Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus
Rongrong Hua, Chunyan Liu, Xing Liu, Jinwu Zhu, Jie Zhang, Lidong Wang, Zhe Shi, Jian Li, Shuangyan Kong, Chenhui Yang, Nan Liu, Lijuan Liu, Jie Sun, Qiong Yang, Yubing Wu, Ying Zhou, Yanfeng Li, Yan Xing, Rongrong Hua, Chunyan Liu, Xing Liu, Jinwu Zhu, Jie Zhang, Lidong Wang, Zhe Shi, Jian Li, Shuangyan Kong, Chenhui Yang, Nan Liu, Lijuan Liu, Jie Sun, Qiong Yang, Yubing Wu, Ying Zhou, Yanfeng Li, Yan Xing
Abstract
Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness. Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function. Results: The analysis of biomarkers from the patients' CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p < 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p < 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ - (-5.505 + 55.314 * ratio of p/T-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505 + 0.553 * percentage of p/T-tau - 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively. Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.
Keywords: Aβ; cerebrospinal fluid biomarkers; idiopathic normal pressure hydrocephalus; tap test; tau.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2021 Hua, Liu, Liu, Zhu, Zhang, Wang, Shi, Li, Kong, Yang, Liu, Liu, Sun, Yang, Wu, Zhou, Li and Xing.
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References
- Abu Hamdeh S., Virhammar J., Sehlin D., Alafuzoff I., Cesarini K. G., Marklund N., et al. . (2018). Brain tissue Aβ42 levels are linked to shunt response in idiopathic normal pressure hydrocephalus. J. Neurosurg. 2018, 1–9. 10.3171/2017.7.JNS171005
- Abu-Rumeileh S., Giannini G., Polischi B., Albini-Riccioli L., Milletti D., Oppi F., et al. . (2019). Revisiting the cerebrospinal fluid biomarker profile in idiopathic normal pressure hydrocephalus: the bologna pro-hydro study. J. Alzheimers Dis. 2019, 1–11. 10.3233/JAD-181012
- Baiardi S., Abu-Rumeileh S., Rossi M., Zenesini C., Bartoletti-Stella A., Polischi B., et al. . (2018). Antemortem CSF Aβ42/Aβ40 ratio predicts Alzheimer’s disease pathology better than Aβ42 in rapidly progressive dementias. Ann. Clin. Transl. Neurol. 6, 263–273. 10.1002/acn3.697
- Chen Z., Liu C., Zhang J., Relkin N., Xing Y., Li Y., et al. . (2017). Cerebrospinal fluid Abeta42, t-tau and p-tau levels in the differential diagnosis of idiopathic normal-pressure hydrocephalus: a systematic review and meta-analysis. Fluids Barriers CNS 14:13. 10.1186/s12987-017-0062-5
- Craven C. L., Baudracco I., Zetterberg H., Lunn M. P. T., Chapman M. D., Lakdawala N., et al. . (2017). The predictive value of T-tau and Aβ1–42 levels in idiopathic normal pressure hydrocephalus. Acta Neurochir. 159, 2293–2300. 10.1007/s00701-017-3314-x
- Graff-Radford N. R. (2014). Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus. Neurology 83, 1573–1575. 10.1212/WNL.0000000000000916
- Graff-Radford N. R., Jones D. T. (2019). Normal pressure hydrocephalus. Continuum 25, 165–186. 10.1212/CON.0000000000000689
- Halperin J. J., Kurlan R., Schwalb J. M., Cusimano M. D., Gronseth G., Gloss D., et al. . (2015). Practice guideline: idiopathic normal pressure hydrocephalus: response to shunting and predictors of response: report of the guideline development, dissemination and implementation subcommittee of the american academy of neurology. Neurology 85, 2063–2071. 10.1212/WNL.0000000000002193
- Herukka S., Rummukainen J., Ihalainen J., Fraunberg M., Koivisto A., Nerg O., et al. . (2015). Amyloid-β and tau dynamics in human brain interstitial fluid in patients with suspected normal pressure hydrocephalus. J. Alzheimers Dis. 46, 146–151. 10.3233/JAD-142862
- Herukka S. K., Rummukainen J., Ihalainen J., von Und Zu Fraunberg M., Koivisto A. M., Nerg O., et al. . (2015). Amyloid-beta and tau dynamics in human brain interstitial fluid in patients with suspected normal pressure hydrocephalus. J. Alzheimers Dis. 46, 261–269. 10.3233/JAD-142862
