Clinical presentation of cytomegalovirus meningoencephalitis in adult patients: A 6-year retrospective study at a single center

Clinical presentation of cytomegalovirus meningoencephalitis in adult patients: A 6-year retrospective study at a single center | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 11 November 2024 V1 Latest version Share on Clinical presentation of cytomegalovirus meningoencephalitis in adult patients: A 6-year retrospective study at a single center Authors : Ching-Hao Hsu , Yi-Tien Hsuan , Yu-Jiun Chan 0000-0001-8065-7421 , and Hsin-Pai Chen 0000-0001-7917-9434 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.173132535.57338782/v1 511 views 270 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Abstract Background: Cytomegalovirus (CMV) is a crucial pathogen in immunocompromised individuals, causing infections such as pneumonitis, colitis, and retinitis. However, research on CMV infections of the central nervous system (CNS) is limited. Objective: This retrospective cohort study enrolled patients with a CMV meningitis or encephalitis diagnosis and analyzed their underlying conditions, clinical manifestations, laboratory findings, treatments, and outcomes. Methods: The study included patients who had positive results in quantitative polymerase chain reaction (PCR) tests of their cerebrospinal fluid (CSF) for CMV at any time between January 2017 and December 2022. Clinical characteristics, laboratory findings, treatment approaches, and outcomes were reviewed and analyzed from electronic medical records. Results: The cohort comprised 12 patients with a median age of 61 years (range, 43–84 years). Stupor and generalized seizures were the most common neurological presentations. Brain imaging in half of the patients revealed nonspecific abnormalities, such as atrophy. CSF protein levels were elevated, with a median of 74.5 mg/dL. CSF pleocytosis was observed in three patients (25%) and was predominantly lymphocytic. The in-hospital mortality rate was 75% (9 out of 12 patients). Conclusions: Although rare, CMV CNS infections are associated with a high mortality rate. CSF pleocytosis is uncommon in such cases, potentially contributing to clinical misdiagnosis or underestimation. CMV meningoencephalitis should be considered in immunocompromised patients who present with unexplained seizures or altered consciousness. Clinical presentation of cytomegalovirus meningoencephalitis in adult patients: A 6-year retrospective study at a single center Ching-Hao Hsu 1,2,3 | Yi-Tien Hsuan 1 | Yu-Jiun Chan 1,4,5 | Hsin-Pai Chen 1,3 1 Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 2 Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 3 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan not-yet-known not-yet-known not-yet-known unknown 4Center for Infection Control, Taipei Veterans General Hospital, Taipei, Taiwan 5 Institue of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan Running head: Cytomegalovirus meningoencephalitis in adults Correspondence Hsin-Pai Chen: Taipei Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei 11247, Taiwan.Email: [email protected] The authors extend their gratitude to Chia-Ling Li for her valuable assistance in clarifying the CMV-PCR testing procedures at the Clinical Virology Laboratory of Taipei Veterans General Hospital. We also acknowledge Wallace Academic Editing for helping editing this artivle. CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest. AUTHOR CONTRIBUTIONS CHH: Conceptualization, formal analysis, data curation, writing - original draft, YTH: Data curation, supervision, writing - review & editing, HPC: Conceptualization, supervision, writing - review & editing. YJC: Resources, supervision, writing - review & editing. