A new test for evaluation of marginal cognitive function deficits in idiopathic normal pressure hydrocephalus through expressing texture recognition by sound symbolic words.

Introduction: The number of dementia patients is increasing with population aging. Preclinical detection of dementia in patients is essential for access to adequate treatment. In previous studies, dementia patients showed texture recognition difficulties. Onomatopoeia or sound symbolic words (SSW) are intuitively associated with texture impressions and are less likely to be affected by aphasia and description of material perception can be easily obtained. In this study, we aimed to create a test of texture recognition ability expressed by SSW to detect the presence of mild cognitive disorders. Methods: The sound symbolic words texture recognition test (SSWTRT) is constructed from 12 close-up photos of various materials and participants were to choose the best SSW out of 8 choices to describe surface texture in the images in Japanese. All 102 participants seen in Juntendo University Hospital from January to August 2023 had a diagnosis of possible iNPH (age mean 77.9, SD 6.7). The answers were scored on a comprehensive scale of 0 to 1. Neuropsychological assessments included MMSE, FAB, and the Rey Auditory Verbal Learning Test (RAVLT), Pegboard Test, and Stroop Test from the EU-iNPH Grading Scale (GS). In study 1 the correlation between SSWTRT and the neuropsychological tests were analyzed. In study 2, participants were divided into two groups: the Normal Cognition group (Group A, n = 37) with MMSE scores of 28 points or above, and the Mild Cognitive Impairment group (Group B, n = 50) with scores ranging from 22 to 27 points, and its predictability were analyzed. Results: In study 1, the total SSWTRT score had a moderate correlation with the neuropsychological test results. In study 2, there were significant differences in the SSWTRT scores between groups A and B. ROC analysis results showed that the SSWTR test was able to predict the difference between the normal and mildly impaired cognition groups. Conclusion: The developed SSWTRT reflects the assessment results of neuropsychological tests in cognitive deterioration and was able to detect early cognitive deficits. This test not only relates to visual perception but is likely to have an association with verbal fluency and memory ability, which are frontal lobe functions.

[Causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus: a two-sample bidirectional Mendelian randomization study].

OBJECTIVE: To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus (iNPH) using two-sample bidirectional Mendelian randomization. METHODS: The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog, FinnGenR10 and MRCIEU GWAS. The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10. We used the inverse-variance weighted (IVW) method to perform the principal analyses. Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger­intercept test performed to evaluate the pleiotropy for sensitivity analyses. RESULTS: IVW result showed that frequent daytime nap was associated with higher odds of iNPH (OR=3.3393, 95 CI% : 1.0646-10.4742, P=0.0270). Cochrane Q-statistics test and MR Egger­intercept test showed that the MR analysis had no pleiotropy or heterogeneity (P > 0.05). The external validation reproduced this result (OR=2.5660, 95 CI% : 1.1680-5.6373, P=0.0189; OR=4.0424, 95 CI% : 1.5709-10.4024, P=0.0038). Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype. CONCLUSION: The frequency of daytime naps is causally associated with iNPH, and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

Forget About Memory: Disentangling the Amnestic Syndrome in Idiopathic Normal Pressure Hydrocephalus.

Background: Idiopathic normal pressure hydrocephalus (iNPH) can present with both episodic amnestic syndrome and biomarkers of Alzheimer's disease (AD) pathology. Objective: To examine the associations between amnestic syndrome and cerebrospinal fluid (CSF) AD biomarkers in iNPH and the CSF tap test response in iNPH patients with amnestic syndrome. Methods: We used the Free and Cued Selective Reminding Test to divide iNPH into amnestic and non-amnestic patients. We compared their clinical, biological, and radiological characteristics and examined the reversibility of gait spatiotemporal parameters and neuropsychological performances after a CSF tap test. Univariate and multiple linear regression models examined the association between memory performance and clinical-biological characteristics. Results: Sixty-two non-amnestic patients (mean age 77.0±7.0 years, 38.7% female) and thirty-eight amnestic patients (mean age 77.0±5.9 years, 36.8% female) presented similar levels of AD biomarkers and clinical-radiological profiles. Global cognition and education levels were lower in the amnestic iNPH group. We found no association between AD biomarkers and memory performances (total tau: ß= -4.50; 95% CI [-11.96;2.96]; p = 0.236; amyloid-ß (1-42): ß= 8.60, 95% CI [-6.30;23.50]; p = 0.240). At baseline, amnestic iNPH patients performed worse on executive functions, attention, and gait speed but improved similarly to the non-amnestic iNPH patients after the tap test. Conclusions: In our clinical sample of iNPH patients, we confirm the lack of specificity of the amnestic profile for predicting AD pathology. Clinicians should not preclude amnestic iNPH patients from undergoing an invasive procedure of CSF derivation.

