OBJECTIVES: Varicella-zoster virus (VZV) is one of the most common etiologies of viral meningitis/encephalitis. The early clinical manifestations and cerebrospinal fluid (CSF) changes of VZV meningitis/encephalitis lack specificity, and it is easy to be misdiagnosed as other viral encephalitides or tuberculous meningitis. This study aims to investigate whether the clinical characteristics, CSF analysis findings, and CSF cytokine levels could distinguish VZV meningitis/encephalitis from central nervous system (CNS) herpes simplex virus (HSV) and Mycobacterium tuberculosis (MTB) infections. METHODS: The medical records from 157 CNS infections, including 49 HSV (45 HSV-1, 4 HSV-2), 55 VZV, and 53 MTB infections between January 2018 and June 2021 in the Cytology Laboratory, Department of Neurology, Third Xiangya Hospital of Central South University were retrospectively reviewed. The data of 3 groups included demographic characteristics, laboratory results, radiographic findings, and outcomes. The levels of 12 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, IFN-γ, IFN-α, and TNF-α) in the CSF of 68 patients (13 HSV, 22 VZV, and 33 MTB infection cases) were quantified. Clinical and laboratory data were compared among the 3 groups. RESULTS: The most common clinical manifestations in the 3 groups were fever, headache, vomiting, and neck stiffness. The clinical manifestations of HSV and VZV CNS disease were similar, although fever and altered consciousness were less common in the VZV group than those in the HSV and MTB groups (63.6% vs 87.8% vs 96.2%, P<0.001, and 14.5% vs 26.5% vs 47.2%, P=0.004, respectively). Seven patients (7/55, 12.7%) presented cutaneous zoster in the VZV group. CSF leukocyte count was significantly higher in the VZV group (230×10⁶ cells/mL) and MTB groups (276×10⁶ cells/mL) than that in the HSV group (87×10⁶ cells/mL, P=0.002). CSF protein level was significantly higher in the VZV than that in the HSV group (1 034 mg/L vs 694 mg/L, P=0.011) but lower than that in the MTB group (1 744 mg/L, P<0.001). IL-6 (VZV vs HSV vs MTB: 2 855.93 pg/mL vs 2 128.26 pg/mL vs 354.77 pg/mL, P=0.029) and IL-8 (VZV vs HSV vs MTB: 4 001.46 pg/mL vs 1 578.11 pg/mL vs 1 023.25 pg/mL, P=0.046) levels were significantly different among the 3 groups and were elevated in the VZV group.Post hoc analysis revealed that IL-6 and IL-8 were significantly higher in the VZV group than those in the MTB group (P=0.002 and P=0.035, respectively), but not in the HSV group (P>0.05). CONCLUSIONS VZV meningitis/encephalitis presents with CSF hypercellularity and proteinemia, challenging the classical view of CSF profiles in viral encephalitis. CSF IL-6 and IL-8 levels are elevated in patients with VZV meningitis/encephalitis, indicating a more intense inflammatory response in these patients.
Humans ; Central Nervous System Infections ; Encephalitis ; Encephalitis, Varicella Zoster/diagnosis* ; Encephalitis, Viral/diagnosis* ; Herpesvirus 3, Human ; Interleukin-6 ; Interleukin-8 ; Meningitis ; Retrospective Studies

Echovirus 30 is one of the major causes of meningitis in children and adults. The purpose of our current study was to investigate whether selected antiviral drugs could provide antiviral activity against echovirus 30. Using RD cells, we assessed the cytopathic effect of echovirus 30, including viral RNA levels as indicators of viral replication. The effects of gemcitabine were compared to rupintrivir, a well-known antiviral drug. To understand the activity gemcitabine exerts on the viral life cycle, time course and time-of-addition assays were implemented. The most effective compounds against echovirus 30 were gemcitabine and rupintrivir, as demonstrated by their concentration-dependent activity. Gemcitabine affects the early stages of echovirus 30 infection by disrupting viral replication. However, gemcitabine failed to directly inactivate echovirus 30 particles or impede viral uptake into the RD cells. Gemcitabine can be considered as a lead candidate in the development of echovirus 30 antiviral drugs, specifically in the early stages of echovirus 30 replication.
Adult ; Antiviral Agents ; Child ; Enterovirus B, Human ; Humans ; In Vitro Techniques ; Life Cycle Stages ; Meningitis ; RNA, Viral

