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Purpose: Idiopathic Normal pressure hydrocephalus (iNPH) is an under-diagnosed in elderly patients but none of the diagnostic tests are currently sufficiently sensitive or specific. The objective of this study was to analyze the dynamics of neurofluids by PC-MRI in relation to clinical evolution as measured using the iNPH grading scale after tap-test., Method: We prospectively included patients with suspected iNPH. All these patients underwent PCMRI to assess craniospinal hemohydrodynamics with analysis of the stroke volume of the cephalospinal fluid (CSF) within the Sylvius' aqueduct, within the high cervical subarachnoid spaces and the arteriovenous stroke volume. By this means, we calculated a compliance index. Morphological analysis was carried out using the DESH score. The infusion test was measuring the resistance to CSF flow. We analysed all these parameters according to the clinical improvement of the patients., Results: 23 patients were included. Compliance index assessed by PC-MRI was significantly higher in the group of patients with improvement > 10% (p = 0.015)., Conclusions: Our study highlights the importance of investigating arteriovenous and CSF interactions in iNPH. This involves understanding the physiological and pathophysiological mechanisms related to the circulation of neurofluids. The analysis of the interactions of these neurofluids allows for a comprehensive understanding of the system., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

A woman in her 70s presented with approximately 2 years of sudden-onset gait and cognitive problems. She had been diagnosed with normal pressure hydrocephalus (NPH) and underwent ventriculoperitoneal shunt (VPS) placement 1 year prior. Before VPS placement, brain imaging showed ventriculomegaly and chronic infarction of the right putamen and claustrum. A lumbar drain trial resulted in modest improvement of gait dysfunction. She underwent VPS placement for suspected NPH, but her symptoms remained unchanged. Examination revealed mild cognitive impairment, left-sided and lower body predominant parkinsonism, as well as disproportionately prominent postural instability. Gait analysis showed increased gait variability, reduced velocity and shortened step length bilaterally. Motor and gait abnormalities did not change after administration of levodopa. Her symptoms have remained stable for up to 52 months since symptom onset. We postulate that the infarction affecting the right putamen and claustrum could have led to a higher-level gait disorder mimicking NPH., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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., (© 2024. The Author(s).)

Objective: The aim of this study is to investigate long-term prognostic factors and clinical outcomes in patients with idiopathic normal pressure hydrocephalus (iNPH) treated with ventriculo-peritoneal shunt (VPS)., Methods: This single-center retrospective observational study of prospectively collected data included patients with probable iNPH treated with VPS surgery. All patients underwent complete preoperative assessment, including past medical history and neurological examination, dynamic cerebrospinal fluid (CSF) flow brain magnetic resonance imaging (MRI), and preoperative CSF samplings. NPH-consistent brain MRI findings and favorable responses to CSF subtraction tests were the main factors considered for VPS surgery eligibility. All patients were subsequently followed up every six to twelve months (mean follow-up time 40 months, minimum to maximum interval 6-150 months)., Results: A total of 238 patients with a diagnosis of probable iNPH treated with VPS were enrolled. Age, comorbidities, and response to CSF samplings were not significantly associated with a better long-term outcome after VPS surgery. The results of our retrospective analysis demonstrated a statistically significant association between the presence of preoperative aqueductal CSF flow acceleration on dynamic brain MRI and neurological outcomes at 12 and 18 months after VPS surgery., Conclusions: Long-term outcomes of iNPH patients treated with VPS surgery do not appear to be directly influenced by preoperative comorbidities, age, or responses to CSF samplings. Alterations in preoperative brain MRI CSF dynamics were found to be related to long-term outcomes following VPS surgery, highlighting the role of radiological assessment as a prognostic factor in patients deemed suitable candidates for VPS surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: Several radiological markers have been linked to clinical improvement after shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). However, iNPH has no pathognomonic feature, and patients are still diagnosed as probable, possible, or unlikely cases based on clinical symptoms, imaging findings, and invasive supplementary tests. The predictive value of the disproportionately enlarged subarachnoid space hydrocephalus (DESH) score is not yet conclusively determined, but it might offer a more accurate diagnostic method. The aim of the present retrospective cohort study was to validate the predictive power of the DESH score for clinical improvement after shunt surgery in iNPH patients., Methods: We retrospectively obtained presurgical MRI and/or CT scans from 71 patients with iNPH who underwent ventriculoperitoneal shunt surgery. Radiological images were evaluated for Evans index (EI), corpus callosal angle (CA), tight high convexity (THC), Sylvian fissure dilation, and focal sulci dilation. These markers were aggregated to determine the DESH score. Patient journal entries were used to subjectively determine the extent of improvement in gait function, urinary incontinence, and/or cognition as a measure of shunt surgery response., Results: Multiple logistic regression analysis, controlling for age and sex (α = 0.05), showed that DESH score was significantly correlated (OR 1.77) with subjective shunt-surgery response at a minimum of 1-month follow-up. Patients with higher DESH scores were more likely to have a favorable response to shunt surgery., Conclusion: Aggregating radiological markers into the DESH score is useful for predicting shunt responders among iNPH patients and can aid the selection of patients for surgery. These findings provide further support for the DESH score as a diagnostic tool for iNPH., Competing Interests: Declaration of Competing Interest We, the authors, declare no conflicts of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To use third ventricle morphometric variables as a tool for the selection of patients with idiopathic normal pressure hydrocephalus (iNPH) who are candidates for ventriculoperitoneal shunts (VPS)., Material and Methods: Retrospective study enrolling patients with iNPH. Katzman infusion test was performed and a Rout > 12 mmHg/mL/min was considered a positive result. The transverse diameter and the volume of the third ventricle were measured in the preoperative MRI. Postoperative improvement was assessed with the NPH score. The results were analysed with SPSS software., Results: 52 patients with a mean age of 76 years were analysed. There was no difference in the diameter of the third ventricle among patients with a positive result and those with a negative result in the infusion test (12.28 vs 11.68 mm; p = 0.14). Neither were difference detected in the ventricle volume of both groups (3.6 vs 3.5cc; p = 0.66). Those patients who improved after VPS had a smaller third ventricle compared to those who did not respond after surgery (11.85 mm vs. 12.96 mm; p = 0.009). Diameter and volume of third ventricle present a significant strong correlation (Pearson correlation coefficient = 0.72; p < 0.0001)., Conclusion: Morphometric variables of third ventricle may be useful in predicting a good response to VPS in patients with idiopathic normal pressure hydrocephalus., (Copyright © 2023 Sociedad Española de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The objective of this study was to develop a computational pipeline that extracts objective features of ventriculomegaly from non-contrast CT (NCCT) for the accurate classification of idiopathic normal pressure hydrocephalus (NPH) from headache controls (HCs), Alzheimer's dementia (AD), and posttraumatic encephalomalacia (PTE)., Methods: Patients with possible NPH (n = 79) and a subset with definite NPH (DefNPH; n = 29) were retrospectively identified in the Veterans Affairs Informatics and Computing Infrastructure system, along with the AD (n = 62), PTE (n = 53), and HC (n = 59) cohorts. Image-processing pipelines were developed to extract a novel feature capturing the maximum eccentricity of the lateral ventricles (MaxEccLV), a proxy splenial angle (p-SA), the Evans indices (EI-x, -y, and -z), callosal angle, normalized maximum third-ventricle width, and CSF to brain volume ratio from their NCCT scans. The authors used t-tests to examine group differences in the features and multivariate logistic regression models for classification. Additionally, the NPH versus HC classifier was validated on external data., Results: When NPH and DefNPH were compared with HC, AD, and PTE, significant differences were found in all features except the p-SA, which only significantly differed between NPH and PTE. The test-set area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were 0.98, 100%, and 98.3% for NPH versus HC classification; 0.94, 87.3%, and 85.5% for NPH versus AD; 0.96, 92.4%, and 90.6% for NPH versus PTE; and 0.96, 94%, and 88% for NPH versus the other groups using logistic regression under five-fold cross-validation. Consistently high performance was noted for DefNPH. The NPH versus HC classifier provided an AUC of 0.84, sensitivity of 76.9%, and specificity of 90% when assessed on external data., Conclusions: Including the novel MaxEccLV, this framework computes useful features of ventriculomegaly, which had not previously been algorithmically assessed on NCCT. This framework successfully classified possible and definite NPH from HC, AD, and PTE. Following validation on larger representative cohorts, this objective and accessible tool may aid in screening for NPH and differentiating it from symptomatic mimics such as AD and PTE.

