Disorders of the Anterior Horn Cell

Julie Thorne Parke

The anterior horn cells may be involved selectively in a number of acquired and inherited diseases. Certain viruses, particularly poliomyelitis, demonstrate a specific affinity for these nerve cells. Herpes zoster and coxsackievirus also occasionally affect anterior horn cells. Inherited conditions influencing the anterior horn cells include the spinal muscular atrophies (SMAs) and numerous metabolic disorders. Damage to the anterior horn cells is characterized clinically by weakness, atrophy, and hyporeflexia. Fasciculations are common findings. Because the dorsal sensory root is not involved in these disorders, sensory abnormalities are not present. Motor nuclei in the brainstem are involved commonly, so bulbar dysfunction is seen frequently.

SPINAL MUSCULAR ATROPHIES

The SMAs are hereditary degenerative diseases affecting the motor neurons of the brain stem and spinal cord. Several distinct clinical presentations exist (Table 406.1), differing by age at onset of symptoms, severity of symptoms, and length of survival. SMA I, SMA II, and SMA III are autosomal recessive disorders, all caused by a mutation of the survival motor neuron gene (SMN) on chromosome 5q13. A large, 500-kilobase duplication is present on 5q, containing two SMN genes. The pathogenic gene SMN1 is in the telomeric copy of the duplication. The homozygous absence of SMN1 is the primary cause of SMA. A centromeric copy of the gene SMN2 differs slightly
and encodes an unstable, truncated protein. The severity of the disease is determined mainly by the number of SMN2 copies present. Most infants with SMA I have one or two copies of SMN2. Most individuals with SMA II or SMA III have three or more copies, thus producing more SMN protein. The SMN protein is an essential factor in the cytoplasmic assembly of spliceosomes. It also may play a role in the renewal or regeneration of spliceosomes in the nucleus. The clinical categories of SMA continue to be useful in describing the severity of disease, although they now are recognized as variants of the same disease (Box 406.1).

TABLE 406.1. PROGRESSIVE SPINAL MUSCULAR ATROPHIES

Disorder	Inheritance	Age of Onset	Clinical Features
Acute infantile SMA (acute Werdnig-Hoffmann disease, SMA type I)	Autosomal recessive	In utero to 6 mo	Frog-leg posture; severe weakness with some movements of fingers and toes; most are unable to sit; areflexia; tongue atrophy and fasciculations; progressive swallowing and respiratory problems; survival <3 years
Intermediate SMA (chronic Werdnig-Hoffmann disease, SMA type II)	Autosomal recessive; rarely autosomal dominant	3 mo to 15 yr	Proximal weakness; most sit, some walk until teens; decreased or absent reflexes; long periods of apparent arrest; high incidence of scoliosis, contractures; unusual tremor (minipolymyoclonus); survival varies several years to third decade
Juvenile SMA (Kugelberg-Welander disease)	Autosomal recessive; rarely autosomal dominant	5–15 yr	May be part of continuous disease spectrum of SMA type II; proximal weakness with hip and shoulder atrophy; calf hypertrophy; decreased or absent reflexes; may remain ambulatory into fourth decade
SMA, spinal muscular atrophy.

Acute Infantile Spinal Muscular Atrophy (Werdnig-Hoffmann Disease, Spinal Muscular Atrophy Type I)

Patients with the most severe form of SMA present a stereotypic picture, with the onset of symptoms occurring within the first 6 months of life. In one-third of cases, the onset occurs in utero, with a notable decrease in fetal movements during the last months of pregnancy. These infants are hypotonic and weak in the neonatal period, and they have significant feeding difficulties and respiratory distress. Other children may appear physiologically normal for the first few weeks of life while generalized weakness of the extremities, trunk, and bulbar muscles gradually develops. A typical frog-leg posture, characterized by abduction of the arms with flexion at the elbows and abduction of the legs with flexion at the knees, is seen in the early stages of the disease.

Physical examination reveals marked hypotonia and generalized and symmetric weakness. Movements may be limited to flickering of the fingers and toes. The tendon reflexes almost invariably are absent. The child is unable to support the head and cannot straighten the trunk when held in ventral suspension. Respirations are shallow, and chest movements may be paradoxic. Feeding difficulties occur early, and secretions pool in the mouth as swallowing becomes further impaired. Visible atrophy and fasciculations of the tongue may be present. The extraocular muscles are not affected. The child appears alert and attentive, and development is normal with the exception of motor skills. Contractures are not seen commonly in the early stages of the disease, although a few patients have congenital contractures or dislocation of the hip. The natural course is one of gradually increasing weakness, with development of feeding difficulties and respiratory compromise. In most cases, death occurs from a pulmonary infection with respiratory failure before the patient reaches 3 years of age.

Only gold members can continue reading. Log In or Register to continue