BackgroundHemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. Central nervous system (CNS) involvement is a severe complication, which can lead to rapid disease development and higher morality. However, this has not been given enough attention in adult HLH. Therefore, we carried out this study to analyze the clinical features, laboratory findings, treatment outcomes, and other characteristics of adult HLH with CNS involvement.

MethodsA retrospective analysis of 96 adult patients with HLH combined with CNS involvement between June 2003 and December 2016 was conducted. Clinical features, cerebrospinal fluid (CSF) features, image changes, and therapeutic outcomes were analyzed.

ResultsAmong the 96 patients, 86 had various CNS symptoms and 33 (38.4%) had already presented symptoms before the HLH diagnosis was confirmed. A total of 59 patients received CSF examinations and showed abnormalities in 23 patients (39.0%). Seventy patients received imaging examinations and the results showed fifty patients with imaging changes (71.4%). Fifty-seven patients received multiple rounds of repeated intrathecal injection therapy and 35 patients improved (61.4%). As for the multiple analyses of effective factors on survival time, the results showed that the effects of combined Epstein-Barr virus (EBV) infection (P = 0.026, Exp(B) = 2.309, 95% confidence interval [CI] [1.108, 4.823) and intrathecal injection therapy (P = 0.013, Exp(B) = 0.422, 95% CI [0.214, 0.831]) on the survival time of the CNS-HLH patients were significant.

ConclusionsComplication with EBV infection is a risk factor, and intrathecal injection is a protective factor. CNS involvement in HLH is not rare, which can result in a poor prognosis. Multiple rounds of repeated intrathecal injection therapy can improve the prognosis of CNS-HLH patients.

Adolescent ; Adult ; Aged ; Central Nervous System ; pathology ; virology ; Epstein-Barr Virus Infections ; pathology ; virology ; Female ; Humans ; Lymphohistiocytosis, Hemophagocytic ; pathology ; virology ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.
Acute Disease ; Brain/diagnostic imaging ; Central Nervous System Diseases/etiology/*pathology ; Child ; Child, Preschool ; Encephalitis/pathology ; Enterovirus A, Human/genetics/*isolation & purification ; Enterovirus Infections/drug therapy/*pathology/virology ; Feces/virology ; Female ; Humans ; Immunoglobulins/administration & dosage ; Infant ; Injections, Intravenous ; Leukocytes/cytology ; Leukocytosis/cerebrospinal fluid/pathology ; Magnetic Resonance Imaging ; Male ; RNA, Viral/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Seasons

In the present study, the complete genomes of four common (4/EV71/Wenzhou/CHN/2014, 15/ EV71/Wenzhou/CHN/2014, 116/EV71/Wenzhou/ CHN/2014, and 120/EV71/Wenzhou/CHN/2014) and two virulent (11/EV71/Wenzhou/CHN/2014 and 109/EV71/Wenzhou/CHN/2014) enterovirus 71 (EV71) isolates were sequenced and described. They are 7405 bp in length and belong to EV71 sub-genotype C4 (C4a cluster). Nucleotide sequence alignment revealed six nucleotide variations (GP151→TP151, GP199→AP199, GP261→TP261, AP328→CP328, GP422→AP422, and GP437→TP437) in the two virulent isolates within the 5'UTR of the IRES element. RNA secondary structure predictions of IRES and FCE indicated that the common isolates shared similar structures, which were different from those of the virulent isolates. Moreover, the GP114→CP114 and GP151→TP151 mutations in the virulent isolates contributed to the formation of the unique RNA secondary structures in SL II. Furthermore, nucleotide/amino acid sequence alignments of 82 EV71 isolates indicated that six sites (TP488 and CP577 in the 5'UTR; AsnP57 in 2A; IleP56 in 3C; CP10 and AP47 in the 3'UTR) are potentially associated with the neurovirulence of EV71. Finally, the 3D structures of 2A were analogous, whereas the structures of VP1 and 3C were variable.
Base Sequence ; Central Nervous System ; virology ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; pathogenicity ; Enterovirus Infections ; virology ; Genome, Viral ; Genomics ; Genotype ; Humans ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; RNA, Viral ; chemistry ; genetics ; Virulence

OBJECTIVEHuman parechovirus (HPeV) is a single-stranded, positive sense RNA virus in the Parechovirus genus within the large family of Picornaviridae. As a possible new pathogen of neonatal sepsis, meningoencephalitis and other infections in young children, HPeV gets more and more attention. This study aimed to better understand the association of HPeV with central nervous system (CNS) infectious diseases and sepsis among hospitalized children in Beijing.

METHODA total of 577 cerebrospinal fluid (CSF) samples were retrospectively collected from 557 children suspected of CNS infections in 2012. Three hundred and fifty-one of them were male and 206 were female. HPeV was screened by reverse transcription-nested PCR (RT-nPCR) with the universal primers which target the highly conserved 5'UTR. The positive samples were genotyped by amplifying and sequencing for the VP3/VP1 junction region. The sequences were compared with the HPeV sequences from GenBank and performed phylogenetic analysis.Some samples other than CSF from HPeV positive children, including serum, nasopharyngeal aspirate and stool, were collected and carried out screening for HPeV.

