Utility of cortical tissue analysis in normal pressure hydrocephalus.

Clinical improvement following neurosurgical cerebrospinal fluid shunting for presumed idiopathic normal pressure hydrocephalus is variable. Idiopathic normal pressure hydrocephalus patients may have undetected Alzheimer's disease-related cortical pathology that confounds diagnosis and clinical outcomes. In this study, we sought to determine the utility of cortical tissue immuno-analysis in predicting shunting outcomes in idiopathic normal pressure hydrocephalus patients. We performed a pooled analysis using a systematic review as well as analysis of a new, original patient cohort. Of the 2707 screened studies, 3 studies with a total of 229 idiopathic normal pressure hydrocephalus patients were selected for inclusion in this meta-analysis alongside our original cohort. Pooled statistics of shunting outcomes for the 229 idiopathic normal pressure hydrocephalus patients and our new cohort of 36 idiopathic normal pressure hydrocephalus patients revealed that patients with Aß + pathology were significantly more likely to exhibit shunt nonresponsiveness than patients with negative pathology. Idiopathic normal pressure hydrocephalus patients with Alzheimer's disease -related cortical pathology may be at a higher risk of treatment facing unfavorable outcomes following cerebrospinal fluid shunting. Thus, cortical tissue analysis from living patients may be a useful diagnostic and prognostic adjunct for patients with presumed idiopathic normal pressure hydrocephalus and potentially other neurodegenerative conditions affecting the cerebral cortex.

Cases of familial idiopathic normal pressure hydrocephalus implicate genetic factors in disease pathogenesis.

Idiopathic normal pressure hydrocephalus is a disorder of unknown pathophysiology whose diagnosis is paradoxically made by a positive response to its proposed treatment with cerebrospinal fluid diversion. There are currently no idiopathic normal pressure hydrocephalus disease genes or biomarkers. A systematic analysis of familial idiopathic normal pressure hydrocephalus could aid in clinical diagnosis, prognosis, and treatment stratification, and elucidate disease patho-etiology. In this 2-part analysis, we review literature-based evidence for inheritance of idiopathic normal pressure hydrocephalus in 22 pedigrees, and then present a novel case series of 8 familial idiopathic normal pressure hydrocephalus patients. For the case series, demographics, familial history, pre- and post-operative symptoms, and cortical pathology were collected. All novel familial idiopathic normal pressure hydrocephalus patients exhibited improvement following shunt treatment and absence of neurodegenerative cortical pathology (amyloid-beta and hyperphosphorylated tau), in contrast to many sporadic cases of idiopathic normal pressure hydrocephalus with variable clinical responses. Analysis of the 30 total familial idiopathic normal pressure hydrocephalus cases reported herein is highly suggestive of an autosomal dominant mechanism of inheritance. This largest-ever presentation of multiply affected idiopathic normal pressure hydrocephalus pedigrees provides strong evidence for Mendelian inheritance and autosomal dominant transmission of an idiopathic normal pressure hydrocephalus trait in a subset of patients that positively respond to shunting and lack neurodegenerative pathology. Genomic investigation of these families may identify the first bona fide idiopathic normal pressure hydrocephalus disease gene.

Efficacy and safety of shunt surgery in patients with idiopathic normal-pressure hydrocephalus: can we predict shunt response by preoperative magnetic resonance imaging (MRI)?

AIM: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. MATERIALS AND METHODS: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. RESULTS: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. CONCLUSION: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

AIM OF THE STUDY: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. CLINICAL RATIONALE FOR STUDY: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. MATERIAL AND METHODS: 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF ß-amyloid 1-40 (Aß1-40), ß-amyloid 1-42 (Aß1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aß1-40/Aß1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. RESULTS: There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aß42/Aß40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). CONCLUSIONS: While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. CLINICAL IMPLICATIONS: These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.

Alpha-Synuclein RT-QuIC in Idiopathic Normal Pressure Hydrocephalus.

This study quantified the occurrence of an underlying synucleinopathy in 50 patients with idiopathic normal pressure hydrocephalus by means of real-time quaking-induced conversion, a highly sensitive and specific technique capable of detecting and amplifying misfolded aggregated forms of α-synuclein in the cerebrospinal fluid. Seven patients were positive and they did not differ from negative cases, except for a more frequent L-dopa responsiveness and gait characterized by a wider base. The two groups did not differ in terms of response rate to tap test or shunt surgery, although step length and gait velocity improved by a lesser extent in positive cases. ANN NEUROL 2022;92:985-991.

