Cerebrospinal fluid metabolites as biomarkers to distinguish between viral and autoimmune encephalitis

LEGATO project
LEGATO projectLEGATO project
Amani Al-Mekhlafi
PhD student
Magdeburg, 27.09.2019
Cerebrospinal fluid metabolites as biomarkers to
distinguish between viral and autoimmune encephalitis
MHH: Martin Stangel, Kurt-Wolfram Sühs (Dept. of Neurology),
Volkhard Kaever (Emeritus, Research Core Unit Metabolomics)
TWINCORE: Maike Kuhn, Frank Pessler
HZI: Frank Klawonn
AGENDA
• Introduction
• Aims
• Study Cohort
• Results
• Next step
Page 3 |
Viral vs. autoimmune CNS disorders
. Viral meningitis/encephalitisAutoimmune neuroinflammation
CMV
HSV
Enteroviruses
Anti-NMDA-r encephalitis
Multiple Sclerosis
Clinical challenge:
similar presentation – different treatments
Name der PräsentationSeite 4 |
Altered mental status, focal neurological deficits, seizures
Mild neuroinflammation
Mild-to-moderate disruption of blood-CSF-barrier
Non-specific changes on imaging (MRI)
Antivirals
(if available for pathogen)
Immunosuppression
Plasmapheresis
B cell depletion
Viral Autoimmune
Pathogen detection (PCR, etc.) Autoantibody detection
CSF Analysis
Seite 5 | Deisenhammer et al. Routine cerebrospinal fluid (CSF) analysis ,2011
Aims
• To identify candidate biomarkers that can accurately differentiate between viral
and autoimmune encephalitis
and
could potentially be developed into a rapid (bedside) diagnostic
• Comparison with standard diagnostic parameters (CSF leukocytes, etc.)
Name der PräsentationSeite 6 |
Study Cohort
Six patient groups
Name der PräsentationSeite 7 |
Total n= 79
Biomaterial: cerebrospinal fluid (CSF)
Name der PräsentationSeite 8 |
1-2 h
Storage
Sample collection
Centrifugation
Clinical diagnostics
Cells Supernatant
Targeted metabolomic profiling
Biocrates AbsoluteIDQ® p180 Kit
Name der PräsentationSeite 9 |
• Mass spectrometry-based assay for biological tissues and fluids, including CSF
• 96-well format
www.biocrates.com, www.sciex.com
API4000
Triple-Quadrupol-MS
(RCU Metabolomics, MHH)
Maike Kuhn
Detectable metabolites
Name der PräsentationSeite 10 | Jones et al., Progress in Lipid Research 2010,
Commons.wikimedia.org, vinmetrica.com, eichler.mgh.harvard.edu
Total n= 188
Name der PräsentationSeite 11 |
Results
Name der PräsentationSeite 12 |
HAUCA Curve
Indicates how much the correlation between the biomarker and the
disease exceed the pure random effect.
Name der PräsentationSeite 13 |
108
15
13
Standard parameter analysis
MS NMDA Ent. men HSV Z.men_enc Chi-square
P vlaue
Kruskal-Wallis test
P value
Demographic
Age (Year)
Mean(sd) 38(11.6) 38(20.5) 41(19.4) 58(16.4) 53(21) 0.04
Median(range) 33(23-58) 30(19-69) 33(22-76) 56(29-76) 55(13-80)
Gender
male 53% 13% 60% 78% 60% 0.14
female 47% 87% 40% 22% 40%
Blood Parameter
Leukocytes count 1000/µl
Mean(sd) 7.9(3.7) 6.3(2.7) 7.5(3.0) 8.5(4) 7.8(3.3) 0.84
Median(range) 6.5(2.8-18.2) 6.4(2.1-9.7) 7.3(4-14) 10.1(1.8-12.8) 6.9(3.8-13.6)
C-reactive Protien mg/l
Mean(sd) 3.2(5.4) 13.01(12.9) 9.3(12.3) 22.1(37.3) 13.6(32.3) 0.14
Median(range) 1(1-23) 11.2(1-37) 4(1-39) 3(1-102) 2 (1-128)
CSF Parameter
Leukocytes count 1/µl
Mean(sd) 10.6(11.6) 49.6(61.04) 129.1(235.3) 187.5(233.4) 199.8(400.2) 0.002
Median(range) 7.7(.7-48) 22.4(1.7-172) 9.2(.7-619) 90.7(16-723) 38(1.7-1536)