PURPOSE: We report two cases of uveo-meningeal syndrome involving the retina, uvea, and optic disc in both eyes after viral meningitis. CASE SUMMARY: A 16-year-old female was referred to our department with blurred vision in both eyes. She was hospitalized in the pediatric ward with viral meningitis. She showed a norma best-corrected visual acuity (BCVA) and normal intraocular pressure in both eyes, but had severe inflammation in the anterior chamber on slit lamp examination, and optic disc edema and multiple whitish lesions on fundus examination. She was treated with intravenous antibiotic injections and steroid eye drops. After close observation, inflammation in the anterior chamber, optic disc edema, and the multiple whitish lesions in the retina were improved. A 27-year-old male who was treated for viral meningitis at the neurology department was referred to us with blurred vision in both eyes. His BCVAs were 0.7 (right eye) and 0.6 (left eye). The intraocular pressure was normal in both eyes. Slit lamp examination revealed inflammation in the anterior chamber and optic disc edema, and a fundus examination revealed multiple infiltrations. He received treatment for presumed herpes virus infection. After close observation, inflammation in the anterior chamber, optic disc edema, and multiple infiltrations with hemorrhage in the retina were improved. CONCLUSIONS: Clinicians should consider the possibility of uveo-meningeal syndrome, which can cause inflammation in the uvea,retina, and optic disc simultaneous with viral meningitis accompanying blurred vision.
Adolescent ; Adult ; Anterior Chamber ; Edema ; Female ; Hemorrhage ; Humans ; Inflammation ; Intraocular Pressure ; Male ; Meningitis ; Meningitis, Viral ; Neurology ; Ophthalmic Solutions ; Retina ; Slit Lamp ; Uvea ; Vision Disorders ; Visual Acuity

BACKGROUND: Tuberculous meningitis (TBM) is associated with high mortality and morbidity despite administering anti-tuberculous chemotherapy to the patients. Differential diagnosis between TBM and viral meningitis (VM) is difficult in some clinical situations. METHODS: We reviewed and analyzed records of adult patients who were admitted and diagnosed with TBM or VM at a tertiary hospital in Korea, between January 2006 and December 2015. Diagnostic criteria for TBM were categorized into three groups: definite, probable, and possible TBM. The VM group included patients with no evidence of other meningitis who achieved complete recovery with only conservative treatments. Clinical, laboratory and radiological findings, as well as outcomes, were compared between the TBM and VM groups. RESULTS: Ninety-eight patients were enrolled. Among the study patients, 47 had TBM and 51 had VM. Based on univariate analysis and multivariate logistic regression, sodium < 135 mmol/L in serum (hyponatremia), lactate dehydrogenase > 70 (U/L) in cerebrospinal fluid (CSF), protein > 160 (mg/dL) in CSF, voiding difficulty, and symptoms of cranial nerve palsy were significant predictive factors for TBM in the final model. We constructed a weighted scoring system with predictive factors from multiple regression analyses. Receiver operating characteristic curve analyses and decision tree analyses were plotted to reveal an optimum cutoff point as 4 with this scoring system (range: 0–13). CONCLUSION: For differential diagnosis between TBM and VM, we created a new weighted scoring system. This scoring system and decision tree analysis are simple and easy to apply in clinical practice to differentiate TBM from VM.
Adult ; Cerebrospinal Fluid ; Cranial Nerve Diseases ; Decision Trees ; Diagnosis, Differential* ; Drug Therapy ; Humans ; Korea ; L-Lactate Dehydrogenase ; Logistic Models ; Meningitis ; Meningitis, Viral* ; Mortality ; ROC Curve ; Sodium ; Tertiary Care Centers ; Tuberculosis, Meningeal*

Neurologic complications associated with varicella zoster virus (VZV) are rare in children. A 13-year-old boy was hospitalized due to headache, fever, and vomiting. Aseptic viral meningitis was strongly suspicious based on findings on physical exam, cerebrospinal fluid examination, and brain magnetic resonance imaging. On the second day of hospitalization, typical zosteriform rashes developed on his left chest wall across the T7-T8 dermatome. Tzanck test of the skin lesion was positive and polymerase chain reaction test for VZV was positive on the second cerebrospinal fluid examination. Serum immunoglobulin levels were within normal range. Intravenous acyclovir was started and symptoms and signs of meningitis gradually improved and the patient was discharged without any complications. In immunocompetent children, VZV meningitis is rare and requires rapid diagnosis and treatment. Therefore, it is necessary to prompt diagnosis and treatment thorough medical history, physical examination and laboratory examination.
Acyclovir ; Adolescent ; Brain ; Cerebrospinal Fluid ; Chickenpox* ; Child* ; Diagnosis ; Exanthema ; Fever ; Headache ; Herpes Zoster* ; Herpesvirus 3, Human ; Hospitalization ; Humans ; Immunoglobulins ; Magnetic Resonance Imaging ; Male ; Meningitis* ; Meningitis, Viral ; Physical Examination ; Polymerase Chain Reaction ; Reference Values ; Skin ; Thoracic Wall ; Vomiting

