Idiopathic normal pressure hydrocephalus cerebrospinal fluid biomarkers [Neurosurgery Wiki]

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====== Idiopathic normal pressure hydrocephalus cerebrospinal fluid biomarkers ======

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The available studies suggest that there is [[evidence]] for the utility of [[cerebrospinal fluid biomarker]]s in predicting shunt responsiveness in Idiopathic normal pressure hydrocephalus 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
((Pfanner T, Henri-Bhargava A, Borchert S. Cerebrospinal Fluid Biomarkers as Predictors of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review. Can J Neurol Sci. 2018 Jan;45(1):3-10. doi: 10.1017/cjn.2017.251. Epub 2017 Nov 10. PMID: 29125088.)).
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The [[osmolality]] of lumbar [[CSF]] is a reliable reflection of the ventricular [[Cerebrospinal fluid osmolality]] and is not elevated in [[idiopathic normal pressure hydrocephalus]] patients. iNPH, therefore, does not appear to arise as a function of osmotic imbalances in the CSF system and CSF osmolality cannot serve as a  [[idiopathic normal pressure hydrocephalus]] [[biomarker]] or as a predictive tool for shunt responsiveness
((Oernbo EK, Steffensen AB, Gredal H, Poulsen HH, Rostgaard N, Rasmussen CH, Møller-Nissen M, Simonsen AH, Hasselbalch SG, Juhler M, MacAulay N. Cerebrospinal fluid osmolality cannot predict development or surgical outcome of idiopathic normal pressure hydrocephalus. Fluids Barriers CNS. 2022 Jun 27;19(1):52. doi: 10.1186/s12987-022-00349-5. PMID: 35761330.)).
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Agren-Wilsson et al. evaluated cerebrospinal fluid (CSF) markers for neuronal degeneration and [[demyelination]] in idiopathic normal pressure hydrocephalus (INPH), [[subcortical arteriosclerotic encephalopathy]] (SAE), and neurologically healthy subjects.
Lumbar CSF concentrations of [[sulfatide]], [[Neurofilament light polypeptide]] (NFL), total-[[tau]] (T-tau), [[hyperphosphorylated tau]] (P-tau), and beta-amyloid(1-42) (Abeta42) were analyzed in 62 INPH patients, 26 SAE patients, and 23 neurologically healthy controls. In INPH patients, samples before and after shunt surgery were analyzed. RESULTS - The CSF concentration of NFL was elevated in INPH and SAE compared with the controls, and levels of T-tau, P-tau, and Abeta42 were lower in INPH compared with SAE and controls. No difference was seen for sulfatide. All markers except Abeta42 were significantly elevated after shunt surgery. 
The most striking finding was the power of the combined pattern of NFL, P-tau, and [[Abeta42]] in distinguishing between the clinical diagnoses of INPH, SAE, and neurologically healthy elderly
((Agren-Wilsson A, Lekman A, Sjöberg W, Rosengren L, Blennow K, Bergenheim AT, Malm J. CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus. Acta Neurol Scand. 2007 Nov;116(5):333-9. doi: 10.1111/j.1600-0404.2007.00890.x. PMID: 17922727.)).
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The [[idiopathic normal pressure hydrocephalus diagnosis]] is sometimes complicated by concomitant Alzheimer's disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-β (Aβ) 42 and 40, and leucine-rich α-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and Aβ42 in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although Aβ42/40 ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of Aβ40 and Aβ42 correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD
((Jingami N, Asada-Utsugi M, Uemura K, Noto R, Takahashi M, Ozaki A, Kihara T, Kageyama T, Takahashi R, Shimohama S, Kinoshita A. Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer's disease. J Alzheimers Dis. 2015;45(1):109-15. doi: 10.3233/JAD-142622. PMID: 25428256.)).
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A combination of CSF biomarkers can predict improvement following shunt surgery for iNPH. However, these measures only modestly discriminate responders from nonresponders following CSF TT. The findings further suggest that abnormal CSF biomarkers in nonresponders may represent comorbid neurodegenerative pathology or a predegenerative phase that presents with an iNPH phenotype
((Darrow JA, Lewis A, Gulyani S, Khingelova K, Rao A, Wang J, Zhang Y, Luciano M, Yasar S, Moghekar A. CSF Biomarkers Predict Gait Outcomes in Idiopathic Normal Pressure Hydrocephalus. Neurol Clin Pract. 2022 Apr;12(2):91-101. doi: 10.1212/CPJ.0000000000001156. PMID: 35733946; PMCID: PMC9208405.))