Corrigendum: Correlation between blood glucose and cerebrospinal fluid glucose levels in patients with differences in glucose metabolism.

[This corrects the article DOI: 10.3389/fneur.2023.1103026.].

Correlation between blood glucose and cerebrospinal fluid glucose levels in patients with differences in glucose metabolism.

Objectives: We aimed to determine a method to identify normal cerebrospinal fluid (CSF) glucose levels by examining the correlation between blood and CSF glucose levels in patients with normal and abnormal glucose metabolism. Methods: One hundred ninety-five patients were divided into two groups according to their glucose metabolism. The glucose levels were obtained from CSF and fingertip blood at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. SPSS 22.0 software was used for the statistical analysis. Results: In both the normal and abnormal glucose metabolism groups, CSF glucose levels increased with blood glucose levels at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. In the normal glucose metabolism group, the CSF/blood glucose ratio range was 0.35-0.95 at 0-6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.43-0.74. In the abnormal glucose metabolism group, the CSF/blood glucose ratio range was 0.25-1.2 at 0-6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.33-0.78. Conclusion: The CSF glucose level is influenced by the blood glucose level 6 h before lumbar puncture. In patients with normal glucose metabolism, direct measurement of the CSF glucose level can be used to determine whether the CSF level is normal. However, in patients with abnormal or unclear glucose metabolism, the CSF/average blood glucose ratio should be used to determine whether the CSF glucose level is normal.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Cerebral Venous Thrombosis : A Meta-Analysis.

OBJECTIVE: A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. METHODS: Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. RESULTS: Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference-0.33×10-3 mm2/s [95% CI, -0.44 to -0.23]; p<0.00001). CONCLUSION: DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Cerebral Aspergillosis.

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA. Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-ß-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls. Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden's index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2. Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA. Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Role of diffusion-weighted imaging in the diagnosis of cerebral venous thrombosis.

OBJECTIVE: To evaluate the hyperintense signal (HIS) performance on diffusion-weighted imaging (DWI) in diagnosing cerebral venous thrombosis (CVT). METHODS: Seventy-eight patients with CVT hospitalized from January 2004 to January 2015 were retrospectively studied alongside 78 controls without intracranial organic diseases. Diagnostic accuracy indices of HIS on DWI or T2-weighted imaging (T2WI) to diagnose CVT at different sites and states were analyzed. RESULTS: The overall sensitivity of HIS on DWI for the diagnosis of CVT was significantly lower than that of HIS on T2WI (34.6% vs. 79.5%). HIS on T2WI was more sensitive than HIS on DWI in detecting thrombosis, especially in the superior sagittal sinus and transverse sinus. HIS on DWI was inversely related to the time between disease onset and imaging. Compared with HIS on T2WI, combining HIS on DWI and T2WI did not increase the sensitivity for detecting CVT. HIS on DWI was not detected in the control group, but HIS on T2WI was detected in 26.3% of control individuals. The specificity of HIS on DWI for CVT was higher than that of HIS on T2WI (97.4% vs. 76.9%). CONCLUSION: HIS on DWI has a lower sensitivity, but a higher specificity, than HIS on T2WI for diagnosing CVT.

Sporadic Creutzfeldt-Jakob Disease: A Retrospective Analysis of 104 Cases.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is an extremely rare fatal and infectious neurodegenerative brain disorder characterized by rapidly progressive dementia, cerebellar ataxia, and visual disturbances. This article summarizes the retrospective analysis of 104 sCJD patients in the First Medical Center of Chinese PLA General Hospital from 2003 to 2019. METHODS: A retrospective analysis of the medical records of the 104 patients diagnosed with sCJD was performed from the aspects of demographic data, clinical manifestations, laboratory examinations, cerebrospinal fluid analysis, electroencephalograms (EEGs), diffusion-weighted imaging (DWI) scans, positron emission tomography (PET) scans, and prion protein gene mutations. RESULTS: In the 104 sCJD patients, pathological evidence of a spongiform change was found in 11 patients, while the remaining 93 patients were probable sCJD. The 104 patients included 57 males and 47 females, with the age of onset ranging from 29 to 82 (mean: 58, median: 60) years. The time from disease onset to death ranged from 1 to 36 months. Most of the patients died 7-12 months after the onset of sCJD. In most patients, rapidly progressive dementia appeared as the initial symptom, followed by cerebellar ataxia, visual disturbances, and neurobehavioral disorders. Most patients' DWI images showed symmetric or asymmetric hyperintensity in the cortex. In terms of EEGs, 38.2% of the patients had periodic sharp wave complexes. The sensitivity of 14-3-3 protein detection was 34.1%. The brain PET scans of 50 patients with sCJD presented 96% sensitivity for the diagnosis of sCJD. CONCLUSIONS: This study indicated that sCJD occurred at an early age in patients in China. The sensitivity of 14-3-3 protein detection was significantly low, but brain PET was highly sensitive in the diagnosis of sCJD.