Background: Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study's objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG's responsiveness to shunt surgery., Methods: Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71-79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared., Results: Twenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups., Conclusions: FoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom., (© 2024. The Author(s).)

Background and Purpose: Normal pressure hydrocephalus is a treatable cause of dementia associated with distinct mechanical property signatures in the brain as measured by MR elastography. In this study, we tested the hypothesis that specific anatomic features of normal pressure hydrocephalus are associated with unique mechanical property alterations. Then, we tested the hypothesis that summary measures of these mechanical signatures can be used to predict clinical outcomes., Materials and Methods: MR elastography and structural imaging were performed in 128 patients with suspected normal pressure hydrocephalus and 44 control participants. Patients were categorized into 4 subgroups based on their anatomic features. Surgery outcome was acquired for 68 patients. Voxelwise modeling was performed to detect regions with significantly different mechanical properties between each group. Mechanical signatures were summarized using pattern analysis and were used as features to train classification models and predict shunt outcomes for 2 sets of feature spaces: a limited 2D feature space that included the most common features found in normal pressure hydrocephalus and an expanded 20-dimensional (20D) feature space that included features from all 4 morphologic subgroups., Results: Both the 2D and 20D classifiers performed significantly better than chance for predicting clinical outcomes with estimated areas under the receiver operating characteristic curve of 0.66 and 0.77, respectively ( P < .05, permutation test). The 20D classifier significantly improved the diagnostic OR and positive predictive value compared with the 2D classifier ( P < .05, permutation test)., Conclusions: MR elastography provides further insight into mechanical alterations in the normal pressure hydrocephalus brain and is a promising, noninvasive method for predicting surgical outcomes in patients with normal pressure hydrocephalus., (© 2024 by American Journal of Neuroradiology.)

Aims: Idiopathic Normal pressure hydrocephalus (iNPH) is a neurodegenerative disease characterized by gait disturbance, dementia, and urinary dysfunction. The neural network mechanisms underlying this phenomenon is currently unknown., Methods: To investigate the resting-state functional connectivity (rs-FC) abnormalities of iNPH-related brain connectivity from static and dynamic perspectives and the correlation of these abnormalities with clinical symptoms before and 3-month after shunt. We investigated both static and dynamic functional network connectivity (sFNC and dFNC, respectively) in 33 iNPH patients and 23 healthy controls (HCs)., Results: The sFNC and dFNC of networks were generally decreased in iNPH patients. The reduction in sFNC within the default mode network (DMN) and between the somatomotor network (SMN) and visual network (VN) were related to symptoms. The temporal properties of dFNC and its temporal variability in state-4 were sensitive to the identification of iNPH and were correlated with symptoms. The temporal variability in the dorsal attention network (DAN) increased, and the average instantaneous FC was altered among networks in iNPH. These features were partially associated with clinical symptoms., Conclusion: The dFNC may be a more sensitive biomarker for altered network function in iNPH, providing us with extra information on the mechanisms of iNPH., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

This study aimed to retrospectively review the frequency and clinical features of 13 patients with progressive supranuclear palsy (PSP) and idiopathic normal pressure hydrocephalus (iNPH). All patients were found to have PSP-Richardson's syndrome (PSP-RS). Shunt surgery was effective in 5 of 11 patients (45.5%). A comparison of these 5 patients who responded to shunt surgery versus the remaining 6 patients revealed a significant difference in the reduction of frontal lobe blood flow on cerebral perfusion single-photon emission computed tomography (SPECT) (P = 0.018). These results suggest that PSP-RS is common in patients with PSP and iNPH and indicate the usefulness of cerebral perfusion SPECT in estimating the effect of shunt surgery.

