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Show Journal of CliniCilI Neuro-ophtha/mology 8(3): 157-159, 1988. Editorial Comment Seronegative Ocular and Neurosyphilis Diagnostic and Therapeutic Pitfalls © 1988 Raven Press, Ltd., New York The excellent article by Currie et al. in this issue merits meticulous scrutiny by every neuro-ophthalmologic clinician. The lessons it so eloquently documents, if not apprehended, will lead the unwary into serious diagnostic and therapeutic traps that can otherwise be avoided. It is doubtful if any greater disparity exists in medicine today between the scientific facts repeatedly documented in the literature for well over 50 years and the information base actually being used by current practitioners than is the case with the diagnosis and treatment of ocular and neurosyphilis. To illustrate this thesis, the reader is invited to take the following brief test at this point as a sort of "pre-test," if you will: 1. A negative serum VDRL test excludes the diag-nosis of clinically active syphilis. True _ False __ 2. A positive CSF VDRL test is necessary for the diagnosis of clinically active neurosyphilis. True __ False __ 3. Clinically active neurosyphilis can be present with a nonreactive CSF FTA Abs test. True __ False __ 4. A negative serum TPI test excludes the possibility of clinically active neurosyphilis. True __ False __ 5. Penicillin therapy given in doses currently recommended by the Communicable Disease Centers cures ocular and neurosyphilis and prevents clinical recurrences thereafter. True __ False __ 6. Clinically symptomatic and progressive neurosyphilis is ruled out by a negative spinal fluid examination (acellular fluid with normal protein and nonreactive VDRL and FTA-Abs tests). True __ False __ 7. The serum FTA-Abs test is always reactive in patients with clinically active late syphilis. True __ False __ Before discussing the pre-test questions above, let us first look at the article by Currie et al. under 157 consideration. There are two ways one could approach this article from the standpoint of editorial analysis. One would be a critical analysis of the data as presented with insightful comments to help, if possible, even the expert in this field. That would probably be an easier job and require a shorter editorial with fewer references. The other would be to try to supplement the information provided by Currie et al. so as to build a better information base for the reader. Time and space restraints preclude all the comments and references that can be given, so an attempt to be selective from both perspectives will be made here. Let us first look at Currie's case 1. A 7-year-old boy developed enuresis, temporal lobe seizures, and his school work deteriorates after blunt head trauma. By age 18, overt neurologic abnormalities (deafness, mental deficiency, pyramidal-tract signs) prompted lumbar puncture, which revealed pleocytosis, elevated globulin, and a positive CSF Wassermann reaction. One should not simply pass by the statement that neurologic symptoms followed the blunt head trauma. In the classic text Modern Clinical Syphilology, Ed. III, by Stokes, Beerman, and Ingraham, W.B. Saunders, Philadelphia, 1945, which will be referred to again in this discussion because it is the last complete text with regard to syphilis before the influence of penicillin, there are interesting comments with regard to the role of trauma in syphilis. On page 14, Stokes states: "Unquestionably the chief significance of trauma appears in the later periods of the disease." Evidence of this relationship is given under several headings. The development of gummas in the scars of healing surgical wounds is well known in operations on nasal septum and pharynx in heredosyphilis (p. 15), Numerous examples of gummatous changes in war wounds were recorded during World War I. Klauder described cases in which the Wassermann reaction became positive after trauma, although repeatedly negative before. One cannot help but remember that point on reading the interesting statement in Currie's article that in case 1 "specific treponemal 158 EDITORIAL COMMENT serology of blood and CSF was always negative except for one positive CSF FTA Abs after surgery." On page 815, Stokes documented the developed of a gumma of the ribs at the site of an injury where a workman had been thrown against a window ledge 10 months earlier, striking the right side of the chest, and in the discussion stated "this is a typical traumatic history in osseous syphilis," and noted that the "pain and swelling do not begin for some days after the injury." It is not our purpose here to belabor a relationship between trauma and syphilis. However, from the ophthalmologic point of view, the main point of interest is that activation of previously quiescent interstitial keratitis by wearing contact lenses in late congenital syphilis was an accepted fact pointed out to this author while at the Wilmer Institute in the 1950s. The next point to be mentioned in Currie's case one was that "despite the absence of any family history of venereal disease," the diagnosis of "congenital tertiary cerebrospinal syphilis" was made in the patient (which in my opinion certainly was correct). One would wonder if the patient's mother was examined along with appropriate blood tests or whether this was simply based on the clinical anamnesis. It would be interesting to know the dose and duration of the course of heavy metals given the patient, but let us pass on. At age 21, Currie's case 1 