levels of medial hamstring activation was found to transfer into high medial hamstring preactivation during a sidecutting maneuver. PMID:28197354

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

Treating pediatric neuromuscular disorders: The future is now

PubMed Central

D. Gonorazky, Hernan; Cohn, Ronald D.; Campbell, Craig

2017-01-01

Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot–Marie–Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies). Historically, pediatric neuromuscular disorders have uniformly been considered to be without treatment possibilities and to have dire prognoses. This perception has gradually changed, starting in part with the discovery and widespread application of corticosteroids for Duchenne muscular dystrophy. At present, several exciting therapeutic avenues are under investigation for a range of conditions, offering the potential for significant improvements in patient morbidities and mortality and, in some cases, curative intervention. In this review, we will present the current state of treatment for the most common pediatric neuromuscular conditions, and detail the treatment strategies with the greatest potential for helping with these devastating diseases. PMID:28889642

Effectiveness of deep versus moderate muscle relaxation during laparoscopic donor nephrectomy in enhancing postoperative recovery: study protocol for a randomized controlled study.

PubMed

Bruintjes, Moira H D; Braat, Andries E; Dahan, Albert; Scheffer, Gert-Jan; Hilbrands, Luuk B; d'Ancona, Frank C H; Donders, Rogier A R T; van Laarhoven, Cornelis J H M; Warlé, Michiel C

2017-03-04

Postoperative recovery after live donor nephrectomy is largely determined by the consequences of postoperative pain and analgesia consumptions. The use of deep neuromuscular blockade has been shown to reduce postoperative pain scores after laparoscopic surgery. In this study, we will investigate whether deep neuromuscular blockade also improves the early quality of recovery after live donor nephrectomy. The RELAX-study is a phase IV, multicenter, double-blinded, randomized controlled trial, in which 96 patients, scheduled for living donor nephrectomy, will be randomized into two groups: one with deep and one with moderate neuromuscular blockade. Deep neuromuscular blockade is defined as a post-tetanic count of 1-2. Our primary outcome measurement will be the Quality of Recovery-40 questionnaire (overall score) at 24 h after extubation. This study is, to our knowledge, the first randomized study to assess the effectiveness of deep neuromuscular blockade during laparoscopic donor nephrectomy in enhancing postoperative recovery. The study findings may also be applicable for other laparoscopic procedures. clinicaltrials.gov, NCT02838134 . Registered on 29 June 2016.

Impact of exercise-induced fatigue on the strength, postural control, and gait of children with a neuromuscular disease.

PubMed

Hart, Raphael; Ballaz, Laurent; Robert, Maxime; Pouliot, Annie; D'Arcy, Sylvie; Raison, Maxime; Lemay, Martin

2014-08-01

Children with a neuromuscular disease are prone to early muscular fatigue. The objective of the present study was to evaluate the effects of fatigue induced by a walking exercise on the strength, postural control, and gait of children with a neuromuscular disease. Maximal isometric knee strength (extension and flexion), quiet standing postural control, and gait were evaluated in 12 children (8.8 [1.4] yrs) with a neuromuscular disease before and after a walking exercise. The participants were asked to stop walking when they considered themselves "very fatigued." After the exercise-induced fatigue, a significant increase in range of motion in pelvis obliquity, hip abduction and adduction, and ankle flexion and extension during gait was reported along with an increase in stride length variability. Fatigue also reduced the knee flexor strength and had a detrimental effect on postural control. Fatigue affects the strength, postural control, and gait of children with a neuromuscular disease and could notably increase the risks of falling and the occurrence of serious injuries.

Modeling and Identification of a Realistic Spiking Neural Network and Musculoskeletal Model of the Human Arm, and an Application to the Stretch Reflex.

PubMed

Sreenivasa, Manish; Ayusawa, Ko; Nakamura, Yoshihiko

2016-05-01

This study develops a multi-level neuromuscular model consisting of topological pools of spiking motor, sensory and interneurons controlling a bi-muscular model of the human arm. The spiking output of motor neuron pools were used to drive muscle actions and skeletal movement via neuromuscular junctions. Feedback information from muscle spindles were relayed via monosynaptic excitatory and disynaptic inhibitory connections, to simulate spinal afferent pathways. Subject-specific model parameters were identified from human experiments by using inverse dynamics computations and optimization methods. The identified neuromuscular model was used to simulate the biceps stretch reflex and the results were compared to an independent dataset. The proposed model was able to track the recorded data and produce dynamically consistent neural spiking patterns, muscle forces and movement kinematics under varying conditions of external forces and co-contraction levels. This additional layer of detail in neuromuscular models has important relevance to the research communities of rehabilitation and clinical movement analysis by providing a mathematical approach to studying neuromuscular pathology.

Imaging of respiratory muscles in neuromuscular disease: A review.

PubMed

Harlaar, L; Ciet, P; van der Ploeg, A T; Brusse, E; van der Beek, N A M E; Wielopolski, P A; de Bruijne, M; Tiddens, H A W M; van Doorn, P A

2018-03-01

Respiratory muscle weakness frequently occurs in patients with neuromuscular disease. Measuring respiratory function with standard pulmonary function tests provides information about the contribution of all respiratory muscles, the lungs and airways. Imaging potentially enables the study of different respiratory muscles, including the diaphragm, separately. In this review, we provide an overview of imaging techniques used to study respiratory muscles in neuromuscular disease. We identified 26 studies which included a total of 573 patients with neuromuscular disease. Imaging of respiratory muscles was divided into static and dynamic techniques. Static techniques comprise chest radiography, B-mode (brightness mode) ultrasound, CT and MRI, and are used to assess the position and thickness of the diaphragm and the other respiratory muscles. Dynamic techniques include fluoroscopy, M-mode (motion mode) ultrasound and MRI, used to assess diaphragm motion in one or more directions. We discuss how these imaging techniques relate with spirometric values and whether these can be used to study the contribution of the different respiratory muscles in patients with neuromuscular disease. Copyright © 2017. Published by Elsevier B.V.

Experience-dependent central vision deficits: Neurobiology and visual acuity.

PubMed

Williams, Kate; Balsor, Justin L; Beshara, Simon; Beston, Brett R; Jones, David G; Murphy, Kathryn M

2015-09-01

Abnormal visual experience during childhood often leads to amblyopia, with strong links to binocular dysfunction that can include poor acuity in both eyes, especially in central vision. In animal models of amblyopia, the non-deprived eye is often considered normal and what limits binocular acuity. This leaves open the question whether monocular deprivation (MD) induces binocular dysfunction similar to what is found in amblyopia. In previous studies of MD cats, we found a loss of excitatory receptors restricted to the central visual field representation in visual cortex (V1), including both eyes' columns. This led us to ask two questions about the effects of MD: how quickly are receptors lost in V1? and is there an impact on binocular acuity? We found that just a few hours of MD caused a rapid loss of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor proteins across all of V1. But after a few days of MD, there was recovery in the visual periphery, leaving a loss of AMPA receptors only in the central region of V1. We reared animals with early MD followed by a long period of binocular vision and found binocular acuity deficits that were greatest in the central visual field. Our results suggest that the greater binocular acuity deficits in the central visual field are driven in part by the long-term loss of AMPA receptors in the central region of V1. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of Chinese medicines on cAMP/PKA signaling in central nervous system dysfunction.

PubMed

Li, Lin; Fan, Xiang; Zhang, Xi-Ting; Yue, Shao-Qian; Sun, Zuo-Yan; Zhu, Jin-Qiang; Zhang, Jun-Hua; Gao, Xiu-Mei; Zhang, Han

2017-06-01

Neuropathological injury in the mammalian adult central nervous system (CNS) may cause axon disruption, neuronal death and lasting neurological deficits. Failure of axon regeneration is one of the major challenges for CNS functional recovery. Recently, the cAMP/PKA signaling pathway has been proven to be a critical regulator for neuronal regeneration, neuroplasticity, learning and memory. Also, previous studies have shown the effects of Chinese medicines on the prevention and treatment of CNS dysfunction mediated in part by cAMP/PKA signaling. In this review, the authors discuss current knowledge of the role of cAMP/PKA signaling pathway in neuronal regeneration and provide an overview of the Chinese medicines that may enable CNS functional recovery via this signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

Coronary artery disease detection - limitations of stress testing in left ventricular dysfunction

PubMed Central

Bomb, Ritin; Kumar, Senthil; Chockalingam, Anand

2017-01-01

Incidental diagnosis of left ventricular systolic dysfunction (LVD) is common in clinical practice. The prevalence of asymptomatic LVD (Ejection Fraction, EF < 50%) is 6.0% in men and 0.8% in women and is twice as common as symptomatic LVD. The timely and definitive exclusion of an ischemic etiology is central to optimizing care and reducing mortality in LVD. Advances in cardiovascular imaging provide many options for imaging of patients with left ventricular dysfunction. Clinician experience, patient endurance, imaging modality characteristics, cost and safety determine the choice of testing. In this review, we have compared the diagnostic utility of established tests - nuclear and echocardiographic stress testing with newer techniques like coronary computerized tomography and cardiac magnetic resonance imaging and highlight their inherent limitations in patients with underlying left ventricular dysfunction. PMID:28515848

Stabilisation splint therapy for temporomandibular pain dysfunction syndrome.

PubMed

Al-Ani, M Z; Davies, S J; Gray, R J M; Sloan, P; Glenny, A M

2004-01-01

Pain dysfunction syndrome (PDS) is the most common temporomandibular disorder (TMD). There are many synonyms for this condition including facial arthromylagia, TMJ dysfunction syndrome, myofacial pain dysfunction syndrome, craniomandibular dysfunction and myofacial pain dysfunction. The aetiology of PDS is multifactorial and many different therapies have been advocated. To establish the effectiveness of stabilisation splint therapy in reducing symptoms in patients with pain dysfunction syndrome. Electronic databases (including the Cochrane Oral Health Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library Issue 2, 2003; MEDLINE (1966 to June 2001); EMBASE (1966 to June 2001)) were searched. Handsearching of relevant journals was undertaken and reference lists of included studies screened. Experts in the field were contacted to identify unpublished articles. There was no language restriction. Randomised or quasi-randomised controlled trials (RCTs), in which splint therapy was compared concurrently to no treatment, other occlusal appliances, or any other active intervention. Data extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third reviewer consulted. The author of the primary study was contacted where necessary. The studies were grouped according to treatment type and duration of follow up. Twenty potentially relevant RCTs were identified. Eight trials were excluded leaving 12 RCTs for analysis. Stabilisation splint therapy was compared to: acupuncture, bite plates, biofeedback/stress management, visual feedback, relaxation, jaw exercises, non-occluding appliance and minimal/no treatment. There was no evidence of a statistically significant difference in the effectiveness of stabilisation splint therapy (SS) in reducing symptoms in patients with pain dysfunction syndrome compared with other active treatments. There is weak evidence to suggest that the use of SS for the treatment of PDS may be beneficial for reducing pain severity, at rest and on palpation, when compared to no treatment. There is insufficient evidence either for or against the use of stabilisation splint therapy for the treatment of temporomandibular pain dysfunction syndrome. This review suggests the need for further, well conducted RCTs that pay attention to method of allocation, outcome assessment, large sample size, and enough duration of follow up. A standardisation of the outcomes of the treatment of PDS should be established in the RCTs.

Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

PubMed Central

Lemmens, Katrien; Vrints, Christiaan J.

