Normal Pressure Hydrocephalus Research Articles

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

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a prevalent neurological disorder, but its diagnosis remains challenging. Dual-task (DT) walking performance is a reliable indicator of iNPH but less is known about the role of cognitive reserve (CR) in predicting DT walking performance.AimsThe objective of this study was to evaluate the contribution of CR on DT walking in healthy controls (HC) and in iNPH patients (iNPH-P).Methods68 iNPH-P (77.2 +/- 6.7 years old) and 28 HC (74.5 +/- 5.7 years old) were evaluated on their single-task walking (Vsimple) and on 4 DT walking (walking and counting or counting backwards, naming animals, naming words beginning with the letter P) (Vcount, VcountB, Vanimals and Vletter respectively). The contribution of CR on the different DT walking speeds was compared between HC and iNPH-P. In iNPH-P, the contribution of CR on the walking speeds was compared with regard to other cognitive, functional, and socio-demographic variables.ResultsSimple linear regression demonstrated a moderate influence of CR on single and DT walking speed in iNPH-P (β > 0.3, p < .001) but not in HC where the relation was not significant. In iNPH-P, results showed that CR played a major role in explaining each of the single and DT walking speeds with NPH-scale.ConclusionAs CR could be improved through the life cycle, these results support the idea of developing and supporting physical activity programs that will enrich social, physical, and cognitive resources to protect against age-related functional decline, especially in iNPH-P patients where the age-related deficits are greater.

Risk Variants Associated With Normal Pressure Hydrocephalus: Genome-Wide Association Study in the FinnGen Cohort.

Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1/GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8). We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.

Automated Idiopathic Normal-Pressure Hydrocephalus Diagnosis via Artificial Intelligence-Based 3D T1 MRI Volumetric Analysis.

Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia, that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan. We quantified iNPH, Parkinson's disease, Alzheimer's disease, and healthy control patients on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing. Automatic component measurement algorithms were developed for Evans' index, Sylvian fissure enlargement, high-convexity tightness, callosal angle, and normalized lateral ventricle volume. XGBoost models were trained for both automated measurements and manual labels for iNPH prediction. A total of 452 patients (200 men; mean age ± standard deviation, 73.2 ± 6.5 years) were included in the training set. Of the 452 patients, 111 (24.6%) had iNPH. We obtained AUC values of 0.956 for automatically measured high-convexity tightness and 0.830 for Sylvian fissure enlargement. Intra-class correlation values of 0.824 for the callosal angle and 0.924 for Evans' index were measured. Using the decision tree of the XGBoost model, the model trained on manual labels obtained an average cross-validation AUC of 0.988 on the training set and 0.938 on the unseen test set, while the fully automated model obtained a cross-validation AUC of 0.983 and an unseen test AUC of 0.936. We demonstrated a machine-learning algorithm capable of diagnosing iNPH from a 3D T1-weighted MRI scan that is robust to the failure. We propose a method to scan large numbers of 3D T1-weighted MRI scans with minimal human intervention, making possible large-scale iNPH screening. iNPH = idiopathic normal-pressure hydrocephalus; PD = Parkinson's disease; AD = Alzheimer's disease; HC = healthy control; CSF = cerebrospinal fluid; DESH = disproportionately enlarged subarachnoid space hydrocephalus; 3D = three-dimensional.

Development of a nomogram for fetal Evans Index.

This study aims to investigate the fetal Evans Index and establish a nomogram for fetuses without any additional fetal anomalies detected during the prenatal period. We conducted our research at Ankara City Hospital, including 894 patients who were admitted and evaluated between gestational weeks 16-40. These patients had no fetal anomalies detected in subsequent gestational weeks. Descriptive data, such as age, gravidity, parity, and body mass index (BMI), were recorded. Gestational week and Evans Index (mean, median, standard deviation, minimum, maximum, and percentile) were also documented. The Evans index was calculated as the ratio between the maximal width of the frontal horns and the maximal width of the inner diameter of the cranium. We evaluated 894 fetuses in pregnant women had no fetal anomalies detected throughout the pregnancy. The evaluation took place at different gestational weeks, and a nomogram for the Evans Index was created. It is relevant for clinicians and researchers to be aware of the range of fetal Evans Index values across different gestational weeks as a prognostic criterion.