The contribution of cognitive reserve in explaining the dual-task walking performance in iNPH patients: comparison with other cognitive, functional, and socio-demographic variables.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance. AIMS: The objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P). METHODS: 68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables. RESULTS: Simple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (ß > 0.3, p < .001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale. CONCLUSION: As CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater.

"Artificial intelligence-driven infection risk prediction in ventriculoperitoneal shunting: a novel approach for normal pressure hydrocephalus treatment".

Idiopathic normal pressure hydrocephalus (iNPH) affects approximately 1.5% of the population, with a higher prevalence in men than women. Ventriculoperitoneal shunting (VPS) is the standard treatment for iNPH, but it poses a notable risk of infection, occurring in 8-10% of cases. Recent advancements in non-invasive diagnostic techniques, such as superb microvascular ultrasound (SMI), have demonstrated potential in evaluating cerebrospinal fluid (CSF) flow within VPS systems. A single-center feasibility study involving 19 asymptomatic patients with VPS systems showed that SMI reliably detected CSF flow in the proximal catheter in all patients and in the distal catheter in 89.5%, while reductions in optic nerve sheath diameter (ONSD) indicated lowered intracranial pressure after shunt activation. These findings suggest that SMI could serve as a safer alternative to invasive methods for assessing shunt function. Additionally, artificial intelligence (AI)-based approaches are being explored to reduce infection risk and enhance shunt efficacy. An artificial neural network (ANN) model achieved an 83.1% accuracy in predicting infection risk, surpassing traditional logistic regression models. However, the study's limitations, including its retrospective design, small sample size, and single-center nature, underscore the need for larger multi-center studies to confirm the generalizability of these findings. Further research is essential to validate the effectiveness of these innovations and their potential to improve patient outcomes in hydrocephalus management.

Artificial Intelligence for Prediction of Shunt Response in Idiopathic Normal Pressure Hydrocephalus: A Systematic Review.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a reversible cause of dementia, typically treated with shunt surgery, although outcomes vary. Artificial intelligence (AI) advancements could improve predictions of shunt response (SR) by analyzing extensive data sets. METHODS: We conducted a systematic review to assess AI's effectiveness in predicting SR in iNPH. Studies using AI or machine learning (ML) algorithms for SR prediction were identified through searches in MEDLINE, EMBASE, and Web of Science up to September 2023, adhering to Synthesis Without Meta-Analysis reporting guidelines. RESULTS: Out of 3541 studies identified, 33 were assessed for eligibility, and 8 involving 479 patients were included. Study sample sizes varied from 28 to 132 patients. Common data inputs included imaging/radiomics (62.5%) and demographics (37.5%), with Support Vector Machine being the most frequently used ML algorithm (87.5%). Two studies compared multiple algorithms. Only four studies reported the Area Under the Curve (AUC) values, which ranged between 0.80 and 0.94. The results highlighted inconsistency in outcome measures, data heterogeneity, and potential biases in the models used. CONCLUSIONS: While AI shows promise for improving iNPH management, there is a need for standardized data and extensive validation of AI models to enhance their clinical utility. Future research should aim to develop robust and generalizable AI models for more effective diagnosis and management of iNPH.

Association between idiopathic normal pressure hydrocephalus and Alzheimer's disease: a bidirectional Mendelian randomization study.

