- lower motor neurons, which regulate voluntary
muscle function in the lower extremities - bulbar motor neurons, which affect the func-
tions of structures in the BRAINthat regulate
coordination of movement throughout the
body
As motor neurons die the muscles they control
can no longer function. As ALS progresses and
muscle cells become inactive, the muscles atrophy
(waste away). These events in combination result
in the debilitating loss of mobility. Regardless of the
disease’s point of origin, it eventually affects all vol-
untary muscles in the body. Because the bulbar
structures in the brain additionally have functions
related to emotion, loss of emotional control is also
common particularly in the disease’s later stages.
Researchers do not know what causes motor neu-
rons to die, nor do they know the precise mecha-
nisms by which cell death occurs.
Symptoms and Diagnostic PathThe development of symptoms varies with the
first location of motor neuron loss. Early symp-
toms of ALS are generally vague, sporadic, and
asymmetrical (one-sided). Among them are
- muscle cramps
- emotional inappropriateness and lability (mood
swings) - difficulty speaking, notably slurred speech
- excessive salivation (SIALORRHEA) and difficulty
swallowing
Symptoms gradually progress, often over the
course of several years, to a level at which they
interfere with normal activities. The diagnostic
path generally starts with BLOODtests to assess thy-
roid and parathyroid function and to detect any
presence of heavy metals, notably lead. HYPERTHY-
ROIDISM,HYPERPARATHYROIDISM, and lead poisoning
can cause symptoms similar to those of ALS. The
diagnostic path also includes electromyography
(EMG) to assess muscle function in affected as
well as unaffected limbs. The neurologist may fur-
ther conduct diagnostic imaging procedures of the
brain and spinal cord, such as MAGNETIC RESONANCE
IMAGING(MRI) of the cervical spine, to rule out
other causes of the symptoms. There are no defin-
itive diagnostic tests for ALS.LOU GEHRIG’S DISEASE
Amyotrophic lateral sclerosis (ALS) struck Ameri-
can baseball legend Lou Gehrig (1903–1941) at
the height of his record-setting career. After
Gehrig struggled for more than a year with the
progressive loss of neuromuscular function char-
acteristic of ALS, doctors made the diagnosis.
Gehrig remained a public figure even as his
health deteriorated, drawing attention to the dis-
ease that finally claimed his life at the age of 38.
Americans more familiarly know ALS as Lou
Gehrig’s disease. However, French neurologist
Jean-Martin Charcot (1825–1893) first described
the symptoms of this rare condition in 1869.
Doctors in France and much of Europe refer to
ALS as Charcot disease.Treatment Options and Outlook
At present treatment for ALS is primarily support-
ive; there is no cure. The medication riluzole,
which blocks release of the NEUROTRANSMITTERglu-
tamate, often can slow the progression of symp-
toms. Glutamate stimulates activity in the brain,
which correspondingly increases nerve signals to
parts of the body such as the muscles. People who
have ALS tend to have elevated blood levels of
glutamate, and some research suggests glutamate
overstimulation may damage motor neurons.
Researchers do not know what causes the eleva-
tion, however, or whether it contributes to or
results from the ALS. The neurologist may
prescribe other medications such as baclofen
and tizanidine to treat muscle spasms and anti-
cholinergic medications to control excessive sali-
vation.
The progressive loss of muscle control eventu-
ally affects vital functions such as swallowing,
which affects the ability to eat, and BREATHING.
Important treatment decisions as ALS progresses
include choices around the insertion of a perma-
nent feeding tube, called a percutaneous endo-
scopic gastrotomy (PEG) tube, to provide adequate
nutrition and assistive breathing devices, including
MECHANICAL VENTILATION. Some people who have
ALS choose full support to extend life as long as
possible and others opt for only those supportive224 The Nervous System