Qalb
Mean(sd) 6.3(1.8) 17.2(15.01) 9.5(5) 26.8(13.5) 14.9(9.9) 1.78e-05
Median(range) 6.2(2.5-9.6) 8.7(6.2-41.1) 8.9(2.7-21.7) 31.8(6.8-44.4) 11.4(4.5-41.1)
Blood-CSF-barrier disruption
no disruption(1) 53% 75% 20% 11% 20% 0.0005
Light(2) 47% 25% 70% 11% 40%
Moderate(3) 0% 0% 10% 11% 27%
Sever(4) 0% 0% 0% 67% 13%
Protein_concentration g/l
Mean(sd) .48(0.11) .45(0.2) .57(.21) 1.3(.62) 0.82(.49) 0.0005
Median(range) .49(0.31-0.66) .42(0.2-0.9) .52(.24-.98) 1.2(.52-2.3) 0.65(0.31-2.05)
Lactate mmol/L
Mean(sd) 1.8(0.42) 2.1(0.4) 2.1(.62) 2.5(.54) 2.8(1.1) 0.003
Median(range) 1.6(1.3-2.4) 2.2(1.4-2.6) 1.9(1.6-3.6) 2.3(1.8-3.4) 2.6(1.5-5.5)
Q_IgG
Mean(sd) 6.3(3.7) 8.2(5.2) 5.2(3.3) 23.4(16.7) 9.1(5.2) 0.004
Median(range) 4.8(1.6-13.2) 7.95(1.6-14.9) 5(1.3-13.6) 19.6(4.5-58.4) 8.5(3.2-21.1)
IgG_Index
Mean(sd) 1.03(.64) 1.1(0.71) .53(.05) .82(.24) 0.63(.17) 0.0002
Median(range) 0.79 (.55-.2.9) 0.71(0.5-2.4) .53(.47-.63) .76(.5-1.3) 0.57(0.5-1.2)
Name der PräsentationSeite 14 |
Qalb MS NMDA Ent.men HSV Z.men_enc Kruskal-Wallis test
Mean 6.3 17.2 9.5 26.8 14.9
1.78e-5
Median 6.2 8.7 8.9 31.8 11.4
First look at biomarker potential – a shimmer of hope
Name der PräsentationSeite 15 |
Autoimmune
Viral
Metabolites
Lipids
Amino acids
Standard parameters
Changes in CSF lipids contribute the most to differences
Name der PräsentationSeite 16 |
Metabolites Standard parameters
CSF metabolites are more accurate biomarkers than
standard diagnostic CSF parameters
for the distinction between viral and autoimmune neuroinflammation
Name der PräsentationSeite 17 |
Standard CSF Parameter AUC Metabolites AUC Selection
frequency
Q-albumin 0.86*** C5 0.93*** 1
Leukocyte count 0.74** PC.aa.C30.0 0.92*** 1
Protein concentration 0.78*** PC.ae.C32.2 0.92*** 1
IgG-index 0.76*** C4 0.92*** 1
Lactate 0.74** SM.C16.0 0.91*** 1
BCB dysfunction 0.79*** PC.aa.C38.0 0.90*** 1
AUC0.5 1.0
Receiver operating characteristic (ROC) curve analysis
perfect biomarkerworthless
Highest CSF concentrations of C5 and C4 in herpes
virus infection
Name der PräsentationSeite 18 |
C5 & C4
C5 C4
Name der PräsentationSeite 19 |
Comparison Q-albumin C5 C4
HSV vs. autoimmune 0.94*** 0.98*** 0.99***
VZV vs. autoimmune 0.89*** 0.95*** 0.92***
Enterovirus vs. autoimmune 0.76*** 0.92*** 0.92***
C5 and C4 are the most accurate biomarkers for CNS infection
by all three viral pathogens
Sensitivity, specificity and predictive values
Sensitivity Specificity PPV NPV
C5 0.879 0.845 0.807 0.904
C4 0.752 0.785 0.720 0.812
Q-albumine 0.483 0.637 0.502 0.619
Name der PräsentationSeite 20 |
Virus-induced mitochondrial dysfunction?
Name der PräsentationSeite 21 |
Beta-oxidation
ATP
Summary
• Acylcarnitines C5 and C4 are highly accurate CSF biomarkers
to distinguish between viral and autoimmune
neuroinflammation
Name der PräsentationSeite 22 |
Next Steps
• Validation in larger cohorts needed
• ?Virus-induced dysregulation of mitochondrial function ?
Name der PräsentationSeite 23 |
Acknowledgement
Name der PräsentationSeite 24 |
Core Unit Metabolomics
Volkhard Kaever
Annette Garbe
Clinic for Neurology
Martin Stangel
Kurt-Wolfram Sühs
& colleagues
MHH - Junge Akademie
Maike Kuhn
Frank Pessler
Frank Klawonn
Magdeburg, 27.09.2019
Thank you for your attention
1 of 25