Observational studies have suggested a bidirectional relationship between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). However, the causal association between these two neurodegenerative disorders remains unclear. This study aimed to explore the causal relationship between iNPH and AD using a two-sample bidirectional Mendelian randomization (MR) method. Large-scale genome-wide association studies of iNPH (Ncase = 767, Ncontrol = 375,610) and AD (Ncase/proxy = 111,326, Ncontrol = 677,663) in European individuals were used to screen genetic instruments for MR analysis. Inverse variance-weighted (IVW) method was used as the main analysis, other MR methods and a series of sensitivity analyses were performed to ensure the reliability. In the forward MR analysis, genetic predisposition to iNPH had no effects on the risk of AD development. Likewise, in the reverse MR analysis, AD did not demonstrate a significant causal effect on iNPH. Sensitivity analyses bolstered the reliability of the MR results. Our MR study indicated no genetic evidence supporting a suggestive association between AD and iNPH in either direction, and provided evidence on the dichotomy between true iNPH and neurodegenerative NPH.

In Vivo Prevalence of Beta-Amyloid Pathology and Alzheimer's Disease Co-Pathology in Idiopathic Normal-Pressure Hydrocephalus-Association with Neuropsychological Features.

Idiopathic normal-pressure hydrocephalus (iNPH) is a clinic-radiological neurological syndrome presenting with cognitive deficits, gait disturbances and urinary incontinence. It often coexists with Alzheimer's disease (AD). Due to the reversible nature of iNPH when promptly treated, a lot of studies have focused on possible biomarkers, among which are cerebrospinal fluid (CSF) biomarkers. The aim of the present study was to determine the rate of beta-amyloid pathology and AD co-pathology by measuring AD CSF biomarkers, namely, amyloid beta with 42 and 40 amino acids (Aß42), the Aß42/Aß40 ratio, total Tau protein (t-Tau) and phosphorylated Tau protein at threonine 181 (p-Tau), in a cohort of iNPH patients, as well as to investigate the possible associations among CSF biomarkers and iNPH neuropsychological profiles. Fifty-three patients with iNPH were included in the present study. CSF Aß42, Aß40, t-Tau and p-Tau were measured in duplicate with double-sandwich ELISA assays. The neuropsychological evaluation consisted of the Mini-Mental State Examination, Frontal Assessment Battery, Five-Word Test and CLOX drawing tests 1 and 2. After statistical analysis, we found that amyloid pathology and AD co-pathology are rather common in iNPH patients and that higher values of t-Tau and p-Tau CSF levels, as well as the existence of the AD CSF profile, are associated with more severe memory impairment in the study patients. In conclusion, our study has confirmed that amyloid pathology and AD-co-pathology are rather common in iNPH patients and that CSF markers of AD pathology and t-Tau are associated with a worse memory decline in these patients.

Correlation between GLCM-based texture features of the lateral pterygoid muscle and cognitive function in patients with idiopathic normal pressure hydrocephalus: a preliminary report.

PURPOSE: The potential relationship between mastication ability and cognitive function in idiopathic normal pressure hydrocephalus (iNPH) patients is unclear. This report investigated the association between mastication and cognitive function in iNPH patients using the gray level of the co-occurrence matrix on the lateral pterygoid muscle. METHODS: We analyzed data from 96 unoperated iNPH patients who underwent magnetic resonance imaging (MRI) between December 2016 and February 2023. Radiomic features were extracted from T2 MRI scans of the lateral pterygoid muscle, and muscle texture parameters were correlated with the iNPH grading scale. Subgroup analysis compared the texture parameters of patients with normal cognitive function with those of patients with cognitive impairment. RESULTS: The mini-mental state examination score correlated positively with the angular second moment (P < 0.05) and negatively with entropy (P < 0.05). The dementia scale (Eide's classification) correlated negatively with gray values (P < 0.05). Gray values were higher in the cognitive impairment group (64.7 ± 16.6) when compared with the non-cognitive impairment group (57.4 ± 13.3) (P = 0.005). Entropy was higher in the cognitive impairment group (8.2 ± 0.3) than in the non-cognitive impairment group (8.0 ± 0.3) (P < 0.001). The area under the receiver operating characteristic curve was 0.681 (P = 0.003) and 0.701 (P < 0.001) for gray value and entropy, respectively. CONCLUSION: Our findings suggest an association between heterogeneity of mastication and impaired cognitive function in iNPH patients and highlight muscle texture analysis as a potential tool for predicting cognitive impairment in these patients.

