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Results for “Muscular Atrophy, Spinal”

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PubMed1998

Somatic mosaicism of the expanded CAG trinucleotide repeat in mRNAs for the responsible gene of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA).

The CAG trinucleotide repeats in mRNAs for the responsible genes of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and X-linked spinal and bulbal muscular atrophy (SBMA) were examined in various neural and nonneural tissues of affected individuals. The tissue-specific variation of expanded CAG repeat alleles were apparent for mRNAs of all three genes. The expanded CAG repeats of the mRNA were shorter in the cerebellum than in other regions of the central nervous system in DRPLA and MJD, but not in SBMA, and were longer in the liver and colon in MJD. Transcripts of the responsible genes with expanded CAG repeats were detected in all tissues studied, and the tissue-specific variation in the CAG repeat size of the mRNA did not correlate with the tissue-specific severity of pathological involvement in these diseases.

Adult↗

PubMed1999

Transforming growth factor-beta2 is elevated in skeletal muscle disorders.

The transforming growth factor betas (TGF-betas) are multifunctional growth factors that act on both fibroblasts and myosatellite cells. In rodent models of muscle diseases, high levels of TGF-beta2 are expressed by myogenic cells. We have examined whether the expression of TGF-beta2 is also elevated in diseased human muscles. The disorders examined were Duchenne muscular dystrophy, myotonic dystrophy, myotubular myopathy, spinal muscular atrophy, and amyotrophic lateral sclerosis. The levels of TGF-beta2 immunoreactivity were elevated in atrophic, necrotic, and regenerating fibers and in fibers with central nuclei or cytoplasmic masses, irrespective of whether fibrosis was present. We therefore suggest that TGF-beta2 is important for muscle repair and that the presence of a TGF-beta within a muscle only leads to fibrosis if certain other factors are present.

Amyotrophic Lateral Sclerosis↗

PubMed2000

Dose-dependent effects of inspiratory muscle training in neuromuscular disorders.

The goal of this study was to show whether a correlation exists between the intensity of specific respiratory muscle training and the improvement of strength and endurance in inspiratory musculature in patients with neuromuscular disorders (NMD). Sixteen patients with NMD (13 with Duchenne muscular dystrophy and 3 with spinal muscular atrophy) performed inspiratory muscle training (IMT) at home with a special training apparatus for 9 months. Maximal inspiratory mouth pressure (PI(MAX)) and 12s-maximum voluntary ventilation (12s-MVV) test served as parameters for inspiratory muscle strength and endurance, respectively. In patients whose inspiratory vital capacity (VC(in)) declined by less than 10% during the year before training began (n = 10), a significant positive correlation was found between the number of successfully completed strength and endurance exercises and the improvement of PI(MAX) (P < 0.05) and 12s-MVV (P < 0.05). In patients whose VC(in)-decline exceeded 10% (n = 6), indicating more progressive respiratory system involvement of the disease, no significant correlation between the improvement of PI(MAX) and 12s-MVV and the intensity of training was found. In patients with NMD, the effects of IMT-runs are dose-dependent, provided that the respiratory system involvement of the disease is only slowly progressive.

Adolescent↗

PubMed2002

Diagnosis of dystrophinopathy by skin biopsy.

We studied the expression of dystrophin in skin biopsy samples from 19 patients with neuromuscular diseases. Immunohistochemical procedures for dystrophin analyses were performed using monoclonal antibodies for three different domains. Arrector pili muscles, which are smooth muscles in the skin, expressed dystrophin in the patients with limb-girdle muscular dystrophy (5), facioscapulohumeral muscular dystrophy (1), and spinal muscular atrophy (3), and in normal controls (2). The C-terminus of dystrophin was slightly expressed in the patients with Duchenne muscular dystrophy, whereas the rod domain and N-terminus were absent. In one patient with Becker muscular dystrophy, the expression of dystrophin was reduced. The mosaic of dystrophin positive and negative smooth muscle fibers was observed in a manifesting carrier of Duchenne muscular dystrophy. Our results suggest that skin biopsy is very useful for the diagnosis of Duchenne/Becker muscular dystrophy and manifesting carrier of Duchenne muscular dystrophy, and can be performed even at an advanced stage of the disease.

