Detection of IgG in cerebrospinal fluid for diagnosis of neurocysticercosis: evaluation of saline and SDS extracts from Taenia solium and Taenia crassiceps metacestodes by ELISA and immunoblot assay

We compared saline (S) and sodium dodecyl sulphate (SDS) extracts from Taenia solium (homologous species - HO) and Taenia crassiceps (heterologous species - HE) metacestodes in order to detect IgG by ELISA and immunoblot assay (IBA) in cerebrospinal fluid (CSF) for the diagnosis of human neurocysticercosis (NC). CSF samples were obtained from 93 patients. Of these, 40 had NC, five had a diagnosis of probable NC, nine had central nervous system schistosomiasis or strongyloidiasis and 39 had other neurological alterations. Samples were analysed by ELISA and the results were compared with IBA in all samples with confirmed and probable NC diagnosis, in all samples with other central nervous system parasitic infection, and in 10 of those with another neurological alterations. ELISA sensitivity was 100%, 85%, 95% and 87.5% for the S-HO, S-HE, SDS-HO and SDS-HE extracts, respectively, and ELISA specificity was 100% for S-HO, S-HE, SDS-HO extracts and 97.9% for SDS-HE antigen. Immunodominant peptides detected by IBA were, by decreasing percentage of recognition: 64-68 and 45 kDa for S-HO; 108-114, 92-95, 64-68, 83 and 88 kDa for S-HE; 64-68, 108-114, 77 and 86 kDa for SDS-HO; and 108-114, 88 and 92-95 kDa for SDS-HE. Overall the homologous antigenic extracts showed higher sensitivity than the heterologous extracts in the diagnosis of NC in CSF samples. The heterologous extracts contained most of the immunodominant peptides presented in the homologous extracts, which are recognized by IgG antibodies in CSF samples.     

Recombinant expression of Taenia solium TS14 antigen and its utilization for immunodiagnosis of neurocysticercosis

In order to evaluate the potential use of TS14 antigen in an enzyme-linked immunosorbent assay (ELISA) for immunodiagnosis of neurocysticercosis (NC), its open reading frame (ORF) was amplified by RT-PCR from mRNA isolated from Taenia solium cysticerci. The ORF was subcloned into the expression vector pET-28a, and was used to transform Escherichia coli BL21 (DE3) cells to produce TS14 antigen. The His-tagged expressed protein was purified on a nickel affinity column. Using the _HISTS14 as antigen, ELISA was positive for 100% of cerebrospinal fluid (CSF) and 97% of serum samples from NC patients. No positive results were observed with sera and CSF samples from control groups. Cross-reactivity with sera from patients with schistosomiasis and Chagas’ disease was not observed. Serum samples from patients with taeniasis were evaluated and 2 of 13 cases showed reactivity in this assay. Our data indicate the usefulness of _HISTS14 in ELISA for an accurate and rapid assay for diagnosis of NC and seroepidemiological studies.     

老年结核性脑膜炎脑积水35例临床分析

目的探讨老年结核性脑膜炎(结脑)并发中?重度脑积水的临床特征与影像学变化?方法回顾性分析经影像学证实的老年结脑并发中?重度脑积水35例?结果大脑导水管梗阻占82.9%,基底池粘连占20.0%?脑脊液(CSF)蛋白定量?白蛋白?IgG升高与脑积水有关?结论脑膜纤维蛋白渗出?粘连与老年性脑室变窄是造成脑积水的主要因素?CT与CSF中蛋白指标监测对脑积水的早期诊断?预后评估具有重要价值?     