Impact of standardized care guidelines featuring next-day discharge on outcome, healthcare consumption, and patient healthcare experience in patients with idiopathic normal pressure hydrocephalus receiving ventriculoperitoneal shunts.

OBJECTIVE: The aim of this study was to evaluate the effect of standardized care guidelines featuring next-day discharge on hospital length of stay (LOS), outcomes, patient experience, and healthcare consumption in patients receiving ventriculoperitoneal shunts (VPSs) for idiopathic normal pressure hydrocephalus (iNPH). METHODS: This single-center population-based observational cohort study included 271 adult iNPH patients who underwent VPS surgery at Karolinska University Hospital. Groups were compared before and after the implementation of new standardized discharge guidelines. The primary outcome was the hospital LOS. Secondary outcomes included postoperative complications, patient experience, and frequency of unscheduled outpatient follow-up appointments. RESULTS: A total of 121 patients were treated with variable hospitalization periods. One hundred fifty patients were managed under the new guidelines stipulating next-day discharge. There was no significant difference in positive surgical outcome (66% vs 71%, p = 0.372) or rates of complication (p ≥ 0.066) between groups. The standardized guidelines group had a significantly shorter period of inpatient hospitalization (1 vs 2 days, p < 0.001) and demonstrated lower levels of unscheduled outpatient healthcare consumption (p < 0.001) while maintaining levels of positive patient experience (p = 0.828). CONCLUSIONS: Standardized discharge guidelines featuring next-day discharge are safe for iNPH patients undergoing VPS surgery, maintain the quality of the patient experience, and are an effective method for mitigating healthcare consumption in an expanding patient group.

Awareness level of idiopathic normal pressure hydrocephalus among health-care providers.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that primarily affects the geriatric population. It was first introduced by Adams et al. in 1965. A gradual decline in cognitive function, urinary incontinence, and gait disturbances characterizes the disease. This condition is believed to be underdiagnosed, and awareness of such pathology is vital, as the treatment is very effective and can reverse the symptoms. Methods: This questionnaire-based cross-sectional study aimed to assess awareness levels regarding iNPH among non-neuroscience healthcare providers in Saudi Arabia. Results: A total of 269 healthcare providers participated in this study, with data collected through an online questionnaire. About 80.6% of the participants had heard of the disease, while 56.5% were aware of the disease symptomology. About 50% of physicians did not encounter iNPH patients in clinical practice. Previous clinical exposure to iNPH patients correlates significantly with an awareness of disease symptoms, investigation, treatment modalities, and outcome. Clinical experience positively impacts physicians' awareness as it correlates with a better understanding of diagnostic methods and disease outcomes. Conclusion: The study highlights the need for targeted educational interventions, especially among family physicians and general practitioners with no previous experience with iNPH patients, as well as interdisciplinary collaboration to address gaps in awareness and enhance early diagnosis of iNPH patients.

Genetics and molecular pathophysiology of normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is characterized by dilation of the cerebral ventricles without increased cerebral pressure. Patients typically present with cognitive impairment, gait abnormalities, and urinary incontinence. Despite current guidelines for diagnosis and surgical intervention, there is little consensus on the pathophysiology of iNPH. Familial cases and genomic studies of iNPH have recently suggested an underappreciated role of genetics in disease pathogenesis, implicating mechanisms ranging from dysregulated CSF dynamics to underlying neurodegenerative or neuroinflammatory processes. In this paper, the authors provide a brief review of genetic insights and candidate genes for iNPH, highlighting the continued importance of integrated genetic analysis and clinical studies to advance iNPH management.

Cerebral venous thrombosis after lumboperitoneal shunting: A case report.

