Cerebrospinal fluid findings in patients with idiopathic Normal pressure hydrocephalus – findings from a cohort study

Cerebrospinal fluid findings in patients with idiopathic Normal pressure hydrocephalus – findings from a cohort study | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Cerebrospinal fluid findings in patients with idiopathic Normal pressure hydrocephalus – findings from a cohort study Sagar Poudel , Sakoon Saggu , Alfonso Fasano , Deepa Dash , Aparna Wagle Shukla , Ajay Garg , Ashish Dutt Upadhyay , Naveet Wig , Roopa Rajan , Animesh Das , MR Divya , Manjari Tripathi , View ORCID Profile Achal K. Srivastava , SS Kale , P Sarat Chandra , Ashish Suri , Pramod K Pal , Hrishikesh Kumar , Deepti Vibha , Rajesh Kumar Singh , Jasmine Parihar , Ranveer Singh Jadon , Ved Prakash Meena , Bindu Prakash , View ORCID Profile Arunmozhimaran Elavarasi doi: https://doi.org/10.1101/2025.11.14.25340207 Sagar Poudel 1 Department of Medicine, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sakoon Saggu 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Alfonso Fasano 3 Department of Biomedical Sciences, Humanitas University , Milan, Italy 4 IRCCS Humanitas Research Hospital , Milan, Italy Find this author on Google Scholar Find this author on PubMed Search for this author on this site Deepa Dash 5 Department of Clinical Neurological Sciences, University of Western Ontario , London, Canada Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aparna Wagle Shukla 6 Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida , Gainesville, Florida, United States of America Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ajay Garg 7 Department of Neuroimaging and Interventional Neuroradiology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ashish Dutt Upadhyay 8 Department of Biostatistics, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Naveet Wig 1 Department of Medicine, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Roopa Rajan 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Animesh Das 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site MR Divya 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Manjari Tripathi 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Achal K. Srivastava 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Achal K. Srivastava SS Kale 9 Department of Neurosurgery, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site P Sarat Chandra 9 Department of Neurosurgery, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ashish Suri 9 Department of Neurosurgery, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pramod K Pal 10 Department of Neurology, National Institute of Mental Health and Neurosciences , Bengaluru, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Hrishikesh Kumar 11 Movement Disorders Program, Institute of Neurosciences , Kolkata, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Deepti Vibha 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rajesh Kumar Singh 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jasmine Parihar 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ranveer Singh Jadon 1 Department of Medicine, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ved Prakash Meena 1 Department of Medicine, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Bindu Prakash 1 Department of Medicine, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Arunmozhimaran Elavarasi 2 Department of Neurology, All India Institute of Medical Sciences , New Delhi, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Arunmozhimaran Elavarasi For correspondence: arun_ela{at}yahoo.com Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Introduction Normal Pressure Hydrocephalus (NPH) is a treatable cause of gait disturbance, cognitive impairment, and urinary incontinence in older adults. The cerebrospinal fluid tap test (CSF-TT) is used as an ancillary test in the evaluation of idiopathic NPH (iNPH). However, there are no systematic studies on the correlation between CSF opening pressures and biochemical parameters with response to the CSF-TT and shunt responsiveness. CSF proteins are known to be mildly elevated in a few patients with iNPH. Periventricular hyperintensities are known to be correlated with intracranial pressure. Methods We compared CSF opening pressure and biochemical parameters between the CSF-TT responders (atleast 1 point reduction in modified Rankin scale 24 hours after CSF-TT) and non-responders. We also compared these parameters between those with and without MRI periventricular hyperintensities. MRI characteristics—including disproportionately enlarged subarachnoid-space hydrocephalus, periventricular white matter changes, Evans index, callosal