Recommended

FISH IN MYELOMA by
 FISH IN MYELOMA FISH IN MYELOMA
FISH IN MYELOMAspa718
1.6K views31 slides
Evan Shegog Slide Presentation Sigma Xi Research Showcase 2014 by
Evan Shegog Slide Presentation Sigma Xi Research Showcase 2014 Evan Shegog Slide Presentation Sigma Xi Research Showcase 2014
Evan Shegog Slide Presentation Sigma Xi Research Showcase 2014 evanshegog
672 views23 slides
Dr. maryalice stetler stevenson lymphoma mrd by
Dr. maryalice stetler stevenson   lymphoma mrdDr. maryalice stetler stevenson   lymphoma mrd
Dr. maryalice stetler stevenson lymphoma mrdHitham Esam
469 views49 slides
Phenotypic identification of subclones in multiple myeloma with different gen... by
Phenotypic identification of subclones in multiple myeloma with different gen...Phenotypic identification of subclones in multiple myeloma with different gen...
Phenotypic identification of subclones in multiple myeloma with different gen...Affymetrix
907 views34 slides
Methyl flyer lo by
Methyl flyer loMethyl flyer lo
Methyl flyer loElsa von Licy
185 views2 slides

More Related Content

What's hot

A Sub-network of Signaling Protein Complexes in AA May Provide New Molecular ... by
A Sub-network of Signaling Protein Complexes in AA May Provide New Molecular ...A Sub-network of Signaling Protein Complexes in AA May Provide New Molecular ...
A Sub-network of Signaling Protein Complexes in AA May Provide New Molecular ...National Alopecia Areata Foundation
1.9K views9 slides
Addressing the growing demand for CNV and UPD detection by
Addressing the growing demand for CNV and UPD detection Addressing the growing demand for CNV and UPD detection
Addressing the growing demand for CNV and UPD detection Oxford Gene Technology
1K views28 slides
Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ... by
Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ...Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ...
Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ...Thermo Fisher Scientific
1.3K views1 slide
Measure Target Cancer Cell Death in Co-Cultures by
Measure Target Cancer Cell Death in Co-CulturesMeasure Target Cancer Cell Death in Co-Cultures
Measure Target Cancer Cell Death in Co-CulturesDiscoverX Corporation
622 views16 slides
The clinical application development and validation of cell free dna assays -... by
The clinical application development and validation of cell free dna assays -...The clinical application development and validation of cell free dna assays -...
The clinical application development and validation of cell free dna assays -...Candy Smellie
2K views24 slides
Oncomine Cancer Research Panel (OCP) | ESHG 2015 Poster PS12.131 by
Oncomine Cancer Research Panel (OCP) | ESHG 2015 Poster PS12.131Oncomine Cancer Research Panel (OCP) | ESHG 2015 Poster PS12.131
Oncomine Cancer Research Panel (OCP) | ESHG 2015 Poster PS12.131Thermo Fisher Scientific
4.2K views1 slide

What's hot(20)

Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ... by Thermo Fisher Scientific
Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ...Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ...
Direct Sanger CE Sequencing of Individual Ampliseq Cancer Panel Targets from ...
The clinical application development and validation of cell free dna assays -... by Candy Smellie
The clinical application development and validation of cell free dna assays -...The clinical application development and validation of cell free dna assays -...
The clinical application development and validation of cell free dna assays -...
Candy Smellie2K views
Primary Cell e Newsletter Issue 18 (jun 2016) Cell Applications by Daniel Schroen, PhD
Primary Cell e Newsletter Issue 18 (jun 2016) Cell ApplicationsPrimary Cell e Newsletter Issue 18 (jun 2016) Cell Applications
Primary Cell e Newsletter Issue 18 (jun 2016) Cell Applications
mRNA-based Therapeutics - Creative Biolabs by Creative-Biolabs
mRNA-based Therapeutics - Creative BiolabsmRNA-based Therapeutics - Creative Biolabs
mRNA-based Therapeutics - Creative Biolabs
Creative-Biolabs1.2K views
Recent Advances in Immune Monitoring Presentation Slides by Covance
Recent Advances in Immune Monitoring Presentation Slides Recent Advances in Immune Monitoring Presentation Slides
Recent Advances in Immune Monitoring Presentation Slides
Covance911 views
New Technology and Workflow for Integrated Collection, Stabilization and Puri... by QIAGEN
New Technology and Workflow for Integrated Collection, Stabilization and Puri...New Technology and Workflow for Integrated Collection, Stabilization and Puri...
New Technology and Workflow for Integrated Collection, Stabilization and Puri...
QIAGEN2.8K views
Monitoring of Minimal Residual Disease Principles and Applications by spa718
Monitoring of Minimal Residual Disease Principles and ApplicationsMonitoring of Minimal Residual Disease Principles and Applications
Monitoring of Minimal Residual Disease Principles and Applications
spa7183.3K views
BiPday 2014 -- Clima Rosanna by eventi-ITBbari
BiPday 2014 -- Clima RosannaBiPday 2014 -- Clima Rosanna
BiPday 2014 -- Clima Rosanna
eventi-ITBbari910 views
Next-Generation Sequencing Clinical Research Milestones Infographic by QIAGEN
Next-Generation Sequencing Clinical Research Milestones InfographicNext-Generation Sequencing Clinical Research Milestones Infographic
Next-Generation Sequencing Clinical Research Milestones Infographic
QIAGEN6.7K views
Rare Mutation Analysis Using Digital PCR on QuantStudio™ 3D to Verify Ion Amp... by Thermo Fisher Scientific
Rare Mutation Analysis Using Digital PCR on QuantStudio™ 3D to Verify Ion Amp...Rare Mutation Analysis Using Digital PCR on QuantStudio™ 3D to Verify Ion Amp...
Rare Mutation Analysis Using Digital PCR on QuantStudio™ 3D to Verify Ion Amp...