Regional volume changes of the brain in migraine chronification.

The pathophysiology of migraine is complex. Neuroimaging studies reveal functional and structural changes in the brains of migraine patients. We sought to explore regional volume differences in intracranial structures in patients with episodic and chronic migraine. Sixteen episodic migraine patients, 16 chronic migraine patients, and 24 normal controls were recruited and underwent 3.0 T MRI scanning. The volumes of 142 brain regions were calculated by an automatic volumetric algorithm and compared with clinical variables. Results demonstrated that the volumes of specific regions in the frontal and occipital lobes, and the right putamen, were increased and the volume of the fourth ventricle was decreased in the episodic migraine patients compared with controls. The volumes of the left basal forebrain, optic chiasm, and, the fourth ventricle were decreased in the chronic migraine patients, while the occipital cortex and the right putamen were larger. Compared to episodic migraine patiants, chronic migraine patients displayed larger left thalamus and smaller frontal regions. Correlation analysis showed that headache frequency was negatively correlated with the volume of the right frontal pole, right lateral orbital gyrus, and medial frontal lobes and positively correlated with the volume of the left thalamus. The sleep disturbance score was negatively correlated with the volume of the left basal forebrain. This suggests that migraine patients have structural changes in regions associated with pain processing and modulation, affective and cognitive processing, and visual perception. The remodeling of selective intracranial structures may be involved in migraine attacks. This study was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2018-027-02) on May 31, 2018.

Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients.

Purpose: We assessed the performance of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis. Methods: This was a prospective multicenter study. Cerebrospinal fluid samples from patients with viral encephalitis and/or meningitis, tuberculous meningitis, bacterial meningitis, fungal meningitis, and non-central nervous system (CNS) infections were subjected to mNGS. Results: In total, 213 patients with infectious and non-infectious CNS diseases were finally enrolled from November 2016 to May 2019; the mNGS-positive detection rate of definite CNS infections was 57.0%. At a species-specific read number (SSRN) ≥2, mNGS performance in the diagnosis of definite viral encephalitis and/or meningitis was optimal (area under the curve [AUC] = 0.659, 95% confidence interval [CI] = 0.566-0.751); the positivity rate was 42.6%. At a genus-specific read number ≥1, mNGS performance in the diagnosis of tuberculous meningitis (definite or probable) was optimal (AUC=0.619, 95% CI=0.516-0.721); the positivity rate was 27.3%. At SSRNs ≥5 or 10, the diagnostic performance was optimal for definite bacterial meningitis (AUC=0.846, 95% CI = 0.711-0.981); the sensitivity was 73.3%. The sensitivities of mNGS (at SSRN ≥2) in the diagnosis of cryptococcal meningitis and cerebral aspergillosis were 76.92 and 80%, respectively. Conclusion: mNGS of cerebrospinal fluid effectively identifies pathogens causing infectious CNS diseases. mNGS should be used in conjunction with conventional microbiological testing. Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020442.

Patient and economic burdens of postherpetic neuralgia in China.

