Progressive Symmetrical Muscle Weakness Research Articles

Gene therapy for spinal muscular atrophy (SMA): First experience with Onasemnogene abeparvovec (Zolgensma®) in a private hospital in Mexico

Spinal muscular atrophy is a hereditary neuromuscular disease characterized by the degeneration of alpha motor neurons of the anterior horn of the spinal cord, leading to progressive symmetrical muscle weakness and a high risk for respiratory complications resulting in the need for some degree of ventilatory support. Two infants are presented with hypotonic syndrome in which spinal muscular atrophy was diagnosed by a genetic study. Gene therapy with Zolgensma® was used to evaluate the clinical improvement in motor function according to the Chop Intend Scale.

Guillain-Barré syndrome: a review of immunotherapy, rehabilitation, and long-term outcomes

Guillain-Barré syndrome (GBS) is a complex autoimmune disorder characterized by the rapid onset of motor weakness and sensory disturbances, often precipitated by preceding infections. GBS is considered a rare disorder, with an estimated annual incidence ranging from 0.6 to 4.0 cases per 100,000 individuals. It constitutes a medical emergency due to its potential for severe disability or mortality. The hallmark clinical features of GBS include progressive symmetric muscle weakness and sensory disturbances. Diagnosis relies on clinical evaluation, cerebrospinal fluid analysis, and electrodiagnostic studies, with the Brighton criteria providing standardized diagnostic criteria. The hallmark clinical features include progressive symmetric muscle weakness, sensory deficits, and areflexia or hyporeflexia. The management of GBS primarily involves supportive care and immunomodulatory therapies. Plasmapheresis, or plasma exchange, and intravenous immunoglobulin (IVIG) are the mainstay treatments aimed at modulating the immune response and shortening the illness duration. Rehabilitation, encompassing physical and occupational therapy, is pivotal for restoring functionality and improving long-term outcomes.

Recurrent acute-onset of chronic inflammatory demyelinating polyneuropathy after COVID-19 vaccination

This is the case of 54-year-old male with a past medical history of Chronic Inflammatory Demyelinating Polyneuropathy (CIPD) who was found to have an acute exacerbation of CIPD shortly after receiving his 1st COVID 19 booster (3rd dose of vaccination series) and was successfully treated with intravenous immunoglobulin (IVIG) and then was found to have another acute exacerbation of CIDP 6 months later after receiving his 2nd COVID 19 booster (4th dose of vaccination series) that required intubation and long term tracheostomy. CIPD is an acquired immune-mediated polyneuropathy that mainly affects the peripheral nerve roots nerves. It typically presents with relapsing/remitting, or progressive symmetrical muscle weakness and sensory involvement and can cause decreased respiratory effort. COVID-19 is mainly a respiratory disease, but it has been associated with a wide variety of neurological conditions. Although there have been several findings of acute inflammatory demyelinating polyneuropathy in association with COVID-19, CIDP exacerbation as a result of COVID-19 has rarely been seen in the literature. Furthermore, CIDP exacerbation as a result of COVID-19 vaccination is even less frequently seen.

Expert consensus on preimplantation genetic testing for spinal muscular atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron degenerative disease, which is the most common fatal neuromuscular disease in pediatrics with a high carrier frequency and can lead to progressive symmetrical muscle weakness and atrophy of the trunk and limbs. Preimplantation genetic testing (PGT) can be used to prevent the birth of children with SMA effectively. To standardize PGT technologies for SMA, experts from the fields of neurology, pediatrics and reproductive genetics have discussed and drafted this consensus for guiding its clinical application.

Spinal Muscular Atrophy: Past, Present, and Future.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by deletions or mutations in the survival motor neuron (SMN1) gene. SMA is characterized by loss of lower motor neurons (anterior horn cells) in the spinal cord and brainstem nuclei, leading to progressive symmetrical muscle weakness and atrophy. It affects approximately 1 in 6,000 to 1 in 10,000 individuals and is the most common inherited cause of childhood mortality, but this may soon change given recent developments. In December 2016, nusinersen, an antisense oligonucleotide drug, was approved by the United States Food and Drug Administration for the treatment of SMA, and in July 2018, SMA was added to the recommended uniform screening panel, a list of conditions that all states are encouraged to include in their newborn screening (NBS) panels. In this review, we begin with a brief clinical history of the diagnosis of SMA, discuss the current SMA clinical classification system, describe the current treatment, and discuss evolving treatment guidelines. We then discuss the path to include SMA in NBS programs as well as the controversies it engenders because the variability in age at symptom onset means early identification of asymptomatic patients who will not require therapy for years or decades. We also consider alternate population screening opportunities. Next, we consider experimental treatments. We conclude by supporting NBS for SMA with the caveat that a long-term follow-up registry is ethically essential to ensure that the benefits outweigh the harms for all screened infants, including those with milder and/or later-onset forms of SMA.

