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Objective: To verify the use and identify advantages of molecular methods for congenital infections diagnosis in cerebrospinal fluid of neonates., Data Source: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under CRD42021274210. The literature search was performed in databases: PubMed, Virtual Health Library/ Latin American and Caribbean Center on Health Sciences Information (VHL/BIREME), Scopus, Web of Science, Excerpta Medica database (EMBASE), Cochrane, ProQuest, and EBSCOhost. The search was carried out from August to October 2021 and updated in December 2022, respecting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The selection sequence was: 1) Duplicate title removal; 2) Examination of titles and abstracts; 3) Full-text retrieval of potentially relevant reports; and 4) Evaluation of the full text according to eligibility criteria by two independent authors. Inclusion criteria considered randomized and non-randomized control trials, longitudinal, cross-sectional, and peer-reviewed studies in humans, published in English, Spanish, Italian, and Portuguese, with newborns up to 28 days old who had congenital neuroinfections by toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH), and others such as Treponema pallidum, Zika, parvovirus B-19, varicella zoster, Epstein-Barr, and SARS-CoV2, diagnosed by polymerase chain reaction (PCR). Two evaluators extracted the following information: author, year of publication, nationality, subjects, study type, methods, results, and conclusion., Data Synthesis: The most studied pathogen was herpes simplex. Several articles reported only nonspecific initial symptoms, motivating the collection of cerebrospinal fluid and performing PCR for etiological investigation., Conclusions: Molecular methods are effective to detect pathogen genomes in cerebrospinal fluid, which can impact clinical evolution and neurological prognosis.

Background: Disseminated herpes simplex virus (HSV) infection has high morbidity and mortality, particularly in neonates, and requires rapid diagnosis for proper treatment. Currently, there are no US FDA-approved assays available to perform HSV testing on blood., Objectives: Our goal was to evaluate the analytical sensitivity and clinical performance of an available sample-to-answer real-time polymerase chain reaction (PCR) platform used as a laboratory-developed test (LDT) for the detection of HSV-1 and -2 in whole blood (WB)., Methods: A clinical comparison study comparing a real-time PCR reference assay to a LDT based on the DiaSorin Simplexa Direct assay kit was performed. Analytical sensitivity studies comparing WB to the FDA-approved specimen type, cerebrospinal fluid (CSF), were also conducted with contrived quantified HSV-1 and -2 samples in WB and CSF matrix., Results: In total, 102 samples were tested using the LDT and reference assay for the clinical correlation study, with 91 negative and 10 positive results for HSV-1 (n = 7) and HSV-2 (n = 3), exhibiting 100% concordance with comparator results. The overall limit of detection (LoD) for HSV-1 and HSV-2 in WB was comparable to that seen in CSF, with the calculated 95% LoD for blood being 1489 ± 16 copies/ml for HSV-1 and 1187 ± 18 copies/ml for HSV-2 and for CSF being 1168 ± 17 copies/ml for HSV-1 and 953 ± 21 copies/ml for HSV-2., Conclusions: The performance of the LDT for detection of HSV-1 and HSV-2 in WB specimens is adequate for clinical use. The LoD for HSV-1 and HSV-2 is comparable to that in CSF, the FDA-approved specimen type.

Herpes simplex virus (HSV) is a cause of a severe disease of the central nervous system (CNS) in humans. The demonstration of specific antibodies in the cerebrospinal fluid (CSF) may contribute to the retrospective neurological diagnosis. However, the commercial immunological tests for HSV infection are for use in serum samples., Objective: The aim of the present study was to adapt a commercial kit anti-HSV IgG used for serum samples to be performed with a CSF sample., Methods: Forty CSF specimens from 38 patients with suspected CNS HSV infection were serially diluted for detecting anti-HSV IgG by enzyme immunoassay (EIA). The same samples were also analyzed with the polymerase chain reaction (PCR)., Results: The sensitivity of EIA test for HSV was 5% (dilution 1:40) and 65% (dilution 1:2) in CSF, and HSV DNA PCR was 15%. The combined analysis of EIA (dilution 1:2) and PCR increased the sensitivity up to 72.5%. The inflammatory CSF was associated with positive HSV PCR., Conclusions: We demonstrated the importance to adapt serological anti-HSV IgG EIA test for CSF assays to increase the accuracy of the analysis, considering the low concentration of specific antibodies in CSF.

In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barré syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Of 27 neonates with herpes simplex virus, DNAemia was observed in 100% with disseminated disease, 57% with central nervous system disease and 28% with skin, eye, mouth disease, suggesting DNAemia occurs frequently in these infants. Herpes simplex virus culture and polymerase chain reaction were performed on surface specimens from 13/27 infants, and ~50% tested positive only by polymerase chain reaction, suggesting the superiority of this technique.

Herpes simplex virus (HSV) infection in infants is a devastating disease with an often subtle presentation. We examined cerebrospinal fluid (CSF) HSV PCR (polymerase chain reaction) testing and empiric acyclovir therapy in young febrile infants. Chart review identified hospitalized infants aged ≤60 days with fever ≥38°C who had undergone lumbar puncture. Previously published criteria were used to define patients at high risk for HSV. Primary outcomes were CSF HSV PCR testing and empiric acyclovir therapy. Of 536 febrile infants, 23% had HSV testing; empiric acyclovir was started in 15%. HSV testing and therapy were associated with younger age, seizure, maternal vaginal lesions, postnatal HSV contact, vesicles, poor tone, CSF pleocytosis, and enteroviral testing. Sixty-two percent of high-risk infants did not undergo HSV testing, and 75% did not receive acyclovir. High-risk infants were untested and untreated at relatively high rates. Evidence-based criteria to guide HSV testing and treatment are needed.

