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Background Leptomeningeal carcinomatosis might happen in late non-small cell lung cancer patients and causes a poor median survival period. CSF of leptomeningeal carcinomatosis patients is a special kind of tumor microenvironment. Exosomes are key components of tumor microenvironment and participate in a variety of physiological and pathological processes. There is a great need of comprehensive proteomic analysis of exosomes in these patients. Methods In this study, exosomes in CSF derived from different groups (leptomeningeal carcinomatosis group, non-small cell lung cancer group without leptomeningeal carcinomatosis and normal group) were isolated by ultracentrifugation and proteomics analysis was performed by label-free method. Results A total of 814 proteins were detected. Bioinformatics analysis revealed their shared function in the complement activation, extracellular region, and complement and coagulation cascades. 20 proteins were differentially expressed between groups. In protein-protein interaction network analysis, ACTB, ENO1, TIMP1 and RTN4R had higher betweenness than others. Conclusions This study is the first comprehensively CSF exosomes proteomic profile of leptomeningeal carcinomatosis patients. Further research is needed to clarify the importance of ACTB, ENO1, TIMP1 and RTN4R in leptomeningeal carcinomatosis patients.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and isolated meningeal PCNSL, without evidence of parenchymal involvement, is even less common, occurring in only 10% to 15% of cases.A 65-years-old female presented to our hospital with progressive lower extremity motor dysfunction and blurred vision. The initial neurological examination revealed decreased muscle strength in both lower extremities and sensory dysfunction of lower extremities, saddle area, and buttocks. Brain magnetic resonance imaging showed no abnormalities. Lumbar enhanced magnetic resonance imaging showed T11 to L3 horizontal meningeal enhancement. Cerebrospinal fluid (CSF) cytology revealed lymphoma cells. Immunohistochemistry and flow cytometry of the CSF were performed as auxiliary methods to establish the diagnosis of lymphoma.The patient was diagnosed primary meningeal central nervous system lymphoma.During hospitalization, the patient was treated with 2 courses of high-dose intrathecal methotrexate and rituximab combined with intrathecal chemotherapy and supportive treatment.After 2 years of follow-up, the patient was able to walk and take care of herself.Cases of PCNSL involving only the meninges are rare. Multimodal analysis of the CSF comprises an important component of the diagnostic work-up for patients with primary meningeal central nervous system lymphoma.

It is very difficult to diagnose and distinguish tuberculous meningitis, and the current laboratory methods are unsubstantial in developing countries. The study is aimed at creating a scoring system on the basis of basic laboratory and clinical achievements that could be used as diagnostic aid for tuberculous meningitis for Chinese patients. A retrospective study of cases was conducted for comparison between clinical characteristics and laboratory features of 241 patients on admission who conformed to inclusion criteria of tuberculous meningitis ( n = 141 ) or bacterial meningitis ( n = 100 ). Logistic regression was employed to establish a diagnostic formula to distinguish between tuberculous meningitis and bacterial meningitis. The receiver operating characteristic curve analysis was applied to determine the best diagnostic critical point of the diagnostic formula. It was found that five variables (disease course, white blood cell count, serum sodium, total white cell count of cerebrospinal fluid, and neutrophil proportion in cerebrospinal fluid) were independently associated with tuberculous meningitis. The 87% sensitivity and 94% specificity were included in the diagnostic scoring system derived from these variables. Especially in the case of limited microbial resources, doctors can use this diagnostic scoring system to distinguish tuberculous meningitis from bacterial meningitis.

Next-generation sequencing (NGS) is an emerging method with the potential of pan-pathogen screening. This study described a case of eosinophilic meningitis (EoM) with enzyme-linked immunosorbent assay (ELISA)-negative results for Angiostrongylus cantonensis (A. cantonensis), Trichinella spiralis and Paragonimus westermani and a positive identification of A. cantonensis by NGS in the cerebrospinal fluid.

