Next-generation Sequencing Of Cerebrospinal Fluid Research Articles

Moxifloxacin treatment for Mycoplasma hominis meningitis in an extremely preterm infant

The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

Cerebral malaria presenting as nonconvulsive status epilepticus: a case report

BackgroundMalaria is an infectious malady caused by Plasmodium parasites, cerebral malaria standing out as one of its most severe complications. Clinical manifestation include elevated body temperature, loss of consciousness, and seizures. However, reports of cerebral malaria presenting as nonconvulsive status epilepticus are extremely rare. The case presented involves psychiatric symptoms, with the electroencephalogram indicated nonconvulsive status epilepticus associated with cerebral malaria.Case presentationA 53-year-old male, was urgently admitted, due to confusion and abnormal behaviour for 10 h. The patient returned to China after developing a fever while working in Tanzania two months ago. The blood smear revealed Plasmodium vivax and Plasmodium falciparum, and he was diagnosed with malaria. He recovered following anti-malarial treatment. After admission, the patient was confused, unable to communicate normally, and unwilling to cooperate with the physical examination. Plasmodium was not found in the blood smear, but the DNA sequence of P. falciparum was discovered using metagenomic next-generation sequencing of cerebrospinal fluid. Brain MRI revealed no significant abnormalities. Continuous electroencephalogram monitoring revealed that the patient had non-convulsive status epilepticus, which was treated with diazepam and levetiracetam. The patient had normal consciousness and behaviour. He received anti-malarial treatment for two weeks and fully recovered.ConclusionsThis case demonstrates that nonconvulsive status epilepticus can be a manifestation of cerebral malaria. It is imperative for attending physicians to heighten vigilance when encountering patients with a history of travel to malaria-endemic regions or a prior malaria infection, especially in the presence of unusual clinical presentations.

Next-generation sequencing in the diagnosis of neurobrucellosis: a case series of eight consecutive patients

BackgroundNeurobrucellosis (NB) presents a challenge for rapid and specific diagnosis. Next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has showed power in detection of causative pathogens, even some infrequent and unexpected pathogens. In this study, we presented 8 cases of NB diagnosed by the NGS of CSF.MethodsBetween August 1, 2018 and September 30, 2020, NGS was used to detect causative pathogens in clinically suspected central nervous system (CNS) infections. Data on demographics, clinical features, and laboratory tests, imaging results and NGS results were collected and reviewed.ResultsAmong the presented 8 patients, Brucella was rapidly detected using NGS of CSF within 1–4 days, despite those eight patients had variable medical history, disease course, clinical manifestations, laboratory tests and imaging findings. NGS showed the sequence reads corresponded to Brucella species were 8 to 448, with genomic coverage of 0.02 to 0.87%. The relative abundance was 0.13% to 82.40% and sequencing depth was 1.06 to 1.24. Consequently, patients were administered with 3 to 6 months of doxycycline, ceftriaxone and rifampicin, double or triple combination, supplemented with symptomatic therapy and were fully recovered except for case 1.ConclusionNGS of CSF provides a powerful tool in detection of Brucella in a prompt and specific manner, and can be considered for first-line diagnostic use in practice.

Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of VZV-Associated Rhombencephalitis

Rhombencephalitis (RE) is a general term for a group of inflammatory diseases of the rhombencephalon caused by different etiologies. Patients of RE caused by the varicella-zoster virus (VZV) are sporadic in medical practice. The VZV-RE is easily misdiagnosed and causes a poor prognosis for patients. In this study, we analyzed the clinical symptoms and imaging features of five patients with VZV-RE diagnosed by the next-generation sequencing (NGS) technique of cerebrospinal fluid. Magnetic resonance imaging (MRI) examination was used to characterize the imaging of the patients. The McNemar test was used to analyze the cerebrospinal fluid testing (CSF) values and MRI test of the 5 patients. We finally used NGS technology to confirm the diagnosis in 5 patients with VZV-RE. MRI revealed T2/FLAIR high signal lesions in the patients' medulla oblongata, pons, and cerebellum. All patients had early signs of cranial nerve palsy; some had herpes or pain in the corresponding cranial nerve distribution areas. The patients develop headaches, fever, nausea, vomiting, and other signs and symptoms of brainstem cerebellar involvement. McNemar's test showed no statistical difference between multi-mode MRI and CSF values for diagnosing VZV-RE (p = 0.513). This study showed that patients with herpes in the skin and mucous membranes at the distribution area of the cranial nerves and with the underlying disease were prone to RE. We suggest that the NGS analysis should be considered and selected based on the level of parameters, such as MRI lesion characteristics.

