Opinions expressed in the Correspondence section are those of the authors, and not necessarily of the editors, ACER or SAEM. The editor reserves the right to edit and publish letters as space permits. Letters not meeting submission criteria will not be considered for publication. See "Instructions for Authors."

CORRESPONDENCE S e r o l o g i c F in d in g s in L y m e D i s e a s e To the Editor." I read with interest the article by Brogan et al, "The Enlarging Clinical Spectrum of Lyme Disease: Lyme Cerebral Vasculitis, a New Disease Entity" [May 1990;19: 572-576]. Unfortunately, it has one serious flaw that renders the authors' conclusions invalid. The authors have totally misinterpreted the Lyme disease serologic findings in the patient's cerebrospinal fluid (CSF). A brief explanation of the methodology of determining CSF Borrelia burgdorferi (Bb) antibody titers is in order. There is passive transfer of IgG antibodies from the systemic circulation into the CSF of all patients (with or without Lyme disease); therefore, small quantities of Bb specific IgG antibody will appear in the spinal fluid of all patients with circulating serum Bb IgG antibodies. In an effort to correct for this passive diffusion, a CSF index is set up.

R o b e r t J Rothstein, MD, FACEP - - S e c t i o n E d i t o r Bethesda, Maryland

The method that the Stony Brook laboratory uses is well outlined in a recent paper by Halperin. l By measurement of total IgG in serum and spinal fluid and then by dilution, equal concentrations of IgG are obtained in a serum and CSF sample. Then ELISAs for Bb antibodies are run simultaneously on the same plate. An antibody level in CSF that is higher than the serum level is considered to be positive. How m u c h higher the CSF optical density (OD) needs to be, compared with the serum OD, is a source of debate, Z,3 but all authorities agree that to call CSF Bb serology positive, a ratio (CSP OD/serum OD) of at least 1.0 is necessary. In Brogan's case report, the CSF/ serum ratio (index) was 0.835, which is not positive for CSF Bb antibodies; rather, in all probability it represents passive transfer of antibodies from the systemic circulation. This misunderstanding of Lyme disease serologic testing renders the conclusions Brogan has drawn invalid. In addition, statements such as "Treatment with 2 g ceftriaxone ... was instituted, resulting in a resolution of symptoms," should not be made unless there is a proven causeand-effect relationship between treatment and results. What can be said about this case is that the patient had a thalamic infarct, beading of cerebral vessels consistent with a vasculitis, a positive Lyme titer in her serum, and no evidence of Bb antibody production in the CSF. This might be called a possible case of Lyme cerebral vasculitfs, but certainly nothing more; however, because negative CSF Bb serology does not rule out CNS Lyme disease, it was certainly appropriate to treat the patient as was done.

Steven W Luger, MD Old Lyme, Connecticut

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1. Halperin JJ, Luft BJ, Anand AK, et ah Lyme neuroborreliosis: Central nervous system manifestations. Neurology 1989;39:753-759. 2. Pachner AR. CNS Lyme disease (letter). Neurology 1990;40:189. 3. Halperin JJ, Luft BJ, Anand AK, et ah CNS Lyme disease (letter). Neurology 1990;40:190.

In Reply: I thank Dr Luger for his comments referring to our manuscript. There are generally two proposed mechanisms for how the spirochete B burgdorferi might be responsible for the CNS pathophysiology that appears to manifest itself as cerebral vasculitis. There is the idea of direct invasion of the spirochete into the CNS and also the notion of an immune-medicated mechanism not requiring local invasion of the spirochete. Although this second postulated mechanism is not well understood, it remains a plausible explanation for some of the pathophysiology reported with other spirochete-induced illnesses. IgM cryoglobulins have been implicated in this immune-medicated model. 1-4 In the previous case report of suspected Lyme vasculitis, the patient demonstrated elevated serum and CSF IgM titers prior to antibiotic therapy, s It has been proposed that the antigenic features of these organisms stimulate formation of antigenantibody complexes that induce damage to the vascular endothelium. 6 As with many of the issues regarding CNS Lyme disease, what critical antibody titer is needed to induce vaseulitis by this mechanism is of course unknown. Dr Luger's letter correctly referred to the method used at the Stony Brook laboratory for determination of serum and CSF optical densities (ODs). Although I agree that the CSF and serum ratios assist us in determining more accurately who has CNS Lyme disease, it too has its limitations. It has been stated that the assay technique has an inherent variability. 7 The difference between an OD ratio of 0.835 and 1.000 may possibly be due to such variability. There also may be a continuum where the CSF has been invaded by the B burgdorferi spirochete, and the patient is in fact producing antibodies to the spirochete, but at the time of the lumbar puncture the levels of IgG to the spirochete are not at a level to yield an OD ratio of 1.000. The article by Halperin has inherent limitations due to the study design. For example, only 14 of 22 patients in group 1 of this study even had lumbar punctures done. In this same group seven of 17 patients' MRI scans were abnormal. However, only four of these seven had CSF analyzed. In group 2 of this study one patient (III-5) had borderline antibody elevation but "was felt to have definite Lyme on clinical grounds, since he was from a highly endemic area, had Bell's palsy and recurrent aseptic meningitis, and improved with ceftriaxone. ''7 It is important to recognize the limitations of this study before drawing conclusions from it. Although it is often difficult to establish cause and effect, a patient presenting in an endemic area, with a posi-

Annals of EmergencyMedicine

19:11 November 1990