To evaluate the infectious etiologies, clinical features, and outcomes of patients with CNS infections at a tertiary care center. Patients that present with a pleocytosis in the cerebral spinal fluid (CSF), defined as a CSF WBC count > 5 cells/mm 3 , from July 2015 to June 2016 at a tertiary care hospital were analyzed for this report. Data from patients with confirmed (n = 43) and presumed (n = 51) CNS infections were analyzed. CNS infection was the leading known cause of CSF pleocytosis (n = 43, 18% of all patients with a pleocytosis in the CSF), and HSV-2 was identified as the leading causative pathogen (n = 10) followed by varicella zoster virus (n = 5). Fifty-three percent of patients with a pleocytosis in the CSF did not receive a diagnosis. In the patients that did not receive a diagnosis, CNS infection was presumed to be the cause in 51 patients (21% of patients with CSF pleocytosis). The mean time to diagnosis for patients with confirmed CNS infection was 16 days, but time to diagnosis was highly variable depending on the causative pathogen. There was a significant overlap in CSF parameters and peripheral white blood cell counts in patients diagnosed with a viral, bacterial, or fungal infection. Neuroimaging changes were present in only 44% of CNS infections. The overall mortality was 7% for CNS infections, and 17% of patients with a CNS infection had a severe neurologic deficit at presentation while only 3% had a severe deficit at the last neurologic assessment. This study provides new insights into the infectious causes of disease in a cohort of patients with pleocytosis in the CSF. The study provides new insights into the time to diagnosis and outcomes in patients that present with pleocytosis in the CSF.

Although neonatal herpes simplex virus (HSV) causes significant morbidity, utilization of the cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) test remains variable. Our objective was to examine the association of CSF HSV PCR testing with length of stay (LOS) in a 20-center retrospective cohort of hospitalized infants aged ≤60 days undergoing evaluation for meningitis after adjustment for patient-level factors and clustering by center. Of 20,496 eligible infants, 7,399 (36.1%) had a CSF HSV PCR test performed, and 46 (0.6% of those tested) had a positive test. Infants who had a CSF HSV PCR test performed had a 23% longer hospital LOS (incident rate ratio 1.23; 95% CI: 1.14-1.33). Targeted CSF HSV PCR testing may mitigate the impact on LOS for low-risk infants.

Objectives: Herpes simplex viruses (HSV) can produce encephalitis (HSE), which requires early detection, typically using polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). However, other neurological conditions not directly caused by HSV may also present with a positive HSV PCR in the CSF (NCNHPCR+). We aimed to analyze the clinical features of both groups of patients (HSE vs. NCNHPCR+) and to consider the potential relevance of this finding in the latter., Methods: A retrospective analysis of clinical presentation, workup (CSF, EEG, and MRI) and outcome of patients with an HSV+ result in CSF was conducted from Jan-2007 to Sep-2015 in our institution. Patients under 18 years and those with nonencephalitic HSV associated disorders were excluded. Group comparison between HSE and NCNHPCR+ patients was conducted using parametric and nonparametric tests accordingly., Results: Sixteen HSE and 23 NCNHPCR+ patients were included. Patients with HSE presented a higher incidence of headache (87.5% vs. 43.5%; P=0.008), meningeal symptoms (50% vs. 17.4%; P=0.04), pleocytosis (75% vs. 18%; P=0.001), EEG abnormalities (46.67% vs. 22%; P=0.02) and typical MRI findings (50% vs. 0%; P<0.001), whereas 35% of patients with NCNHPCR+ had an underlying immunologic disorder (35% vs. 0%; P=0.012)., Conclusions: The pathogenic role of HSV in NCNHPCR+ is uncertain. This finding must be interpreted in the appropriate clinical, EEG, and neuroimaging context. Immunocompromise and neuroinflammation states could be related to a higher presence of HSV in CSF.

We compared the clinical course of neonates with persistence of herpes simplex virus (HSV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF) after 21 days of treatment with high-dose acyclovir to that of neonates with clearance of the CSF after 21 days of therapy. Neonates with persistence of HSV DNA had a more severe clinical course with worse neurodevelopmental outcomes.

Background and Objectives: Herpes simplex virus (HSV) is rare in neonates but carries significant morbidity and mortality in that group. Emergency department (ED) clinicians have little guidance to decide when to test for HSV and give acyclovir. We created an institutional guideline to provide guidance in patients younger than 6 weeks. Our objective was to evaluate whether guideline implementation affected the ED's decision to test for HSV, and ED use of HSV polymerase chain reactions (PCRs) and acyclovir., Methods: We reviewed charts for patients 1 year before implementation and 1 year after implementation of our guideline. Inclusion criteria were younger than 60 days, admitted through the ED, symptom onset younger than 6 weeks, and any one of the following criteria: (1) ED blood culture obtained, (2) ED or inpatient HSV PCR obtained, and (3) ED or inpatient acyclovir treatment. Premature patients and transfer patients were excluded. We compared whether the decision to initiate HSV testing, ED use of HSV PCRs, serum alanine aminotransferase, and acyclovir use changed post-guideline implementation., Results: We reviewed 173 charts pre-implementation and 129 post-implementation. We found a significant decrease in ED testing for HSV among patients who did not meet guideline criteria (P < 0.01). We saw an improvement in the use of alanine aminotransferase among patients who met criteria for testing (P = 0.02), but no change in the use of HSV PCRs or acyclovir use among tested patients., Conclusions: Guideline implementation reduced HSV evaluations in low-risk patients, but did not improve test utilization or acyclovir administration among those tested. Additional work is needed to improve guideline utilization.