Idiopathic normal pressure hydrocephalus (iNPH), a syndrome characterized by cognitive impairment, gait abnormalities, and urinary incontinence attributable to cerebrospinal fluid circulatory insufficiency, is associated with an obscure etiology. Several methodologies and imaging analysis techniques, including visualization of cerebral hemodynamics and diffusion tensor imaging have emerged in recent years to determine functional alterations in cases of iNPH. These advancements have led to more comprehensive understanding of the pathophysiological mechanisms underlying iNPH. In this article, we discuss the historical evolution of imaging modalities for iNPH and contemporaneous imaging techniques designed to acquire deeper insight into this disease.

Introduction: Enlarged perivascular spaces (ePVS) may be an indicator of glymphatic dysfunction. Limited studies have evaluated the role of ePVS in idiopathic normal pressure hydrocephalus (iNPH). We aimed to characterize the distribution and number of ePVS in iNPH compared to controls., Methods: Thirty-eight patients with iNPH and a pre-shunt MRI were identified through clinical practice. Age- and sex-matched controls who had negative MRIs screening for intracranial metastases were identified through a medical record linkage system. The number of ePVS were counted in the basal nuclei (BN) and centrum semiovale (CS) using the Wardlaw method blinded to clinical diagnosis. Imaging features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), callosal angle, Fazekas white matter hyperintensity (WMH) grade, and the presence of microbleeds and lacunes were also evaluated., Results: Both iNPH patients and controls had a mean age of 74 ± 7 years and were 34% female with equal distributions of hypertension, dyslipidemia, diabetes, stroke, and history of smoking. There were fewer ePVS in the CS of patients with iNPH compared to controls (12.66 vs. 20.39, p < 0.001) but the same in the BN (8.95 vs. 11.11, p = 0.08). This remained significant in models accounting for vascular risk factors (p = 0.002) and MRI features of DESH and WMH grade (p = 0.03)., Conclusions: Fewer centrum semiovale ePVS may be a biomarker for iNPH. This pattern may be caused by mechanical obstruction due to upward displacement of the brain leading to reduced glymphatic clearance., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Very divergent prevalence rates for idiopathic normal pressure hydrocephalus (iNPH) are reported, probably due to differences in study sample selection and diagnostic criteria. This MRI-based study aimed to determine the prevalence of iNPH and iNPH-specific radiologic changes and their association with clinical symptoms in a large, 70-year-old population-based cohort (Gothenburg H70)., Methods: In this cross-sectional study, disturbances in gait and balance, cognition, and urinary continence were assessed using clinical examination and self-report. MRI was evaluated for iNPH-specific imaging markers. iNPH was diagnosed according to International Guidelines (I.G.). Based on radiologic findings, participants were allocated to 1 of 4 groups: (A) Evans index (EI) ≤0.3 (reference), (B) EI >0.3 without other iNPH-typical radiologic findings, (C) radiologically probable iNPH according to I.G., and (D) radiologically holistically probable ( h -probable) iNPH fulfilling radiologic criteria according to I.G. plus highly iNPH-specific changes according to an experienced neuroradiologist., Results: The Gothenburg H70 Studies include 791 individuals (377 men, 414 women) born in 1944 who underwent brain MRI. The prevalence of iNPH was 1.5% (2.1% for men, 0.96% for women) according to I.G. Ninety participants (11%) had EI >0.3 without other iNPH-typical radiologic findings, 29 (3.7%) fulfilled the I.G. radiologic probable iNPH criteria alone, and 11 (1.4%) were classified as radiologically h -probable iNPH. Forty participants (5.1%) had I.G. radiologic features of iNPH (70% men vs 30% women, p = 0.005). Gait disturbances were more common in participants with EI >0.3 without other radiologic iNPH features (B) (33%) compared with the reference group (A) (19%) ( p = 0.006). All clinical symptoms were more common in participants with I.G. radiologic features of iNPH (C + D) than they were in the reference group (A) ( p < 0.03)., Discussion: The iNPH prevalence of 1.5% among 70-year-olds, which is considerably higher than earlier reported in this age group, suggests that iNPH may be more common than previously assumed. This is supported by the 5.1% total prevalence of imaging signs of iNPH. Ventriculomegaly without other iNPH-typical radiologic findings may be an early sign of developing iNPH in some patients.

Aim: To prove the superiority of the electromagnetic (EM) neuronavigation technique to increase the accuracy of intraventicular shunt catheter placement, and to reduce accompanying complications., Material and Methods: A total of 21 patients with hydrocephalus [age range (years): 53-84] were studied. All of them had undergone thin-slice, navigation-compatible, computed tomography (CT) preoperatively. Shunt surgery was performed under the guidance of EM neuronavigation technology. All patients underwent follow-up CT the next day to evaluate catheter tip placement and were followed up at 1, 3, 6, and 12 months., Results: All catheter tips were placed properly in front of the foramen of Monro in the desired position, except in one case in which the tip migrated to the perimesencephalic cistern and underwent reoperation in the early postoperative period. No complications due to infection and obstruction were observed in the medium- and long-term follow-ups. The complication rate due to the incorrect catheter positioning was 4.76% of the total cases., Conclusion: The placement of the ventricular catheter under EM-guided navigation technology reduces the proximal-end failure caused by malpositioning, obstruction, and infection.