The difference type and disease severity in a family with spinal muscular atrophy (SMA)

Background: SMA is a fatal neuromuscular disease with autosomal resessive inheritance, characterized by degeneration of motor neurons, leading to the progressive symmetrical muscle weakness and atrophy. Most of SMA patient lack SMN1, and SMN1 is recognized as an SMA-causing gene.The clinical severity is modified by copy number of a highly homologous gene, SMN2.

FEATURES DIAGNOSTIC FINDING IN DERMATOMYOSITIS (CLINICAL OBSERVATION)

In connection with the polymorphism of clinical manifestations of dermatomyositis, patients in the onset of the disease can apply to doctors of any specialty. However, the statement of this diagnosis causes considerable difficulties for practical doctors who do not work in the field of rheumatology. To a large extent this is due to the fact that inflammation of the muscle tissue can have not only an autoimmune origin, but also be observed with a variety of infections and intoxications. Diagnosis of dermatomyositis is associated with the need to eliminate tumor processes in the body, accompanying it in 20% of cases. The article presents a clinical case of subacute dermatomyositis, which occurred in a man 49 years after massive insolation against the background of photosensitization with fluoroquinolones in the treatment of prostatitis. After detecting a significant increase in the level of serum “muscle” enzymes and electromyographic signs of inflammatory myopathy, a patient with characteristic progressive symmetrical muscle weakness of the proximal limb and skin changes was diagnosed with primary idiopathic dermatomyositis with the activity of III degree. Diagnostic search required the exclusion of infectious and neoplastic diseases. Timely formulation of the diagnosis made it possible in time to prescribe immunosuppressive therapy with glucocorticosteroids, achieving a decrease in the activity of the disease and improving the prognosis.

Spinal Muscular Atrophy: Overview of Molecular Diagnostic Approaches.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease and the most common genetic cause of infant mortality, affecting ∼1 in 10,000 live births. The disease is characterized by progressive symmetrical muscle weakness resulting from the degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei. The disease is classified on the basis of age of onset and clinical course. SMA is caused by mutations in the telomeric copy of the survival motor neuron 1 (SMN1) gene, but all patients retain a centromeric copy of the gene, SMN2. The homozygous absence of the SMN1 exon 7 has been observed in the majority of patients and is being utilized as a reliable and sensitive SMA diagnostic test. In the majority of cases, the disease severity correlates inversely with an increased SMN2 gene copy number. Carrier detection, in the deletion cases, relies on the accurate determination of the SMN1 gene copies. Since SMA is one of the most common lethal genetic disorders, with a carrier frequency of 1 in 40 to 1 in 60, direct carrier dosage testing has been beneficial to many families. This unit attempts to highlight the molecular genetics of SMA with a focus on the advantages and limitations of the current molecular technologies.

Transverse myelitis and acute motor sensory axonal neuropathy due toLegionella pneumophila: A case report

Guillain-Barré syndrome is a rapidly progressive symmetrical muscle weakness associated with acute inflammatory disease. Transverse myelitis (TM) is the inflammation of the spinal cord characterized by rapidly evolving muscle weakness in the lower extremities, defects in sensory level and sphincter dysfunction. Guillain-Barré syndrome, and TM association occurs very rarely in childhood. A 7-year-old girl presented with complaints of neck pain, spout-style vomiting, cough, shortness of breath, and acute paraparesis with sensory and sphincter disturbance. The patient was intubated because of increased respiratory distress. A positive direct fluorescein antigen test in bronchoalveolar lavage confirmed Legionella pneumophila infection. Imaging and neurophysiologic studies were diagnostic for TM with acute motor and sensory axonal neuropathy. She was treated with a combination of high-dose methylprednisolone and intravenous immunoglobulins, and we observed incomplete recovery. The presented case is the first child with concomitant TM and acute motor and sensory axonal neuropathy related to L. pneumophila infection.

Anesthesia and spinal muscle atrophy

Spinal muscle atrophy (SMA) is autosomal recessive and one of the most common inherited lethal diseases in childhood. The spectrum of symptoms of SMA is continuous and varies from neonatal death to progressive symmetrical muscle weakness first appearing in adulthood. The disease is produced by degeneration of spinal motor neurons and can be described in three or more categories: SMA I with onset of symptoms before 6months of age; SMAII with onset between 6 and 18months and SMA III, which presents later in childhood. Genetics: The disease is in more than 95% of cases caused by a homozygous deletion in survival motor neuron gene 1 (SMN1). The loss of full-length functioning SMN protein leads to a degeneration of anterior spinal motor neurons which causes muscle weakness. Anesthetic risks: Airway: Tracheal intubation can be difficult. Respiration: Infants with SMA I almost always need postoperative respiratory support. Patients with SMA II sometimes need support, while SMA III patients seldom need support. Circulation: Circulatory problems during anesthesia are rare. Anesthetic drugs: Neuromuscular blockers: Patients with SMA may display increased sensitivity to and prolonged effect of nondepolarizing neuromuscular blockers. Intubation without muscle relaxation should be considered. Succinylcholine should be avoided. Opioids: These should be titrated carefully. Anesthetic techniques: All types of anesthetic technique have been used. Although none is absolutely contraindicated, none is perfect: anesthesia must be individualized. The perioperative risks can be considerable and are mainly related to the respiratory system, from respiratory failure to difficult/impossible intubation.