Change in Morphological Features of Enlarged Subarachnoid Spaces Following Treatment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Focally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and should be differentiated from atrophy. PURPOSE: To evaluate for change in FES size and pituitary height after shunt placement in iNPH. STUDY TYPE: Retrospective. SUBJECTS: A total of 125 iNPH patients who underwent shunt surgery and 40 age-matched controls. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w. ASSESSMENT: FES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls. STATISTICAL TESTS: Wilcoxon signed-rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P < 0.05. RESULTS: Fifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI. DATA CONCLUSION: Decrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less-well recognized feature of altered CSF dynamics. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Prediction of shunt response in idiopathic normal pressure hydrocephalus by combined lumbar infusion test and preoperative imaging scoring.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a potentially treatable disorder, but prognostic tests or biomarkers are lacking. The aim was to study the predictive power of clinical, neuroimaging and lumbar infusion test parameters (resistance to outflow Rout , cardiac-related pulse amplitude PA and the PA to intracranial pressure ICP ratio). METHODS: In all, 127 patients diagnosed with iNPH who had a lumbar infusion test, a subsequent ventriculo-peritoneal shunt operation and at least 2 months of postoperative follow-up were retrospectively included. Preoperative magnetic resonance images were visually scored for NPH features using the iNPH Radscale. Preoperative and postoperative assessment was performed using cognitive testing, as well as gait and incontinence scales. RESULTS: At follow-up (7.4 months, range 2-20 months), an overall positive response was seen in 82% of the patients. Gait was more severely impaired at baseline in responders compared to non-responders. The iNPH Radscale score was borderline significantly higher in responders compared with non-responders, whereas no significant differences in infusion test parameters were seen between responders and non-responders. Infusion test parameters performed modestly with high positive (75%-92%) but low negative (17%-23%) predictive values. Although not significant, PA and PA/ICP seemed to perform better than Rout , and the odds ratio for shunt response seemed to increase in patients with higher PA/ICP, especially in patients with lower iNPH Radscale scores. CONCLUSION: Although only indicative, lumbar infusion test results increased the likelihood of a positive shunt outcome. Pulse amplitude measures showed promising results that should be further explored in prospective studies.

Longitudinal post-shunt outcomes in idiopathic normal pressure hydrocephalus with and without comorbid Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity. METHODS: Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24-60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively. RESULTS: There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence. CONCLUSION: iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.

Predictive Ability of Frontal Assessment Battery for Cognitive Improvement After Shunt Surgery in Individuals With Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: The predictive ability of the Frontal Assessment Battery (FAB) for postoperative cognitive improvement in idiopathic normal pressure hydrocephalus (iNPH) is unstudied. OBJECTIVE: To compare the predictive ability of the FAB and the Mini-Mental State Examination (MMSE) for postoperative cognitive improvement in individuals with iNPH after shunt surgery. METHOD: We retrospectively reviewed the medical records of individuals with iNPH who had shunt surgery between January 2016 and October 2018. Individuals had completed the tap test and clinical evaluations (FAB, MMSE, Timed Up and Go [TUG]) both before and 24-48 hours after CSF tapping and after surgery. We excluded individuals without complete clinical evaluations and those with shunt surgery performed >6 months after CSF tapping. Factors associated with postoperative FAB and MMSE improvement as per the 2011 iNPH guidelines were extracted using univariate and multivariate logistic regression analyses. Independent variables were baseline FAB and MMSE scores, FAB and MMSE score changes and TUG amelioration rate after CSF tapping, Evans index, age, and days from CSF tapping to surgery and from surgery to postoperative assessment. RESULTS: The mean number of days from CSF tapping to surgery and from surgery to postoperative assessment were 77.5 (SD = 36.0) and 42.0 (SD = 14.5), respectively. Logistic regression analyses showed significant associations in the univariate analyses of postoperative FAB improvement with baseline FAB scores ( P = 0.043) and with FAB score changes after CSF tapping ( P = 0.047). CONCLUSION: The FAB may help predict postoperative cognitive improvement after shunt surgery better than the MMSE.

Effect of cerebrospinal fluid area mask correction on 123I-FP-CIT SPECT images in idiopathic normal pressure hydrocephalus.

