Long-term neurologic consequences of CNS therapy

Certain chemotherapeutic agents, in particular vincristine, cisplatinum, paclitaxel and thalidomide are well known to cause peripheral neuropathies. The neurotoxicity associated with these agents is typically related to both the dose and duration of therapy, and hence limits their potential efficacy. Unfortunately, assessment of chemotherapy-induced peripheral neuropathies is exceedingly difficult in the young child. Most studies report a combination of subjective and objective criteria to assess peripheral neuropathies.1 Subjective complaints include paresthesias and numbness, signs and symptoms, which are particularly difficult to elicit in young children. Although motor abnormalities, such as foot drop, may be identified on clinical examination, subtle weakness of dorsiflexion of the feet may be missed in a young child. This is particularly true in the infant or young child who is non-ambulatory. Furthermore, objective neurophysiologic evaluations of children with nerve conduction velocities and electromyography are obtained only when specifically indicated because the procedures are both painful and frightening. Therefore, much of the literature on chemotherapy-induced peripheral neuropathy in children is suboptimal. Extrapolating from adult studies is problematic because adults often have complicating neurotoxic factors, such as diabetes, alcohol use, remote effects of carcinoma, and other pre-existing diseases. Finally, most studies report neurotoxicity based on combination chemotherapy making firm conclusions regarding a single agent difficult. It is clear that, since the neurotoxicity of many agents is both dose-and time-dependent, the pediatric neurology community will need to develop a better system for assessing neurotoxicity in young children.