Experiments done in dogs to throw light on the correlation between epilepsy in patients and large doses of penicillin during cardiopulmonary bypass showed that bypass itself did not cause penicillin to be epileptogenic. However mild transient brain damage such as could occur during a bypass operation, in association with a high concentration of penicillin in the blood, could lead to epilepsy. Although intra-arterial air or i.v. penicillin alone always failed to cause epilepsy, a small (1·0 ml.) intra-arterial air embolus within 1 hr of an i.v. dose of 4 × 105 units benzylpenicillin/kg. nearly always caused epilepsy. The incidence of epilepsy was lower when the dose of penicillin was smaller.
Assays of penicillin in CSF showed the highest levels in dogs which fitted but there was so much overlap with those which did not fit that CSF penicillin assays are not of diagnostic significance.