Human herpesvirus 7 encephalitis in an immunocompetent adult and a literature review

BackgroundHuman herpesvirus 7 (HHV-7) is a common virus that infects children early and is accompanied by lifelong latency in cells, which is easy to reactivate in immunodeficient adults, but the underlying pathological mechanism is uncertain in immunocompetent adults without peculiar past medical history. Even though the clinical manifestation of the encephalitis caused by HHV-7 is uncommon in immunocompetent adults, the HHV-7 infection should not be neglected for encephalitis for unknown reasons.Case presentationWe reported here a case of HHV-7 encephalitis with epileptic seizures. While the brain computer tomography was standard, electroencephalography displayed slow waves in the temporal and bilateral frontal areas, then HHV-7 DNA was detected in the metagenomic next-generation sequencing of cerebrospinal fluid. Fortunately, the patient recovered after treatment and was discharged 2 months later. We also collected the related cases and explored a better way to illuminate the underlying mechanism.ConclusionThe case indicates clinicians should memorize HHV-7 as an unusual etiology of encephalitis to make an early diagnosis and therapy.

Clinical observation of 8 cases with central nervous system anaerobic infection diagnosed by metagenomic next-generation sequencing of cerebrospinal fluid

The current study summarized the clinical characteristics of 8 patients with central nervous system anaerobic infections who visited the Second Hospital of Hebei Medical University from June 2019 to June 2021. Among the 8 patients, 7 cases had headache and fever as the first symptoms, and 1 case had left-sided limb weakness as the first symptom. Four patients had a previous history of diabetes (1 patient had a history of tooth extraction before the onset of the disease), 1 patient had a previous history of sinusitis, 1 patient had a history of tooth extraction before the onset of the disease, and 2 patients had chronic extensive periodontitis or periapical periodontitis. Five cases showed abnormal intracranial and/or meningeal enhancement on cranial magnetic resonance imaging (MRI), and 1 case showed swelling of the whole brain tissue on cranial computed tomography (CT). After treatment, symptoms of 4 cases were improved, symptoms of 1 case were aggravated, and 3 cases died. Anaerobic infections can occur in various parts of the body:the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin and soft tissues. It is generally believed that anaerobic bacteria rarely cause central nervous system infection, therefore, anaerobic culture of cerebrospinal fluid is usually not performed. Moreover, anaerobic culture is affected by many factors, and thus it is difficult to obtain positive results. Metagenomic next-generation sequencing can identify multiple pathogens (viral, bacterial, fungal, or parasitic) from samples based on DNA and/or RNA sequences and has advantages in diagnosing anaerobic infections of the central nervous system. Prompt empirical antimicrobial therapy is essential for the prognosis of the patients.

Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid (S27.004)

Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid (S27.004)

Polymicrobial Anaerobic Meningitis Detected by Next-Generation Sequencing: Case Report and Review of the Literature

BackgroundAnaerobic meningitis is a severe central nervous system infection associated with significant neurological sequelae and high mortality. However, the precise detection of causative pathogen(s) remains difficult because anaerobic bacteria are difficult to culture. Next-generation sequencing is a technology that was developed recently and has been applied in many fields. To the best of our knowledge, the use of next-generation sequencing for cerebrospinal fluid analysis in the diagnosis of anaerobic meningitis has been rarely reported.Case presentationHere, we report a case of polymicrobial anaerobic meningitis diagnosed using next-generation sequencing of cerebrospinal fluid in a 16-year-old girl. Five species of anaerobic bacteria (Porphyromonas gingivalis, Prevotella enoeca, Campylobacter rectus, Fusobacterium uncleatum, and Actinomyces israelii) were detected by next-generation sequencing and treated with antibacterial agents (ceftriaxone, vancomycin, and metronidazole). The patient responded well to antibacterial treatment. Further inspection revealed bone destruction at the base of the skull, which further confirmed that these bacteria had originated from the oral cavity. One month later, the patient's condition improved significantly. At the same time, we performed a literature review on anaerobic meningitis using studies published in the last 20 years.ConclusionsThis case emphasizes the importance of applying metagenomic next-generation sequencing to clinch the clinical diagnosis for patients with central nervous system infection. Metagenomic next-generation sequencing has been reported to be an important diagnostic modality for identifying uncommon pathogens.

Next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent and young adult brain tumor patients.

Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests. We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient's disease course. We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care.

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)-β-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.

A pediatric case of primary amoebic meningoencephalitis due to Naegleria fowleri diagnosed by next-generation sequencing of cerebrospinal fluid and blood samples

BackgroundPrimary amoebic meningoencephalitis (PAM) is a rare, acute and fatal disease of the central nervous system caused by infection with Naegleria fowleri (Heggie, in Travel Med Infect Dis 8:201–6, 2010). Presently, the majority of reported cases in the literature have been diagnosed through pathogen detection pathogens in the cerebrospinal fluid (CSF). This report highlights the first case of pediatric PAM diagnosed with amoeba infiltration within CSF and bloodstream of an 8-year-old male child, validated through meta-genomic next-generation sequencing (mNGS).Case presentationAn 8-year-old male child was admitted to hospital following 24 h of fever, headache and vomiting and rapidly entered into a coma. CSF examination was consistent with typical bacterial meningitis. However, since targeted treatment for this condition proved to be futile, the patient rapidly progressed to brain death. Finally, the patient was referred to our hospital where he was confirmed with brain death. CSF and blood samples were consequently analyzed through mNGS. N. fowleri was detected in both samples, although the sequence copy number in the blood was lower than for CSF. The pathogen diagnosis was further verified by PCR and Sanger sequencing.ConclusionsThis is the first reported case of pediatric PAM found in mainland China. The results indicate that N. fowleri may spread outside the central nervous system through a damaged blood–brain barrier.

Next-generation sequencing of cerebrospinal fluid for diagnosis of atypical herpes simplex encephalitis.

ObjectivesHerpes simplex encephalitis (HSE) is one of the most common causes of severe viral encephalitis. The characteristic manifestations of HSE include cerebrospinal fluid with mild cytopenia, dominated by lymphocytes, elevated protein, and normal blood glucose values (3.9–6.1 mmol/L). Although it is not difficult to diagnose classical HSE, diagnosing clinically atypical cases is more difficult.MethodsWe reviewed the results of next-generation sequencing (NGS) of CSF in a series of patients diagnosed with atypical HSE.ResultsFour patients lacking classical clinical manifestations of HSE, including no fever, headache, or other typical neurological deficit symptoms, 1–2 × 106 cells/L CSF leucocyte count, and no typical imaging features, were diagnosed with atypical HSE by NGS of CSF. The NGS reads corresponding to herpes simplex virus type 1 ranged from 2 to 13,174.ConclusionsMild HSE may not present with classic frontotemporal lobe syndrome and fever may not be an inevitable symptom in patients with immunosuppression. However, the possibility of HSE should be considered in patients with atypical intracranial infection, and these patients should be tested by NGS.

Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid

Cerebrospinal fluid (CSF) cytologic testing and flow cytometry are insensitive for diagnosing neoplasms of the central nervous system (CNS). Such clinical phenotypes can mimic infectious and autoimmune causes of meningoencephalitis. To ascertain whether CSF metagenomic next-generation sequencing (mNGS) can identify aneuploidy, a hallmark of malignant neoplasms, in difficult-to-diagnose cases of CNS malignant neoplasm. Two case-control studies were performed at the University of California, San Francisco (UCSF). The first study used CSF specimens collected at the UCSF Clinical Laboratories between July 1, 2017, and December 31, 2019, and evaluated test performance in specimens from patients with a CNS malignant neoplasm (positive controls) or without (negative controls). The results were compared with those from CSF cytologic testing and/or flow cytometry. The second study evaluated patients who were enrolled in an ongoing prospective study between April 1, 2014, and July 31, 2019, with presentations that were suggestive of neuroinflammatory disease but who were ultimately diagnosed with a CNS malignant neoplasm. Cases of individuals whose tumors could have been detected earlier without additional invasive testing are discussed. The primary outcome measures were the sensitivity and specificity of aneuploidy detection by CSF mNGS. Secondary subset analyses included a comparison of CSF and tumor tissue chromosomal abnormalities and the identification of neuroimaging characteristics that were associated with test performance. Across both studies, 130 participants were included (median [interquartile range] age, 57.5 [43.3-68.0] years; 72 men [55.4%]). The test performance study used 125 residual laboratory CSF specimens from 47 patients with a CNS malignant neoplasm and 56 patients with other neurological diseases. The neuroinflammatory disease study enrolled 12 patients and 17 matched control participants. The sensitivity of the CSF mNGS assay was 75% (95% CI, 63%-85%), and the specificity was 100% (95% CI, 96%-100%). Aneuploidy was detected in 64% (95% CI, 41%-83%) of the patients in the test performance study with nondiagnostic cytologic testing and/or flow cytometry, and in 55% (95% CI, 23%-83%) of patients in the neuroinflammatory disease study who were ultimately diagnosed with a CNS malignant neoplasm. Of the patients in whom aneuploidy was detected, 38 (90.5%) had multiple copy number variations with tumor fractions ranging from 31% to 49%. This case-control study showed that CSF mNGS, which has low specimen volume requirements, does not require the preservation of cell integrity, and was orginally developed to diagnose neurologic infections, can also detect genetic evidence of a CNS malignant neoplasm in patients in whom CSF cytologic testing and/or flow cytometry yielded negative results with a low risk of false-positive results.

Idiopathic thrombocytopenic purpura with brain abscess caused by Nocardia farcinica diagnosed using metagenomics next-generation sequencing of the cerebrospinal fluid: a case report

BackgroundBrain abscesses caused by Nocardia farcinica are rare, and mostly occur in immunocompromised individuals. Rapid and accurate diagnosis of nocardiosis is challenging. Due to the inadequate performance of conventional diagnostic methods for Nocardia infection, metagenomics next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) has the potential to improve the diagnosis intracranial nocardiosis.Case presentationWe report a case of 50-year-old man with brain abscess caused by Nocardia farcinica. The patient had a idiopathic thrombocytopenic purpura complication that required long-term methylprednisolone administration. His chest image showed multiple lesions, which had been misdiagnosed as lung cancer, and his head image showed multiple intracranial metastases. No pathogen was detected in routine examinations including blood culture, sputum culture and traditional culture methods of cerebrospinal fluid. In order to accurately identify the pathogen, mNGS was used to detect Nocardia in CSF. Although the patient’s condition improved after using sensitive antibiotics, he transferred to the local hospital for treatment because of many complicated diseases and family financial limitations.ConclusionThis case highlights the value of mNGS in the diagnosis of Nocardia brain abscess, and emphasizes the inadequate sensitivity of conventional diagnostic methods for Nocardia infection. Using mNGS can facilitate early and accurate detection of Norcadia-associated of meningitis in immunocompromised patients, thereby reducing unnecessary use of antibiotics and reducing mortality of the disease.

