The therapeutic value of cerebrospinal fluid ctDNA detection by next-generation sequencing for meningeal carcinomatosis: a case report

Abstract 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.

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Diagnosis of Streptococcus suis Meningoencephalitis with metagenomic next-generation sequencing of the cerebrospinal fluid: a case report with literature review

BMC Infectious Diseases ◽

10.1186/s12879-020-05621-3 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Xiaobo Zhang ◽

Zhaoping Wu ◽

Kai Wang

Keyword(s):

Cerebrospinal Fluid ◽

Case Report ◽

Next Generation Sequencing ◽

Early Diagnosis ◽

Disease Onset ◽

Streptococcus Suis ◽

Diagnostic Techniques ◽

Next Generation ◽

Gram Staining ◽

Generation Sequencing

Abstract Background Streptococcus suis meningoencephalitis is a zoonotic disease that mostly infects slaughterhouse workers. Rapid diagnosis of Streptococcus suis meningoencephalitis is critical for effective clinical management of this condition. However, the current diagnostic techniques are not effective for early diagnosis of this condition. To the best of our knowledge, the use of cerebrospinal fluid metagenomic next generation sequencing in the diagnosis of Streptococcus suis meningoencephalitis has been rarely reported. Case presentation Here, we report a case of Streptococcus suis meningoencephalitis in a 51-year-old female patient. The patient had a history of long-term contact with pork and had a three-centimeter-long wound on her left leg prior to disease onset. Conventional tests, including blood culture, gram staining and cerebrospinal fluid culture, did not reveal bacterial infection. However, Streptococcus suis was detected in cerebrospinal fluid using metagenomic next generation sequencing. Conclusions Metagenomic next generation sequencing is a promising approach for early diagnosis of central nervous system infections. This case report indicates that cases of clinical meningeal encephalitis of unknown cause can be diagnosed through this method.

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Evaluating the Cerebrospinal Fluid ctDNA detection by Next-Generation Sequencing in the diagnosis of Meningeal Carcinomatosis

10.21203/rs.2.9575/v1 ◽

2019 ◽

Author(s):

Yue Zhao ◽

Jun-Ying He ◽

Yue-Li Zou ◽

Xiao-Su Guo ◽

Jun-Zhao Cui ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Next Generation Sequencing ◽

Primary Tumor ◽

Brain Mri ◽

Gene Mutations ◽

Meningeal Carcinomatosis ◽

Next Generation ◽

Csf Cytology ◽

Contrast Enhanced ◽

Generation Sequencing

Abstract 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 signs and symptoms, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging (contrast-enhanced brain MRI and/or CT) 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. Methods A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF tumor-derived circulating tumor DNA (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, 74.29%), followed by gastric cancer (2/35, 5.71%), breast cancer (2/35, 5.71%), prostatic cancer (1/35, 2.86%), parotid gland carcinoma (1/35, 2.86%) and lymphoma (1/35, 2.86%) 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; 71.43%) 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; 62.86%) were consistent with MC. The sensitivity of the neuroimaging was 88.00% (95% confidence intervals [95% CI], 75.26 to 100) (p=22/25) and 62.86% (95% CI, 46.85 to 78.87) (p=22/35) compared to those of CSF cytology and CSF ctDNA, respectively. The sensitivity of the CSF cytology was 71.43% (95% CI, 56.46 to 86.40) (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. The utilizing CSF ctDNA as liquid biopsy technology for the diagnosis of MC based on the detection of cancer-associated gene mutations in ctDNA from CSF offers an alternative and DNA-based test for the diagnosis of MC, especially for cases with persistently negative CSF cytology and/or negative neuroimaging findings.

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Direct Diagnosis of Echovirus 12 Meningitis Using Metagenomic Next Generation Sequencing

Pathogens ◽

10.3390/pathogens10050610 ◽

2021 ◽

Vol 10 (5) ◽

pp. 610

Author(s):

Madjid Morsli ◽

Christine Zandotti ◽

Aurelie Morand ◽

Philippe Colson ◽

Michel Drancourt

Keyword(s):

Cerebrospinal Fluid ◽

Case Report ◽

Next Generation Sequencing ◽

Point Of Care ◽

Pediatric Population ◽

Next Generation ◽

Viral Genotype ◽

Acute Meningitis ◽

Current Point ◽

Generation Sequencing

The current point-of-care diagnosis of enterovirus meningitis does not identify the viral genotype, which is prognostic. In this case report, more than 81% of an Echovirus 12 genome were detected and identified by metagenomic next-generation sequencing, directly from the cerebrospinal fluid collected in a 6-month-old child with meningeal syndrome and meningitis: introducing Echovirus 12 as an etiological agent of acute meningitis in the pediatric population.

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Evaluating the Cerebrospinal Fluid ctDNA detection by Next-Generation Sequencing in the diagnosis of Meningeal Carcinomatosis

10.21203/rs.2.9575/v2 ◽

2019 ◽

Author(s):

Yue Zhao ◽

Jun-Ying He ◽

Yue-Li Zou ◽

Xiao-Su Guo ◽

Jun-Zhao Cui ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Next Generation Sequencing ◽

Primary Tumor ◽

Brain Mri ◽

Gene Mutations ◽

Meningeal Carcinomatosis ◽

Next Generation ◽

Csf Cytology ◽

Contrast Enhanced ◽

Generation Sequencing

Abstract 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 signs and symptoms, positive cerebrospinal fluid (CSF) cytology, and/or neuroimaging (contrast-enhanced brain MRI and/or CT) 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.Methods A total of 35 CSF samples were collected from 35 patients with MC for CSF cytology examination, CSF tumor-derived circulating tumor DNA (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.

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