Description

• Primary lateral sclerosis (PLS) is a rare progressive degenerative disease of the corticospinal and corticobulbar tracts (upper motor neurons [UMNs]), which spares the anterior horn cells.
• Characterized by leg weakness, spasticity, and bulbar symptoms like dysphagia and dysarthria
• Additional features include cognitive impairment, eye movement abnormalities, and urinary dysfunction.
• Part of the spectrum of motor neuron diseases (MNDs) because some patients with PLS evolve to develop amyotrophic lateral sclerosis (ALS)
• Conversion from PLS to ALS has been reported up to 27 years after the onset of spasticity.

Epidemiology

• Found in 1–3% of patients with motor neuron disorder
• Onset is usually after age 40 years, although a juvenile form has been described.
• Mean age at symptom onset is 54 years.
• There is a slight male predominance, which is similar to ALS.

Incidence
Incidence is difficult to determine due to rarity, misdiagnosis, and changing diagnosis. An estimated 1/10 million per year or 300 to 500 people in the United States are diagnosed yearly.

Prevalence
Estimated prevalence is 10 to 20 per million.

Etiology and Pathophysiology

PLS is usually sporadic with no known cause; potential role of TAR DNA–binding protein 43 (TDP-43) (1)

Genetics

• Juvenile PLS and juvenile ALS has been correlated with a mutation in the ALS2 gene on chromosome 2. It is inherited in an autosomal recessive pattern.
• Mutation of the ERLIN2 gene, a component of the endoplasmic reticulum lipid raft has been linked to juvenile PLS.

General Prevention

There is no known means of prevention.