2017-01-01

Although the burden of heart failure with preserved ejection fraction (HFpEF) is increasing, there is no therapy available that improves prognosis. Clinical trials using beta blockers and angiotensin converting enzyme inhibitors, cardiac-targeting drugs that reduce mortality in heart failure with reduced ejection fraction (HFrEF), have had disappointing results in HFpEF patients. A new “whole-systems” approach has been proposed for designing future HFpEF therapies, moving focus from the cardiomyocyte to the endothelium. Indeed, dysfunction of endothelial cells throughout the entire cardiovascular system is suggested as a central mechanism in HFpEF pathophysiology. The objective of this review is to provide an overview of current knowledge regarding endothelial dysfunction in HFpEF. We discuss the molecular and cellular mechanisms leading to endothelial dysfunction and the extent, presence, and prognostic importance of clinical endothelial dysfunction in different vascular beds. We also consider implications towards exercise training, a promising therapy targeting system-wide endothelial dysfunction in HFpEF. PMID:28706575

Neuromuscular Scoliosis

MedlinePlus

... degree of neuromuscular involvement. Diagnosis Incidence of Scoliosis Cerebral palsy (2 limbs involved) 25% Myelodysplasia (lower lumbar) 60% Spinal muscle atrophy 67% Friedreich ataxia 80% Cerebral palsy (4 limbs involved) 80% Duchenne muscular dystrophy 90% ...

Dysfunction of bulbar central pattern generator in ALS patients with dysphagia during sequential deglutition.

PubMed

Aydogdu, Ibrahim; Tanriverdi, Zeynep; Ertekin, Cumhur

2011-06-01

The aim of this study is to investigate a probable dysfunction of the central pattern generator (CPG) in dysphagic patients with ALS. We investigated 58 patients with ALS, 23 patients with PD, and 33 normal subjects. The laryngeal movements and EMG of the submental muscles were recorded during sequential water swallowing (SWS) of 100ml of water. The coordination of SWS and respiration was also studied in some normal cases and ALS patients. Normal subjects could complete the SWS optimally within 10s using 7 swallows, while in dysphagic ALS patients, the total duration and the number of swallows were significantly increased. The novel finding was that the regularity and rhythmicity of the swallowing pattern during SWS was disorganized to irregular and arhythmic pattern in 43% of the ALS patients. The duration and speed of swallowing were the most sensitive parameters for the disturbed oropharyngeal motility during SWS. The corticobulbar control of swallowing is insufficient in ALS, and the swallowing CPG cannot work very well to produce segmental muscle activation and sequential swallowing. CPG dysfunction can result in irregular and arhythmical sequential swallowing in ALS patients with bulbar plus pseudobulbar types. The arhythmical SWS pattern can be considered as a kind of dysfunction of CPG in human ALS cases with dysphagia. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

PubMed Central

Boengler, Kerstin; Kosiol, Maik; Mayr, Manuel; Schulz, Rainer

2017-01-01

Abstract Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best‐known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high‐energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed. PMID:28432755

A Comparison of Cough Assistance Techniques in Patients with Respiratory Muscle Weakness.

PubMed

Kim, Sun Mi; Choi, Won Ah; Won, Yu Hui; Kang, Seong Woong

2016-11-01

To assess the ability of a mechanical in-exsufflator (MI-E), either alone or in combination with manual thrust, to augment cough in patients with neuromuscular disease (NMD) and respiratory muscle dysfunction. For this randomized crossover single-center controlled trial, patients with noninvasive ventilator-dependent NMD were recruited. The primary outcome was peak cough flow (PCF), which was measured in each patient after a cough that was unassisted, manually assisted following a maximum insufflation capacity (MIC) maneuver, assisted by MI-E, or assisted by manual thrust plus MI-E. The cough augmentation techniques were provided in random order. PCF was measured using a new device, the Cough Aid. All 40 enrolled participants (37 males, three females; average age, 20.9±7.2 years) completed the study. The mean (standard deviation) PCFs in the unassisted, manually assisted following an MIC maneuver, MI-E-assisted, and manual thrust plus MI-E-assisted conditions were 95.7 (40.5), 155.9 (53.1), 177.2 (33.9), and 202.4 (46.6) L/min, respectively. All three interventions significantly improved PCF. However, manual assistance following an MIC maneuver was significantly less effective than MI-E alone. Manual thrust plus MI-E was significantly more effective than both of these interventions. In patients with NMD and respiratory muscle dysfunction, MI-E alone was more effective than manual assistance following an MIC maneuver. However, MI-E used in conjunction with manual thrust improved PCF even further.

Occupational Neurotoxic Diseases in Taiwan

PubMed Central

Liu, Chi-Hung; Huang, Chu-Yun

2012-01-01

Occupational neurotoxic diseases have become increasingly common in Taiwan due to industrialization. Over the past 40 years, Taiwan has transformed from an agricultural society to an industrial society. The most common neurotoxic diseases also changed from organophosphate poisoning to heavy metal intoxication, and then to organic solvent and semiconductor agent poisoning. The nervous system is particularly vulnerable to toxic agents because of its high metabolic rate. Neurological manifestations may be transient or permanent, and may range from cognitive dysfunction, cerebellar ataxia, Parkinsonism, sensorimotor neuropathy and autonomic dysfunction to neuromuscular junction disorders. This study attempts to provide a review of the major outbreaks of occupational neurotoxins from 1968 to 2012. A total of 16 occupational neurotoxins, including organophosphates, toxic gases, heavy metals, organic solvents, and other toxic chemicals, were reviewed. Peer-reviewed articles related to the electrophysiology, neuroimaging, treatment and long-term follow up of these neurotoxic diseases were also obtained. The heavy metals involved consisted of lead, manganese, organic tin, mercury, arsenic, and thallium. The organic solvents included n-hexane, toluene, mixed solvents and carbon disulfide. Toxic gases such as carbon monoxide, and hydrogen sulfide were also included, along with toxic chemicals including polychlorinated biphenyls, tetramethylammonium hydroxide, organophosphates, and dimethylamine borane. In addition we attempted to correlate these events to the timeline of industrial development in Taiwan. By researching this topic, the hope is that it may help other developing countries to improve industrial hygiene and promote occupational safety and health care during the process of industrialization. PMID:23251841

Intractable Polyuria Mimicking Diabetes Insipidus-Source Traced to Vecuronium Infusion.

PubMed

Haldar, Rudrashish; Samanta, Sukhen; Singla, Ankush

2016-01-01

Continuous infusion of vecuronium is a commonly used technique for patients requiring prolonged neuromuscular blockade for mechanical ventilation. As compared with older neuromuscular blocking agents, it confers the advantages of rapid excretion and intermediate duration of action. Prolongation of neuromuscular blockade and muscle weakness are the known complications of continuous vecuronium infusion. This report attempts to describe polyuria, as a hitherto unknown complication of vecuronium infusion, which can occur due to the mannitol present in commercially available preparation of vecuronium bromide.

Neuromuscular disorders in the intensive care unit.

PubMed

Marinelli, William A; Leatherman, James W

2002-10-01

Neuromuscular disorders encountered in the ICU can be categorized as muscular diseases that lead to ICU admission and those that are acquired in the ICU. This article discusses three neuromuscular disorders can lead to ICU admission and have a putative immune-mediated pathogenesis: the Guillian-Barré syndrome, myasthenia gravis, and dermatomyositis/polymyositis. It also reviews critical care polyneuropathy and ICU acquired myopathy, two disorders that, alone or in combination, are responsible for nearly all cases of severe ICU acquired muscle weakness.

Long-term Non-Invasive Ventilation in Infants: A Systematic Review and Meta-Analysis.

PubMed

Bedi, Prabhjot K; Castro-Codesal, Maria Luisa; Featherstone, Robin; AlBalawi, Mohammed M; Alkhaledi, Bashar; Kozyrskyj, Anita L; Flores-Mir, Carlos; MacLean, Joanna E

2018-01-01

The use of long-term non-invasive ventilation (NIV) to treat sleep and breathing disorders in children has increased substantially in the last decade; however, less data exist about its use in infants. Given that infants have distinct sleep and breathing patterns when compared to older children, the outcomes of infants on long-term NIV may differ as well. The aim of this study is to systematically review the use and outcomes of long-term NIV in infants. Ovid Medline, Ovid Embase, CINAHL (via EbscoHOST), PubMed, and Wiley Cochrane Library were systematically searched from January 1990 to July 2017. Studies on infants using long-term NIV outside of an acute care setting were included. Data were extracted on study design, population characteristics, and NIV outcomes. A total of 327 studies were full-text reviewed, with final inclusion of 60. Studies were distributed across airway (40%), neuromuscular (28%), central nervous system (10%), cardio-respiratory (2%), and multiple (20%) disease categories. Of the 18 airway studies reporting on NIV outcomes, 13 (72%) reported improvements in respiratory parameters. Of the 12 neuromuscular studies exclusively on spinal muscular atrophy type 1 (SMA1), six (50%) reported decreased hospitalizations and nine (75%) reported on mortality outcomes. Risk of bias was moderate to serious, and quality of the evidence was low to very low for all studies. Most studies had an observational design with no control group, limiting the potential for a meta-analysis. The outcomes reported in studies differed by the disease category being studied. Studies on airway conditions showed improvements in respiratory parameters for infants using NIV. Studies on neuromuscular disorder, which were almost exclusively on SMA1, reported decreased hospitalizations and prolonged survival. Overall, it appears that NIV is an effective long-term therapy for infants. However, the high risk of bias and low quality of the available evidence limited strong conclusions.

Central Motor Conduction Studies and Diagnostic Magnetic Resonance Imaging in Children with Severe Primary and Secondary Dystonia

ERIC Educational Resources Information Center

McClelland, Verity; Mills, Kerry; Siddiqui, Ata; Selway, Richard; Lin, Jean-Pierre

2011-01-01

Aim: Dystonia in childhood has many causes. Imaging may suggest corticospinal tract dysfunction with or without coexistent basal ganglia damage. There are very few published neurophysiological studies on children with dystonia; one previous study has focused on primary dystonia. We investigated central motor conduction in 62 children (34 males, 28…

Central serous chorioretinopathy due to tadalafil use.

PubMed

Türkcü, Fatih Mehmet; Yüksel, Harun; Şahin, Alparslan; Murat, Mehmet; Bozkurt, Yaşar; Çaça, Ihsan

2013-04-01

Phosphodiesterase-5 (PDE5) inhibitors are commonly used in the treatment of erectile dysfunction. There are a small number of case reports that associate this agent with central serous chorioretinopathy (CSCR). Our report presents the treatment approach to a 42-year-old patient who described blurred vision and metamorphopsia and was diagnosed with CSCR following the use of tadalafil, a PDE5 inhibitor.

21 CFR 888.1240 - AC-powered dynamometer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand. (b) Classification. Class...

21 CFR 888.1240 - AC-powered dynamometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand. (b) Classification. Class...

Effects of whole body vibration exercise on neuromuscular function for individuals with knee osteoarthritis: study protocol for a randomized controlled trial.

