Funded By:
The neuromuscular system includes the anterior horn cells in the spinal cord, the peripheral (motor) nerves, the myoneural junctions (MNJs), and the muscles. Acting as a single functional unit, this system is called the “motor unit.” The anterior horn cells are connected to both the brain and the peripheral nerves. The axons (it may be helpful to picture them as the electric wires that connect telephone poles) in the peripheral nerves are connected to the muscles via the myoneural junctions.
Different neuromuscular diseases can affect one or more components of this unit and may be either acquired or hereditary. The major symptoms are weakness and/or atrophy of skeletal muscle. Examples of NMDs are summarized below.
AFFECTED COMPONENT |
ETIOLOGY |
|
ACQUIRED |
HEREDITARY |
|
Anterior horn cell |
Amyotrophic lateral sclerosis Poliomyelitis and post-polio syndrome |
Spinal muscular atrophy |
Peripheral nerves and motor nerve roots |
Physical injury |
Charcot Marie Tooth |
Myoneural junctions |
Myasthenia gravis |
Hereditary myasthenia gravis |
Muscle |
Polymyositis |
Muscular dystrophies |
Characteristics common to the major neuromuscular diseases include:
• Weakness and/or fatigue (all NMDs).
• Limb contractures: Duchenne dystrophy, early onset spinal muscular atrophy, Charcot Marie Tooth syndrome.
• Spinal deformity/scoliosis: Duchenne dystrophy, spinal muscular atrophy, Friedreich's ataxia.
• Restrictive lung disease: all NMDs over time (rapidly progressive in Duchenne muscular dystrophy and amyotrophic lateral sclerosis).
• Cardiac dysfunction: Duchenne muscular dystrophy, myotonic muscular dystrophy.
• Cognitive defects: congenital myotonic muscular dystrophy, Duchenne muscular dystrophy (30% of boys with Duchenne muscular dystrophy have some cognitive impairment).
DEFINITION OF TERMS IN DISEASE DESCRIPTIONS
ORGAN |
IMPAIRMENT |
DISABILITY |
DISADVANTAGE |
Skeletal Muscle |
Decreased strength and endurance
|
Decreased motor performance |
Decreased quality of life
|
Bone and Joint |
Joint contractures |
Decreased function |
Decreased educational opportunities |
Lungs |
Decreased pulmonary function |
Increased restrictive lung disease |
Decreased employment opportunities |
Heart |
Cardiomyopathy |
Decreased cardiopulmonary capacity |
Increased dependency |
Central Nervous System |
May decrease intellectual capacity |
|
|
Disease description definitions are taken from the World Health Organization (WHO) classification of disablement. While impairment and disability characterize a person's functional limitations, these definitions don't necessarily define an individual's capabilities or potential. It is often social attitudes and misperceptions that lead to “DISADVANTAGE.” The table below shows how these terms are interpreted in cases of neuromuscular disease.
AUTOSOMAL: Gene is carried on one of the non-sex chromosomes. In autosomal diseases, both males and females may be affected.
CHROMOSOMES: There are 23 pairs of chromosomes in the cells of each individual (46 chromosomes). Of these, females have two X chromosomes and males have one X and one Y (sex chromosomes). NMDs may be inherited as autosomal dominant autosomal recessive, or X-linked (sex-linked) recessive disorders. Genes, the basic units of heredity, are located on the chromosomes.
DOMINANT: Abnormal gene masks the normal gene. Dominant diseases usually appear in every generation, and are transmitted by either parent to male or female offspring with a 50% probability of developing the disease.
RECESSIVE: Abnormal gene is not expressed unless there is no normal gene to counteract its presence. Recessive diseases tend to skip generations. Autosomal recessive diseases are transmitted to up to 25% of male and female offspring when both parents carry the abnormal gene. Sex-linked recessive diseases are transmitted through the clinically unaffected female to 50% of the male offspring, who develop the disease, and 50% of the female offspring, who are carriers of the abnormal gene.
The neuromuscular disease descriptions (and disease progression graphs) have been organized by major category, and then by specific disease within that category, as follows. (This is not an all-inclusive list of NMDs. It represents those NMDs that would most likely be encountered by Rehabilitation Counselors.) For more complete information about each disease, visit the RehabInfo Network web site at http://www.rehabinfo.net.
Type of inheritance:
These diseases are mostly acquired through a sporadic genetic mutation of unknown cause; approximately 10% of ALS cases are the result of family inheritance.
Clinical onset:
Typically after 50 years of age.
Clinical Description (characteristics):
ALS - anterior horn cells and the central nervous system (CNS) are involved. Onset of weakness and spasticity that is usually preceded by fatigue, cramping and muscle fasciculations (twitching). Usually weakness of pharyngeal muscles with marked difficulty in chewing, swallowing and speaking.