Neurosarcoidosis (NS) is a rare subtype of sarcoidosis with a poor prognosis and diverse clinical presentations that often poses a diagnostic and therapeutic challenge. We describe the case of a 53-year-old male with an initial diagnosis of lingual sarcoidosis, who subsequently developed ataxia and rapidly progressive cognitive impairment. A lumbar puncture revealed hypoglycorrhachia, hyperproteinorrachia, lymphocytic pleocytosis, and elevated IL-6 levels (600 pg/ml). Cerebrospinal fluid flow cytometry showed an elevated CD4 lymphocyte concentration and a CD4+/CD8+ ratio of 3.91, indicative of NS. Brain MRI showed hyperintense periventricular and subcortical lesions on FLAIR/T2 resembling progressive multifocal leukoencephalopathy (PML), although negative PCR for JC virus ruled out the differential diagnosis. Following a favorable evolutionary course with corticosteroid pulses, the patient relapsed with normotensive hydrocephalus, treated with immunosuppressants and ventriculoperitoneal shunting with a good response to date. This case underscores the importance of maintaining a high index of suspicion for NS in individuals with sarcoidosis and neurologic symptoms. In these cases, cerebrospinal fluid biomarkers such as IL-6 and CD4+/CD8+ ratio are essential to guide the diagnosis. Furthermore, it highlights that hydrocephalus is a rare complication and requires a multidisciplinary approach, including medical and neurosurgical treatment.

Idiopathic normotensive hydrocephalus (iNH) is a widespread disease in elderly patients. The effectiveness of iNG treatment and the subsequent quality of patients' lives directly depends on timely and early diagnosis. The criteria for diagnosing iNG that are used in neuroimaging can also be found in patients without clinical manifestations of this disease, and the widely used tap-test is an invasive technique with a rather low sensitivity. The need for early diagnosis and initiation of treatment before the development of irreversible damage to brain structures determines the relevance of the search for an accessible, minimally invasive, accurate and safe diagnostic method. The article presents a clinical observation of the use of phase-contrast MRI of cerebrospinal fluid (CSF) in a female patient with a positive response to the tap test with a quantitative analysis of changes in CSF flow parameters and ALVI and Evans indices depending on the time after CSF evacuation. Phase-contrast MRI of CSF with a quantitative assessment of CSF flow parameters in combination with an assessment of the ALVI index has the potential to increase the accuracy of diagnosing iNH and is of scientific interest for further research.

Background: Determination of the ventricle size in idiopathic normal pressure hydrocephalus (iNPH) is essential for diagnosis and follow-up of shunt results. Fully automated segmentation methods are anticipated to optimize the accuracy and time efficiency of ventricular volume measurements. We evaluated the accuracy of preoperative and postoperative ventricular volume measurements in iNPH by a magnetic resonance imaging (MRI)-based licensed software for fully automated quantitative assessment., Methods: Forty-eight patients diagnosed with iNPH were retrospectively analyzed. All patients received a ventriculoperitoneal shunt and had symptom grading and routine MRI preoperatively and 3-6 months postoperatively. Ventricular volumes, generated by fully automated T1-weighted imaging volume sequence segmentation, were compared with semiautomatic measurements and routine radiologic reports. The relation of postoperative ventricular size change to clinical response was evaluated., Results: Fully automated segmentation was achieved in 95% of the MRIs, but showed various rates of 8 minor segmentation errors. The correlation between both segmentation methods was very strong (r >0.9) and the agreement very good using Bland-Altman analyses. The ventricular volumes differed significantly between semiautomated and fully automated segmentations and between preoperative and postoperative MRI. The fully automated method systematically overestimated the ventricles by a median 15 mL preoperatively and 14 mL postoperatively; hence, the magnitudes of volume changes were equivalent. Routine radiologic reports of ventricular size changes were inaccurate in 51% and lacked association with treatment response. Objectively measured ventricular volume changes correlated moderately with postoperative clinical improvement., Conclusions: A fully automated volumetric method permits reliable evaluation of preoperative ventriculomegaly and postoperative ventricular volume change in idiopathic normal pressure hydrocephalus., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Interest in interstitial fluid dynamics has increased since the proposal of the glymphatic system hypothesis. Abnormal dynamics of the interstitial fluid have been pointed out to be an important factor in various pathological statuses. In this article, we propose the concept of central nervous system interstitial fluidopathy as a disease or condition in which abnormal interstitial fluid dynamics is one of the important factors for the development of a pathological condition. We discuss the aspects of interstitial fluidopathy in various diseases, including Alzheimer's disease, Parkinson's disease, normal pressure hydrocephalus, and cerebral small vessel disease. We also discuss a method called "diffusion tensor image analysis along the perivascular space" using MR diffusion images, which is used to evaluate the degree of interstitial fluidopathy or the activity of the glymphatic system.

