The general definition of a neuromuscular disorder is a disease pertaining to both the nerves and the muscles. However, the term appeared to be interpreted differently within the various disciplines. Hence, a more specific definition was proposed. In this guideline, a neuromuscular disorder is defined as a defective function of the peripheral nerve system, the neuromuscular junction, or muscles, causing muscle weakness in the patient. Disorders of the central nervous system, such as cerebral palsy or spina bifida, are not included in this definition. Within this definition, neuromuscular disorders are the result of defective anterior horn cell function in the spinal cord (e.g. SMA), defects of the peripheral nerves (neuropathies), the neuromuscular junction (myasthenia gravis), structural defects of the muscle cells (myopathies), muscle cell degradation (muscular dystrophies), or metabolic myopathies (glycogenosis, mitochondrial myopathy). Most of these disorders are rare. Therefore, the relatively frequent occurring progressive disorders DMD and SMA, both associated with a high incidence of scoliosis, were taken as paradigm for the treatment of neuromuscular scoliosis.
Duchenne Muscular Dystrophy (DMD)
DMD is an X-linked (Xp21) recessive inherited disease. Affected males inherited the genetic mutation from the mother, or developed the condition by spontaneous mutations in the gene. Usually, the affected boy has a slightly delayed motor development during infancy. Hereafter, symptoms are a rapidly progressive muscle weakness associated with muscle wasting associated with a progressive difficulty to walk. Most boys are wheelchair-bound at the age of 10. Major changes during puberty are the progressive muscle weakness in hands, arms, and torso, associated with the development of scoliosis. In this phase, the respiratory function is gradually deteriorating, with need of respiratory assistance, and a possible cardiomyopathy may induce problems. Mild mental retardation is present in approximately 40% of DMD patients.
DMD is diagnosed by repeated determination of extremely elevated Creatine Kinase (CPK-MM) levels in the bloodstream and mutations in the dystrophin gene on the X-chromosome, or by the absence of the gene product dystrophin in a muscle biopsy.
Spinal Muscular Atrophy (SMA)
SMA includes a number of genetic disorders, all presenting with a manifestation of weakness due to loss of the motor neurons of the spinal cord and brainstem. The most common form of SMA is caused by a mutation of the Survival Motor Neuron (SMN) gene, located on chromosome 5q13. It is an autosomal recessive form which manifests over a wide range of severity affecting infants through adults. The spectrum has been classified into four types based on the onset of the symptoms and the level of weakness.
SMA type 1, also known as severe infantile SMA or Werdnig Hoffmann disease, is the most severe, and manifests in the first year of life with the inability to ever maintain an independent sitting position. Children with SMA type 1 deteriorate rapidly and have a life expectancy of less than two years.
SMA type 2, or intermediate SMA, describes those children who are wheelchair-bound very early in life. Usually, they are never able to walk and a severe dystrophy associated with considerable scoliosis develops already around the age of four. Some of the children depend on respiratory assistance during the night, and later around the clock, with or without tracheostomy. The onset of weakness is usually recognized some time between 6 and 18 months. Within the first three years SMA types 1 and 2 cannot be distinguished based on determination of the genetic lesion. Consequently, this is a very uncertain period for the parents.
SMA type 3, also called juvenile SMA or Kugelberg-Welander disease has a more moderate course. Patients with SMA type 3 preserve their ability to walk until the second or third decade, and they develop less scoliosis and respiratory problems.
In SMA type 4, or adult SMA weakness usually begins in the third decade. The course of disease is much slower and has little or no impact on life expectancy.
This guideline is directed at the group of patients with SMA type 2.
SMA is diagnosed by the typical clinical symptoms and by the SMN gene test.
Scoliosis is a complex deformation that involves abnormal lateral and rotational curvature of the spine. Both in DMD and SMA type 2 scoliotic deformations are frequent. The deformation is mostly a progressive thoracolumbar C-curve with development of pelvic obliquity. Either an increased kyphosis or thoracic lordosis can be part of the deformity. The consequences of the deformity are loss of sitting balance, shortening of the trunk, and compression of the hart and lungs. The mobility of the ribs is reduced by rotation and deformation of the trunk, causing obstruction of the breathing capacity.