Assessment of neurofluid dynamics in relation to clinical improvement after tap-test: pilot study.

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. 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. 23 patients were included. Compliance index assessed by PC-MRI was significantly higher in the group of patients with improvement > 10% (p = 0.015). 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.

Dynamic plain abdominal film provides simple and effective diagnosis of delayed shunt insufficiency caused by abdominal adhesions after VP shunt

BackgroundMany complications may occur after placement of the ventriculoperitoneal shunt (VP shunt) for hydrocephalus, and delayed shunt insufficiency (DSI) is among the most common. It is often caused by abdominal adhesions, which increases the difficulty of diagnosis. This study aimed to explore the clinical value of dynamic plain abdominal radiography (DPAR) as a simple diagnostic method for patients with DSI due to terminal adhesion of the peritoneal shunt after VP surgery.MethodsA total of 30 patients with high suspicion of DSI due to abdominal adhesions after VP surgery were included. DPAR was used for prospective assessment. The interval between the first and second PAR was 4–6 h before surgery. If two plain abdominal radiography at different times indicated that the end of the shunt tube in the abdominal segment was fixed, it was diagnosed as DSI due to adhesion of the shunt tube at the abdominal end. The peritoneal end of the shunt tube was surgically repositioned. Postoperative DPAR was repeated to evaluate the distance of the shunt outlet within the abdominal segment.ResultsAll cases showed clinical symptoms or imaging findings of shunt insufficiency. The diagnostic accuracy of DPAR was 96.67% (29/30). The end of the shunt tube in the abdominal segment of the preoperative group was fixed with abdominal plain film twice with a mean difference of 1.74 ± 1.18 cm. The mean postoperative change in the position of the end of the shunt tube in the abdominal section was 9.36 ± 2.64 cm, showing a significant difference compared with the preoperative group (P < 0.001). The mean postoperative EVANs index (0.37 ± 0.08) was significantly lower than the preoperative (0.42 ± 0.08) (P = 0.007), Glasgow coma scale score (12.8 ± 2.69) was higher than the mean preoperative score (11.36 ± 2.43) (P = 0.013).ConclusionDPAR is a simple and effective method for the diagnosis of shunt insufficiency caused by delayed abdominal end adhesion after VP shunt.

18F-FDG brain PET: a metabolic predictive factor for gait improvement after cerebrospinal fluid shunting in normal pressure hydrocephalus?

The pathophysiology of normal pressure hydrocephalus (NPH) has not been fully elucidated. Treating NPH with cerebrospinal fluid shunts to improve gait disturbances may have some risks and inconsistent benefits. No clear predictive factor has been identified thus far. This preliminary study aimed to evaluate the predictive value of preoperative brain 18F-FDG positron emission tomography (PET) on overall gait response in patients with NPH. Sixteen patients with NPH who underwent 18F-FDG PET before shunt surgery between 2012 and 2022 were included retrospectively and separated into two groups based on their gait response one year after surgery: responders (R) or nonresponders (NR). Brain glucose metabolism was assessed using visual and semiquantitative analyses using SPM8 software (Welcome Department of Cognitive Neurology, University College, London, UK). Five regions of interest were selected: global cortex, cerebellum, thalamus, striatum, and midbrain. Visual interpretation showed more frequent hypometabolism of the striatum, thalamus and global cortex in NR. None of the patients showing hypometabolism of these regions were R. Based on these results, the visual interpretation allowed us to identify 3/8 NR and 8/8 R. Semiquantitative analysis confirmed significantly lower thalamic metabolism in the NR group (P=0.037) and a trend towards lower metabolism of the striatum (P=0.075) with an area under the curve of 0.77 for thalamic metabolism to discriminate between R and NR. This preliminary study using brain 18F-FDG PET suggests that reduced brain metabolism in the thalamus and striatum along with cortical hypometabolism may be associated with poorer gait response to CSF shunting in normal pressure hydrocephalus (NPH). Although these findings suggest that preoperative brain 18F-FDG PET could potentially aid in selecting appropriate candidates for shunt surgery, further research with larger sample sizes is needed to confirm these results.

Clinical application of single-shot fast spin-echo sequence for cerebrospinal fluid flow MR imaging.

