Creatine phosphokinase level in neuromuscular disorders. Effect of dilution and dialysis

Serum creatine phosphokinase (CPK) activity has been shown to be greatly altered following dilution as well as dialysis in neuromuscular disorders like Duchenne MD, dermatomyositis and in one case of spinal muscular atrophy. Under similar experimental conditions, there is no such great variation in serum CPK levels in other neuromuscular disorders or in normal controls. The implications of these results are discussed.     

New medicine for neuromuscular diseases: An evolving paradox for patient and family hopes and expectations

Recent developments in novel therapies for neuromuscular diseases offer parents new perspectives on their affected children's future. This article examines how the emergence of new therapies impacts the lives of parents of children with Duchenne muscular dystrophy or spinal muscular atrophy type 2, two genetic neuromuscular disorders characterized by progressive muscle degeneration. Aiming for a first-person perspective, fieldwork was conducted utilizing participant observation, semistructured interviews, and several internet sources. Six families with a total of 12 persons, all living in Denmark, were included in the interviews. Two types of parents were identified who were at opposite ends in dealing with the new therapies—the cure optimists and the cure pragmatists. Different hopes resulted in different narratives for their children's futures. The article raises questions about how and when children with chronic diseases should be involved in their parent's hopes for a cure and highlights the dilemmas facing health professionals working in the field of children with chronic diseases for which the prospects of a cure are improving. We conclude that health professionals must find a way to carefully balance guidance and information about experimental medicines, including the fact that experimental medicine sometimes fails, does not work as well as hoped for, or does not become available, with sustaining parental hopes for their children's future.     

High-frequency chest-wall oscillation in a noninvasive-ventilation-dependent patient with type 1 spinal muscular atrophy

With the recent increased use of noninvasive ventilation, the prognoses of children with neuromuscular disease has improved significantly. However, children with muscle weakness remain at risk for recurrent respiratory infection and atelectasis. We report the case of a young girl with type 1 spinal muscular atrophy who was dependent on noninvasive ventilation, and in whom conventional secretion-clearance physiotherapy became insufficient to clear secretions. We initiated high-frequency chest-wall oscillation (HFCWO) as a rescue therapy, and she had improved self-ventilation time. This is the first case report of HFCWO for secretion clearance in a severely weak child with type 1 spinal muscular atrophy. In a patient with neuromuscular disease and severe respiratory infection and compromise, HFCWO can be used safely in combination with conventional secretion-clearance physiotherapy.     

Echocardiography in storage and neuromuscular disorders

Storage disorders and neuromuscular disorders may lead to cardiac involvement which can be visualized by echocardiography. In storage disorders like hypothyroidism, haemochromatosis, amyloidosis, mucopolysaccharidosis and Fabry's disease, myocardial thickening and systolic dysfunction can be found. In amyloidosis, atrial enlargement and abnormal texture of the myocardium are additional findings. In advanced haemochromatosis all cardiac chambers may be dilated. In hypothyroidism and amyloidosis, a pericardial effusion can be present. In haemochromatosis and amyloidosis, a restrictive filling pattern may be detected using Doppler-sonography. Mucopolysaccharidosis and Gaucher's disease may lead to aortic and mitral stenosis. In neuromuscular disorders like glycogenosis, mitochondriopathy and myotonic dystrophy, myocardial thickening and systolic dysfunction are found, in spinal muscular atrophy myocardial thickening and in muscular dystrophy Becker/Duchenne systolic dysfunction. An abnormal myocardial texture may be present in glycogenosis, isolated left ventricular abnormal trabeculation (ILVAT) in mitochondriopathy, myotonic dystrophy and muscular dystrophy Becker/Duchenne. Using Doppler-sonography an impaired relaxation of the left ventricle may be detected in mitochondriopathy, myotonic dystrophy and spinal muscular atrophy. Most of these echocardiographic findings are unspecific and may be overlooked, especially if the storage or neuromuscular disorder is yet unknown. Establishing a correct diagnosis is important, since healing or functional improvement is possible in many of these disorders.     

High-frequency ultrasonography of skeletal muscle in children with neuromuscular disease.