Background The inflammatory or non-inflammatory changes caused by the virus entering the nervous system and related tissues are central nervous system virus infections. Viral infection is a common infectious disease of the central nervous system, of which herpes simplex virus encephalitis is the most common. However, conventional laboratory techniques to detect an infectious agent are difficult to achieve etiological diagnosis. Case presentation Here we present a patient with severe and progressive encephalitis, requiring diagnosis of the specific pathogen to guide clinical treatments. Conclusions Application of next-generation sequencing provided a quick and definite diagnosis of the etiology of encephalitis and enabled our patient to be treated appropriately.

Background It is usually very complicated to treat meningeal carcinomatosis, and it is important to treat it as soon as possible. Case presentation The 19-Del mutation was found in the exon for the epidermal growth factor receptor gene in the pleural effusion of a patient on March 11th, 2015. He took 250 mg of oral gefitinib once a day for 11 months beginning in December of 2015. On the 3rd of November 2016, he arrived at the hospital and presented with dizziness, headache and transient blurred vision. At this time, he began to take 4 mg of oral zoledronic acid once a month to prevent bone metastases. The result of a cytology exam of the cerebrospinal fluid showed that the man had meningeal carcinomatosis. The 19-Del mutation and the 20-T790 M mutation in the exon of the epidermal growth factor receptor gene was found by the next generation sequencing of the CSF. Then, he discontinued taking gefitinib and began to take 90–100 mg of oral AZD9291 once a day in November 2016. After adjusting the medication dose based on the NGS, his headache was noticeably reduced, and his condition gradually stabilized. Conclusions Cerebrospinal fluid ctDNA detection by next generation sequencing may become a suitable biomarker to monitor clinical treatment response in meningeal carcinomatosis.

Objective To investigate the clinical efficacy and safety of different doses of intrathecal methotrexate in the treatment of leptomeningeal carcinomatosis. Methods 53 patients admitted to the Second Hospital of Hebei Medical University with leptomeningeal carcinomatosis were recruited. They were divided into two groups: 15-mg-group received 15 mg methotrexate intrathecally, while the other received 10 mg methotrexate. All patients were followed up to 31 December 2020 or until death. Primary endpoint was the response rate. Secondary endpoints were survival and safety. Treatment-related adverse events were recorded. Results The intrathecal chemotherapy was regularly maintained in 42 cases. Most primary cancers were lung (60.4%), stomach (18.9%) or breast (5.7%). The clinical response rate was higher in the 15 mg group than the 10 mg group (62.5 vs. 34.5%, P = 0.042). In the 15 mg group, two cases showed myelosuppression and one case showed seizures. In the 10 mg group, one patient appeared fever, three patients appeared myelosuppression and one showed leukoencephalopathy. However, there were no serious irreversible adverse reactions in neither of the two groups. In terms of survival, the median survival was 15.7 weeks in the 15 mg group and 27.1 weeks in the 10 mg group (P = 0.116). Multivariate analysis showed that only targeted therapy improved the survival (P Conclusion Increased dose of methotrexate did not prolong the overall survival, but it was more effective in relieving clinical symptoms with no increased adverse reactions. Targeted therapy might improve the survival.

Background: Neoplastic meningitis refers to malignant tumors invading the meninges and subarachnoid spaces, causing intracranial metastases similar to meningitis. Discovery of tumor cells in the cerebrospinal fluid is the gold standard for its diagnosis. In China, meningeal metastasis of breast cancer is a relatively rare type. Methods: The clinical characteristics, imaging data, cerebrospinal fluid cytology and treatment options of 6 patients with meningeal metastasis of breast cancer treated in our hospital were analyzed. Results: The median age of Neoplastic meningitis was 50 years old. The cerebrospinal fluid pressure of the 6 patients increased to varying degrees and tumor cells were found in the cerebrospinal fluid. Of the 6 patients, 2 received only supportive care, and the rest received chemotherapy and intrathecal injection. The shortest survival time was 1 week, and the longest survival time was over 33.2 weeks. Conclusions: Patients whose initial Karnofsky Performance Scale scores were good and who received active and regular treatment after the diagnosis of NM had long overall survival time.