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions. FUNDING STATEMENT This research received no external funding. not-yet-known not-yet-known not-yet-known unknown ORCID CHH: 0000-0001-7917-9434 YTH: 0009-0005-3009-4428 HPC: 0000-0002-5956-0526 YJC: 0000-0001-8065-7421 Abstract Background: Cytomegalovirus (CMV) is a crucial pathogen in immunocompromised individuals, causing infections such as pneumonitis, colitis, and retinitis. However, research on CMV infections of the central nervous system (CNS) is limited. Objective: This retrospective cohort study enrolled patients with a CMV meningitis or encephalitis diagnosis and analyzed their underlying conditions, clinical manifestations, laboratory findings, treatments, and outcomes. Methods: The study included patients who had positive results in quantitative polymerase chain reaction (PCR) tests of their cerebrospinal fluid (CSF) for CMV at any time between January 2017 and December 2022. Clinical characteristics, laboratory findings, treatment approaches, and outcomes were reviewed and analyzed from electronic medical records. Results: The cohort comprised 12 patients with a median age of 61 years (range, 43–84 years). Stupor and generalized seizures were the most common neurological presentations. Brain imaging in half of the patients revealed nonspecific abnormalities, such as atrophy. CSF protein levels were elevated, with a median of 74.5 mg/dL. CSF pleocytosis was observed in three patients (25%) and was predominantly lymphocytic. The in-hospital mortality rate was 75% (9 out of 12 patients). Conclusions: Although rare, CMV CNS infections are associated with a high mortality rate. CSF pleocytosis is uncommon in such cases, potentially contributing to clinical misdiagnosis or underestimation. CMV meningoencephalitis should be considered in immunocompromised patients who present with unexplained seizures or altered consciousness. KEYWORDS cytomegalovirus, central nerve system infection, meningoencephalitis, immunocompromised 1 | INTRODUCTION Cytomegalovirus (CMV), a globally prevalent member of the herpesvirus family, exhibits seroprevalence rates that vary geographically, ranging from 66% to 90%. In Taiwan, the seroprevalence of CMV is approximately 90% in adults, 87% in pregnant women, and 0.5% in newborns. 1–3 In healthy individuals, CMV infection is often asymptomatic or presents with mild mononucleosis-like symptoms before entering a latent phase, during which the virus remains dormant for life. However, in immunocompromised patients, such as stem cell or organ transplant recipients and individuals with HIV infection, primary infection or reactivation of CMV can result in severe manifestations, such as viremia, pneumonitis, hepatitis, corneal retinitis, colitis, and menigoencephalitis. These complications largely contribute to both morbidity and mortality in these populations. 4–6 CMV central nervous system (CNS) infection is a rare cause of meningoencephalitis, with most studies primarily focusing on children 7–9 and adults with AIDS. The pathophysiology of CMV-related CNS infection remains poorly understood. However, brain damage is hypothesized to result from either direct viral attack or an inflammatory response. This response is characterized by the recruitment of activated immune cells and the expression of proinflammatory cytokines and interferon (IFN)-regulated genes. 10 CMV CNS infections can present as encephalitis, ventriculitis, meningitis, and myelitis and manifest with clinical symptoms such as seizure, aphasia and cranial nerves palsies. Some cerebrospinal fluid (CSF) findings that are characteristic of such infection include lymphocytic pleocytosis, elevated protein levels, and hypoglycorrhachia. 8,11 Neuroimaging in neonates may reveal calcifications in periventricular regions, cerebellar hypoplasia, or hydrocephalus, whereas magnetic resonance imaging (MRI) in other patients often reveals necrotizing encephalitis, ependymitis, ventriculitis, and periventricular enhancement. The prognosis is particularly poor in individuals with advanced immunosuppressive illnesses such as AIDS. This study reports 12 adult cases of CMV encephalitis from East Asia, providing an evaluation of underlying conditions, clinical presentations, laboratory findings, and responses to antiviral therapy. 2 | MATERIALS AND METHODS 2.1 | Patient recruitment and study design This single-center retrospective study was approved by the Institutional Review Board of Taipei Veterans General Hospital in northern Taiwan. Between January 2017 and December 2022, 12 adult patients (age > 20 years) with confirmed CMV CNS infection were included. The definition of confirmed CMV CNS infection in this study followed criteria from previously described studies 12,13 and encompassed patient presenting with a clinical syndrome consistent with encephalitis or aseptic meningitis and who had positive results on polymerase chain reaction (PCR) tests of their CSF for CMV viral load. For each included patient, medical records were reviewed to gather information on baseline demographics, clinical features, laboratory findings, immune status, neurologic examinations, brain imaging findings, duration of antiviral therapy, comorbidity, and outcomes. The requirement for informed consent was waived as the study involved no intervention, and all identifiable information was encrypted in the database. 