P-Tau as prognostic marker in long term follow up for patients with shunted iNPH

Migliorati, Karol; Panciani, Pier Paolo; Pertichetti, Marta; Borroni, Barbara; Archetti, Silvana; Rozzini, Luca; Padovani, Alessandro; Terzi, Lodovico; Bruscella, Sara; Fontanella, Marco Maria

doi:10.1080/01616412.2020.1831300

Cited by 11 publications

(50 citation statements)

References 29 publications

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“…Of these, three studies reported that T-Tau was a prognostic biomarker that displayed a significant difference between shunt-responsive and non-responsive patients when comparing the pre-operative lumbar levels of T-Tau. Craven et al (2017) [15] and Migliorati et al (2020) [51] Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart outlining the study selection process demonstrated that this significant difference was in lumbar CSF levels of T-Tau (p = 0.04 and p = 0.02, respectively), whereas Tarnaris et al (2011) [70] demonstrated a significant difference in ventricular CSF levels of T-Tau.…”

Section: Total-taumentioning

confidence: 99%

“…Abu Hamdeh et al (2018) [1], Ågren-Wilsson et al (2007) [4], Hong et al (2018) [33], Tullberg et al (2008) [73], and Vanninen et al (2021) [74] found no differences in the levels of T-Tau in lumbar CSF between shunt responders and shunt non-responders, and Craven et al (2017) [15] found no differences in the levels of ventricular T-Tau between shunt-responsive and shunt-non-responsive patients. However, Migliorati et al (2020) [51] performed a univariate logistic regression showing that lumbar CSF levels of T-Tau were significantly associated with the worse clinical outcomes following shunt surgery if lumbar CSF T-Tau levels exceeding 731.7 ng/l (p = 0.024). The best cut-off identified by ROC analysis was at the level of 233.9 ng/L, with a sensitivity of 81.8% and a specificity of 72.4% for predicting shunt response.…”

Section: Total-taumentioning

confidence: 99%

“…In the study by Migliorati et al (2021) [51], two patients experienced infection at the catheter site and therefore had the shunt removed. In that study, of the total study population, 24 patients were lost to follow-up [51]. Three patients died within 1 year of shunt surgery [33,51].…”

Section: Complicationsmentioning

confidence: 99%

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Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis

et al. 2022

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Background Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease and dementia subtype involving disturbed cerebrospinal fluid (CSF) homeostasis. Patients with iNPH may improve clinically following CSF diversion through shunt surgery, but it remains a challenge to predict which patients respond to shunting. It has been proposed that CSF and blood biomarkers may be used to predict shunt response in iNPH. Objective To conduct a systematic review and meta-analysis to identify which CSF and venous biomarkers predict shunt-responsive iNPH most accurately. Methods Original studies that investigate the use of CSF and venous biomarkers to predict shunt response were searched using the following databases: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR. Included studies were assessed using the ROBINS-I tool, and eligible studies were evaluated utilising univariate meta-analyses. Results The study included 13 studies; seven addressed lumbar CSF levels of amyloid-β 1–42, nine studies CSF levels of Total-Tau, six studies CSF levels of Phosphorylated-Tau, and seven studies miscellaneous biomarkers, proteomics, and genotyping. A meta-analysis of six eligible studies conducted for amyloid-β 1–42, Total-Tau, and Phosphorylated-Tau demonstrated significantly increased lumbar CSF Phosphorylated-Tau (− 0.55 SMD, p = 0.04) and Total-Tau (− 0.50 SMD, p = 0.02) in shunt-non-responsive iNPH, though no differences were seen between shunt responders and non-responders for amyloid-β 1–42 (− 0.26 SMD, p = 0.55) or the other included biomarkers. Conclusion This meta-analysis found that lumbar CSF levels of Phosphorylated-Tau and Total-Tau are significantly increased in shunt non-responsive iNPH compared to shunt-responsive iNPH. The other biomarkers, including amyloid-β 1–42, did not significantly differentiate shunt-responsive from shunt-non-responsive iNPH. More studies on the Tau proteins examining sensitivity and specificity at different cut-off levels are needed for a robust analysis of the diagnostic efficiency of the Tau proteins.

