Herpesviruses and human endogenous retroviral sequences in the cerebrospinal fluid of multiple sclerosis patients

OBJECTIVE: To analyze the possible role of human herpesvirus (HHVs) and human endogenous retroviruses (HERVs) infection in multiple sclerosis (MS) pathogenesis. METHODS: A total of 92 cerebrospinal fluid (CSF) samples were collected: 48 from MS patients at the first clinically evident demyelinating event, 23 from patients with other inflammatory neurological diseases (OINDs) and 21 from patients with other non-inflammatory neurological diseases (ONINDs). Total DNA and RNA were isolated, and the prevalences and viral loads of herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, HERV-H and HERV-W in the CSF of MS patients and controls were evaluated using a quantitative real-time polymerase chain reaction assay. RESULTS: (i) For HSV, 1/48 (2.1%, 86 copies/ml of CSF) MS patients and 1/23 (4.3%, 115.2 copies/ml of CSF) OIND patients (a myelitis case) had HSV sequences in the CSF; (ii) for EBV, only 1/48 (2.1%, 72 copies/ml of CSF) MS patients was positive for EBV; (iii) for HHV-6, only 5/48 (10.4%) MS patients had HHV-6 genomes in their CSF (128.1 copies/ml of CSF); (iv) we did not find any positive cases for VZV, CMV, HERV-H and HERV-W among MS patients or controls; (v) no cases of co-infections were found; (vi) the whole prevalence of HHVs was 7/48 (14.6%) for MS patients and 1/44 (2.3%) for controls (p = 0.038). CONCLUSION: The findings described here show that HHV infection is more frequent in the CSF of MS patients than in patients with other neurological diseases; however, only HHV-6 seems to be involved in the pathogenesis of MS in a subset of patients.     

Human herpes virus 6 and human herpes virus 8 DNA sequences in brains of multiple sclerosis patients, normal adults and children

In order to determine whether the newly discovered human herpesviruses (HHVs) are involved in multiple sclerosis (MS), we investigated by polymerase chain reaction the presence of specific deoxyribonucleic acid (DNA) sequences belonging to human herpesvirus 6 (HHV-6) and to human herpesvirus 8 (HHV-8), in the peripheral blood mononuclear cells (PBMCs), and in the brain and spinal cord plaques from MS patients. Normal adult and stillborn children’s brains were investigated as controls. PBMCs from 56 MS patients contained HHV-6 DNA in only 3 cases and in none were there HHV-8 sequences. The cerebral DNA from 5 MS patients was positive for HHV-8 and not for HHV-6 sequences, while the nervous tissue of one patient who died with neuromyelitis optica was positive for HHV-6 and negative for HHV-8. The brains of 4/8 adult controls were positive for HHV-6, as were 3/8 for HHV-8; none of the 7 stillborn children’s cerebral tissue contained HHV-6 sequences, while 2 contained HHV-8 DNA. Although these data do not support a hypothesis that there is a role for these two HHVs in the pathogenesis of MS, nevertheless it may be suggested that (1) the two viruses possess strong neurotropism and the central nervous system seems to be a reservoir for them (2) HHV-6 infection is probably not transmitted maternally, but is acquired later in infancy. Received: 6 February 1997 Received in revised form: 18 April 1997 Accepted: 18 April 1997     

Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack

To verify the possible role of human herpesviruses as triggering or aggravating factors in relapsing-remitting multiple sclerosis (RRMS) clinical acute attack, we studied the prevalence of some herpesviruses in the peripheral blood mononuclear cells (PBMCs) collected from 22 MS patients during an MS relapse and in a stable phase and from 18 healthy controls (HC). DNA belonging to Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), Human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and Human Herpes virus 6 (HHV-6) has been searched by specific nested polymerase chain reaction (n-PCR). EBV and HHV6 DNA has been detected with high frequency in acute and stable MS and in healthy controls without significant differences. HCMV DNA was observed both in acute and stable MS but not in HC, and, more interestingly, HSV-1 DNA was only found in 13% of acute MS, while both stable MS and healthy controls were negative. On the basis of these results we focused on HSV-1, and to confirm them and to demonstrate that HSV-1 is actively replicating in MS patients during clinical relapse, we searched both messenger RNA (mRNA) and DNA of HSV-1 in the PBMCs of 15 acute MS patients and 15 healthy controls. We found HSV-1 mRNA and DNA in a significant number of acute MS patients but not in the control group. On the whole these data indicate that HSV-1 reactivate in the peripheral blood of MS patients during clinical acute attack and probably play a role in the triggering of MS relapses.     