2.2 | CSF laboratory studies Routine laboratory assessments of CSF included cell count, protein levels, and chemical analysis. Microbiological evaluations comprised Gram staining and bacterial culture as well as staining and culture for mycobacteria and Cryptococcus using India-ink staining or fungal culture. For CMV quantitation in CSF, viral nucleic acid extraction was performed using the QIAamp DNA Mini Kit in conjunction with the QIAcube Purification system (Qiagen, Hilden, Germany) until June 2020, after which the LabTurbo Virus Kit with the LabTurbo 48C system (LabTurbo Biotech Corporation, Taipei, Taiwan) was employed. CMV PCR was performed using COBAS AmpliPrep/COBAS TaqMan CMV Test (Roche Molecular Diagnostics, USA) before January 2019, which measured CMV DNA ranging from 150 to 10,000,000 copies/mL. After 2019, the COBAS 6800 CMV Test (Roche Molecular Diagnostics, USA) was used, offering a detection range of 34.5–10,000,000 copies/mL. Additional molecular PCR tests for identifying pathogens were conducted using the BIOFIRE FILMARRAY Meningitis–Encephalitis (ME) Panel (BioFire Diagnostics, Salt Lake City, UT, USA), which is capable of detecting 14 common pathogens: Escherichia coli K1, Haemophilus influenzae , Listeria monocytogenes , Neisseria meningitidis , Streptococcus agalactiae , Streptococcus pneumoniae , Cryptococcus neoformans/gattii, enterovirus, herpes simplex virus-1(HSV-1), HSV-2, human herpesvirus 6, human parechovirus, varicella-zoster virus, and CMV. 3 | RESULTS 3.1 | Demographic characteristic and clinical presentation Between January 2017 and December 2022, 546 CSF specimens were tested for CMV through PCR. Of these, 12 patients were identified with CMV CNS infection and included in the study. The cohort comprised three women (25%) and nine men (75%), with a median age of 61.0 years (range: 43–84 years). The majority of patients (n = 11 out of 12) were immunocompromised, including those with hematologic malignancies (n = 3, 25%), HIV/AIDS (n = 2, 17%), those with solid tumors and undergoing recent chemotherapy (n = 2, 17%), brain tumors (n = 2, 17%), and those receiving steroid treatment (n = 2, 17%). Among these immunocompromised patients, three (27%) had undergone intrathecal injections for underlying disease control during the same hospital admission. The most common clinical presentations were stupor, fever, and altered mental status, which were observed in all patients. Additionally, generalized seizures occurred in four patients (33%), muscle weakness in two patients (17%), paraplegia in one patient (8%), and personality changes in one patient (8%; Table 1). Other typical signs of CNS infection, such as photophobia, neck stiffness, nausea and vomiting, were not observed in the included patients. 3.2 | Laboratory and brain imaging findings Lumbar punctures were performed for all patients in this study. The median CSF white blood cell (WBC) count was 1 cell/μL (range, 0–120 cells/μL), with the absence of CSF pleocytosis noted in nine patients (75%). Three patients (25%) exhibited CSF pleocytosis, two of whom had lymphocytic predominance. CSF protein levels were generally elevated, with a median value of 74.5 mg/dL (range, 18.9–3200.0 mg/dL). Among the nine patients tested for lactate, the median level was 28 mg/dL (range, 14.2–2924.0 mg/dL), whereas CSF lactate dehydrogenase (LDH) levels were elevated in four patients (median, 28.0 U/L; range, 12.0–940.0 U/L; Table 2). Routine microbiological tests, including bacterial cultures, mycobacterial cultures with acid-fast staining for Mycobacterium tuberculosis complex, and India-ink stain for Cryptococcus, were conducted in all cases. None of the patients received a diagnosis of or underwent any treatment for bacterial meningitis. Multiplex PCR testing was available after December 2019; among the six patients who underwent multiplex PCR tests, no CMV was detected in three (50%) of them. All patients underwent cerebral imaging within the first week of disease onset, with the findings summarized in Table 3. Four patients received both MRI and computed tomography (CT), three underwent MRI only, and five received only CT scans. One patient exhibited no abnormalities on imaging. Nonspecific brain lesions, such as brain atrophy and ventricle dilation, were observed in six patients (50%). Additionally, two patients had intense enhancing lesions in the brain (16.6%), one had swollen brain parenchyma (8.3%), one had chronic stroke (8.3%), and one had insular restricted diffusion on diffusion-weighted imaging (8.3%). 