Background: Infectious encephalitis and meningitis are often treated empirically without identification of the causative pathogen, even if comprehensive conventional diagnostic technologies are applied. Metagenomic next-generation sequencing (mNGS) is a high throughput technology that enables the detection of pathogens independent of prior clinical or laboratory information.Methods: The present study was a multicentre prospective evaluation of mNGS of cerebrospinal fluid (CSF) for the diagnosis of suspected central nervous system infections in China, where routine PCR was not widely used. Results: A total of 276 patients were enrolled in this study between Jan 1, 2017 and Jan 1, 2018. Identification of an aetiologic pathogen in CSF by mNGS was achieved in 101 patients (36.6%). mNGS detected 11 bacterial species, 7 viral species, 2 fungal species, and 2 parasitic species. The leading positive detections were Mycobacterium tuberculosis (14), Listeria monocytogenes (8), Brucella (7), varicella-zoster virus (17), herpes simplex virus 1 (12), Epstein-Barr virus (12), and Cryptococcus neoformans (7). False positives occurred in 12 (4.3%) patients with bacterial infections known to be widespread in hospital environments. False negatives occurred in 16 (5.8%) patients and included bacterial, viral and fungal aetiologies. Conclusions: This study shows that mNGS of CSF is a powerful diagnostic method to identify the pathogen for many central nervous system infections. The result of mNGS should be interpreted with clinical information sometimes.

Background This study profiled the somatic gene mutations and the copy number variations (CNVs) in cerebrospinal fluid (CSF)-circulating tumor DNA (ctDNA) from patients with neoplastic meningitis (NM).Methods A total of 62 CSF ctDNA samples were collected from 58 NM patients for the next generation sequencing. The data were blasted in GenBank and bioinformatically analyzed.Results Cancer-associated gene mutations occurred in all 62 CSF ctDNA samples in TP53 (54/62; 87.10%), EGFR (44/62; 70.97%), PTEN (39/62; 62.90%), CDKN2A (32/62; 51.61%), APC (27/62: 43.55%), TET2 (27/62; 43.55%), GNAQ (18/62; 29.03%), NOTCH1 (17/62; 27.42%), VHL (17/62; 27.42%), FLT3 (16/62; 25.81%), PTCH1 (15/62; 24.19%), BRCA2 (13/62; 20.97%), KDR (10/62; 16.13%), KIT (9/62; 14.52%), MLH1 (9/62; 14.52%), ATM (8/62; 12.90%), CBL (8/62; 12.90%), and DNMT3A (7/62; 11.29%). The mutated genes enriched by the KEGG pathway analysis were the PI3K-Akt, which included the genes of TP53 , EGFR , PTEN , KIT and KDR. After receiving intrathecal and systemic chemotherapy, the ERK1/2 signaling pathways of these CSF samples were activated. Furthermore, the CNVs of these genes were also identified in these 62 samples.Conclusions This study identified gene mutations in all CSF ctDNA samples, indicating that such an approach could be useful as a second-line diagnostic strategy for NM patients. PI3K-Akt signaling may be the potential NM metastasis mechanism.

BackgroundInfectious encephalitis and meningitis are often treated empirically without identification of the causative pathogen. Metagenomic next-generation sequencing (mNGS) is a high throughput technology that enables the detection of pathogens independent of prior clinical or laboratory information.MethodsThe present study was a multicentre prospective evaluation of mNGS of cerebrospinal fluid (CSF) for the diagnosis of suspected central nervous system infections.ResultsA total of 276 patients were enrolled in this study between Jan 1, 2017 and Jan 1, 2018. Identification of an etiologic pathogen in CSF by mNGS was achieved in 101 patients (36.6%). mNGS detected 11 bacterial species, 7 viral species, 2 fungal species, and 2 parasitic species. The five leading positive detections were varicella-zoster virus (17), Mycobacterium tuberculosis (14), herpes simplex virus 1 (12), Epstein-Barr virus (12), and Cryptococcus neoformans (7). False positives occurred in 12 (4.3%) patients with bacterial infections known to be widespread in hospital environments. False negatives occurred in 16 (5.8%) patients and included bacterial, viral and fungal aetiologies.ConclusionsmNGS of CSF is a powerful diagnostic method to identify the pathogen for many central nervous system infections.