PubMed

Lai, Zhangqi; Wang, Xueqiang; Lee, Seullee; Hou, Xihe; Wang, Lin

2017-09-20

Knee osteoarthritis (KOA) is a leading cause of public disability. Neuromuscular function contributes to the development and/or progression of KOA. Whole body vibration (WBV) exercise improve the neuromuscular function of patients with neurological disorders and even that of older patients with limited exercise options. Therefore, WBV exercise may offer an efficient and alternative treatment for individuals with KOA. However, the effects of WBV training on the neuromuscular function of individuals with KOA remain unclear. Therefore, this study attempts to investigate the effect of a 12-week WBV exercise on the neuromuscular function of individuals with KOA. We will conduct a prospective, single-blind randomized controlled trial on 180 KOA patients. Participants will be randomly assigned to the WBV exercise, lower extremity resistance training, and health education groups. The WBV exercise group will participate in a 12-week WBV training. The lower extremity resistance training group will undergo a 12-week lower extremity resistance training of both lower limbs. The control group will receive health education for 12 weeks. After the intervention, the participants will be followed up for 3 months with no active intervention. Primary outcome measures will include anthropometric measurements, gait analysis during walking and stair climbing, muscle strength test of the knee and ankle, proprioception test of the knee and ankle, and neuromuscular response of the leg muscles. Secondary outcome measures will include self-reported pain and physical functional capacity, and physical performance measures. Furthermore, adverse events will be recorded and analyzed. If any participant withdraws from the trial, intention-to-treat analysis will be performed. Important features of this trial mainly include intervention setting, outcome measure selection, and study duration. This study is intended for estimating the effect of WBV intervention on neuromuscular control outcomes. Study results may provide evidence to support the beneficial effects of WBV exercise on the physical performance and neuromuscular control of individuals with KOA to fill the research gap on the efficacy of WBV. Chinese Clinical Trial Registry, ID: ChiCTR-IOR-16009234 . Registered on 21 September 2016.

Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single-Planar versus Multi-Planar Support Perturbations in Young, Active Adults.

PubMed

Malfait, Bart; Staes, Filip; de Vries, Aijse; Smeets, Annemie; Hawken, Malcolm; Robinson, Mark A; Vanrenterghem, Jos; Verschueren, Sabine

2015-01-01

An anterior cruciate ligament (ACL) injury involves a multi-planar injury mechanism. Nevertheless, unexpected multi-planar perturbations have not been used to screen athletes in the context of ACL injury prevention yet could reveal those more at risk. The objective of this study was to compare neuromuscular responses to multi-planar (MPP) and single-planar perturbations (SPP) during a stepping-down task. These results might serve as a basis for future implementation of external perturbations in ACL injury screening programs. Thirteen young adults performed a single leg stepping-down task in eight conditions (four MPP and four SPP with a specified amplitude and velocity). The amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior centre of mass (COM) displacements, the peak knee flexion and abduction angles were compared between conditions using an one-way ANOVA. Number of stepping responses were monitored during all conditions. Significantly greater muscle activity levels were found in response to the more challenging MPP and SPP compared to the less challenging conditions (p < 0.05). No differences in neuromuscular activity were found between the MPP conditions and their equivalents in the SPP. Eighteen stepping responses were monitored in the SPP versus nine in the MPP indicating that the overall neuromuscular control was even more challenged during the SPP which was supported by greater COM displacements in the SPP. The more intense MPP and SPP evoked different neuromuscular responses resulting in greater muscle activity levels compared to small perturbations. Based on the results of COM displacements and based on the amount of stepping responses, dynamic neuromuscular control of the knee joint appeared less challenged during the MPP. Therefore, future work should investigate extensively if other neuromuscular differences (i.e. co-activation patterns and kinetics) exist between MPP and SPP. In addition, future work should examine the influence on the neuromuscular control of the magnitude of the perturbations and the magnitude of stepping height and stepping distance.

Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

PubMed

Jacobson, Lisa A; Rane, Shruti; McReynolds, Lisa J; Steppan, Diana A; Chen, Allen R; Paz-Priel, Ido

2016-07-01

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Copyright © 2016 by the American Academy of Pediatrics.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: from molecular genetics to clinical features.

PubMed

Zhou, Yaoyao; Zhang, Junfeng

2014-09-20

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare but fatal autosomal recessive multisystem disorder caused by mutations in the VPS33B or VIPAR gene. The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, central nervous system malformation, platelet anomalies, and severe failure to thrive. Diagnosis of ARC syndrome relies on clinical features, organ biopsy, and mutational analysis. However, no specific treatment currently exists for this syndrome. This is an overview of the latest knowledge regarding the genetic features and clinical manifestations of ARC syndrome. Greater awareness and understanding of this syndrome should allow more timely intervention with potential for improving long-term outcome.

Advances in the treatment of erectile dysfunction: what’s new and upcoming?

PubMed Central

Patel, Chintan K.; Bennett, Nelson

2016-01-01

Erectile dysfunction adversely affects up to 20% of all men and is the most commonly treated sexual disorder. The public health implications of this condition are significant and represent a challenge for our healthcare system. The physiological pathways responsible for erections have been extensively studied, and much advancement has been made since the introduction of phosphodiesterase 5 inhibitors. Newer agents, such as dopaminergic and melanocortin receptor agonists, which target central erectogenic pathways, are under investigation. Newer formulations and delivery methods of existing medications such as alprostadil will also be introduced in the near future. Furthermore, low-intensity shockwave lithotripsy and stem cell regenerative techniques are innovative approaches to the treatment of erectile dysfunction. PMID:27516878

Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases

ClinicalTrials.gov

2015-08-24

Spinal Muscular Atrophy; Charcot-Marie-Tooth Disease; Muscular Dystrophy; Spinal Muscular Atrophy With Respiratory Distress 1; Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Disease; Peroneal Muscular Atrophy; Fragile X Syndrome

Intermittent hypercapnia induces long-lasting ventilatory plasticity to enhance CO2 responsiveness to overcome dysfunction

NASA Astrophysics Data System (ADS)

Mosher, Bryan Patrick

The ability of the brain to detect (central CO2 chemosensitivity) and respond to (central CO2 chemoresponsiveness) changes in tissue CO2/pH, is a homeostatic process essential for mammalian life. Dysfunction of the serotonin (5-HT) mechanisms compromises ventilatory CO 2 chemosensitivity/responsiveness and may enhance vulnerability to pathologies such as the Sudden Infant Death Syndrome (SIDS). The laboratory of Dr. Michael Harris has shown medullary raphe contributions to central chemosensitivity involving both 5-HT- and gamma-aminobutyric acid (GABA)-mediated mechanisms. I tested the hypothesis that postnatal exposure to mild intermittent hypercapnia (IHc) induces respiratory plasticity, due in part to strengthening of bicuculline- and saclofen-sensitive mechanisms (GABAA and GABAB receptor antagonists respectively). Rats were exposed to IHc-pretreatment (8 cycles of 5 % CO2) for 5 days beginning at postnatal day 12 (P12). I subsequently assessed CO2 responsiveness using an in situ perfused brainstem preparation. Hypercapnic responses were determined with and without pharmacological manipulation. In addition, IHc-pretreatment effectiveness was tested for its ability to overcome dysfunction in the CO2 responsiveness induced by a dietary tryptophan restriction. This dysfunctional CO2 responsiveness has been suggested to arise from a chronic, partial 5-HT reduction imparted by the dietary restriction. Results show IHc-pretreatment induced plasticity sufficient for CO2 responsiveness despite removal of otherwise critical ketanserin-sensitive mechanisms. CO2 responsiveness following IHc-pretreatment was absent if ketanserin was combined with bicuculline and saclofen, indicating that the plasticity was dependent upon bicuculline- and saclofen-sensitive mechanisms. IHc--induced plasticity was also capable of overcoming the ventilatory defects associated with maternal dietary restriction. Duration of IHc-induced plasticity was also investigated and found to last far into life (up to P65). Furthermore, I performed experiments to investigate if IHc-induced plasticity was more robust at a specific developmental period. No such critical period was identified as IHc-pretreatment induced robust respiratory plasticity when administered at all developmental periods tested (P12-16, P21-25 and P36-0). I propose that IHc-induced plasticity may be able to reduce the severity of reflex dysfunctions underlying pathologies such as SIDS.

American Association of Neuromuscular & Electrodiagnostic Medicine

MedlinePlus

... on diagnostic approaches to neuromuscular diseases. We recommend Principles of Clinical Electromyography Case Studies. Learn more Enhance ... offers your company the chance to meet its marketing objectives through participation at the AANEM Annual Meeting ...

Unlike myofibers, neuromuscular junctions remain stable during prolonged muscle unloading.

PubMed

Deschenes, Michael R; Will, Kristin M; Booth, Frank W; Gordon, Scott E

2003-06-15

This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fischer 344 rats were randomly assigned to either a hindlimb suspension (unloaded) or control group (N=8/group) for 16 days. Following this intervention period, pre- and postsynaptic features of the neuromuscular junctions (NMJs) of soleus muscles were stained with cytofluorescent techniques, and myofibers were histochemically stained for ATPase activity. The data indicate that 16 days of muscle unloading resulted in significant (P<0.05) atrophy among myofibers (>50%) that was evident among all three major fiber types (I, IIA and IIX), but failed to significantly alter any aspect of NMJ morphology quantified. These results demonstrate an impressive degree of NMJ resilience despite dramatic remodeling of associated myofibers. This may be of benefit during post-unloading rehabilitative measures where effective neuromuscular communication is essential.

The use of in-flight foot pressure as a countermeasure to neuromuscular degradation

NASA Technical Reports Server (NTRS)

Layne, C. S.; Mulavara, A. P.; Pruett, C. J.; McDonald, P. V.; Kozlovskaya, I. B.; Bloomberg, J. J.

1998-01-01

The purpose of this study was to determine whether applying foot pressure to unrestrained subjects during space flight could enhance the neuromuscular activation associated with rapid arm movements. Four men performed unilateral arm raises while wearing--or not wearing--specially designed boots during a 81- or 115-day space flight. Arm acceleration and surface EMG were obtained from selected lower limb and trunk muscles. Pearson r coefficients were used to evaluate similarity in phasic patterns between the two in-flight conditions. In-flight data also were magnitude normalized to the mean voltage value of the muscle activation waveforms obtained during the no-foot-pressure condition to facilitate comparison of activation amplitude between the two in-flight conditions. Foot pressure enhanced neuromuscular activation and somewhat modified the phasic features of the neuromuscular activation during the arm raises.

Autoimmune Neuromuscular Disorders

PubMed Central

Kraker, Jessica; Živković, Saša A

2011-01-01

Autoimmune neuromuscular disorders affecting peripheral nerves, neuromuscular junction or muscle have a wide clinical spectrum with diverse pathogenetic mechanisms. Peripheral nervous system may be targeted in the context of complex immune reactions involving different cytokines, antigen-presenting cells, B cells and different types of T cells. Various immunomodulating and cytotoxic treatments block proliferation or activation of immune cells by different mechanisms attempting to control the response of the immune system and limit target organ injury. Most treatment protocols for autoimmune neuromuscular disorders are based on the use of corticosteroids, intravenous immunoglobulins and plasmapheresis, with cytotoxic agents mostly used as steroid-sparing medications. More recently, development of specific monoclonal antibodies targeting individual cell types allowed a different approach targeting specific immune pathways, but these new treatments are also associated with various adverse effects and their long-term efficacy is still unknown. PMID:22379454

Total hip arthroplasty in patients with neuromuscular imbalance.

PubMed

Konan, S; Duncan, C P

2018-01-01

Patients with neuromuscular imbalance who require total hip arthroplasty (THA) present particular technical problems due to altered anatomy, abnormal bone stock, muscular imbalance and problems of rehabilitation. In this systematic review, we studied articles dealing with THA in patients with neuromuscular imbalance, published before April 2017. We recorded the demographics of the patients and the type of neuromuscular pathology, the indication for surgery, surgical approach, concomitant soft-tissue releases, the type of implant and bearing, pain and functional outcome as well as complications and survival. Recent advances in THA technology allow for successful outcomes in these patients. Our review suggests excellent benefits for pain relief and good functional outcome might be expected with a modest risk of complication. Cite this article: Bone Joint J 2018;100-B(1 Supple A):17-21. ©2018 The British Editorial Society of Bone & Joint Surgery.

Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.

PubMed

Elgadi, Aziz; Arvidsson, C-G; Janson, Annika; Marcus, Claude; Costagliola, Sabine; Norgren, Svante

2005-08-01

Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms. The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations. Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy. The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.

Hexosamine Biosynthetic Pathway Mutations Cause Neuromuscular Transmission Defect

PubMed Central

Senderek, Jan; Müller, Juliane S.; Dusl, Marina; Strom, Tim M.; Guergueltcheva, Velina; Diepolder, Irmgard; Laval, Steven H.; Maxwell, Susan; Cossins, Judy; Krause, Sabine; Muelas, Nuria; Vilchez, Juan J.; Colomer, Jaume; Mallebrera, Cecilia Jimenez; Nascimento, Andres; Nafissi, Shahriar; Kariminejad, Ariana; Nilipour, Yalda; Bozorgmehr, Bita; Najmabadi, Hossein; Rodolico, Carmelo; Sieb, Jörn P.; Steinlein, Ortrud K.; Schlotter, Beate; Schoser, Benedikt; Kirschner, Janbernd; Herrmann, Ralf; Voit, Thomas; Oldfors, Anders; Lindbergh, Christopher; Urtizberea, Andoni; von der Hagen, Maja; Hübner, Angela; Palace, Jacqueline; Bushby, Kate; Straub, Volker; Beeson, David; Abicht, Angela; Lochmüller, Hanns

2011-01-01

Neuromuscular junctions (NMJs) are synapses that transmit impulses from motor neurons to skeletal muscle fibers leading to muscle contraction. Study of hereditary disorders of neuromuscular transmission, termed congenital myasthenic syndromes (CMS), has helped elucidate fundamental processes influencing development and function of the nerve-muscle synapse. Using genetic linkage, we find 18 different biallelic mutations in the gene encoding glutamine-fructose-6-phosphate transaminase 1 (GFPT1) in 13 unrelated families with an autosomal recessive CMS. Consistent with these data, downregulation of the GFPT1 ortholog gfpt1 in zebrafish embryos altered muscle fiber morphology and impaired neuromuscular junction development. GFPT1 is the key enzyme of the hexosamine pathway yielding the amino sugar UDP-N-acetylglucosamine, an essential substrate for protein glycosylation. Our findings provide further impetus to study the glycobiology of NMJ and synapses in general. PMID:21310273

Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.

PubMed

Bülbül, Mehmet; İzgüt-Uysal, V Nimet; Sinen, Osman; Birsen, İlknur; Tanrıöver, Gamze

2016-02-15

Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway. Copyright © 2016 the American Physiological Society.

Effect of hypnotic suggestion on knee extensor neuromuscular properties in resting and fatigued states

PubMed Central

Antonini Philippe, Roberta; Guglielmo, Luiz Guilherme A.

2018-01-01

Purpose The aim of this study was to investigate whether hypnotic suggestions can alter knee extensor neuromuscular function at rest and during exercise. Methods Thirteen healthy volunteers (8 men and 5 women, 27 ± 3 years old) took part in this counterbalanced, crossover study including two experimental (hypnosis and control) sessions. Knee extensor neuromuscular function was tested before and after hypnosis suggestion by using a combination of voluntary contraction, transcutaneous femoral nerve electrical stimulation and transcranial magnetic stimulation (TMS). A fatiguing exercise (sustained submaximal contraction at 20% maximal voluntary contraction (MVC) force) was also performed to evaluate the potential influence of hypnosis on the extent and origin of neuromuscular adjustments. Results Hypnosis did not (p>0.05) alter MVC force or knee extensor neural properties. Corticospinal excitability, assessed with the amplitude of knee extensor motor evoked potentials, was also unchanged (p>0.05), as was the level of intracortical inhibition assessed with paired pulse TMS (short-interval intracortical inhibition, SICI). Time to task failure (~300 s) was not different (p>0.05) between the two sessions; accordingly, hypnosis did not influence neuromuscular adjustments measured during exercise and at task failure (p>0.05). Conclusion Hypnotic suggestions did not alter neuromuscular properties of the knee extensor muscles under resting condition or during/after exercise, suggesting that hypnosis-induced improvement in exercise performance and enhanced corticospinal excitability might be limited to highly susceptible participants. PMID:29684047

Ephedrine fails to accelerate the onset of neuromuscular block by vecuronium.

PubMed

Komatsu, Ryu; Nagata, Osamu; Ozaki, Makoto; Sessler, Daniel I

2003-08-01

The onset time of neuromuscular blocking drugs is partially determined by circulatory factors, including muscle blood flow and cardiac output. We thus tested the hypothesis that a bolus of ephedrine accelerates the onset of vecuronium neuromuscular block by increasing cardiac output. A prospective, randomized study was conducted in 53 patients scheduled for elective surgery. After the induction of anesthesia, the ulnar nerve was stimulated supramaximally every 10 s, and the evoked twitch response of the adductor pollicis was recorded with accelerometry. Patients were maintained under anesthesia with continuous infusion of propofol for 10 min and then randomly assigned to ephedrine 210 microg/kg (n = 27) or an equivalent volume of saline (n = 26). The test solution was given 1 min before the administration of 0.1 mg/kg of vecuronium. Cardiac output was monitored with impedance cardiography. Ephedrine, but not saline, increased cardiac index (17%; P = 0.003). Nonetheless, the onset of 90% neuromuscular block was virtually identical in the patients given ephedrine (183 +/- 41 s) and saline (181 +/- 47 s). There was no correlation between cardiac index and onset of the blockade. We conclude that the onset of the vecuronium-induced neuromuscular block is primarily determined by factors other than cardiac output. The combination of ephedrine and vecuronium thus cannot be substituted for rapid-acting nondepolarizing muscle relaxants. Ephedrine increased cardiac index but failed to speed onset of neuromuscular block with vecuronium. We conclude that ephedrine administration does not shorten the onset time of vecuronium.

Neuromuscular disease and respiratory physiology in children: putting lung function into perspective.

PubMed

Fauroux, Brigitte; Khirani, Sonia

2014-08-01

Neuromuscular diseases represent a heterogeneous group of disorders of the muscle, nerve or neuromuscular junction. The respiratory muscles are rarely spared in neuromuscular diseases even if the type of muscle involvement, severity and time course greatly varies among the different diseases. Diagnosis of respiratory muscle weakness is crucial because of the importance of respiratory morbidity and mortality. Presently, routine respiratory evaluation is based on non-invasive volitional tests, such as the measurement of lung volumes, spirometry and the maximal static pressures, which may be difficult or impossible to obtain in some young children. Other tools or parameters are thus needed to assess the respiratory muscle weakness and its consequences in young children. The measurement of oesogastric pressures can be helpful as they allow the diagnosis and quantification of paradoxical breathing, as well as the assessment of the strength of the inspiratory and expiratory muscles by means of the oesophageal pressure during a maximal sniff and of the gastric pressure during a maximal cough. Sleep assessment should also be part of the respiratory evaluation of children with neuromuscular disease with at least the recording of nocturnal gas exchange if polysomnography is not possible or unavailable. This improvement in the assessment of respiratory muscle performance may increase our understanding of the respiratory pathophysiology of the different neuromuscular diseases, improve patient care, and guide research and innovative therapies by identifying and validating respiratory parameters. © 2014 Asian Pacific Society of Respirology.

Immediate effects of different treatments for the wrist joints of subdominant hands, using electromechanical reaction time.

PubMed

Hu, Chunying; Huang, Qiuchen; Yu, Lili; Zhou, Yue; Gu, Rui; Cui, Yao; Ge, Meng; Xu, Yanfeng; Liu, Jianfeng

2016-08-01

[Purpose] The aim of this study was to examine the immediate effects of muscle strength training and neuromuscular joint facilitation distal resistance training on wrist joints by using electromechanical reaction time. [Subjects and Methods] The subjects were 12 healthy young people (24.2 ± 3.1 years, 169.7 ± 6.5 cm, 65.3 ± 12.6 kg). Two kinds of isotonic contraction techniques were applied on the wrist joint: the wrist joint extension muscle strength training and the wrist joint extension pattern of neuromuscular joint facilitation. The electromechanical reaction time, premotor time, and motor time of the left upper limb were measured before and after each intervention session of muscle strength training and neuromuscular joint facilitation. [Results] The neuromuscular joint facilitation group showed significant shortening of the electromechanical reaction time and motor time after the intervention. [Conclusion] These results suggest that the electromechanical reaction time and motor time of the wrist joint can be improved by neuromuscular joint facilitation together with proximal resistance training, which can be used as a new form of exercise for improving the functions of subdominant hand wrist joints.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

PubMed

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Computational model to investigate the relative contributions of different neuromuscular properties of tibialis anterior on force generated during ankle dorsiflexion.

PubMed

Siddiqi, Ariba; Poosapadi Arjunan, Sridhar; Kumar, Dinesh Kant

2018-01-16

This study describes a new model of the force generated by tibialis anterior muscle with three new features: single-fiber action potential, twitch force, and pennation angle. This model was used to investigate the relative effects and interaction of ten age-associated neuromuscular parameters. Regression analysis (significance level of 0.05) between the neuromuscular properties and corresponding simulated force produced at the footplate was performed. Standardized slope coefficients were computed to rank the effect of the parameters. The results show that reduction in the average firing rate is the reason for the sharp decline in the force and other factors, such as number of muscle fibers, specific force, pennation angle, and innervation ratio. The fast fiber ratio affects the simulated force through two significant interactions. This study has ranked the individual contributions of the neuromuscular factors to muscle strength decline of the TA and identified firing rate decline as the biggest cause followed by decrease in muscle fiber number and specific force. The strategy for strength preservation for the elderly should focus on improving firing rate. Graphical abstract Neuromuscular properties of Tibialis Anterior on force generated during ankle dorsiflexion.

Sugammadex as a reversal agent for neuromuscular block: an evidence-based review

PubMed Central

Schaller, Stefan Josef; Fink, Heidrun

2013-01-01

Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing. PMID:24098155

The relationship between the target effective site concentration of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients

PubMed Central

Fan, Xiaochong; Ma, Minyu; Li, Zhisong; Gong, Shengkai; Zhang, Wei; Wen, Yuanyuan

2015-01-01

Objective: To study the relationship between the target effective site concentration (Ce) of rocuronium and the degree of recovery from neuromuscular blockade in elderly patients. Methods: 50 elderly patients (ASA grade II) scheduled for selective surgical procedure under general anaesthesia were randomly divided into two groups, A and B, with 25 cases in each group. The Ce of rocuronium for intubation was 3 μg·ml-1 in both groups, and the Ce during operation were 0.8 and 1.0 μg·ml-1 in group A and B, respectively. When target controlled infusion of rocuronium was stopped, without the administration of reversal agents for neuromuscular blockade, the relationship between Ce and the first twitch height (T1) was studied by regression analysis. Results: There was a significant linear relationship between Ce and T1, and there was no statistical difference in regression coefficient and interception between group A and B (P>0.05). Conclusion: The degree of recovery from neuromuscular blockade could be judged by the target effective site concentration of rocuronium at the time of reversal from neuromuscular blockade in the elderly patients. PMID:26629159

[Neuromuscular deficits in chronic ankle instability. Frequency and significance - multicenter study].