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of External Ventricular and Lumbar Drainage-Associated Ventriculitis and Meningitis.

Metagenomic next-generation sequencing (mNGS) has become a widely used technology that can accurately detect individual pathogens. This prospective study was performed between February 2019 and September 2019 in one of the largest clinical neurosurgery centers in China. The study aimed to evaluate the performance of mNGS on cerebrospinal fluid (CSF) from neurosurgical patients for the diagnosis of external ventricular and lumbar drainage (EVD/LD)-associated ventriculitis and meningitis (VM). We collected CSF specimens from neurosurgical patients with EVD/LD for more than 24 h to perform conventional microbiological studies and mNGS analyses in a pairwise manner. We also investigated the usefulness of mNGS of CSF for the diagnosis of EVD/LD-associated VM. In total, 102 patients were enrolled in this study and divided into three groups, including confirmed VM (cVM) (39), suspected VM (sVM) (49), and non-VM (nVM) (14) groups. Of all the patients, mNGS detected 21 Gram-positive bacteria, 20 Gram-negative bacteria, and five fungi. The three primary bacteria detected were Staphylococcus epidermidis (9), Acinetobacter baumannii (5), and Staphylococcus aureus (3). The mNGS-positive coincidence rate of confirmed EVD/LD-associated VM was 61.54% (24/39), and the negative coincidence rate of the nVM group was 100% (14/14). Of 15 VM pathogens not identified by mNGS in the cVM group, eight were negative with mNGS and seven were inconsistent with the conventional microbiological identification results. In addition, mNGS identified pathogens in 22 cases that were negative using conventional methods; of them, 10 patients received a favorable clinical treatment; thus, showing the benefit of mNGS-guided therapy.

Next-generation Sequencing of Cerebrospinal Fluid: How Can a Liquid be Like a Solid?

The APOLLO investigators showed that next-generation sequencing of cerebrospinal fluid can reveal molecular alterations-how should this affect our management approach?See related article by Xing et al., p. 6168.

Clinical features of aseptic meningitis with varicella zoster virus infection diagnosed by next-generation sequencing: case reports

BackgroundThe aseptic meningitis caused by varicella zoster virus (VZV) reactivation was less described in the literature, most of which were detected by means of polymerase chain reaction. The authors presented 4 adult immunocompetent patients with acute aseptic meningitis with VZV infection diagnosed by next-generation sequencing (NGS).Case presentationFour patients were admitted to the hospital with headache and fever between March 2018 and August 2019. The median ages were 37 years (range 22–52 years). The median symptoms onset to clinic time was 3.5 days (range 3–6 days). Two patients had signs of meningeal irritation. Rash occurred after the meningitis symptoms in 1 patient (time from meningitis symptoms to rash, 2 days). No other sign or symptom was reported. The brain Magnetic resonance imaging and electroencephalography were normal in all patients. Cerebrospinal fluid (CSF) samples were obtained at a median of 4 days (range 3–7 days) from the meningitis symptoms onset. Opening pressure of lumbar puncture after admission were high in these cases (median 256 mm H2O; range 165–400 mm H2O). White blood cell counts and protein levels were significantly elevated in CSF samples (median 317 × 10^6/L, range 147–478 × 10^6/L; median 1.41 g/L, range 0.57–1.79 g/L). The cytology of CSF demonstrated a lymphocytic pleocytosis, and most multinuclear cells. The culture of CSF was negative for all 4 cases, while T-cell spot test was positive for 2 cases, who were administrated with anti-tuberculosis treatment for suspicious tuberculous meningitis. NGS of CSF (the Vision Medical Research Institute) detected specific sequences of VZV in the 4 cases within 72 h after admission. The inappropriate treatment were stopped while acyclovir were continued intravenously for 10–14 days. All patients recovered completely.ConclusionsVZV is an infectious agent that causes aseptic meningitis in immunocompetent adults and could not be accompanied by skin manifestations. The NGS of CSF is a rapid detection for the identification and differentiation of meningitis in patients, which is of great importance for providing the rapid and accurate diagnosis and the targeted antimicrobial therapy for central nervous system infection.