BACKGROUND: Little is known about the patient-reported and economic burdens of postherpetic neuralgia (PHN) among China's urban population. METHODS: This noninterventional study was conducted among adults ≥40 years with PHN who were seeking medical care at eight urban hospitals in China. At one study site, patients completed a questionnaire evaluating the patient-reported disease burden (N=185). The questionnaire consisted of validated patient-reported outcomes including the Brief Pain Inventory (BPI), 5-dimension, 3-level EuroQol (EQ-5D-3L), Medical Outcomes Study Sleep Scale, and Work Productivity and Activity Impairment Questionnaire for Specific Health Problems. Questions on non-pharmacologic therapy and out-of-pocket (OOP) expenses were also included. At all study sites, physicians (N=100) completed a structured review of patient charts (N=828), which was used to derive health care resource utilization and associated costs from the societal perspective. Annual costs in Chinese Yuan Renminbi (RMB) for the year 2016 were converted to US dollars (US$). RESULTS: Patients (N=185, mean age 63.0 years, 53.5% female) reported pain of moderate severity (mean BPI score 4.6); poor sleep quantity (average of 5.3 hrs per night) and quality; and poorer health status on the EQ-5D-3L relative to the general Chinese population. Respondents also reported average annual OOP costs of RMB 16,873 (US$2541) per patient, mainly for prescription PHN medications (RMB 8990 [US$1354]). Substantial work impairment among employed individuals resulted in annual indirect costs of RMB 28,025 (US$4221). In the chart review, physicians reported that patients (N=828) had substantial health resource utilization, especially office visits; 98% had all-cause and 95% had PHN-related office visits. Total annual direct medical costs were RMB 10,002 (US$1507), mostly driven by hospitalizations (RMB 8781 [US$1323]). CONCLUSION: In urban China, PHN is associated with a patient-reported burden, affecting sleep, quality-of-life, and daily activities including work impairment, and an economic burden resulting from direct medical costs and indirect costs due to lost productivity. These burdens suggest the need for appropriate prevention and management of PHN.

MiR-148a inhibits the proliferation and migration of glioblastoma by targeting ITGA9.

Glioblastoma is a common malignant primary intracranial tumor characterized by rapid invasive growth and a high recurrence rate after surgery. MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis, and abnormal miRNA expression is associated with the occurrence and progression of various tumors, including glioblastomas. The aim of this study was to determine the levels of miR-148a and integrin subunit alpha 9 (ITGA9) in glioblastoma tissues and cells and their involvement in cancer cell proliferation and migration. Glioblastoma tissues from 19 patients and two glioblastoma cell lines (U87 and LN229) were used in this study. The effects of miR-148a on cell viability, proliferation, colony formation, migration, and invasion were assessed. Glioblastomas were xenografted in nude mice to examine the effects of miR-148a overexpression on tumor growth in vivo. Levels of ITGA9 mRNA and protein in glioblastoma tissues were detected by quantitative reverse transcription PCR and western blot analysis, respectively. The interaction between miR-148a and ITGA9 was determined by a dual-luciferase reporter gene assay. We found that the overexpression of miR-148a decreases the proliferation, clustering, migration, and invasiveness of U87 and LN229 cells and inhibits the tumorigenicity of xenografted glioblastomas. We confirmed that ITGA9 is the target of miR-148a. Restoration of ITGA9 expression reversed the decreased viability, migration, and invasiveness of glioblastoma cells induced by miR-148a overexpression. Our findings indicate that miR-148a can suppress the malignant phenotype of glioblastoma by targeting ITGA9 and identify ITGA9 as a potential therapeutic target for glioblastoma.

Apparent performance of metagenomic next-generation sequencing in the diagnosis of cryptococcal meningitis: a descriptive study.

INTRODUCTION: In recent years, metagenomic next-generation sequencing (mNGS) has become widely used in medical microbiology to detect pathogen infection. AIM: We aimed to assess the diagnostic performance of mNGS of cerebrospinal fluid (CSF) for prediction of cryptococcal meningitis (CM). METHODOLOGY: A comparative evaluation of mNGS (performed on CSF samples) and conventional methods, including India ink staining, culture for fungi and cryptococcal-antigen (CrAg) detection by enzyme immunoassay, was performed on 12 consecutive non-HIV-infected patients with chronic or subacute CM. RESULTS: India ink staining and culture of the CSF were positive for Cryptococcus in 83.33 % (10/12) of the samples; 100 % (11/11) were positive via CrAg EIA. The mNGS results of the CSF identified DNA sequences corresponding to Cryptococcus in 75 % of samples (9/12). However, the DNA of both C. neoformans s.l. and C. gattii s.l. was detected concurrently in 33.33 % (4/12). CONCLUSION: mNGS is helpful for identifying Cryptococcus species. The application of mNGS, together with India ink staining, culture methods, and CrAg, may significantly improve the diagnostic precision in CM, thereby informing choice of appropriate antifungal treatment courses.