Progressive spinal muscular atrophy (PSMA) - only the anterior horn cells are involved so the only finding is progressive weakness.
PBP (a form of ALS) - manifested by progressive weakness of pharyngeal muscles.
Distribution of weakness:
ALS - in most cases weakness is asymmetrical. Typically, the disease begins with painless weakness and wasting of the muscles of one hand or one foot, which becomes generalized and severe. Progressive spasticity accompanies the weakness.
PSMA - progressive weakness.
PBP - progressive weakness of pharyngeal muscles
Progression:
ALS - the most common and rapidly progressive anterior horn cell disease. Disease leads to loss of ambulation 1-2 years after onset.
Other forms (above) - progress more slowly.
Life expectancy:
ALS - 3-5 years following onset.
Other forms - variable.
Treatment:
None. Medical rehabilitation can improve quality of life.
Training / work outlook:
ALS - very poor.
PSMA - with some individuals may be good.
Others - variable, usually limited.
Spinal Muscular Atrophies.
The spinal muscular atrophies (SMAs) consist of a large group of heterogeneous disorders. Some have a proximal distribution of weakness, others distal or generalized. Progression may be rapid to very slow. All are inherited. Most are autosomal recessive, with males usually more severely affected than females.
Childhood Spinal Muscular Atrophy (SMA Type II)
Type of inheritance:
Autosomal recessive.
Clinical onset:
Six to 24 months of age.
Distribution of weakness:
Usually generalized but initially may be primarily evident in the proximal muscles of the lower extremities. There is also weakness in arms, legs, upper and lower torso.
Progression:
Usually relatively slow.
Clinical characteristics:
Delayed motor development landmarks.
No cognitive defects.
Loss of ambulation variable.
65% incidence of significant contractures.
57% have spine deformity.
Restrictive lung disease common.
Good psychosocial adjustment.
Life expectancy:
Age at death variable; 70% of individuals are alive at 25 years.
Treatment:
Medical rehabilitation can retard the progression of contractures and spine deformity.
Training / work outlook:
Impairment and disability high. Historical employment rate 63%. Education level 13 +/- 5 years.
Juvenile Spinal Muscular Atrophy (Kugelberg-Welander syndrome, SMA Type III)
Type of inheritance:
Usually autosomal recessive.
Clinical onset:
After 18 months of age to early adolescence.
Distribution of weakness:
Symmetrical proximal limb weakness usually commencing in the lower extremities.
Progression:
Slow.
Clinical characteristics:
Loss of ambulation variable.
Low incidence of contractures, spine deformity, restrictive lung disease, and cardiac involvement.
Good psychosocial adjustment.
High incidence of calf hypertrophy.
No cognitive defects.
Life expectancy:
Most have normal life span.
Treatment:
Medical rehabilitation can retard the progress of contractures.
Training / work outlook:
Usually good.
Low impairment, disability, and handicap.
Historical employment rate 63%.
Education level 13 +/- 5 years.
Type of inheritance:
An acquired disease.
Two variants: Neonatal Myasthenia.
Congenital Myasthenia.
Clinical onset:
Occurs in all decades of life, most frequently at about age 40.
Among young adults, women more affected than men.
Differential diagnosis:
Main characteristic is muscle fatigue or temporary weakness, rather than permanent loss of strength.
Tendency to recover after rest.
Most common presenting symptoms relate to weakness of eye muscles, causing ptosis or diplopia.
Distribution of weakness:
Fatigue (temporary weakness) is generalized
Progression:
At onset, may last only a few days, then disappear, only to return weeks or months later.
If after 1-2 years, myasthenia is still restricted to the ocular muscles, it is unlikely to become generalized.
Clinical characteristics:
Difficulty chewing.
Dysarthria and dysphagia common.
Since there is primary fatigue rather than weakness, muscle atrophy does not occur except in patients with a severe chronic course.
The nature of the disease in any given patient is usually established within a few months of onset, with fluctuations afterward.
Life expectancy:
Mortality from Myasthenia is less than 10%.
Treatment:
Good control of disease and symptoms with proper medical treatment.
Training / work outlook:
Impairment, disability and handicap low, with proper treatment.
Work outlook is good for most individuals.
Hereditary Motor and Sensory Neuropathy (HMSN).
Charcot Marie Tooth syndrome (CMT) is the most common type of HMSN.
Type of inheritance:
Most are autosomal dominant.
Clinical onset:
Usually first and second decade of life.
Distribution of weakness:
Distal weakness usually starting in the foot dorsiflexors (foot drop) and progressing to the hand and forearm muscles and foot plantar flexors.
