Normal Pressure Hydrocephalus Patients Research Articles

442 A Ventriculomegaly Feature Computation Pipeline to Improve the Screening of Normal Pressure Hydrocephalus on Computed Tomography

INTRODUCTION: Normal pressure hydrocephalus (NPH) commonly presents with a triad of gait disturbance, incontinence, and memory impairment. Shunt placement effectively treats symptoms; however, NPH is commonly misdiagnosed with below 20% of patients receiving a diagnosis. Given undiagnosed NPH elderly patients often present to the emergency room (ER) with falls, algorithmic identification of NPH using non-contrast CT (NCCT) may improve diagnosis rate. METHODS: NCCTs for 84 patients with NPH, 72 headache controls (HC), 97 Alzheimer’s Disease (AD) patients, and 61 post-traumatic encephalomalacia (PTE) patients were identified using Veterans Affairs Informatics and Computing Infrastructure. Image processing pipelines were developed to extract a novel feature capturing lateral ventricle eccentricity (MaxEccLV), a proxy-Splenial Angle (p-SA), the Evans indices (EI-x, y, z), Callosal angle (CA), third ventricle width (NMax-3VW), and CSF to brain volume ratio (CSF2BVR). T-tests were used to examine group differences and logistic regression to classify between NPH, AD, PTE, and HC. RESULTS: The AUC, sensitivity, and specificity for NPH versus AD+HC+PTE was 0.94, 83.0%, and 87.0% respectively. For NPH versus HC, it was 0.98, 98.8%, and 98.6% respectively. For NPH versus AD, it was 0.90, 84.5%, and 82.5% respectively. For NPH versus PTE, it was 0.95, 91.7%, and 86.9% respectively. Significant differences were seen between NPH and HC, AD, and PTE in MaxEccLV and all other features. CONCLUSIONS: The computational pipeline proposed here can identify NPH from HCs and ventriculomegaly-causing conditions using NCCT with a high sensitivity and specificity. This may help capture undiagnosed NPH patients receiving a NCCT due to presentation to the ER as a fall.

Cognitive changes after tap test in patients with normal pressure hydrocephalus: a before-and-after study

Normal pressure hydrocephalus (NPH) leads to cognitive impairment (CI) as part of its triad of symptoms. Assessment of CI before and after a tap test can be used to inform diagnosis, differentiate NPH symptoms from alternative or concomitant causes of CI, and suggest the potential benefits of valve placement. The aims of this study are: to describe cognitive performance in patients with NPH diagnosis before and after a tap test, and to compare CI between patients with NPH meeting criteria for a dementia diagnosis (D +) and those without criteria for dementia (D−) at both baseline and after the tap-test. We performed a Before-and-after study evaluating clinical features and performance on cognitive tests (CERAD, ADAS-COG, SVF, PVF, ROCF and IFS). We included 76 NPH patients, with a median age of 81 years. 65 patients (87.8%) improved cognitive performance after tap test. ROCF (p = 0.018) and IFS (p < 0.001) scores significantly change after the tap test. Dementia was concomitant in 68.4% of patients. D + group showed higher proportion of patients with altered performance in IFS, PVF, SVF, and ROCF than D- group at baseline (p < 0.05). A significant improvement in SVF and IFS was observed exclusively in the D− group after tap test. Our results suggest that executive function and praxis are the cognitive domains more susceptible to improvement after a tap test in a 24-h interval in NPH patients. Moreover, the D− group showed a higher proportion of improvement after the tap test in executive function and verbal fluency test compared with the D + group.

Functional analysis of the human perivascular subarachnoid space

The human subarachnoid space harbors the cerebrospinal fluid, which flows within a landscape of blood vessels and trabeculae. Functional implications of subarachnoid space anatomy remain far less understood. This study of 75 patients utilizes a cerebrospinal fluid tracer (gadobutrol) and consecutive magnetic resonance imaging to investigate features of early (i.e. within 2-3 h after injection) tracer propagation within the subarachnoid space. There is a time-dependent perivascular pattern of enrichment antegrade along the major cerebral artery trunks; the anterior-, middle-, and posterior cerebral arteries. The correlation between time of first enrichment around arteries and early enrichment in nearby cerebral cortex is significant. These observations suggest the existence of a compartmentalized subarachnoid space, where perivascular ensheathment of arteries facilitates antegrade tracer passage towards brain tissue. Periarterial transport is impaired in subjects with reduced intracranial pressure-volume reserve capacity and in idiopathic normal pressure hydrocephalus patients who also show increased perivascular space size.

