scholarly journals Time Trends of Cerebrospinal Fluid Biomarkers of Neurodegeneration in Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Vol 80 (4) ◽  
pp. 1629-1642
Author(s):  
Heikki Lukkarinen ◽  
Ina Tesseur ◽  
Darrel Pemberton ◽  
Peter Van Der Ark ◽  
Maarten Timmers ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Apoe Genotype ◽  
Brain Biopsy ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Shunt ◽  
Csf Biomarkers ◽  
Post Surgery ◽  
T Tau

Background: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. Objective: To examine alteration of CSF biomarkers reflecting Alzheimer’s disease (AD)-related amyloid-β (Aβ) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. Methods: L-CSF was collected prior to shunt placement and, together with V-CSF, 3–73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed Aβ plaques in frontal cortical brain biopsy and 13 iNPH patients without Aβ pathology. CSF Amyloid-β42 (Aβ42), total tau (T-tau), phosphorylated tau (P-tau181), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. Results: All biomarkers but Aβ42 increased notably by 140–810% in L-CSF after CSF diversion and then stabilized. Aβ42 instead showed divergent longitudinal decrease between Aβ-positive and -negative patients in L-CSF, and thereafter increase in Aβ-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (Aβ42 R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (Aβ42 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only Aβ42 showed higher concentration in non-carriers of allele ɛ4. Conclusion: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy Aβ pathology, while NFL normalized toward its pre-shunt levels. Aβ42 as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V- than L-CSF yet showing strong correlations.

scholarly journals Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients with Suspected Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Author(s):  
Rongrong Hua ◽  
Chunyan Liu ◽  
Xing Liu ◽  
Jinwu Zhu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Predictive Value ◽  
Test Group ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Binary Logistic Regression Analysis ◽  
Csf Biomarkers ◽  
Tap Test ◽  
T Tau

Abstract Background: The value of cerebrospinal fluid (CSF) biomarkers for idiopathic normal pressure hydrocephalus (iNPH) needs to be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH, and its predictive value for tap test responsiveness.Methods: Thirty-nine suspected iNPH patients were recruited, contributed qualified CSF, and accepted a tap test and unified pre- and post-test evaluation of neurological function. Results: The analysis of biomarkers from their CSF showed a decrease of tau and its phosphorylated form, especially in the tap test (+) group. In addition, the responsiveness of the tap test was also related to the number of combined symptoms (p<0.01). A correlation was also found between the end pressure or pressure difference of CSF and tap test responsiveness (p<0.05). The results of binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e ^ - (-5.505+55.314 * ratio of p/T-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505+0.553* percentage of p/T-tau - 1.586 * numbers of combined symptoms) gave the highest sensitivity and specificity, which were 94.12% and 72.73%, respectively.Conclusions: It may be accessed in judgment of tap test responsiveness, which is beneficial for the feasibility of clinical application.

scholarly journals Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Author(s):  
Rongrong Hua ◽  
Chunyan Liu ◽  
Xing Liu ◽  
Jinwu Zhu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Predictive Value ◽  
Test Group ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Binary Logistic Regression Analysis ◽  
Csf Biomarkers ◽  
Tap Test ◽  
T Tau

Abstract Background The value of cerebrospinal fluid (CSF) biomarkers for idiopathic normal pressure hydrocephalus (iNPH) needs to be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH, and its predictive value for tap test responsiveness.Case presentation Thirty-nine suspected iNPH patients were recruited, contributed qualified CSF, and accepted a tap test and unified pre- and post-test evaluation of neurological function. The analysis of biomarkers from their CSF showed a decrease of tau and its phosphorylated form, especially in the tap test (+) group. In addition, the responsiveness of the tap test was also related to the number of combined symptoms (p<0.01). A correlation was also found between the end pressure or pressure difference of CSF and tap test responsiveness (p<0.05). The results of binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e ^ - (-5.505+55.314 * ratio of p/T-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505+0.553* percentage of p/T-tau - 1.586 * numbers of combined symptoms) gave the highest sensitivity and specificity, which were 94.12% and 72.73%, respectively. Conclusions The combined indicators calculated from p/T-tau and the numbers of combined symptoms may be accessed in judgment of tap test responsiveness, which is beneficial for the feasibility of clinical application.

