Epileptic seizures associated with intrathecal baclofen (ITB) application have been observed in patients with traumatic brain injury. A higher incidence of seizures has also been reported in patients with multiple sclerosis (MS) receiving ITB. To our knowledge, no case of a first epileptic seizure has been reported in the context of ITB bolus testing in MS. We report a 41-year-old female patient with primary progressive MS receiving olanzapine and oxcarbazepine for psychotic disorder. Five years prior she began to develop severe spastic quadriparesis, rendering her a candidate for ITB treatment. After ITB test bolus application, however, she experienced a first epileptic seizure. Our observation indicates that ITB may trigger seizures in patients with MS. The observed seizure occurred during ITB bolus testing despite antiepileptic co-medication, which concurs with previous reports suggesting that rapid changes in the dose of ITB may carry a higher risk of seizure induction.