Biopsy↗

PubMed1994

Swallowing problems in neuromuscular disorders.

Feeding problems in patients with neuromuscular diseases are frequently underestimated and poorly analyzed. To gain a better understanding of the most common complaints, we surveyed 451 patients and received 409 responses representing seven disorders. Difficulties in the pre-oral phase of swallowing were encountered primarily in Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy (LGMD), facio-scapulo-humoral muscular dystrophy (FSHMD), and spinal muscular atrophy (SMA). A limitation in the ability to open the mouth was also noted in SMA. Some features are characteristic of certain diseases such as macroglossia in DMD and dryness of the mouth in dermatomyositis and polymyositis (DMPM) and myasthenia gravis (MG). Posterior swallowing time is especially affected in MG, dermatomyositis and polymyositis, LGMD, and SMA. Overall prevalence of feeding disability in five disorders (SMA, myotonic dystrophy [MD], DMPM, FSHMD, MG) was 34.9%. A better understanding of the swallowing problems associated with these disorders may help in choosing treatment possibilities, technical aids, adaptation of the consistency of foods, swallowing rehabilitation, and nutritional support by the non-oral route.

Adolescent↗

PubMed2005

Impaired primary hemostasis with normal platelet function in Duchenne muscular dystrophy during highly-invasive spinal surgery.

A defective, normal or enhanced hemostasis has been reported in Duchenne muscular dystrophy (DMD). A retrospective analysis of intra-and postoperative (up to 36 h) estimated blood losses was performed in 156 patients undergoing spinal surgery for: DMD (n = 31), idiopathic scoliosis (IS) (n = 70), poliomyelitis (n = 10), cerebral palsy (CP) (n = 28), spinal muscular atrophy (SMA) (n = 17). Platelet aggregation and bleeding times were also investigated in DMD patients. Immunohistochemistry for dystrophin was performed in platelets, megakaryocytes and blood vessels of normal tissues. DMD patients showed significantly higher intraoperative estimated blood losses (DMD: 3495+/-890 ml; IS: 2269+/-804 ml; poliomyelitis: 2582+/-1252 ml; CP: 2071+/-683 ml; SMA: 2464+/-806 ml; P < 0.05), while postoperative blood losses were similar among different groups. Higher estimated blood losses in DMD were independent of the duration of surgery, body weight, gender, age, vertebral levels or preoperative Cobb angle. DMD children had significantly prolonged bleeding times, but retained normal platelet function. From control samples dystrophin was expressed in vascular smooth muscle cells, but not in platelets. DMD appears to be characterized by immediate bleeding during highly-invasive surgery and increased bleeding time without platelet abnormalities. Considering dystrophin expression in normal vascular smooth muscle cells, these results altogether suggest a selective defect of primary hemostasis in DMD, likely to be due to impaired vessel reactivity.

Adolescent↗

PubMed2005

Ethical aspects of home long term ventilation in children with neuromuscular disease.

Increasing numbers of children and young adults are now receiving home ventilation. Whereas in some neuromuscular conditions the outcome and quality of life gains are clear cut; in others eg Spinal Muscular Atrophy Type I there are a few outcome studies with conflicting results and it is more difficult to balance the ethical concepts of beneficence, non-maleficence, autonomy and distributive justice. As a result there are widespread variations in the clinical management of these children. This article examines decision-making in these areas seen from the perspective of the individual, the family and society.

Child↗

PubMed2006

[A motor function measurement scale for neuromuscular diseases - description and validation study].

