Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology

ABSTRACTBackground: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. Methods: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. Results: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. Conclusions: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-β2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-β1, TBR-II, homocysteine, and interleukins (particularly IL-1β, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aβ42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

Download Full-text

Comment: Invasive tests for predicting shunt response in idiopathic normal pressure hydrocephalus—the risk aspect

Acta Neurochirurgica ◽

10.1007/s00701-021-05049-x ◽

2021 ◽

Author(s):

Santhosh G. Thavarajasingam ◽

Mahmoud El-Khatib ◽

Mark Rea

Keyword(s):

Normal Pressure Hydrocephalus ◽

Normal Pressure ◽

Idiopathic Normal Pressure Hydrocephalus ◽

Shunt Response

Download Full-text

High-Convexity Tightness Predicts the Shunt Response in Idiopathic Normal Pressure Hydrocephalus

American Journal of Neuroradiology ◽

10.3174/ajnr.a4838 ◽

2016 ◽

Vol 37 (10) ◽

pp. 1831-1837 ◽

Cited By ~ 23

Author(s):

W. Narita ◽

Y. Nishio ◽

T. Baba ◽

O. Iizuka ◽

T. Ishihara ◽

...

Keyword(s):

Normal Pressure Hydrocephalus ◽

Normal Pressure ◽

Idiopathic Normal Pressure Hydrocephalus ◽

Shunt Response

Download Full-text

Prevalence of C9ORF72 Expansion in a Large Series of Patients with Idiopathic Normal-Pressure Hydrocephalus

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000497306 ◽

2019 ◽

Vol 47 (1-2) ◽

pp. 91-103 ◽

Cited By ~ 1

Author(s):

Ville E. Korhonen ◽

Anne M. Remes ◽

Seppo Helisalmi ◽

Tuomas Rauramaa ◽

Anna Sutela ◽

...

Keyword(s):

Normal Pressure Hydrocephalus ◽

Psychiatric Symptoms ◽

Age At Onset ◽

Normal Pressure ◽

Idiopathic Normal Pressure Hydrocephalus ◽

Study Cohort ◽

C9orf72 Expansion ◽

Personality Changes ◽

Clinically Significant ◽

Shunt Response

Background/Aims: The C9ORF72 expansion is known to cause frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We aim to identify the prevalence of the C9ORF72 expansion in idiopathic normal pressure hydrocephalus (iNPH). Methods: We analysed the C9ORF72 expansion in a large cohort of patients with possible iNPH (n = 487) and cognitively intact elderly controls (n = 432; age > 65 years). Results: While the C9ORF72 expansion was detected in 1.6% (n = 8/487) of cases with possible iNPH, no control subject was found to carry the mutation. The mean age at onset of symptoms of C9ORF72 expansion carriers was 59 years (range: 52–67 years), 11 years less than non-carriers (p = 0.0002). The most frequent initial/main symptom pertained to gait difficulties. Despite identified mutation, only 3 of the patients fulfilled the criteria for the FTLD-ALS spectrum. Clinically significant shunt response was detected in 6 out of 7 shunted C9ORF72 expansion carriers. Conclusion: This is the first study cohort identifying the underlying C9ORF72 expansion in patients with iNPH providing evidence for the potential comorbidity between iNPH and the FTLD-ALS spectrum. Analysis of the C9ORF72 expansion should be considered for patients with probable iNPH presenting with frontal atrophy and personality changes or other severe psychiatric symptoms.

Download Full-text

Elevated CSF LRG and Decreased Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus

Journal of Clinical Medicine ◽

10.3390/jcm10051105 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1105

Author(s):

Aleksi Vanninen ◽

Madoka Nakajima ◽

Masakazu Miyajima ◽

Tuomas Rauramaa ◽

Merja Kokki ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Normal Pressure Hydrocephalus ◽

Brain Biopsy ◽

Normal Pressure ◽

Idiopathic Normal Pressure Hydrocephalus ◽

Potential Biomarker ◽

Shunt Response ◽

T Tau ◽

The Brain

Leucine-rich-alpha-2-glykoprotein (LRG) is suggested as a potential biomarker for idiopathic normal pressure hydrocephalus (iNPH). Our goal was to compare the cerebrospinal fluid (CSF) LRG levels between 119 iNPH patients and 33 age-matched controls and with the shunt responses and the brain biopsy Alzheimer’s disease (AD) pathology among the iNPH patients. CSF LRG, Aβ1-42, P-tau181, and T-tau were measured by using commercial ELISAs. The LRG levels in the CSF were significantly increased in the iNPH patients (p < 0.001) as compared to the controls, regardless of the AD pathology. However, CSF LRG did not correlate with the shunt response in contrast to the previous findings. The CSF AD biomarkers, i.e., Aβ1-42, T-tau, and P-tau correlated with the brain biopsy AD pathology as expected but were systematically lower in the iNPH patients when compared to the controls (<0.001). Our findings support that the LRG levels in the CSF are potentially useful for the diagnostics of iNPH, independent of the brain AD pathology, but contrary to previous findings, not for predicting the shunt response. Our findings also suggest a need for specific reference values of the CSF AD biomarkers for the diagnostics of comorbid AD pathology in the iNPH patients.

Download Full-text