Next-generation sequencing of cerebrospinal fluid for the diagnosis of neurocysticercosis

ObjectiveNeurocysticercosis (NCC) is the most common parasitic disease of the human central nervous system (CNS). However, a diagnosis of NCC may be hard to make if the specific clinical and routine neuroimaging manifestations are lacking, which hinders physicians from considering further immunodiagnostic tests. Patients and methodsSeven patients presented with fever, headache, nausea, cognitive decline, confusion, or progressive leg weakness. There were no pathogens found in the cerebrospinal fluid (CSF); patients were clinically suspected of meningoencephalitis or cerebrovascular disease. To clearly determine the etiology, next generation sequencing (NGS) of the CSF was used to detect pathogens in these seven patients. ResultsTaenia solium DNA sequences were detected in the seven patients, but not in the non-template controls (NTCs) or the other patients with clinically suspected CNS infections. Based on the patients' medical data and the diagnostic criteria for NCC, seven patients were diagnosed with probable NCC. The unique reads aligning to Taenia solium ranged from 6 to 261064, with genomic coverage ranging from 0.0003% to 14.8079%. The number of unique reads and genomic coverage dropped in three of the seven patients after antiparasitic treatment, consistent with the relief of symptoms. ConclusionThis study showed that NGS of the CSF might be an auxiliary diagnostic method for NCC patients. Larger studies are required.

Corrigendum: Afatinib for Advanced Non-small Cell Lung Cancer in a Case With an Uncommon Epidermal Growth Factor Receptor Mutation (G719A) Identified in the Cerebrospinal Fluid.

[This corrects the article DOI: 10.3389/fonc.2019.00628.].

P051 A Novel Model for Estimating Survival in Lung Cancer Patients with Leptomeningeal Metastasis

Leptomeningeal metastasis (LM) occurs in 3%-5% of patients with advanced non-small-cell lung cancer (NSCLC). However, its incidence has increased in patients with driver gene mutations owing to their prolonged survival from target therapies. The prognosis of NSCLC patients with LM has improved to 3-11months in the era of precision medicine. Understanding how prognosis varies across this heterogeneous patient population is essential to individualize care and design future clinical trials. We retrospectively reviewed the medical records of 301 lung cancer patients, who were diagnosed as LM by brain MRI or cytology or next-generation sequencing of cerebrospinal fluid between January 2011 and April 2018. Their clinicopathological characteristics and prognostic data were analyzed. All prognostic factors were weighted for significance by hazard ratios (HR). Among the 301 patients, the median age was 55 years (26-86). Most of them were adenocarcinoma (96.3%，290/301). There were 149 males and 152 females. The median overall survival of the 301 patients was 7.1 months from LM diagnosis. Multivariate analysis revealed that KPS score <60 (HR, 4.30, 3.15-5.87), presence of extracranial metastases (ECM) (HR, 1.79, 1.27-2.52), EGFR negative or unknown and ALK negative or unknown (HR, 1.83, 1.27-2.62) were the independent prognostic factors for poor overall survival. Based on the HR, we made a novel molGPA scoring criteria for LM modified from the molGPA for brain metastasis (BM) and developed a novel molGPA model stratified patients into three categories. The median overall survival for patients with the novel molGPA scores of 0, 0.5-1.0, and1.5-2.0 was 0.3, 4.2, and 12.8 months, respectively (p < 0.001). The C-index of this model was 0.69 (95%CI: 0.65-0.72). We developed a novel molGPA model, which could help clinicians to stratify lung cancer patients with LM in the era of precision medicine. Further research is needed to validate and improve this model.