Motor neuron disease is not one but a
group of rare neurological conditions in which motor neurons - the nerve cells
that control skeletal muscle movement – are progressively degenerated. Loss of motor
neurons results in muscle weakness that gradually worsens over time, impairing the body’s
ability to move, eat, speak, or even breathe. Usually, motor instructions from the brain
are transmitted to the muscles via 2 neurons: an upper motor neuron starts in the
primary motor cortex of the cerebrum; and a lower motor neuron continues
from the brainstem or spinal cord, forming the corticobulbar and corticospinal
tracts, respectively. The corticobulbar tracts control muscles of the face, head, and neck and
are responsible for facial expression, speech, swallowing, among others. The corticospinal
tracts control muscles of the torso and limbs. Lesions of upper and lower motor neurons
affect the muscles in different ways. A loss of upper motor neuron function often
leads to increased muscle tone, muscle stiffness, known as spasticity, and overresponsive reflexes.
On the other hand, lower motor neuron lesions often result in reduced muscle tone, flaccid
paralysis, and muscle wasting and twitching. The many forms of motor neuron disease are
classified according to whether the loss of neuron function is inherited or sporadic, and whether the
condition affects upper or lower motor neurons. The most common form is amyotrophic lateral
sclerosis, ALS, which affects both upper and lower motor neurons. Patients typically present
with spastic paralysis and overactive reflexes in the lower limbs; and flaccid paralysis and
reduced responses in the upper limbs, along with tongue twitching. In the later stage, symptoms
may also include slurred speech, and difficulty swallowing and breathing. Most people with ALS
die from respiratory failure, typically within a few years from diagnosis, although a small number
of patients may survive for a much longer time. ALS usually strikes in midlife, but it can occur
in people of any age. Most ALS cases are sporadic, only about 10% are inherited, with
at least a dozen of genes involved. Progressive bulbar palsy, PBP, affects the lower
motor neurons that originate from the brainstem, also known as the bulbar region. Symptoms include
difficulty chewing, swallowing, and speaking. PBP is sometimes considered a subtype of
ALS, because most PBP patients eventually also develop widespread muscle weakness.
Primary lateral sclerosis, PLS, affects only upper motor neurons. The lower limbs are often
the first to be affected, followed by the torso, upper limbs, and eventually, the muscles
involved in chewing, swallowing, and speaking. PLS progresses much more slowly than ALS and is
not usually fatal. However, because a number of ALS cases start out as PLS, a PLS diagnosis is
considered definitive only after at least 4 years. Spinal muscular atrophy, SMA, is a group
of genetic disorders affecting lower motor neurons. There are many different forms
of SMA, caused by mutations in different genes, with different modes of inheritance. The three
main forms are due to defects in the same gene, but differ in age of onset and severity.
Spinobulbar muscular atrophy, or Kennedy’s disease, is a form of SMA caused by mutations in
the androgen receptor gene on the X chromosome. This disease typically strikes in adulthood and
affects mostly men but is transmitted by their mothers and daughters who carry the mutation.
Early symptoms include tremor, lower limb weakness, and tongue twitching. Late symptoms
include widespread muscle weakness and wasting. The disease however progresses very slowly,
with most patients having a normal lifespan. Post-polio syndrome, PPS, is a condition
that affects polio survivors, sometimes decades after the initial illness. Symptoms
include muscle and joint weakness and pain, twitches, muscle wasting, and intolerance to cold.
Some patients may also have difficulty breathing and swallowing. PPS is usually not fatal.
There is no cure for motor neuron disease, but supportive treatments can relieve symptoms
and may help maintain quality of life.