Ultrasonography of the thigh and calf was performed in 24 children who had primary neuromuscular disease and in 20 healthy children. The ultrasound image was clearly abnormal in all patients with progressive muscular dystrophy, and in the majority of children with benign myopathic disorders; the principal changes were increased muscular echogenicity and increased attenuation of ultrasound with a reduced bone surface echo. In 13 patients, the ultrasound findings were correlated with pathologic changes seen in muscle biopsy specimens: a clear correlation (r = .85) was found. Muscular dystrophies had a higher score of abnormal ultrasonographic and microscopic findings, while the more benign muscular diseases had a lower score.     

Respirator use in progressive neuromuscular diseases

A survey was conducted to acquire information on the current pattern of respiratory device usage for patients with progressive neuromuscular diseases. Questionnaires were sent to 240 directors of Muscular Dystrophy Association (MDA) clinics. Of the 132 respondents, 32 (24%) physicians provide no respiratory support systems, 44 (33%) prescribe such systems routinely, and 56 (42%) provide the devices under specialized circumstances. A wide variety of negative and positive pressure ventilators are employed for patients having diseases such as amyotropic lateral sclerosis, Duchenne muscular dystrophy, spinal muscular atrophy. In the MDA clinics responding, 495 patients were found to be receiving some form of assisted ventilation. Of that number, 214 (43%) have permanent tracheostomies. We conclude that ventilators are being supplied to individuals with progressive neuromuscular disorders throughout the USA. However, there appear to be no standardized patient selection process or established protocol for respirator use in such cases.     

The progress of AAV-mediated gene therapy in neuromuscular disorders

Introduction: The well-defined genetic causes and monogenetic nature of many neuromuscular disorders, including Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), present gene therapy as a prominent therapeutic approach. The novel variants of adeno-associated virus (AAV) can achieve satisfactory transduction efficiency of exogenous genes through the central nervous system and body-wide in skeletal muscle.

Areas covered: In this review, we summarize the strategies of AAV gene therapy that are currently under preclinical and clinical evaluation for the treatment of degenerative neuromuscular disorders, with a focus on diseases such as DMD and SMA. In addition to gene replacement strategy, we provide an overview of other approaches such as AAV-mediated RNA therapy and gene editing in the treatment of muscular dystrophies.

Expert opinion: AAV gene therapy has achieved striking therapeutic efficacy in clinical trials in infants with SMA. Promising results have also come from the preclinical studies in small and large animal models of DMD and several clinical trials are now on the way. This strategy shows great potential as a therapy for various neuromuscular disorders. Further studies are still required to confirm its long-term safety and improve the efficacy.     

Physical medicine respiratory muscle aids to avert respiratory complications of pediatric chest wall and vertebral deformity and muscle dysfunction

The purpose of this article was to describe the use of noninvasive inspiratory and expiratory muscle aids to prevent chest wall deformities including pectus excavatum, to prevent respiratory complications of vertebral surgery, to prevent acute and long-term ventilatory insufficiency and failure in children with paralytic disorders who develop these deformities, and to permit the extubation and tracheostomy tube decanulation of "unweanable" patients. Noninvasive airway pressure aids can provide up to continuous ventilator support for patients with little or no vital capacity and can provide for effective cough flows for patients with severely dysfunctional expiratory muscles. An April 2010 consensus of clinicians from 20 centers in 14 countries reported over 1500 spinal muscular atrophy type 1 (SMA1), Duchenne muscular dystrophy (DMD), and amyotrophic lateral sclerosis (ALS) patients who survived using continuous ventilatory support without tracheostomy tubes. Four of the centers routinely extubated unweanable DMD patients so that none of their over 250 such patients has undergone tracheotomy.     

Bilateral multifocal muscular hemorrhage in the triceps surae during antiplatelet therapy: a case report

Hemorrhagic complications are often reported following antiplatelet therapy; however, simultaneous multifocal hemorrhages in both legs are uncommon. The patient was a 75-year-old man diagnosed with ST elevation myocardial infarction who underwent percutaneous coronary intervention in the right coronary artery. He was prescribed oral acetylsalicylic acid and ticagrelor. Three days after initial drug treatment, he complained of bilateral leg pain that was aggravated by walking and moving his ankle across a broad range of motion. No deep vein thrombosis was detected on Doppler ultrasonography; however, muscular hemorrhage was suspected according to musculoskeletal ultrasonography. Multifocal muscular hemorrhage was confirmed in the soleus and gastrocnemius muscles on magnetic resonance imaging. To reduce the risk of bleeding, we changed the medication from ticagrelor to clopidogrel. The patient performed leg elevation exercises, compression, and applied an ice pack. He also performed range of motion exercises and gait training in addition to receiving drug treatment. With these therapies, his pain score improved from 5 to 3 on a visual analog scale, without further complications. Multifocal muscular hemorrhage rarely occurs bilaterally; however, when it does occur, an appropriate treatment plan can be developed based on musculoskeletal ultrasonography.     

