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.