Lumboperitoneal shunt (LPS) has been an effective treatment of idiopathic normal pressure hydrocephalus (iNPH) but sometimes causes serious complications. Here we present the first reported case of cerebral venous thrombosis (CVT) after LPS. A 76-year-old man underwent LPS for iNPH and a week later developed weakness of the right arm and a generalized tonic-clonic seizure. Brain computed tomography and magnetic resonance imaging showed bilateral subdural hematoma (SDH) and left cortical vein thrombosis. Intravenous heparin was administered, followed by surgical evacuation of the SDH. The patient experienced gradual improvement and was subsequently discharged. It is conceivable that overdrainage of cerebrospinal fluid led to the development of both SDH and CVT. CVT is potentially fatal and should be recognized early as a possible complication after LPS to allow prompt treatment.

Reduced awareness of cognitive deficits in idiopathic normal pressure hydrocephalus and its change following lumbar puncture.

OBJECTIVE: Awareness of cognitive deficits is related to executive functions and may, therefore, be sensitive to the effects of lumbar puncture (LP) in idiopathic normal pressure hydrocephalus (iNPH). Although a reduction in awareness of cognitive deficits (RACD) has been previously described in iNPH, there is a lack of systematic, psychometrically validated reports. In this study, we investigated RACD and its LP-related changes in iNPH patients and compared them with those in clinical and healthy control groups. METHODS: RACD was assessed before and after lumbar puncture (LP) in 24 patients (14 iNPH, 10 other age-associated cognitive syndromes; AACS) and compared with 23 healthy controls (HC), employing two RACD measures alongside cognitive examination. Local metacognition was measured using a visual percentile-based rating system and operationalized as the t-scaled distance between the participants' task-specific performance estimations and their objective test performance (ΔTSPE). Global metacognition, targeting broader estimates of cognitive functioning (ECF), was quantified by subtracting self- from informant-obtained sum scores on a questionnaire evaluating participants' dysexecutive problems (DEX-DS). Within-group and between-group differences in ΔTSPE and DEX-DS scores were compared non-parametrically, focusing on post-LP changes. RESULTS: Averaged ΔTSPE was higher in the patient groups and mirrored the groups' lower objective test performance, while averaged DEX-DS showed no group difference. Following LP, group comparisons revealed iNPH-specific decrease in both RACD measures. CONCLUSION: Our study revealed LP-related RACD changes in iNPH patients compared to those in AACS and HC participants. The results suggest a mitigation of impaired metacognitive abilities in iNPH, possibly resulting from LP-induced improvements in (local) metacognitive performance, facilitating ECF adjustment alongside a metacognitively stimulating testing procedure.

Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis.

Background and objective: Neuroinflammatory processes have been identified as playing a crucial role in the pathophysiology of various neurodegenerative diseases, including idiopathic normal-pressure hydrocephalus (iNPH). iNPH, defined as a common disease of cognitive impairment in older adults, poses major challenges for therapeutic interventions owing to the stringent methodological requirements of relevant studies, clinical heterogeneity, unclear etiology, and uncertain diagnostic criteria. This study aims to assess the relationship between circulating inflammatory biomarkers and iNPH risk using bidirectional two-sample Mendelian randomization (MR) combined with meta-analysis. Methods: In our bidirectional MR study, genetic data from a genome-wide association study (GWAS) involving 1,456 iNPH cases and 409,726 controls of European ancestry were employed. Single-nucleotide polymorphisms (SNPs) associated with exposures served as instrumental variables for estimating the causal relationships between iNPH and 132 types of circulating inflammatory biomarkers from corresponding GWAS data. Causal associations were primarily examined using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode analyses. In the results, heterogeneity was assessed using the Cochran Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers test. Sensitivity analysis was conducted through leave-one-out analysis. Reverse MR analyses were performed to mitigate bias from reverse causality. Meta-analyses of identical inflammatory biomarkers from both data sources strengthened the findings. Results: Results indicated a genetically predicted association between Interleukin-16 (IL-16) [OR: 1.228, 95% CI: 1.049-1.439, p = 0.011], TNF-related apoptosis ligand (TRAIL) [OR: 1.111, 95% CI: 1.019-1.210, p = 0.017] and Urokinase-type plasminogen activator (uPA) [OR: 1.303, 95% CI: 1.025-1.658, p = 0.031] and the risk of iNPH. Additionally, changes in human Glial cell line-derived neurotrophic factor (hGDNF) [OR: 1.044, 95% CI: 1.006-1.084, p = 0.023], Matrix metalloproteinase-1 (MMP-1) [OR: 1.058, 95% CI: 1.020, 1.098, p = 0.003] and Interleukin-12p70 (IL-12p70) [OR: 0.897, 95% CI: 0.946-0.997, p = 0.037] levels were identified as possible consequences of iNPH. Conclusion: Our MR study of inflammatory biomarkers and iNPH, indicated that IL-16, TRAIL, and uPA contribute to iNPH pathogenesis. Furthermore, iNPH may influence the expression of hGDNF, MMP-1, and IL-12p70. Therefore, targeting specific inflammatory biomarkers could be promising strategy for future iNPH treatment and prevention.