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein–Barr virus

Background and purpose

Epstein–Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection.

Methods

In the Ausimmune case–control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein–Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates.

Results

In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08–4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 10⁶ copies/mL).

Conclusions

HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.     

A single tube PCR assay for simultaneous amplification of HSV-1/-2, VZV, CMV, HHV-6A/-6B, and EBV DNAs in cerebrospinal fluid from patients with virus-related neurological diseases

Cerebrospinal fluid (CSF) specimens from 27 patients with encephalitis, meningitis, and other neurological diseases were studied for the presence of herpes simplex virus types 1 and 2 (HSV-1/-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesviruses 6A and 6B (HHV-6A/-6B) and Epstein-Barr virus (EBV) DNA using the polymerase chain reaction (PCR) method. The DNAs were amplified using two sets of consensus primer pairs in a single tube, bringing simultaneous amplification of the herpesviruses. The PCR products were analyzed by agarose gel electrophoresis, and Southern blot hybridization with virus-type specific probes, thus allowing discrimination between the different types of herpesviruses to be made. Each virus-specific probe was highly specific for identifying the PCR product. Thirty CSF specimens from 13 patients with encephalitis and 10 specimens from 10 patients with meningitis, respectively, were examined using this method. Eight patients with encephalitis and six with meningitis were positive for different herpesviruses, including patients with coinfections (HSV-1/-2 and VZV, VZV and CMV). Among four CSF specimens from four patients with other neurological disorders, dual amplification of CMV and EBV was present. Since identification of the types of herpesviruses in this system requires a very small amount of CSF, and is completed with one PCR, it is useful for routine diagnosis of herpesvirus infections in diagnostic laboratories. The viruses responsible for central nervous system infection are easily detected with various coinfection and serial patterns of herpesviruses, by this consensus primer-based PCR method. This may give an insight into the relationship between virus-related neurological diseases (VRNDS) and herpesvirus infections.     

Leukotropic herpesviruses in multiple sclerosis

Detection frequency of human herpesvirus 6 (HHV-6) and Epstein Barr virus (EBV) DNA in multiple sclerosis (MS) patients and controls was investigated. DNA of peripheral blood mononuclear leukocytes (PBL) was isolated and amplified by polymerase chain reaction techniques. EBV DNA was detected in all patients and controls. HHV-6 DNA was detected in 7% of MS patients and in 14% of controls. Results are compared with other investigations of HHV-6 DNA in PBL, serum, CSF and brain of patients with MS. Results of the present study and other investigations do not show an association between HHV-6 in PBL and MS. Multiple Sclerosis (2000) 6, 66 - 68     

Human herpesviruses in MS

Environmental factors operate on a background of genetic susceptibility in MS pathogenesis; the human herpesviruses (HHV) are likely candidates for such factors. HHV share a number of properties: they are almost ubiquitous, they are highly prevalent worldwide, they all cause latent infections and they are capable of reactivation. Epstein Barr virus (EBV), HHV-6A and varicella zoster virus (VZV) are consistently linked with MS, particularly with respect to epidemiology, antibody responses in serum (EBV) and cerebrospinal fluid (EBV and HHV-6A), and with MS exacerbations that are associated with viral reactivation (VZV, HHV-6A and EBV). HHV have the potential for a causal role in MS--they may be key players in the disease process--and this role could be mediated through several direct or indirect mechanisms.     

