The neurological form of canine distemper virus (CDV) infection can occur concurrently with systemic signs or develop following apparent recovery. There are no specific antiviral or immunomodulatory therapies recognized for treatment of CDV infections, and the neurological form typically carries with it a high mortality rate. The intrathecal injection of a modified live Newcastle disease virus vaccine (NDV-MLV) has been proposed for the treatment of the neurological forms of CDV infections. Thirteen dogs confirmed to have canine distemper infections by polymerase chain reaction testing and with neurological signs consistent with CDV infection were treated with an intrathecal injection of NDV-MLV and were scheduled for re-evaluation 3–4 mo later. Six dogs survived to follow-up and four dogs survived long term (>3 yr). Cerebrospinal fluid cytokines were measured and reported. Changes in cerebrospinal fluid cytokines and long-term survival could not be attributed to the intrathecal injection of NDV-MLV, and this therapy cannot be recommended for treatment of dogs with neurological forms of CDV infection.