Idiopathic normal-pressure hydrocephalus

Jeppsson, Anna; Zetterberg, Henrik; Blennow, Kaj; Wikkelsø, Carsten

doi:10.1212/wnl.0b013e31828c2fda

Cited by 146 publications

(134 citation statements)

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“…A total of 413 patients with iNPH, 186 patients with AD, and 147 healthy controls were included in this meta-analysis. 2 studies were performed in the United States [21, 22], 2 in Japan [23, 24], 2 in Sweden [12, 25], 1 in Greece [13], 1 in Finland [26], 1 in South Korea [27] and 1 in Italy [28]. These studies were published between 2007 and 2015.…”

Section: Resultsmentioning

confidence: 99%

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

Chen

Liu

Zhang

et al. 2017

Fluids Barriers CNS

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ObjectivesThe purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls.MethodsStudies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016. The standardized mean difference (SMD) and 95% confidence interval (CI), comparing CSF Aβ42, t-tau, and p-tau levels between iNPH, AD and healthy controls, were calculated using random-effects models. Subgroup analyses were created according to ethnicity (Caucasian or Asian) and CSF type (lumbar or ventricular), and the publication bias was estimated using Egger’s test and the Begg’s test.ResultsA total of 10 studies including 413 patients with iNPH, 186 patients with AD and 147 healthy controls were included in this systematic review and meta-analysis. The concentrations of CSF t-tau, and p-tau were significantly lower in iNPH patients compared to AD (SMD = −1.26, 95% CI −1.95 to −0.57, P = 0.0004; SMD = −1.54, 95% CI −2.34 to −0.74, P = 0.0002, respectively) and lower than healthy controls (SMD = −0.80, 95% CI −1.50 to −0.09, P = 0.03; SMD = −1.12, 95% CI −1.38 to −0.86, P < 0.00001, respectively). Patients with iNPH had significantly lower Aβ42 levels compared with controls (SMD = −1.14, 95% CI −1.74 to −0.55, P = 0.0002), and slightly higher Aβ42 levels compared with AD patients (SMD = 0.32, 95% CI 0.00–0.63, P = 0.05). Subgroup analyses showed that the outcomes may have been influenced by ethnicity and CSF source. Compared to AD, overall sensitivity in differentiating iNPH was 0.813 (95% CI 0.636–0.928) for Aβ42, 0.828 (95% CI 0.732–0.900) for t-tau, 0.943 (95% CI 0.871–0.981) for p-tau. Relative to AD, overall specificity in differentiating iNPH was 0.506 (95% CI 0.393–0.619) for Aβ42, 0.842 (95% CI 0.756–0.907) for t-tau, 0.851 (95% CI 0.767–0.914) for p-tau.ConclusionThe results of our meta-analysis suggest that iNPH may be associated with significantly reduced levels of CSF Aβ42, t-tau and p-tau compared to the healthy normal state. Compared to AD, both t-tau and p-tau were significantly decreased in iNPH, but CSF Aβ42 was slightly increased. Prospective studies are needed to further assess the clinical utility of these and other CSF biomarkers in assisting in the diagnosis of iNPH and differentiating it from AD and other neurodegenerative disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12987-017-0062-5) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

Chen

Liu

Zhang

et al. 2017

Fluids Barriers CNS

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“…26 In PCS due to rcTBI, we instead observed a general downregulation of all 3 isoforms, similar to what has been reported in multiple sclerosis and normal pressure hydrocephalus. 27,28 Thus, the results per se do not indicate cerebral Ab deposition, but rather a more generalized alteration in the Ab metabolism. The CSF Ab42/Ab40 ratio was reduced in the PCS group, but the ratio was still above the cutoff for amyloid positivity we use in clinical laboratory practice (0.09) for most of the athletes with PCS.…”

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confidence: 85%

Astroglial activation and altered amyloid metabolism in human repetitive concussion

et al. 2017

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Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment.Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (Ab38, Ab40, Ab42, sAPPa, and sAPPb), and BBB function (CSF:serum albumin ratio).Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS .1 year. Athletes with PCS .1 year had higher RPQ scores and number of concussions than athletes with PCS ,1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS .1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of Ab40 and Ab42 than controls. The CSF:serum albumin ratio was unaltered.Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and b-amyloid (Ab) dysmetabolism in the brain. There was no clear evidence of Ab deposition as Ab40 and Ab42 were reduced in parallel. The CSF:serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS. Neurology ® 2017;88:1400-1407 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; APP 5 amyloid precursor protein; BBB 5 blood-brain barrier; cTBI 5 concussive traumatic brain injury; CTE 5 chronic traumatic encephalopathy; DSM-IV 5 Diagnostic and Statistical Manual of Mental Disorders, 4th edition; GFAP 5 glial fibrillary acidic protein; LP 5 lumbar puncture; NFL 5 neurofilament light; PCS 5 postconcussion syndrome; rcTBI 5 repetitive concussive traumatic brain injury; RPQ 5 Rivermead Post-Concussion Symptoms Questionnaire; sAPPa 5 a-cleaved soluble amyloid precursor protein; sAPPb 5 b-cleaved soluble amyloid precursor protein; TBI 5 traumatic brain injury.Concussion is a type of mild traumatic brain injury (TBI) (concussive TBI [cTBI]) caused by rapid rotational acceleration of the head, which causes the brain to deform, resulting in tissue damage, particularly to vulnerable white matter axons.1 While most individuals with cTBI recover completely within days to weeks, about 10%-15% of individuals display persistent neurobehavioral symptoms for more than 3 months, a condition referred to as postconcussion syndrome (PCS).2 A proportion of individuals exposed to repetitive concussive TBI (rcTBI) may develop a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy (CTE).3,4 CTE is characterized by tau and, less consistently...

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“…These mixed CSF findings are very common in unselected patients undergoing evaluation because of suspected neurodegenerative disease [150]. NFL is also a useful biomarker for damage severity in several other conditions characterized by white matter lesions and injury to subcortical brain regions such as idiopathic normal pressure hydrocephalus [151], ALS [152], various CNS infections [88], and stroke [153].…”

Section: Biomarkers For Subcortical Axonal Degenerationmentioning

confidence: 99%

CSF in Alzheimer's Disease

Zetterberg

Lautner

Skillbäck

et al. 2014

Advances in Clinical Chemistry

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Idiopathic normal-pressure hydrocephalus

Abstract: We interpret our data as iNPH pathophysiology to be characterized by a reduced periventricular metabolism and axonal degeneration but no major cortical damage.

Cited by 146 publications

References 39 publications

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

Cerebrospinal fluid Aβ42, t-tau, and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis

Astroglial activation and altered amyloid metabolism in human repetitive concussion

CSF in Alzheimer's Disease

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