Background Meningeal carcinomatosis (MC) is the most severe form of brain metastasis and causes significant morbidity and mortality. Currently, the diagnosis of MC is routinely confirmed on the basis of clinical manifestation, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging features. However, negative rate of CSF cytology and neuroimaging findings often result in a failure to diagnose MC from the patients who actually have the disease. Here we evaluate the CSF circulating tumor DNA (ctDNA) in the diagnosis of MC. Methods A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF ctDNA extraction and cancer-associated gene mutations detection by next-generation sequencing (NGS) at the same time. Results The most frequent primary tumor in this study was lung cancer (26/35, 74%), followed by gastric cancer (2/35, 6%), breast cancer (2/35, 6%), prostatic cancer (1/35, 3%), parotid gland carcinoma (1/35, 3%) and lymphoma (1/35, 3%) while no primary tumor could be found in the remaining 2 patients in spite of using various inspection methods. Twenty-five CSF samples (25/35; 71%) were found neoplastic cells in CSF cytology examination while all of the 35 CSF samples (35/35; 100%) were revealed having detectable ctDNA in which cancer-associated gene mutations were detected. All of 35 patients with MC in the study underwent contrast-enhanced brain MRI and/or CT and 22 neuroimaging features (22/35; 63%) were consistent with MC. The sensitivity of the neuroimaging was 88% (95% confidence intervals [95% CI], 75 to 100) (p = 22/25) and 63% (95% CI, 47 to 79) (p = 22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71% (95% CI, 56 to 86) (n = 25/35) compared to that of CSF ctDNA. Conclusions This study suggests a higher sensitivity of CSF ctDNA than those of CSF cytology and neuroimaging findings. We find cancer-associated gene mutations in ctDNA from CSF of patients with MC at 100% of our cohort, and utilizing CSF ctDNA as liquid biopsy technology based on the detection of cancer-associated gene mutations may give additional information to diagnose MC with negative CSF cytology and/or negative neuroimaging findings.

Ziehl-Neelsen (Z-N) staining of cerebrospinal fluid (CSF) for acid-fast bacilli (AFB) is the cornerstone of the laboratory diagnosis of tuberculous meningitis (TBM). However, the sensitivity of conventional Z-N staining for the detection of AFB in CSF specimens is suboptimal. The present study aimed to compare the practicality of modified Z-N staining with light microscopy and fluorescence microscopy in the same smear without auramine O. A total of 155 patients with 223 CSF specimens were enrolled and grouped according to the uniform case definition. The smears of each CSF specimen were subjected to modified Z-N staining and then observed using a light microscope under transmitted light and under fluorescence with a green-excitation wavelength in the same microscopic field. The results for different groups, inspection times, and prior to and following treatment were compared. Results indicated that the fuchsin-stained AFB were visible as bright orange-red fluorescing rods under fluorescence, or as red, lightly curved rods under transmitted light. The sensitivity of fluorescence microscopy was 96.2% while that of light microscopy was 84.6%. The positive rate of fluorescence microscopy was 79.2% prior to treatment compared with 61.7% post-treatment. In the same microscopic field, a greater number of AFB were observed using fluorescence compared with transmitted light, and AFB that were not visible under transmitted light were clearly observed under fluorescence. Furthermore, transmitted light and fluorescence could be interchanged directly when equivocal smears were encountered. The combination of modified Z-N staining and fluorescence microscopy without auramine O is sensitive and convenient for the diagnosis of TBM.

