Penicillin in Neurosyphilis

General ObservationsPenicillin, introduced into therapeutics in 1941, was at first restricted to the treatment of certain specified infec- tions.This limitation was by Government direction, and was mainly due to the necessity for conserving the some- what scanty supplies.It is only within the last year that penicillin has become available for more general use, and especially for experimental therapeutics.Nevertheless, penicillin already has an established place in the treatment of neurosyphilis.It was recognized quite early that the substance had a definite antispirochaetal action, and in 1943 Mahoney, Arnold, and Harris published the results of treating a series of cases of early syphilis with penicillin.From these and the subsequent observations of other workers it became apparent that the immediate results of treatment with penicillin in early syphilis equalled if they did not exceed those obtained with intensive arsenical and bismuth therapy.Further, there was the added advantage that with penicillin there was little or no risk of toxic reactions.Subsequently, rapid improvement in both the clinical condition and the cerebrospinal fluid changes in various forms of late syphilis was reported.From the follow-up of cases of early syphilis treated with penicillin alone, however, it became apparent that a moderately high rate of relapse occurred.In addition, it was noted that the percentage of cases relapsing was roughly inversely proportional to the total dosage of penicillin given, in the earlier cases treated this had no doubt been in- adequate.These observations finally determined what was considered an optimal total dosage expressed in so many Oxford (now international) units.By June, 1944,,penicillin was adopted as the " drug of choice " for the treatment of early syphilis in the U.S. Army in Europe, and, in the autumn of 1944, in the Royal Navy, R.A.F., and the British Army.The standard course was fixed at a total dosage of 2,400,000 units given in doses of 40,000 units every three hours, day and night (60 injections), over a period of seven and a half days.Even with this dosage the average relapse rate in early syphilis appears to have been as high as 15% in some series of cases (Marshall, 1946; King, 1946), while others report an 8% (Marshall, 1946) and 7% (Moore, 1945) relapse rate.Dosage and Methods of Administration Most of the present-day experiences of penicillin in neurosyphilis are based on the results of a dosage and a frequency of administration similar to those of the standard *The opening paper read at a joint discussion between La Socidt6 de Ndvrologie de Paris and the Section of Neurology, Royal Society of Medicine, on April 15, 1947.