Ventriculoperitoneal shunt patients and glaucoma: a cohort analysis of the NPH registry.

BACKGROUND: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a chronic condition affecting the elderly. It is characterized by a triad of symptoms and radiological findings. Glaucoma is the leading cause of irreversible blindness worldwide. Earlier studies have proposed that the rate of glaucoma is higher in iNPH patients, and of a possible link between ventriculoperitoneal shunt (VP) treatment and the development of glaucoma. OBJECTIVES: This study aimed to determine the prevalence of glaucoma among iNPH patients and assess the impact of VPs on glaucoma prevalence. METHODS: A cohort study was conducted at Kuopio University Hospital (KUH), including 262 patients with a ventriculoperitoneal shunt. Clinical data were obtained from the Kuopio NPH Registry and medical records. Patients were grouped by iNPH status: iNPH (+) - probable/possible iNPH (n = 192), and iNPH (-) - other causes of hydrocephalus (congenital, secondary, obstructive) (n = 70). We conducted statistical analysis using the Independent Samples T-test, Fisher's exact test, and Pearson Chi-Square. We compared demographics, glaucoma prevalence, brain biopsies positive for Amyloid-ß (Aß) and hyperphosphorylated tau (HPτ) as well as comorbidities for hypertension and diabetes medication. Age stratification assessed glaucoma prevalence in the full cohort. RESULTS: Both iNPH (+) and iNPH (-) groups had comparable demographic and comorbidity profiles. The prevalence of glaucoma in the iNPH (+) group was 11.5% (n = 22) and 11.4% (n = 8) in the iNPH (-) group without a statistically significant difference (p = 1.000). Brain biopsies positive for Amyloid-ß (Aß) and hyperphosphorylated tau (HPτ) were similar. CONCLUSIONS: Neither shunted iNPH patients nor those with a comorbid condition other than iNPH showed a markedly higher prevalence of glaucoma. Instead, both groups exhibited age-related increases in glaucoma prevalence, similar to the trends observed in population-based studies. Our data does not suggest a correlation between VP shunts and an elevated rate of glaucoma.

CSF formation rate-a potential glymphatic flow parameter in hydrocephalus?

BACKGROUND: Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort. METHODS: CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978. RESULTS: Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135). CONCLUSIONS: The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.

Diffusion spectrum imaging in patients with idiopathic normal pressure hydrocephalus: correlation with ventricular enlargement.