In normal-pressure hydrocephalus, disturbances in cerebrospinal fluid (CSF) circulation occur; therefore, understanding CSF dynamics is crucial. The two-dimensional phase-contrast (2D-PC) method, a common approach for visualizing CSF flow on MRI, often presents challenges owing to prominent vein signals and excessively high contrast, hindering the interpretation of morphological information. Therefore, we devised a new imaging method that utilizes T2-weighted high-signal intensification of the CSF and saturation pulses, without requiring specialized imaging sequences. This sequence utilized a T2-weighted single-shot fast spin-echo combined with multi-phase imaging synchronized with a pulse wave. Optimal imaging conditions (repetition time, presence/absence of fast recovery, and echo time) were determined using self-made contrast and single-plate phantoms to evaluate signal-to-noise ratio, contrast ratio, and spatial resolution. In certain clinical cases of hydrocephalus, confirming CSF flow using 2D-PC was challenging. However, our method enabled the visualization of CSF flow, proving to be useful in understanding the pathophysiology of hydrocephalus.

Clinical correlates of obstructive sleep apnoea in idiopathic normal pressure hydrocephalus.

The pathogenesis of idiopathic normal pressure hydrocephalus (iNPH) remains controversial. Limited studies have indicated a high prevalence of obstructive sleep apnoea (OSA) amongst iNPH patients. The aim was to investigate the clinical correlates of OSA in iNPH patients. In this cross-sectional observational study, consecutive iNPH patients were prospectively enrolled. Evaluations included the iNPH Rating Scale, the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the time and number of steps to walk 10 m, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, a complete neuropsychological evaluation, 3-T brain MRI, full-night video-polysomnography, tap test and cerebrospinal fluid (CSF) neurodegeneration biomarkers. Fifty-one patients were screened, of whom 38 met the inclusion criteria. Amongst the recruited patients, 19/38 (50%) exhibited OSA, with 12/19 (63.2%) presenting moderate to severe disorder. OSA+ iNPH patients required more time (p = 0.02) and more steps (p = 0.04) to complete the 10-m walking test, had lower scores on the gait subitem of the iNPH Rating Scale (p = 0.04) and demonstrated poorer performance on specific neuropsychological tests (Rey Auditory Verbal Learning Test immediate recall, p = 0.03, and Rey-Osterrieth Complex Figure, p = 0.01). Additionally, OSA+ iNPH patients had higher levels of total tau (p = 0.02) and phospho-tau (p = 0.03) in their CSF but no statistically significant differences in beta-amyloid (1-42) levels compared to OSA- iNPH patients. Obstructive sleep apnoea is highly prevalent in iNPH patients, particularly at moderate to severe levels. OSA is associated with worse motor and cognitive performance in iNPH. The CSF neurodegeneration biomarker profile observed in OSA+ iNPH patients may reflect OSA-induced impairment of cerebral fluid dynamics.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact. We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. AD pathology on biopsy correlates with CSF β-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data. As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking. AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with β-amyloid pathology.

A comprehensive approach to lateral ventricular tumor resection: techniques, technologies, and outcomes.

This study reviews lateral ventricular tumors (LVTs), which are rare brain lesions accounting for 0.64-3.5% of brain tumors, and the unique challenges they present due to their location and growth patterns. Once deemed inoperable, advancements in microneurosurgery, imaging, and tumor pathobiology have significantly improved treatment outcomes. This letter summarizes recent studies and key findings in the management of LVTs. Research by S.A. Maryashev et al. identified risk factors for early hemorrhagic complications following the surgical resection of lateral ventricular neoplasms, highlighting the significance of patient characteristics, tumor location, and surgical approach. The study found that factors such as gender, hydrocephalus, tumor blood flow, and Evans index correlate with a higher risk of hemorrhage, with the transcallosal approach having a greater risk compared to the transcortical approach. The utilization of navigation technologies, including fMRI, neuronavigation, and intraoperative brain mapping, has been shown to reduce surgical complications and enhance patient outcomes in the treatment of lateral ventricular meningiomas. Moreover, endoscopic and endoport-assisted endoscopic techniques have proven to be valuable in intraventricular tumor surgery, enabling minimally invasive procedures with better visualization and fewer complications. The integration of advanced surgical techniques, neuroimaging, and neurophysiological monitoring emphasizes the necessity of a multidisciplinary approach to optimize patient outcomes. To improve the study's validity and applicability, further research with larger sample sizes and advanced statistical analyses is needed. This letter advocates for the continued exploration of innovative surgical techniques and technologies to enhance the management of lateral ventricular tumors.