3.3 | CMV viral load, treatment, and outcomes The median CSF CMV viral load was 590 copies/mL (range, 77–515,919 copies/mL). Nine patients (75%) underwent CMV PCR testing from blood samples, with seven exhibiting CMV viremia (median, 981 copies/mL; range, undetected–2,981,000 copies/mL). A total of 10 patients (83%) received ganciclovir treatment for a median duration of 16 days. One patient’s family refused treatment due to concerns about the side effects of ganciclovir, whereas another patient refused treatment due to the rapid progression of the disease. Half of the patients in this study received care in the intensive care unit (ICU). The mortality rate during hospitalization was 75% (9 out of 12 patients; Table 3). All survivors experienced neurological sequelae following CMV CNS infection, including disturbances in consciousness, cognitive impairment, and muscle weakness. 4 | DISCUSSION This study is the first to report CMV meningitis and encephalitis in an adult population in East Asia. Although the clinical characteristics and manifestations of CMV CNS infections have been extensively reported, research addressing the underlying conditions, risk factors for CMV reactivation, and the clinical progression of these infections remains limited. This retrospective study presents a detailed analysis of 12 adult patients with confirmed CMV meningitis or encephalitis, offering insights into their underlying diseases, clinical presentations, and outcomes. The majority of reports on adult CMV meningoencephalitis have focused on individuals with HIV/AIDS 14–16 and those who have undergone allogeneic stem cell transplantation, 17,18 with only a few isolated case reports addressing immunocompetent individuals. In a multicenter, retrospective cohort study analyzing the characteristics of viral meningoencephalitis in the United States, 72% of the CMV cases occurred in patients with HIV/AIDS. By contrast, our cohort included an even distribution of cases among patients with solid tumors, hematologic malignancies, systematic steroid treatment, and HIV/AIDS, all considered high-risk groups for CMV reactivation or disease. The increased reports of CMV CNS infection in immunocompromised hosts other than those with HIV/AIDS may be attributed to heightened clinical awareness of CMV CNS infection. We hypothesize that all patients in our study had prior CMV exposure, as suggested by a CMV antibody seroprevalence survey conducted in Taiwan. 1 These latent infections, typically controlled by a robust immune response, may have reactivated when the immune system was compromised, leading to end-organ disease in these individuals. 19 The precise mechanism through which cytomegalovirus disseminates from the periphery to the developing CNS remains unclear. However, CMV is hypothesized to access the CNS either in a cell-free form, by directly infecting peripheral neurons or cells of the blood–brain barrier, or in a cell-associated form, through infected brain-infiltrating mononuclear cells. 20 In the present study, half of the enrolled patients exhibited CMV viremia, which may enhance the virus’s ability to breach the blood–brain barrier through hematogenous dissemination. Additionally, five patients in our cohort had underlying conditions that contributed to brain tissue damage and impaired immunity, included tumor invasion and the administration of intrathecal chemotherapy injections. These findings align with those of previous studies on other CMV-related end-organ diseases. Chen and colleagues demonstrated that CMV was detected in nearly half of colorectal cancer tumors, suggesting a potential role for tumor biology in virus invasion. 