Background: Neurocutaneous melanocytosis (NCM) is a poorly understood disease due to its rarity. This study aimed to summarize the characteristics of adult NCM and improve the awareness of this disease. Methods: The clinical data of 13 adult patients with NCM were retrospectively reviewed, including neuroimages, cerebrospinal fluid (CSF), and histological features. Results: There were 9 males and 4 females. The mean age at symptom onset was 36.5 years. The initial symptoms included intracranial hypertension in 8 patients and seizure in 4 patients. Ten patients had large and/or multiple congenital melanocytic nevi. MRI revealed hydrocephalus and diffuse thickening of the leptomeninges with T1 shortening in all patients. Post-contrast T1-weighted images showed diffuse linear enhancement of the leptomeninges. Lumbar punctures showed increased open pressure, and elevated protein levels and decreased glucose concentrations in CSF. Cells with intracytoplasmic coarse black granules were found in the CSF and were positive for S100, HMB45, and vimentin. Histopathology of the cutaneous lesions and meninges showed melanocytes but no evidence of malignant melanoma. Conclusion: Adult NCM patients present a diversity of clinical manifestations. Brain MRI showing diffuse thickening of the leptomeninges with T1 shortening is useful in diagnosing NCM. Heterocellular melanin may be of great value for early diagnosis of NCM in challenging cases.

Background Tuberculous meningitis is the most lethal form of tuberculosis, but current diagnostic methods are inadequate. The measurement of cerebrospinal fluid parameters can provide early information for diagnosis. The present study focus on the validity of the cut-off value of cerebrospinal fluid parameters according to the Lancet consensus of scoring system for diagnosis of tuberculous meningitis. Method A total of 100 confirmed patients were enrolled in this study. We evaluated significance of protein level (>1 g/l), chloride level ( 50%), and neutrophil predominance (>50%) in early diagnosis of tuberculous meningitis. Result The cerebrospinal fluid parameters were significantly different between the tuberculous meningitis group and the control group. The independent factors for diagnosis of tuberculous meningitis were protein level (>1 g/l), glucose level ( 50%). Neutrophil predominance (>50%) performed the best with the area under the curve of 89.7%. The sensitivity of protein level (>1 g/l), glucose level ( 50%) for diagnosis of tuberculous meningitis were 66%, 58%, 86%, and 54%, and the specificity were 84%, 98%, 32%, and 98%. There are 84% patients in tuberculous meningitis group at least having two positive parameters among the four independent parameters, while only 10% in control group. Conclusion The cerebrospinal fluid parameters can help the clinicians to make a prompt diagnosis in the early stage of the disease. Diagn. Cytopathol. 2015;43:701–704. © 2015 Wiley Periodicals, Inc.

We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyze the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes.Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated.Of the 11 patients, seven were males, and a mean age at presentation of 63 years (range: 47-79 years). The major clinical features include cognitive decline (9/11), epilepsy (10/11), mental and behavioral disorders (6/11), involuntary movement (4/11), sleep disorders (2/11), hearing loss (1/11), disturbance of consciousness (4/11) and fever (3/11). GABA-B receptor antibody was positive in serum and/or cerebrospinal fluid in 11 patients. Small-cell lung cancer was detected in five patients. Electroencephalogram monitoring demonstrated abnormal discharge in 10 cases. Epileptiform activities were found in five patients. Four patients showed abnormality in hippocampal region, parahippocampal gyrus, temporal and occipital lobe on magnetic resonance imaging. Ten patients accepted first-line immune therapy. Five patients with small-cell lung cancer received oncologic treatment. During a median follow-up of 11 months, eight patients showed a good outcome, two patients (cases 8 and 9) with tumors had a poor one and one patient (case 10) died of status epilepticus.Anti-GABAB receptor encephalitis is an uncommon autoimmune disease, which has been known to be often associated with cancer. Generally, patients associated with GABABR GABA-B receptor antibody encephalitis respond well to immunotherapy, especially if started early.