Evaluation of an antigen from Taenia crassiceps cysticercus for the serodiagnosis of neurocysticercosis

We report here the evaluation of an antigen from Taenia crassiceps cysticercus as a potential reagent in an enzyme-immunoelectrotransfer blotting assay (EITB) and an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of neurocysticercosis (NC) using clinical specimens obtained from patients in different phases of the disease. Serum and cerebrospinal fluid (CSF) samples from 64 patients suspected of having NC according to clinical manifestation and brain computed tomography were tested by ELISA with Taenia solium total saline antigen (ELISA-Tso) and by immunoblotting with T. crassiceps glycoproteins antigen (EITB-gpTcra). Forty-five serum samples were also tested immunoblotting with T. solium glycoproteins antigen (EITB-gpTso) and 30 were tested by ELISA with T. crassiceps 14 kDa glycoprotein (ELISA-gp14Tcra). Serum samples from apparently healthy individuals without any parasitic disease and from patients with other parasitic diseases were included as controls. The results of ELISA-Tso analysis with CSF obtained from 64 patients with NC showed that 53 (83%) were reactive. EITB-gpTcra analysis with serum from the same group of patients showed a sensitivity of 91%. Results of EITB-gpTso and EITB-gpTcra analysis with serum samples demonstrated an agreement of 100% between both tests. ELISA-gp14Tcra was positive in 23 (77%) sera, 22 with paired CSF positive. When ELISA-gp14Tcra results were compared to EITB-Tso results, a relative sensitivity of 95% was observed. All serum samples from the control group were negative in ELISA-gp14Tcra and only one serum from an individual with Taenia saginata was reactive in this assay, showing a specificity of 99% for ELISA-gp14Tcra. This fraction was purified in only one step with a good yield for use in immunoassays. We suggest that the gp14Tcra antigen can be used for detecting anti-cysticercus antibodies in serum samples for epidemiological investigation purposes and also for diagnostic screening of NC patients.     

Soluble CD23 in cerebrospinal fluid: a marker of AIDS-related non-Hodgkin's lymphoma in the brain.

BACKGROUND: AIDS-related non-Hodgkin's lymphoma (NHL) includes systemic lymphomas, often with brain involvement, and primary central nervous system (CNS) lymphomas. OBJECTIVE: To examine if measurement of soluble CD23 (sCD23) in cerebrospinal fluid (CSF) is useful in the diagnosis and follow-up of AIDS-related NHL. METHOD: sCD23 was measured by enzyme-linked immunosorbent assay and EBV DNA by nested polymerase chain reaction for a group of 134 patients. The NHL group included 14 patients with primary HIV-1 CNS lymphoma, 12 patients with brain involvement of systemic HIV-1 NHL and 10 patients with systemic HIV-1 NHL without brain involvement. These were compared with HIV-1-infected patients with cerebral toxoplasmosis (19), progressive multifocal leukoencephalitis (PML; 8) and AIDS-related dementia (17) and with asymptomatic HIV-1 carriers (54) and uninfected individuals (50). The levels of sCD23 were compared with the presence of Epstein-Barr virus (EBV) DNA in CSF. RESULTS: Significantly higher levels of sCD23 were found in the CSF of the patients with brain lymphoma than in those with systemic NHL (P < 0.002) or with cerebral toxoplasmosis, PML and AIDS-related dementia (P < 0.0001). The sensitivity and specificity of sCD23 in CSF as a marker for detection of brain NHL were 77% and 94%, respectively. High levels of sCD23 were found in CSF from patients with brain NHL independently of the presence (18 out of 26) or absence (8 out of 26) of EBV DNA. CONCLUSIONS: The sCD23 in CSF of HIV-1-infected patients may represent an additional, non-invasive marker for diagnosis of brain involvement in AIDS-related NHL.     

Detection of Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid by inhibition ELISA and its diagnostic potential in tuberculous meningitis

Inhibition ELISA was used to quantitate Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid (CSF) specimens of 40 patients with a clinical diagnosis of tuberculous meningitis. In all 10 culture-proven patients, the assay was positive; in 30 culture-negative patients, the assay yielded positive results for 21. CSF antigen 5 concentrations ranged from 9 to 82 ng/ml (mean +/- SD, 45.5 +/- 6.2). In 40 patients with nontuberculous neurologic diseases, mean concentration was 1.45 ng/ml. Thus, inhibition ELISA for the detection of M. tuberculosis antigen 5 in CSF has definite diagnostic potential during the active phase of the disease and should be a routine diagnostic test, particularly when bacteriologic cultures in CSF are negative for M. tuberculosis.     