Study Objective: We determine the optimal correction factor for cerebrospinal fluid WBC counts in infants with traumatic lumbar punctures., Methods: We performed a secondary analysis of a retrospective cohort of infants aged 60 days or younger and with a traumatic lumbar puncture (cerebrospinal fluid RBC count ≥10,000 cells/mm 3 ) at 20 participating centers. Cerebrospinal fluid pleocytosis was defined as a cerebrospinal fluid WBC count greater than or equal to 20 cells/mm 3 for infants aged 28 days or younger and greater than or equal to 10 cells/mm 3 for infants aged 29 to 60 days; bacterial meningitis was defined as growth of pathogenic bacteria from cerebrospinal fluid culture. Using linear regression, we derived a cerebrospinal fluid WBC correction factor and compared the uncorrected with the corrected cerebrospinal fluid WBC count for the detection of bacterial meningitis., Results: Of the eligible 20,319 lumbar punctures, 2,880 (14%) were traumatic, and 33 of these patients (1.1%) had bacterial meningitis. The derived cerebrospinal fluid RBCs:WBCs ratio was 877:1 (95% confidence interval [CI] 805 to 961:1). Compared with the uncorrected cerebrospinal fluid WBC count, the corrected one had lower sensitivity for bacterial meningitis (88% uncorrected versus 67% corrected; difference 21%; 95% CI 10% to 37%) but resulted in fewer infants with cerebrospinal fluid pleocytosis (78% uncorrected versus 33% corrected; difference 45%; 95% CI 43% to 47%). Cerebrospinal fluid WBC count correction resulted in the misclassification of 7 additional infants with bacterial meningitis, who were misclassified as not having cerebrospinal fluid pleocytosis; only 1 of these infants was older than 28 days., Conclusion: Correction of the cerebrospinal fluid WBC count substantially reduced the number of infants with cerebrospinal fluid pleocytosis while misclassifying only 1 infant with bacterial meningitis of those aged 29 to 60 days., (Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Herpes simplex virus type 1 (HSV-1) encephalitis causes a deleterious inflammation and elevated intracranial pressure. As a step towards examining the origin of the inflammation, we here report the response of circulating proteasomes and complement factors in blood and cerebrospinal fluid (CSF) in rats infected with HSV-1. Infection was via the nasal route, with 1.1 × 10 4 plaque-forming units of HSV-1 strain 2762 given in one or both nostrils. A sandwich enzyme-linked immunosorbent assay was used to study the level of 26S proteasomes and their complex formation with complement factors 3 and 4. HSV-1 infection in the rat causes a complex formation between complement factors and proteasomes, which we designate compleasomes. In the first experiment, with HSV-1 given in both nostrils, compleasomes containing complement factors 3 and 4 increased significantly in both blood plasma and CSF. The concentration of proteasomes in plasma was similar in controls and infected rats (320 ± 163 vs. 333 ± 125 ng/ml). In the second experiment, with HSV-1 given in one nostril, CSF levels were 1 ± 1 ng/ml in controls and 56 ± 22 ng/ml in the HSV-1 group, whereas the total protein concentration in CSF remained the same in the two groups. The compleasome response was limited to CSF, with a highly significant difference between infected rats and controls (n = 11, p < 0.001). It was possible to mimic the reaction between proteasomes and complements 3 and 4 in vitro in the presence of ATP.

Objective: To evaluate the utility of quantitative herpes simplex virus (HSV) polymerase chain reaction (PCR) levels for prognosis and management of neonatal HSV disease., Study Design: Clinical and virologic data were abstracted by medical record review from neonatal HSV cases treated at Seattle Children's Hospital between 1993 and 2012. HSV PCR results from plasma (n = 47), cerebrospinal fluid (n = 56), or both (n = 40) at the time of diagnosis were available from 63 infants; 26 with skin-eye-mouth (SEM), 18 with central nervous system (CNS), and 19 with disseminated (DIS) disease., Results: Plasma HSV PCR was positive in 78% of the infants with SEM, 64% with CNS and 100% with DIS disease. Mean plasma viral level was 2.8 log10 copies/mL in SEM, 2.2 log10 copies/mL in CNS, and 7.2 log10 copies/mL in DIS infants. The HSV levels were higher among infants who died compared with surviving infants, 8.1 log10 copies/mL (range 7.7-8.6) vs 3.8 log10 copies/mL (range 0.0-8.6), P = .001, however, level of HSV DNA in the cerebrospinal fluid or in plasma did not correlate with neurologic outcome. Dynamics of HSV clearance from plasma during high-dose acyclovir treatment showed single-phase exponential decay with a median viral half-life of 1.26 days (range: 0.8-1.51)., Conclusions: Plasma HSV levels correlate with clinical presentation of neonatal HSV disease and mortality, but not neurologic outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report a case of a 62-year-old female with seizures and encephalitis. Molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (HSV-1 and HSV-2). To our knowledge, this is the first report of simultaneous detection of HSV-1 and HSV-2 in cerebrospinal fluid., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Aseptic meningitis associated with herpes simplex virus type 2 often has a relapsing-remitting clinical phenotype. Factors that lead to disease activation and reactivation are currently incompletely understood., Case Presentation: We describe the case of a 49-year-old Caucasian man who developed recurrent episodes of herpes simplex virus type 2-associated aseptic meningitis in the setting of heat exposure and bicycling. This case is compelling in that substantial data were available to the examining physicians on the amount of physical exercise and heat exposure. Strenuous physical activities or heat exposure in isolation did not cause re-occurrence of clinical signs and symptoms., Conclusions: This case illustrates that the dual activation of mechanical and temperature receptors in dorsal root ganglia may lead to the recurrent reactivation and afferent dissemination of latent herpes simplex virus type 2 in some patients.