Objective: Idiopathic normal pressure hydrocephalus (iNPH) affects elderly individuals and is characterized by a progressive deterioration of gait, urinary continence, and cognition. In most cases, it is reversible with treatment. INPH is not uncommonly an unrecognized cause of dementia. We wish to raise awareness of iNPH among primary care providers who are seeing these patients first., Methods: We reviewed the current epidemiological data regarding iNPH as well as epidemiological data regarding Alzheimer disease. We searched for the most sensitive radiological screening test for iNPH., Results: Alzheimer disease comprises 60%-70% of all dementia cases, in 2023 is affecting 6.7 million Americans, about 10.7% of people 65 and older. Epidemiological data from the Scandinavian countries confirmed that 3.7% of people older than 65 have iNPH. Surgical studies confirmed the presence of early Alzheimer's pathology in about 25% of operated patients with iNPH. Useful radiological findings of iNPH include an Evans Index greater than 0.30, and a disproportionally enlarged subarachnoid space hydrocephalus (DESH). However, the callosal angle is thought to represent the best tool to discriminate iNPH from its mimics., Conclusions: According to the available epidemiological data iNPH is underdiagnosed. We strongly encourage the primary care physicians and geriatricians to ask the radiologist to measure the callosal angle on the initial brain computed tomography (or magnetic resonance) image. If the callosal angle is ≤71°, it is appropriate to refer the patient to neurosurgery for further diagnostic work-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This review makes the case that idiopathic normal pressure hydrocephalus (iNPH) is an outdated term because new information indicates that the syndrome is less idiopathic and that the cerebrospinal fluid (CSF) pressure of normal individuals is affected by several factors such as body mass index, age, and sex. Our review updates the epidemiology of iNPH and provides a clinical approach to the management of these patients. All the clinical features of iNPH are common in older individuals, and each has many causes, so the diagnosis is difficult. The first step in reaching an accurate diagnosis is to address the possible contributory factors to the gait abnormality and determine what if any role iNPH may be playing. The two best diagnostic tests are neuroimaging and cerebrospinal fluid (CSF) diversion (large volume lumbar puncture or external lumbar drainage) with pre/post gait evaluation. This review provides an update on the growing evidence that vascular disease, impaired CSF absorption, congenital, and genetic factors all contribute to the pathogenesis of iNPH. We suggest replacing the term iNPH with the term Hakim syndrome (HS) in acknowledgement of the first person to describe this syndrome. Lastly, we discuss the improvements in shunt technology and surgical techniques that have decreased the risks and long-term complications of shunt surgery.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by the triad of gait disturbance, cognitive impairment, and urinary incontinence. The condition is diagnosed mainly in older adults and is associated with ventricular enlargement without an increase in cerebrospinal fluid pressure. The clinical assessment involves a detailed medical history, physical examination, and cognitive testing. Neuroimaging is an essential part of the diagnostic workup for iNPH. However, to determine the suitability of patients for shunt surgery, a range of invasive preoperative investigations are employed. This narrative review aims to provide a comprehensive analysis of the current literature on invasive preoperative investigations in iNPH, focusing primarily on the lumbar infusion test, cerebrospinal fluid drainage tests, and continuous intracranial pressure monitoring. The strengths and limitations of each method, as well as their potential impact on treatment outcomes, are discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity., (© 2023. The Author(s).)

While the cause of altered mentation in the elderly may be multifactorial, infectious etiologies may be missed. This case report aims to detail an account of a patient with dementia, found to have Lyme meningitis in the setting of a normal pressure hydrocephalus (NPH). The patient smelled of urine and presented with ambulatory dysfunction, fitting the "wet, wacky, and wobbly" triad of NPH while also having subjective chills and leukocytosis. Non-contrast brain CT scan showed dilated ventricles. Cerebrospinal fluid (CSF) studies suggested aseptic meningitis. Serum studies using a modified two-tiered algorithm confirmed the diagnosis of Lyme disease. Treatment of the underlying condition with a prolonged course of doxycycline improved symptoms and clinical course. Review of the literature on the association between Lyme meningitis and NPH reveals that few cases of Lyme-related NPH have been reported worldwide and further research into the pathophysiology, diagnostic approach, treatment modalities, and management of NPH secondary to Lyme meningitis may be warranted., (Copyright © 2023 Marshfield Clinic Health System.)

Background and Purpose: : Post-shunt MRI is usually performed at 1.5T under the general assumption that shunt-related susceptibility artifacts would be greater at higher field strengths., Purpose: The purpose is to show that imaging post-shunt idiopathic normal pressure hydrocephalus (iNPH) patients at 3T is feasible and with reduced artifacts as compared to 1.5T., Methods: We manually measured transverse dimensions of artifact at the levels of lateral ventricles, cerebral aqueduct, and cerebellar hemisphere. Areas/volumes of artifacts were calculated assuming an elliptic/ellipsoid shape. Relative extent of shunt-related artifact between field strengths was rated by 3 readers on a 5-point Likert scale. A Wilcoxon Signed Rank Test was used to compare artifact at 1.5T vs 3T for each sequence, with a significance level set at p < 0.05., Results: Artifact areas were calculated in 22 iNPH patients; artifacts were on average smaller at 3T vs 1.5T on MPRAGE, DWI, and GRE sequences. On T2 FLAIR and T2 FSE, artifacts at 3T were larger than 1.5T. On the qualitative analysis, artifact effects were less at 3T vs 1.5T on DWI, greater at 3T on T2 FSE, and had mixed results on GRE., Conclusion: Our results indicate feasibility of post-shunt imaging with the CERTAS Plus valve at 3T based on shunt-related artifact that is less than or equal in extent to that on 1.5T on most standard clinical imaging sequences. Our findings, corroborated by the qualitative image review, suggest that dedicated clinical imaging sequences for devices may allow for reduction in artifact extent at both 1.5T and 3T., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (C a BV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of C a BV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals., Methods: The C a BV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the C a BV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable C a BV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC)., Results: The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the C a BV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001)., Conclusions: The findings suggest that in NPH, the ascending slope of the C a BV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings., (© 2023. The Author(s).)

Identification of patients with idiopathic normal pressure hydrocephalus (iNPH) in a collective with suspected neurodegenerative disease is essential. This study aimed to determine the metabolic spatial covariance pattern of iNPH on FDG PET using an established technique based on scaled subprofile model principal components analysis (SSM-PCA).We identified 11 patients with definite iNPH. By applying SSM-PCA to the FDG PET data, they were compared to 48 age-matched healthy controls to determine the whole-brain voxel-wise metabolic spatial covariance pattern of definite iNPH (iNPH-related pattern, iNPHRP). The iNPHRP score was compared between groups of patients with definite iNPH, possible iNPH (N = 34), Alzheimer's (AD, N = 38), and Parkinson's disease (PD, N = 35) applying pairwise Mann-Whitney U tests and correction for multiple comparisons.SSM-PCA of FDG PET revealed an iNPHRP that is characterized by relative negative voxel weights at the vicinity of the lateral ventricles and relative positive weights in the paracentral midline region. The iNPHRP scores of patients with definite iNPH were substantially higher than in patients with AD and PD (both p < 0.05) and non-significantly higher than those of patients with possible iNPH. Subject scores of the iNPHRP discriminated definite iNPH from AD and PD with 96% and 100% accuracy and possible iNPH from AD and PD with 83% and 86% accuracy.We defined a novel metabolic spatial covariance pattern of iNPH that might facilitate the differential diagnosis of iNPH versus other neurodegenerative disorders. The knowledge of iNPH-associated alterations in the cerebral glucose metabolism is of high relevance as iNPH constitutes an important differential diagnosis to dementia and movement disorders., (© 2023. The Author(s).)