- Iliff J. J., Wang M., Liao Y., Plogg B. A., Peng W., Gundersen G. A., et al. . (2012). A paravascular pathway facilitates csf flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci. Transl. Med. 4:147ra111. 10.1126/scitranslmed.3003748
- Ishikawa M., Hashimoto M., Mori E., Kuwana N., Kazui H. (2012). The value of the cerebrospinal fluid tap test for predicting shunt effectiveness in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 9:1. 10.1186/2045-8118-9-1
- Janelidze S., Zetterberg H., Mattsson N., Palmqvist S., Vanderstichele H., Lindberg O., et al. . (2016). Cerebrospinal fluid Aβ42/Aβ40 and Aβ42/Aβ38 as biomarkers of Alzheimer’s disease. Neurobiol. Aging 39:S28. 10.1016/j.neurobiolaging.2016.01.122
- Jeppsson A., Höltta M., Zetterberg H., Blennow K., Wikkelsø C., Tullberg M. (2016). Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus. Fluids Barriers CNS 13:13. 10.1186/s12987-016-0037-y
- Jeppsson A., Zetterberg H., Blennow K., Wikkelso C. (2013). Idiopathic normal-pressure hydrocephalus: pathophysiology and diagnosis by CSF biomarkers. Neurology 80, 1385–1392. 10.1212/WNL.0b013e31828c2fda
- Jingami N., Asada-Utsugi M., Uemura K., Noto R., Takahashi M., Ozaki A., et al. . (2015a). Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer’s disease. J. Alzheimers Dis. 45, 109–115. 10.3233/JAD-142622
- Jingami N., Uemura K., Noto R., Asada M., Kinoshita A. (2015b). Idiopathic normal pressure hydrocephalus has a different cerebrospinal fluid biomarker profile from Alzheimer’s disease. J. Alzheimers Dis. 45, 109–115. 10.3233/JAD-142622
- Jingami N., Uemura K., Asada-Utsugi M., Kuzuya A., Yamada S., Ishikawa M., et al. . (2019). Two-Point dynamic observation of Alzheimer’s disease cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus. J. Alzheimers Dis. 72, 271–277. 10.3233/JAD-190775
- Liew B. S., Takagi K., Kato Y., Duvuru S., Thanapal S., Mangaleswaran B., et al. . (2019). Current updates on idiopathic normal pressure hydrocephalus. Asian J. Neurosurg. 14, 648–656. 10.4103/ajns.AJNS_14_19
- Lim T., Choi J., Park S., Youn Y., Lee H., Kim B., et al. . (2014). Evaluation of coexistence of Alzheimer’s disease in idiopathic normal pressure hydrocephalus using ELISA analyses for CSF biomarkers. BMC Neurol. 14, 1–8. 10.1186/1471-2377-14-66
- Mori E., Ishikawa M., Kato T., Kazui H., Miyake H., Miyajima M., et al. . (2012). Guidelines for management of idiopathic normal pressure hydrocephalus: second edition. Neurol. Med. Chir. 52, 775–809. 10.2176/nmc.52.775
- Relkin N., Marmarou A., Klinge P., Bergsneider M., Black P. M. (2005). Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery 57, S4–S16. 10.1227/01.neu.0000168185.29659.c5
- Riemenschneider M., Wagenpfeil S., Vanderstichele H., Otto M., Wiltfang J., Kretzschmar H., et al. . (2003). Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Mol. Psychiatry 8, 343–347. 10.1038/sj.mp.4001220
- Ritchie C., Smailagic N., Ladds E. C., Noeltorr A. H., Ukoumunne O., Martin S., et al. . (2013). CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst. Rev. 3:CD010803. 10.1002/14651858.CD010803.pub2
- Santangelo R., Cecchetti G., Bernasconi M. P., Cardamone R., Barbieri A., Pinto P., et al. . (2017). Cerebrospinal fluid Amyloid-β 42, total tau and phosphorylated tau are low in patients with normal pressure hydrocephalus: analogies and differences with Alzheimer’s disease. J. Alzheimers Dis. 60, 183–200. 10.3233/JAD-170186
- Toma A. K., Papadopoulos M. C., Stapleton S., Kitchen N. D., Watkins L. D. (2013). Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus. Acta Neurochir. (Wien) 155, 1977–1980. 10.1007/s00701-013-1835-5
- Williams M. A., Malm J. (2016). Diagnosis and treatment of idiopathic normal pressure hydrocephalus. Continuum 22, 579–599. 10.1212/CON.0000000000000305
- Xie L., Kang H., Xu Q., Chen M. J., Liao Y., Thiyagarajan M., et al. . (2013). Sleep drives metabolite clearance from the adult brain. Science 342, 373–377. 10.1126/science.1241224
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