Use of cerebrospinal fluid amyloid-β and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocephalus

2011 ◽  
Vol 115 (1) ◽  
pp. 145-150 ◽  
Author(s):  
Andrew Tarnaris ◽  
Ahmed. K. Toma ◽  
Miles D. Chapman ◽  
Geoff Keir ◽  
Neil D. Kitchen ◽  
...  
Keyword(s):  
Normal Pressure Hydrocephalus ◽  
Tau Protein ◽  
Surgical Outcomes ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Favorable Outcome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Total Tau

Object The prognostic value of CSF biomarkers in patients with idiopathic normal pressure hydrocephalus (iNPH) has not been adequately studied to date. The aim of this study was to identify CSF markers of favorable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt. Methods Ventricular CSF was collected intraoperatively from 22 patients with iNPH and enzyme-linked immunosorbent assay was used to analyze the levels of amyloid-β 1–42 (Aβ1–42) and total tau protein. The Black grading scale was used to assess outcomes at 6 months. Receiver operating characteristic (ROC) curves were obtained and discriminant function analysis was undertaken to provide sensitivity and specificity figures for each marker as well as their combination. Results The mean age of the patients was 71.45 years (± 9.5 years [SD]). Follow-up was achieved in 21 patients. Seventeen patients had a favorable outcome and 4 patients had unfavorable outcome at 6 months. An Aβ1–42 level of 180 pg/ml had a sensitivity of 35% and a specificity of 20% for predicting a favorable outcome at 6 months. A total tau level of 767 pg/ml will have a sensitivity of 17% and a specificity of 20% for predicting a favorable outcome at 6 months. A combination of Aβ1–42 and total tau levels predicted favorable outcomes with a sensitivity of 80% and specificity of 82.4%. Conclusions In this pilot study a combination of Aβ1–42 levels and total tau protein levels predicted favorable surgical outcomes at 6 months with adequate accuracy to be of clinical use. Further study in a larger group with longer follow-up is warranted.

scholarly journals Predictors of favorable response to implanted of ventriculoperitoneal shunt in patients with idiopathic normal pressure hydrocephalus

2020 ◽  
Vol 1 (1) ◽  
pp. 81-86
Author(s):  
Mario Emiliano Ricciardi ◽  
Ismael Calandri ◽  
Lucas Alessandro ◽  
Mauricio Farez ◽  
Juan Villalonga ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Retrospective Study ◽  
Normal Pressure Hydrocephalus ◽  
Ventriculoperitoneal Shunt ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Response To Treatment ◽  
Clinical Factors ◽  
A Prospective Study

Introduction: The indication of a ventriculoperitoneal shunt (VPS) is discussed in patients with idiopathic normal pressure hydrocephalus (iNPH), due to the heterogeneity of the response to treatment and the risks involved in neurosurgery. Objective: To search for clinical factors and complementary studies in order to determine predictors of a favorable response to the VPS placement in patients with iNPH. Methodology: A retrospective study of patients with probable iNPH (according to international guidelines) treated with VPS assisted in a neurological clinic from January 2014 to January 2017 was conducted. A univariate statisticalanalysis of the variables considered as possible prognostic factors was performed. Results: 58 patients were included. Women presented 3.68 times more chances of improvement after the VPS (p=0.019). Good response to the gait test was associated with better response to the VPS (p=0.024). Conclusions: Female sex and good response to the gait test could be considered as predictors of a favorable response to the VPS placement in patients with iNPH. A prospective study is necessary to achieve a homogeneous diagnostic evaluation and a more extensive longitudinal follow-up to evaluate the clinical evolution in this group of patients.

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 Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus

2019 ◽  
Vol 40 (9) ◽  
pp. 1849-1858 ◽  
Author(s):  
Per Kristian Eide ◽  
Lars Magnus Valnes ◽  
Are Hugo Pripp ◽  
Kent-Andre Mardal ◽  
Geir Ringstad
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Choroid Plexus ◽  
Normal Pressure Hydrocephalus ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Resonance Imaging ◽  
Lateral Ventricles

Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6–9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.

scholarly journals Pathological mitochondria in neurons and perivascular astrocytic endfeet of idiopathic normal pressure hydrocephalus patients

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Md Mahdi Hasan-Olive ◽  
Rune Enger ◽  
Hans-Arne Hansson ◽  
Erlend A. Nagelhus ◽  
Per Kristian Eide
Keyword(s):  
Endoplasmic Reticulum ◽  
Normal Pressure Hydrocephalus ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Synaptic Activity ◽  
Autophagic Vacuoles ◽  
Contact Sites ◽  
Neuronal Soma ◽  
Mitochondrial Pathology

Abstract Background A growing body of evidence suggests that the accumulation of amyloid-β and tau (HPτ) in the brain of patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) is associated with delayed extravascular clearance of metabolic waste. Whether also clearance of intracellular debris is affected in these patients needs to be examined. Hypothetically, defective extra- and intra-cellular clearance of metabolites may be instrumental in the neurodegeneration and dementia characterizing iNPH. This study explores whether iNPH is associated with altered mitochondria phenotype in neurons and astrocytes. Methods Cortical brain biopsies of 9 reference (REF) individuals and 30 iNPH patients were analyzed for subcellular distribution and morphology of mitochondria using transmission electron microscopy. In neuronal soma of REF and iNPH patients, we identified normal, pathological and clustered mitochondria, mitochondria-endoplasmic reticulum contact sites and autophagic vacuoles. We also differentiated normal and pathological mitochondria in pre- and post-synaptic nerve terminals, as well as in astrocytic endfoot processes towards vessels. Results We found a high prevalence of pathological mitochondria in neuronal soma and pre- and post-synaptic terminals, as well as increased mitochondrial clustering, and altered number of mitochondria-endoplasmic reticulum contact sites in iNPH. Non-fused autophagic vacuoles were more abundant in neuronal soma of iNPH patients, suggestive of cellular clearance failure. Moreover, the length of postsynaptic densities was reduced in iNPH, potentially related to reduced synaptic activity. In astrocytic endfoot processes, we also found increased number, area and area fraction of pathological mitochondria in iNPH patients. The proportion of pathological mitochondria correlated significantly with increasing degree of astrogliosis and reduced perivascular expression of aquaporin-4 (AQP4), assessed by light microscopy immunohistochemistry. Conclusion Our results provide evidence of mitochondrial pathology and signs of impaired cellular clearance in iNPH patients. The results indicate that iNPH is a neurodegenerative disease with close similarity to Alzheimer’s disease.

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