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

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

Utilizing kinematic analysis of postural instability as an objective measure to aid in distinguishing between normal pressure hydrocephalus and Parkinson's disease

ObjectivePatients with normal pressure hydrocephalus (NPH) and Parkinson's Disease (PD) can clinically appear quite similar at baseline evaluation. We sought to investigate the use of kinematic assessment of postural instability (PI) using inertial measurement units (IMUs) as a mechanism of differentiation between the two disease processes. Methods20 patients with NPH, 55 patients with PD, and 56 age-matched, healthy controls underwent quantitative pull test examinations while wearing IMUs at baseline. Center of mass and foot position data were used to compare velocity and acceleration profiles, pull test step length, and reaction times between groups and as a function of Unified Parkinson's disease Rating Scale Pull Test (UPDRSPT) score. ResultsOverall, the reactive postural response of NPH patients was characterized by slower reaction times and smaller steps compared to both PD patients and healthy controls. However, when patients were grouped by UPDRSPT scores, no reliable objective difference between groups was detected. ConclusionAt their initial evaluation, very few NPH patients demonstrate “normal” or “mild” PI as they appear to be older upon presentation compared to PD patients. As a result, kinematic assessment utilizing IMUs may not be helpful for differentiating between NPH and PD as a function of UPDRSPT score, but rather as a more fine-tuned method to define disease progression. We emphasize the need for further evaluation of incorporating objective kinematic data collection as a way to evaluate PI and improve patient outcomes.

Intravoxel incoherent motion magnetic resonance imaging in the assessment of brain microstructure and perfusion in idiopathic normal-pressure hydrocephalus.

To determine the relationship between intravoxel incoherent motion (IVIM) MRI parameters and clinical changes post-tap test (TT) in idiopathic normal-pressure hydrocephalus (iNPH) patients. Forty-four probable iNPH patients underwent 3T MRI before and after TT. IVIM parameters were calculated from eight different bilateral regions of interest in basal ganglia, centrum semiovale, and corona radiata. Patients were categorized based on TT response into positive (group 1) and negative (group 2) groups. A Welch two-sample t-test was used to compare differences in D, D*, f, and ADC between the two groups, while a paired t-test was employed to assess the changes within each group before and after TT. These parameters were then correlated with clinical results. In the lenticular and thalamic nuclei, D value was significantly lower in the group 1 compared to group 2 both pre- and post-TT (p = 0.002 and p = 0.007 respectively). Post-TT, the positive response group exhibited a notably reduced D* value (p = 0.012) and significantly higher f values (p = 0.028). In the corona radiata and centrum semiovale, a significant post-TT reduction in D* was observed in the positive response group (p = 0.017). Within groups, the positive response cohort showed a significant post-TT increase in ADC (p < 0.001) and a decrease in D* (p = 0.007). IVIM permits the acquisition of important non-invasive information about tissue and vascularization in iNPH patients. Enhanced perfusion in the lenticular and thalamic nuclei may suggest the role of re-established microvascular and glymphatic pathways, potentially elucidating the functional improvement in motor function after TT in iNPH patients.

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus

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.

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

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

Patients of idiopathic normal-pressure hydrocephalus have small dural sac in cervical and upper thoracic levels: A supposed causal association.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder presenting a triad including dementia and ventricular enlargement. The mechanism causing excessive cerebrospinal fluid (CSF) accumulation in the ventricles in iNPH is poorly understood. We hypothesized that the age-related degradation of the spinal shock-absorbing system composed of a spinal dural sac (SDS) and surrounding soft tissue, preventing ventricular enlargement caused by wide CSF pulsation driven by heartbeats, may be involved in the ventricular enlargement observed in iNPH. Sixty-four patients with iNPH in their seventies who underwent a lumboperitoneal shunt and a control group of 79 people in the same age group who underwent brain check-ups were included in the study. We compared the sizes of the cervical and upper parts of the thoracic SDS using magnetic resonance imaging between the two groups. The anterior-posterior distances of the dural sac at C5 were shorter in patients with iNPH of both sexes than those in the control group (P = 0.0008 in men and P = 0.0047 in women). The number of disc levels with disappeared CSF space surrounding the cervical cord was more in iNPH (P = 0.0176 and P = 0.0003). The midsagittal area of the upper part of the spinal sac, C2-Th4, was smaller in iNPH (P = 0.0057 and P = 0.0290). Narrowing of the cervical dural sac and midsagittal area in the upper part of the SDS in patients with iNPH may reflect the degradation of the shock-absorbing mechanism for CSF pressure pulsations, which may cause iNPH or at least aggravate iNPH by other unknown causes.

