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 Clinical predictors of shunt response in the diagnosis and treatment of idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Santhosh G. Thavarajasingam ◽  
Mahmoud El-Khatib ◽  
Mark Rea ◽  
Salvatore Russo ◽  
Johannes Lemcke ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Test ◽  
Normal Pressure Hydrocephalus ◽  
Meta Analysis ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Future Research ◽  
Clinical Predictors ◽  
Timed Up And Go ◽  
Shunt Response

Abstract Background Positive shunt response (SR) remains the gold standard for diagnosing idiopathic normal pressure hydrocephalus (iNPH). However, multiple pathologies mimic iNPH symptoms, making it difficult to select patients who will respond to shunt surgery. Although presenting features, extended lumbar drainage (ELD), infusion test (IT), intracranial pressure monitoring (ICPM), and tap test (TT) have been used to predict SR, uncertainty remains over which diagnostic test to choose. Objective To conduct a systematic review and meta-analysis to identify clinical predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most effective diagnostic tests. Methods Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating clinical predictors of SR in iNPH patients. Included studies were assessed using the QUADAS-2 tool, and eligible studies were evaluated using univariate and bivariate meta-analyses. Results Thirty-five studies were included. Nine studies discussed the diagnostic use of presenting clinical features, 8 studies ELD, 8 studies IT, 11 studies ICPM, and 6 studies TT. A meta-analysis of 21 eligible studies was conducted for TT, ELD, IT, and ICPM. ICPM yielded the highest diagnostic effectiveness, with diagnostic odds ratio (DOR) = 50.9 and area under curve (AUC) = 0.836. ELD yielded DOR = 27.70 and AUC = 0.753, IT had DOR = 5.70 and AUC = 0.729, and TT scored DOR = 3.86 and AUC = 0.711. Conclusion Intraparenchymal ICPM is statistically the most effective diagnostic test, followed by ELD, IT, and lastly TT. Due to the higher accessibility of TT and IT, they are recommended to be used first line, using a timed-up-and-go improvement ≥ 5.6 s or a Rout cut-off range between 13 and 16 mmHg, respectively. Patients who test negative should ideally be followed up with ICPM, using mean ICP wave amplitude $$\ge$$ ≥ 4 mmHg, or 1- to 4-day ELD with an MMSE cut-off improvement $$\ge$$ ≥ 3. Future research must use standardized methodologies for each diagnostic test and uniform criteria for SR to allow better comparison.

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 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 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.

Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus

2018 ◽  
Vol 130 (1) ◽  
pp. 121-129 ◽  
Author(s):  
Sami Abu Hamdeh ◽  
Johan Virhammar ◽  
Dag Sehlin ◽  
Irina Alafuzoff ◽  
Kristina Giuliana Cesarini ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Normal Pressure Hydrocephalus ◽  
Surgical Outcome ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Biomarkers ◽  
Vp Shunt ◽  
Tissue Levels ◽  
Shunt Procedure ◽  
Shunt Treatment

OBJECTIVEThe authors conducted a study to test if the cortical brain tissue levels of soluble amyloid beta (Aβ) reflect the propensity of cortical Aβ aggregate formation and may be an additional factor predicting surgical outcome following idiopathic normal pressure hydrocephalus (iNPH) treatment.METHODSHighly selective ELISAs (enzyme-linked immunosorbent assays) were used to quantify soluble Aβ40, Aβ42, and neurotoxic Aβ oligomers/protofibrils, associated with Aβ aggregation, in cortical biopsy samples obtained in patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt surgery. Patients underwent pre- and postoperative (3-month) clinical assessment with a modified iNPH scale. The preoperative CSF biomarkers and the levels of soluble and insoluble Aβ species in cortical biopsy samples were analyzed for their association with a favorable outcome following the VP shunt procedure, defined as a ≥ 5-point increase in the iNPH scale.RESULTSThe brain tissue levels of Aβ42 were negatively correlated with CSF Aβ42 (Spearman’s r = −0.53, p < 0.05). The Aβ40, Aβ42, and Aβ oligomer/protofibril levels in cortical biopsy samples were higher in patients with insoluble cortical Aβ aggregates (p < 0.05). The preoperative CSF Aβ42 levels were similar in patients responding (n = 11) and not responding (n = 9) to VP shunt treatment at 3 months postsurgery. In contrast, the presence of cortical Aβ aggregates and high brain tissue Aβ42 levels were associated with a poor outcome following VP shunt treatment (p < 0.05).CONCLUSIONSBrain tissue measurements of soluble Aβ species are feasible. Since high Aβ42 levels in cortical biopsy samples obtained in patients with iNPH indicated a poor surgical outcome, tissue levels of Aβ species may be associated with the clinical response to shunt treatment.

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.

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