PubMed

Schmidt, R; Becker, H P; Rauhut, F; Tannheimer, M

2014-08-01

The peroneal reaction time (PRT) is used in the assessment of neuromuscular deficits in chronic functional ankle instability. Powered by the Editorial Manager and Preprint Manager from Aries Systems Corporation the present study was conducted to determine the PRT in a large collective of patients with chronic ankle instability because it is unclear if this parameter of neuromuscular deficit is prolonged. In this study 186 patients underwent a diagnostic algorithm consisting of anamnesis, clinical examination, X-ray and determination of the PRT on a tilting platform. A prolonged PRT as a manifestation of a neuromuscular deficit could be detected in the majority of the patients (n = 143, 77%). Comparing the affected and healthy legs 77 patients (41%) showed a significant difference in talar shift (p = 0.002) and talar tilt (p = 0.04) in the radiological stress views. Of these 77 patients only 15 (8%) showed radiological evidence of a mechanical problem. As a consequence of recurring ankle sprains a post-traumatic deficit in proprioception has to be expected in most cases. In general a conservative therapy approach should be followed including specific training to improve neuromuscular and proprioceptive deficits.

Knee joint kinaesthesia and neuromuscular coordination during three phases of the menstrual cycle in moderately active women.

PubMed

Fridén, Cecilia; Hirschberg, Angelica Lindén; Saartok, Tönu; Renström, Per

2006-04-01

An increased incidence of sports related injuries in the premenstrual phase as well as in the menstrual phase of the menstrual cycle has been described. This may be explained by alterations in proprioception and neuromuscular coordination due to hormonal variations. Prospective, within women analysis of knee joint kinesthesia and neuromuscular coordination were performed by repeated measures analysis of variance in three hormonally verified phases of three consecutive menstrual cycles. Thirty-two healthy, moderately active female subjects volunteered to participate in the study. Twenty-five of the subjects performed at least one hormonally verified menstrual cycle. A specially designed device was used to investigate knee joint kinaesthesia and neuromuscular coordination was measured with the square hop test. These tests were carried out in the menstrual phase, ovulation phase and premenstrual phase determined by hormone analyses in three consecutive menstrual cycles. An impaired knee joint kinaesthesia was detected in the premenstrual phase and the performance of square hop test was significantly improved in the ovulation phase compared to the other two phases. The results of this study indicate that the variation of sex hormones in the menstrual cycle has an effect on performance of knee joint kinaesthesia and neuromuscular coordination.

Neuromuscular blocking properties of some bistropinium esters

PubMed Central

Haining, C. G.; Johnston, R. G.

1962-01-01

The neuromuscular blocking, anti-acetylcholine and ganglion blocking properties of two series of bistropinium esters were examined. The neuromuscular blocking activities of the mandelic acid esters of NN'-polymethylenebis(tropinium halides) were found to depend upon the number of carbon atoms (n) in the linking chain. Potency was enhanced more than 50 times as n was increased from 2 to 7. Compounds in which n equalled 7, 8, 9, 10 and 12 differed little in activity, but were generally more potent than tubocurarine in cats and rabbits. A peak of ganglion blocking action was obtained at the pentamethylene member. Esterification enhanced the feeble neuromuscular blocking properties of NN'-decamethylenebis(tropinium halide), the mandelic acid ester being more effective than the tropic, benzoic or phenylacetic acid esters in cats and rabbits. When two benzoic or mandelic acid esters of tropine were linked through their nitrogen atoms by a phenylenedimethyl grouping (-CH2.C6H4.CH2-), meta substitution was more effective than was ortho or para in producing neuromuscular block. The effectiveness of esterifying acids in m-phenylenedimethyl derivatives decreased in the following order, phenylacetic> tropic or mandelic>benzoic>acetic and diphenylacetic. PMID:13903721

Electrophysiological diagnosis and patterns of response to treatment of botulism with neuromuscular respiratory failure.

PubMed

Kongsaengdao, Subsai; Samintarapanya, Kanoksri; Rusmeechan, Siwarit; Sithinamsuwan, Pasiri; Tanprawate, Surat

2009-08-01

In this study we describe the electrophysiological findings in botulism patients with neuromuscular respiratory failure from major botulism outbreaks in Thailand. High-rate repetitive nerve stimulation testing (RNST) of the abductor digiti minimi (ADM) muscle of 17 botulism patients with neuromuscular respiratory failure showed mostly incremental responses, especially in response to >20-HZ stimulation. In the most severe stage of neuromuscular respiratory failure, RNST failed to elicit a compound muscle action potential (CMAP) of the ADM muscle. In the moderately severe stage, the initial CMAPs were of very low amplitude, and a 3-HZ RNST elicited incremental or decremental responses. A 10-HZ RNST elicited mainly decremental responses. In the early recovery stage, the initial CMAP amplitudes of the ADM muscle improved, with initially low amplitudes and an incremental response to 3- and 10-HZ RNSTs. Improved electrophysiological patterns of the ADM muscle correlated with improved respiratory muscle function. Incremental responses to 20-HZ RNST were most useful for diagnosis. The initial electrodiagnostic sign of recovery following treatment of neuromuscular respiratory failure was an increased CMAP amplitude and an incremental response to 10-20-HZ RNST. Muscle Nerve 40: 271-278, 2009.

Conservative management of neuromuscular scoliosis: personal experience and review of literature.

PubMed

Kotwicki, Tomasz; Jozwiak, Marek

2008-01-01

The principles of conservative management of neuromuscular scoliosis in childhood and adolescence are presented. Analysis of personal experience and literature review. The topic is discussed separately for patients with flaccid or spastic paresis. These demonstrate that conservative management might be proposed for patients with neuromuscular scoliosis in many clinical situations. In spastic disorders, it maintains the symmetry around the hip joints. Bracing is technically difficult and often is not tolerated well by cerebral palsy children. In patients with flaccid paresis, the fitting and the use of brace is easier than in spastic patients. The flexibility of the spinal curvature is more important. Functional benefits of conservative management of neuromuscular scoliosis comprise stable sitting, easier use of upper limbs, discharge of the abdomen from the collapsing trunk, increased diaphragm excursion, and, not always, prevention of curve progression. Specific natural history and multiple medical problems associated with the disease make the treatment of children with neuromuscular scoliosis an extremely complex issue, best addressed when a team approach is applied. Continuously improving techniques of conservative management, comprising bracing and physiotherapy, together with correctly timed surgery incorporated in the process of rehabilitation, provide the optimal care for patients.

It's more than just physical therapy: reported utilization of physiotherapy services for adults with neuromuscular disorders attending a specialist centre.

PubMed

Hartley, Sandra; Stockley, Rachel

2013-02-01

The purpose of this study is to evaluate service users' perceptions of their utilization of the physiotherapy service at a specialist Neuromuscular Centre and to identify their reasons for and barriers to attending. A prospective survey design, consisting of a 13-item questionnaire was completed by 104 registered users of a physiotherapy service at a Neuromuscular Centre in northwest England. Descriptive statistics was employed to analyse data from Likert style questions and thematic analysis conducted on responses to open-ended questions. Over 79% of respondents were satisfied with the frequency and duration of their treatment. Respondents attended physiotherapy to obtain physical therapy, for general wellbeing and to access specialized resources. Barriers to attendance included work commitments, travel cost and time, and lack of Centre resources. Clients attending physiotherapy valued the specialist service including advice from therapists, perceived benefit from social interaction with other clients and physical therapy. Adults with neuromuscular disorders identified psychosocial as well as physical benefits from attending physiotherapy at the Neuromuscular Centre. The findings highlight the importance of service users' views in service provision and suggest that a collaborative commitment to patient management could by advantageous when developing physiotherapy services.

Acute flaccid paraparesis (cauda equina syndrome) in a patient with Bardet-Biedl syndrome.

PubMed

Viswanathan, Vibhu Krishnan; Kanna, Rishi Mugesh; Shetty, Ajoy Prasad; Rajasekaran, S

2017-01-01

Bardet-Biedl syndrome (BBS) is a rare, autosomal-recessive, debilitating genetic disorder, which can present with multitudinous systemic clinical features including rod-cone dystrophy, polydactyly, Frohlich-like central obesity, mental retardation, hypogonadism, and renal anomalies. Diverse neuromuscular manifestations in patients afflicted by this heterogeneous disorder include ataxia, cervical, and thoracic canal stenoses, presenting as spastic quadriparesis and other gait disturbances. We report a young patient with BBS, who had presented with acute flaccid paraparesis due to severe primary lumbar canal stenosis. She underwent immediate lumbar decompression and discectomy following which she recovered significantly. Acute cauda equina syndrome due to primary lumbar canal stenosis has not been reported as a clinical feature of BBS previously.

Genetic disorders of thyroid metabolism and brain development

PubMed Central

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

Teaching Visually Impaired Adults with a Neuromuscular Disorder.

ERIC Educational Resources Information Center

Williams, Susan

1983-01-01

The effects of four neuromuscular disorders (stroke, Parkinson's disease, Huntington's disease, and Lou Gehrig's disease) on concommitant visual impairments are considered. Rehabilitation approaches and equipment that help clients cope with the condition are described. (CL)

Muscle wasting in myotonic dystrophies: a model of premature aging.

PubMed

Mateos-Aierdi, Alba Judith; Goicoechea, Maria; Aiastui, Ana; Fernández-Torrón, Roberto; Garcia-Puga, Mikel; Matheu, Ander; López de Munain, Adolfo

2015-01-01

Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are multisystem disorders of genetic origin. Progressive muscular weakness, atrophy and myotonia are the most prominent neuromuscular features of these diseases, while other clinical manifestations such as cardiomyopathy, insulin resistance and cataracts are also common. From a clinical perspective, most DM symptoms are interpreted as a result of an accelerated aging (cataracts, muscular weakness and atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased risk of developing tumors. From this point of view, DM1 could be described as a progeroid syndrome since a notable age-dependent dysfunction of all systems occurs. The underlying molecular disorder in DM1 consists of the existence of a pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9 (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and (CCUG)n-containing RNA, respectively, which form secondary structures and sequester RNA-binding proteins, such as the splicing factor muscleblind-like protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors, such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of downstream genes linked to the clinical features of these diseases. Skeletal muscle regeneration relies on muscle progenitor cells, known as satellite cells, which are activated after muscle damage, and which proliferate and differentiate to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction seems to be a common feature of both age-dependent muscle degeneration (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases. This review aims to describe the cellular, molecular and macrostructural processes involved in the muscular degeneration seen in DM patients, highlighting the similarities found with muscle aging.

Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis.

PubMed

Miquel, Ernesto; Cassina, Adriana; Martínez-Palma, Laura; Souza, José M; Bolatto, Carmen; Rodríguez-Bottero, Sebastián; Logan, Angela; Smith, Robin A J; Murphy, Michael P; Barbeito, Luis; Radi, Rafael; Cassina, Patricia

2014-05-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron degeneration that ultimately results in progressive paralysis and death. Growing evidence indicates that mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in ALS. To further explore the hypothesis that mitochondrial dysfunction and nitroxidative stress contribute to disease pathogenesis at the in vivo level, we assessed whether the mitochondria-targeted antioxidant [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl]triphenylphosphonium methane sulfonate (MitoQ) can modify disease progression in the SOD1(G93A) mouse model of ALS. To do this, we administered MitoQ (500 µM) in the drinking water of SOD1(G93A) mice from a time when early symptoms of neurodegeneration become evident at 90 days of age until death. This regime is a clinically plausible scenario and could be more easily translated to patients as this corresponds to initiating treatment of patients after they are first diagnosed with ALS. MitoQ was detected in all tested tissues by liquid chromatography/mass spectrometry after 20 days of administration. MitoQ treatment slowed the decline of mitochondrial function, in both the spinal cord and the quadriceps muscle, as measured by high-resolution respirometry. Importantly, nitroxidative markers and pathological signs in the spinal cord of MitoQ-treated animals were markedly reduced and neuromuscular junctions were recovered associated with a significant increase in hindlimb strength. Finally, MitoQ treatment significantly prolonged the life span of SOD1(G93A) mice. Our results support a role for mitochondrial nitroxidative damage and dysfunction in the pathogenesis of ALS and suggest that mitochondria-targeted antioxidants may be of pharmacological use for ALS treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

[The clinical phenomenology of Rett's syndrome].