21 Additionally, localized tissue inflammatory responses, such as those observed in ulcerative colitis, have been documented in relation to CMV colitis. 22,23 As for the CSF laboratory findings, previous studies have indicated that lymphocytic pleocytosis and hypoglycorrhachia are typically present in both immunocompetent and immunocompromised patients. 11,14 Notably, in our study, the absence of CSF pleocytosis was noted in the majority of the patients (75%), with a median CSF white cell count of just 1 cell/μL. Another noteworthy finding is that despite various imaging findings, including subependymal curvilinear lesions on hyperintense T2 FLAIR sequences indicative of the classical “owl’s eye” sign and white matter nodular signal abnormalities 24–26 reported in CMV-related encephalitis or meningitis, most patients in our study did not present the typical imaging findings but instead exhibited only nonspecific presentations. We hypothesize that this lack of significant inflammatory reactions, both in imaging and experimental data, may be attributed to the functional paralysis of infected tissue macrophages and dendritic cells caused by CMV invasion, resulting in suppression of the immune response. 27 This phenomenon is particularly relevant in immunocompromised patients, whose bodies may be less likely to mount a robust inflammatory response to CMV infection. This study has several limitations that should be acknowledged. The primary limitation lies in its retrospective design, which may have introduced bias in the collection of medical data across the 6-year study period. Additionally, the study’s findings may not be generalizable to the broader population, because the study was conducted at a single tertiary care center. However, our cohort, unlike those of previous studies that predominantly focused on patients with HIV/AIDS, included individuals with diverse immunocompromising conditions, which may have reduced potential information bias. Additionally, some patients in our study were too critically ill to undergo MRI examinations, potentially resulting in lost data on significant imaging abnormalities that might not have been detectable through brain CT scans alone. Lastly, the predominantly immunocompromised status of our patients raises the question of whether CMV exacerbates the disease or merely acts as a bystander in the context of severe illness. Future prospective trials are essential to address these points of uncertainty and account for both known and unknown confounding factors. In summary, this study highlighted both well-established and emerging risk factors for CMV reactivation, including hematological malignancies, solid tumors, and systemic steroid use, as along with localized brain conditions, such as brain tumors and intrathecal therapy, as contributors to the development of CMV CNS infection. Clinicians should remain vigilant for CMV CNS infections, even in cases where CSF pleocytosis or characteristic imaging findings of CMV meningoencephalitis are absent, as these indicators may be obscured by suppressed inflammatory responses in immunocompromised patients. These findings offer important guidance for the effective management of CMV CNS infections in adult populations. REFERENCES 1. Lu SC, Chin LT, Wu FM, et al. 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Aseptic meningitis: case definition and guidelines for collection, analysis and presentation of immunization safety data. Vaccine 2007;25:5793-5802. 13. Venkatesan A, Tunkel AR, Bloch KC, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013;57:1114-1128. 14. Arribas JR, Storch GA, Clifford DB, Tselis AC. Cytomegalovirus encephalitis. Ann Intern Med 1996;125:577-587. 15. Holland NR, Power C, Mathews VP, Glass JD, Forman M, McArthur JC. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS). Neurology 1994;44:507-514. 16. Anduze-Faris BM, Fillet AM, Gozlan J, et al. Induction and maintenance therapy of cytomegalovirus central nervous system infection in HIV-infected patients. Aids 2000;14:517-524. 17. Reddy SM, Winston DJ, Territo MC, Schiller GJ. 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TABLE 1 Demographic and clinical characteristics of the 12 patients diagnosed as having CMV CNS infection at the time of diagnosis. 