Rarely involves upper arm, shoulder, thigh or hip muscles until late in the disease.
Progression:
Usually slow.
Clinical characteristics:
Primary distal distribution of weakness.
Associated sensory loss, usually mild and late in the disease.
Most patients can ambulate, with short leg braces, long after the onset
16% (low) incidence of contractures, mostly pes cavus.
29% spinal deformity, mostly kyphosis.
Restrictive lung disease in some cases.
Cardiac involvement rare.
No cognitive defects.
Good psychosocial adjustment.
Life expectancy:
Most have normal life span.
Treatment:
Medical rehabilitation can prevent or retard the progress of weakness and contractures.
Training / work outlook:
Work outlook is good.
Low impairment, disability and handicap.
Historical employment rate 67%.
Educational level 12 +/- 3 years.
Hereditary Motor Neuropathy (HMN) (with subtypes)
Hereditary Sensory and Autonomic Neuropathy (HSAN) (with subtypes)
Type of inheritance:
Most autosomal dominant.
Characteristics:
Most inherited types of peripheral nerve diseases have a primarily distal distribution of weakness.
Progression:
Variable, but usually slow.
Becker Muscular Dystrophy (BMD)
Type of inheritance:
Sex (X)-linked recessive.
Clinical onset:
Typically 6-20 years of age.
Differential diagnosis:
Precise methods for diagnosis and carrier detection available.
Can be confused with the rare late onset Duchenne muscular dystrophy, limb girdle syndrome with early onset, and SMA Type 3.
Distribution of weakness:
Similar to Duchenne muscular dystrophy (DMD).
Clinical characteristics:
Cognitive impairment not a characteristic.
Similar to Duchenne muscular dystrophy with delayed course. 43% with mild contractures.
Spine deformity rare.
Restrictive lung disease rare.
Cardiac involvement common.
Good psychosocial adjustment.
Rate of progression:
Usually slow.
Inability to ambulate in most cases at 15-25 years after onset.
Life expectancy:
Often normal life span.
Treatment:
Medical rehabilitation valuable for reducing complications.
Training / Work outlook:
Usually good work outlook.
Impairment, disability, handicap low.
Historical employment rate 80%.
Educational level 12 years +/- 2.
Duchenne Muscular Dystrophy (DMD)
Type of inheritance:
Sex (X)-linked recessive.
Transmitted through unaffected females to males.
50% probability male offspring will be affected.
50% probability female offspring will be carriers.
Clinical onset:
Age range 1-5 years.
Differential diagnosis:
Precise methods for diagnosis and carrier detection are now available.
DMD can be confused with Becker's dystrophy, and limb girdle syndrome of early onset with calf hypertrophy.
Distribution of weakness:
Early selective involvement of hip muscles rapidly followed by weakness of the shoulder girdle muscles.
Clinical characteristics:
Cognitive impairment in 30% of cases.
Other early development normal followed by lordosis (sway back); waddling gait; toe walking; difficulty rising; difficulty climbing stairs.
Involvement usually symmetrical. Ultimately involves all skeletal muscles.
Calf hypertrophy until nonambulatory.
74% have severe progressive contractures.
63% have scoliosis.
81% have significantly reduced pulmonary function, restrictive lung disease and cardiac involvement.
Rate of progression:
Consistently progressive.
Loss of ambulation age 9-11 years.
Death usually from respiratory complications (18-25 years old).
Treatment:
Medical rehabilitation can improve quality of life.
Training / Work outook:
Extremely limited.
Impairment, disability, handicap high.
Usually poor Department of Rehabilitation candidates.
Fascioscapulohumeral Muscular Dystrophy (FSHD; Landouzy-Dejerine)
Type of inheritance:
Autosomal dominant.
Transmitted by either parent to children of both sexes with 50% probability of incidence.
Clinical onset:
Range 7-25 years of age.
Differential diagnosis:
Sometimes confused, early in disease, with the ocular myopathies, myasthenia gravis (MG), congenital ptosis, and congenital facial diplegia.
Distribution of weakness:
Initial involvement of face muscles (lack of facial mobility).
Initial involvement of shoulder girdle muscles (difficulty raising arms overhead).
Leads to forward slope of shoulders.
Subsequent slow spread to hip girdle muscles.
Distal arm / hand muscles affected late in disease.
Often asymmetric weakness and atrophy.
Progression:
Usually very slow progression of weakness.
No apparent progression for several years, in some cases.
Loss of ambulation uncommon.
Clinical characteristics:
Considerable variation among and within families.
Unlined face, pouting appearance of lips, difficulty closing eyes and inability to whistle.
