Methods of treating, preventing and/or managing central nervous system disorders, such as Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease) and related syndromes are disclosed. Specific methods encompass the administration of an immunomodulatory compound of the invention, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, clathrate, or prodrug thereof, alone or in combination with a second active ingredient. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.