OBJECTIVES: To compare the epidemiology, clinical presentation, laboratory findings, seasonality and hospital course of enteroviral meningitis (EM) and non-enteroviral meningitis (NEM) cases in infants under 3 months of age. METHODS: A retrospective chart review was performed of infants under 3 months of age or less with viral meningitis admitted to Ewha Womans University Mokdong Hospital between January 2010 and December 2016. RESULTS: EM patients were more likely to have siblings compared with NEM. Most of EM was diagnosed during the summer season. Almost 80% of EM was diagnosed between July and September. Fever lasted longer in EM patients compared to NEM. White blood cell count (WBC) from the cerebrospinal fluid was higher in EM patients compared with NEM patients. WBC in blood were lower in EM patients compared with NEM patients. C-reactive protein was lower in EM patients compared with NEM patients. Most of the patients were initially started on antibiotics therapy to rule out bacterial meningitis. EM patients received shorter duration of antibiotic treatment compared with NEM patients. CONCLUSION: This study was conducted to augment the understanding of the incidence, epidemiology, transmission in infants, clinical presentation, laboratory findings, seasonality and hospital courses of enteroviral meningitis compared to NEM. Early recognition, rapid diagnosis and proper clinical management can reduce duration of antibiotic treatment.
Anti-Bacterial Agents ; C-Reactive Protein ; Cerebrospinal Fluid ; Diagnosis ; Enterovirus ; Epidemiology* ; Female ; Fever ; Humans ; Incidence ; Infant* ; Leukocyte Count ; Meningitis* ; Meningitis, Bacterial ; Meningitis, Viral ; Polymerase Chain Reaction ; Retrospective Studies ; Seasons ; Siblings

PURPOSE: To report two cases of acute retinal necrosis following viral meningitis. CASE SUMMARY: A 52-year-old woman who has had viral meningitis presented with visual loss of right eye. Slit-lamp examination showed conjunctival injection and inflammatory cells (2+) in the anterior chamber of the right eye. Funduscopic examination showed multiple yellow-whitish spots in the peripheral retina. Fluorescein fundus angiography showed early hypofluorescence and the late vascular leak in the peripheral retina. After the patient was diagnosed with Acute retinal necrosis (ARN), intravenous acyclovir (2,100 mg/m²/day) was administered. During the treatment period, the retinal detachment of the right eye was found, so the authors performed pars plana vitrectomy. After the surgery, new retinal lesions weren't observed in both eyes during follow-up. A 57-year-old man previously treated with possible viral meningitis presented with visual loss of his right eye. Funduscopic examination showed multiple yellow-whitish spots in the peripheral retina. Fluorescein fundus angiography showed the late vascular leak in the peripheral retina. In the systemic evaluation, Herpes simplex virus and Cytomegalovirus immunoglobulin G were detected. With the impression of ARN, intravenous acyclovir (2,100 mg/m²/day) was administered. No new retinal lesions were observed in both eyes during follow-up. CONCLUSIONS: We report rare cases of ARN occurring after viral meningitis. Uveitis in patients with recent history of meningitis should be examined carefully under the suspicion of ARN.
Acyclovir ; Angiography ; Anterior Chamber ; Cytomegalovirus ; Female ; Fluorescein ; Follow-Up Studies ; Humans ; Immunoglobulin G ; Meningitis ; Meningitis, Viral* ; Middle Aged ; Retina ; Retinal Detachment ; Retinal Necrosis Syndrome, Acute* ; Retinaldehyde ; Simplexvirus ; Uveitis ; Vitrectomy

