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Research Article
Giacomo Stroffolini
University of Turin
Corresponding Author
License:
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Background
Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasing number of evidences show a possible role for infective agents in developing neurodegenerative diseases.
Methods
We retrospectively included 13 HIV-negative patients presenting with meningeal tuberculosis. Lumbar punctures were performed for clinical reasons and CSF biomarkers were routinely available: we analyzed blood brain barrier permeability (CSF to serum albumin ratio, “CSAR”), intrathecal IgG synthesis, (CSF to serum IgG ratio), inflammation (neopterin), amyloid deposition (Aβ1-42), neuronal damage (T-tau, P-tau, 14.3.3) and astrocytosis (S-100 β).
Results
Patients were 83% male and 67 % Caucasian with a median age of 51 years (24.5-63.5 IQR). Apart from altered CSAR (median value 18.4, 17.1-30.9 IQR), neopterin (14.3 ng/ml, 9.7-18.8) and IgG ratios (15.4, 7.9-24.9), patients showed very low levels of Aβ1-42 in their CSF (348.5 pg/mL,125-532.2). Protein 14.3.3. tested altered in 38.5% cases. T-tau, ptau and S100Beta were in the range of normality. Altered low level of Aβ1-42 correlated over time with classical TBm findings and altered neuromarkers.
Conclusions
CSF Biomarkers from patients with TBM were compatible with inflammation, blood brain barrier damage and impairment in amyloid-beta metabolism. Amyloid-beta could be tested as a prognostic markers, backing the routine use of available neuromarkers. To our knowledge this is the first case showing such low levels of Aβ1-42 in TBM; its accumulation, drove by neuroinflammation related to infections, can be central in understanding neurodegenerative diseases.
Keywords
tuberculosis, meningitis, Alzheimer’s disease, amyloid-beta, neuromarkers, dementia
Figure 1
Figure 2
Figure 3
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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Subject Areas
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This preprint is under consideration at BMC Neurology. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Giacomo Stroffolini
University of Turin
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 17 Mar, 2021
No community comments so far
Reviewers invited
Invitations sent on 16 Mar, 2021
Editor assigned
On 16 Mar, 2021
Editor invited
On 15 Mar, 2021
Submission checks complete
On 14 Mar, 2021
First submitted
On 03 Mar, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Tuberculous meningitis (TBM) is an important disease leading to morbidity, disability and mortality that primarily affects children and immune-depressed patients. Specific neuromarkers predicting outcomes, severity and inflammatory response are still lacking. In recent years an increasing number of evidences show a possible role for infective agents in developing neurodegenerative diseases.
Methods
We retrospectively included 13 HIV-negative patients presenting with meningeal tuberculosis. Lumbar punctures were performed for clinical reasons and CSF biomarkers were routinely available: we analyzed blood brain barrier permeability (CSF to serum albumin ratio, “CSAR”), intrathecal IgG synthesis, (CSF to serum IgG ratio), inflammation (neopterin), amyloid deposition (Aβ1-42), neuronal damage (T-tau, P-tau, 14.3.3) and astrocytosis (S-100 β).
Results
Patients were 83% male and 67 % Caucasian with a median age of 51 years (24.5-63.5 IQR). Apart from altered CSAR (median value 18.4, 17.1-30.9 IQR), neopterin (14.3 ng/ml, 9.7-18.8) and IgG ratios (15.4, 7.9-24.9), patients showed very low levels of Aβ1-42 in their CSF (348.5 pg/mL,125-532.2). Protein 14.3.3. tested altered in 38.5% cases. T-tau, ptau and S100Beta were in the range of normality. Altered low level of Aβ1-42 correlated over time with classical TBm findings and altered neuromarkers.
Conclusions
CSF Biomarkers from patients with TBM were compatible with inflammation, blood brain barrier damage and impairment in amyloid-beta metabolism. Amyloid-beta could be tested as a prognostic markers, backing the routine use of available neuromarkers. To our knowledge this is the first case showing such low levels of Aβ1-42 in TBM; its accumulation, drove by neuroinflammation related to infections, can be central in understanding neurodegenerative diseases.
Figure 1
Figure 2
Figure 3
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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