Occasionally have indistinct speech.
33% incidence of mild contractures.
Significant restrictive lung disease in some cases.
35% with spine deformity (usually hyperlordosis).
No calf hypertrophy.
Cognitive impairment not associated with this disease.
Good psychosocial adjustment.
Life expectancy:
Normal .
Treatment:
May benefit from medical rehabilitation.
Training / Work outlook:
Impairment, disability and handicap low.
Historical employment rate 88%,
Educational level 14 years +/-3.
Limb Girdle Muscular Dystrophy (LGMD; limb girdle syndrome)
Type of inheritance:
Autosomal recessive is most common. About 10% of cases representing at least six subtypes are autosomal dominant.
Clinical onset:
Generally before age 20 for autosomal recessive forms.
Differential diagnosis:
Prior to availability of genetic testing, many disorders presenting with muscle weakness in a limb-girdle distribution led to diagnostic confusion, including spinal muscular atrophy (SMA) and the mitochondrial and metabolic myopathies. LGMD has also been mistaken for fascioscapulohumeral muscular dystrophy and congenital muscular dystrophy.
Distribution of weakness:
Patients with LGMD generally show weakness and wasting restricted to the limb musculature, proximal greater than distal. Most patients with LGMD show relative sparing of the heart and bulbar muscles, although subtypes 1B (laminopathy) and 2C-2F (sarcoglycanopathies) have an associated cardiomyopathy that may be the predominant feature, rather than muscle weakness.
Clinical Characteristics:
Spine deformity, restrictive lung disease and cardiac involvement are relatively rare.
No facial involvement or cognitive impairment.
Good psychosocial adjustment all subtypes.
Life expectancy:
Usually normal with good medical management of secondary complications.
Treatment:
Medical rehabilitation can improve quality of life.
Training / work outlook:
Impairment, disability and handicap low in adult-onset subtypes.
Work outlook can be poor with LGMD onset in childhood.
Educational level 13 +/- 2 years.
Historical employment rate 71%.
Myotonic Muscular Dystrophy (Steinert's disease)
Type of inheritance:
Autosomal dominant.
Transmitted by either parent to children of both sexes with 50% probability of incidence.
Clinical onset:
Weakness at age 5-35 years.
Myotonia usually occurs before weakness.
Differential diagnosis:
Sometimes confused with congenital myotonia and paramyotonia during early stages of the disease.
Distribution of weakness:
Weakness and atrophy usually generalized but primarily proximal in early stages with later weakening of the hand and forearm muscles.
Facial muscles are sometimes involved.
Progression:
Variable but usually very gradual
Clinical characteristics:
Myotonia (inability to relax muscles) and stiffness primarily noted in hand muscles.
Multiple organ system involvement
19% with significant contractures.
15% with deformity of the spine.
Restrictive lung disease in some cases.
High incidence of cardiac involvement, especially life threatening conduction defects.
Often have indistinct speech.
May have cataracts.
Life expectancy:
Variable, depending on severity of cardiac involvement.
Treatment:
None for weakness.
Myotonia and heart conduction defects may be reduced by drug treatment.
Cataracts can be corrected with surgery.
Training / work outlook:
Impairment and disability usually low, but handicap high, apparently due to poor psychosocial adjustment.
Usually poor work outlook
Historical employment rate 39%
Educational level 13 +/- 2 years.
Polymyositis and Dermatomyositis Syndromes
Type of inheritance:
Acquired disease that is more common in females.
Five types:
Adult polmyositis.
Dermatomyositis.
Childhood polymyositis.
Myositis with malignancy.
Myosits associated with other connective tissue diseases.
Clinical onset:
At any age, but usually second to fifth decade.
Differential diagnosis:
May be confused in early stages with limb girdle muscular dystrophy.
Distribution of weakness:
Primarily severe (acute) and proximal.
Weakness of anterior neck and pharyngeal muscles very common.
Usually symmetrical
Progression:
Most types are rapidly progressive without treatment. With the exception of the childhood type and myositis with malignancy, most patients respond well to drug therapy.
Clinical characteristics:
Weakness present in all cases.
Over 50% experience pain or muscle tenderness.
33% arthritic features.
Contractures and muscle atrophy rare (except in cases of long-standing resistance to treatment).
Occasional cardiac interstitial fibrosis and pneumonitis in acute stage.
Disease usually self-limiting with successful treatment.
Life expectancy:
May be fatal in childhood polmyositis. Normal with successful treatment.
Treatment:
Drug therapy usually successful
Training / work outlook:
Impairment, disability and handicap high only in chronic form.
Good work outlook in most cases but poor in chronic form and childhood type.