Current status of penicillin therapy in neurosyphilis

Abstract

I N 1943 Mahoney, Arnold and Harris’ reported that penicillin was an active spirocheticide and an effective agent in the treatment of early syphilis. Almost immediately penicillin was tried in the treatment of the various forms of neurosyphilis. Here again it was demonstrated to be efficacious. In most cases of asymptomatic neurosyphilis and syphilitic meningitis the drug cleared up the cerebrospinal fluid in a very short time and relieved the symptoms of meningitis. (It should be borne in mind that this type of neurosyphilis has responded well in many instances to almost all forms of arsenical treatment and very well indeed to fever.) The problem remaining after the first survey of penicillin was that of adequate dosage. It soon became evident that an aqueous solution of amorphous penicillin, 3 million units given over a period of seven to fifteen days at six-hour intervals, was likely to give a favorable outcome in a great majority of cases. This conclusion was arrived at by trying a number of schedules differing in the amount of penicillin administered and the duration of the course and the time interval between injections. The development of new forms of penicillin, such as the slowly absorbed forms of penicillin like procaine penicillin in oil, has made it difficult to be more specific than this about dosage at the present time. General Paresis. The problem of the best form of treatment for the more destructive forms of neurosyphilis (general paresis and tabes dorsalis) was not so readily arrived at; in fact, there is at this time a considerable difference of opinion among various investigators. It early became evident that in general paresis penicillin was remarkably effective in improving the spinal fluid abnormalities. Three million units of the drug at six-hour intervals over a two-week course almost invariably produces in the course of three to six months a marked reduction in the spinal fluid cell count and total protein. However, with the dosage limited to 3 million units, spinal fluid relapse takes place in not a few cases, suggesting that in all probability the .cerebral syphilis had not been adequately controlled. On the basis of such relapsing tendencies the dosage was increased by most investigators to 6, 9 and 12 million units. Other investigators gave repeated courses of penicillin, with an interval of one month or more between the courses. Another question about the effectiveness of penicillin in the treatment of general paresis relates to the improvement of the psychotic state when this exists. There is a great difference of opinion about this. Reports from the Mayo Clinic,2 Johns Hopkins3 and the Boston Psychopathic Hospital4 indicate that the psychologic response of the paretic psychosis is by no means as good when penicillin alone is relied upon as when fever treatment is given. On the other hand, investigators at the University of Pennsylvania Clinic’ and Bellevue Hospital6 are strongly of the opinion that the clinical results are equally good if not better with penicillin alone. The Michigan group’ first reported that the psychosis did not respond as well with