Neuromuscular Diseases

This primary degenerative process, first described by Wilhelm Erb in 1891, affects the muscular fibers, not the nerves or end plates. In spite of extensive research, the cause has not yet been firmly established, although genetic factors are receiving strong consideration. A variety of types and classifications have been proposed, but all are based on age of onset, symptomatology, and rate of progression. One simple classification system includes: progressive muscular dystrophy or Duchenne type; facioscapulohumeral or Landouzy and Dé jerine type; and limb-girdle dystrophies including distal muscular dystrophy, ocular myodystrophy, and myotonic dystrophy.

Progressive muscular dystrophy (Duchenne type) is the most important one of the group and the best studied. It accounts for almost 70% of all dystrophies, affects males five times more frequently than females, and almost always begins in the first five years of life. It is an inherited sex-linked recessive trait, and the abnormal gene is at the Xp21 locus. Its incidence is 1 in 3,600 in newborn males. Muscular weakness is noted first in the pelvis, shoulder girdle, and spine, and spreads peripherally to the extremities, especially to the legs. This weakness results in a waddling gait, an insecure stance on a wide base, and a lordotic (forward curved) posture. Weakness continues to spread all over the body, although some of the involved muscles appear to grow larger secondary to an invasion of muscle tissue by peculiar fat cells. This is especially evident in the calf muscles. Victims rarely survive to maturity.

Blood enzyme tests can detect the abnormalities associated with progressive muscular dystrophy early on, even before symptoms are clearly evident. Muscle tissue is rich in creatine and, when muscles are diseased, the creatine leaks into the blood and can be measured as creatine kinase (CK). The normal level of CK is about 160 IU/L, but an individual with Duchene muscular dystrophy may have CK levels as high as 15,000-35,000 IU/L. If the diagnosis is in doubt, genetic studies and muscle biopsy can also be done. The recent isolation of the Duchenne gene and the discovery that dystrophin is the abnormal encoded protein makes a precise molecular diagnosis possible. It also offers hope that the genetic basis for other dystrophies will be discovered soon.

Facioscapulohumeral muscular dystrophy or Landouzy-Dé jerine dystrophy differs from the more common types in that it involves primarily the upper extremities, face muscles, and shoulder girdle. The condition starts later in life (usually by age 10) and may appear even in the elderly. Because it has a slower progress and longer duration, patients may develop irregular cardiac rhythms or even damage to the heart muscle. CK enzymes vary greatly, and electromyograms (EMGs) are not diagnostic. A muscle biopsy is the only way to confirm the presence of this condition. As in all other dystrophies, no satisfactory therapy is yet available.

Limb-girdle dystrophies also follow a slow course and often cause only slight disability. When the disease begins in the fingers and then spreads centrally toward the body, the term "distal" is employed. When paralysis starts in the eyelids and facial muscles, it is classed as "ocular." The causes of these conditions are obscure.

Although once considered rare, myotonic dystrophy is now being recognized with increasing frequency. It is an inheritable or familial condition that primarily affects young adults. The muscle groups of the hands, feet, and face ("taper mouth" is secondary to atrophy of face muscles) are most commonly involved. An individual with this condition may be easily able to shake hands but may have difficulty relaxing his grip. There are many accompanying glandular disturbances, changes in bones, and elevated blood cholesterol. Since so many body functions are affected by this disease, it is not surprising that death (from heart attacks) usually occurs before middle age.