Non-invasive assessment of motor unit activation in relation to motor neuron level and lesion location in stroke and spinal muscular atrophy

BackgroundNeuromuscular disorders e.g. spinal muscular atrophy and stroke have a negative impact on functional movement capability. These disorders affect lower and upper motor neurons respectively.MethodsIn this study high spatial resolution electromyography was used to record the motor unit activity in 3 groups: healthy subjects, a spinal muscular atrophy group and a stroke group. 7 clinically sensitive parameters were used to analyze the activation patterns of a few motor units.FindingsIn the case of spinal muscular atrophy there was no effect on motor unit activation but on their number. Stroke was characterized by fewer active motor units and a significantly reduced firing rate with low variability.InterpretationThe results suggest, that for stroke, information from the brain is modified thereby resulting in motor units firing at their natural frequency. Thus, high spatial resolution electromyography and the chosen parameters facilitate non-invasive, objective differentiation and analysis of the activation patterns of motor units in neuromuscular disorders.     

Real-time ultrasonography in neuromuscular problems in children

Ultrasound imaging of 20 cases of progressive muscular dystrophy and 10 cases of suspected infantile spinal muscular atrophy in children was performed by us, as a double-blind plot study matched against 25 controls. Open muscle biopsy was restricted to the muscular dystrophy group. The ultrasonographic findings were correlated with parameters such as functional disability of muscle and muscle biopsy features in the dystrophy group. It was interesting to observe that the muscle echogram was abnormal in both types of neuromuscular problems, the controls giving a normal muscle echogram. Ultrasonography was helpful in detection of unequivocal changes in our cases with mild clinical disability. It had a close correlation with changes in gross muscle architecture, as seen on muscle biopsy.     

Medical Complications of Spinal Cord Injury

Recent medical advances have greatly improved the prognosisfor people who sustain spinal cord injury (about 10000 peopleinitially survive spinal cord injury each year in the US). Physiciansmay become involved with the acute care of spinal cord injuredpersons or care for complications which develop later. Certainconditions such as heterotopic bone formation and autonomicdysreflexia are seen almost exclusively in this group of patients;other complications such as urinary tract and soft tissue infectionsoccur quite often. Common medical complications of spinal cordinjured persons are reviewed, as well as their diagnosis andtreatment.     

The changing role of pediatric electrodiagnosis

Electrodiagnosis is one of several useful diagnostic tests in infants and children who have anterior horn cell disease, neuropathy, neuromuscular junction disorders, or myopathy. It is also used for intraoperative monitoring in children. For hypotonic infants and for older children with a nonspecific presentation of weakness, EDX may provide direction for more specific diagnostic testing, such as DNA testing with or without muscle biopsy. Genetic testing has an increasingly important role in the diagnosis of children with neuromuscular disorders. Future improvements in motor unit quantitation, which do not require active patient cooperation and require less time than current methodologies, may make EDX more specific and useful for diagnosing neuromuscular disease in children.     

Medical complications of spinal cord injury

Recent medical advances have greatly improved the prognosis for people who sustain spinal cord injury (about 10 000 people initially survive spinal cord injury each year in the US). Physicians may become involved with the acute care of spinal cord injured persons or care for complications which develop later. Certain conditions such as heterotopic bone formation and autonomic dysreflexia are seen almost exclusively in this group of patients; other complications such as urinary tract and soft tissue infections occur quite often. Common medical complications of spinal cord injured persons are reviewed, as well as their diagnosis and treatment.     