angle, and cerebral infarcts—were also compared between patients with elevated versus normal CSF protein levels. Results CSF-TT responders had significantly higher CSF opening pressures (p = 0.04) compared to non-responders, while there were no differences in CSF biochemical parameters. Among MRI features, the callosal angle was significantly lower in patients with higher CSF protein levels (p = 0.02). Conclusion Higher CSF opening pressure within the diagnostic range was associated with CSF-TT responsiveness, while routine CSF biochemistry was not predictive. Elevated CSF protein was associated with a narrower callosal angle, highlighting the value of integrating pressure and imaging features in iNPH evaluation. Introduction Normal pressure hydrocephalus is a disorder of characterized by a triad of gait disturbance, cognitive dysfunction, and urinary disturbance that responds to a Ventriculoperitoneal shunt or Lumbo-peritoneal shunt. The CSF tap test (CSF-TT) has been considered a crucial ancillary investigation prior to shunt surgery. 1 , 2 Additionally, CSF findings, such as opening pressure, cellularity, and routine CSF biochemistry, are routinely performed in patients being evaluated with a large-volume CSF tap. Although the phrase ‘Normal pressure hydrocephalus’ implies that the pressure is normal, what constitutes normal is not precisely defined. It is known that the pressure may be higher in responders. 3 Though elevated opening pressures may be suggestive of secondary causes of hydrocephalus, the range of normal pressures in idiopathic NPH(iNPH) is not clearly defined. The Japanese guidelines consider a diagnosis of probable INPH at an opening pressure cutoff of <200 mm of H2O. 4 On the other hand, the Relkin guidelines 5 consider a cutoff of <245 mm H2O. Several experts 3 are of the opinion that the CSF pressure in INPH is not really ‘normal’ and have even called for a change in terminology to ‘chronic hydrocephalus’ instead of INPH. It is known that the CSF pressure waves often show numerous B waves, thereby signaling a tendency to intermittently high CSF pressures, and these patients have a better outcome than those without B waves. 6 , 7 It is possible that there is a CSF pressure continuum, with individuals having pressures above a particular range exhibiting a better response to the CSF-TT. Periventricular white matter hyperintensities, commonly seen in INPH, likely reflect transependymal CSF flow and ischemic changes, and prior studies have shown that specific imaging features correlate strongly with CSF-TT results and may serve as predictors of shunt effectiveness. 8 Some studies report higher than normal protein levels in up to 38% patients with iNPH. 9 However, the studies on CSF proteins in iNPH are conflicting. 10 , 11 CSF protein levels and biomarker analysis are recognized as potential predictors of shunt responsiveness and may provide valuable prognostic information in INPH. 12 In this exploratory study, we compared CSF opening pressures and biochemical profiles between CSF-TT responders and non-responders, as well as between shunt responders and non-responders. We also report the comparison of CSF findings in those with and without periventricular white matter changes on imaging and compare the imaging findings between those with normal and elevated CSF proteins. Methods In this ambispective cohort study of patients, we recruited consecutive patients who had hydrocephalus on MR imaging and features suggestive of iNPH, such as a reduced callosal angle and DESH with dilated sylvian fissures. These patients underwent a detailed history and clinical examination. The diagnosis of probable iNPH was made clinico-radiologically. These patients underwent the CSF-TT. The methodology has been described in detail elsewhere 13 , 14 Patients underwent assessment at baseline and 24 hours after a 30-50 mL CSF-TT as per the institutional protocol. 13 They were offered VP shunting, based on clinico-radiologic criteria, irrespective of the findings of the CSF-TT or CSF parameters. Patients who had at least one point improvement on the modified Rankin scale 24 hours following the CSF-TT were classified as tap responders. Those with a similar improvement at 24 weeks after VP shunt insertion were classified as shunt responders. The study was designed and reported as per the STROBE reporting guidelines for observational studies. Statistical analysis Data were collected and managed using REDCap (Research Electronic Data Capture), a secure, web-based application designed to support data capture for research studies hosted by the All India Institute of Medical Sciences (AIIMS), New Delhi, India. Data were exported and cleaned using Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Descriptive statistics, including frequencies and percentages, were used to describe categorical variables. Mean and standard deviations were used for continuous variables with a normal distribution, while medians and interquartile ranges were used for non-parametric data. For comparisons between groups, an independent samples t-test was used for normally distributed data, and the Mann–Whitney U test was used for non-normally distributed data. Dichotomous variables were compared using the Chi-squared test or Fisher’s exact test. ROC curve analysis was used to evaluate the ability of the CSF opening pressure to predict shunt responsiveness. The area under the curve (AUC) and the 95% confidence interval were computed, and the optimal cutoff was determined using the Youden index. Sensitivity and specificity were calculated at the chosen threshold. All statistical analyses were performed using Stata version 17 (StataCorp, College Station, TX, USA). A p-value of <0.05 was considered statistically significant. Results We screened 48 patients with clinical or imaging features of iNPH and recruited a total of 40 patients who had probable iNPH and underwent CSF-TT during the period from 2019 to 2024. 13 , 14 We report the comparison of the various CSF parameters between CSF-TT responders and non-responders in Table 1 . The mean opening pressure was significantly higher in responders compared to non-responders. Other CSF biochemical parameters, including cell count, protein, glucose, and the CSF-to-blood glucose ratio, did not differ significantly between groups. View this table: View inline View popup Download powerpoint Table 1: Comparison of CSF findings between CSF tap test responders and non-responders The comparison of these parameters between shunt responders (n=15) and non-responders (n=9) is reported in Supplementary Table 1 . There was a trend towards higher CSF opening pressures in the shunt responders [18(15-21) vs 10(6-20) cm H2O] as compared to shunt non responders; however, this difference was not statistically significant. CSF protein levels were significantly higher in shunt responders compared with non-responders. View this table: View inline View popup Download powerpoint Supplementary Table 1: Comparison of CSF findings between shunt responders and non-responders ROC analysis ( Figure 1 ) of CSF opening pressure as a predictor of tap responsiveness yielded an area under the ROC curve (AUROC) of 0.74 (95% CI: 0.54–0.94), indicating moderate discriminatory ability. The optimal cutoff, identified by the Youden index, was ≥18 cm H 2- O, yielding a sensitivity of 66.7% and specificity of 83.3%. We also found that one patient had an opening pressure of 28 cm H2O. However, the rest of the clinico-radiologic profile fitted into a diagnosis of normal-pressure hydrocephalus. The ROC analysis ( supplementary figure 1 ) of CSF opening pressure as a predictor of shunt responsiveness had an AUROC of 0.71 (0.4-1). Download figure Open in new tab Supplementary Figure 1. Receiver operating characteristic (ROC) curve for CSF opening pressure in predicting shunt responsiveness Download figure Open in new tab Figure 1. Receiver operating characteristic (ROC) curve for CSF opening pressure in predicting CSF-TT responsiveness We compared the CSF findings between patients with and without MRI periventricular hyperintensities. ( Table 2 ). There were no significant differences in the CSF pressures or biochemical parameters between those with and without periventricular hyperintensities on MRI. View this table: View inline View popup Download powerpoint Table 2: Comparison of patients with and without periventricular T2/FLAIR hyperintensities on MRI Brain We also investigated the relationship between CSF protein levels and MRI features ( Table 3 ). There were no differences in the proportion of those with hydrocephalus, periventricular white matter changes, DESH, widened temporal horns, dilation of the third ventricle, or Evans ratio between those with normal CSF proteins and elevated protein levels. Silent infarcts were more commonly found in the lower CSF protein group; however, the difference was not statistically significant. Patients with higher CSF protein had a significantly reduced callosal angle compared to those with normal protein levels (p = 0.02). View this table: View inline View popup Download powerpoint Table 3: Comparison of patients with normal and raised CSF proteins Discussion This study provides valuable insights into the correlation between CSF opening pressure and response to the CSF-TT. Our findings suggest that opening pressure may have a predictive value for CSF-TT responsiveness, whereas routine CSF biochemistry did not differ significantly between these groups. Prior reports have highlighted that CSF pressure in iNPH is not strictly normal, with fluctuations such as B waves indicating intermittent intracranial hypertension, which is associated with better shunt outcomes. 