BACKGROUND: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [123I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation. METHODS: We enrolled 25 patients with iNPH who were assessed using 123I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR. RESULTS: The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region. CONCLUSIONS: The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021.

The necessity of gait evaluation on the 7th day after tap tests for the idiopathic normal pressure hydrocephalus patients.

BACKGROUND: A tap test is established as an evaluation method to indicate shunt surgery for hydrocephalus, especially idiopathic normal pressure hydrocephalus (iNPH). The timing of gait assessment after the test is still controversial, while some studies reported the effectiveness of the gait evaluation up to 2nd day after tap tests. Our study explored whether the gait evaluation on the 7th day after a tap test is necessary. METHODS: We retrospectively evaluated 129 consecutive cases with possible iNPH who performed gait assessment on all 1st, 3rd, and 7th days after tap tests between May 2020 and February 2022. We reviewed the following items of the patients: age, sex, modified Rankin scale, iNPH grading scale, Mini-Mental State Evaluation (MMSE), and neurological imaging. The number of probable iNPH patients who improved their gait each day after the test was analyzed. We also assessed the number of definite iNPH patients and revealed the background characteristics of the patients who showed gait improvement on the 7th day after the tests. RESULTS: Of the 129 patients who met our inclusion criteria, 57 were judged as probable iNPH on the 1st day, 28 were new on the 3rd, and 23 were new on the 7th. The number of probable iNPH patients up to the 7th day after tests was significantly more extensive than that of those up to the 3rd (108 [83.7%] vs. 85 [65.9%]; 95% confidence interval [CI], p < 0.0001). The number of definite iNPH patients was also significantly more prominent when the evaluation after the tests was performed on all of the 1st, the 3rd, and the 7th days than just on the 1st (72 vs. 42; 95% CI, p = 0.00016) or both of the 1st and the 3rd (72 vs. 61; 95% CI, p = 0.00074). No statistically significant difference existed in the patients' backgrounds except for the pre-tap test MMSE. CONCLUSION: Gait evaluation on the 7th day after tap tests, in addition to the first few days, may reduce the number of iNPH patients who miss the opportunity of getting beneficial treatment.

Diffusion tensor imaging helps identify shunt-responsive normal pressure hydrocephalus patients among probable iNPH cohort.

The aim of this study was to investigate whether white matter changes as measured by diffusion tensor imaging (DTI) can help differentiate shunt-responsive idiopathic normal pressure hydrocephalus (iNPH) patients from patients with other causes of gait disturbances and/or cognitive decline with ventriculomegaly whose clinical symptoms do not improve significantly after cerebrospinal fluid derivation (non-iNPH). Between 2017 and 2022, 85 patients with probable iNPH underwent prospective preoperative magnetic resonance imaging (MRI) and comprehensive clinical workup. Patients with clinical symptoms of iNPH, positive result on lumbar infusion test, and gait improvement after 120-h lumbar drainage were diagnosed with iNPH and underwent shunt-placement surgery. Fractional anisotropy (FA) and mean diffusivity (MD) values for individual regions of interest were extracted from preoperative MRI, using the TBSS pipeline of FSL toolkit. These FA and MD values were then compared to results of clinical workup and established diagnosis of iNPH. An identical MRI protocol was performed on 13 age- and sex-matched healthy volunteers. Statistically significant differences in FA values of several white matter structures were found not only between iNPH patients and healthy controls but also between iNPH and non-iNPH patients. ROI that showed best diagnostic ability when differentiating iNPH among probable iNPH cohort was uncinate fasciculus, with AUC of 0.74 (p < 0.001). DTI methods of white matter analysis using standardised methods of ROI extraction can help in differentiation of iNPH patients not only from healthy patients but also from patients with other causes of gait disturbances with cognitive decline and ventriculomegaly.