Similar to Cerebrospinal fluid metabolites as biomarkers to distinguish between viral and autoimmune encephalitis

Automated hematology analyzer as a cost effective aid to screen and monitor s... by
Automated hematology analyzer as a cost effective aid to screen and monitor s...Automated hematology analyzer as a cost effective aid to screen and monitor s...
Automated hematology analyzer as a cost effective aid to screen and monitor s...nisaiims
578 views32 slides
dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete... by
dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete...dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete...
dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete...dkNET
43 views48 slides
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio... by
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...Rafael Casiano
145 views1 slide
MS Genetics Presentation_Julia_Feb 2014Invesot by
MS Genetics Presentation_Julia_Feb 2014InvesotMS Genetics Presentation_Julia_Feb 2014Invesot
MS Genetics Presentation_Julia_Feb 2014InvesotDr. Julia Rothman
624 views25 slides
Metabolomics in the 21st century - perspective by
Metabolomics in the 21st century - perspectiveMetabolomics in the 21st century - perspective
Metabolomics in the 21st century - perspectiveDinesh Barupal
345 views60 slides

Similar to Cerebrospinal fluid metabolites as biomarkers to distinguish between viral and autoimmune encephalitis (20)

Automated hematology analyzer as a cost effective aid to screen and monitor s... by nisaiims
Automated hematology analyzer as a cost effective aid to screen and monitor s...Automated hematology analyzer as a cost effective aid to screen and monitor s...
Automated hematology analyzer as a cost effective aid to screen and monitor s...
nisaiims578 views
dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete... by dkNET
dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete...dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete...
dkNET Webinar: Leveraging Computational Strategies to Identify Type 1 Diabete...
dkNET43 views
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio... by Rafael Casiano
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...
A novel platform for in situ, multiomic, hyper-plexed analyses of systems bio...
Rafael Casiano145 views
MS Genetics Presentation_Julia_Feb 2014Invesot by Dr. Julia Rothman
MS Genetics Presentation_Julia_Feb 2014InvesotMS Genetics Presentation_Julia_Feb 2014Invesot
MS Genetics Presentation_Julia_Feb 2014Invesot
Dr. Julia Rothman624 views
Metabolomics in the 21st century - perspective by Dinesh Barupal
Metabolomics in the 21st century - perspectiveMetabolomics in the 21st century - perspective
Metabolomics in the 21st century - perspective
Dinesh Barupal345 views
Use of Affymetrix Arrays (GeneChip® Human Transcriptome 2.0 Array and Cytosca... by Affymetrix
Use of Affymetrix Arrays (GeneChip® Human Transcriptome 2.0 Array and Cytosca...Use of Affymetrix Arrays (GeneChip® Human Transcriptome 2.0 Array and Cytosca...
Use of Affymetrix Arrays (GeneChip® Human Transcriptome 2.0 Array and Cytosca...
Affymetrix2.5K views
Novel approach to diagnosis of mycobacterial and bacterial by NeurologyKota
Novel approach to diagnosis of mycobacterial and bacterialNovel approach to diagnosis of mycobacterial and bacterial
Novel approach to diagnosis of mycobacterial and bacterial
NeurologyKota353 views
Kshivets O. Lung Cancer Surgery by Oleg Kshivets
Kshivets O. Lung Cancer SurgeryKshivets O. Lung Cancer Surgery
Kshivets O. Lung Cancer Surgery
Oleg Kshivets1.1K views
Maldi tof-ms analysis in identification of prostate cancer by Moustafa Rezk
Maldi tof-ms analysis in identification of prostate cancerMaldi tof-ms analysis in identification of prostate cancer
Maldi tof-ms analysis in identification of prostate cancer
Moustafa Rezk66 views
Impact of Big Data & Artificial Intelligence in Drug Discovery & Development ... by Nick Brown
Impact of Big Data & Artificial Intelligence in Drug Discovery & Development ...Impact of Big Data & Artificial Intelligence in Drug Discovery & Development ...
Impact of Big Data & Artificial Intelligence in Drug Discovery & Development ...
Nick Brown39 views
Practical issues in MULTIPLE SCLEROSIS by Amr Hassan
Practical issues in MULTIPLE SCLEROSISPractical issues in MULTIPLE SCLEROSIS
Practical issues in MULTIPLE SCLEROSIS
Amr Hassan2.7K views
PPT Bonora "Clinica e terapia dell'HIV" by StopTb Italia
PPT Bonora "Clinica e terapia dell'HIV"PPT Bonora "Clinica e terapia dell'HIV"
PPT Bonora "Clinica e terapia dell'HIV"
StopTb Italia458 views
Kshivets O. Lung Cancer Surgery by Oleg Kshivets
Kshivets O. Lung Cancer SurgeryKshivets O. Lung Cancer Surgery
Kshivets O. Lung Cancer Surgery
Oleg Kshivets800 views
Affy by arnimat
AffyAffy
Affy
arnimat229 views
Affy by arnimat
AffyAffy
Affy
arnimat232 views
GLAGOV Information Session Slides.pptx by AdelSALLAM4
GLAGOV Information Session Slides.pptxGLAGOV Information Session Slides.pptx
GLAGOV Information Session Slides.pptx
AdelSALLAM437 views
Personalized & Translational Medicine - KineMed, Inc. - Marc Hellerstein, MD,... by KineMed, Inc.
Personalized & Translational Medicine - KineMed, Inc. - Marc Hellerstein, MD,...Personalized & Translational Medicine - KineMed, Inc. - Marc Hellerstein, MD,...
Personalized & Translational Medicine - KineMed, Inc. - Marc Hellerstein, MD,...
KineMed, Inc.1.2K views