Manuelle Medizin bei kindlichen muskuloskelettalen Schmerzen

The incidence and intensity of musculoskeletal pain are the same in both children and adults. Thus, a diagnosis should be made and treatment begun using the same ethical and professional guidelines. The suffering of children, however, is often not taken seriously. There is no chronic or recurring musculoskeletal pain without muscular reactions. Although the motor system is not always the etiological source of pain, muscular dysfunction as part of the pain symptoms can be used for diagnostic and therapeutic purposes. So far, the indications experienced in manual medicine have been painful tonus imbalance in babies, tension headache, migraine, functional stomach ache, limb pain, back and neck pain, and pain in the knee and heel.     

Vivre et vieillir avec la poliomyélite

More than 50,000 people are affected by the consequences of poliomyelitis in France. After the recovery phase, neuromuscular effects caused by poliomyelitis are considered stable but patients suffer from late complications that affect the musculoskeletal, neuromuscular and cardio-respiratory systems. New symptoms such as pain, fatigue and weakness occur and affect quality of life. A medical follow-up is justified in cases of late complications of poliomyelitis. Rehabilitation may be necessary and coping strategies are also recommended in cases of fatigue and overwork.     

Respiratory disorders in neurologic diseases

Various neurologic diseases such as multiple sclerosis and Parkinson disease can cause pulmonary complications. Pulmonary disorders often manifest late in a neuromuscular disease, but occasionally a respiratory problem may be the first sign. Often the first signs are sleep disturbances and nocturnal desaturation. Although the diseases are diverse, common principles apply in their management.     

Bilateral dorsal foot pain in a young tennis player managed by neurodynamic treatment techniques

Exercise-related lower limb pain represents one of the most common presentations in sports medicine practice. This is usually caused by musculoskeletal overuse injuries but not uncommonly, a neuropathic cause may be suspected. A review of the literature revealed that peripheral neuropathic pain has never been documented in a child. It is possible that peripheral neuropathic pain of spinal origin may be more prevalent in children than previously recognized. This case report describes the presentation of a 12 year old tennis player with bilateral dorsal foot pain, who presented with positive findings of peripheral nerve sensitization which was successfully managed using neurodynamic treatment techniques. Differential diagnoses are considered and treatment and management described. A discussion of the clinical reasoning which led to the patient’s diagnosis is included. This case report suggests the effectiveness of neurodynamic treatment in a child with bilateral foot pain who fulfilled published criteria for peripheral nerve sensitization. However, the single case methodology employed in this study limits generalization of its findings. Further studies are warranted to investigate the role of neurodynamics in musculoskeletal pain disorders in children.     

Muscle ultrasound in children: normal values and application to neuromuscular disorders

In this study, 105 healthy children (45 to 156 months old, 57 girls) were examined using ultrasound (US) imaging to obtain reference values of muscle dimensional and aspect parameters. We measured biceps and quadriceps sizes and subcutaneous tissue thickness. To quantify muscle aspect, we calculated muscle density, inhomogeneity and white-area index by digital image analysis. Age-, weight- and gender-dependencies were discussed. We demonstrated earlier that the complete set of parameters allows for differentiation between myopathies and neuropathies in adults, with high sensitivity. In this study, we investigated if these parameters have additional value in the diagnostic evaluation of 36 children with proven neuromuscular disease (20 Duchenne muscular dystrophy, 16 neuropathies). We found that density analysis provides a sensitive method for distinguishing between healthy children and children with neuromuscular disorders. We have also found that more detailed aspect analysis is necessary to further distinguish between these types of neuromuscular disorders in children. In conclusion, this set of normal muscle parameters can be used to help diagnose neuromuscular disorders in children. It will also facilitate follow-up in disease progression and therapy.     

Glyoxalase enzyme system in human muscular dystrophy.

Glyoxalase I and glyoxalase II activities were determined in skeletal muscle of control subjects and of patients with Duchenne dystrophy, other major forms of muscular dystrophies and certain neuromuscular disorders. The glyoxalase I activity was normal in all diseases examined except in Duchenne and limb girdle types of muscular dystrophy, where it showed a significant moderate decrease. The glyoxalase II activity in normal human muscle was very low, and the activity was unaltered in muscle of patients with Duchenne and other major forms of muscular dystrophies and spinal muscular atrophy. The selective decrease of glyoxalase I activity in recessively inherited muscular dystrophies may have some relevance to some phases of these disease processes.