We describe, to our knowledge, the first case of arterial ischemic stroke after primary herpes simplex virus type 1 (HSV1) infection in a previously healthy child, without signs of encephalitis. A 10-year-old previously healthy girl was admitted to our hospital with acute left-sided hemiparesis which involved the lower half of her face. Submandibular lymphadenitis and oral vesicular lesions were present. MRI confirmed the suspicion of an acute ischemic stroke. Immunoglobulin M antibodies to HSV1 were detected. Cerebrospinal fluid polymerase chain reaction for herpes virus was negative. She was treated with aspirin (3mg/kg) and intravenous acyclovir (10mg/kg every 8 hours) for 21 days. Immunoglobulin G antibodies to HSV1 appeared 16 days after admission. Twelve months after her hospitalization the patient's examination was normal. Stroke should be considered a possible complication of HSV1 primary infection. Guidelines for the management of acute stroke in children are needed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A syndrome involving acute urinary retention in combination with sacral radiculitis and cerebrospinal fluid pleocytosis was first described by the American neurosurgeon Charles Elsberg in 1931. In many instances the aetiology is herpes simplex virus type 2 (HSV-2) reactivation from sensory neurons. In this case report we present a 34-year-old pregnant woman with previous undiagnosed sensory lumbosacral symptoms. She was hospitalized with HSV-2 meningitis and lumbosacral radiculitis but no genital rash. A week after the onset of symptoms she developed acute urinary retention, thus indicating Elsberg syndrome.

Protein microarrays have been developed to study antibody reactivity against a large number of antigens, demonstrating extensive perspective for clinical application. We developed a viral antigen array by spotting four recombinant antigens and synthetic peptide, including glycoprotein G of herpes simplex virus (HSV) type 1 and 2, phosphoprotein 150 of cytomegalovirus (CMV), Rubella virus (RV) core plus glycoprotein E1 and E2 as well as a E1 peptide with the optimal concentrations on activated glass slides to simultaneously detect IgG and IgM against HSV1, HSV2, CMV and RV in clinical specimens of sera and cerebrospinal fluids (CSFs). The positive reference sera were initially used to measure the sensitivity and specificity of the array with the optimal conditions. Then clinical specimens of 144 sera and 93 CSFs were tested for IgG and IgM antibodies directed against HSV1, HSV2, CMV and RV by the antigen array. Specificity of the antigen array for viral antibodies detection was satisfying compared to commercial ELISA kits but sensitivity of the array varied relying on quality and antigenic epitopes of the spotting antigens. In short, the recombinant antigen array has potential to simultaneous detect multiple viral antibodies using minute amount (3 µl) of samples, which holds the particularly advantage to detect viral antibodies in clinical CSFs being suspicious of neonatal meningitis and encephalitis.

Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration of valacyclovir treatment following the first episode was 10 days (range 3 to 14 days, n = 13). The median duration of valacyclovir treatment following a subsequent meningitic episode was 9 days (range 7 days to indefinite period, n = 9). No patient was reported to have seizures, neurological disability, or death in extended follow-up (mean follow-up 3.4 years). Recurrence of meningitic symptoms was not universal.

Objectives: To determine the prevalence of central nervous system (CNS) herpes simplex virus (HSV) infection in neonates evaluated in the emergency department and to identify factors associated with cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) testing. An existing testing paradigm was then applied to determine its potential impact on testing frequency., Methods: This nested case-control study included infants aged 0 to 28 days who had lumbar puncture in the emergency department. Multivariate logistic regression was used to identify factors associated with CSF HSV PCR testing., Results: The CSF HSV PCR testing was performed in 266 (47%) of 570 neonates. The prevalence of CNS HSV infection was 0.5% compared with 1.6% for bacterial meningitis. Performance of CSF HSV PCR testing was not associated with known HSV risk factors. Application of a known HSV testing paradigm would have reduced the proportion of infants tested by 21% without missing any of the cases of CNS HSV infection., Conclusions: The HSV testing remains common despite the low prevalence of HSV infection. The CSF HSV PCR testing is not well aligned with known risk factors. Future testing strategies should incorporate community HSV prevalence, known neonatal risk factors, and clinical judgment.

Objective: To report a case of bilateral vocal cord abductor paralysis in the context of primary herpes simplex infection., Case Report: A 63-year-old man was urgently admitted to hospital with laryngeal dyspnoea associated with dysphagia but without dysphonia. Physical examination demonstrated the vocal cords in a paramedian position with paralysis of abduction. The patient reported primary herpes simplex infection two weeks prior to this episode. HSV serology indicated recent infection and lumbar puncture demonstrated the presence of herpes simplex virus type 1 in the cerebrospinal fluid. Complete resolution of respiratory symptoms was observed after 21 days of treatment with intravenous aciclovir., Discussion and Conclusion: Gerhardt syndrome comprises inspiratory dyspnoea without dysphonia. It used to be mainly due to syphilis, but is now mostly observed in the setting of neurodegenerative disease. The authors report a case of Gerhardt syndrome occurring after an episode of primary herpes simplex infection with the presence of herpes simplex virus in the CSF. Treatment by intravenous antiviral drugs allowed rapid resolution of the symptoms. The pathophysiology of Gerhardt syndrome remains unexplained, but the possible role of herpes simplex infection should be considered in cases of laryngeal palsy., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE., Methods: Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined., Results: Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%)., Conclusions: Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.