A new scale for motor function measurement has been developed for neuromuscular diseases. After the study of a preliminary and a first version, the validation study included 303 patients, aged 6 to 62 years. Seventy-two patients had Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30 limb-girdle muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic dystrophy, 21 congenital myopathy, 10 congenital muscular dystrophy, 35 spinal muscular atrophy and 35 hereditary neuropathy. The sensitivity for change was evaluated with 152 patients one year after. The scale comprised 32 items, in three dimensions: standing position and transfers, axial and proximal motor function, distal motor function. High correlations (>0.80) were found between the total score and other scores: Vignos and Brooke grades, Functional Independence Measure, the global severity of disability evaluated with visual analog scales by physicians and physiotherapists. This scale is reliable, does not require any special equipment and is well accepted by patients. It takes an average of 36 min (range 8-75) to complete the scale. Preliminary results of the second evaluation showed good sensitivity to change since last visit, considering rating by patient, investigator or physiotherapist. Also, significant differences in scores are obtained with the greatest deterioration observed in Duchenne patients.

Adolescent↗

PubMed2003

The floppy infant: contribution of genetic and metabolic disorders.

The floppy infant syndrome is a well-recognized entity for pediatricians and neonatologists. The condition refers to an infant with generalized hypotonia presenting at birth or in early life. The diagnostic work up in many instances is often complex, and requires multidisciplinary assessment. Advances in genetics and neurosciences have lead to recognition of newer diagnostic entities (several congenital myopathies), and rapid molecular diagnosis is now possible for several conditions such as spinal muscular atrophy (SMA), congenital muscular dystrophies (CMD), several forms of congenital myopathies and congenital myotonic dystrophy. The focus of the present review is to describe the advances in our understanding in the genetic, metabolic basis of neurological disorders, as well as the investigative work up of the floppy infant. An algorithm for the systematic evaluation of infants with hypotonia is suggested for the practicing pediatrician/neonatologist.

Diagnosis, Differential↗

PubMed1997

Segmental distribution of muscle weakness in SMA III: implications for deterioration in muscle strength with time.

We examined 26 spinal muscular atrophy type III (SMA III) patients with SMNt deletions, searching for possible segmental distribution of muscle weakness. In those with disease duration of < or = 11 years, the weakest muscles were upper lumbar innervated ones in the lower extremities. In the upper extremities, early involvement of triceps muscle suggested the possibility of lower cervical (C7) onset. Electrophysiologically, weaker muscles had a more severe reduction in the recruitment pattern, particularly in the lower extremities. However, severe reduction in recruitment was sometimes also observed in clinically strong muscles. In patients with disease duration of > or = 16 years and regardless of disease duration, in those with disease onset at < or = 3 years of age, weakness and severe electrophysiological changes were more widespread. These findings may suggest a progression in muscle weakness with time. When compared to 12 patients with Becker muscular dystrophy (BMD), early stage SMA III with weak iliopsoas-strong gluteus maximus stood in contrast to BMD with weak gluteus maximus-strong iliopsoas.

Adolescent↗

PubMed1998

Orthopedic management of neuromuscular disorders in children.

In many cases, the orthopedic surgeon may be the first consultant requested to assess complaints of lower extremity weakness or deformity to result from such conditions and must remain alert to the primary diagnosis. In addition, the orthopedic surgeon should be prepared to guide appropriate physical therapy, prescribe orthotics, and perform surgery to improve function, prevent deformity, or provide comfort when necessary. Most deformities of the extremities result from a combination of muscle weakness and imbalance, and surgical procedures are aimed at correcting existing deformity and rebalancing existing musculature by release or transfer. Skeletally immature patients with neuromuscular disorders are also susceptible to the development of scoliosis, which may impair comfortable sitting or already compromised pulmonary function. This article reviews the clinical manifestation and orthopedic management of Duchenne's muscular dystrophy, spinal muscular atrophy, facioscapulohumeral dystrophy, and Charcot-Marie-Tooth disease.

Adolescent↗

PubMed1998

Nutrition and swallowing in pediatric neuromuscular patients.

