Hereditary neuromuscular diseases

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Abstract

This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

Section snippets

Definition

Neuromuscular diseases are described as diseases of a series of functional entities called motor units. A motor unit consists of a motor neuron situated either in the anterior horn of the spinal cord or in a number of motor nuclei of the brain stem. Its axon travels through a peripheral nerve towards a particular muscle in which several muscle cells are contacted by means of neuromuscular junctions. According to the site of the lesion within the motor unit, neuromuscular diseases are given

Radiological findings in neuromuscular diseases

The diagnosis of a neuromuscular disease can be established through a comprehensive work-up involving a complete physical and neurological examination, routine hematological and biochemical investigations, muscle power testing, electromyography (EMG), clinical biochemistry, serum creatine kinase (CK) and pyruvate kinase levels, muscle biopsy, mode of inheritance and genetic analysis [5].

CT imaging of muscle provides information that is otherwise not obtainable by clinical examination, and it

Clinical presentation and pathogenesis of muscular dystrophies

All muscular dystrophies present with muscular weakness, insidious onset and progressive nature, but the age of onset of symptoms and the rate of progression vary from one type of muscular dystrophy to another [14].

Becker and Duchenne muscular dystrophy

Duchenne and Becker MD cause similar patterns of weakness and disability and are both inherited as X-linked recessive manner. The responsible gene is mapped on locus Xp21, encoding dystrophin protein [15]. Becker MD is a less severe form of Duchenne MD. The prevalence for Duchenne MD

Myotonic dystrophy (Steinert's disease, congenital myotonic dystrophy)

Myotonic dystrophy, dystrophia myotonica or Steinert's disease is an autosomal dominant hereditary condition [11], with a prevalence of 1/8000 [35]. The association with myotonia, relatively mild muscular weakness and other system involvement separate the disease from the other muscular dystrophies. The genetic defect has recently been shown to result from an unstable DNA sequence of the myotonin protein kinase gene, located on chromosome 19q13 [36]. The disease can be divided into three

Congenital myopathies

Most cases of myopathies start in infancy and very rarely the disease may be present at birth. Due to myopathic nature of the disease, there is usually no obvious muscle weakness and no remarkable radiologic abnormality. Later on, the child may show delayed motor development, and non- or slowly-progressive muscle weakness, affecting the facial muscles, and the proximal musculature. The specific diagnosis of myopathy is made by muscle biopsy.

Metabolic myopathies

Metabolic myopathies are a group of disorders in which metabolic abnormalities either intrinsic to muscle or secondary to other influences result in a variable spectrum of muscle weakness. In general, the weakness tends to be proximal. The radiologic findings in patients with metabolic myopathies are not remarkable, if existing not specific.

Inherited auto-immune and inflammatory myopathies or myositis

Inclusion body myositis (IBM) is a slowly progressive inflammatory myopathy characterized by slowly progressive limb-girdle muscle weakness, dysphagia, and mixed myopathic and neurogenic changes on EMG. The radiological features include both dystrophic and neurogenic type of involvement, namely atrophy and fatty infiltration, that are not specific for disease and highly variable. According to literature, quadriceps muscles are remarkable spared, but our experience does not share this finding.

Spinal muscular atrophy (SMA)

The disorder is characterized by degeneration of the anterior horn cells leading to symmetrical muscle weakness and wasting of voluntary muscles. Patients with spinal muscular atrophy have been classified into three types based on the age of onset and severity.

The responsible gene in all three types is mapped on chromosome 5q13 [46].

Hereditary motor and sensory neuropathies

The term hereditary motor and sensory neuropathy (HMSN) is used to describe a group of conditions marked by slowly progressive weakness and wasting of the muscles below the knees and often those of the hands. Radiologically, there is a typical distribution of lesions. While shoulder and upper limb muscles are normal, the lower limb muscles, especially those below the level of pelvic floor show remarkable neurogenic characteristics of involvement, namely atrophy. The involvement is symmetric (

Conclusion

The radiological features of neuromuscular diseases include changes of muscle volume and attenuation values. This includes atrophy, hypertrophy, pseudohypertrophy and fatty infiltration. CT of patients with hereditary neuromuscular disease discloses large differences in the type of abnormal density, the distribution of atrophic and hypertrophic muscle lesions between individual muscles. In the course of the disease, certain muscles are significantly more or less affected than others. Although

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