Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF.

OBJECTIVE: To determine the frequency of mild/atypical herpes simplex virus encephalitis (HSVE) among patients with CSF specimens submitted to a university diagnostic virology laboratory for HSV PCR. BACKGROUND: HSVE is the most commonly recognized cause of acute sporadic encephalitis in the United States. Recognized clinical features are based on autopsy- or brain biopsy-confirmed cases. This is likely to produce ascertainment bias for features associated with severe disease and under-recognition of mild or atypical cases. Amplification of HSV DNA by PCR from CSF provides a sensitive and specific method for diagnosis of HSVE. METHODS: Results of all HSV CSF PCR tests sent to a university diagnostic virology laboratory (January 1, 1993, to December 31, 1996) were reviewed. Clinical information was prospectively collected and retrospectively reviewed. Patients with positive HSV CSF PCR tests were classified as having meningitis, encephalitis, or neonatal infection. Encephalitis was considered typical or atypical based on published criteria. RESULTS: A total of 7.6% of 1,224 CSF specimens were positive for HSV DNA. CSF HSV DNA-positive patients had meningitis (52%), encephalitis (26%), neonatal infection (17%), or nonclassifiable disease (5%). A total of 17% of HSVE patients had mild or atypical disease characterized by the absence of focal findings and slow progression in the absence of antiviral therapy. Atypical HSVE was associated with HSV-2 infection (two of the four patients), immunosuppression by steroid therapy or coexisting HIV infection (three of the four patients), or disease predominantly involving the nondominant temporal lobe (two of the four patients). CONCLUSIONS: Approximately one-fifth of HSVE patients have mild or atypical disease. CSF PCR for HSV DNA should be performed in patients with febrile encephalopathy even in the absence of focal features, initial CSF pleocytosis, or abnormal CT. Mild or atypical HSVE may be associated with infection with either HSV-1 or HSV-2. Mild or atypical HSVE was frequently associated with immunocompromise or asymmetric HSV infection affecting predominantly the nondominant temporal lobe.

Localization and imaging with radioiodine-labeled monoclonal antibodies in a xenogeneic tumor model for human B-cell lymphoma.

Two MoAbs directed towards human B-cell malignancies have been studied in a preclinical animal model to evaluate their potential for in vivo imaging and therapy of B-cell lymphomas. Anti-B1 reacts with virtually all immunoglobulin-bearing malignancies and non-T acute lymphoblastic leukemia. Anti-J5 reacts with the common acute lymphoblastic leukemia antigen found on non-T acute lymphoblastic leukemia and follicular lymphomas. Anti-T1 which recognizes the CD5 antigen on most T-cell leukemias and lymphomas was used as a control antibody. These monoclonal antibodies were radiolabeled with 125I or 131I by the ICl method. Namalwa (B-cell) and MOLT-4 (T-cell) tumors were grown s.c. in irradiated nude mice. The highest tissue concentration of 125I-labeled anti-J5 in Namalwa-bearing mice was in blood and tumor. The tumor/blood ratio ranged from 0.7-1.2, with the highest ratio 4 days after injection. Pharmacokinetic analysis indicated that the t1/2 beta of anti-J5 from blood and other tissues ranged from 40-50 h, while the t1/2 beta for tumor averaged 65 h. The area under the curve of tumor was 2- to 5-fold higher than the area under the curve of liver, kidney, skin, and muscle. The peak tissue levels of 125I-labeled anti-B1 in Namalwa-bearing mice were again in blood and tumor and 6 days following injection more than 5-fold greater activity was found in tumor compared to normal tissues other than blood. The tumor/blood ratio was 1.2 and 0.7 at 4 and 6 days after injection. 125I-labeled anti-B1 showed minimal uptake in antigen-negative MOLT-4 tumors and 125I-labeled anti-T1 showed little uptake in Namalwa tumors. Scintigraphic images were obtained following the injection of 131I-labeled anti-J5 and anti-B1 in nude mice bearing Namalwa tumors. These results indicate that radiolabeled anti-J5 and anti-B1 show promise as diagnostic and possibly therapeutic agents for human B-cell lymphoma, although there may be a limitation to clinical utility due to cross-reactivity with some normal cells.