The management of the patient with neuromuscular disease is complex. Every child should be seen as a distinct individual and therefore merits patient-specific assessment and intervention. This article reviews nutritional management using spinal muscular atrophy and Duchenne's muscular dystrophy as representative models. The history of nutritional intake, nutritional needs, and underlying medical problems with physical examination, anthropometric, body composition, and biochemical markers are all important parts of the assessment and should be done at regular intervals. Intervention may include calorie restriction or calorie supplementation. Treatment strategies that follow diagnosis of dysphagia include positioning, increased sensory input, or direct maneuvers, such as volume changes or thickening liquid. Percutaneous endoscopic gastrostomy can be safely placed in almost all situations with minimal risk. Patients benefit most from a multidisciplinary and systematic management program.

Adolescent↗

PubMed1999

A morphological analysis of the macro motor unit potential.

The technique of macro EMG is used to investigate the motor unit architecture in a number of pathological conditions. Amplitude and area are the most commonly used criteria, but these parameters alone are not sufficient to assess the complexity of the macro MUP morphology. In an attempt to examine the morphology of the macro MUP in more detail, additional measures were investigated including, (i) average power, (ii) duration, and (iii) number of phases. Macro MUP duration was defined as the time parameter that contains a particular fraction (90%) of the total power of the potential. The above mentioned parameters were evaluated for normal subjects and for patients suffering with motor neuron disease (MND), spinal muscular atrophy (SMA), and Becker's muscular dystrophy (BMD). It is shown that high amplitude and average power macro MUPs give shorter macro MUP duration than macro MUPs with normal amplitude. In contrast, in low amplitude macro MUPs there is a tendency towards a higher duration measure, as compared with the duration of the normal amplitude macro MUPs. Also, t-test results for the duration measure gave a significant difference between the NOR-MND, and no significant difference between the NOR-BMD and NOR-SMA groups at P<0. 05. Significant difference between the NOR and the three disease groups investigated was obtained for the parameters log amplitude, log area, and log average power. The number of phases was not significantly different between the NOR and the rest of the groups. In conclusion, the average power and duration parameters can possibly be used as additional discriminators to detect abnormalities of the macro motor unit potential in both needle and surface EMG but further investigation is necessary.

Biopsy↗

PubMed2000

[Computer-supported tissue characterization in musculoskeletal ultrasonography].

A new diagnostic system combining conventional gray-scale ultrasonography (US) and computer-assisted texture analysis of sonograms makes it possible to differentiate more easily between specific neuromuscular diseases. The first step involves myosonography with strictly standardized US. In a group of 72 patients with histologically and molecular-genetically confirmed diagnosis 63 patients (88%) were diagnosed by conventional US as having Duchenne's muscular dystrophy, spinal muscular atrophy, hereditary sensomotor neuropathy or inflammatory myopathy. Secondly, in a double blind setting computer-assisted texture analysis was used on the same sample of subjects. Tissue Texture can be characterized by the brightness as well as the micro- and macro-structure of the tissue. The use of these parameters leads to a sensitivity of 77 to 94% and a specificity of 81 to 98%. In conclusion, the combination of both techniques allows us to avoid invasive diagnostic procedures in a substantial group of patients.

Diagnosis, Computer-Assisted↗

PubMed1999

Genetic disorders of motor neurons.

Disorders of the motor neuron are etiologically and clinically heterogeneous and cause serious disability and death. Whereas mendelian inheritance can be demonstrated in a subset of these disorders, the genetic contribution to the sporadic forms of motor neuron degeneration are not well understood. In families with spinal muscular atrophy, Kennedy disease and amyotrophic lateral sclerosis, genetic linkage analysis and positional cloning have proven to be extremely productive. The genetics of these neurodegenerative disorders are reviewed.

Amyotrophic Lateral Sclerosis↗

PubMed2006

Symptoms, clinical and physiological findings motivating home mechanical ventilation in patients with neuromuscular diseases.