More from LEGATO project

Scrooge Attack: Undervolting ARM Processors for Profit by
Scrooge Attack: Undervolting ARM Processors for ProfitScrooge Attack: Undervolting ARM Processors for Profit
Scrooge Attack: Undervolting ARM Processors for ProfitLEGATO project
75 views15 slides
A practical approach for updating an integrity-enforced operating system by
A practical approach for updating an integrity-enforced operating systemA practical approach for updating an integrity-enforced operating system
A practical approach for updating an integrity-enforced operating systemLEGATO project
90 views65 slides
TEEMon: A continuous performance monitoring framework for TEEs by
TEEMon: A continuous performance monitoring framework for TEEsTEEMon: A continuous performance monitoring framework for TEEs
TEEMon: A continuous performance monitoring framework for TEEsLEGATO project
57 views28 slides
secureTF: A Secure TensorFlow Framework by
secureTF: A Secure TensorFlow FrameworksecureTF: A Secure TensorFlow Framework
secureTF: A Secure TensorFlow FrameworkLEGATO project
94 views10 slides
PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep... by
PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep...PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep...
PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep...LEGATO project
37 views13 slides
LEGaTO: Machine Learning Use Case by
LEGaTO: Machine Learning Use CaseLEGaTO: Machine Learning Use Case
LEGaTO: Machine Learning Use CaseLEGATO project
131 views18 slides

More from LEGATO project(20)

Scrooge Attack: Undervolting ARM Processors for Profit by LEGATO project
Scrooge Attack: Undervolting ARM Processors for ProfitScrooge Attack: Undervolting ARM Processors for Profit
Scrooge Attack: Undervolting ARM Processors for Profit
LEGATO project75 views
A practical approach for updating an integrity-enforced operating system by LEGATO project
A practical approach for updating an integrity-enforced operating systemA practical approach for updating an integrity-enforced operating system
A practical approach for updating an integrity-enforced operating system
LEGATO project90 views
TEEMon: A continuous performance monitoring framework for TEEs by LEGATO project
TEEMon: A continuous performance monitoring framework for TEEsTEEMon: A continuous performance monitoring framework for TEEs
TEEMon: A continuous performance monitoring framework for TEEs
LEGATO project57 views
secureTF: A Secure TensorFlow Framework by LEGATO project
secureTF: A Secure TensorFlow FrameworksecureTF: A Secure TensorFlow Framework
secureTF: A Secure TensorFlow Framework
LEGATO project94 views
PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep... by LEGATO project
PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep...PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep...
PipeTune: Pipeline Parallelism of Hyper and System Parameters Tuning for Deep...
LEGATO project37 views
LEGaTO: Machine Learning Use Case by LEGATO project
LEGaTO: Machine Learning Use CaseLEGaTO: Machine Learning Use Case
LEGaTO: Machine Learning Use Case
LEGATO project131 views
LEGaTO: Low-Energy Heterogeneous Computing Use of AI in the project by LEGATO project
LEGaTO: Low-Energy Heterogeneous Computing Use of AI in the projectLEGaTO: Low-Energy Heterogeneous Computing Use of AI in the project
LEGaTO: Low-Energy Heterogeneous Computing Use of AI in the project
LEGATO project49 views
LEGaTO: Software Stack Programming Models by LEGATO project
LEGaTO: Software Stack Programming ModelsLEGaTO: Software Stack Programming Models
LEGaTO: Software Stack Programming Models
LEGATO project56 views
LEGaTO: Software Stack Runtimes by LEGATO project
LEGaTO: Software Stack RuntimesLEGaTO: Software Stack Runtimes
LEGaTO: Software Stack Runtimes
LEGATO project62 views
LEGaTO: Low-Energy Heterogeneous Computing Workshop by LEGATO project
LEGaTO: Low-Energy Heterogeneous Computing WorkshopLEGaTO: Low-Energy Heterogeneous Computing Workshop
LEGaTO: Low-Energy Heterogeneous Computing Workshop
LEGATO project50 views
TZ4Fabric: Executing Smart Contracts with ARM TrustZone by LEGATO project
TZ4Fabric: Executing Smart Contracts with ARM TrustZoneTZ4Fabric: Executing Smart Contracts with ARM TrustZone
TZ4Fabric: Executing Smart Contracts with ARM TrustZone
LEGATO project49 views
Infection Research with Maxeler Dataflow Computing by LEGATO project
Infection Research with Maxeler Dataflow ComputingInfection Research with Maxeler Dataflow Computing
Infection Research with Maxeler Dataflow Computing
LEGATO project149 views
FPGA Undervolting and Checkpointing for Energy-Efficiency and Error-Resiliency by LEGATO project
FPGA Undervolting and Checkpointing for Energy-Efficiency and Error-ResiliencyFPGA Undervolting and Checkpointing for Energy-Efficiency and Error-Resiliency
FPGA Undervolting and Checkpointing for Energy-Efficiency and Error-Resiliency
LEGATO project57 views
Device Data Directory and Asynchronous execution: A path to heterogeneous com... by LEGATO project
Device Data Directory and Asynchronous execution: A path to heterogeneous com...Device Data Directory and Asynchronous execution: A path to heterogeneous com...
Device Data Directory and Asynchronous execution: A path to heterogeneous com...
LEGATO project46 views
Scheduling Task-parallel Applications in Dynamically Asymmetric Environments by LEGATO project
Scheduling Task-parallel Applications in Dynamically Asymmetric EnvironmentsScheduling Task-parallel Applications in Dynamically Asymmetric Environments
Scheduling Task-parallel Applications in Dynamically Asymmetric Environments
LEGATO project38 views