6 , 7 Our results add support to the concept that a higher baseline pressure, while still within diagnostic thresholds (<200 mm H 2 O in Japanese guidelines, <245 mm H 2 O in Relkin criteria), may identify patients more likely to benefit from shunting. 4 , 5 We also had one patient with an opening pressure slightly above these thresholds. We now know from physiologic testing that CSF pressure is not uniform throughout and has peaks and pressure waves during the course of the day. Idiopathic NPH may be a continuum, with some patients experiencing intraday fluctuations, which were captured during the CSF-TT. Even the recent survey on the practice trends of Indian physicians to manage iNPH did not capture what opening pressure cutoffs they used to diagnose iNPH. 15 Similarly, in the systematic review by our group, 16 it was found that each study had different ranges of opening pressures, and Wikkelsö et al. 1986 had included patients with a maximum CSF opening pressure of 30 cm H20 (22 mm Hg). 17 Though the shunt responders had a higher CSF opening pressure as compared to non responders, this did not reach statistical significance, probably because of low sample sizes, which were not powered to detect these differences. Our findings did not demonstrate a significant association between routine CSF protein levels and CSF-TT responsiveness. However, shunt responders had significantly higher CSF protein levels compared to non-responders. We did not perform CSF biomarker analysis, such as tau proteins; however, previous studies suggest that, beyond total protein, specific biomarkers, including t-tau and p-tau, may have a potential role in iNPH. 18 According to a CSF biomarker study, elevated CSF t-tau and p-tau are linked to shunt non-responsiveness in iNPH, likely reflecting underlying neurodegeneration and poorer outcomes. In contrast, lower levels predict better postoperative gait and cognitive improvement. A meta-analysis confirmed that p-tau and t-tau, but not Aβ1-42, differentiate between shunt responders and non-responders. 7 Biomarker panels combining t-tau, Aβ40, and MCP-1 show promise for improving diagnostic accuracy and distinguishing iNPH from cognitive and movement disorders. 19 We found that a narrower callosal angle was significantly associated with higher proteins. This finding has to be confirmed in larger cohorts. Periventricular white matter changes are another biomarker, which likely reflects the raised intraventricular pressure leading to trans-ependymal pressure gradient. This leads to increased water content in the white matter in contrast to the ischemic white matter changes as seen on diffusion microstructure imaging sequences, and there is evidence to suggest that these patients respond better to surgery than those without. Increased water retention could be differentiated from white matter microstructural changes, and these imaging techniques should be studied systematically to generate new imaging biomarkers. 20 This study has several limitations. First, it was conducted with a relatively small sample size at a single center, which may introduce bias and limit the generalizability of our findings. Second, as this was a hypothesis-generating study not originally designed for these outcomes, the observed association between higher CSF opening pressure and CSF-TT responsiveness, although statistically significant, requires validation in larger and more diverse cohorts. Third, we relied on a single time-point measurement of CSF opening pressure. Continuous or repeated measurements of CSF pressure and physiology could provide greater insight into fluctuations and help establish cutoffs with optimal sensitivity and specificity. Similarly, CSF-TT responsiveness was assessed at a single 24-hour time point. Multiple assessments over time, with improvement defined at any of these intervals, may increase sensitivity, particularly for patients who exhibit delayed responses that our study may have missed. Finally, there is no current diagnostic category for patients with imaging features of INPH and elevated opening pressures. This group may represent a distinct subgroup with prognostic differences compared to patients with lower pressures. Longitudinal studies with extended follow-up are needed to better define the natural history and clinical trajectory of these patients. Conclusion Our study suggests that higher CSF opening pressure, even within accepted diagnostic ranges, is