Multi-parametric MRI Diagnoses Cerebellar Hemangioblastoma: A Case Report.

We performed contrast-enhanced T2 fluid-attenuated inversion recovery (T2-FLAIR) and dynamic contrast enhanced MRI to illustrate the imaging characteristics of one case of hemangioblastoma. T2-FLAIR showed a large cyst located in the right cerebellum with mural nodule. The intensely enhancing cyst wall was observed on enhanced T2-FLAIR images acquired from 5.6 to 23 minutes after contrast administration, and quantitative dynamic contrast enhanced-MRI demonstrated that both the cyst wall and mural nodule presented high Ktrans, Kep and Ve values compared with the contralateral normal cerebellar tissues. The cyst showed gradual enhancement and reached the highest signal intensity at 67 minutes after contrast administration on enhanced T2-FLAIR images. In conclusion, early enhancement of cyst wall on T2-FLAIR might be the characteristic imaging findings for cystic hemangioblastoma, which may assist in the diagnosis of hemangioblastoma preoperatively.

Volume Gain of Brainstem on Medication-Overuse Headache Using Voxel-Based Morphometry.

BACKGROUND: Histopathology identified the anatomical and molecular abnormalities of brainstem nuclei in migraine patients. However, the exact whole brainstem structural changes in vivo have not yet been identified in medication-overuse headache (MOH) transformed from migraine. The aim of this study was to investigate the regional volume changes over the whole brainstem in the MOH patients using voxel-based morphometry (VBM) in vivo. METHODS: High-resolution three-dimensional structural images were obtained using a 3.0-Tesla magnetic resonance system from 36 MOH patients and 32 normal controls (NCs) who were consecutively recruited from the International Headache Center, Chinese People's Liberation Army General Hospital, from March 2013 to June 2016. VBM was used to assess the brainstem structural alteration in the MOH patients, and voxel-wise correlation was performed to evaluate the relationship with the clinical characteristics. RESULTS: The brainstem region with increased volume located in the left ventrolateral periaqueductal gray (MNI coordinate: -1, -33, -8), ventral tegmental area (MNI coordinate: 0, -22, -12), bilateral substantia nigra (MNI coordinate: -8, -16, -12, 9, -16, -12), and trigeminal root entry zone (MNI coordinate: -19, -29, -31; 19, -32, -29) in MOH patients compared with NCs. The headache visual analog scale score was positively related with the left rostral ventromedial medulla (RVM) (MNI coordinate: -1, -37, -56; cluster size: 20; r = 0.602) in the MOH patients. CONCLUSIONS: The regional volume gain of brainstem could underlie the neuromechanism of impaired ascending and descending pathway in the MOH patients, and the left RVM volume alteration could imply the impaired tolerance of nociceptive pain input and could be used to assess the headache disability in the MOH patients.

Stiff person syndrome with elevated titers of antibodies against cardiolipin and ß2 glycoprotein 1: a case report and literature review.

We reported a Stiff person syndrome (SPS) patient with elevated autoantibodies against cardiolipin and ß2 glycoprotein 1 but without glutamic acid decarboxylase (GAD) antibodies. A 40-year male was admitted due to limited mouth opening for 1 week. His blood routine, biochemical, infectious diseases, tumor markers, radiographic examinations were all normal. At day 3 (D3) after admission, he developed paroxysmal systemic muscle rigidity. At D6, the on-duty physician occasionally gave oral clonazepam, which effectively relieved the symptom. At D13, the titers of cardiolipin and ß2 glycoprotein 1 autoantibodies elevated but the remaining autoantibodies were all in normal ranges. After clonazepam treatment for 1 week, the symptoms were basically relieved, and the titers of these two antibodies returned to normal range with the relief of symptoms. During the 3 years of follow-up, the symptoms did not present again, and the titers of both antibodies were stable in the normal ranges. He had no tumor and other immune system diseases. In summary, we reported a SPS case with elevated cardiolipin and ß2 glycoprotein 1 autoantibodies. The patient was highly responsive to clonazepam therapy, and had favorable outcome in the 3 years follow-up. Our report is helpful for better understand the heterogeneous feature of SPS.