Objective: MRI volumetry could be used as an alternative to invasive tests of shunt function. In this study, the authors aimed to assess the difference in ventricular volume (VV) before and after surgery and at different performance levels (PLs) of the shunt., Methods: This study was a randomized, double-blind trial with a crossover design. The study sample consisted of 36 patients (25 men, 11 women) with a median age of 76 years. All patients had idiopathic normal pressure hydrocephalus (iNPH) and received a Strata shunt at the regional hospital in Östersund, Sweden, with an initial PL of 1.5. Participants underwent MRI with volumetric sequences before surgery and four times postoperatively: at 1 month before randomization to either PL 1.0 (n = 15) or 2.5 (n = 17); at 2 months before crossover to PL 2.5 or 1.0; at 3 months before lowering the PL to 0.5; and finally, at 3 months and 1 day after surgery before resetting the PL to 1.5. VV was measured semiautomatically using quantitative MRI. Both the patient and the examiner of clinical tests and volumetry were blinded to the PL., Results: VV changed significantly between the presurgical level (median 129 ml) and the different shunt settings, i.e., PL 1.0 (median 115 ml), 1.5 (median 120 ml), and 2.5 (median 128 ml; p < 0.001). A unidirectional change in VV was observed for all participants between PL 1.0 and PL 2.5 (median 12 ml, range 2.1-40.7 ml, p < 0.001). No significant change was noted in VV after 24 hours at PL 0.5. Eight participants had asymptomatic subdural effusions at PL 1.0., Conclusions: The consistent decrease in VV after shunt surgery and between PL 2.5 and 1.0 supports the idea that MRI volumetry could be a noninvasive method for evaluating shunt function in iNPH, preventing unnecessary shunt revisions. However, further studies on retest variability of VV as well as verification against advanced testing of shunt function are needed before a clinical implementation of this method can be performed. Clinical trial registration no.: NCT04599153 (ClinicalTrials.gov).

Aims: The clinical triad of idiopathic normal pressure hydrocephalus (iNPH) includes gait disturbance, dementia, and urinary incontinence. These symptoms are also frequently observed in patients with proximal femoral fracture (PFF). The aim of this study was to investigate the relationship between PFF and iNPH retrospectively., Patients and Methods: Of the130 patients over 80-years-old with PFF included in this study, 48 were assigned to the PFF group. Forty-eight patients with peripheral vertigo matched with the PFF group for age and sex were included in the control group. We compared the Evans' index (EI), which is a head computed tomography finding of iNPH, and the percentages of patients with EI>0.3 between the two groups. The PFF group was further divided into two subgroups depending on whether EI was higher or lower than 0.3 (the higher or lower subgroup, respectively). We compared the patient's gait abilities before PFF, causes of PFF, cognitive functions, and occurrence of urinary incontinence between both groups., Results: The mean value of EI in the PFF group was significantly higher than that in the control group (PFF group, 0.301; control group, 0.284; p=0.008). The percentages of patients with EI>0.3 in the PFF and control groups were 62.5% and 35.4%, respectively (p=0.014). In subgroup analyses, the gait ability before injury was worse in the higher subgroup than that in the lower subgroup and was prominent among individuals who could walk only with human assistance (p=0.018). There were no significant differences in other parameters., Conclusion: Elderly patients with PFF may have underlying idiopathic normal pressure hydrocephalus., Level of Evidence: III; case-control comparative study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Normal Pressure Hydrocephalus (iNPH) typically affects the elderly and can cause cognitive decline, resulting in its differential diagnosis with other neurodegenerative conditions. Moreover, it is probably underdiagnosed; such under- and misdiagnosis prevents the patient from receiving the right treatment and significantly affects the quality of life and life expectancy. This investigation is an in-depth analysis of the actual incidence of iNPH in the population of the province served by our hospital (circa 580,000 individuals). The first phase of this study was conducted by visualizing a total of 1232 brain CT scans performed in the Emergency Departments of the four hospitals of our network on patients who were admitted for different complaints yet screened as suspicious for iNPH. Subsequently, corresponding Emergency Department medical records were investigated to understand the medical history of each patient in search of elements attributable to an alteration of CSF dynamics. The cohort of positive CT scans, according to the radiological and clinical inclusion criteria, included 192 patients. Among the reasons to require acute medical care, "Fall" was the most common. The cumulative incidence of CT scans suggestive of iNPH among the patients undergoing CT scans was as high as 15.58%, and the period prevalence calculated for the total amount of patients accessing the Emergency Departments was 1.084%. The real incidence of iNPH in the population may be underestimated, and the social burden linked to the assistance of patients suffering from such untreated conditions could be significantly relieved.

The pathophysiology of idiopathic intracranial hypertension (IIH) and idiopathic normal-pressure hydrocephalus (iNPH) differs in terms of cerebrospinal fluid (CSF) pressure and imaging-related characteristics. A 51-year-old man presented with optic nerve papillary edema, visual disturbance, bilateral abducens nerve palsy, and a wide-based gait. Imaging showed characteristic findings of IIH and disproportionately enlarged subarachnoid space hydrocephalus (DESH) - characteristic of iNPH. A CSF examination revealed marked CSF hypertension. IIH with iNPH-like imaging features (DESH) was diagnosed, and ventriculoperitoneal shunt surgery was performed. Postoperatively, the visual acuity and visual field improved. This report also describes the distinct and overlapping pathophysiological mechanisms of IIH and iNPH.