Activation of endogenous retrovirus reverse transcriptase in multiple sclerosis patient lymphocytes by inactivated HSV-1, HHV-6 and VZV

Human endogenous retroviruses (HERVs) and herpesviruses have been associated with the development of multiple sclerosis (MS). These virus groups interact with each other and have been shown to induce synergistic immune responses. Here, we focus on the possible role of herpesviruses as contributing factors in HERV activation. We demonstrate the ability of HSV-1, HHV-6, and VZV antigens to induce higher RT activity in peripheral lymphocytes from MS patients vs. controls during the first 6 days post-antigen stimulation. On subsequent days, only VZV can sustain the increase in the RT expression in cells from MS patients. The RT induction does not depend on herpes replication.     

The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point.

In this study, we searched for evidence for reactivation of three latent herpesviruses, Epstein-Barr virus (EBV), herpes simplex virus type-1 (HSV-1), and human herpesvirus 6 (HHV-6), in West Point cadets experiencing two different stressors. Blood samples were obtained from cadets before and after a 6-week training period known as "Cadet Basic Training" (CBT), at a baseline prior to final examinations, and then once again during the week of final examinations. Antibody titers to latent HSV-1, EBV, and HHV-6 were determined as a measure of the steady-state expression of latent virus. EBV virus capsid antigen (VCA) IgG antibody titers were unchanged in blood samples obtained prior to and immediately after CBT. However, EBV antibody titers were significantly higher in the blood sample obtained during examination week than in the baseline period before examination; they were also higher than antibody titers before/after CBT. None of the serum samples were positive for EBV VCA IgM antibodies, indicating that the changes in antibody titers to EBV were not associated with recent EBV infections in the class. No significant changes in antibody titers to HSV-1 or HSV-6 were found over the identical time periods, including examination week. Academic stress but not CBT modulated the steady-state expression of latent EBV, resulting in the reactivation of latent virus. The same stressors, however, did not affect the steady-state expression of latent HSV-1 or HSV-6, at least as measured by changes in antibody titers. The data provide additional evidence of the impact of different psychological stressors on the steady-state expression of latent herpesviruses.     

Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients: associations with disease activity

OBJECTIVE: To assess the presence of Epstein-Barr virus (EBV) and human herpesvirus 6B (HHV-6B) DNA in saliva and plasma from multiple sclerosis (MS) patients enrolled in a randomized, double-blind, placebo-controlled valacyclovir treatment study. METHODS: DNA was prepared following ultracentrifugation of saliva and plasma. EBV and HHV-6B DNAs were determined by real-time polymerase chain reaction. RESULTS: EBV and HHV-6B DNAs were detected in 41% and 65% of saliva samples, respectively. In patients treated with valacyclovir, the percentage of saliva samples with EBV was significantly reduced (9%; P = 0.000017), whereas the frequency of HHV-6B positive samples was unchanged (57%; P = 0.38). Longitudinal studies demonstrated a time-dependent reduction in the frequency of saliva samples containing EBV following valacyclovir treatment. In contrast, plasma contained EBV and HHV-6B DNAs in 17% and 25% of the samples, respectively, and these numbers were not significantly reduced following valacylovir treatment (13% and 16%, respectively), nor were they different from those of healthy controls (6% and 39%, respectively). Patients with high disease activity had a significantly higher frequency of EBV (P = 0.018) and HHV-6B (P = 0.023) positive samples than did patients with low disease activity. The presence of EBV and HHV-6B was strongly correlated in plasma (P < 0.00000001), but not in saliva (P = 0.41). CONCLUSION: MS patients express EBV and HHV-6B in both saliva and plasma, but only the expression of EBV in saliva is significantly reduced following valacyclovir treatment. Although EBV and HHV-6B DNAs can be detected in plasma from healthy individuals, the co-expression of both these viruses in MS patients is highly significant and further associated with clinical activity. The observations of viral DNA in plasma are consistent with an underlying immunologic defect in MS.     

