Respiratory muscle training in neuromuscular disease: a systematic review and meta-analysis.

BACKGROUND: Neuromuscular disease causes a progressive decline in ventilatory function which respiratory muscle training may address. Previous systematic reviews have focussed on single diseases, whereas this study systematically reviewed the collective evidence for respiratory muscle training in children and adults with any neuromuscular disease. METHODS: Seven databases were searched for randomised controlled trials. Three reviewers independently reviewed eligibility, extracted characteristics, results, determined risk of bias and combined results using narrative synthesis and meta-analysis. RESULTS: 37 studies (40 publications from 1986-2021, n=951 participants) were included. Respiratory muscle training improved forced vital capacity (standardised mean difference (SMD) 0.40 (95% confidence interval 0.12-0.69)), maximal inspiratory (SMD 0.53 (0.21-0.85)) and maximal expiratory pressure (SMD 0.70 (0.35-1.04)) compared to control (usual care, sham or alternative treatment). No impact on cough, dyspnoea, voice, physical capacity or quality of life was detected. There was high degree of variability between studies. DISCUSSION: Study heterogeneity (children and adults, different diseases, interventions, dosage and comparators) suggests that the results should be interpreted with caution. Including all neuromuscular diseases increased the evidence pool and tested the intervention overall. CONCLUSIONS: Respiratory muscle training improves lung volumes and respiratory muscle strength in neuromuscular disease, but confidence is tempered by limitations in the underlying research.

Intermittent Abdominal Pressure Ventilation: An Alternative for Respiratory Support.

Intermittent abdominal pressure ventilation is a positive pressure ventilation technique that works with abdominal compressions. It has been known since 1938; however, for many years, it was out of production. In recent years, a new device has been produced that has captured the attention to this old respiratory support technique. We considered eight patients with respiratory failure secondary to a neuromuscular disease (congenital myopathy, Duchenne dystrophy, and amyotrophic lateral sclerosis) intolerant to daytime noninvasive ventilation (NIV). IAPV was proposed as an alternative to NIV. We performed baseline and post-IAPV respiratory function assessment. All patients, two years later, are still using intermittent abdominal ventilation. Intermittent positive abdominal mechanical ventilation can be a valid alternative to noninvasive mechanical ventilation with a nasal or face mask. It improves gas exchange, symptoms, and quality of life, decreases the incidence of pneumonia, and can avert the need for intubation and tracheotomy.

Taste disorder in facial onset sensory and motor neuronopathy: a case report.

BACKGROUND: Taste disorder is a common symptom in the general population. Several studies have shown that patients with neurological disorders, such as amyotrophic lateral sclerosis and Parkinson's disease, develop taste disturbance. Facial onset sensory and motor neuronopathy (FOSMN) is a rare disease characterized by sensory disturbance and weakness spreading from the face to the limbs caudally. We describe a patient with FOSMN who showed taste disorder as the sole initial symptom. CASE PRESENTATION: A 49-year-old man who smoked cigarettes developed taste disturbance. Despite using zinc supplements, an herbal medication, and an ointment, his taste disorder worsened. 4 years later, a tingling feeling emerged at the tip of his tongue and gradually spread to his entire lips. At 55 years of age, he showed difficulty in swallowing, followed by facial paresthesia, muscle atrophy, and weakness in the face and upper limbs without apparent upper motor neuron sign. Cessation of smoking did not improve his taste disturbance, and he was unable to discriminate different tastes on the entire tongue. In an electrogustometric study, electrical stimulation did not induce any type of taste sensation. Blink reflex showed delayed or diminished R2 responses. Needle electromyography revealed severe chronic neurogenic changes in the tongue and masseter muscles. Mild chronic neurogenic changes were also observed in the limbs. In the thoracic paraspinal muscles, active neurogenic changes were detected. Findings of hematological and cerebrospinal fluid analyses, and magnetic resonance images of the brain and spinal cord were unremarkable. One cycle of intravenous immunoglobulin therapy did not improve his symptoms. We diagnosed him as having FOSMN with the sole initial symptom of taste disorder. Nine years after the onset of taste disorder, he developed impaired sensation of touch in the right upper limb and required tube feeding and ventilator support. CONCLUSION: Taste disorder can be the initial manifestation of FOSMN and might involve the solitary nucleus.

Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease.

Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental results and are at different stages of regulatory approval. The antisense oligonucleotides can modulate the protein expression via targeting hnRNAs or mRNAs and inducing interference with splicing, mRNA degradation, or arrest of translation, finally, resulting in rescue or reduction of the target protein expression. Different classes of antisense oligonucleotides are being tested in several clinical trials, and limitations of their clinical efficacy and toxicity have been reported for some of these compounds, while more encouraging results have supported the development of others. New generation antisense oligonucleotides are also being tested in preclinical models together with specific delivery systems that could allow some of the limitations of current antisense oligonucleotides to be overcome, to improve the cell penetration, to achieve more robust target engagement, and hopefully also be associated with acceptable toxicity. This review article describes the chemical properties and molecular mechanisms of action of the antisense oligonucleotides and the therapeutic implications these compounds have in neuromuscular diseases. Current strategies and carrier systems available for the oligonucleotides delivery will be also described to provide an overview on the past, present and future of these appealing molecules.

Diagnosis and management of adult hereditary cardio-neuromuscular disorders: A model for the multidisciplinary care of complex genetic disorders.

Genetic disorders that disrupt the structure and function of the cardiovascular system and the peripheral nervous system are common enough to be encountered in routine cardiovascular practice. Although often these patients are diagnosed in childhood and come to the cardiologist fully characterized, some patients with hereditary neuromuscular disease may not manifest until adulthood and will present initially to the adult cardiologist for an evaluation of an abnormal ECG, unexplained syncope, LV hypertrophy, and or a dilated cardiomyopathy of unknown cause. Cardiologists are often ill-equipped to manage these patients due to lack of training and exposure as well as the complete absence of practice guidelines to aid in the diagnosis and management of these disorders. Here, we review three key neuromuscular diseases that affect the cardiovascular system in adults (myotonic dystrophy type 1, Friedreich ataxia, and Emery-Dreifuss muscular dystrophy), with an emphasis on their clinical presentation, genetic and molecular pathogenesis, and recent important research on medical and interventional treatments. We also advocate the development of interdisciplinary cardio-neuromuscular clinics to optimize the care for these patients.

[Case Report - Really a diving accident?]. / Kasuistik - Tatsächlich ein Tauchunfall?

A 17 y old male SCUBA diver presents himself for hospital admission after a suspected diving accident. All clinical signs are favouring the initial diagnosis: loss of leg motor function, paresthesia, disturbed vision and headache. What are your further diagnostic and therapeutic steps? Can you proof the initial diagnosis? What differential diagnoses are relevant or even mimicked?

Effect of therapeutic horseback riding on balance in community-dwelling older adults with balance deficits.