OBJECTIVE: To clarify the relationship between symptoms, clinical signs and physiological abnormalities that were motivating the initiation of home mechanical ventilation in patients suffering from neuromuscular diseases. METHODS: From The Swedish Home Mechanical Ventilation Register we identified 352 patients with neuromuscular diseases and we looked at circumstances (acute vs elective) and clinical motives for starting ventilatory support. RESULTS: Home mechanical ventilation was commenced electively in 268 patients (76%) and among these daytime sleepiness was the most common motive, being reported in 56% of the patients. In the 24 children with spinal muscular atrophy, however, 96% started ventilation electively and cough insufficiency was the most common motive. The patients were moderately hypercapnic (PaCO(2): 7.0 kPa, SD 1.3). None of the clinical motives were related to the PaCO(2) level. Average PaO(2) was above 8 kPa in all groups, but lowest in the patients with post-polio and dystrophia myotonica. Mean vital capacity was close to 40% of predicted, but significantly lower in the Duchenne patients (26% of predicted). CONCLUSION: Daytime sleepiness was the most common clinical symptom motivating home mechanical ventilation in this group of patients with chronic hypercapnic respiratory insufficiency secondary to neuro/myopathies. Respiratory function testing is therefore suggested to be included in the diagnostic work up of daytime sleepiness in these patients.

Adolescent↗

PubMed2000

A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes.

A growing number of medical research teams have begun to explore the experimental advantages of using a genetic animal model, the nematode worm Caenorhabditis elegans, with a view to enhancing our understanding of genes underlying human congenital disorders. In this study, we have compared sequences of positionally cloned human disease genes with the C.elegans database of predicted genes. Drawing on examples from spinal muscular atrophy, polycystic kidney disease, muscular dystrophy and Alzheimer's disease, we illustrate how data from C.elegans can yield new insights into the function and interactions of human disease genes.

Amino Acid Sequence↗

PubMed1999

Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception.

PURPOSE: Deterioration of respiratory muscle function in patients with neuromuscular disorders is primarily responsible for the high morbidity and mortality associated with these diseases. METHODS: The potential benefit of respiratory muscle training (RMT) on preservation of respiratory muscle strength and respiratory load perception (RLP) was examined in 21 children (mean age: 12.2 +/- 1.8 yr [SD], 16 male) with Duchenne's muscular dystrophy or spinal muscular atrophy type III, and in 20 age-, weight-, and sex-matched controls. Subjects were randomly allocated to undergo incremental RMT with resistive inspiratory and expiratory loads for a period of 6 months (trained group, TR) or to perform similar exercises with no load (NT). Maximal static inspiratory (Pi(max)) and expiratory (Pe(max)) pressures and RLP (modified Borg visual analog scale 0-10) were assessed on two separate occasions before beginning of the training protocol, monthly throughout RMT duration, and every 3-6 months upon cessation of RMT for 1 yr. RESULTS: In controls, no significant changes in maximal static pressures or load perception occurred during RMT or thereafter. Training in neuromuscular disorder (NMD) patients was associated with improvements in Pi(max) (mean delta max: +19.8 +/- 3.8 cmH2O in TR vs +4.2 +/- 3.6 cmH2O in NT; P < 0.02) and in Pe(max) (mean delta max: +27.1 +/- 4.9 cmH2O in TR vs -1.8 +/- 3.4 cmH2O in NT; P < 0.004). Similarly, RLP significantly decreased during the RMT period in TR (mean delta: 1.9 +/- 0.3; P < 0.01) but did not change in NT (-0.2 +/- 0.2). In addition, with cessation of RMT, static pressures returned to pretraining values in TR within approximately 3 months. However, RLP was still improved after 12 months. CONCLUSIONS: We conclude that in children with NMD, although RMT-induced increases in expiratory muscle strength are rapidly reversible, long-lasting improvements in RLP occur and could be associated with decreased respiratory symptoms.

Airway Resistance↗