CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Jeppsson, Anna; Wikkelsø, Carsten; Blennow, Kaj; Zetterberg, Henrik; Constantinescu, Radu; Remes, Anne M.; Herukka, Sanna‐Kaisa; Rauramaa, Tuomas; Nägga, Katarina; Leinonen, Ville; Tullberg, Mats

doi:10.1136/jnnp-2019-320826

Cited by 67 publications

(71 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the lower NFL levels in our patients with iNPH may have been due to a lower Fazekas score. Two other studies reported equal levels of NFL in patients with iNPH and large vessel vascular dementia (VaD) [37,38].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease

Manniche

Simonsen

Hasselbalch

et al. 2020

JAD

Self Cite

View full text Add to dashboard Cite

Background Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail. Objective To determine if novel CSF biomarkers neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40) and the core Alzheimer's disease (AD) biomarkers amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau) can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes. Methods Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays. Results Lower levels of NFL, NG, Aβ42, and t-tau (p = 0.0037) were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and Aβ42 were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with Aβ42, t-tau, and p-tau resulted 4 in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined. Conclusion An addition of NFL to the CSF panel of Aβ42, t-tau, and p-tau may improve the differentiation of iNPH from SIVD.

show abstract

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease

Manniche

Simonsen

Hasselbalch

et al. 2020

JAD

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is unknown whether this subarachnoid fibrosis also contributes to the development of iNPH. Other inflammation modulators, such as monocyte chemoattractant protein‐1 (MCP‐1) and IL‐6, were also changed in the CSF after iNPH 66‐69,74,75 (Table 1). The exact roles of each inflammatory factor and their interactions in the pathogenesis and pathophysiology of iNPH await further elucidation.…”

Section: Hypoperfusion Leads To Neurophysiological Changes 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

“…We showed that CSF ATP levels were higher in patients with ALS with advanced muscle weakness and were inversely correlated with the MRC sum score. In this report, we assayed CSF samples from patients with iNPH as a control, because in patients with iNPH, the levels of CSF neuro lament light chain (NfL), known as a marker of neuronal damage, was not signi cantly different from those in healthy control [32].…”

Section: Discussionmentioning

confidence: 99%

Increased Cerebrospinal Fluid Adenosine 5'-triphosphate in Patients with Amyotrophic Lateral Sclerosis

Nukui

Matsui

Niimi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Extracellular adenosine 5'-triphosphate (ATP) has been suggested to cause neuroinflammation and motor neuron degeneration by activating microglia and astrocytes in amyotrophic lateral sclerosis (ALS). Since we have developed a highly sensitive ATP assay system, we examined CSF ATP levels in patients with ALS whether it can be a useful biomarker in ALS. Methods: Forty-eight CSF samples from 45 patients with ALS were assayed for ATP with a newly established, highly sensitive assay system using luciferase luminous reaction. CSF samples from patients with idiopathic normal pressure hydrocephalus (iNPH) were assayed as a control. Patients were divided into two groups depending on their disease severity, as evaluated using the Medical Research Council (MRC) sum score. Correlations between the CSF ATP levels and other factors, including clinical data and serum creatinine levels, were evaluated. Results: ALSFRS-R (37.9 ± 5.7 vs. 42.4 ± 2.8, p<0.01) and serum creatinine levels (0.51 ± 0.13 vs. 0.68 ± 0.23 mg/dL, p < 0.05) were significantly lower in the severe group than in the mild group respectively. CSF ATP levels were significantly higher in the more severe group than in the iNPH group (6860 ± 8312 vs. 716 ± 411 pmol/L, p < 0.05) and mild group (6860 ± 8312 vs. 2676 ± 3959 pmol/L, p < 0.05) respectively. A negative correlation of CSF ATP levels with MRC sum score was demonstrated in the correlation analysis (r = -0.3862, p < 0.01). Conclusions: Extracellular ATP is particularly increased in the CSF of patients with advanced ALS. CSF ATP levels may be a useful biomarker for evaluating disease severity in patients with ALS.

show abstract

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Cited by 67 publications

References 43 publications

Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease

Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease

Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus

Increased Cerebrospinal Fluid Adenosine 5'-triphosphate in Patients with Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About