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 R out , 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 R out , 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., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The present study aims to investigate the choroidal morphology and microvascular structure in eyes of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with the eyes of healthy age-matched individuals, and to assess the choroidal structure in eyes of iNPH patients before and after shunt surgery using Optical Coherence Tomography (OCT). The primary objective was to assess the choroidal morphology in eyes of iNPH patients before and after ventriculo-peritoneal (VP) surgery compared to age and sex-matched healthy individuals. The secondary objective was to compare the choroidal morphology of iNPH patients before and after a mean of 56 days from shunt surgery. Eighteen consecutive patients diagnosed with iNPH and 18 healthy controls were prospectively recruited between November 2021 and October 2022. Spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) was conducted before and within 4 months after shunt surgery. Images were binarized using the ImageJ software, and the choroidal vascular index (CVI) was calculated. Sub-foveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were significantly increased in iNPH patients before surgery compared to the control group (p < 0.05). SFCT, TCA, and SCA were significantly increased in iNPH patients after surgery compared to the control group (p < 0.05). There were no differences in the CVI between iNPH patients and controls. No statistical differences in the choroidal structure were observed before and after VP shunt surgery (p > 0.05). In conclusion, the choroid was thicker in iNPH patients before and after VP shunt compared to age-matched healthy individuals. However, there were no difference in the choroidal microstructure in the eyes of iNPH patients before and after a mean of 3 months from VP shunt surgery., (© 2023. Springer Nature Limited.)

Objective: Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)-by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space-has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity., Methods: Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool., Results: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00-1.15] vs 1.49 [1.36-1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47-1.67] vs 1.33 [1.14-1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = -0.644, p < 0.001), number of steps to complete TUG (r = -0.571, p < 0.001), 10-m walk time (r = -0.637, p < 0.001), and 10-m walk steps (r = -0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = -0.39, p < 0.001, R2 = 0.459), female sex (B = 0.232, p = 0.002, R2 = 0.157), and Evans index (B = -4.151, p < 0.001, R2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R2 = 0.626) than analysis of each of these factors alone., Conclusions: The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.

Objectives: To develop and validate a nomogram based on MRI features for predicting iNPH., Methods: Patients aged  ≥ 60 years (clinically diagnosed with iNPH, Parkinson's disease, or Alzheimer's disease or healthy controls) who underwent MRI including three-dimensional T1-weighted volumetric MRI were retrospectively identified from two tertiary referral hospitals (one hospital for derivation set and the other for validation set). Clinical and imaging features for iNPH were assessed. Deep learning-based brain segmentation software was used for 3D volumetry. A prediction model was developed using logistic regression and transformed into a nomogram. The performance of the nomogram was assessed with respect to discrimination and calibration abilities. The nomogram was internally and externally validated., Results: A total of 452 patients (mean age ± SD, 73.2 ± 6.5 years; 200 men) were evaluated as the derivation set. One hundred eleven and 341 patients were categorized into the iNPH and non-iNPH groups, respectively. In multivariable analysis, high-convexity tightness (odds ratio [OR], 35.1; 95% CI: 4.5, 275.5), callosal angle  < 90° (OR, 12.5; 95% CI: 3.1, 50.0), and normalized lateral ventricle volume (OR, 4.2; 95% CI: 2.7, 6.7) were associated with iNPH. The nomogram combining these three variables showed an area under the curve of 0.995 (95% CI: 0.991, 0.999) in the study sample, 0.994 (95% CI: 0.990, 0.998) in the internal validation sample, and 0.969 (95% CI: 0.940, 0.997) in the external validation sample., Conclusion: A brain morphometry-based nomogram including high-convexity tightness, callosal angle  < 90°, and normalized lateral ventricle volume can help accurately estimate the probability of iNPH., Key Points: • The nomogram with MRI findings (high-convexity tightness, callosal angle, and normalized lateral ventricle volume) helped in predicting the probability of idiopathic normal-pressure hydrocephalus. • The nomogram may facilitate the prediction of idiopathic normal-pressure hydrocephalus and consequently avoid unnecessary invasive procedures such as the cerebrospinal fluid tap test, drainage test, and cerebrospinal fluid shunt surgery., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

We report the case of 74-year-old patient suspected of post-traumatic external hydrocephalus (EH) following a mild traumatic brain injury with a progressive neurological decline and a concomitant enlargement of subarachnoid spaces without ventriculomegaly on CT scan. A lumbar puncture revealed raised ICP and a careful CSF withdrawal was performed, resulting in an immediate neurological improvement, confirming the diagnosis of EH. During the 20-month follow-up, the patient presented progressive signs of normal pressure hydrocephalus (NPH): gait and cognitive decline, ventriculomegaly and the lumbar infusion study confirmed disturbed CSF dynamics. The patient underwent a ventriculoperitoneal shunt surgery, resulting in a long-lasting improvement.

Objective: The presence of tightened sulci in the high-convexities (THC) is a key morphological feature for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH), but the exact localization of THC has yet to be defined. The purpose of this study was to define THC and compare its volume, percentage, and index between iNPH patients and healthy controls., Methods: According to the THC definition, the high-convexity part of the subarachnoid space was segmented and measured the volume and percentage from the 3D T1-weighted and T2-weighted magnetic resonance images in 43 patients with iNPH and 138 healthy controls., Results: THC was defined as a decrease in the high-convexity part of the subarachnoid space located above the body of the lateral ventricles, with anterior end on the coronal plane perpendicular to the anterior commissure-posterior commissure (AC-PC) line passing through the front edge of the genu of corpus callosum, the posterior end in the bilateral posterior parts of the callosomarginal sulci, and the lateral end at 3 cm from the midline on the coronal plane perpendicular to the AC-PC line passing through the midpoint between AC and PC. Compared to the volume and volume percentage, the high-convexity part of the subarachnoid space volume per ventricular volume ratio < 0.6 was the most detectable index of THC on both 3D T1-weighted and T2-weighted magnetic resonance images., Conclusions: To improve the diagnostic accuracy of iNPH, the definition of THC was clarified, and high-convexity part of the subarachnoid space volume per ventricular volume ratio <0.6 proposed as the best index for THC detection in this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The authors describe an 82-year-old female with a right frontal ventriculoperitoneal (VP) shunt for long-standing normal pressure hydrocephalus (NPH) who presented with worsening incontinence and gait instability. She was found to have right lateral ventricle collapse around the shunt catheter and subsequently underwent shunt revision, which failed to improve her symptoms. Magnetic resonance imaging (MRI) was obtained on postoperative day two, which demonstrated a ventricular lesion. Endoscopic brain biopsy was performed and a diagnosis of primary central nervous system lymphoma (PCNSL) was made. The authors believe this is the first published case of PCNSL presenting as a VP shunt complication in a patient with NPH.