Neurodegeneration, along with inflammatory demyelination, is an important component of multiple sclerosis (MS) pathogenesis. Autophagy is known to play a pivotal role in neuronal homeostasis and is implicated in several neurodegenerative disorders. However, whether autophagy is involved in the mechanisms of neuronal damage during MS remains to be investigated. Experimental autoimmune encephalomyelitis (EAE), an in vivo model of MS, was induced in female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein p35-55. After that, autophagic flux in the spinal cord of mice was evaluated by detection of LC3-II and Beclin1 protein expressions. EAE mice were then administered with rapamycin and 3-methyladenine (3-MA) for 10 days. Afterward, the changes in LC3-II, Beclin1, and p62 expression, number of infiltrated inflammatory cells, demyelinated lesion area, and neuronal damage, as well as clinical scores, were assessed. Further, apoptotic cell rate and apoptosis-related protein expressions were monitored. We observed an impaired autophagic flux and increased neuronal damage in the spinal cords of EAE mice. We also found that rapamycin, an autophagy inducer, mitigated EAE-induced autophagy decrease, inflammation, demyelination and neuronal injury, as well as the abnormal clinical score. In addition, rapamycin suppressed cell apoptosis, and decreased Bax/Bcl-2 ratio and cleaved caspase-3 expression. Conversely, the effect of autophagy inhibitor 3-MA on EAE mice resulted in completely opposite results. These results indicated that autophagy deficiency, at least in part, contributed to EAE-induced neuronal injury and that pharmacological modulation of autophagy might be a therapeutic strategy for MS.

Multiple myeloma (MM) with central nervous system (CNS) infiltration is uncommon and the diagnosis is more complicated than that of MM. Here we report two cases of CNS MM that was diagnosed by cerebrospinal fluid cytology examination. Cerebrospinal fluid cytology examination can help to detect malignant cells and immunocytochemistry stain is of great value in identifying an unknown tumor. Diagn. Cytopathol. 2017;45:66-68. © 2016 Wiley Periodicals, Inc.

Tuberculous meningitis is the most lethal form of tuberculosis, but current diagnostic methods are inadequate. The measurement of cerebrospinal fluid parameters can provide early information for diagnosis. The present study focus on the validity of the cut-off value of cerebrospinal fluid parameters according to the Lancet consensus of scoring system for diagnosis of tuberculous meningitis.A total of 100 confirmed patients were enrolled in this study. We evaluated significance of protein level (1 g/l), chloride level (120 mmol/l), glucose level (2.2 mmol/l), cell counts (10-500 cells/μl, lymphocytic pleocytosis (50%), and neutrophil predominance (50%) in early diagnosis of tuberculous meningitis.The cerebrospinal fluid parameters were significantly different between the tuberculous meningitis group and the control group. The independent factors for diagnosis of tuberculous meningitis were protein level (1 g/l), glucose level (2.2 mmol/l), cell counts (10-500 cells/μl and neutrophil predominance50%). Neutrophil predominance (50%) performed the best with the area under the curve of 89.7%. The sensitivity of protein level (1 g/l), glucose level (2.2 mmol/l), cell counts (10-500 cells/μl) and neutrophil predominance (50%) for diagnosis of tuberculous meningitis were 66%, 58%, 86%, and 54%, and the specificity were 84%, 98%, 32%, and 98%. There are 84% patients in tuberculous meningitis group at least having two positive parameters among the four independent parameters, while only 10% in control group.The cerebrospinal fluid parameters can help the clinicians to make a prompt diagnosis in the early stage of the disease.

Infections caused by rarely encountered fungal pathogens have increased in recent decades. Phialemonium species are widely distributed in the environment and are also involved in human infections, affecting both immunocompromised and immunocompetent patients. The present study describes a case of meningitis caused by Phialemonium curvatum .