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Section: Total-taumentioning

confidence: 99%

Section: Total-taumentioning

confidence: 99%

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Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis

et al. 2022

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“…Biomechanically, the impact of altered brain structure and neurodegeneration due to underlying comorbidities may also significantly predispose patients to developing NPH early in life, perhaps conceptually related to the high comorbidity of Alzheimer’s Disease-like pathology which has been appreciated in adult (but not pediatric) NPH [ 36 , 37 , 38 , 39 , 40 ]. While the overlap between childhood conditions resulting in cerebral malformation or neurodegeneration is not nearly as well studied as that between Alzheimer’s Disease and adult NPH, which may co-occur in up to 75% of some subsets of NPH patients [ 40 ], we did find anecdotal evidence of this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Reappraisal of Pediatric Normal-Pressure Hydrocephalus

Leary

Svokos

Klinge

2021

JCM

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While normal-pressure hydrocephalus (NPH) is most commonly diagnosed in older adulthood, a significant body of literature has accumulated over half a century documenting the clinical phenomenon of an NPH-like syndrome in pediatric patients. As in adult NPH, it is likely that pediatric NPH occurs due to a heterogeneous array of developmental, structural, and neurodegenerative pathologies, ultimately resulting in aberrant cerebrospinal fluid (CSF) flow and distribution within and around the brain. In this review, we aimed to systematically survey the existing clinical evidence supporting the existence of a pediatric form of NPH, dating back to the original recognition of NPH as a clinically significant subtype of communicating hydrocephalus. Leveraging emergent trends from the old and more recent published literature, we then present a modern characterization of pediatric NPH as a disorder firmly within the same disease spectrum as adult NPH, likely with overlapping etiology and pathophysiological mechanisms. Exemplary cases consistent with the diagnosis of pediatric NPH selected from the senior author’s neurosurgical practice are then presented alongside the systematic review to aid in discussion of the typical clinical and radiographic manifestations of pediatric NPH. Common co-morbidities and modern surgical treatment options are also described.

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“…Another recent study looked at a composite of several AD markers in 50 iNPH shunt recipients, and reported that both tTau and pTau181 could predict patients' outcomes after shunt surgery. 35 Nevertheless, their criteria for improvement in any gait parameter were low, at 5% in any gait measure and 1 point on the Mini Mental Status Examination.…”

Section: Selection Of Patients For Shunt Surgerymentioning

confidence: 95%

CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus

et al. 2022

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Objective:The assessment of biomarkers in selecting idiopathic normal pressure hydrocephalus (iNPH) patients for shunt surgery has been limited to small cohort studies and those with limited follow-up. We assessed the potential for cerebrospinal fluid (CSF) biomarkers in predicting immediate response to CSF tap test (TT) and long-term response after shunt surgery.Methods:CSF was obtained from iNPH patients referred for CSF TT after baseline assessment of cognition and gait. CSF neurofilament-light (NFL), β-amyloid-42 (Aβ1-42), β-amyloid-40 (Aβ1-40), total tau (t-Tau), and phosphorylated-tau-181(pTau181) and leucine-rich-alpha-2-glycoprotein1 (LRG1) were measured by ELISA. The ability of these measures to predict immediate improvement following CSF TT and long-term improvement following shunt surgery was compared by univariate and adjusted multivariate regression.Results:Lower NFL, pTau181, tTau and Aβ1-40 were individually predictive of long-term improvement in gait outcomes after shunt surgery. A multivariate model of these biomarkers and MRI Evan's index, adjusted for age, improved prediction (AUC-ROC: 0.76, (95% CI [0.66, 0.86]). tTau, pTau181 and Aβ1-40 levels were statistically different in those whose gait improved after CSF TT compared to those who did not. Using a multivariate model, combining these markers with Evan's index and transependymal flow did not significantly improve prediction of an immediate response to CSF TT.Conclusion:A combination of CSF biomarkers can predict improvement following shunt surgery for iNPH. However, these measures only modestly discriminate responders from non-responders following CSF TT. The findings further suggest that abnormal CSF biomarkers in non-responders may represent comorbid neurodegenerative pathology or a pre-degenerative phase that presents with an iNPH phenotype.

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P-Tau as prognostic marker in long term follow up for patients with shunted iNPH

Cited by 11 publications

References 29 publications

Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis

Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis

Reappraisal of Pediatric Normal-Pressure Hydrocephalus

CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus

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