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., (© 2023. The Author(s).)

Background and Objective: The pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Homocysteine may reduce the compliance of intracranial arteries and damage the endothelial function of the blood-brain barrier (BBB), which may be the underlying mechanism of iNPH. The overlap cases between deep perforating arteriopathy (DPA) and iNPH were not rare for the shared risk factors. We aimed to investigate the relationship between serum homocysteine and iNPH in DPA., Methods: A total of 41 DPA patients with iNPH and 49 DPA patients without iNPH were included. Demographic characteristics, vascular risk factors, laboratory results, and neuroimaging data were collected. Multivariable logistic regression analysis was performed to investigate the relationship between serum homocysteine and iNPH in DPA patients., Results: Patients with iNPH had significantly higher homocysteine levels than those without iNPH (median, 16.34 mmol/L versus 14.28 mmol/L; P = 0.002). There was no significant difference in CSVD burden scores between patients with iNPH and patients without iNPH. Univariate logistic regression analysis demonstrated that patients with homocysteine levels in the Tertile3 were more likely to have iNPH than those in the Tertile1 (OR, 4.929; 95% CI, 1.612-15.071; P = 0.005). The association remained significant after multivariable adjustment for potential confounders, including age, male, hypertension, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia, and eGFR level., Conclusion: Our study indicated that high serum homocysteine levels were independently associated with iNPH in DPA. However, further research is needed to determine the predictive value of homocysteine and to confirm the underlying mechanism between homocysteine and iNPH., (© 2023. The Author(s).)

Background: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [ 123 I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane ( 123 I-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 123 I-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., (© 2023. The Author(s).)

Objective: Temporary drainage of CSF with lumbar puncture or lumbar drainage has a high predictive value for identifying patients with suspected idiopathic normal pressure hydrocephalus (iNPH) who may benefit from ventriculoperitoneal shunt insertion. However, it is unclear what differentiates responders from nonresponders. The authors hypothesized that nonresponders to temporary CSF drainage would have patterns of reduced regional gray matter volume (GMV) as compared with those of responders. The objective of the current investigation was to compare regional GMV between temporary CSF drainage responders and nonresponders. Machine learning using extracted GMV was then used to predict outcomes., Methods: This retrospective cohort study included 132 patients with iNPH who underwent temporary CSF drainage and structural MRI. Demographic and clinical variables were examined between groups. Voxel-based morphometry was used to calculate GMV across the brain. Group differences in regional GMV were assessed and correlated with change in results on the Montreal Cognitive Assessment (MoCA) and gait velocity. A support vector machine (SVM) model that used extracted GMV values and was validated with leave-one-out cross-validation was used to predict clinical outcome., Results: There were 87 responders and 45 nonresponders. There were no group differences in terms of age, sex, baseline MoCA score, Evans index, presence of disproportionately enlarged subarachnoid space hydrocephalus, baseline total CSF volume, or baseline white matter T2-weighted hyperintensity volume (p > 0.05). Nonresponders demonstrated decreased GMV in the right supplementary motor area (SMA) and right posterior parietal cortex as compared with responders (p < 0.001, p < 0.05 with false discovery rate cluster correction). GMV in the posterior parietal cortex was associated with change in MoCA (r2 = 0.075, p < 0.05) and gait velocity (r2 = 0.076, p < 0.05). Response status was classified by the SVM with 75.8% accuracy., Conclusions: Decreased GMV in the SMA and posterior parietal cortex may help identify patients with iNPH who are unlikely to benefit from temporary CSF drainage. These patients may have limited capacity for recovery due to atrophy in these regions that are known to be important for motor and cognitive integration. This study represents an important step toward improving patient selection and predicting clinical outcomes in the treatment of iNPH.

Objective: Normal pressure hydrocephalus (NPH) is a neurodegenerative disease that is potentially reversible by shunt surgery in approximately 60% of patients. Imaging may provide a means to investigate brain tissue viability and oxygen metabolism in NPH patients., Methods: Oxygen extraction fraction (OEF) mapping was generated from 3D multi-echo gradient echo MRI (mGRE) data using QQ-CCTV algorithm and cerebral blood flow (CBF) using 3D arterial spin labeling (ASL) MRI data, thereby calculating the cerebral metabolic rate of oxygen (CMRO 2  = CBF × OEF × [H] a ) in 16 NPH patients. Regression analyses using cortical gray matter and deep gray matter regions were conducted with age, gender, CSF stroke volume and normalized ventricular volume as independent variables., Results: OEF showed significant negative correlations with normalized brain ventricular volumes in the whole brain (p = 0.004, q = 0.01), cortical gray matter (p = 0.004, q = 0.01), caudate (p = 0.02, q = 0.04), and pallidum (p = 0.03, q = 0.04), but no significant correlation with CSF stroke volume (q > 0.05). There was no significant finding with CBF or CMRO 2 ., Conclusion: In NPH patients, low OEF in several regions was significantly correlated with large ventricular volumes, indicating decreased tissue oxygen metabolism with increased NPH severity. OEF mapping may provide a functional understanding of neurodegeneration in NPH and may improve monitoring of disease course and treatment outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)