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

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

Examining The Relationship Between Lateral Ventricle Volumetric Index and Linear Indexes in Childhood and Adolescence: A Retrospective MRI Study

Objective: Indexes obtained from two-dimensional and three-dimensional measurements are used to evaluate the brain's lateral ventricle (LV) structure. However, there were limited studies on how well the Evans index (EI) and the Bicaudate index (BI), which estimate LV volume, represent the LV volumetric index (LVVI) in the childhood and adolescence period. This study investigated the relationship between LVVI and linear indexes (EI and BI) in the pediatric period regarding age and sex factors. Method: This study was performed retrospectively in 588 individuals (267 [45.4%] females) aged 1-18 years with normal brain magnetic resonance images (MRI) between 2012 and 2021. LVVI was obtained by segmenting three-dimensional T1-weighted MRIs with volBrain1.0. LVVI was obtained by dividing the LV absolute volume by the total intracranial volume. We made linear measurements for EI and BI with the 3D Slicer. In this study, we compared the data obtained from individuals in 16 different age ranges between 1-18 years old with SPSS (ver.28). Results: In our study, we found the mean value of LVVI to be 0.656±0.372%. The mean values of EI and BI were 0.242±0.025 and 0.070±0.022, respectively. In the pediatric population, we found that mean values of EI and BI were significantly higher in males than in females (p

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

Idiopathic normal-pressure hydrocephalus (iNPH) is a clinic-radiological neurological syndrome presenting with cognitive deficits, gait disturbances and urinary incontinence. It often coexists with Alzheimer's disease (AD). Due to the reversible nature of iNPH when promptly treated, a lot of studies have focused on possible biomarkers, among which are cerebrospinal fluid (CSF) biomarkers. The aim of the present study was to determine the rate of beta-amyloid pathology and AD co-pathology by measuring AD CSF biomarkers, namely, amyloid beta with 42 and 40 amino acids (Aβ42), the Aβ42/Aβ40 ratio, total Tau protein (t-Tau) and phosphorylated Tau protein at threonine 181 (p-Tau), in a cohort of iNPH patients, as well as to investigate the possible associations among CSF biomarkers and iNPH neuropsychological profiles. Fifty-three patients with iNPH were included in the present study. CSF Aβ42, Aβ40, t-Tau and p-Tau were measured in duplicate with double-sandwich ELISA assays. The neuropsychological evaluation consisted of the Mini-Mental State Examination, Frontal Assessment Battery, Five-Word Test and CLOX drawing tests 1 and 2. After statistical analysis, we found that amyloid pathology and AD co-pathology are rather common in iNPH patients and that higher values of t-Tau and p-Tau CSF levels, as well as the existence of the AD CSF profile, are associated with more severe memory impairment in the study patients. In conclusion, our study has confirmed that amyloid pathology and AD-co-pathology are rather common in iNPH patients and that CSF markers of AD pathology and t-Tau are associated with a worse memory decline in these patients.

Diagnosis, clinical symptoms and treatment of Hakim-Adams syndrome

Diagnosis, clinical symptoms and treatment of Hakim-Adams syndrome

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

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

Blood-brain barrier-associated biomarker correlated with cerebral small vessel disease and shunt outcome in normal pressure hydrocephalus: a prospective cohort study.