Cerebrospinal fluid and serum carcinoembryonic antigen in brain tumors

Carcinoembryonic antigen (CEA) has been indicated to be a marker for brain tumors. In this study CEA was measured in serum and cerebrospinal fluid (CSF) of 14 patients with benign brain lesions, 16 with primary brain tumors and 8 with metastatic brain tumors by radioimmuno assay. Tumor cyst fluid CEA of 6 patients having intracranial tumors was also measured. The control group (n=20) had no neurological disease. The mean CEA levels in CSF for the control group, patients with benign tumors, primary tumors and metastatic tumors were 0.22 ng/ml, 0.31 ng/ml, 0.92 ng/ml, and 6.3 ng/ml respectively. Corresponding serum CEA levels were 2.5, 2.7, 3.0 and 5.2 ng/ml. Results showed that CEA level in CSF may play an important role in differential diagnosis of primary and metastatic brain tumors and consequently management of the treatment. To our knowledge this is the first such study on brain tumors from India.     

阿尔茨海默病和帕金森痴呆患者脑脊液中tau蛋白和β淀粉样蛋白水平的研究

目的探讨在阿尔茨海默病(AD)和帕金森痴呆(PDD)患者脑脊液(CSF)中tau蛋白和β淀粉样蛋白(Aβ1-42)的水平及临床意义。方法同时将符合美国国立神经病、语言障碍和脑卒中研究所-老年性痴呆及相关性疾病协会的“很可能AD”标准的22例AD组患者与20例PDD组患者和21例性别、年龄相匹配的无中枢神经系统疾患、无痴呆表现的心理疾病患者作为对照组(NC组)进行研究。结果3组CSF中tau蛋白平均浓度比较,AD组明显高于NC组(P<0.05);AD组与PDD组差异无显著性意义(P>0.05)。3组CSF中A1β-42平均浓度比较,AD组明显低于NC组(P<0.05),PDD组与NC组差异无显著性意义(P>0.05)。结论AD患者CSF中tau蛋白和Aβ1-42浓度变化是其重要的实验室表现,可以作为AD的辅助诊断指标和与PDD早期鉴别诊断的可能生物学指标。     

Detection of antigen B of Cysticercus cellulosae in cerebrospinal fluid for the diagnosis of human neurocysticercosis

Neurocysticercosis (NCC) is a major cause of morbidity and mortality in developed and developing countries. The diagnosis of this disease remains a problem. We report the detection of specific antigenic fraction (antigen B) of Cysticercus cellulosae by enzyme-linked immunosorbent assay (ELISA) in various fractions of cerebrospinal fluid (CSF) obtained by high performance liquid chromatographic (HPLC) separation, for the diagnosis of human NCC. Forty patients attending or admitted to Nehru Hospital, Chandigarh were included in the study: 10 with suspected NCC, 20 with other neurological diseases and 10 undergoing surgery under spinal anaesthesia for non-neurological conditions, who served as controls. CSF samples collected from all patients and controls were subjected to chromatographic separation on an HPLC system. Antigen B (AgB) was detected in separated fractions by an ELISA test and compared with the detection of antibody response in CSF samples by indirect haemagglutination (IHA) technique. Antigen B was detected in 9 out of 10 patients with suspected NCC based on clinical symptoms and radioimaging reports, but in none of the control subjects. However, antigen B was also detected in 9 out of 20 patients with other neurological disorders, mostly tubercular meningitis. Antibody response by IHA was found positive in only 2 of 10 cases clinically suspected of NCC. In conclusion, antigen B detection in CSF samples may be a useful adjunct to clinical suspicion and radiological reports for the diagnosis of NCC as there is no gold standard criteria to confirm this disease. However, the test needs to be evaluated on more patients in countries where tuberculosis and cysticercosis are endemic due to the high cross reactivity with samples from tubercular meningitis patients.     