Comparison Between Ventricular and Spinal Infusion Tests in Suspected Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is an often-overlooked or misdiagnosed brain disorder characterized by overt ventriculomegaly and associated with gait disturbances, cognitive impairment, and urinary incontinence. If correctly diagnosed, it is considered the only form of dementia treatable with surgery, namely through a ventriculoperitoneal or ventriculoatrial shunt with programmable valves.Among the 856 spinal and ventricular infusion tests performed from 2001 to 2017 at our institution, we analyzed 106 cases selected for suspected normotensive hydrocephalus. In all cases, Intracranial Elastance Index (IEI) and outflow resistance (Rout) values were calculated: 52 of these patients underwent Spinal Katzman Test (SKT), and the remaining 54 underwent an intraventricular infusion test (IVKT). Of the 40 patients in the SKT group with pathological elastance (71%), 17 also had a Rout >12 mmHg and 23 a Rout <12 mmHg. Of the 50 patients in the IVKT group with pathological elastance (92%), 38 also had a Rout >12 mmHg and 12 a Rout <12 mmHg.IVKT and SKT to date represent two useful tools in the diagnosis of normal pressure hydrocephalus. Despite being more invasive, IVKT, including both the intracranial elastance index (IEI) and Rout analysis, could be considered more reliable than SKT and therefore could be reserved for the most controversial cases.

The impact of cerebrospinal fluid shunting on quality of life in idiopathic normal pressure hydrocephalus: a long-term analysis.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) represents an insidious type of dementia considered reversible after shunt placement. Although the clinical outcome has been widely studied, few studies have reported on quality of life (QOL) after surgery. This study evaluated the long-term clinical and QOL outcomes of iNPH patients after ventriculoperitoneal shunt (VPS) implantation. Factors influencing QOL in iNPH were also investigated. METHODS: From 2009 to 2020, a single-institution retrospective study was conducted to compare shunted iNPH patients with a homogeneous control group. QOL was analyzed using the SF-36 questionnaire with yearly follow-up for as long as 11 years. Severity of symptoms, comorbidities, and clinical data were also recorded. RESULTS: Among 187 treated patients, 15 had died at the time of the authors' evaluation, and 45 did not match the inclusion criteria. The mean ± SD (range) follow-up was 118.5 ± 4.2 (18-132) months. QOL improved in 103/130 (79%) patients through 5 years after shunt surgery, although it remained lower than that of the control group (p < 0.0001). The SF-36 score reduced progressively, reaching baseline at 5-7 years of follow-up and decreased to below baseline at 7-11 years of follow-up (p < 0.0001). Predictors of improved QOL were younger age (p < 0.001), lower body mass index (BMI) (p < 0.001), and better Mini-Mental State Examination (MMSE) performance (p < 0.001) before surgery. Decreased postoperative QOL was associated with cerebrovascular disease, diabetes, and severity of symptoms (gait and cognition) at presentation (p < 0.001). CONCLUSIONS: VPS implantation, along with a strict and comprehensive follow-up, has been shown to improve QOL in iNPH patients for as long as 5 years after surgery. Younger age, lower BMI, and better MMSE score are positive predictors of improved QOL after shunt placement.

CSF dynamics in long-standing overt ventriculomegaly in adults.

OBJECTIVE: Long-standing overt ventriculomegaly in adults (LOVA) is a form of chronic hydrocephalus and its pathophysiology and treatment remain debated. An analysis of CSF dynamics in this condition has rarely been reported. The aim of this study was to analyze hydrodynamic characteristics of patients with suspected LOVA to discuss its pathophysiological mechanisms and the importance of CSF dynamics analysis for diagnosis and treatment of these patients. METHODS: This retrospective cohort study, conducted between May 2018 and October 2022, included adult patients aged > 18 years investigated in a department of neurosurgery through a lumbar infusion study for suspicion of LOVA (n = 23). These patients were then compared with a control cohort explored for suspicion of idiopathic normal pressure hydrocephalus (iNPH; n = 30). Clinical symptoms, radiological findings, and hydrodynamic parameters were analyzed. The authors specifically compared two hydrodynamic parameters: resistance to CSF outflow, or Rout, which relies on CSF resorption, and pressure-volume index (PVI), which reflect overall craniospinal compliance. The lumbar infusion study was considered pathological (confirming the diagnosis of chronic hydrocephalus) when at least one of these two parameters was altered. RESULTS: Rout was significantly less frequently increased (cutoff ≥ 12 mm Hg/ml/min) in patients with LOVA (52%) than in those with iNPH (97%; p < 0.001). In contrast, PVI was impaired (cutoff ≤ 25 ml) in both cohorts, i.e., in 61% of patients with LOVA and in 83% of patients with iNPH. Overall, the rate of pathological lumbar infusion study in LOVA (87%) was not statistically different than in iNPH (100%). However, PVI was the only impaired parameter most frequently found in those with LOVA (35%) compared with those with iNPH (3%; p = 0.002). CONCLUSIONS: This study suggests that there is a differential CSF dynamics pattern when comparing patients with LOVA versus those with iNPH. A higher proportion of patients with LOVA showed isolated compliance impairment. These findings highlight the utility of CSF dynamics analysis for the evaluation of patients with suspected chronic obstructive hydrocephalus such as LOVA. Future research with larger case series may help define diagnosis and treatment algorithms of chronic obstructive hydrocephalus based on CSF dynamics analysis, in addition to clinical and radiological criteria.