Treatment of Idiopathic Normal Pressure Hydrocephalus with a Novel Programmable Valve: Prospective Evaluation of Costs, Efficacy, and Safety.

Objective  Programmable valves provide an equal or superior neurological outcome when compared with fixed pressure ones, with fewer complications, in treating idiopathic normal pressure hydrocephalus (iNPH) patients. Long-term costs of these treatments have not been properly compared in literature. We sought to compare costs, efficacy, and safety of 1-year treatment of iNPH patients with programmable valve Sphera Pro and a fixed pressure valve. Materials and Methods  A prospective cohort of iNPH patients treated with programmable valve was compared with a historical cohort of iNPH patients treated with fixed pressure valve. Our primary outcome was mean direct cost of treating iNPH up to 1 year. Efficacy in treating iNPH and safety were assessed as secondary outcomes. Statistical Analysis  Proportions were compared using chi-square or Fisher's exact tests. Normally distributed variables were compared using the Student's t -test or the Mann-Whitney's U test. Differences in the evolution of the variables over time were assessed using generalized estimating equations. All tests were two-sided, with an α of 0.05. Results  A total of 19 patients were analyzed in each group (mean age 75 years, the majority male). Comorbidities and clinical presentation were similar between groups. Both fixed pressure and programmable valve patients had neurological improvement over time ( p  < 0.001), but no difference was seen between groups ( p  = 0.104). The fixed pressure valve group had more complications than the programmable valve group (52.6% vs. 10.5%, respectively, p  = 0.013). Annual treatment cost per patient was US$ 3,820 ± 2,231 in the fixed pressure valve group and US$ 3,108 ± 553 in the programmable valve group. Mean difference was US$712 (95% confidence interval, 393-1,805) in favor of the programmable valve group. Conclusion  The Sphera Pro valve with gravitational unit had 1 year treatment cost not higher than that of fixed pressure valve, and resulted in similar efficacy and fewer complications.

Heterogeneity in phenotypical and treatment response in a cohort of normal pressure hydrocephalus patients

Heterogeneity in phenotypical and treatment response in a cohort of normal pressure hydrocephalus patients

Prevalence of Fecal Incontinence in Normal Pressure Hydrocephalus: A Prospective Evaluation of 100 Patients

Normal pressure hydrocephalus (NPH) is a frequent disease in elderly patients. The main symptoms are gait disturbance, urine incontinence, and cognitive decline. Fecal urgency and incontinence are described as rare additional symptoms; however, no exact numbers are known. The aim of this study was to investigate the prevalence of fecal disturbances in NPH patients. Patients who presented to our department with confirmed diagnosis of NPH between January and December 2021 were interviewed prospectively about fecal function. Additionally, the extent of gait disturbance, cognitive decline, ventriculomegaly (EvansIndex), disproportionate enlarged subarachnoid space hydrocephalus (DESH presence), age, gender, and length of history were documented. In those who were operated with a hydrocephalus shunt postoperative development of stool incontinence was followed up. One hundred patients were evaluated (67 males, 33 females, medium age 77.5years, medium Evans Index: 0.37; 87 with disproportionate enlarged subarachnoid space hydrocephalus). 97 patients showed gait disturbance, 84 cognitive decline, and 87 bladder dysfunctions. 78 patients had the complete Hakim triad. 32 patients complained about fecal incontinence (20 with urge incontinence, 12 with complete incontinence). Twenty nine patients were shunted, of which 17 (57%) recovered completely, 9 (31%) partially, and 3 (10%) did not show any change. Fecal urgency and incontinence is a frequent finding in NPH (32%) and is essential for the quality of life. In the general population, fecal incontinence in elderly is found in up to 15%. The more than two-fold higher prevalence in NPH patients and the high percentage of postshunted improvement suggests that NPH causes often directly fecal disturbance.