Herpesviruses in brains in Alzheimer's and Parkinson's diseases

We evaluated the association of HSV-1, HHV-6, and VZV with Alzheimer's disease (AD) and Parkinson's disease (PD). Brain specimens for viral DNA polymerase chain reaction represented 34 patients with AD, 40 with PD, and 40 controls. One AD patient (2.9%) was positive for HSV-1 DNA, 88.2% for HHV-6 DNA, and 26.5% for VZV DNA; 17.5% of PD patients were HSV-1 DNA-positive and 75% HHV-6-positive, whereas 40% had VZV DNA. Twenty-five percent of the controls were positive for HSV-1 DNA, 87.5% for HHV-6, and 27.5% for VZV. HSV-1, VZV, or HHV-6 DNA in brains was no additional risk factor for AD.     

A potential role for human herpesvirus type 6 in nervous system disease

Human herpesvirus type 6 (HHV-6) is a new representative of the herpesvirus family which was associated with a spectrum of diseases, including myalgic encephalitis, meningitis and the chronic fatigue syndrome. We set out to study the potential role of HHV-6 in multiple sclerosis (MS) (n = 21), facial palsy (FP) (n = 19) and Guillain-Barré-syndrome (GBS) (n = 7). Results were compared with a control group (CG) (n = 16). We analyzed paired samples of serum and cerebrospinal fluid (CSF) with the polymerase chain reaction (PCR) for the presence of HHV-6 DNA. The studies were complemented by ELISA determination of serum antibodies against HHV-6. In the MS group we detected HHV-6 DNA in the CSF from three of 21 (14.3%) patients but not in the corresponding serum samples. In FP, GBS and controls CSF and serum PCRs were negative in all cases. HHV-6 serum antibody titers were significantly higher in MS compared with FP, GBS and controls. These findings suggest that HHV-6 may play a role in MS.     

Lack of association of herpesviruses with brain tumors

Gliomas are the most frequent primary brain tumors in humans. Many studies have been carried out on their etiology; however, the only confirmed risk factors are hereditary predisposing conditions and high dose of ionizing radiation. Recently, human cytomegalovirus (HCMV) gene products and nucleic acids were reported to be present in all of 27 glioma samples investigated in contrast to other brain tissues, and it was hypothesized that HCMV might play a role in glioma pathogenesis. To evaluate these findings, samples of 40 gliomas, 31 meningiomas, and 6 acoustic neurinomas (ACNs) were analyzed for the presence of HCMV macromolecules using polymerase chain reaction (PCR) and immunohistochemistry. Additionally, corresponding blood samples from 72 patients were analyzed for the presence of HCMV DNA to check for a possible contamination of tumor tissues with HCMV-infected blood cells. No HCMV DNA sequences were found, neither in brain tumor tissues nor in corresponding blood samples. Immunohistochemistry did not detect HCMV-specific proteins. Addressing a possible role of other herpesviruses as has been suggested in seroepidemiological studies, seroprevalence of antibodies to HCMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) were determined by enzyme-linked immunosorbent assay (ELISA). Serological analyses of brain tumor patients showed no significant differences in the prevalences of antibodies to HCMV, HSV, EBV, or VZV compared to the general population. Thus, the data of the present study do not support the hypothesis of an association of herpesviruses with the development of primary brain tumors.     

Prevalence of herpesvirus DNA in MS patients and healthy blood donors

OBJECTIVES: The aim of this study is to determine the DNA prevalence of different members of Herpesviridae in multiple sclerosis (MS) patients and to describe the possible effect of beta-interferon treatment on such prevalence. MATERIAL AND METHODS: With a nested polymerase chain reaction (PCR) assay we have studied the DNA of the peripheral blood mononuclear cells (PBMCs) of 204 whole blood samples, [102 from patients with relapsing-remitting MS (RRMS), of which 62 were treated with beta-interferon, and 102 from healthy blood donors]. RESULTS: We only found a statistically significant difference for human herpesvirus type 6 (HHV-6) DNA prevalence (P < 0.0001): HHV-6 is 2.26 times more frequent in MS patients than in healthy donors. There was no difference in the HHV-6 prevalence between beta-interferon treated and untreated patients. CONCLUSION: 1. Among the herpesviruses, HHV-6 was the only one showing altered prevalence. This either indicates that HHV-6 is involved in the pathogenesis of MS, or it simply indicates that MS influences latency or reactivation of HHV-6 without any direct involvement of HHV-6 in the disease process of MS. 2. Treatment with beta-interferon does not make a difference on the DNA prevalence of the herpesviruses studied in our MS patients.     