We describe a 26-year-old man treated with azathioprine for myasthenia gravis who developed acute left-sided peripheral facial weakness. Brain magnetic resonance imaging (MRI) revealed enhancement in the left geniculate ganglion and in the intracanalicular and tympanic segments of the facial nerve. Analysis of cerebrospinal fluid (CSF) and serum revealed intrathecal synthesis of anti-varicella zoster virus (VZV) IgG antibody. Although previous analyses of saliva, blood mononuclear cells, serum antibodies, middle ear fluid, and auricular and geniculate zone skin scrapings have shown that a small but definite proportion of patients with idiopathic peripheral facial palsy ("Bell's palsy") have the Ramsay Hunt syndrome zoster sine herpete (RHS ZSH), this is the first confirmation of RHS ZSH by intrathecal synthesis of anti-VZV IgG antibody. In addition, herpes simplex virus (HSV)-1 DNA was found in saliva of the patient on 3 consecutive days. Simultaneous reactivation of two alphaherpesviruses (HSV-1 and VZV) in our immunosuppressed patient underscores the need to consider opportunistic infection as a cause of facial weakness., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Herpes simplex virus type 2 (HSV-2) can cause radiculo-myelitis as a neurological manifestation. We report a case of ongoing HSV-2 DNA positivity in the cerebrospinal fluid (CSF) of at least eight weeks under antiviral therapy with acyclovir in a highly immunocompromised hemato-oncologic patient with HSV-2-associated radiculitis. Upon admission, the patient presented with pain, leg paresis, and urinary incontinence, as well as pleocytosis in the CSF. Quantitative real-time PCR of the CSF at day 3 after admission revealed HSV-2 with a concentration of 2.0×10(5) copies/ml and treatment with acyclovir intravenously and prednisolone by mouth was started. Clinical symptoms resolved almost completely after approximately 3 weeks of antiviral therapy. However, CSF samples of day 12, 19, 26, 33, 39, 48 and 54 after admission showed a slow decline of HSV-2 DNA concentrations. HSV-2 DNA was still detectable (1.6×10(4) copies/ml) at day 54 after admission. Genotypic resistance testing showed, as far as available, no mutations indicative for acyclovir resistance. Since an increasing specific antibody index for HSV was observed, we speculate that the prolonged detectability of HSV-2 DNA in the CSF might not necessarily indicate ongoing viral replication but neutralized virus. Other hypotheses and the consequences on treatment are discussed. To our knowledge this is the first report about the long-term viral load kinetics of HSV-2 in the CSF of a patient with radiculitis under antiviral therapy, highlighting the need for further studies on HSV DNA kinetics in the CSF and their significance for an appropriate antiviral treatment.

Herpes simplex encephalitis (HSE) is a rare complication of neurosurgical procedures but must be considered in early deterioration of the postoperative patient. This is the first report of HSE following spinal cord tumor resection. A 65-year-old woman had C2-C5 laminectomy for subtotal resection of intramedullary ependymoma. Six days postoperatively she developed fever, vomiting and rapid decline in mental status. Brain MRI revealed enhancement of left insular cortex. Polymerase chain reaction on cerebrospinal fluid (CSF) identified herpes simplex virus type 1 (HSV-1) as the causal agent. Twenty-one days of acyclovir led to improvement. Three subsequent admissions to neurological intensive care unit were required for deterioration in mental status, including pneumonia, hydrocephalus and deep vein thromboses. Ventriculoperitoneal shunt (VPS), tracheotomy, percutaneous intravenous central catheter (PICC) line and percutaneous endoscopic gastrostomy (PEG) were placed. She was discharged to skilled nursing home care. Acyclovir is effective therapy against HSV, though outcomes may be poor even in optimally treated cases. Empiric treatment must be started even in the absence of serologic evidence of HSV infection if suspicion for HSE is high.

Central nervous system (CNS) demyelination has been suggested to be associated with infections caused by the Epstein-Barr virus (EBV) or herpes simplex virus (HSV)-1. CNS inflammatory demyelinating disease (IDD) rarely presents as a large lesion. We evaluated samples of serum and cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assay to detect recent infection with these viruses and analyzed CSF and brain specimens by polymerase chain reaction (PCR) or immunohistochemical studies for evidence of these viruses in three patients with biopsy-proven CNS IDD. The results of PCR tests for EBV and HSV in CSF or brain specimens were negative. Elevated anti-EBV or -HSV antibody levels were not found in serum or CSF in any patient. Immunohistochemical studies showed that IDD lesions were negative for latent membrane protein (LMP)-1, Epstein-Barr nuclear antigen (EBNA)-2, and EBNA noncoding RNA (EBER)-1. These results suggest a negative association between CNS IDD and EBV or HSV.