Evaluation of an IgG-ELISA strategy using Taenia solium metacestode somatic and excretory-secretory antigens for diagnosis of neurocysticercosis revealing biological stage of the larvae

Diagnosis of neurocysticercosis (NCC) is complicated because of the variability in clinical presentations and course of the disease where viability of parasite is a major determinant. The present study describes evaluation of ELISAs using Taenia solium metacestode somatic and excretory-secretory (ES) antigens for detection of anti-T. solium metacestode IgG antibodies in serum and cerebrospinal fluid (CSF). And results of the ELISAs in cases with a definitive diagnosis of NCC are correlated with the biological stages of the parasite such as live vesicular or degenerated stage. The sensitivity of the IgG-ELISA using ES antigen is observed to be much higher in serum (88.2%) than in CSF (64.28%) although it is only marginally higher in serum (76.4%) than in CSF (75%) when somatic antigen is used in the ELISA. Whereas, the specificities of the ELISA using either somatic or ES antigen for detection of IgG antibodies in serum (97.97%; 96.96%) and CSF (96.42%; 97.61%) are comparable. A strong association is observed between live stage of the parasite and detection of antibodies in sera and CSF from more number of NCC patients by ELISA using ES antigens. Similarly, detection of antibodies by ELISA using somatic antigens could be associated with the dead or degenerated stage of the parasite in brain. The IgG-ELISA strategy developed in the present study opens up an avenue for diagnosis of NCC in hospitals or in population prevalence studies. The use of crude extracts of ES proteins might improve the serodiagnosis of the cases of NCC carrying live vesicular stage of the parasite larvae.     

Severe Cysticercal Meningitis: Clinical and Imaging Characteristics

In disease-endemic areas, severe cysticercal meningitis (SCM) is characterized by intense inflammatory cerebrospinal fluid (CSF) and negative bacterial and fungal cultures. There have been no systematic studies of SCM. We characterized patients with SCM and compare them with neurocysticercosis (NC) patients with mild CSF abnormalities by conducting a nine-year retrospective review at a neurological referral center. Two groups of patients were compared: group A, those with severe CSF pleocytosis > 1,000 cells/mm³ (n = 12), and group B, those with CSF pleocytosis ≤ 1,000 cells/mm³ (n = 126). All patients had positive CSF results in an enzyme-linked immunosorbent assay for cysticercal antigens and negative CSF cultures for bacteria, fungi, and mycobacteria. Intracranial hypertension, meningeal signs, CSF hypoglycorrachia, and a longer clinical course of NC were more frequently seen in group A. It is likely that SCM often goes unrecognized. Its correct identification may reduce morbidity and risks of unnecessary surgery in patients with chronic NC and CSF shunts.     

Sarcoidosis: clinical, hormonal, and magnetic resonance imaging (MRI) manifestations of hypothalamic-pituitary disease in 9 patients and review of the literature

Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency.In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations.     

99m锝-多聚白蛋白动态肺灌注扫描在肝肺综合征早期诊断中的意义

目的探讨99mTcMAA与肺功能测定在肝肺综合征(HPS)早期诊断中的意义.方法选择HPS患者(28例)和无HPS肝硬化患者(30例)测定其肺功能和99mTcMAA,同时以健康人(21例)作为对照.结果HPS组动脉血氧分压(PaO2)、动脉血氧饱和度(SaO2)和肺一氧化碳弥散量(DLco)(分别为6.3、76.3、62.0kpa)显著低于肝硬化组(分别为11.7、90.6、81.6 kPa)(P＜0.01)和对照组(P＜0.01),P(A-a)O2显著增高(P＜0.001);99mTcMAA显示,HPS患者均有肺外脏器(脾、肾、肝和脑)显影,肺内动-静脉分流比和吸入纯氧气时Qs/QT均显著高于肝硬化组(P＜0.01)和对照组(P＜0.001).肝硬化组与对照组比较,DLco显著减低(P＜0.05),P(A-a)O2、肺内动-静脉分流比和吸入100%氧气时Qs/QT显著增高(P＜0.001和P＜0.001),其中有3例(10%)有肺外脏器显影.结论肺功能测定和99mTcMAA是HPS早期诊断的较敏感的指标.     