Recently uploaded

Experimental animal Guinea pigs.pptx by
Experimental animal Guinea pigs.pptxExperimental animal Guinea pigs.pptx
Experimental animal Guinea pigs.pptxMansee Arya
38 views16 slides
ALGAL PRODUCTS.pptx by
ALGAL PRODUCTS.pptxALGAL PRODUCTS.pptx
ALGAL PRODUCTS.pptxRASHMI M G
6 views17 slides
별헤는 사람들 2023년 12월호 전명원 교수 자료 by
별헤는 사람들 2023년 12월호 전명원 교수 자료별헤는 사람들 2023년 12월호 전명원 교수 자료
별헤는 사람들 2023년 12월호 전명원 교수 자료sciencepeople
63 views30 slides
DEVELOPMENT OF FROG.pptx by
DEVELOPMENT OF FROG.pptxDEVELOPMENT OF FROG.pptx
DEVELOPMENT OF FROG.pptxsushant292556
11 views21 slides
BLOTTING TECHNIQUES SPECIAL by
BLOTTING TECHNIQUES SPECIALBLOTTING TECHNIQUES SPECIAL
BLOTTING TECHNIQUES SPECIALMuhammadImranMirza2
7 views56 slides
MILK LIPIDS 2.pptx by
MILK LIPIDS 2.pptxMILK LIPIDS 2.pptx
MILK LIPIDS 2.pptxabhinambroze18
9 views15 slides

Recently uploaded(20)

Experimental animal Guinea pigs.pptx by Mansee Arya
Experimental animal Guinea pigs.pptxExperimental animal Guinea pigs.pptx
Experimental animal Guinea pigs.pptx
Mansee Arya38 views
별헤는 사람들 2023년 12월호 전명원 교수 자료 by sciencepeople
별헤는 사람들 2023년 12월호 전명원 교수 자료별헤는 사람들 2023년 12월호 전명원 교수 자료
별헤는 사람들 2023년 12월호 전명원 교수 자료
sciencepeople63 views
Evaluation and Standardization of the Marketed Polyherbal drug Patanjali Divy... by Anmol Vishnu Gupta
Evaluation and Standardization of the Marketed Polyherbal drug Patanjali Divy...Evaluation and Standardization of the Marketed Polyherbal drug Patanjali Divy...
Evaluation and Standardization of the Marketed Polyherbal drug Patanjali Divy...
Effect of Integrated Nutrient Management on Growth and Yield of Solanaceous F... by SwagatBehera9
Effect of Integrated Nutrient Management on Growth and Yield of Solanaceous F...Effect of Integrated Nutrient Management on Growth and Yield of Solanaceous F...
Effect of Integrated Nutrient Management on Growth and Yield of Solanaceous F...
SwagatBehera95 views
Small ruminant keepers’ knowledge, attitudes and practices towards peste des ... by ILRI
Small ruminant keepers’ knowledge, attitudes and practices towards peste des ...Small ruminant keepers’ knowledge, attitudes and practices towards peste des ...
Small ruminant keepers’ knowledge, attitudes and practices towards peste des ...
ILRI8 views
A giant thin stellar stream in the Coma Galaxy Cluster by Sérgio Sacani
A giant thin stellar stream in the Coma Galaxy ClusterA giant thin stellar stream in the Coma Galaxy Cluster
A giant thin stellar stream in the Coma Galaxy Cluster
Sérgio Sacani18 views
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe... by Anmol Vishnu Gupta
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...
Study on Drug Drug Interaction Through Prescription Analysis of Type II Diabe...
Open Access Publishing in Astrophysics by Peter Coles
Open Access Publishing in AstrophysicsOpen Access Publishing in Astrophysics
Open Access Publishing in Astrophysics
Peter Coles1.2K views
Factors affecting fluorescence and phosphorescence.pptx by SamarthGiri1
Factors affecting fluorescence and phosphorescence.pptxFactors affecting fluorescence and phosphorescence.pptx
Factors affecting fluorescence and phosphorescence.pptx
SamarthGiri17 views
ELECTRON TRANSPORT CHAIN by DEEKSHA RANI
ELECTRON TRANSPORT CHAINELECTRON TRANSPORT CHAIN
ELECTRON TRANSPORT CHAIN
DEEKSHA RANI10 views

