Retrospective Evaluation of Various Serological Assays and Multiple Parameters for Optimal Diagnosis of Lyme Neuroborreliosis in a Routine Clinical Setting

Gorkom, Tamara van; Voet, W.; Arkel, Gijs H J van; Heron, Michiel; Hoeve-Bakker, B. J. A.; Notermans, Daan W.; Thijsen, Steven; Kremer, Kristin

doi:10.1128/spectrum.00061-22

Cited by 7 publications

(8 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we demonstrate that the molecular composition of ventricular CSF differs from that of the lumbar compartment. A range of common neuropathologies, e.g., Alzheimer's disease [7][8][9], multiple sclerosis [10], neuroborreliosis [11][12][13], and Creutzfeldt Jakob's disease [14][15][16] relies on diagnostic CSF analysis during the clinical work-up. For this purpose, CSF is sampled from the lumbar region, for ethical reasons and technical ease, rather than from the ventricular compartment, in which the CSF is in direct contact with the brain tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, CSF analysis is commonly used as a surrogate measure for pathological conditions in the brain, and proteins detected in the CSF are used as biomarkers of disease both as a screening tool and as a supplementary information to diagnostic investigations [1][2][3][4][5][6]. CSF used for diagnostic workup is routinely accessed through lumbar puncture, which is performed widely on several clinical indications, e.g., Alzheimer's disease [7][8][9], multiple sclerosis [10], neuroborreliosis [11][12][13], and Creutzfeldt-Jakob's disease [14][15][16]. Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations, rather than from the ventricular compartment, which is envisaged to re ect the brain pathology more correctly.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Rostgaard

Olsen

Ottenheijm

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Pathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue. Methods: CSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-β (Aβ40, Aβ42), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullar cistern closely related to the ventricles. Results: In total 1,231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer’s disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, Aβ40, Aβ42) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF. Conclusions: For a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF. However, the overall proteomic profile differs between these compartments, and so does the distribution of clinically employed biomarkers. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Rostgaard

Olsen

Ottenheijm

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Here, we demonstrate that the molecular composition of ventricular CSF differs from that of the lumbar compartment in iNPH patients. A range of common neuropathologies, e.g., Alzheimer’s disease [ 7 – 9 ], multiple sclerosis [ 10 ], neuroborreliosis [ 11 – 13 ], and Creutzfeldt Jakob’s disease [ 14 – 16 ] relies on diagnostic CSF analysis during the clinical work-up. For this purpose, CSF is sampled from the lumbar region, for ethical reasons and technical ease, rather than from the ventricular compartment, in which the CSF is in direct contact with the brain tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, CSF analysis is commonly used as a surrogate measure for pathological conditions in the brain, and proteins detected in the CSF are used as biomarkers of disease both as a screening tool and as a supplementary information to diagnostic investigations [ 1 – 6 ]. CSF used for diagnostic workup is routinely accessed through lumbar puncture, which is performed widely on several clinical indications, e.g., Alzheimer’s disease [ 7 – 9 ], multiple sclerosis [ 10 ], neuroborreliosis [ 11 – 13 ], and Creutzfeldt-Jakob’s disease [ 14 – 16 ]. Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations, rather than from the ventricular compartment, which is envisaged to reflect the brain pathology more correctly.…”

Section: Introductionmentioning

confidence: 99%

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Rostgaard

Olsen

Ottenheijm

et al. 2023

Fluids Barriers CNS

View full text Add to dashboard Cite

Background Pathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue. Methods CSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-β (Aβ40, Aβ42), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles. Results In total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer’s disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, Aβ40, Aβ42) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF. Conclusions The overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.

show abstract

“…Diagnosis of borreliosis, and in our case of neuroborreliosis, can be difficult and is clearly underestimated. Laboratory diagnosis of LNB is challenging and a diagnostic algorithm is lacking [ 11 ]. Serological testing is an initial screening test (ELISA or CLIA) based on antibodies against BB: anti-Borrelia IgM (positive after 2 weeks) and anti-Borrelia IgG (positive after 6 weeks), which has good sensitivity but lower specificity, resulting in false positives.…”

Section: Discussionmentioning

confidence: 99%

Case report: Successive ipsilateral and contralateral laryngeal nerve palsy as probable manifestation of neuroborreliosis

Finck,

Gambron,

Benchimol

et al. 2023

Heliyon

View full text Add to dashboard Cite

Retrospective Evaluation of Various Serological Assays and Multiple Parameters for Optimal Diagnosis of Lyme Neuroborreliosis in a Routine Clinical Setting

Abstract: The diagnosis of LNB is established by clinical symptoms, pleocytosis, and proof of intrathecal synthesis of Borrelia -specific antibodies. Laboratory diagnosis of LNB is challenging, and validated diagnostic algorithms are lacking.

Cited by 7 publications

References 65 publications

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Case report: Successive ipsilateral and contralateral laryngeal nerve palsy as probable manifestation of neuroborreliosis

Contact Info

Product

Resources

About