检测血清和脑脊液中囊尾蚴循环抗原诊断脑囊虫病的研究

目的：用抗血清检测脑囊虫病患者血清和脑脊液（ Ｃ Ｓ Ｆ）中囊尾蚴循环抗原（ Ｃ Ａｇ）诊断脑囊虫病。方法：用 Ｓ Ｄ Ｓ Ｐ Ａ Ｇ Ｅ提纯的蛋白质分子量为 ６４ ｋ Ｄａ、５３ ｋ Ｄａ、３２ ｋ Ｄａ～３０ ｋ Ｄａ 的囊尾蚴抗原分别免疫家兔,制备相应的抗血清,以双夹心 Ｅ Ｌ Ｉ Ｓ Ａ 检测患者血清和 Ｃ Ｓ Ｆ中 Ｃ Ａｇ。结果：抗５３ ｋ Ｄａ 抗原抗血清对 ３２ 例脑囊虫病活动型患者血清和 Ｃ Ｓ Ｆ中 Ｃ Ａｇ 的检出率分别为９３．８％ 和９１．７％ ,１６ 例脑囊虫病非活动型患者仅１ 例 Ｃ Ｓ Ｆ Ｃ Ａｇ 阳性。 Ｃ Ａｇ 检出率明显高于用抗６４ ｋ Ｄａ、３２ ｋ Ｄａ～３０ ｋ Ｄａ 囊尾蚴抗原抗血清检测的结果（ Ｐ＜ ０．０５）。结论：抗５３ ｋ Ｄａ 囊尾蚴抗原抗血清检测活动型脑囊虫病患者血清和 Ｃ Ｓ Ｆ中的 Ｃ Ａｇ 敏感性较高,特异性较强,可用于活动型脑囊虫病的诊断和疗效考核。     

Circulating parasite antigen in patients with hydrocephalus secondary to neurocysticercosis

End stages of neurocysticercosis include residual intraparenchymal brain calcifications and hydrocephalus. Although brain calcifications alone have a benign prognosis, hydrocephalus is frequently associated with chronic inflammation and intracranial hypertension, together with a protracted clinical evolution, and may lead to patient deaths. By using a monoclonal-based antigen detection enzyme-linked immunosorbent assay, we measured the levels of circulating parasite antigen in the sera of 56 patients with neurocysticercosis: 27 with calcifications only and 29 with hydrocephalus. The assay gave positive results in 14 of 29 patients with hydrocephalus but was consistently negative in patients with calcifications. Circulating parasite antigen in hydrocephalus secondary to neurocysticercosis indicates the presence of live parasites in these patients and thus a potential benefit from antiparasitic therapy.     

Clincal, Cerebrospinal Fluid and Pathological Findings and Outcomes in HIV-Positive and HIV-Negative Patients with Tuberculous Meningitis

Background: The early diagnosis of tuberculous (TB) meningitis remains difficult. In South Africa, the HIV epidemic has shifted the spectrum of meningitis towards chronic infections (mainly tuberculosis [TB] and cryptococcosis). This study aimed to analyse clinical, cerebrospinal fluid (CSF) and pathological findings and outcomes in TB meningitis to evaluate whether HIV infection significantly influences the characteristic findings. Patients and Methods: 40 consecutive patients with TB meningitis presenting at the Pretoria Academic Hospital were evaluated clinically and chest-X-raxs (CXR), computerized tomography (CT) brain scans, CSF profiles, HIV and routine blood tests were analyzed. Postmortem examinations (PM) were performed in seen patients and outcomes were assessed after treatment. Results: 20 patients were HIV-positive and 17 were netgative (three not tested). History and clinical findings were similar in both groups. The mean Glasgow Coma Scale (GCS) value on admission was 13 in both groups, while CXR showed abnormalities consistent with TB in 9/17 with HIV and 7/15 without, with abnormal CT brain scans in 15/19 patients with HIV and 12/16 without. Dilated ventricles and infarcts occurred more commonly in HIV-positive patients. The CSF results showed similar results in both groups. PM in three HIV-positive patients showed weakly formed granulomas and extensive endarteritis and infarcts. Outcomes were similar in the two groups, but a low GCS value on admission was a better prognostic indicator thant the CD4-count in HIV-positive patients. Conclusion: HIV infection does not significantly alter clinical and CSF findings in TB meningitis in South Africa, but ventricular dilatation and infarcts are more frequent in HIV-positive patients. The GCS gives a better indicator of prognosis than the CD4-count. Received: November 10, 2000 · Revision accepted: June 2, 2001     