Blood-brain barrier (BBB) breakdown is associated with neurodegeneration and cognitive impairment. Cerebral small vessel disease (CSVD) is also common in idiopathic normal pressure hydrocephalus (iNPH). Biomarkers in the cerebrospinal fluid (CSF) may reflect the severity of neuropathological damage and indicate a relationship between BBB integrity and iNPH and its surgical outcome. We investigated the association of CSVD and comorbidity-related CSF biomarkers with shunt outcomes in iNPH. This prospective cohort study recruited 53 patients with iNPH, who were subgrouped by CSVD severity. CSF proteins were analyzed, including soluble platelet-derived growth factor receptor-β (sPDGFR-β), Alzheimer's disease biomarkers, neurofilament light chain (NfL), and triggering receptor expressed on myeloid cells 2 (Trem2). We assessed symptom improvement, investigated its association with biomarkes levels, calculated protein cutoffs for surgical outcomes using receiver operating characteristic (ROC) curves, and compared model predictions using different proteins using hierarchical regression analysis. Among patients with iNPH, 74% had comorbid CSVD. Patients with severe CSVD exhibited significantly higher sPDGFR-β levels (P=0.019) and better postoperative performance (β=0.332, t=2.174, P=0.039; r=0.573, P=0.001). Analysis of the predictive potential of the biomarkers showed that sPDGFR-β was predictive of surgical outcomes (area under curve=0.82, sensitivity=66.8%, specificity=94.7%). A Comparison of the models revealed a greater effect of sPDGFR-β (Adjusted R2=0.247, ∆R2=0.160, ∆F(1, 37)=8.238, P=0.007) on cognitive improvement. This study highlighted the relevance of CSF biomarkers in assessing CSVD severity and predicting iNPH surgical outcome. CSF shunt surgery may provide an alternative treatment for neurodegenerative diseases with BBB breakdown and dysfunctional CSF clearance.

Predictors of Hydrocephalus Risk After Stereotactic Radiosurgery for Vestibular Schwannomas: Utility of the Evans Index.

Hydrocephalus after Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannomas is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on hydrocephalus risk remains poorly defined. A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® SRS for unilateral vestibular schwannomas from 2011 to 2021 was performed. Patients with prior hydrocephalus and cerebrospinal fluid diversion or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)-maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull-were measured on axial postcontrast T1-weighted magnetic resonance imaging. A total of 378 patients met the inclusion criteria; 14 patients (3.7%) developed symptomatic communicating hydrocephalus and 10 patients (2.6%) underwent shunt placement and 4 patients (1.1%) were observed with milder symptoms. The median age of patients who developed hydrocephalus was 69 years (IQR, 67-72) and for patients younger than age 65 years, the risk was 1%. For tumor volumes <1 cm3, the risk of requiring shunting was 1.2%. The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (P = .024) and tumor volume >3 cm3 (P = .007), respectively, in multivariate analysis. Fourth ventricle distortion on pre-SRS imaging was significantly associated with hydrocephalus incidence (P < .001). Patients with vestibular schwannoma with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. These patients should be counseled regarding risk of hydrocephalus and carefully monitored after SRS.

A Brief Review on Normal Pressure Hydrocephalus Diagnosis in Primary Neuropsychiatric Care Settings

Normal pressure hydrocephalus (NPH) is clinically characterized by the triad of mental deterioration, gait disturbance, and urinary incontinence. Correct diagnosis and referral of patients is important because NPH is a potentially treatable cause of cognitive decline and should be distinguished from more common forms of irreversible dementia. Unfortunately, it remains to be a rather underdiagnosed and controversial neuropsychiatric entity even in countries with modern healthcare systems. The diagnostic process is complicated by diverse clinical presentations, especially when the classical triad is incomplete or atypical such as with psychiatric symptoms. This manuscript aims to briefly review atypical clinical presentations of NPH and basic radiologic findings associated with it, and outline some recommendations to primary care physicians for diagnosis and referral.

Green Solid Lipid Nanoparticles by Fatty Acid Coacervation: An Innovative Nasal Delivery Tool for Drugs Targeting Cerebrovascular and Neurological Diseases.

Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, a common disease in older adults. Potential pharmacological treatments, based upon intranasal administration, are worthy of investigation because they might improve symptoms and avoid surgery by overcoming the blood-brain barrier and avoiding hepatic metabolism. Nasal lipid nanocarriers, such as solid lipid nanoparticles, may increase the nasal retention and permeation of drugs. To this aim, green solid lipid nanoparticles, obtained by coacervation from natural soaps, are promising vehicles due to their specific lipid matrix composition and the unsaponifiable fraction, endowed with antioxidant and anti-inflammatory properties, and thus suitable for restoring the neurovascular unit function. In this experimental work, such green solid lipid nanoparticles, fully characterized from a physico-chemical standpoint, were loaded with a drug combination suitable for reverting hydrocephalus symptoms, allowing us to obtain a non-toxic formulation, a reduction in the production of the cerebrospinal fluid in vitro, and a vasoprotective effect on an isolated vessel model. The pharmacokinetics and biodistribution of fluorescently labelled nanoparticles were also tested in animal models.