showed bilaterally "choked" disks, but because the acuity was normal one would suspect this was either true papilledema or syphilitic optic perineuritis. Unfortunately, the CSF pressure was not given at the time of that examination. Another thought that entered the mind is in noting that at age 24, the patient had three lumbar punctures done over a 3-month interval that showed 36, 0, and 42 lymphocytes, respectively. A 3-week course of penicillin was given "without effect." One would like to know the time that the penicillin was given with regard to these spinal fluid examinations. It would have been interesting if the course of penicillin had been given between the first and second spinal fluid examinations listed, and if that might have been related to the transient clearing of the lymphocytic pleocytosis. There appeared subsequently to be definitely more involvement that a superior orbital fissure syndrome, for a classic march of cranial nerve palsies across the base was documented with regard to II, III, IV, V, VI, VII, VIII, X, XII on the right at least. At any rate, the clinical course continued to progress despite at least two courses of penicillin therapy (3 weeks on one occasion, and 300,000 U b.i.d. for 18 days on J Clin Neuro-ophthalmol. Vol. 8, No.3, 1988 another, without evident effect), and also despite nonreactive serum VORL and FTA-Abs tests, and culminated in the mystery finally being resolved by craniotomy and the histologic di~gnosi~ of a posterior fossa gumma. It would certamly be mteresting to have that tissue specimen reexa~nedby appropriate silver stains by someone particularly interested in the subject such as Dr. Alan MacDonald to see if spirochetal forms could be found in the surgical tissue after the prior penicillin therapy. It was encouraging that the patient did show a significant change after the then rather heroic course of 504 million U of intravenous penicillin given postoperatively. Currie's case 2 illustrates other extremely interesting points. Just as a "hard-core" syphilologist might not accept either of these cases as "absolutely" seronegative (in that case 1 had one positive CSF Wassermann test and showed a reactive CSF FTA-Abs test on one occasion after surgery, and case 2 had reactive serum FTA-Abs tests on two occasions), certainly the clinicians who saw these patients obtained many serologic tests on both peripheral blood and spinal fluid with usually negative results. Another interesting point was the negative TPI test (presumably on serum) noted in case 2. The TPI test has been considered in some quarters as the absolute "gold standard" for the serodiagnosis of syphilis, but even this test, although an excellent one despite being difficult for the clinician to obtain in this country, has failed on other occasions besides this report (see "The false-negative Treponema pallidum immobilization test in syphilis. Pseudo-biologic false positive syndrome," JAMA 199: 128, 1967). Finally, the presence of a visible mass in the nasopharynx in case 2 proven by biopsy to show inflammatory tissue is reminiscent of another case of a nasopharynx biopsy with tissue mimicking a gumma previously documented in Spirochetes in Late Seronegative Syphilis, Penicillin Notwithstanding, published by C. C. Thomas, Springfield, IL, 1969. Although that book is now out of print, a copy can be obtained from an appropriate library and would make interesting reading to anyone who desires to pursue this subject further. There simply is not the space here to go into the topic appropriately. Let the reader remember that The ,New York Times, Sunday, October 4, 1987 reported that "the number of syphilis cases has more than doubled in New York City, is up 97 percent in Los Angeles County and has risen 86 percent in Florida, according to state and local officials." With the increasing number of AIDS cases influencing not only the incidence of syphilis EDITORIAL COMMENT 159 cases, but also their severity (see Johns DR, et al., "Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus," N Engl JMed 316(25):1569-1572, June 18, 1987) and possibly even masking the seroresponses (see Hicks CB, et al., "Seronegative secondary syphilis in a patient infected with the human immunodeficiency virus with Kaposi sarcoma," Ann Intern Med 107:492-495, October 1987), it is evident that clinicians not only need to relearn the old information about syphilis that has been forgotten from modern medical school curricula (see Jeremiah 6:16-17) but also to remember that syphilis is not extinct but is alive and well and hides itself to that ophthalmologist or neurologist who only orders a serum VORL or RPR test and forgets to routinely get a serum FTA-Abs test. Although the serum FTA-Abs test may be rarely nonreactive, as documented in Currie's report, it still will serve the clinician well when considering the differential diagnosis of this disease. It probably isn't appropriate to mention here that 22% of cases of Lyme disease have been reported showing reactive serum FTA-Abs tests, at least at a 1:5 dilution. Thank you, Drs. Currie, Coppeto, and Lessell, for this extremely important article. It is important that it comes from geographical "nonbastions" of the disease. I believe their article will give the answers to the "pre-test," by the way. Clinical neuro-ophthalmology becomes more exciting and challenging every day! J. Lawton Smith, M.D. Bascom Palmer Eye Institute University of Miami School of Medicine Miami, Florida JGill Neuro-Ol'hthalmol, Vol. 8, No.3, 1988 |