Comparative Study of Paired Serum and Cerebrospinal Fluid Samples from Neurocysticercosis Patients for the Detection of Specific Antibody to Taenia solium Immunodiagnostic Antigen

Neurocysticercosis (NCC) is an important disease of the central nervous system caused by infection with Taenia solium metacestodes. In addition to the clinical findings and the imaging analysis, the results of immunological tests are informative for the diagnosis of NCC. To compare the usefulness of serum and cerebrospinal fluid (CSF) samples for antibody detection, paired serum and CSF samples from patients with NCC and other neurological diseases were examined by an enzyme-linked immunosorbent assay with low-molecular-weight antigens purified from T. solium cyst fluid in a blinded fashion. The sensitivity of both serum and CSF samples was 25.0% in inactive NCC cases (n = 4) and 90.9% in active NCC cases (n = 33), and the specificity of serum and CSF was 100% and 95.8%, respectively. When the serum and CSF samples were combined, the sensitivity in active NCC cases became 100%. There was no difference in test performance between serum and CSF samples. Based on these results, we recommend the detection of specific antibodies in serum for the diagnosis of active NCC because of the ease of collection. When the antibody test is negative, however, CSF should be used to confirm NCC and to rule out other medical disorders of the central nervous system. Antibody detection test using only serum or CSF has a limited diagnostic value and cannot be recommended for the diagnosis of suspected inactive NCC cases.     

Production and characterization of monoclonal antibodies identifying breast tumor-associated antigens.

We have generated a mouse monoclonal antibody (H23) against the retrovirus-like particles (human mammary tumor virus) released in vitro by the human breast adenocarcinoma cell line T47D. This antibody reacts specifically with a glycoprotein with an apparent molecular mass of 68 kDa (gp68) that is detected in the growth medium of T47D cells as well as in pleural effusion fluids from breast adenocarcinoma patients. No detectable levels of this antigen could be observed in pleural effusions of patients with cancers other than of breast origin. The H23-related antigen was localized in the cytoplasm of breast tumor cells as well as on the cell surface of both T47D cells and metastatic cells from breast cancer patients. A survey of tissue from 812 patients was performed by using H23 in an indirect immunoperoxidase assay. The results showed that the antigen was detectable in 91% of all breast tumors tested. No cytoplasmic staining was observed in either normal tissues or nonbreast carcinomas. Only one of the benign breast tissues tested (out of a total of 56 samples of tissue) was positive for this antigen. Given the ability of this antibody to specifically detect breast tumor cells, H23 may be of importance in diagnosis and in clinical follow-up of patients for the detection of metastatic lesions by imaging and for therapy.     

Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid.

Polymerase chain reaction (PCR) assay was used to detect herpes simplex virus (HSV) DNA in mouth, skin, sera, or cerebrospinal fluid (CSF) from seven neonates with HSV infection. In a culture-negative patient, the diagnosis was confirmed by detection of HSV DNA. Serial examinations revealed that HSV DNA remained in the serum and/or CSF from several patients for 1-2 weeks after the beginning of treatment. Next, the results of PCR assay in neonatal HSV infections were compared with those in older children with herpes simplex encephalitis (HSE). HSV DNA was detected in CSF from four neonates with central nervous system involvement and in CSF from all nine children with HSE. Sera were positive for HSV DNA in five of seven neonates, including two cases of localized infections, but in none of the children with HSE. These results suggest that HSV may be spread principally via viremia in neonates. PCR assay could be useful for the confirmative diagnosis of neonatal HSV infections, especially in culture-negative cases.     

Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment

STUDY OBJECTIVES: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS: Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.