Objective assessment of patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement using activity-monitoring data: pilot study.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH. METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement. RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase). CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

Slope until reaching the plateau: a new predictor of valve response obtained by lumbar infusion test for idiopathic normal pressure hydrocephalus.

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.

The benefits of automated CSF drainage in normal pressure hydrocephalus.

BACKGROUND: The commonly used cerebrospinal fluid (CSF) drainage system remains the manual drip-chamber drain. The LiquoGuard (Möller Medical GmbH, Germany) is an automated CSF management device with dual functionality, measuring intracranial pressure and automatic pressure- or volume-led CSF drainage. There is limited research for comparison of devices, particularly in the neurosurgical field, where it has potential to reshape care. OBJECTIVE: This study aims to compare manual drip-chamber drain versus LiquoGuard system, by assessing accuracy of drainage, associated morbidity and impact on length of stay. METHOD: Inclusion criteria consisted of suspected normal pressure hydrocephalus (NPH) patients undergoing extended lumbar drainage. Patients were divided into manual drain group versus automated group. RESULTS: Data was analysed from 42 patients: 31 in the manual group versus 11 in the LiquoGuard group. Volumetric over-drainage was seen in 90.3% (n = 28) versus 0% (p < 0.05), and under-drainage in 38.7% (n = 12) versus 0% (p < 0.05), in the manual and automatic group, respectively. Symptoms of over-drainage were noted in 54.8% (n = 17) of the manual group, all of which had episodes of volumetric over-drainage, versus 18.2% (n = 2) in automated group, of which neither had actual over-drainage (p < 0.05). Higher over-drainage symptoms of manual drain is likely due to increased fluctuation of CSF drainage, instead of smooth CSF drainage seen with LiquoGuard system. An increased length of stay was seen in 38.7% (n = 12) versus 9% (n = 1) (p < 0.05) in the manual and LiquoGuard group, respectively. CONCLUSION: The LiquoGuard device is a more superior way of CSF drainage in suspected NPH patients, with reduced morbidity and length of stay.

Radiological predictors of shunt response in the diagnosis and treatment of idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

BACKGROUND: Patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) may improve clinically following cerebrospinal fluid (CSF) diversion (shunt) surgery, though the predictors of shunt response remain debated. Currently, radiological features play an important role in the diagnosis of iNPH, but it is not well established which radiological markers most precisely predict shunt responsive iNPH. OBJECTIVE: To conduct a systematic review and meta-analysis to identify radiological predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most predictive radiological features. METHODS: Embase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating radiological predictors of shunt response in iNPH patients. Included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using a univariate meta-analysis. RESULTS: Overall, 301 full-text papers were screened, of which 28 studies were included, and 26 different radiological features were identified, 5 of these met the inclusion criteria for the meta-analysis: disproportionately enlarged subarachnoid space (DESH), callosal angle, periventricular white matter changes, cerebral blood flow (CBF), and computerized tomography cisternography. The meta-analysis showed that only callosal angle and periventricular white matter changes significantly differentiated iNPH shunt responders from non-responders, though both markers had a low diagnostic odds ratio (DOR) of 1.88 and 1.01 respectively. None of the other radiological markers differentiated shunt responsive from shunt non-responsive iNPH. CONCLUSION: Callosal angle and periventricular changes are the only diagnostically effective radiological predictors of shunt responsive iNPH patients. However, due to the DORs approximating 1, they are insufficient as sole predictors and are advised to be used only in combination with other diagnostic tests of shunt response. Future research must evaluate the combined use of multiple radiological predictors, as it may yield beneficial additive effects that may allow for more robust radiological shunt response prediction.