Objective: To examine whether ordering testing of cerebrospinal fluid (CSF) for herpes simplex virus (HSV) by polymerase chain reaction (PCR) in neonates and young infants is associated with increased hospital length of stay (LOS) or increased hospital charges., Study Design: This retrospective cohort study enrolled infants age

Childhood ischemic stroke is a rare complication of herpes simplex virus type-1 encephalitis. We describe a previously healthy 3-year-old girl who presented with bilateral occipital ischemic stroke, attributable to herpes simplex virus type-1 encephalitis, highlighting the importance of viral diagnostics in cerebrospinal fluid.

Background: Herpes simplex type-2 (HSV-2) causes both primary and recurrent lymphocytic meningitis, but optimal patient management is not well defined., Methods: In this retrospective observational study, we reviewed the medical records of patients with HSV-2-positive cerebrospinal fluid samples in our laboratory between January 2001 and January 2005., Results: During the study period, 23 patients, aged 16 to 83 years, had HSV-2 detected in spinal fluid. Nineteen (83%) had meningitis and 4 (17%) had evidence of meningoencephalitis. Seventy-four percent were female. Two (8.7%) had a history of prior genital herpes, and one (4.3%) had genital lesions noted at the time of presentation. Genital examinations were performed at presentation in only 3 patients. Seven (30.4%) patients reported previous episodes of meningitis. Two celibate women developed HSV-2 meningitis or meningoencephalitis following lumbar steroid injection for spinal stenosis. One woman developed HSV-2 meningoencephalitis 3 days postpartum following cesarean section. Antiviral treatment for uncomplicated HSV-2 meningitis varied from none (4 patients) to 14-21 days of intravenous (IV) acyclovir therapy (4 patients). The 11 remaining patients with meningitis received 1-7 days of IV therapy, followed by 7-21 days of oral antiviral therapy. Three of 4 patients with meningoencephalitis received 21 days of IV acyclovir, and one received 3 days IV acyclovir followed by 14 days of oral therapy., Conclusions: HSV-2 meningitis presents most often without a history of genital herpes, recurrent meningitis, or genital symptoms. Current management practices are highly variable and may lead to unnecessary hospitalization and prolonged intravenous therapy.

Background: In this retrospective study, our objective was to review the epidemiology of viral meningitis and to compare clinical features associated with enterovirus, herpes simplex virus (HSV), and varicella zoster virus (VZV) infections in immunocompetent adults., Methods: Data on cerebrospinal fluid (CSF) samples submitted to the Trust Virology Laboratory (Sheffield, UK) from April 2004 through April 2007 were reviewed. Notes on immunocompetent adults who were polymerase chain reaction (PCR) positive for enterovirus, HSV type 2, or VZV and who had presented to local clinical departments were scrutinized (4 patients were positive for HSV type 1 and did not meet the inclusion criteria)., Results: A total of 2045 samples were analyzed for viral pathogens during the 3-year period. Of the 109 PCR-positive samples, 38 (35%) were from immunocompetent adults, of whom 22 were infected with enterovirus, 8 were infected with HSV type 2, and 8 were infected with VZV. The median ages were 32 years (range, 16-39 years), 39 years (range, 22-53 years), and 47.5 years (range, 26-80 years), respectively. Rash occurred after the meningitis symptoms in 5 patients infected with VZV (median time from meningitis symptoms to rash, 6 days). Protein levels were significantly higher in CSF samples from patients infected with HSV type 2 (median, 1205 mg/L) and in samples from those infected with VZV (median, 974 mg/L) than in samples from those infected with enterovirus (median, 640 mg/L; P = .001 and P = .01, respectively). White blood cell counts were significantly higher in CSF samples from patients infected with HSV type 2 (median, 240 x 10(6) cells/L) than in samples from those infected with enterovirus (median, 51 x 10(6) cells/L; P = .01)., Conclusions: Enterovirus infection was the most common cause of viral meningitis in immunocompetent adults in this study. White blood cell counts and protein levels were significantly higher in CSF samples from patients infected with HSV type 2 than in samples from patients with enterovirus infection. Zoster rash often occurs after meningitis. PCR testing provides a rapid and specific etiological diagnosis.

Objective: The incidence of perinatal transmission of neonatal herpes infection has recently been reported at 1 in 3200 births. The main objective of this study was to determine a population-based incidence of neonatal herpes simplex virus infection., Study Design: This was a retrospective chart review of newborn infants presenting with herpes infection established by cerebrospinal fluid polymerase chain reaction or lesion culture between 1999 and 2003. Only infants delivered at our institution were considered to establish a population-based incidence., Results: Four cases of neonatal herpes infection were identified based on polymerase chain reaction and culture diagnosis. During the study period 78,115 infants were delivered at our institution yielding an incidence of 1 in 20,000 live births., Conclusion: The incidence of neonatal herpes infection at our institution is lower than reported elsewhere. A national surveillance program of neonatal herpes is needed to measure the burden of disease across the United States.

Identification of the aetiology of central nervous system infections requires the detection of either the organism or a microbe-specific immune response within the brain or cerebrospinal fluid. We describe a screening assay to detect herpes simplex virus, varicella zoster virus, cytomegalovirus, measles and Toxoplasma gondii specific antibodies in cerebrospinal fluid. Antigen-specific immunoblotting of oligoclonal IgG and IgM was used to confirm the presence of antibody. Of 51 consecutive cerebrospinal fluid samples received by the laboratory from patients with suspected central nervous system infection 18 (35%) were screen positive for one or more antigen. In only 7 of these were antigen-specific oligoclonal IgG or IgM bands confirmed. The assay provides a simple, cheap assay to screen for microbial-specific antibody in the cerebrospinal fluid samples of patients with suspected neurological infections.

Objectives: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events., Methods: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase)., Results: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis., Conclusion: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.