RESULTWith the RT-nPCR by universal primers, HPeVs were detected in 18 out of 577 CSF samples obtained from 18 children with a positive rate of 3.1%. The ratio of male and female was 2: 1. There were no statistically significant differences on infection rate between boys (12/351, 3.4%) and girls (6/206, 2.9%). All of 18 positive CSF samples were negative for enterovirus, Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), and herpes simplex virus 1 and 2 (HSV).HPeVs from 10 positive CSF samples were genotyped successfully, consisting of 7 HPeV3 and 3 HPeV1. In addition, 2 of 8 serum samples were positive for HPeV3 and 1 of 2 stool samples were positive for HPeV 1. HPeVs were identified in CSF from children aged from 15 days to 14 years, in which 7 cases were infants younger than 3 months and 5 cases were infants from 3 months to one year. Three children older than the age of 9 years (9, 13 and 14 years) were positive for HPeV. Most of the children (6/8) infected with HPeV3 were younger than 3 months and were diagnosed as sepsis, while the rest of HPeV3 positive children were diagnosed as meningitis and bronchopneumonia. HPeV3 infection clustered in August, while HPeV1 in January.

CONCLUSIONHPeVs were associated with CNS infections and sepsis in hospitalized children in Beijing, especially in children younger than one year.HPeV3 was the predominant type identified in CSF.

Adolescent ; Age Distribution ; Central Nervous System Infections ; cerebrospinal fluid ; epidemiology ; virology ; Cerebrospinal Fluid ; virology ; Child ; Child, Hospitalized ; Child, Preschool ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Parechovirus ; classification ; genetics ; isolation & purification ; Picornaviridae Infections ; cerebrospinal fluid ; epidemiology ; virology ; RNA, Viral ; genetics ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Seasons ; Sepsis ; cerebrospinal fluid ; epidemiology ; virology ; Sequence Analysis, DNA

Central Nervous System Viral Diseases ; complications ; virology ; Child ; Epstein-Barr Virus Infections ; complications ; virology ; Female ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; Lymphocytosis ; etiology ; virology ; T-Lymphocytes

This report describes the naturally occurring atypical neuropathological manifestation of systemic canine distemper virus (CDV) infection in two 16-day-old Pit Bull pups. CDV-induced changes affected the gray and white matter of the forebrain while sparing the hindbrain. Histologically, there was necrosis with destruction of the nervous parenchyma due to an influx of inflammatory and reactive cells associated with eosinophilic intranuclear inclusion bodies within glial cells. Positive immunoreactivity against CDV antigens was predominantly observed within astrocytes and neurons. RT-PCR was used to amplify CDV-specific amplicons from brain fragments. These findings suggest the participation of CDV in the etiopathogenesis of these lesions.
Animals ; Antigens, Viral ; Central Nervous System/pathology/virology ; Distemper/*virology ; *Distemper Virus, Canine ; Dogs ; Encephalitis/pathology/*veterinary/virology ; Necrosis/pathology/*veterinary/virology

The incidence of specific intracranial parenchymal lesions of HIV-infected patients varies considerably between countries. In the Republic of Korea, the number of HIV-infected patients is increasing, but little is known regarding the spectrum of intracranial parenchymal lesions in these patients. The aim of the present study was to obtain this information. To identify HIV patients with intracranial parenchymal lesions, the electronic database of radiological reports for 1,167 HIV-infected patients, seen from 1999 to 2008 at the Seoul National University Hospital, were reviewed. Neuroradiologic studies were performed on 165 of these patients, and intracranial parenchymal lesions were detected in 40 (3.4%) of them. Thirty-seven were male, and median age was 41 yr (range, 26-61). At the time of the diagnosis of intracranial parenchymal lesions, median CD4+ lymphocyte count was 40 cells/microL (range 5-560) and in 33 (82.5%) patients, it was less than 200 cells/microL. Progressive multifocal leukoencephalopathy (12 patients) is the most frequent intracranial parenchymal lesions, followed by intracranial tuberculoma (7 patients), primary central nervous system lymphoma (7 patients), intracranial cryptococcoma (4 patients), Toxoplasma encephalitis (4 patients), and disseminated non-tuberculous mycobacterial infection (3 patients).
AIDS-Related Opportunistic Infections/epidemiology/*pathology/physiopathology/virology ; Adult ; Central Nervous System Diseases/epidemiology/*pathology/physiopathology/*virology ; Female ; HIV Infections/*pathology/physiopathology/virology ; Humans ; Male ; Middle Aged ; Republic of Korea/epidemiology

OBJECTIVETo investigate the possible relationship between variation of coxsackievirus B3 (CoxB3) VP1 sequence from cerebrospinal fluid of children with severe and mild central nervous system (CNS) infection and damage to CNS in children from Shandong province.