PubMed

Calderón-González, R; Calderón-Sepulveda, R F; Treviño-Welsh, J

1999-01-01

The work was done to facilitate the clinical diagnosis and understanding of Rett syndrome (RS) by grouping the symptoms and signs in areas of neurological disfunction. This is a retrospective, longitudinal and observational study of 30 young females whose clinical manifestations were grouped using a modified Fitzgerald et al. scale for motor and behavior evaluation of patients with RS. All patients were videotaped at least during one or several appointments during their follow-up for a period of 1 to 10 years. All patients and videotapes were reviewed independently by the three authors. We followed the clinical diagnostic criteria of classic RS, and grouped the symptoms and signs in 12 groups of clinical phenomenology that represented specific areas of central or peripheral nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3) respiratory function disorders (brain stem reticular system disfunction); 4) sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico-subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction and 12) others (microcephaly and bruxism). In clinical practice, we recommend the use of this grouping of symptoms and signs because it makes facilities the clinical study, definition of areas of dysfunction and diagnosis of the patient with RS.

Mitochondrial Dysfunction in Lysosomal Storage Disorders

PubMed Central

de la Mata, Mario; Cotán, David; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M.; Tiscornia, Gustavo; Oropesa-Ávila, Manuel

2016-01-01

Lysosomal storage diseases (LSDs) describe a heterogeneous group of rare inherited metabolic disorders that result from the absence or loss of function of lysosomal hydrolases or transporters, resulting in the progressive accumulation of undigested material in lysosomes. The accumulation of substances affects the function of lysosomes and other organelles, resulting in secondary alterations such as impairment of autophagy, mitochondrial dysfunction, inflammation and apoptosis. LSDs frequently involve the central nervous system (CNS), where neuronal dysfunction or loss results in progressive neurodegeneration and premature death. Many LSDs exhibit signs of mitochondrial dysfunction, which include mitochondrial morphological changes, decreased mitochondrial membrane potential (ΔΨm), diminished ATP production and increased generation of reactive oxygen species (ROS). Furthermore, reduced autophagic flux may lead to the persistence of dysfunctional mitochondria. Gaucher disease (GD), the LSD with the highest prevalence, is caused by mutations in the GBA1 gene that results in defective and insufficient activity of the enzyme β-glucocerebrosidase (GCase). Decreased catalytic activity and/or instability of GCase leads to accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the lysosomes of macrophage cells and visceral organs. Mitochondrial dysfunction has been reported to occur in numerous cellular and mouse models of GD. The aim of this manuscript is to review the current knowledge and implications of mitochondrial dysfunction in LSDs. PMID:28933411

Cardiovascular risk reduction by reversing endothelial dysfunction:ARBs, ACE inhibitors, or both? Expectations from The ONTARGET Trial Programme

PubMed Central

Ruilope, Luis Miguel; Redón, Josep; Schmieder, Roland

2007-01-01

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008. PMID:17583170

Sacral neuromodulation for lower urinary tract dysfunction.

PubMed

Van Kerrebroeck, Philip E V; Marcelissen, Tom A T

2012-08-01

To review the technique, indications, results and working mechanisms of sacral neuromodulation (SNM) for lower urinary tract dysfunction. The available literature on SNM for lower urinary tract dysfunction was searched. Based on the information available in the literature and also based on personal experience, the urological indications, technique, mechanisms of action and results of SNM are presented and discussed. SNM for lower urinary tract dysfunction involves stimulation of the 3rd sacral nerve with an electrode implanted in the sacral foramen and connected to a pulse generator. The technique is accepted by the FDA since 1997. Currently, SNM for lower urinary tract dysfunction has been successfully used in about 26,000 patients with various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. The actual procedure of SNM consists of a minimal invasive technique and is effective in about 70% of the patients who have been implanted with a permanent system. Also, in pelvic pain, interesting results have been described. SNM modulates the micturition reflexes at different levels in the central nervous system. Sacral neuromodulation is a safe and effective therapy for various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. It should be the first choice after failure of maximal conservative therapy.

The central role of renal microcirculatory dysfunction in the pathogenesis of acute kidney injury.

PubMed

Ince, Can

2014-01-01

Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. Injury is caused by inflammatory activation involving endothelial leucocyte interactions in combination with dysregulation of the homeostatis between oxygen, nitric oxide, and reactive oxygen species. Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed. 2014 S. Karger AG, Basel.

Percutaneous endoscopic sigmoid colostomy for irrigation in the management of bowel dysfunction of adults with central neurologic disease.

PubMed

Ramwell, A; Rice-Oxley, M; Bond, A; Simson, J N L

2011-10-01

Bowel dysfunction results in a major lifestyle disruption for many patients with severe central neurologic disease. Percutaneous endoscopic sigmoid colostomy for irrigation (PESCI) allows antegrade irrigation of the distal large bowel for the management of both incontinence and constipation. This study prospectively assessed the safety and efficacy of PESCI. A PESCI tube was placed endoscopically in the sigmoid colon of 25 patients to allow antegrade irrigation. Control of constipation and fecal incontinence was improved for 21 (84%) of the 25 patients. These patients were followed up for 6-83 months (mean, 43 months), with long-term success for 19 (90%) of the patients. No PESCI had to be removed for technical reasons or for PESCI complications. Late removal of the PESCI was necessary for 2 of the 21 patients. A modified St. Marks Fecal Incontinence Score to assess bowel function before and after PESCI showed a highly significant improvement (P < 0.0001). There were no procedure-related deaths. Complications included minor sepsis at the initial PESCI tube site in four patients and bumper migration in two patients, but there were no complications related to the button device. This study showed that PESCI is a simple, safe, and effective technique for distal antegrade irrigation in the management bowel dysfunction for selected patients with central neurologic disease. A successful PESCI is very likely to continue functioning satisfactorily for a long time without technical problems or local complications.

The Boundaries of the Cognitive Phenotype of Autism: Theory of Mind, Central Coherence and Ambiguous Figure Perception in Young People with Autistic Traits

ERIC Educational Resources Information Center

Best, Catherine S.; Moffat, Vivien J.; Power, Michael J.; Owens, David G. C.; Johnstone, Eve C.

2008-01-01

Theory of Mind, Weak Central Coherence and executive dysfunction, were investigated as a function of behavioural markers of autism. This was irrespective of the presence or absence of a diagnosis of an autistic spectrum disorder. Sixty young people completed the Social Communication Questionnaire (SCQ), false belief tests, the block design test,…

A Markov computer simulation model of the economics of neuromuscular blockade in patients with acute respiratory distress syndrome

PubMed Central

Macario, Alex; Chow, John L; Dexter, Franklin

2006-01-01

Background Management of acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) is clinically challenging and costly. Neuromuscular blocking agents may facilitate mechanical ventilation and improve oxygenation, but may result in prolonged recovery of neuromuscular function and acute quadriplegic myopathy syndrome (AQMS). The goal of this study was to address a hypothetical question via computer modeling: Would a reduction in intubation time of 6 hours and/or a reduction in the incidence of AQMS from 25% to 21%, provide enough benefit to justify a drug with an additional expenditure of $267 (the difference in acquisition cost between a generic and brand name neuromuscular blocker)? Methods The base case was a 55 year-old man in the ICU with ARDS who receives neuromuscular blockade for 3.5 days. A Markov model was designed with hypothetical patients in 1 of 6 mutually exclusive health states: ICU-intubated, ICU-extubated, hospital ward, long-term care, home, or death, over a period of 6 months. The net monetary benefit was computed. Results Our computer simulation modeling predicted the mean cost for ARDS patients receiving standard care for 6 months to be $62,238 (5% – 95% percentiles $42,259 – $83,766), with an overall 6-month mortality of 39%. Assuming a ceiling ratio of $35,000, even if a drug (that cost $267 more) hypothetically reduced AQMS from 25% to 21% and decreased intubation time by 6 hours, the net monetary benefit would only equal $137. Conclusion ARDS patients receiving a neuromuscular blocker have a high mortality, and unpredictable outcome, which results in large variability in costs per case. If a patient dies, there is no benefit to any drug that reduces ventilation time or AQMS incidence. A prospective, randomized pharmacoeconomic study of neuromuscular blockers in the ICU to asses AQMS or intubation times is impractical because of the highly variable clinical course of patients with ARDS. PMID:16539706

Neuromuscular electrical stimulation improves exercise tolerance in patients with advanced heart failure on continuous intravenous inotropic support use-randomized controlled trial.

PubMed

Forestieri, Patrícia; Bolzan, Douglas W; Santos, Vinícius B; Moreira, Rita Simone Lopes; de Almeida, Dirceu Rodrigues; Trimer, Renata; de Souza Brito, Flávio; Borghi-Silva, Audrey; de Camargo Carvalho, Antonio Carlos; Arena, Ross; Gomes, Walter J; Guizilini, Solange

2018-01-01

To evaluate the impact of a short-term neuromuscular electrical stimulation program on exercise tolerance in hospitalized patients with advanced heart failure who have suffered an acute decompensation and are under continuous intravenous inotropic support. A randomized controlled study. Initially, 195 patients hospitalized for decompensated heart failure were recruited, but 70 were randomized. Patients were randomized into two groups: control group subject to the usual care ( n = 35); neuromuscular electrical stimulation group ( n = 35) received daily training sessions to both lower extremities for around two weeks. The baseline 6-minute walk test to determine functional capacity was performed 24 hours after hospital admission, and intravenous inotropic support dose was daily checked in all patients. The outcomes were measured in two weeks or at the discharge if the patients were sent back home earlier than two weeks. After losses of follow-up, a total of 49 patients were included and considered for final analysis (control group, n = 25 and neuromuscular electrical stimulation group, n = 24). The neuromuscular electrical stimulation group presented with a higher 6-minute walk test distance compared to the control group after the study protocol (293 ± 34.78 m vs. 265.8 ± 48.53 m, P < 0.001, respectively). Neuromuscular electrical stimulation group also demonstrated a significantly higher dose reduction of dobutamine compared to control group after the study protocol (2.72 ± 1.72 µg/kg/min vs. 3.86 ± 1.61 µg/kg/min, P = 0.001, respectively). A short-term inpatient neuromuscular electrical stimulation rehabilitation protocol improved exercise tolerance and reduced intravenous inotropic support necessity in patients with advanced heart failure suffering a decompensation episode.

Neuromuscular blocking agent administration for emergent tracheal intubation is associated with decreased prevalence of procedure-related complications.