associated with better tap test responsiveness and may serve as a simple predictor of shunt responsiveness in iNPH. Routine CSF biochemical parameters were not predictive, though higher protein levels correlated with a narrower callosal angle on MRI. These findings support the role of integrating opening pressure with imaging features in the preoperative evaluation of iNPH and prognostication. Larger, prospective multicenter studies are warranted to investigate longitudinal changes in opening pressures, incorporating advanced CSF biomarkers and standardized imaging scales, to refine prognostication and improve patient selection for shunting. Data Availability All data produced in the present work are contained in the manuscript Funding sources and conflict of interest No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the previous 12 months The authors declare that there are no additional disclosures to report. Ethical Compliance Statement The study was reviewed and approved by the Institute Ethics Committee at the All India Institute of Medical Sciences, New Delhi (No. IECPG-222/20.4.23, RT-14/07.06.23). The participants and their legal guardians provided informed consent to participate in this study. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. References 1. ↵ Hakim S , Adams RD . The special clinical problem of symptomatic hydrocephalus with normal cerebrospinal fluid pressure . Observations on cerebrospinal fluid hydrodynamics. J Neurol Sci . 1965 ; 2 ( 4 ): 307 – 327 . doi: 10.1016/0022-510x(65)90016-x OpenUrl CrossRef PubMed 2. ↵ Hereitová I , Griffa A , Allali G , Dorňák T. Gait characteristics in idiopathic normal pressure hydrocephalus: a review on the effects of CSF tap test and shunt surgery . Eur J Med Res . 2024 ; 29 ( 1 ): 633 . doi: 10.1186/s40001-024-02162-2 OpenUrl CrossRef PubMed 3. ↵ Bret P , Guyotat J , Chazal J. Is normal pressure hydrocephalus a valid concept in 2002? A reappraisal in five questions and proposal for a new designation of the syndrome as “chronic hydrocephalus.” J Neurol Neurosurg Psychiatry . 2002 ; 73 ( 1 ): 9 – 12 . doi: 10.1136/jnnp.73.1.9 OpenUrl Abstract / FREE Full Text 4. ↵ Nakajima M , Yamada S , Miyajima M , et al. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus . Neurol Med Chir (Tokyo) . 2021 ; 61 ( 2 ): 63 – 97 . doi: 10.2176/nmc.st.2020-0292 OpenUrl CrossRef PubMed 5. ↵ Relkin N , Marmarou A , Klinge P , Bergsneider M , Black PM . Diagnosing idiopathic normal-pressure hydrocephalus . Neurosurgery . 2005 ; 57 ( 3 Suppl ): S4 – 16 ; discussion ii-v. doi: 10.1227/01.neu.0000168185.29659.c5 OpenUrl CrossRef PubMed 6. ↵ Vanneste JA . Diagnosis and management of normal-pressure hydrocephalus . J Neurol . 2000 ; 247 ( 1 ): 5 – 14 . doi: 10.1007/s004150050003 OpenUrl CrossRef PubMed Web of Science 7. ↵ PRESSURE WAVES IN SO-CALLED LOW-PRESSURE HYDROCEPHALUS . The Lancet . 1972 ; 300 ( 7790 ): 1291 – 1292 . doi: 10.1016/S0140-6736(72)92658-X OpenUrl CrossRef 8. ↵ Ishikawa M , Oowaki H , Matsumoto A , Suzuki T , Furuse M , Nishida N. Clinical Significance of Cerebrospinal Fluid Tap Test and Magnetic Resonance Imaging/Computed Tomography Findings of Tight High Convexity in Patients With Possible Idiopathic Normal Pressure Hydrocephalus . Neurol Med Chir (Tokyo) . 2010 ; 50 ( 2 ): 119 – 123 . doi: 10.2176/nmc.50.119 OpenUrl CrossRef PubMed 9. ↵ Wood JH , Bartlet D , James AE , Udvarhelyi GB . Normal-pressure hydrocephalus: diagnosis and patient selection for shunt surgery . Neurology . 1974 ; 24 ( 6 ): 517 – 526 . doi: 10.1212/wnl.24.6.517 OpenUrl CrossRef PubMed 10. ↵ Jensen F. Acquired hydrocephalus . Acta Neurochir (Wien) . 1979 ; 46 ( 1 ): 119 – 133 . doi: 10.1007/BF01407686 OpenUrl CrossRef PubMed 11. ↵ Ojemann RG , Fisher CM , Adams RD , Sweet WH , New PFJ . Further Experience with the Syndrome of “Normal” Pressure Hydrocephalus . Published online September 1, 1969 . doi: 10.3171/jns.1969.31.3.0279 OpenUrl CrossRef PubMed Web of Science 12. ↵ Weiner S , Junkkari A , Sauer M , et al. Novel cerebrospinal fluid biomarkers correlating with shunt responsiveness in patients with idiopathic normal pressure hydrocephalus . Fluids Barriers CNS . 