Cerebrospinal fluid metabolites as biomarkers to distinguish between viral and autoimmune encephalitis

  • 1. Amani Al-Mekhlafi PhD student Magdeburg, 27.09.2019 Cerebrospinal fluid metabolites as biomarkers to distinguish between viral and autoimmune encephalitis MHH: Martin Stangel, Kurt-Wolfram Sühs (Dept. of Neurology), Volkhard Kaever (Emeritus, Research Core Unit Metabolomics) TWINCORE: Maike Kuhn, Frank Pessler HZI: Frank Klawonn
  • 2. AGENDA • Introduction • Aims • Study Cohort • Results • Next step
  • 3. Page 3 | Viral vs. autoimmune CNS disorders . Viral meningitis/encephalitisAutoimmune neuroinflammation CMV HSV Enteroviruses Anti-NMDA-r encephalitis Multiple Sclerosis
  • 4. Clinical challenge: similar presentation – different treatments Name der PräsentationSeite 4 | Altered mental status, focal neurological deficits, seizures Mild neuroinflammation Mild-to-moderate disruption of blood-CSF-barrier Non-specific changes on imaging (MRI) Antivirals (if available for pathogen) Immunosuppression Plasmapheresis B cell depletion Viral Autoimmune Pathogen detection (PCR, etc.) Autoantibody detection
  • 5. CSF Analysis Seite 5 | Deisenhammer et al. Routine cerebrospinal fluid (CSF) analysis ,2011
  • 6. Aims • To identify candidate biomarkers that can accurately differentiate between viral and autoimmune encephalitis and could potentially be developed into a rapid (bedside) diagnostic • Comparison with standard diagnostic parameters (CSF leukocytes, etc.) Name der PräsentationSeite 6 |
  • 7. Study Cohort Six patient groups Name der PräsentationSeite 7 | Total n= 79
  • 8. Biomaterial: cerebrospinal fluid (CSF) Name der PräsentationSeite 8 | 1-2 h Storage Sample collection Centrifugation Clinical diagnostics Cells Supernatant
  • 9. Targeted metabolomic profiling Biocrates AbsoluteIDQ® p180 Kit Name der PräsentationSeite 9 | • Mass spectrometry-based assay for biological tissues and fluids, including CSF • 96-well format www.biocrates.com, www.sciex.com API4000 Triple-Quadrupol-MS (RCU Metabolomics, MHH) Maike Kuhn
  • 10. Detectable metabolites Name der PräsentationSeite 10 | Jones et al., Progress in Lipid Research 2010, Commons.wikimedia.org, vinmetrica.com, eichler.mgh.harvard.edu Total n= 188
  • 13. HAUCA Curve Indicates how much the correlation between the biomarker and the disease exceed the pure random effect. Name der PräsentationSeite 13 | 108 15 13
  • 14. Standard parameter analysis MS NMDA Ent. men HSV Z.men_enc Chi-square P vlaue Kruskal-Wallis test P value Demographic Age (Year) Mean(sd) 38(11.6) 38(20.5) 41(19.4) 58(16.4) 53(21) 0.04 Median(range) 33(23-58) 30(19-69) 33(22-76) 56(29-76) 55(13-80) Gender male 53% 13% 60% 78% 60% 0.14 female 47% 87% 40% 22% 40% Blood Parameter Leukocytes count 1000/µl Mean(sd) 7.9(3.7) 6.3(2.7) 7.5(3.0) 8.5(4) 7.8(3.3) 0.84 Median(range) 6.5(2.8-18.2) 6.4(2.1-9.7) 7.3(4-14) 10.1(1.8-12.8) 6.9(3.8-13.6) C-reactive Protien mg/l Mean(sd) 3.2(5.4) 13.01(12.9) 9.3(12.3) 22.1(37.3) 13.6(32.3) 0.14 Median(range) 1(1-23) 11.2(1-37) 4(1-39) 3(1-102) 2 (1-128) CSF Parameter Leukocytes count 1/µl Mean(sd) 10.6(11.6) 49.6(61.04) 129.1(235.3) 187.5(233.4) 199.8(400.2) 0.002 Median(range) 7.7(.7-48) 22.4(1.7-172) 9.2(.7-619) 90.7(16-723) 38(1.7-1536) Qalb Mean(sd) 6.3(1.8) 17.2(15.01) 