Human herpesviruses types 6 and 7 and febrile seizures

The frequency was studied with which human herpesviruses types 6 and 7 (HHV-6 and HHV-7) occur in the cerebrospinal fluid (CSF) of patients with febrile seizures and matched control patients. CSF samples were prospectively collected from a case series of patients with febrile seizures and from age-, sex-, and race-matched control patients without febrile seizures, all of whom were evaluated in the emergency department of an urban, tertiary care, pediatric medical center. Using polymerase chain reaction, the samples were examined for the presence of viral DNA from HHV-6, HHV-7, herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2), and cytomegalovirus (CMV). CSF from a subset of both groups was also examined for RNA from enteroviruses. During the 7-month, 2-week collection period, a total of 174 patients were evaluated for fever and seizures. Of these, 23 (13.2%) met the study criteria. Their mean age was 1.4 +/- 0.7 years. Sixteen (70%) of the 23 were male. The 23 patients were matched to 21 control subjects. None of the samples from the patients or control subjects had polymerase chain reaction evidence of HHV-6, HHV-7, HSV-1, or HSV-2. All samples from the patients were negative for CMV. One control subject was positive for CMV. The 10 patients and seven control subjects tested for enteroviral RNA were negative. Neither HHV-6 nor HHV-7 appears to be present in the CSF of patients with febrile seizures. What role, if any, they have in the pathogenesis of febrile seizures merits further study.     

Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients

Several reports have suggested an association of human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) based on immunohistochemical demonstration of HHV-6 antigens in inflammatory lesions, detection of increased HHV-6 specific serum antibody titers, and amplification of HHV-6 DNA from sera and cerebrospinal fluid of MS patients but not in controls. Characterization of the cellular immune response of MS patients to HHV-6 may further clarify the role of HHV-6 in MS and provide insight into the pathogenesis of this immune-mediated disease. We have compared lymphoproliferative responses to HHV-6A (U1102)-, HHV-6B (Z29)-, and HHV-7 (H7SB)-infected cell lysates in healthy controls and patients with MS. Most healthy controls (71%) proliferated to HHV-6B lysate, and fewer (33%) responded to the HHV-6A lysate. In contrast, 67% of MS patients had a lymphoproliferative response to HHV-6A, which is a significant increase in comparison with healthy controls. A similar frequency of lymphoproliferative response (78%) to HHV-6B was demonstrated in MS patients. Lymphoproliferation to HHV-7 lysate was demonstrated in 23% of healthy controls and 28% of MS patients. These results indicate that the lymphoproliferative response to the HHV-6A variant, which was recently reported to have greater neurotropism, is increased in MS patients.     

A pilot study on the antibodies to HHV-6 variants and HHV-7 in CSF of MS patients

In the possible role for human herpesviruses (HHV) in the pathogenesis of multiple sclerosis (MS) neither clear distinction between the two variants of HHV-6, nor the involvement of HHV-7 have been described. Therefore, we quantitated HHV-6 variant specific and HHV-7 reacting antibodies in the CSF of 13 patients with MS or other neurological disorders by ELISA. Predominance in the positivity of IgG (67%) and IgM (44%) to HHV-6B over that of IgG (44%) with no detectable IgM to HHV-6A, and no antibodies to HHV-7 were found in the CSF of MS patients. None of these antibodies were found in the CSF of controls. This suggests that, intrathecal chronic active or primary HHV-6B infection might contribute to MS progression, while the local effects of HHV-6A and HHV-7 seem to be less important.     