Neonatal herpes simplex virus (HSV) can be a devastating illness and may be difficult to diagnose in those cases without a typical skin rash. As a result, physicians often rely on HSV polymerase chain reaction of cerebrospinal fluid to rule out HSV encephalitis. We developed a real-time polymerase chain reaction assay for HSV using the SmartCycler II (Cepheid, Sunnyvale, CA). End point dilution studies showed sensitivity comparable to that of two national reference laboratories that use LightCycler. In-house turnaround time was approximately 1.5 days versus approximately 5.2 days for sending the test to a reference laboratory. We hypothesized that the rapid availability of a negative test result would allow physicians to discharge appropriate patients earlier. Six months after implementation, clinical case analysis identified 12 pediatric patients who were discharged earlier based on more rapid test results, with a projected savings of approximately 55.2 hospital days throughout the first year. Actual length of stay for patients tested in-house was significantly less than that of historical controls and was projected to save approximately 70.2 hospital days in the first year. Including projected annual laboratory cost/test savings of approximately $11,000, a total savings of $38,000 to $43,000 was estimated for the first year of implementation, more than offsetting startup instrument and development cost.

Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method that amplifies DNA with high specificity, efficiency, and speed under isothermal conditions. To evaluate the usefulness of LAMP for diagnosing central nervous system infection with herpes simplex virus (HSV), we compared the LAMP method with real-time PCR, using samples that were previously tested by nested PCR. We examined 69 cerebrospinal fluid (CSF) samples from patients suspected of having HSV infection of the central nervous system. The results of the real-time PCR analysis and nested PCR assay were in complete accord. When nested PCR was regarded as standard, the sensitivity of LAMP was 81%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 90%. Although further improvement is necessary for the wide spread use, the LAMP method might be applicable to diagnosis of HSV infection of the central nervous system.

We report 4 cases of human immunodeficiency virus infection associated with lumbosacral radicular dysfunction and urinary retention. Three of these cases had the so-called Elsberg syndrome in that their symptoms were associated with genital herpes. In 1 case, different herpes simplex virus types were isolated from the cerebrospinal fluid and genital swabs. Lumbosacral radiculoneuropathy with urinary retention caused by herpes viruses can develop not only with an initial genital herpes infection, but also due to reactivation of a latent herpes virus., (Copyright 2005 S. Karger AG, Basel.)

Mycoplasma pneumoniae infections have extrapulmonary complications that involve the nervous system. The neurologic manifestations are diverse. Although the prognosis is usually favorable, the patients can undergo severe permanent sequelae. We present a young female adult with acute meningoencephalitis as a complication of a lower respiratory infection, which followed a benign course without neurologic sequelae.

Background and Objectives: The optimal strategy for the diagnosis of herpes simplex virus (HSV) and varizella-zoster virus (VZV) disease of the central nervous system is the detection of viral DNA by polymerase chain reaction assay (PCR) in cerebrospinal fluid (CSF) and the examination of intrathecal production of specific antibodies. However, in acute neurological disease caused by either HSV or VZV, dual intrathecal synthesis of HSV-1, 2- as well as VZV-specific antibodies may be detectable and thus can hamper accurate aetiological diagnosis. This paper illustrates such equivocal findings in two case reports, investigates their frequency and discusses the possible reasons., Methods: Consecutive CSF/serum pairs of two patients with central nervous system (CNS) disease were tested by HSV-1-, HSV-2-, and VZV-specific PCR and by different serological assays for detection of neurotropic viruses and bacteria. Additionally, the results of microbiological investigations of 1'155 CSF/serum samples were retrospectively analyzed for coincident intrathecal antibody synthesis against HSV-1, 2 and VZV., Results: Although only HSV-1 and VZV-specific DNA was detectable in the CSF of two patients with encephalitis and chronic meningitis, respectively, increasing intrathecal antibody production against both virus species could be demonstrated. Retrospective analysis of 1155 CSF/serum pairs revealed 55 (4.8%) pairs with evidence for intrathecally produced antibodies against either HSV-1, 2 (30/55) or VZV (14/55). Eleven of these 55 (20%) pairs showed intrathecal antibody-production against both virus species., Conclusions: Patients with CNS infection with HSV and VZV can be diagnosed by detecting intrathecally produced virus-specific antibodies, in addition to virus-specific PCR. However, in an appreciable proportion of patients a correct diagnosis is hampered by coincidentally detected antibodies in CSF against both virus species. Possible reasons for these equivocal findings are given.

Mollaret meningitis is a rare disease characterized by recurrent and self-limited episodes of aseptic meningitis. It is considered a disease with benign etiology and it has been related to viral infections: Epstein-Barr virus and herpes simplex virus (HSV), type 2 most frequently. Herpes simplex 1 virus has been rarely isolated in the cerebrospinal fluid in patients with Mollaret meningitis; to this end culture, expansion with PCR, and inmunoblot has been utilized. In this article a case of Mollaret meningitis related to type 1 HSV is described. The interest is the demonstration of the herpes simplex virus type 1 within the cytoplasm of the Mollaret cells with a immunohistochemical technique (ABC-peroxidase method) using monoclonal antibodies anti HSV-1 in order to support the diagnosis, being this the first case described in the literature.