METHODSThe enteroviruses were detected using VP1 typing and sequencing primer for enteroviruses from 73 enterovirus-infected cases confirmed by detection of cerebrospinal fluid by enteroviruses common primer. VP1 sequences (450 nucleotides) were determined and analyzed for 21 CoxB3 enteroviruses strains isolated in Qingdao and Binzhou, and were compared with that of BLAST search procedures from GeneBank in NCBI. The variation of VP1 gene and amino acids sequence of CoxB3 enteroviruses was analyzed for severe and mild CNS infection.

RESULTSThe nucleotide homogeneity of these CoxB3 appeared to be 97% - 99%, however, the homogeneity among different genotypes were 83% - 76%. Replacement of glutamine by histidine at amino acid locus 856 of VP1 CoxB3 was found in 4 cases with severe encephalitis. There were different variation in VP1 nucleotide sequence of CoxB3 in 3 cases with mild encephalitis and 14 cases with meningitis, but amino acids sequences had no regular variation. The modified Glasgow's coma score was below 7 in all the 4 cases with severe encephalitis. Of these 4 cases, 3 had consciousness disturbance for less than 3 days. Lethargy, restlessness and psychiatric symptoms were major manifestations, of whom 3 also had dysphagia, 1 had encephalatrophy obviously, Glasgow's coma score was 3, deep coma lasted for 9 days, and had concomitant fatal epileptic attacks. Of these 4 cases, 2 completely recovered, 1 had high muscle tone, 1 remained under anti-epileptic drug treatment at follow-up 6 months later.

CONCLUSIONThere were a small epidemic of CoxB3 CNS infection in children in 2005 in this area. The amino acid variation of CoxB3 VP1 possibly caused increased viral virulence and caused damage to CNS.

Amino Acid Sequence ; Base Sequence ; Capsid Proteins ; cerebrospinal fluid ; genetics ; Central Nervous System ; pathology ; virology ; Child ; Coxsackievirus Infections ; cerebrospinal fluid ; epidemiology ; virology ; Encephalitis ; virology ; Enterovirus B, Human ; genetics ; pathogenicity ; Female ; Humans ; Male ; Molecular Sequence Data ; RNA, Viral ; genetics ; Virulence

Central Nervous System Diseases ; complications ; virology ; Child ; China ; epidemiology ; Enterovirus ; Enterovirus A, Human ; Female ; Hand, Foot and Mouth Disease ; complications ; epidemiology ; Humans

OBJECTIVESIt is confirmed that most neonatal subependymal cysts (SEC) are closely correlated with intrauterine infection and the short-term prognosis of SEC is not very good. Little information about the long-term prognosis of SEC is available. The purpose of the present study was to explore the short-term and long-term prognosis of neonatal SEC cases via a 6-year follow up.

METHODSSeventy SEC neonates detected by cranial ultrasound between October 1993 and October 1994 were enrolled into SEC group and 70 healthy neonates into control group. Serum antibodies (IgG and IgM) to cytomegalovirus (CMV), toxoplasma and rubella virus and PCR for these pathogens (except for rubella virus) were measured in the two groups. CMV-PCR was also performed for urine specimens. Cranial sonography assessment, physical growth evaluation, Bayley developmental scale or Wyeth developmental scale, brain-stem auditory evoked potential (BAEP) and vision examination were undertaken at 3, 6, 12 months and 6 years in the two groups.

RESULTSThe positive rate of CMV-IgM and blood CMV-PCR in SEC group was significantly higher than those of control group (19.1% vs. 5.7%, 12.9% vs. 2.9%). The positive rate of urine CMV-PCR in SEC group was also significantly higher (40% vs 17.1%). No significant difference could be found in the positive rate of PCR for toxoplasma and rubella-IgM between the two groups. The weight and height of infants with SEC were obviously lower than those in control group during the first year after birth. The parameters of the physical development in SEC infants reached the similar level as controls till 6 years old. However, the index of mental development below 80 was more often seen in infants with SEC comparing to that in control group during the whole six years. There were no abnormal findings either in BAEP or vision examination in the two groups.

CONCLUSIONInfants with SEC may show a transient retardation of physical growth after birth, while their mental developmental retardation might last for longer time. It is suggested that cranial ultrasound examination should be performed in all neonates for the detection of SEC, and a longer follow-up should be done for infants with SEC.

Antibodies ; Brain Diseases ; diagnostic imaging ; virology ; Central Nervous System Cysts ; diagnostic imaging ; virology ; Cysts ; diagnostic imaging ; virology ; Cytomegalovirus ; immunology ; Follow-Up Studies ; Humans ; Infant, Newborn ; Prognosis ; Prospective Studies ; Ultrasonography