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

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

Normal Pressure Hydrocephalus and Comorbidities: A Quality Study of the University Hospital Münster

Idiopathic normal pressure hydrocephalus (NPH) is commonly accompanied by diverse comorbidities that impact the postoperative course and result in a distinction between shunt responders and shunt non-responders. This study aimed to enhance diagnostics by identifying prognostic differences between NPH patients, individuals with comorbidities, and those with other complications. The data of 119 patients with NPH coding at the University Clinic Münster from January 2009 to June 2017 were examined. The study primarily concentrated on examining symptoms, comorbidities, and radiological measurements, including callosal angle (CA) and Evans index (EI). To evaluate the progression of symptoms, a novel scoring system was developed to quantitatively assess the course at specific time points: 5-7weeks, 1-1.5years, and 2.5years after the operation. This scoring system aimed to provide a standardized approach for measuring and tracking the development of symptoms over time. Logistic regression analyses were employed to identify predictor associated with 3 key outcomes: shunt implantation, surgical success, and the development of complications. Among the comorbidities observed, hypertension was the most prevalent. Gait disturbance, in the absence of polyneuropathy, was identified as a predictor of a favorable surgical outcome. Hygroma development was associated with a combination of vascular factors and cognitive disorders. The presence of spinal/skeletal changes, diabetes, and vascular constellations were found to increase the likelihood of developing complications. The evaluation of comorbidities accompanied by NPH holds significant importance and necessitates meticulous observation, expertise, and multidisciplinary care.

Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients

Normal pressure hydrocephalus (NPH) is an intracranial disease characterized by an abnormal accumulation of cerebrospinal fluid (CSF) in brain ventricles within the normal range of intracranial pressure. Most NPH in aged patients is idiopathic (iNPH) and without any prior history of intracranial diseases. Although an abnormal increase of CSF stroke volume (hyper-dynamic CSF flow) in the aqueduct between the third and fourth ventricles has received much attention as a clinical evaluation index in iNPH patients, the biomechanical effects of this flow on iNPH pathophysiology are poorly understood. This study aimed to clarify the potential biomechanical effects of hyper-dynamic CSF flow through the aqueduct of iNPH patients using magnetic resonance imaging-based computational simulations. Ventricular geometries and CSF flow rates through aqueducts of 10 iNPH patients and 10 healthy control subjects were obtained from multimodal magnetic resonance images, and these CSF flow fields were simulated using computational fluid dynamics. As biomechanical factors, we evaluated wall shear stress on the ventricular wall and the extent of flow mixing, which potentially disturbs the CSF composition in each ventricle. The results showed that the relatively high CSF flow rate and large and irregular shapes of the aqueduct in iNPH resulted in large wall shear stresses localized in relatively narrow regions. Furthermore, the resulting CSF flow showed a stable cyclic motion in control subjects, whereas strong mixing during transport through the aqueduct was found in patients with iNPH. These findings provide further insights into the clinical and biomechanical correlates of NPH pathophysiology.

Increasing brain N-acetylneuraminic acid alleviates hydrocephalus-induced neurological deficits.

This metabolomic study aimed to evaluate the role of N-acetylneuraminic acid (Neu5Ac) in the neurological deficits of normal pressure hydrocephalus (NPH) and its potential therapeutic effect. We analyzed the metabolic profiles of NPH using cerebrospinal fluid with multivariate and univariate statistical analyses in a set of 42 NPH patients and 38 controls. We further correlated the levels of differential metabolites with severity-related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS). We then established kaolin-induced hydrocephalus in mice and treated them using N-acetylmannosamine (ManNAc), a precursor of Neu5Ac. We examined brain Neu5Ac, astrocyte polarization, demyelination, and neurobehavioral outcomes to explore its therapeutic effect. Three metabolites were significantly altered in NPH patients. Only decreased Neu5Ac levels were correlated with NPHGS scores. Decreased brain Neu5Ac levels have been observed in hydrocephalic mice. Increasing brain Neu5Ac by ManNAc suppressed the activation of astrocytes and promoted their transition from A1 to A2 polarization. ManNAc also attenuated the periventricular white matter demyelination and improved neurobehavioral outcomes in hydrocephalic mice. Increasing brain Neu5Ac improved the neurological outcomes associated with the regulation of astrocyte polarization and the suppression of demyelination in hydrocephalic mice, which may be a potential therapeutic strategy for NPH.

Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus.

Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.

Field strength difference in extent of artifacts induced by CERTAS Plus valves in patients with idiopathic normal pressure hydrocephalus.

: 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. 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. 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. 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. 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.

Cerebrospinal Fluid Neurofilament Light as a Marker of Neuro-axonal Injury in Normal Pressure Hydrocephalus (P10-6.001)

<h3>Objective:</h3> To compare Cerebrospinal fluid (CSF) Neurofilament-light chain (NfL) and NfL/amyloid beta₄₂ (Abeta42) ratio levels in normal pressure hydrocephalus (NPH) patients with healthy controls (HC), Alzheimer’s disease (AD), and Frontotemporal lobar degeneration (FTLD). <h3>Background:</h3> Levels of CSF NfL have been shown to be a marker of neuro-axonal injury and are elevated in neurodegenerative disease. One putative etiology of NPH involves axonal injury; however, low CSF Abeta42 has been reported in NPH. To control for the higher volume of CSF in NPH, the NfL/Abeta42 ratio was used. <h3>Design/Methods:</h3> 120 patients with CSF analysis: (a) 46 NPH: ventriculomegaly on MRI or CT, negative AD biomarkers, clinical symptoms of NPH, improvement in gait after tap test; (b) 39 FTLD: 5 behavioural-variant frontotemporal dementia, 14 corticobasal syndrome, 4 frontotemporal dementia with motor neuron disease, 12 progressive supranuclear palsy, 2 semantic-variant primary progressive aphasia (PPA), and 2 non-fluent PPA; (c) 29 AD; and (d) 6 HC. Levels of CSF NfL were measured using single molecule array (Simoa) technology while Abeta42 was measured using a sandwich ELISA method (Innotest). All statistical analyses were corrected for multiple comparisons and age. <h3>Results:</h3> Log transformed NfL levels in the NPH group were significantly higher than HC (p &lt; 0.05), but lower than FTLD and AD group (p &lt;0 .001). Log transformed CSF NfL/Abeta42 ratio was significantly higher in the NPH group compared to HC (p&lt;0.05); but no significant difference with FTLD and AD groups. <h3>Conclusions:</h3> Intermediate CSF NfL levels in NPH patients suggest that there is some neuro-axonal injury present - although less than in FTLD and AD. Further investigations are warranted to determine whether the NfL normalizes after shunting or the neuroaxonal injury is irreversible. NfL in NPH may help elucidate the pathophysiology of the disease. <b>Disclosure:</b> Ms. Davenport has nothing to disclose. Dr. Taghdiri has nothing to disclose. Anna Vasilevskaya has nothing to disclose. Ms. Anastassiadis has received research support from Fonds de Recherche du Québec - Santé (FRQS). Dr. Thapa has nothing to disclose. Dr. Dimal has nothing to disclose. Namita Multani, 14039 has nothing to disclose. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Fasano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sunovion. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ceregate. The institution of Dr. Fasano has received research support from Boston Scientific. The institution of Dr. Fasano has received research support from Medtronic. The institution of Dr. Fasano has received research support from Abbvie. Dr. Fasano has received publishing royalties from a publication relating to health care. Dr. Tang-Wai has nothing to disclose. Dr. Tartaglia has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Tartaglia has received research support from NIH. The institution of Dr. Tartaglia has received research support from University of Toronto.

Investigation of probability maps in deep-learning-based brain ventricle parcellation.

Normal Pressure Hydrocephalus (NPH) is a brain disorder associated with ventriculomegaly. Accurate segmentation of the ventricle system into its sub-compartments from magnetic resonance images (MRIs) could help evaluate NPH patients for surgical intervention. In this paper, we modify a 3D U-net utilizing probability maps to perform accurate ventricle parcellation, even with grossly enlarged ventricles and post-surgery shunt artifacts, from MRIs. Our method achieves a mean dice similarity coefficient (DSC) on whole ventricles for healthy controls of 0.864 ± 0.047 and 0.961 ± 0.024 for NPH patients. Furthermore, with the benefit of probability maps, the proposed method provides superior performance on MRI with grossly enlarged ventricles (mean DSC value of 0.965 ± 0.027) or post-surgery shunt artifacts (mean DSC value of 0.964 ± 0.031). Results indicate that our method provides a high robust parcellation tool on the ventricular systems which is comparable to other state-of-the-art methods.