BACKGROUND: To investigate the association between white matter changes and ventricular expansion in idiopathic normal pressure hydrocephalus (iNPH) based on diffusion spectrum imaging (DSI). METHODS: We included 32 patients with iNPH who underwent DSI using a 3T MRI scanner. The lateral ventricles were manually segmented, and ventricular volumes were measured. Two methods were utilised in the study: manual region-of-interest (ROI) delineation and tract diffusion profile analysis. General fractional anisotropy (GFA) and fractional anisotropy (FA) were extracted in different white matter regions, including the bilateral internal capsule (anterior and posterior limbs) and corpus callosum (body, genu, and splenium) with manual ROI delineation. The 18 main tracts in the brain of each patient were extracted; the diffusion metrics of 100 equidistant nodes on each fibre were calculated, and Spearman's correlation coefficient was used to determine the correlation between diffusion measures and ventricular volume of iNPH patients. RESULTS: The GFA and FA of all ROI showed no significant correlation with lateral ventricular volume. However, in the tract diffusion profile analysis, lateral ventricular volume was positively correlated with part of the cingulum bundle, left corticospinal tract, and bilateral thalamic radiation posterior, whereas it was negatively correlated with the bilateral cingulum parahippocampal (all p < 0.05). CONCLUSIONS: The effect of ventricular enlargement in iNPH on some white matter fibre tracts around the ventricles was limited and polarizing, and most white matter fibre tract integrity changes were not associated with ventricular enlargement; this reflects that multiple pathological mechanisms may have been combined to cause white matter alterations in iNPH.

Is endoscopic third ventriculostomy a viable treatment option for normal pressure hydrocephalus? A systematic review.

Background: Endoscopic third ventriculostomy (ETV) is considered an alternative treatment for hydrocephalus and has become a standard of care for obstructive hydrocephalus. Recent studies have also explored its role in normal pressure hydrocephalus (NPH). We conducted a systematic review aiming to assess the outcomes of this minimally invasive endoscopic technique as a viable treatment option for NPH. Methods: A systematic literature search was performed using PubMed and Scopus databases, using iterations of search terms "Endoscopic third ventriculostomy," "Idiopathic normal pressure hydrocephalus," and "Normal pressure hydrocephalus." To be eligible for inclusion in the review, articles had to report the usage of ETV as a primary treatment modality for NPH, report its outcomes, and be published in the English language. Results: Out of the 13 studies selected for qualitative synthesis, nine supported the use of ETV for NPH as an effective treatment option with improvement in the preoperative symptoms. Two studies favored shunt over ETV, stating that quality of life is better with VP shunt insertion. One study reported that ETV has higher perioperative mortality rates that outweigh its benefits. One study reported it to be an ineffective surgical option. Conclusion: The current review of evidence does not support the use of ETV for the treatment of NPH, except perhaps in a small subset of patients. These patients have a shorter duration of symptoms and a better preoperative neurological status. The lumbar infusion test and ventricular infusion test are modalities useful for selecting these candidates.

Evaluation of imaging indicators in differentiating idiopathic normal pressure hydrocephalus from Alzheimer's disease.

BACKGROUND: There are currently many imaging indicators for idiopathic normal pressure hydrocephalus (iNPH). However, their diagnostic performance has not been well compared, especially in differentiating iNPH from Alzheimer's disease (AD). This study aimed to evaluate the diagnostic performance of these imaging indicators in differentiating iNPH from AD. METHODS: We retrospectively collected patients with iNPH from the West China Hospital between June 2016 and December 2023. Age-sex-matched patients with AD and healthy controls (HCs) are included as controls (ChiCTR2300070078, March 2023). Twelve imaging indicators were evaluated on MRI, including disproportionately enlarged subarachnoid space hydrocephalus (DESH), Evans' index (EI), callosal angle, z-EI, temporal horn, dilated Sylvian fissure, focal sulcal dilation, tight high convexity, deep white matter hyperintensities, periventricular hyperintensities, DESH scale, and Simplified Radscale. We analyzed the receiver operating characteristic curves and calculated the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. RESULTS: A total of 46 patients with iNPH (mean age: 73.1 ± 6.5; 35 males), 46 patients with AD (mean age: 73.0 ± 6.6; 35 males), and 46 HCs (mean age: 73.0 ± 5.9; 35 males) were included. The largest area under the receiver operating characteristic curve (AUC) was found in EI (0.93; 95 % CI: 0.89-0.98) and z-EI (0.93; 95 % CI: 0.87-0.98). DESH scale ≥ 6 had the highest specificity (93 %, 43/46). CONCLUSION: EI and z-EI had the best diagnostic performance in differentiating iNPH from AD. The DESH scale could assist in diagnosing iNPH due to its high specificity.