Effects of interferon-beta therapy on elements in the antiviral immune response towards the human herpesviruses EBV, HSV, and VZV, and to the human endogenous retroviruses HERV-H and HERV-W in multiple sclerosis

Effects of treatment of multiple sclerosis patients with IFN-β on elements of the antiviral immune response to herpesviruses were analysed in a longitudinal study. We found significantly increased seroreactivity to EBV EBNA-1, and to VZV, in patients who did not respond to IFN-β therapy. We found no significant changes in seroreactivity to EBV EA, or to HSV. For the same patient cohort, we have previously demonstrated significant decreases in seroreactivities to envelope antigens for the two human endogenous retroviruses HERV-H and HERV-W, closely linked to efficacy of therapy. We further searched for correlations between seroreactivities to EBV, HSV, and VZV, and levels of mannan-binding lectin (MBL), and MBL-associated serine protease 3. We found no such correlations. Our results are in accord with recent reports of increased seroreactivity to EBV EBNA-1, and to VZV in active MS, and they support that the herpesviruses EBV and VZV together with HERV-H/HERV-W and the antiviral immune response may play a role in MS development.     

Prevalence of human herpesvirus U94/REP antibodies and DNA in Tunisian multiple sclerosis patients

Human herpesvirus 6 (HHV-6) has been linked to the pathogenesis of multiple sclerosis (MS). Based on antibody detection and quantitative HHV-6 polymerase chain reaction assay, this study aimed to analyze the possible association between infection with HHV-6 and MS. A total of 131 serum samples were analyzed by ELISA for the presence of specific antibodies to HHV-6 latency-associated U94/REP protein: 68 serum samples from 60 MS patients (20 in relapse and 48 in remission phase) and 63 serum samples from 63 healthy controls. Real-time quantitative PCR for HHV-6 U94/rep DNA was also performed in total blood of MS patients and healthy controls. The serological analysis by ELISA showed that MS patients had increased prevalence and titers of anti-U94/REP immunoglobulins in comparison with control group (seroprevalence 51.47 % versus 28.57 % and mean titer of positive samples 1:248 versus 1:110; p?=?0.0005), with significant difference between relapse and remission phases. HHV-6 DNA was detected in 4 of 60 MS patients (6.66 %) and in 2 of 63 healthy controls (3.17 %), confirming previous data of prevalence obtained by qualitative nested PCR. However, viral load was higher in MS patients compared to controls, and differences were statistically significant (p?=?0.02). The results show that, in spite of the low presence of HHV-6 DNA in peripheral blood, MS patients have increased prevalence and titer of IgGs reacting with HHV-6 latency-associated U94/REP protein.     

三种疱疹病毒性脑炎及一般脑炎的脑脊液细胞学表现

目的:比较三种常见疱疹病毒性脑炎的脑脊液细胞学表现,为临床鉴别诊断提供依据。方法:利用病毒抗体特异性指数对临床诊断的病毒性脑炎进行病原学诊断,获得三种较为常见的病毒性脑炎类型-单纯疱疹病毒性脑炎、EB病毒性脑炎、巨细胞病毒性脑炎;设立非病毒性脑炎组为对照组。对单纯疱疹病毒性脑炎、EB病毒性脑炎、巨细胞病毒性脑炎的脑脊液细胞学进行动态观察,分析比较脑脊液细胞学表现的差异;并且把脑炎组与对照组的脑脊液细胞学的异常类型进行比较。结果:单纯疱疹病毒性脑炎患者的脑脊液细胞学最为突出的特点是脑脊液中出现较多的红细胞,和红细胞吞噬细胞;EB病毒性脑炎和巨细胞病毒性脑炎患者脑脊液细胞学符合一般病毒性脑炎脑脊液细胞学特点:即典型脑脊液细胞学图象-淋巴样细胞反应。脑炎组与对照组脑脊液细胞学异常类型有明显差异。结论:单纯疱疹病毒性脑炎脑脊液中出现红细胞是一个特征性的现象;脑脊液细胞学在病毒性脑炎的鉴别诊断中有重要意义。