Causes

In primary lateral sclerosis, the nerve cells in the brain that control movement (upper motor neurons) slowly break down and fail over time. This makes the nerves unable to activate the motor neurons in the spinal cord, which control voluntary muscles. This loss causes movement problems, such as difficulty with balance, weakness, slowed movement and clumsiness, and problems with speech and swallowing.

Adult-onset primary lateral sclerosis

The cause of PLS that begins in adulthood is unknown. In most cases, it's not an inherited disease, and it's not known why or how it begins.

Juvenile primary lateral sclerosis

Juvenile PLS is caused by mutations in a gene called ALS2.

Although researchers don't understand how this gene causes the disease, they know that the ALS2 gene gives instructions for creating a protein called alsin, which is present in motor neuron cells. When the instructions are changed in someone with juvenile PLS, the protein alsin becomes unstable and doesn't work properly, which in turn impairs normal muscle function.

Juvenile PLS is an autosomal recessive inherited disease, meaning that both parents have to be carriers of the gene to pass it to their child, even though they don't have the disease themselves.