2023 ; 20 ( 1 ): 40 . doi: 10.1186/s12987-023-00440-5 OpenUrl CrossRef PubMed 13. ↵ Poudel S. Diagnostic Accuracy of CSF Tap-Test Parameters in Predicting Shunt Responsiveness in Normal Pressure Hydrocephalus: A Cohort Study . doi: 10.2139/ssrn.5413559 OpenUrl CrossRef 14. ↵ Poudel S , Dash D , Garg A , et al. CSF Tap Test Parameters and Short-Term Outcomes in operated and non-operated patients with idiopathic Normal Pressure Hydrocephalus: A Cohort Study . medRxiv . Preprint posted online September 2, 2025 :2025.08.31.25334780. doi: 10.1101/2025.08.31.25334780 OpenUrl Abstract / FREE Full Text 15. ↵ Elavarasi A. Current Practice Patterns Among Indian Neurologists in the Evaluation and Management of Normal Pressure Hydrocephalus: A Nationwide Cross-Sectional Survey . Preprint posted online July 10, 2025 . doi: 10.2139/ssrn.5376438 OpenUrl CrossRef 16. ↵ Aliyar A , Dash D , Fasano A , et al. Accuracy of CSF Tap Test and Lumbar Infusion Test in Predicting Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review and Meta-Analysis . medRxiv . Preprint posted online November 10, 2025 :2025.11.09.25339846. doi: 10.1101/2025.11.09.25339846 OpenUrl Abstract / FREE Full Text 17. ↵ Wikkelsö C , Andersson H , Blomstrand C , Lindqvist G , Svendsen P. Normal pressure hydrocephalus . Predictive value of the cerebrospinal fluid tap-test. Acta Neurol Scand . 1986 ; 73 ( 6 ): 566 – 573 . doi: 10.1111/j.1600-0404.1986.tb04601.x OpenUrl CrossRef PubMed 18. ↵ Thavarajasingam SG , El-Khatib M , Vemulapalli KV , et al. Cerebrospinal fluid and venous biomarkers of shunt-responsive idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis . Acta Neurochir (Wien) . 2022 ; 164 ( 7 ): 1719 – 1746 . doi: 10.1007/s00701-022-05154-5 OpenUrl CrossRef PubMed 19. ↵ Jeppsson A , Wikkelsö C , Blennow K , et al. CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics . J Neurol Neurosurg Psychiatry . 2019 ; 90 ( 10 ): 1117 – 1123 . doi: 10.1136/jnnp-2019-320826 OpenUrl Abstract / FREE Full Text 20. ↵ Rau A , Reisert M , Kellner E , Hosp JA , Urbach H , Demerath T. Increased interstitial fluid in periventricular and deep white matter hyperintensities in patients with suspected idiopathic normal pressure hydrocephalus . Sci Rep . 2021 ; 11 : 19552 . doi: 10.1038/s41598-021-98054-0 OpenUrl CrossRef PubMed View the discussion thread. Back to top Previous Next Posted November 15, 2025. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Cerebrospinal fluid findings in patients with idiopathic Normal pressure hydrocephalus – findings from a cohort study Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Cerebrospinal fluid findings in patients with idiopathic Normal pressure hydrocephalus – findings from a cohort study Sagar Poudel , Sakoon Saggu , Alfonso Fasano , Deepa Dash , Aparna Wagle Shukla , Ajay Garg , Ashish Dutt Upadhyay , Naveet Wig , Roopa Rajan , Animesh Das , MR Divya , Manjari Tripathi , Achal K. Srivastava , SS Kale , P Sarat Chandra , Ashish Suri , Pramod K Pal , Hrishikesh Kumar , Deepti Vibha , Rajesh Kumar Singh , Jasmine Parihar , Ranveer Singh Jadon , Ved Prakash Meena , Bindu Prakash , Arunmozhimaran Elavarasi medRxiv 2025.11.14.25340207; doi: https://doi.org/10.1101/2025.11.14.25340207 Share This Article: Copy Citation Tools Cerebrospinal fluid findings in patients with idiopathic Normal pressure hydrocephalus – findings from a cohort study Sagar Poudel , Sakoon Saggu , Alfonso Fasano , Deepa Dash , Aparna Wagle Shukla , Ajay Garg , Ashish Dutt Upadhyay , Naveet Wig , Roopa Rajan , Animesh Das , MR Divya , Manjari Tripathi , Achal K. Srivastava , SS Kale , P Sarat Chandra , Ashish Suri , Pramod K Pal , Hrishikesh Kumar , Deepti Vibha , Rajesh Kumar Singh , Jasmine Parihar , Ranveer Singh Jadon , Ved Prakash Meena , Bindu Prakash , Arunmozhimaran Elavarasi medRxiv 2025.11.14.25340207; doi: https://doi.org/10.1101/2025.11.14.25340207 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Neurology Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (300) Cardiovascular Medicine (4435) Dentistry and Oral Medicine (444) Dermatology (382) Emergency Medicine (608) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1509) Epidemiology (15229) Forensic Medicine (30) Gastroenterology (1124) Genetic and Genomic Medicine (6600) Geriatric Medicine (668) Health Economics (997) Health Informatics (4536) Health Policy (1368) Health Systems and Quality Improvement (1613) Hematology (541) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15916) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (146) Nephrology (667) Neurology (6599) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1144) Occupational and Environmental Health (957) Oncology (3332) Ophthalmology (974) Orthopedics (369) Otolaryngology (420) Pain Medicine (436) Palliative Medicine (130) Pathology (663) Pediatrics (1693) Pharmacology and Therapeutics (691) Primary Care Research (711) Psychiatry and Clinical Psychology (5447) Public and Global Health (9232) Radiology and Imaging (2198) Rehabilitation Medicine and Physical Therapy (1370) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (712) Sports Medicine (530) Surgery (712) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a00bcc8fcb943fe2',t:'MTc3OTYyMDQ1MQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();