Technical standards and guidelines for spinal muscular atrophy testing

Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. The disease is characterized by progressive symmetrical muscle weakness resulting from the degeneration and loss of anterior horn cells in the spinal cord and brainstem nuclei. The disease is classified on the basis of age of onset and clinical course. Two almost identical SMN genes are present on 5q13: the SMN1 gene, which is the spinal muscular atrophy-determining gene, and the SMN2 gene. The homozygous absence of the SMN1 exon 7 has been observed in the majority of patients and is being used as a reliable and sensitive spinal muscular atrophy diagnostic test. Although SMN2 produces less full-length transcript than SMN1, the number of SMN2 copies has been shown to modulate the clinical phenotype. Carrier detection relies on the accurate determination of the SMN1 gene copies. This document follows the outline format of the general Standards and Guidelines for Clinical Laboratories. It is designed to be a checklist for genetic testing professionals who are already familiar with the disease and methods of analysis.

Review of Duchenne Muscular Dystrophy (DMD) for the Pediatricians in the Community

Duchenne muscular dystrophy (DMD), an inherited X-linked recessive disorder, is characterized by progressive symmetric muscle weakness and gait disturbance, with onset in early childhood. DMD is the most common muscular dystrophy in children, and incidence ranges from 1 in 3600 to 4700 live male births. Early diagnosis (screening, confirmation, and genetic counseling), treatment, and long-term follow-up of affected individuals in routine pediatric practice can be challenging and are the focus of this review.

Epidemiología, etiología y clasificación

Idiopathic inflammatory myopathies are a group of heterogeneous striated muscle acquired autoimmune diseases, characterized by progressive symmetrical muscle weakness, elevated serum levels of muscle enzymes, electromyographic abnormalities and inflammatory infiltrates on muscle biopsy. This group of diseases comprises polymyositis, dermatomyositis and inclusion-body myositis. They are considered rare autoimmune diseases, with an overall incidence range of 2 to 10 new cases per million persons at risk per year, with differences in distribution according to age, gender and race. Their etiology is largely unknown, but it likely involves both genetic and environmental factors that contribute to autoimmune disorders, with striated muscle as a common target.

Spinal Muscular Atrophy Genetic Counseling Access and Genetic Knowledge: Parents' Perspectives

Spinal muscular atrophy is characterized by degeneration of alpha motor neurons in the anterior horns of the spinal cord, which leads to progressive symmetrical muscle weakness and atrophy. Spinal muscular atrophy is the leading fatal autosomal recessive disorder in infancy, and genetic counseling is an essential component of the care of families of these patients. However, little guidance is available in the published literature regarding the process and benefit of genetic counseling for families. Accordingly, the authors designed a questionnaire to assess parents' knowledge of the disease, gauge their access to genetic counseling, and determine how parents use information gained from counseling to guide choices for future pregnancies. The questionnaire specifically targeted when genetic counseling was received, from whom, parental knowledge regarding spinal muscular atrophy genetics, parental choices regarding spinal muscular atrophy and their child, frequency of prenatal testing, perceived relevance of newborn screening, and opinions regarding the disease. Most families clearly received some type of genetic counseling. Yet how and from whom they received the information varied greatly, as did their genetic knowledge of spinal muscular atrophy. The highest percentage of families received counseling from neurologists, who may not be appropriately prepared to provide formal genetic counseling. Many respondents reported having a negative experience with genetic counseling, possibly because it occurred at the time of diagnosis or shortly afterward, a period of great emotional turmoil. These data suggest that a consistent approach for facilitating how and when genetic counseling is received is greatly needed.

Autonomic dysfunction as the presenting feature of Guillain-Barré syndrome

Autonomic dysfunction has been demonstrated in various conditions associated with peripheral neuropathy such as acute intermittent porphyria, amyloidosis, and Guillain-Barré syndrome (GBS). In the latter, hypertension is an associated complication that typically occurs after neurological signs are already present. We report a case of a patient with autonomic dysfunction as the presenting feature who was admitted to the coronary unit with chest pain and hypertension. Subsequently, he developed progressive symmetric muscle weakness, sensory changes, and areflexia. GBS was then diagnosed based on the clinical picture, albuminocytologic dissociation in the cerebrospinal fluid, and electrodiagnostic abnormalities suggestive of demyelinative polyneuropathy with conduction block. Few cases in the literature have reported autonomic dysfunction as the presenting feature of GBS, such as in this case. In a previously asymptomatic patient, acute onset of autonomic dysfunction should alert the physician to the possibility of an acute polyneuropathy, such as GBS.