PubMed

Wilcox, Susan R; Bittner, Edward A; Elmer, Jonathan; Seigel, Todd A; Nguyen, Nicole Thuy P; Dhillon, Anahat; Eikermann, Matthias; Schmidt, Ulrich

2012-06-01

Emergent intubation is associated with a high rate of complications. Neuromuscular blocking agents are routinely used in the operating room and emergency department to facilitate intubation. However, use of neuromuscular blocking agents during emergent airway management outside of the operating room and emergency department is controversial. We hypothesized that the use of neuromuscular blocking agents is associated with a decreased prevalence of hypoxemia and reduced rate of procedure-related complications. Five hundred sixty-six patients undergoing emergent intubations in two tertiary care centers, Massachusetts General Hospital, Boston, MA, and the University of California Los Angeles, Ronald Reagan Medical Center, Los Angeles, CA, were enrolled in a prospective, observational study. The 112 patients intubated during cardiopulmonary resuscitation were excluded, leaving 454 patients for analysis. All intubations were supervised by attendings trained in Critical Care Medicine. We measured intubating conditions, oxygen saturation during and 5 mins following intubation. We assessed the prevalence of procedure-related complications defined as esophageal intubation, traumatic intubation, aspiration, dental injury, and endobronchial intubation. The use of neuromuscular blocking agents was associated with a lower prevalence of hypoxemia (10.1% vs. 17.4%, p = .022) and a lower prevalence of procedure-related complications (3.1% vs. 8.3%, p = .012). This association persisted in a multivariate analysis, which controlled for airway grade, sedation, and institution. Use of neuromuscular blocking agents was associated with significantly improved intubating conditions (laryngeal view, p = .014; number of intubation attempts, p = .049). After controlling for the number of intubation attempts and laryngoscopic view, muscle relaxant use is an independent predictor of complications associated with emergency intubation (p = .037), and there is a trend towards improvement of oxygenation (p = .07). The use of neuromuscular blocking agents, when used by intensivists with a high level of training and experience, is associated with a decrease in procedure-related complications.

Reversible central neural hyperexcitability: an electroencephalographic clue to hypocalcaemia.

PubMed

Patel, Bhagyadhan A; Chakor, Rahul T; Kothari, Kaumil V; Nadaf, Swaleha

2017-08-01

A 23-year-old male patient presented with cognitive decline and seizures. Examination revealed Chvostek's and Trousseau's signs. Investigations revealed hypocalcaemia, hyperphosphatemia and normal intact parathyroid hormone levels. Imaging showed calcifications in bilateral basal ganglia, thalamus and dentate nuclei. Interictal electroencephalogram showed theta range slowing of background activity and bilateral temporo-occipital, irregular, sharp and slow wave discharges, which accentuated during hyperventilation, photic stimulation and eye closure. Appearance of epileptiform discharges after eye closure, hyperventilation and photic stimulation may suggest presence of central neural hyperexcitability due to hypocalcaemia. These features may be an equivalent of peripheral neuromuscular hyperexcitability (Chvostek's and Trousseau's signs) that occurs in hypocalcaemia. The clinical and electroencephalographic features completely reversed with correction of serum calcium without antiepileptic medications. It is important for clinicians to recognise these reversible changes, as it can help to avoid misdiagnosis and long-term administration of antiepileptic becomes unnecessary. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy.

PubMed

Patel, Sita Sharan; Udayabanu, M

2013-09-27

Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin (STZ) induced diabetic neuropathy. STZ (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50 mg/kg, oral) and rosiglitazone (5 mg/kg, oral) for 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Undiagnosed neurological disease as a potential cause of male lower urinary tract symptoms.

PubMed

Wei, Diana Y; Drake, Marcus J

2016-01-01

In the central nervous system there are many regulatory processes controlling the lower urinary tract. This review considers the possibility that urinary dysfunction may precede diagnosis of neurological disease. Lower urinary tract symptoms (LUTS) occur early in multiple system atrophy, Parkinson's disease and normal pressure hydrocephalus, and may present before neurological diagnosis. Some people present with LUTS and subsequently are diagnosed with multiple sclerosis or a spinal condition. In male LUTS, the symptoms could reflect early stages of a neurological disease, which has not yet been diagnosed ('occult neurology'). Key symptoms include erectile dysfunction, retrograde ejaculation, enuresis, loss of filling sensation or unexplained stress urinary incontinence. Directed questioning should enquire about visual symptoms, back pain, anosmia, bowel dysfunction and incontinence, or memory loss. Examination features can include resting tremor, 'croaky' speech, abnormal gait, orthostatic hypotension, ataxia, or altered perineal sensation. Imaging, such as MRI scan, should only be requested after expert neurological examination, to ensure the correct parts of the central nervous system are scanned with appropriate radiological protocols. Urologists should consider an undiagnosed neurological condition can be present in a few cases. Any finding should be further evaluated by colleagues with relevant expertise.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

PubMed Central

Patten, Shunmoogum A.; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary A.B.; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J. Alexander

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease. PMID:29202456

[Neuromuscular blocking and respiratory depressing actions of sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate].

PubMed

Cao, B J; Chen, Z K; Chi, Z Q

1990-05-01

The neuromuscular blocking and respiratory depressing actions of the new insecticide sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate (SCD) were investigated. In peroneal-tibialis anterior nerve-muscle preparations of urethane anesthetized rabbit, SCD 6.5 mg/kg iv completely depressed the indirectly elicited twitch tension but not the directly elicited one. This compound also caused initial potentiation of the indirectly elicited twitch tension. In the partially paralyzed preparations, potentiation of contractions occurred following a brief period of indirectly tetanic stimulation. Nereistoxin but not SCD blocked the indirectly elicited twitch tension of isolated rat diaphragm. The neuromuscular blockade induced by SCD and nereistoxin was antagonized by neostigmine and 4-aminopyridine. SCD and nereistoxin had little or no effect on arterial blood pressure and phrenic nerve discharge of rabbits. The results indicated that SCD-poisoned rabbits died of respiratory paralysis following the neuromuscular blockade.

Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

PubMed

Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

2017-11-16

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

Transmitter release in the neuromuscular synapse of the protein kinase C theta-deficient adult mouse.

PubMed

Besalduch, Núria; Santafé, Manel M; Garcia, Neus; Gonzalez, Carmen; Tomás, Marta; Tomás, Josep; Lanuza, Maria A

2011-04-01

We studied structural and functional features of the neuromuscular junction in adult mice (P30) genetically deficient in the protein kinase C (PKC) theta isoform. Confocal and electron microscopy shows that there are no differences in the general morphology of the endplates between PKC theta-deficient and wild-type (WT) mice. Specifically, there is no difference in the density of the synaptic vesicles. However, the myelin sheath is not as thick in the intramuscular nerve fibers of the PKC theta-deficient mice. We found a significant reduction in the size of evoked endplate potentials and in the frequency of spontaneous, asynchronous, miniature endplate potentials in the PKC theta-deficient neuromuscular preparations in comparison with the WT, but the mean amplitude of the spontaneous potentials is not different. These changes indicate that PKC theta has a presynaptic role in the function of adult neuromuscular synapses. Copyright © 2010 Wiley-Liss, Inc.

[Prolonged neuromuscular block in a patient with butyrylcholinesterase deficiency].

PubMed

Mabboux, I; Hary, B; Courcelle, S; Ceppa, F; Delacour, H

2016-05-01

Succinylcholine is a neuromuscular block whose duration of action depends on rapid hydrolysis by butyrylcholinesterase (BChE). In patients with common BChE activities, succinylcholine duration of action is short (10min). BChE deficiency induces a slower hydrolysis of the drug and consequently prolonged neuromuscular block, leading to apnea. We report a case of prolonged neuromuscular block after administration of succinylcholine in a 14-year-old boy. Biological investigations revealed a marked BChE deficiency (1099U/L) related to the presence of three point mutations in the BCHE gene in a compound heterozygous state: p.Asp70Gly (rs1799807), p.Ala539Tyr (rs1803274), and p.Phe118Valfs*12 (rs398124632). The diagnosis of genetic BChE deficiency (OMIM 177400) was retained. This case is intended to present the pathophysiology of genetic BChE deficiency, its management, and the diagnostic strategy to be implemented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interaction of antibiotics on pipecuronium-induced neuromuscular blockade.

PubMed

de Gouw, N E; Crul, J F; Vandermeersch, E; Mulier, J P; van Egmond, J; Van Aken, H

1993-01-01

To measure the interaction of two antibiotics (clindamycin and colistin) on neuromuscular blockade induced by pipecuronium bromide (a new long-acting, steroidal, nondepolarizing neuromuscular blocking drug). Prospective, randomized, placebo-controlled study. Inpatient gynecologic and gastroenterologic service at a university medical center. Three groups of 20 ASA physical status I and II patients with normal kidney and liver function, taking no medication, and undergoing elective surgery under general anesthesia. Anesthesia was induced with propofol and alfentanil intravenously (IV) and maintained with a propofol infusion and 60% nitrous oxide in oxygen. Pipecuronium bromide 50 micrograms/kg was administered after reaching a stable baseline of single-twitch response. At 25% recovery of pipecuronium-induced neuromuscular blockade, patients received one of two antibiotics, clindamycin 300 mg or colistin 1 million IU, or a placebo. The recovery index (RI, defined as time from 25% to 75% recovery of neuromuscular blockade) was measured using the single-twitch response of the adductor pollicis muscle with supramaximal stimulation of the ulnar nerve at the wrist. RI after administration of an antibiotic (given at 25% recovery) was measured and compared with RI of the control group using Student's unpaired t-test. Statistical analyses of the results showed a significant prolongation of the recovery time (from 25% to 75% recovery) of 40 minutes for colistin. When this type of antibiotic is used during anesthesia with pipercuronium as a muscle relaxant, one must be aware of a significant prolongation of an already long-acting neuromuscular blockade and (although not observed in this study) possible problems in antagonism.

Effects of Neuromuscular Training on Children and Young Adults with Down Syndrome: Systematic Review and Meta-Analysis.

PubMed

Sugimoto, Dai; Bowen, Samantha L; Meehan, William P; Stracciolini, Andrea

2016-08-01

To synthesize existing research evidence and examine effects of neuromuscular training on general strength, maximal strength, and functional mobility tasks in children and young adults with Down syndrome. PubMed and EBSCO were used as a data source. To attain the aim of this study, literature search was performed under following inclusion criteria: (1) included participants with Down syndrome, (2) implemented a neuromuscular training intervention and measured outcome variables of general strength, maximal strength, and functional mobility tasks, (3) had a group of participants whose mean ages were under 30 years old, (4) employed a prospective controlled design, and (5) used mean and standard deviations to express the outcome variables. Effect size was calculated from each study based on pre- and post-testing value differences in general strength, maximal strength, and functional mobility tasks between control and intervention groups. The effect size was further classified in to one of the following categories: small, moderate, and large effects. Seven studies met inclusion criteria. Analysis indicated large to moderate effects on general strength, moderate to small effects on maximal strength, and small effect on functional mobility tasks by neuromuscular training. Although there were limited studies, the results showed that neuromuscular training could be used as an effective intervention in children and young adults with Down syndrome. Synthesis of seven reviewed studies indicated that neuromuscular training could be beneficial to optimize general and maximal muscular strength development in children and young adults with Down syndrome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stunted PFC activity during neuromuscular control under stress with obesity.

PubMed

Mehta, Ranjana K

2016-02-01

Obesity is an established risk factor for impaired cognition, which is primarily regulated by the prefrontal cortex (PFC). However, very little is known about the neural pathways that underlie obesity-related declines in neuromuscular control, particularly under stress. The purpose of this study was to determine the role of the PFC on neuromuscular control during handgrip exertions under stress with obesity. Twenty non-obese and obese young adults performed submaximal handgrip exertions in the absence and presence of a concurrent stressful task. Primary dependent measures included oxygenated hemoglobin (HbO2: a measure of PFC activity) and force fluctuations (an indicator of neuromuscular control). Higher HbO2 levels in the PFC were observed in the non-obese compared to the obese group (P = 0.009). In addition, higher HbO2 levels were observed in the stress compared to the control condition in the non-obese group; however, this trend was reversed in the obese group (P = 0.043). In general, force fluctuations increased by 26% in the stress when compared to the control condition (P = 0.001) and obesity was associated with 39% greater force fluctuation (P = 0.024). Finally, while not significant, obesity-related decrements in force fluctuations were magnified under stress (P = 0.063). The current study provides the first evidence that neuromuscular decrements with obesity were associated with impaired PFC activity and this relationship was augmented in stress conditions. These findings are important because they provide new information on obesity-specific changes in brain function associated with neuromuscular control since the knowledge previously focused largely on obesity-specific changes in peripheral muscle capacity.