[Altered Brainstem Volume in Medication-overuse Headache: A Pilot Magnetic Resonance Imaging Evaluation].

Objective To investigate the altered brainstem volume in patients with medication-overuse headache(MOH). Methods The high-resolution structural images were obtained from 36 MOH patients and 32 normal controls(NC).The brainstem was segmented into midbrain,pons,and medulla,whose volume were measured respectively.Results There was a significantly smaller midbrain volume in MOH patients [(5.80±0.53) ml] than that in NC [(6.14±0.67)ml](t=2.36,P=0.02).The volumes of pons,medulla,and whole brainstem showed no significant difference in MOH patients [(13.13±1.42)ml,(4.55±0.51)ml,and(23.48±2.23)ml,respectively] compared with those in NC [(13.67±1.61) ml,(4.66±0.44) ml,and(24.47±2.56) ml,respectively](tpons=1.47,Ppons=0.15;tmedulla=0.93,Pmedulla=0.35;and tbrainstem=1.71,Pbrainstem=0.09,respectively).Conclusion A smaller midbrain volume may be one of the specific features of pain pathway in MOH,and the automated brainstem subfield segmentation and volumetry may be useful tools for evaluating brainstem alternation in MOH patients.

Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder.

Purpose To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD). Materials and Methods Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups. Results Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t1 = 0.536, t2 = 0.534, t3 = 0.523, t4 = 0.510, and t5 = 0.501; P < .05) and increased global efficiency (t1 = 0.499, t2 = 0.497, t3 = 0.486, t4 = 0.473, and t5 = 0.465; P < .05) and clustering coefficient (t1 = 0.673, t2 = 0.750, t3 = 0.757, t4 = 0.738, and t5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network. Conclusion Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD. © RSNA, 2018.

Two de novo variations identified by massively parallel sequencing in 13 Chinese families with children diagnosed with autism spectrum disorder.

Autism spectrum disorder (ASD) is a genetically heterogeneous neurodevelopmental disorder characterized by impairments in social interaction and communication, and by restricted and repetitive behaviors. The genetic architecture of ASD has been elucidated, including chromosomal rearrangements, de novo or inherited rare variants, and copy number variants. However, the genetic mechanism of Chinese families with ASD children is explored rarely. To identify genetic pathogenesis, we performed massively parallel sequencing on 13 Chinese ASD trio families, and found two de novo variations. The novel de novo splice alteration c.664 + 2T > G in the DEAF1 gene and the novel de novo missense mutation c.95 C > T in the AADAT gene associated with ASD may be important clues for exploring the etiology of this disorder.

Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study.

BACKGROUND: There are sparse and limited studies on small sample size reporting the application of next-generation sequencing (NGS) in the detection of central nervous system (CNS) viral infections. We assessed the diagnostic performance of NGS of cerebrospinal fluid (CSF) for predicting viral infections of the CNS caused by the neurotropic herpes viruses in a pilot population. MATERIALS AND METHODS: We prospectively collected CSF samples from 24 patients with CNS viral infection from April 2017 to October 2018. Of the 24 patients, 19 patients were infected with herpes simplex virus 1 (HSV-1), 1 patient with HSV-2, and 4 patients with varicella-zoster virus (VZV). All CSF samples were screened for viral DNA using NGS technologies to detect viral CNS infections. RESULTS: Of the 24 patients with confirmed viral CNS infection caused by the neurotropic herpes viruses, 10 (10/24, 41.67%) patients exhibited positive NGS results. With the help of NGS, HSV-1 DNA was detected in the CSF of 6 patients (6/19; 31.58%). HSV-2 DNA was detected in 1 patient (1/1; 100%) and VZV DNA was detected in 3 patients (3/4; 75%). The positive rate of virus detected by NGS decreased with time. The positive rates of NGS of CSF in the first, second, and third weeks were 54.5% (6/11), 44.4% (4/9), and 0% (0/4), respectively. CONCLUSIONS: NGS method is a promising pathogen detection tool for identifying viral CNS infections. It should be recommended to sequence viral DNA of CSF in the early stage of CNS viral infections.