Thalidomide neuropathy

Thalidomide is both an old and a new drug, whose history is steeped in controversy. It was originally introduced in 1957 as a sedative-hypnotic and antiemetic drug for use during pregnancy. It was withdrawn in late 1961 because of its potent teratogenic effects on limb development (amelia, absence of limb; phocomelia, seal limb) and other congenital abnormalities. Interestingly, particularly in light of two articles in this issue of Neurology,1,2⇓ it was concern over early reports of peripheral neuropathy in adults that prevented approval of the drug in the United States by the Food and Drug Administration (FDA), largely averting the tragic consequences seen in 46 other countries.3

Thalidomide is a glutamic acid derivative that has several actions. These include a role in modifying integrin receptors, altering tumor necrosis factor-α (TNFα) production, and inhibiting angiogenesis.4 It down-regulates TNFα synthesis by accelerating its mRNA degradation, an action that may alter the course of nerve Wallerian degeneration but that may also paradoxically lessen neuropathic pain.5,6⇓ Among these actions, why it causes clinical neuropathy is unclear because neither TNFα nor angiogenesis appears necessary to intact peripheral nerves. A direct action at the level of the cell …