Effects of mirror therapy combined with neuromuscular electrical stimulation on motor recovery of lower limbs and walking ability of patients with stroke: a randomized controlled study.

PubMed

Xu, Qun; Guo, Feng; Salem, Hassan M Abo; Chen, Hong; Huang, Xiaolin

2017-12-01

To investigate the effectiveness of mirror therapy combined with neuromuscular electrical stimulation in promoting motor recovery of the lower limbs and walking ability in patients suffering from foot drop after stroke. Randomized controlled study. Inpatient rehabilitation center of a teaching hospital. Sixty-nine patients with foot drop. Patients were randomly divided into three groups: control, mirror therapy, and mirror therapy + neuromuscular electrical stimulation. All groups received interventions for 0.5 hours/day and five days/week for four weeks. 10-Meter walk test, Brunnstrom stage of motor recovery of the lower limbs, Modified Ashworth Scale score of plantar flexor spasticity, and passive ankle joint dorsiflexion range of motion were assessed before and after the four-week period. After four weeks of intervention, Brunnstrom stage ( P = 0.04), 10-meter walk test ( P < 0.05), and passive range of motion ( P < 0.05) showed obvious improvements between patients in the mirror therapy and control groups. Patients in the mirror therapy + neuromuscular electrical stimulation group showed better results than those in the mirror therapy group in the 10-meter walk test ( P < 0.05). There was no significant difference in spasticity between patients in the two intervention groups. However, compared with patients in the control group, patients in the mirror therapy + neuromuscular electrical stimulation group showed a significant decrease in spasticity ( P < 0.001). Therapy combining mirror therapy and neuromuscular electrical stimulation may help improve walking ability and reduce spasticity in stroke patients with foot drop.

Is time to peak effect of neuromuscular blocking agents dependent on dose? Testing the concept of buffered diffusion.

PubMed

Proost, J H; Houwertjes, M C; Wierda, J M K H

2008-07-01

For neuromuscular blocking agents, an inverse relationship between potency and time to peak effect has been observed. To test the hypothesis that this relationship is due to buffered diffusion, we investigated the influence of dose on time to peak effect. Pharmacokinetic-pharmacodynamic simulations were performed to support the expected relationships between potency, dose, peak effect and time to peak effect. Pigs (20-28 kg body weight) were anaesthetized with ketamine and midazolam, followed by pentobarbital and fentanyl intravenously. Neuromuscular block was measured by stimulating the peroneal nerve supramaximally at 0.1 Hz and measuring the response of the tibialis anterior muscle mechanomyographically. After an initial dose to establish the individual ED90 of a neuromuscular blocking agent (rocuronium, vecuronium, pipecuronium or d-tubocurarine), five different doses of the same compound were administered to each animal, aiming at 20%, 40%, 60%, 75% or 90% block, in a random order. Doses were given 45 min after complete recovery of the twitch response. For rocuronium and pipecuronium, time to peak effect increased with dose, whereas dose did not affect time to peak effect of vecuronium and d-tubocurarine. Simulations predict that time to peak effect decreases with dose if buffered diffusion is taken into account. The results suggest that buffered diffusion does not play a dominant role in the time to peak effect of neuromuscular blocking agents. Therefore it is unlikely that the observed inverse relationship between potency and time to peak effect of neuromuscular blocking agents in the clinical range is due to buffered diffusion.

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

PubMed Central

Gelfand, Bradley D.; Ambati, Jayakrishna

2016-01-01

Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

Drug-induced sexual dysfunction.

PubMed

Aldridge, S A

1982-01-01

Commonly used drugs that may cause sexual dysfunction are reviewed. The anatomy and physiology of the normal sexual response are reviewed. The influence of drugs on neurogenic, hormonal, and vascular mechanisms may result in diminished libido, impotence, ejaculatory and orgasmic difficulties, inhibited vaginal lubrication, menstrual irregularities, and gynecomastia in men or painful breast enlargement in women. Parasympatholytic agents, which interfere with cholinergic transmission, may affect erectile potency, while adrenergic inhibiting agents may interfere with ejaculatory control. Central nervous system depressants or sedating drugs, drugs producing hyperprolactinemia, and antiandrogenic drugs also may affect the normal sexual response. Drugs such as antihypertensive and antipsychotic agents may induce sexual dysfunction that can result in patient noncompliance. Usually, drug-induced side effects are reversible with discontinuation of the offending agent.

A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters.

PubMed

Tebbi, Cameron; Costanzi, John; Shulman, Robert; Dreisbach, Luke; Jacobs, Brian R; Blaney, Martha; Ashby, Mark; Gillespie, Barbara S; Begelman, Susan M

2011-08-01

To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes. Tenecteplase was administered to 246 patients. Mean patient age was 44 years (range, 0-92 y); 72 patients (29%) were younger than 17 years of age. Chemotherapy was the most common reason for catheter insertion. Restoration of CVC function was achieved in 177 patients (72%) within 120 minutes after the first dose. After instillation of a maximum of two doses of tenecteplase, CVC function was restored in 200 patients (81%), with similar frequencies in pediatric (83%) and adult (80%) patients. Adverse events (AEs) were reported in 31 patients (13%); fever (2%), neutropenia (1%), and nausea (0.8%) were most common. One serious AE, an allergic hypersensitivity reaction, was judged to be related to tenecteplase and/or a chemotherapeutic agent that the patient was receiving concurrently. Consecutive administration of one or two doses of tenecteplase into CVCs showed efficacy in the restoration of catheter function in patients with dysfunctional CVCs. Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.

British Thoracic Society guideline for respiratory management of children with neuromuscular weakness: commentary.

PubMed

Hull, Jeremy

2012-07-01

The British Thoracic Society guideline for respiratory management of children with neuromuscular weakness summarises the available evidence in this field and provides recommendations that will aid healthcare professionals in delivering good quality patient care.

The use of an online support group for neuromuscular disorders: a thematic analysis of message postings.

PubMed

Meade, Oonagh; Buchanan, Heather; Coulson, Neil

2017-06-08

People affected by neuromuscular disorders can experience adverse psychosocial consequences and difficulties accessing information and support. Online support groups provide new opportunities for peer support. The aim of this study was to understand how contributors used the message board function of a newly available neuromuscular disorders online support group. Message postings (n = 1951) from the first five months of the message board of a newly formed online support group for neuromuscular disorders hosted by a charitable organization were analyzed using inductive thematic analysis. Members created a sense of community through disclosing personal information, connecting with people with similar illness experiences or interests, welcoming others and sharing aspirations for the development of a resourceful community. Experiences, emotional reactions and support were shared in relation to: delayed diagnosis; symptom interpretation; illness management and progression; the isolating impact of rare disorders; and the influence of social and political factors on illness experiences. This study provided a novel insight into individuals' experiences of accessing a newly available online support group for rare conditions hosted by a charitable organization. The findings highlight how the online support group provided an important peer support environment for members to connect with others, exchange information and support and engender discussion on political and social issues unique to living with often-rare neuromuscular disorders. Online support groups may therefore provide an important and easily accessible support outlet for people with neuromuscular disorders as well as a platform for empowering members to raise awareness about the impact of living with these conditions. Further research is needed to examine member motivations for using such groups and any effects of participation in greater detail. Implications for rehabilitation Online support groups may provide a unique forum for information sharing and peer support between people affected by often rare, neuromuscular conditions. Rehabilitation professionals may wish to signpost those affected by neuromuscular disorders to such groups. An advantage is that these groups are freely available and can be accessed from anywhere and at any time. Members may be able to learn about the diagnosis and symptom experiences of others, discuss coping strategies, validate illness experiences and discuss social and political issues relating to living with these conditions. Further research is needed before researchers and clinicians can fully understand participants' motivations for, and experiences of, using such groups and any potential psychosocial benefits.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-02-01

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their unpredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-06-01

Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction, many bind to muscarinic cholinergic receptors on ganglia and smooth muscle, and alter parasympathetically mediated heart rate and airway calibre. Most benzylisoquinolinium muscle relaxants can induce histamine release, especially when they are administered rapidly, which can lead to disturbances of cardiovascular function. In addition, nondepolarising neuromuscular blockers have been implicated in causing generalised weakness following their long term administration to patients on an intensive care unit. The problem with these adverse drug reactions is their upredictable nature. Therefore, prompt recognition with appropriate therapy can help to improve the outcome.

The Influence of Robotic Assistance on Reducing Neuromuscular Effort and Fatigue during Extravehicular Activity Glove Use

NASA Technical Reports Server (NTRS)

Madden, Kaci E.; Deshpande, Ashish D.; Peters, Benjamin J.; Rogers, Jonathan M.; Laske, Evan A.; McBryan, Emily R.

2017-01-01

The three-layered, pressurized space suit glove worn by Extravehicular Activity (EVA) crew members during missions commonly causes hand and forearm fatigue. The Spacesuit RoboGlove (SSRG), a Phase VI EVA space suit glove modified with robotic grasp-assist capabilities, has been developed to augment grip strength in order to improve endurance and reduce the risk of injury in astronauts. The overall goals of this study were to i) quantify the neuromuscular modulations that occur in response to wearing a conventional Phase VI space suit glove (SSG) during a fatiguing task, and ii) determine the efficacy of Spacesuit RoboGlove (SSRG) in reversing the adverse neuromuscular modulations and restoring altered muscular activity to barehanded levels. Six subjects performed a fatigue sequence consisting of repetitive dynamic-gripping interspersed with isometric grip-holds under three conditions: barehanded, wearing pressurized SSG, and wearing pressurized SSRG. Surface electromyography (sEMG) from six forearm muscles (flexor digitorum superficialis (FDS), flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), extensor digitorum (ED), extensor carpi radialis longus (ECRL), and extensor carpi ulnaris (ECU)) and subjective fatigue ratings were collected during each condition. Trends in amplitude and spectral distributions of the sEMG signals were used to derive metrics quantifying neuromuscular effort and fatigue that were compared across the glove conditions. Results showed that by augmenting finger flexion, the SSRG successfully reduced the neuromuscular effort needed to close the fingers of the space suit glove in more than half of subjects during two types of tasks. However, the SSRG required more neuromuscular effort to extend the fingers compared to a conventional SSG in many subjects. Psychologically, the SSRG aided subjects in feeling less fatigued during short periods of intense work compared to the SSG. The results of this study reveal the promise of the SSRG as a grasp-assist device that can improve astronaut performance and reduce the risk of injury by offsetting neuromuscular effort. Modifications to the experimental protocol are needed, however, to improve the outcome of the neuromuscular fatigue metrics and determine the effectiveness of SSRG in increasing astronaut endurance. Nevertheless, these findings will improve the understanding of astronaut-spacesuit interaction and provide direction toward designing improved spacesuit gloves and robotic-assist devices, like the SSRG.

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia.

PubMed

Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J; Robinson, Benjamin M; Ruffle, Abigail; Hahn, Britta; Gold, James M; Luck, Steven J

2017-04-05

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia. Copyright © 2017 the authors 0270-6474/17/373813-11$15.00/0.

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia

PubMed Central

Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J.; Robinson, Benjamin M.; Ruffle, Abigail; Hahn, Britta; Gold, James M.

2017-01-01

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia. PMID:28283557