9.5(5) 26.8(13.5) 14.9(9.9) 1.78e-05 Median(range) 6.2(2.5-9.6) 8.7(6.2-41.1) 8.9(2.7-21.7) 31.8(6.8-44.4) 11.4(4.5-41.1) Blood-CSF-barrier disruption no disruption(1) 53% 75% 20% 11% 20% 0.0005 Light(2) 47% 25% 70% 11% 40% Moderate(3) 0% 0% 10% 11% 27% Sever(4) 0% 0% 0% 67% 13% Protein_concentration g/l Mean(sd) .48(0.11) .45(0.2) .57(.21) 1.3(.62) 0.82(.49) 0.0005 Median(range) .49(0.31-0.66) .42(0.2-0.9) .52(.24-.98) 1.2(.52-2.3) 0.65(0.31-2.05) Lactate mmol/L Mean(sd) 1.8(0.42) 2.1(0.4) 2.1(.62) 2.5(.54) 2.8(1.1) 0.003 Median(range) 1.6(1.3-2.4) 2.2(1.4-2.6) 1.9(1.6-3.6) 2.3(1.8-3.4) 2.6(1.5-5.5) Q_IgG Mean(sd) 6.3(3.7) 8.2(5.2) 5.2(3.3) 23.4(16.7) 9.1(5.2) 0.004 Median(range) 4.8(1.6-13.2) 7.95(1.6-14.9) 5(1.3-13.6) 19.6(4.5-58.4) 8.5(3.2-21.1) IgG_Index Mean(sd) 1.03(.64) 1.1(0.71) .53(.05) .82(.24) 0.63(.17) 0.0002 Median(range) 0.79 (.55-.2.9) 0.71(0.5-2.4) .53(.47-.63) .76(.5-1.3) 0.57(0.5-1.2) Name der PräsentationSeite 14 | Qalb MS NMDA Ent.men HSV Z.men_enc Kruskal-Wallis test Mean 6.3 17.2 9.5 26.8 14.9 1.78e-5 Median 6.2 8.7 8.9 31.8 11.4
  • 15. First look at biomarker potential – a shimmer of hope Name der PräsentationSeite 15 | Autoimmune Viral Metabolites Lipids Amino acids Standard parameters
  • 16. Changes in CSF lipids contribute the most to differences Name der PräsentationSeite 16 | Metabolites Standard parameters
  • 17. CSF metabolites are more accurate biomarkers than standard diagnostic CSF parameters for the distinction between viral and autoimmune neuroinflammation Name der PräsentationSeite 17 | Standard CSF Parameter AUC Metabolites AUC Selection frequency Q-albumin 0.86*** C5 0.93*** 1 Leukocyte count 0.74** PC.aa.C30.0 0.92*** 1 Protein concentration 0.78*** PC.ae.C32.2 0.92*** 1 IgG-index 0.76*** C4 0.92*** 1 Lactate 0.74** SM.C16.0 0.91*** 1 BCB dysfunction 0.79*** PC.aa.C38.0 0.90*** 1 AUC0.5 1.0 Receiver operating characteristic (ROC) curve analysis perfect biomarkerworthless
  • 18. Highest CSF concentrations of C5 and C4 in herpes virus infection Name der PräsentationSeite 18 | C5 & C4 C5 C4
  • 19. Name der PräsentationSeite 19 | Comparison Q-albumin C5 C4 HSV vs. autoimmune 0.94*** 0.98*** 0.99*** VZV vs. autoimmune 0.89*** 0.95*** 0.92*** Enterovirus vs. autoimmune 0.76*** 0.92*** 0.92*** C5 and C4 are the most accurate biomarkers for CNS infection by all three viral pathogens
  • 20. Sensitivity, specificity and predictive values Sensitivity Specificity PPV NPV C5 0.879 0.845 0.807 0.904 C4 0.752 0.785 0.720 0.812 Q-albumine 0.483 0.637 0.502 0.619 Name der PräsentationSeite 20 |
  • 21. Virus-induced mitochondrial dysfunction? Name der PräsentationSeite 21 | Beta-oxidation ATP
  • 22. Summary • Acylcarnitines C5 and C4 are highly accurate CSF biomarkers to distinguish between viral and autoimmune neuroinflammation Name der PräsentationSeite 22 |
  • 23. Next Steps • Validation in larger cohorts needed • ?Virus-induced dysregulation of mitochondrial function ? Name der PräsentationSeite 23 |
  • 24. Acknowledgement Name der PräsentationSeite 24 | Core Unit Metabolomics Volkhard Kaever Annette Garbe Clinic for Neurology Martin Stangel Kurt-Wolfram Sühs & colleagues MHH - Junge Akademie Maike Kuhn Frank Pessler Frank Klawonn
  • 25. Magdeburg, 27.09.2019 Thank you for your attention