OBJECTIVES: Falls are an important cause of morbidity in older adults. Equine-assisted activities including therapeutic riding (TR) benefit balance and neuromuscular control in patients with neurological disabilities but have not been systematically studied in older adults at greater risk for falls due to balance deficits. The effect of an 8-week TR program on measures of balance and quality of life in community-dwelling older adults with established balance deficits was evaluated. DESIGN: This was a pretest-post-test single-group trial of a TR program on measures of balance and quality of life. SETTING: The study was conducted at a Professional Association of Therapeutic Horsemanship (PATH) International Premier riding center. SUBJECTS: The subjects comprised 9 adults (5 female, 4 males) with a mean age 76.4 years (range 71-83 years). INTERVENTIONS: This included an 8-week observation period followed by an 8-week TR program consisting of 1 hour per week of supervised horseback riding and an 8-week follow-up period. SUBJECTS received balance testing at weeks 0, 8, 16, and 24 using the Fullerton Advanced Balance Scale (FABS), and quality of life was measured at weeks 8 and 16 using the Rand SF (short form) 36 quality-of-life measure. OUTCOME MEASURES: OUTCOME MEASURES were change in the FABS and Rand SF 36. RESULTS: There was no significant difference in balance scores between the start and end of the observation period. There was a significant improvement in the balance score and perception of general health from the start to the end of the intervention period, and no significant difference between the end of the intervention and the end of study, suggesting that improvements may have been sustained. CONCLUSIONS: TR is a safe activity for older adults with mild to moderate balance deficits and leads to both improvements in balance and quality of life. Longer and larger studies to assess the benefit of equine-assisted activities on improvements in balance and reduction in fall risk are needed.

Hospital readmissions and repeat emergency department visits among children with medical complexity: an integrative review.

Children with medical complexity (CMC) have chronic conditions, intense healthcare needs, and high healthcare utilization. Proposed changes in the healthcare environment initiated by the Affordable Care Act have led to efforts toward preventing hospital readmissions. The purpose of this integrative review is to explore the current empirical literature and examine how hospital readmissions and repeat emergency department visits have been studied among CMC. A computer database search and ancestry search were conducted, resulting in a sample of 26 studies. The results of the integrative review are presented along with gaps in the literature and implications for nursing practice and research.

[Comparison of treatment results of idiopathic and non-idiopathic congenital clubfoot : prospective evaluation of the Ponseti therapy]. / Vergleich der Behandlungsergebnisse bei kongenitalen idiopathischen und nichtidiopathischen Klumpfüßen : Prospektive Evaluation der Ponseti-Therapie.

BACKGROUND: Clubfoot deformity is one of the most common congenital musculoskeletal deformities and occurs in newborns with different neuromuscular diseases. To date the Ponseti method is the gold standard for the treatment of idiopathic clubfeet but not for non-idiopathic clubfeet which are associated with neuromuscular diseases. The results of the treatment for congenital idiopathic and non-idiopathic clubfeet according to Ponseti performed in our department since 2004 were compared concerning results and relapse surgery with particular reference to the compliance of the parents concerning the use of an abduction splint. PATIENTS AND METHODS: A total of 101 children (28 female and 73 male) with 159 clubfeet were treated with the Ponseti method and included in this prospective non-randomized cohort study. Of these children 27 with 48 affected feet suffered from neuromuscular diseases which are associated with clubfoot deformity, such as myelomeningocele (n=4), arthrogryposis (n=9) and various other syndromes (n=14). The degree of the deformity was evaluated with the Pirani score initially, after casting and at follow-up. Parents were asked at follow-up to state subjectively how compliant they were with the abduction splint treatment. The necessity of surgical treatment of relapses was recorded. Statistical analysis was performed applying χ(2) and Kruskal-Wallis tests for the comparison of idiopathic and non-idiopathic clubfeet. RESULTS: The average period of follow-up was 36 month (range 6-75 months) and non-idiopathic clubfeet were initially significantly more severely deformed according to the Pirani-score (p=0.013). Treatment of non-idiopathic clubfeet was started significantly later than that of idiopathic clubfeet (p=0.003) and took significantly longer (p <0.001). A correlation between the initiation of casting and the duration of casting was not found (p=0.399). At the end of the casting period no significant differences were found between correction of idiopathic and non-idiopathic clubfeet with respect to the Pirani score (p=0.8). The mean score after casting was 0.1 in both groups. At mid-term follow-up the score increased in both groups but stayed below 0.5 with non-idiopathic clubfeet showing a significantly higher score than idiopathic clubfeet (p=0.014). Relapse surgery was necessary in 11% of the patients. No significant difference in the revision rate was found between the two groups (p=0.331) and peritalar release was not necessary in either group. The rate of revisions correlated with the compliance concerning the use of the abduction splint (p <0.001). Only 61% of the parents stated that they adhered strictly to the abduction splint treatment recommendations with no significant difference between the groups (p=0.398). CONCLUSION: This study shows good initial results after Ponseti treatment for idiopathic as well as non-idiopathic clubfeet. Based on the good functional results all clubfeet should initially be treated with the Ponseti method regardless of the etiology.