1 43.0 Male Personality change HIV/AIDS HIV/AIDS 2 46.7 Male Muscle weakness CNS diffuse large B cell lymphoma Hematological malignancy 3 61.2 Male Generalized seizure No previous history N/A 4 84.3 Male Generalized seizure Urothelial carcinoma, recent chemotherapy Cancer with recent chemotherapy 5 60.7 Male Stupor, Paraplegia HIV/AIDS HIV/AIDS 6 48.9 Male Generalized seizure Eosinophilic granulomatosis Corticosteroid therapy 7 67.4 Male Generalized seizure Diffuse large B cell lymphoma Hematological malignancy 8 61.5 Female Stupor Breast cancer, brain metastasis with recent IT Cancer with recent chemotherapy and IT 9 57.5 Female Muscle weakness Myasthenia gravis crisis, steroid therapy Corticosteroid therapy 10 53.6 Female Stupor Burkitt’s lymphoma Hematological malignancy, with recent IT 11 62.3 Male Stupor T-cell leukemia/lymphoma Hematological malignancy, with recent IT 12 83.1 Male Stupor Lung small cell carcinoma Cancer with recent chemotherapy Abbreviations: CMV, cytomegalovirus; CNS , central nervous system; IT, intrathecal injection . TABLE 2 Laboratory data and viral load of the 12 patients with CMV central nervous system infection. WBC (Cells/uL) Lym. (%) LDH (U/L) Glucose (mg/dl) Protein (mg/dl) Lactate (mg/dl) CSF Blood 1 0 - 12.0 56 64.1 26.8 ND 6198 ND Negative 2 1 - ND 60 75.0 ND ND 542 588 Negative 3 120 30 27.0 92 54.0 15.1 ND 1031 UD Negative 4 1 - 16.0 169 46.3 18.3 ND 302 UD Negative 5 0 - 124.3 64 3200.0 2942.0 ND 2952 1870 Negative 6 3 - 42.5 30 42.5 ND Negative 224 ND Negative 7 0 - ND 105 76.6 ND CMV 35395 2981000 Negative 8 8 87 940.0 5 458.4 91.0 Negative 298 298 Negative 9 0 - 28.0 61 18.9 14.2 Negative 638 981 Negative 10 1 - ND 104 315.4 28.0 CMV 515919 2010 Negative 11 2 - 25.0 121 74.2 57.0 CMV 126 2450 Negative 12 118 69 321.0 118 518.1 74.0 ND 77 ND Negative Abbreviations: CMV, cytomegalovirus; CSF, cerebrospinal fluid; Lym, lymphocyte; LDH, lactate dehydrogenase; PCR, polymerase chain reaction; HSV, herpes simplex virus; ND, not done; UD, undetected. TABLE 3 Treatment regimens, brain imaging findings, and clinical outcomes for the 12 patients with CMV CNS infection. Drug Duration (days) Given date (days of onset) 1 GAN 11 0 MRI, CT Brain atrophy Deceased 2 GAN 10 −1 a MRI, CT Multiple intense enhancing lesions Deceased 3 GAN 8 1 MRI Insular restricted diffusion on DWI Survived b 4 GAN 15 1 MRI, CT Chronic stroke over right corona Deceased 5 GAN 18 −3 a CT No significant abnormal Deceased 6 GAN 20 4 MRI, CT Ventricular dilation Survived c 7 GAN 8 −3 a CT Brain atrophy Deceased 8 ND ND ND MRI leptomeningeal enhance Deceased 9 GAN 20 3 MRI Brain atrophy Survived d 10 GAN 91 0 CT Swollen brain parenchyma Deceased 11 GAN 17 −7 a CT Brain atrophy Deceased 12 ND ND ND CT Brain atrophy Deceased Abbreviations: CMV, cytomegalovirus; GAN , ganciclovir; ND: not done; MRI, magnetic resonance imaging; CT, computed tomography; DWI: diffusion-weighted imaging. a Ganciclovir treatment was initiated prior to the collection of the specimens. b The patient survived but experienced sequelae related to disturbances in consciousness. c The patient survived but exhibited sequelae characterized by decreased muscle power bilaterally. d The patient survived with developed cognitive changes as a sequela. Information & Authors Information Version history V1 Version 1 11 November 2024 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords cytomegalovirus human cytomegalovirus immune responses infection inflammation reactivation virus classification Authors Affiliations Ching-Hao Hsu Taipei Veterans General Hospital Department of Internal Medicine View all articles by this author Yi-Tien Hsuan Taipei Veterans General Hospital Department of Internal Medicine View all articles by this author Yu-Jiun Chan 0000-0001-8065-7421 Taipei Veterans General Hospital Department of Internal Medicine View all articles by this author Hsin-Pai Chen 0000-0001-7917-9434 [email protected] Taipei Veterans General Hospital Department of Internal Medicine View all articles by this author Metrics & Citations Metrics Article Usage 511 views 270 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ching-Hao Hsu, Yi-Tien Hsuan, Yu-Jiun Chan, et al. Clinical presentation of cytomegalovirus meningoencephalitis in adult patients: A 6-year retrospective study at a single center. Authorea . 11 November 2024. DOI: https://doi.org/10.22541/au.173132535.57338782/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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