PURPOSE: Urinary tract infection (UTI) is the most common serious bacterial infection in infants younger than 3 months of age. Lumbar puncture is routinely performed to evaluate febrile young infants for sepsis. However, there is no clear consensus on the use of routine lumbar puncture to diagnose concomitant meningitis in infants with UTI. We evaluated the prevalence of coexisting bacterial meningitis and sterile cerebrospinal fluid (CSF) pleocytosis in young infants with UTI. METHODS: We retrospectively reviewed the medical records of 85 infants with UTI, aged from 29 to 99 days, who were admitted to Daegu Catholic University Medical Center from January 2013 to May 2016. We included 80 patients who had undergone lumbar puncture. Demographic features, clinical features, and laboratory findings were analyzed. Patients were divided into two groups based on the presence of sterile CSF pleocytosis and we compared these groups and assessed the differences between them. RESULTS: Of the 80 UTI patients enrolled, 34 (43%) had sterile CSF pleocytosis. None had bacterial meningitis, and CSF polymerase chain reaction for enterovirus was positive in two patients without CSF pleocytosis. There were no significant differences between the two groups with regards to age, body temperature, peripheral white blood cell count, urinalysis, and duration of hospital stay. CONCLUSIONS: Though sterile CSF pleocytosis is common in young UTI patients, coexisting bacterial or viral meningitis is very rare. Indications for lumbar puncture in these patients depend on clinical condition.
Academic Medical Centers ; Bacterial Infections ; Body Temperature ; Cerebrospinal Fluid ; Consensus ; Daegu ; Enterovirus ; Humans ; Infant* ; Length of Stay ; Leukocyte Count ; Leukocytosis ; Medical Records ; Meningitis ; Meningitis, Bacterial ; Meningitis, Viral ; Polymerase Chain Reaction ; Prevalence ; Retrospective Studies ; Sepsis ; Spinal Puncture* ; Urinalysis ; Urinary Tract Infections* ; Urinary Tract*

OBJECTIVES: Echovirus 30 is a major cause of meningitis in children and adults. The aim of this study was to investigate whether the antifungal drug itraconazole could exhibit antiviral activity against echovirus 30. METHODS: The cytopathic effect and viral RNA levels were assessed in RD cells as indicators of viral replication. The effects of itraconazole were compared to those of two known antiviral drugs, rupintrivir and pleconaril. The time course and time-of-addition assays were used to approximate the time at which itraconazole exerts its activity in the viral cycle. RESULTS: Itraconazole and rupintrivir demonstrated the greatest potency against echovirus 30, demonstrating concentration-dependent activity, whereas pleconaril showed no antiviral activity. Itraconazole did not directly inactivate echovirus 30 particles or impede viral uptake into RD cells, but did affect the initial stages of echovirus 30 infection through interference with viral replication. CONCLUSION: Itraconazole can be considered a lead candidate for the development of antiviral drugs against echovirus 30 that may be used during the early stages of echovirus 30 replication.
Adult ; Antiviral Agents ; Child ; Enterovirus B, Human* ; Humans ; In Vitro Techniques* ; Itraconazole* ; Meningitis ; RNA, Viral

BACKGROUND AND PURPOSE: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an immune-mediated chorioretinal disease that causes acute visual symptoms with characteristic ophthalmoscopic findings. Neurological complications are rarely reported in the literature. Here we report two new cases of APMPPE that presented with neurological manifestations, one of which was associated with peripheral neuropathy, which has not been described before. METHODS: A retrospective database review of all patients with a diagnosis of APMPPE was performed. Clinical, ophthalmological, and neurological data were analyzed, and only cases of APMPPE with neurological complications were included. A literature review of several databases was also performed, and previous case reports were reviewed and analyzed in detail. RESULTS: In total, 56 cases of APMPPE-associated neurological complications were included in the analyses: 54 from the literature and 2 from our own practice. The most common complication was cerebral vasculitis, which affected 28 patients (50%), followed by headaches in 15 patients (26.8%). The other complications include sixth-cranial-nerve palsy, transient hearing loss, meningoencephalitis, cavernous sinus thrombosis, and viral meningitis. CONCLUSIONS: This report adds to the literature of a novel association of APMPPE with peripheral neuropathy, and comprehensively reviews the neurological manifestations of this disease. A high level of suspicion should be applied when dealing with a case of APMPPE. We recommend applying detailed clinical neurological examinations and magnetic resonance imaging to APMPPE patients, and then early steroid treatment if the examination is positive or even suspicious. Early treatment with steroids and long-term treatment with immunosuppressive azathioprine with interval neurological evaluations will contribute positively to the outcomes and avoid fatal complications, namely strokes.
Adrenal Cortex Hormones ; Azathioprine ; Cavernous Sinus Thrombosis ; Diagnosis ; Headache ; Hearing Loss ; Humans ; Magnetic Resonance Imaging ; Meningitis, Viral ; Meningoencephalitis ; Neurologic Examination ; Neurologic Manifestations* ; Paralysis ; Peripheral Nervous System Diseases ; Retrospective Studies ; Steroids ; Stroke ; Vasculitis, Central Nervous System