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U N I T 1 0
Nervous System
Upper Motor Neuron Disorders
Upper motor neuron disorders involve neurons that
are fully contained within the CNS. They include the
motor neurons arising in the motor areas of the cortex
and their fibers as they project through the brain and
descend in the spinal cord. Disorders that affect UMNs
include multiple sclerosis and spinal cord injury. Stroke,
which is a common cause of UMN damage, is discussed
in Chapter 37. Amyotrophic lateral sclerosis is a mixed
UMN and LMN disorder.
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as
Lou
Gehrig disease
after the famous New York Yankees
baseball player, is a devastating neurologic disorder that
selectively affects motor function. Amyotrophic lateral
sclerosis has an annual incidence of about 2 cases per
100,000 population. It is primarily a disorder of middle
to late adulthood, with men being affected more fre-
quently than women. The disease typically follows a
progressive course, with a mean survival period of 2 to
5 years from the onset of symptoms.
Amyotrophic lateral sclerosis is characterized by the loss
of anterior LMNs in the spinal cord and motor nuclei of the
brain stem and UMNs that originate in the motor cortex
and descend via the pyramidal tract to synapse with the
LMNs.
42–44
The death of LMNs leads to denervation, with
subsequent muscle fiber atrophy and shinkage of skeletal
muscles. It is this fiber atrophy, called
amyotrophy,
that
appears in the name of the disease. The loss of nerve fibers
in lateral columns of the white matter of the spinal cord,
along with fibrillary gliosis, imparts a firmness or sclerosis
to this CNS tissue; the term
lateral sclerosis
designates these
changes. A remarkable feature of the disease is that the
entire sensory system, the regulatory mechanisms of control
and coordination of movement, and the intellect remain
intact. The neurons for ocular motility and the parasym-
pathetic neurons in the sacral spinal cord are also spared.
The pathogenesis ofALS is largelyunknown, despite the
identification of a number of genetic associations.
18,37,42,43,45
Approximately 5% to 10% of cases are familial ALS,
mostly with autosomal dominant inheritance. The rest
are believed to be sporadic, with no family history of the
disease. The gene for a subset of familial ALS has been
mapped to the superoxide dismutase 1 (
SOD1
) gene on
chromosome 21. SOD1 is a critical enzyme involved in
protecting neurons from oxidative damage. Other sug-
gested mechanisms of nerve injury are alterations in
transport of molecules necessary for maintenance of the
axon, neurofilament abnormalities, and glutamate-medi-
ated excitotoxicity (see Chapter 37).
Manifestations of amyotrophic lateral sclerosis
include those of both UMN and LMN dysfunction.
42–45
Muscle cramps involving the distal legs often are an
early symptom. The most common clinical presenta-
tion is slowly progressive weakness and atrophy in dis-
tal muscles of one upper extremity. This is followed by
regional spread of muscle weakness, reflecting involve-
ment of neighboring areas of the spinal cord. Eventually,
UMNs and LMNs involving multiple limbs and the
head are affected. In the more advanced stages, mus-
cles of the palate, pharynx, tongue, neck, and shoulders
become involved, causing impairment of chewing, swal-
lowing (dysphagia), and speech. Dysphagia with recur-
rent aspiration and weakness of the respiratory muscles
produces the most significant acute complications of the
disease. Death usually results from involvement of cra-
nial nerves and respiratory musculature.
There are no specific tests for ALS. Diagnosis is
based on a careful medical history, detailed physical
and neurological examination, and electrophysiologi-
cal studies.
43,44
Currently, there is no cure for ALS. The
treatment of persons with ALS, which requires man-
agement of medical problems, severe disability, and
psychosocial problems, is best provided by a multidis-
ciplinary team.
42–44
Measures to assist persons with the
disorder manage their symptoms (e.g., weakness and
muscle spasms, dysphagia, communication difficulty,
excessive salivation, and emotional lability), nutritional
status, and respiratory muscle weakness increase sur-
vival time. An antiglutamate drug, riluzole, is the only
drug approved for the treatment of ALS.
42
The drug is
designed to decrease glutamate accumulation and slow
the progression of the disease.
Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune demyelinat-
ing disorder characterized by inflammation and selective
destruction of CNS myelin.
37,38,46–51
It affects approxi-
mately 350,000 persons in the United States and more
than 1 million worldwide.
46
The age of onset is typically
between 18 and 45 years.
46
Women are affected twice as
frequently as men.
As with other autoimmune disorders, the pathogen-
esis appears to involve both genetic and environmental
influences. The risk for developing MS is 15-fold higher
when the disease is present in a first-degree relative, and
is even greater in monozygotic twins.
37
People with the
human leukocyte antigen (HLA)-DR2 haplotype (see
and controlled skilled movements. Disorders
of the basal ganglia are characterized by
involuntary movements, alterations in muscle
tone, and disturbances in posture.
■■
Parkinsonism is a disorder in which there is an
imbalance between the dopaminergic inhibitory
effects and excitatory cholinergic functions of
the basal ganglia, and is manifested by resting
tremor, increased muscle tonus and rigidity,
slowness of movement (i.e., bradykinesia), gait
disturbances, and impaired postural responses.
SUMMARY CONCEPTS
(continued)
