[1] There is no evidence of the degeneration of spinal motor neurons or muscle wasting (amyotrophy) that occurs in amyotrophic lateral sclerosis (ALS).

Onset of PLS usually occurs spontaneously after age 50 and progresses gradually over a number of years, or even decades.

[4] PLS is not considered hereditary when onset is in adulthood; however, juvenile primary lateral sclerosis (JPLS) has been linked to a mutation in the ALS2 gene which encodes the cell-signalling protein alsin.

[8] Primary lateral sclerosis (PLS) usually presents with gradual-onset, progressive, lower-extremity stiffness and pain due to muscle spasticity.

[citation needed] Researchers do not fully understand what causes PLS, although it is thought it could be due to a combination of environmental and genetic factors.

[9] Studies are being done to evaluate the possible causes, although linking causality can be difficult due to the relatively low number of people who are diagnosed with PLS.

Hoffman's sign and Babinski reflex may be present and indicative of upper motor neuron damage.

[3] Patients with PLS may find it beneficial to have an evaluation, as well as follow-up visits at multidisciplinary clinics, similar to those available for people with ALS.

[2] Patients can often live with PLS for many years and very often outlive their neurological disease and succumb to some unrelated condition.