A one-page orofacial myofunctional assessment form: a proposal.

The author presents her own proposal of a one-page orofacial myofunctional assessment and for each item on the list a brief rationale is provided. The protocol is an easy but comprehensive form that can be faxed or emailed to referral sources as needed. As science provides more objective assessment and evaluation tools, this one-page form can be easily modified.

Renal, ocular, and neuromuscular involvements in patients with CLDN19 mutations.

BACKGROUND AND OBJECTIVES: The objective of this study was to describe the renal and extrarenal findings in patients with recessively inherited familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) associated with CLDN19 mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Medical records of three patients from two French unrelated families with CLDN19 mutations were retrospectively examined. RESULTS: Direct sequencing of CLDN19 identified a known variant (p.Gly20Asp) in all patients and a new missense mutation (p.Val44Met) in one (compound heterozygous). The patients' renal phenotype closely mimicked CLDN16-related nephropathy: low serum Mg2+ (<0.65 mmol/L) despite oral supplementation, hypercalciuria partly thiazide-sensitive, and progressive renal decline with ESRD reached at age 16 and 22 years in two individuals. Primary characteristics (failure to thrive, recurrent urinary tract infections, or abdominal pain), age at onset (0.8 to 16 years), and rate of renal decline were highly heterogeneous. Ocular involvement was identified in all patients, although two patients did not have visual loss. Additionally, exercise intolerance with pain, weakness, and electromyographical alterations mimicking a Ca2+/K+ channelopathy (pattern V) were observed in two of three individuals. These features persisted despite the normalization of serum K+ and Mg2+ after renal transplantation. CONCLUSIONS: Ocular manifestations, even subtle, and exercise intolerance mimicking mild to moderate periodic paralysis are two symptoms that need to be searched for in patients with FHHNC and may indicate CLDN19 mutations.

Impaired laryngeal mobility and entrapment neuropathies.

Entrapment neuropathies are rarely mentioned in phoniatrics because a definite diagnosis is very difficult to make. However, several clinical examples described here strongly support this etiology, which should now be considered in the diagnosis of both partial and complete laryngeal immobility as well as in minor neuromuscular disorders.

Recomendaciones para los cuidados respiratorios del niño y adolescente con enfermedades neuromusculares / Respiratory care for the children and adolescents with neuromuscular diseases

El compromiso del sistema respiratorio repercute directamente en la morbimortalidad de niños y adolescentes con enfermedades neuromusculares (ENM). Un enfoque integral que incluya la aproximación a un diagnostico neurológico específico, evaluación funcional respiratoria, de los trastornos respiratorios de sueño, comorbilidades y afecciones secundarias, permiten orientar a el tipo, grado y pronóstico respiratorio; además de otorgar herramientas objetivas para modificar la historia natural de la enfermedad. Utilizar criterios estrictos de selección, una mirada interdisciplinaria y actividades complementarias de rehabilitación; que incorporen en forma programática la ventilación no invasiva domiciliaria, protocolos de tos asistida y métodos para aumentar la capacidad máxima de insuflación, cambia la evolución, disminuye la morbimortalidad y evita la traqueostomía, en una alta proporción de niños y adolescentes portadores de ENM.

Are auricular maps reliable for chronic musculoskeletal pain disorders? A double-blind evaluation.