Aim: Neoplastic meningitis (NM) from solid tumors is an advanced malignancy with poor prognosis. Intrathecal chemotherapy is a reliable treatment, and we have obtained some experiences in the treatment of NM with intrathecal dexamethasone and methotrexate (IT DXM and MTX). Methods: Retrospective study of 23 patients with NM from lung cancer ( n = 11), breast cancer ( n = 3), gastric cancer ( n = 1), malignant melanoma ( n = 1), unknown cancer ( n = 7) was conducted. Among these patients, eight received IT DXM and MTX treatment, and 15 patients were placed into a palliative care group. Overall survival (OS) was compared, and the patients' characteristics, symptoms, and some laboratory examinations were analyzed to find the risk factors affecting OS. Results: OS of IT DXM and MTX group was significantly longer than that of the palliative care group ( P = 0.01). The median survival (MS) of palliative care group was 7.53 weeks (5.50-9.57; n = 15), and of the IT DXM and MTX group, 28.63 weeks (12.50-44.75; n = 8); IT DXM and MTX prolonged the OS of NM patients (regression coefficient = −2.923), with odds ratio (OR) being 0.054 (0.09-0.323). Spinal nerves damage decreased the OS (regression coefficient = 1.595), with OR being 4.928 (1.382-17.579). Conclusion: IT DXM and MTX have prolonged the patients' MS, which could be used as a fundamental treatment of NM. Time of induction treatment should be flexible and individualized, and induction treatment could restart when central nervous system relapse. Patients with spinal nerves damage are apt to live shorter.

Non- albicans candida meningitis is a relatively rare disease, with nonspecific clinical manifestation, which makes the misdiagnosis occur sometimes, especially in the early stage of the disease. Abuse of broad-spectrum antibiotics, corticosteroids, central vein cannulas, senility, big operation, malignancy, and total parenteral alimentation were all the susceptible factors of non- albicans candida infection. We present a case of this type of non- albicans infection in a 42-year-old woman who was early misdiagnosed as tuberculous meningitis and was treated with antibiotics and antituberculosis agents. The diagnosis of non- albicans infection was confirmed by fungus culture of the cerebrospinal fluid (CSF) with a low detectable rate. This case reminds us that the non- albicans candida meningitis had a nonspecific clinical presentations and laboratory data, and was difficult to differentiate from tuberculosis meningitis. Hence, we should highly suspect this disease if central nervous system infections with uncertain pathogens. Test cell counts; protein and fungus culture of CSF should be used to confirm the diagnosis. Once the diagnosis was established, the patients should receive antifungal treatment based on drug sensitivity tests as early as possible.

Aim: Japanese encephalitis (JE) is caused by a mosquito-borne flavivirus and demonstrates high mortality and serious sequelae. Imaging and cytological examinations are important for the diagnosis of JE. We performed this study to analyze the imaging and cytological characteristics of JE. Methods: This study enrolled 92 JE patients with 108 cerebral spinal fluid (CSF) samples. Diagnosis was based on clinical features and positive immunoglobulin M antibodies against JE virus, which were measured using enzyme-linked immunosorbent assay. All patients received detailed neurological examinations, relevant cerebrospinal fluid tests, and brain neuroimaging (computed tomography, magnetic resonance imaging, or both). Results: Prominent involvement in the hippocampus was observed in 10 patients on neuroimaging, in addition to classic involvement in the thalamus and basal ganglia. Lumbar puncture pressure was normal in 61 CSF samples. White cell count increased in 81.19% of CSF samples, 67.65% and 83.33% of CSF samples demonstrated normal chloride and glucose concentrations, respectively, and 82.52% of CSF samples demonstrated >0.4 g/L protein content. JE patients demonstrate mixed-cell reaction on cerebrospinal fluid cytology in the early phase, which subsequently mainly develop as mainly lymphocyte reaction or typical lymphocyte reaction. Conclusion: JE imaging is characterized by bilateral thalamic involvement, and the basal ganglia and hippocampus are also commonly affected. The mixed-cell reaction in JE lasts longer than in general viral encephalitis. This may facilitate the differential diagnosis of JE.