Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus

Schirinzi, Tommaso; Sancesario, Giulia Maria; Lazzaro, Giulia Di; D'Elia, Alessio; Imbriani, Paola; Scalise, Simona; Pisani, Antonio

doi:10.1007/s00702-018-1842-z

Cited by 32 publications

(25 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The pathophysiological profile in iNPH opens up for the possibility of using CSF biomarkers as a tool for diagnosing iNPH in a mixed clinical setting, as proposed in Schirinzi et al 40. For that purpose, we constructed a prediction plot that can complement clinical and radiological examination.…”

Section: Discussionmentioning

confidence: 99%

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Jeppsson

Wikkelsø

Blennow

et al. 2019

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Jeppsson

Wikkelsø

Blennow

et al. 2019

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

show abstract

“…According to Kazui and colleagues, attenuation of cognitive impairment is a major factor contributing to the caregiver analysis through Zarit burden interviews [ 36, 37 ]. The diagnosis of iNPH remains challenging, especially at early stages, when presenting symptoms that largely overlap with those of other neurodegenerative diseases [ 38 ]. In particular, cognitive function is affected most strongly by AD comorbidity, leading to a poor response to shunting intervention [ 25, 39 ].…”

Section: Discussionmentioning

confidence: 99%

Preoperative Phosphorylated Tau Concentration in the Cerebrospinal Fluid Can Predict Cognitive Function Three Years after Shunt Surgery in Patients with Idiopathic Normal Pressure Hydrocephalus

Nakajima

Miyajima

Ogino

et al. 2018

JAD

View full text Add to dashboard Cite

Background: Idiopathic normal pressure hydrocephalus (iNPH) is commonly treated by cerebrospinal fluid (CSF) shunting. However, the long-term efficacy of shunt intervention in the presence of comorbid Alzheimer’s disease (AD) pathology is debated.Objective: To identify AD-associated CSF biomarkers predictive of shunting surgery outcomes in patients with iNPH.Methods: Preoperative levels of total and phosphorylated Tau (p-Tau) were measured in 40 patients with iNPH divided into low (<30 pg/mL) and high (≥30 pg/mL) p-Tau groups and followed up for three years after lumboperitoneal shunting. The modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Frontal Assessment Battery, and iNPH Grading Scale scores were compared between the age-adjusted low (n = 24; mean age 75.7 years [SD 5.3]) and high (n = 11; mean age 76.0 years [SD 5.6]) p-Tau groups.Results: Cognitive function improved early in the low p-Tau group and was maintained thereafter (p = 0.005). In contrast, the high p-Tau group showed a gradual decline to baseline levels by the third postoperative year (p = 0.040). Although the p-Tau concentration did not correlate with the preoperative MMSE score, a negative correlation appeared and strengthened during follow-up (R2 = 0.352, p < 0.001). Furthermore, the low p-Tau group showed rapid and sustained mRS grade improvement, whereas mRS performance gradually declined in the high p-Tau group.Conclusions: Preoperative CSF p-Tau concentration predicted some aspects of cognitive function after shunt intervention in patients with iNPH. The therapeutic effects of shunt treatment were shorter-lasting in patients with coexisting AD pathology.

show abstract

“…Neurofilament light chain (NFL) is a protein that functions to maintain axonal architecture. Myelin basic protein (MBP) is a vital structural protein of myelin 107,108 . NFL and MBP are commonly used to assess axonal and myelin integrity, respectively.…”

Section: White Matter Injury In Inphmentioning

confidence: 99%

Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus

Wang

Zhang

et al. 2020

CNS Neurosci Ther

View full text Add to dashboard Cite

First defined in 1965, idiopathic normal pressure hydrocephalus (iNPH)is a surgically reversible neurological disorder in adults. It is characterized by dementia, gait disturbance, and urinary incontinence (known as Hakim's triad). 1,2 INPH is not a rare clinical entity. The prevalence of iNPH has been estimated to be 10 per 100 000 to 22 per 100 000 overall, with 1.30% in those aged ≥65 years and 5.9% in those aged ≥80 years. 3,4 One of the core features of iNPH is that the cerebrospinal fluid (CSF) pressure of an iNPH patient is within normal ranges. 2 Typical brain imaging of iNPH displays ventriculomegaly, periventricular hyperintensities, wide Sylvian fissures, narrowed subarachnoid space, and cortical sulci at the high convexity. 5 In contrast to the secondary normal pressure hydrocephalus with known etiology, the exact cause of iNPH is unknown. 6 Its specific pathogenesis also remains elusive, although several

show abstract

Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus

Cited by 32 publications

References 65 publications

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Preoperative Phosphorylated Tau Concentration in the Cerebrospinal Fluid Can Predict Cognitive Function Three Years after Shunt Surgery in Patients with Idiopathic Normal Pressure Hydrocephalus

Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus

Contact Info

Product

Resources

About