scholarly journals Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Ville Leinonen ◽  
Lata G. Menon ◽  
Rona S. Carroll ◽  
Donna Dello Iacono ◽  
Jeremy Grevet ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Biomarkers ◽  
Cerebrospinal Fluid Biomarkers ◽  
In The Beginning ◽  
Related Proteins ◽  
Selection Of Patients ◽  
Selection Of

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, Aβ42, NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-αconcentration was low in iNPH patients.

scholarly journals Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Vol 13 ◽  
Author(s):  
Rongrong Hua ◽  
Chunyan Liu ◽  
Xing Liu ◽  
Jinwu Zhu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Predictive Value ◽  
Clinical Symptoms ◽  
Test Group ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Binary Logistic Regression Analysis ◽  
Csf Biomarkers ◽  
Tap Test

Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness.Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function.Results: The analysis of biomarkers from the patients’ CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p &lt; 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p &lt; 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ − (−5.505 + 55.314 * ratio of p/T-tau − 1.586 * numbers of combined symptoms). The combined indicators (−5.505 + 0.553 * percentage of p/T-tau − 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively.Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.

scholarly journals CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

2019 ◽  
Vol 90 (10) ◽  
pp. 1117-1123 ◽  
Author(s):  
Anna Jeppsson ◽  
Carsten Wikkelsö ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Radu Constantinescu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Normal Pressure Hydrocephalus ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Prediction Algorithm ◽  
Csf Biomarkers ◽  
T Tau

ObjectiveTo examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer’s disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders.MethodsThe study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson’s disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer’s disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1).ResultsPatients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers.ConclusionsThe combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.

scholarly journals Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review

2017 ◽  
Vol 45 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Tyler Pfanner ◽  
Alexandre Henri-Bhargava ◽  
Stephanie Borchert
Keyword(s):  
Systematic Review ◽  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Future Research ◽  
Csf Biomarkers ◽  
Level Of Evidence ◽  
Shunt Procedure ◽  
Shunt Response

ABSTRACTBackground: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. Methods: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. Results: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. Conclusions: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-β2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-β1, TBR-II, homocysteine, and interleukins (particularly IL-1β, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aβ42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

scholarly journals Elevated CSF LRG and Decreased Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Vol 10 (5) ◽  
pp. 1105
Author(s):  
Aleksi Vanninen ◽  
Madoka Nakajima ◽  
Masakazu Miyajima ◽  
Tuomas Rauramaa ◽  
Merja Kokki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Normal Pressure Hydrocephalus ◽  
Brain Biopsy ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Potential Biomarker ◽  
Shunt Response ◽  
T Tau ◽  
The Brain

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer’s disease (AD) pathology among the iNPH patients. CSF LRG, Aβ1-42, P-tau181, and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p < 0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., Aβ1-42, T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls (<0.001). Our findings support that the LRG levels in the CSF are potentially useful for the diagnostics of iNPH, independent of the brain AD pathology, but contrary to previous findings, not for predicting the shunt response. Our findings also suggest a need for specific reference values of the CSF AD biomarkers for the diagnostics of comorbid AD pathology in the iNPH patients.

scholarly journals Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e91974 ◽  
Author(s):  
Okko T. Pyykkö ◽  
Miikka Lumela ◽  
Jaana Rummukainen ◽  
Ossi Nerg ◽  
Toni T. Seppälä ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Brain Biopsy ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Fluid Biomarker

scholarly journals Lumboperitoneal Shunts for the Treatment of Idiopathic Normal Pressure Hydrocephalus: A Comparison of Small-Lumen Abdominal Catheters to Gravitational Add-On Valves in a Single Center

2018 ◽  
Vol 15 (6) ◽  
pp. 634-642 ◽  
Author(s):  
Madoka Nakajima ◽  
Masakazu Miyajima ◽  
Chihiro Akiba ◽  
Ikuko Ogino ◽  
Kaito Kawamura ◽  
...  
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Normal Pressure ◽  
Standing Position ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Shunt ◽  
Csf Biomarkers ◽  
Grading Scale ◽  
Event Rates ◽  
State Examination ◽  
Lps Treatment

Abstract BACKGROUND Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage. OBJECTIVE To investigate whether LPSs, including gravitational “add-on” and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes. METHODS We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated. RESULTS Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group. CONCLUSION This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.

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