The consequences of neonatal herpes simplex virus (HSV) infection can be severe. Disease can be localized to skin, eye and mouth (SEM disease), involve the central nervous system (CNS) or manifest as disseminated infection involving multiple organs. Most surviving infants in the latter two categories have neurological sequelae, and the mortality rate in the absence of therapy is very high (80%) for babies in the latter category. The International Herpes Management Forum (IHMF) has produced guidelines on the diagnosis, prevention and effective management of neonatal herpes. Neonatal herpes may occur in the absence of skin lesions, so if the infection is suspected, swabs of the oropharynx, conjunctiva, rectum, skin lesions, mucosal lesions and urine should be promptly taken and submitted for virus culture. Cerebrospinal fluid (CSF) should be submitted for polymerase chain reaction (PCR) detection of HSV DNA. Evidence for disseminated or CNS infection should be sought using liver function tests, complete blood cell count, CSF analysis and chest X-ray, if respiratory abnormalities are present. Neonates with suspected HSV infection should be treated with intravenous aciclovir (20 mg/kg) every 8 h for 21 days. If disease is localized to the SEM, treatment should be limited to 14 days. The neutrophil count for children receiving intravenous aciclovir should be monitored. If the absolute neutrophil count falls below 500/mm3, decreasing the aciclovir dose or administering granulocyte colony stimulating factor (GCSF) should be considered. At the end of therapy in CNS and disseminated disease, PCR assessment of CSF should be used and treatment continued if the child remains PCR positive at this site.

Objective: To assess the performance of a polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF) for the diagnosis of nervous system infections caused by herpesvirus, and to estimate the incidence of encephalitis due to herpes simplex virus type 1 in the adult population of the island of Gran Canaria., Methods: We studied 330 CSF specimens from 312 patients (281 HIV-negative and 31 HIV-positive) remitted to investigate clinically suspected encephalitis or meningitis, or to study neuropathy or demyelinating disease. A multiplex PCR technique was used to detect herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), human cytomegalovirus (CMV), Epstein-Barr virus and human herpesvirus type 6. The patients' clinical records were reviewed to establish the definite diagnosis., Results: Nine samples from eight patients (2.6%) showed positive results (9.7% of patients with pathological CSF and none with normal CSF). The eight patients had clinical and analytic findings of herpesvirus nervous system infection: HSV-1 DNA in four patients with encephalitis, HSV-2 DNA in one patient with meningitis, VZV DNA in two patients with meningitis and CMV DNA in one HIV-positive patient with encephalitis. Herpesvirus was the cause of 50% of encephalitis cases and 10% of meningitis cases. The incidence of HSV-1 encephalitis was five cases per million inhabitants per year., Conclusions: Diagnosis of herpesvirus nervous system infections by PCR in CSF is not appropriate when CSF parameters are normal. We found a higher incidence of herpesvirus encephalitis than has been reported in other studies.

We reviewed the clinical and demographic characteristics and outcomes for 13 immunocompromised patients with herpes simplex virus (HSV)-induced meningitis. Eleven patients were receiving chemotherapy for leukemia or lymphoma, and 10 had acquired immunodeficiency syndrome. Patients presented with acute febrile meningitis. The median white blood cell count at the onset of symptoms was 400 cells/mm3. Examination of cerebrospinal fluid (CSF) specimens showed lymphocytic meningitis, but activated lymphocytes and low glucose levels were both noted in 7 patients. HSV DNA was detected in all CSF specimens, and HSV type 2 was identified in 7. Eight patients had suspected HSV-associated mucocutaneous lesions at the time of meningitis onset. Six patients had initial radiculalgia, with sphincter involvement in 2. Eleven patients received intravenous antiviral therapy, but treatment was delayed for 6 patients. Two of the 6 patients for whom treatment was delayed developed encephalitis and died, whereas 2 others experienced persistent neurological symptoms. HSV-2 can cause severe meningitis in immunocompromised patients. Early recognition and treatment might improve the outcome of such infections.

Background: Clinical criteria (symptoms) are not reliable enough to differentiate between different causes of encephalitis. The clinical presentation of herpes simplex virus encephalitis (HSVE) is not classically constant and in such a patient, therefore, it is vital to make early diagnosis., Aims: To investigate satisfactory and crucial clinical signs as guide to perform HSV-PCR in a rapid diagnosis of herpes simplex virus encephalitis., Material and Methods: A total of 156 CSF specimens from 70 patients with clinically suspected HSVE or meningoencephalitis were tested. The criteria for cases suspected of HSVE were fever >380C, altered mental status and other critical manifestations. CSF features, irregularity in brain CT scan and MRI findings were also assessed. All the specimens were collected before and after Acyclovir treatment. Polymerase chain reaction was performed using primers, which amplified DNA sequences for both HSV-1 and HSV-2., Statistical Analysis: To analyze data, two-tailed Fisher's exact test and the X2-test with Yates' correction were used as appropriate. The odds ratio was used to express the strength of association between the clinical factors and the PCR results., Results: HSV-DNA was detected in 18% of the specimens, belonging to 25.7% of the patients. Results indicate that the majority of the clinical symptoms are not specific to definitive clinical diagnosis of HSVE, except alteration in the level of consciousness--odds ratio [0.27 (0.07-0.96) (P=0.033)]; and lateralization sign--odds ratio [4.7 (0.98-22.6) (P=0.023)]. However, laboratory data, including total white blood cell count, especially the number of lymphocytes, and MRI findings could be suggested for HSV-PCR examination., Conclusion: At the first admission, a preliminary finding of at least two important clinical features mentioned above along with the pattern of CSF cell and differential counts could be sufficient to perform HSV-PCR which could ultimately result in a rapid and correct diagnosis of herpes simplex encephalitis.