AIM: To examine the proposed somatotopic relation between the regions in which patients report musculoskeletal pain and tender points located on the external ears according to a map based on commonly used auricular acupuncture maps. METHODS: Twenty-five patients (16 women) from a chronic pain clinic were included. Patients were asked, before examination of the external ears, if they had past or present musculoskeletal pain in any of 11 body regions. An ear map, collapsed into 11 zones representing the musculoskeletal system, was used. The ear examiner was blinded to the patients' pain conditions, medical history and ongoing treatment. Patients communicated with the examiner only to express if tenderness was present in the external ear on palpation using a spring-loaded pressure stylus commonly used for auricular acupuncture. The degree of tenderness was registered on a 5-point scale and dichotomised (no tenderness or tenderness). Agreements between the patients' painful body regions and tenderness in the external ear zones were presented as percentage, kappa values, sensitivity and specificity. RESULTS: The 25 patients reported 116 past or present musculoskeletal pain regions and had 110 tender ear zones. No statistically significant agreements were found between the painful body regions and the corresponding tender ear zones. CONCLUSIONS: Our results did not show agreements between patients' reported musculoskeletal pain regions and tender zones in the external ears assessed according to commonly used maps in auricular acupuncture using a pressure stylus. However, very tender points occur on the external ear in a population with chronic musculoskeletal pain.

Management of the child with weakness.

With increased life expectancy associated with improved respiratory care and research advances in pediatric neuromuscular diseases leading to clinical trials involving potential curative treatments, the goal in the care of the child with weakness is to optimize survival and quality of life. The care of the child with weakness includes management of motor dysfunction because of weakness, orthopedic complications of contractures and scoliosis, and comorbid complications specific to each neuromuscular disease. Optimal holistic integrative care of the multisystemic problems of such patients is best provided by the collaborative efforts of health care providers of an interdisciplinary team.

IX Antonio Arrigo Award. Clinical neurophysiology in neuromuscular disorders: usefulness and limitations.

This lecture focuses on the impact of classic and modern electrophysiological techniques on the diagnostic approach to patients with neuromuscular disorders, placing emphasis on the limitations of currently used techniques and on the future prospects of clinical neurophysiology. The refinement of old techniques together with the development of new ones will hopefully improve the diagnostic capability of neurophysiology, improve understanding of the complex pathogenic mechanisms underlying neuromuscular disorders and help further the research of new therapeutic strategies.

Searching biomedical databases on complementary medicine: the use of controlled vocabulary among authors, indexers and investigators.

BACKGROUND: The optimal retrieval of a literature search in biomedicine depends on the appropriate use of Medical Subject Headings (MeSH), descriptors and keywords among authors and indexers. We hypothesized that authors, investigators and indexers in four biomedical databases are not consistent in their use of terminology in Complementary and Alternative Medicine (CAM). METHODS: Based on a research question addressing the validity of spinal palpation for the diagnosis of neuromuscular dysfunction, we developed four search concepts with their respective controlled vocabulary and key terms. We calculated the frequency of MeSH, descriptors, and keywords used by authors in titles and abstracts in comparison to standard practices in semantic and analytic indexing in MEDLINE, MANTIS, CINAHL, and Web of Science. RESULTS: Multiple searches resulted in the final selection of 38 relevant studies that were indexed at least in one of the four selected databases. Of the four search concepts, validity showed the greatest inconsistency in terminology among authors, indexers and investigators. The use of spinal terms showed the greatest consistency. Of the 22 neuromuscular dysfunction terms provided by the investigators, 11 were not contained in the controlled vocabulary and six were never used by authors or indexers. Most authors did not seem familiar with the controlled vocabulary for validity in the area of neuromuscular dysfunction. Recently, standard glossaries have been developed to assist in the research development of manual medicine. CONCLUSIONS: Searching biomedical databases for CAM is challenging due to inconsistent use of controlled vocabulary and indexing procedures in different databases. A standard terminology should be used by investigators in conducting their search strategies and authors when writing titles, abstracts and submitting keywords for publications.