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

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

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

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

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

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

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

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

Profiling iNPH features through cluster analysis: an aid for clinical suspicion and diagnosis.

PURPOSE: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a neurological syndrome defined by gait disturbance, cognitive impairment and urinary incontinence. However, its clinical presentation can vary widely due to overlapping syndromes and common comorbidities in older adults. This study aims to provide practical guidance to aid in the clinical suspicion and support the diagnostic and therapeutic processes for these patients. METHODS: Six quantitative variables regarding clinical, functional, and demographic aspects were considered for a large sample of patients with diagnosed iNPH. Principal component analysis (PCA) was adopted to define the main dimensions explaining the variability of the phenomenon. Then, two clusters of iNPH patients were described. RESULTS: 178 patients were included in the analysis. The PCA produced two dimensions covering 61.8% of the total variability. The first one relied mainly on both clinical (mRS, iNPHGs) and functional (TUG, Tinetti) variables, while the second one was represented mainly on the demographic pattern (age and education). Cluster analysis depicted two main groups of patients. Cluster n.1 is composed of individuals who are older, more disabled, with poor functional performances, and highly symptomatic. Cluster n.2 patients are slightly younger, more educated, fitter, and with more nuanced clinical aspects. CONCLUSIONS: Profiling iNPH patients using quantitative variables and cluster analysis can help identify distinct characteristics of these patients, aiding in the guidance of both medical and surgical interventions.

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

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

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

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

'Watkins' & 'Watkins2.0': Smart phone applications (Apps) for gait-assessment in normal pressure hydrocephalus and decompensated long-standing overt ventriculomegaly.

OBJECTIVE: Gait disturbance is one of the features of normal pressure hydrocephalus (NPH) and decompensated long-standing overt ventriculomegaly (LOVA). The timed-up-and-go (TUG) test and the timed-10-m-walking test (10MWT) are frequently used assessments tools for gait and balance disturbances in NPH and LOVA, as well as several other disorders. We aimed to make smart-phone apps which perform both the 10MWT and the TUG-test and record the results for individual patients, thus making it possible for patients to have an objective assessment of their progress. Patients with a suitable smart phone can perform repeat assessments in their home environment, providing a measure of progress for them and for their clinical team. METHODS: 10MWT and TUG-test were performed by 50 healthy adults, 67 NPH and 10 LOVA patients, as well as 5 elderly patients as part of falls risk assessment using the Watkins2.0 app. The 10MWT was assessed with timed slow-pace and fast-pace. Statistical analysis used SPSS (version 25.0, IBM) by paired t-test, comparing the healthy and the NPH cohorts. Level of precision of the app as compared to a clinical observer using a stopwatch was evaluated using receiver operating characteristics curve. RESULTS: As compared to a clinical observer using a stopwatch, in 10MWT the app showed 100% accuracy in the measure of time taken to cover distance in whole seconds, 95% accuracy in the number of steps taken with an error ± 1-3 steps, and 97% accuracy in the measure of total distance covered with error of ± 0.25-0.50 m. The TUG test has 100% accuracy in time taken to complete the test in whole seconds, 97% accuracy in the number of steps with an error of ± 1-2 steps and 87.5% accuracy in the distance covered with error of ± 0.50 m. In the measure of time, the app was found to have equal sensitivity as an observer. In measure of number of steps and distance, the app demonstrated high sensitivity and precision (AUC > 0.9). The app also showed significant level of discrimination between healthy and gait-impaired individuals. CONCLUSION: 'Watkins' and 'Watkins2.0' are efficient apps for objective performance of 10MWT and the TUG-test in NPH and LOVA patients and has application in several other pathologies characterised by gait and balance disturbance.

The benefits of ventriculoperitoneal shunting in normal pressure hydrocephalus patients-a follow-up of three years.

OBJECTIVE: The ventriculoperitoneal shunt (VPS) is an established approach in treating normal pressure hydrocephalus (NPH). This study aims to examine the long-term effects of VPS regarding clinical and radiological outcomes, to explore interdependencies with comorbidities and medication, and to determine a suitable opening pressure of the programmable valve. METHODS: 127 patients with VPS were retrospectively evaluated. The Hakim triad along with Evans index (EI) and callosal angle (CA) were examined preoperatively and postoperatively at various time points up to over thirty-six months. Preexisting comorbidities and medication were considered. Adjustments to valve settings were documented along with symptom development and complications. Wilcoxon and paired-sample t-tests were used to analyze postoperative change. Chi-square, Eta-squared, and Pearson coefficients were used in correlation analyses. RESULTS: Relief from individual symptoms was most prominent within the first 6 months (p < 0.01). EI and CA significantly decreased and increased, respectively (p < 0.05). Postoperative clinical and radiological improvement was largely maintained over the follow-up period. Diabetes mellitus and apoplexy correlated with surgical outcomes (p < 0.05). The median opening pressure as a function of overall symptom management was determined to be 120 mmH2O for women and 140 mmH2O for men. CONCLUSION: VPS is effective in treating NPH with respect to both clinical and radiological outcomes, although these two components are independent of each other. Improvement is most pronounced in short-term and maintained in the long-term. Comorbidities have significant influence on the course of NPH. The valve setting does not forecast change in radiological findings; consequently, priority should be placed on the patient's clinical condition.

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

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

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

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

Combining Unilateral Biportal Endoscopic Surgery with Lumboperitoneal Shunt Surgery for Patients with Coexisting Normal-Pressure Hydrocephalus and Lumbar Spinal Stenosis: A Technical Note.

BACKGROUND: Normal-pressure hydrocephalus (NPH) is a condition characterized by an abnormal cerebrospinal fluid homeostasis in the brain, resulting in cognitive decline, gait disturbances, and urinary incontinence. Globally, the frequency of NPH becomes has become a major clinical concern with an increase in the elderly population. A lumboperitoneal (LP) shunt surgery is one therapeutic intervention, which diverts cerebrospinal fluid from the brain to the peritoneal cavity to mitigate NPH symptoms. However, LP shunt surgery can be precluded by lumbar spine degeneration. METHODS: In the cases of comorbidity involving NPH and lumbar spine degeneration, the combination of unilateral biportal endoscopic surgery, which is a minimally invasive spinal procedure, and LP shunt surgery is a new alternative. Both spinal degeneration and NPH are concurrently addressed in this approach. RESULTS: A 70-year-old patient with NPH and severe lumbar stenosis successfully underwent the aforementioned combined surgery, with remarkable improvement in symptoms. CONCLUSIONS: While the result is promising, the efficacy of this method warrants validation by conducting larger studies. Nonetheless, combining unilateral biportal endoscopic and LP shunt surgeries could redefine treatment for elderly patients with NPH and spinal stenosis.

Genetics and molecular pathophysiology of normal pressure hydrocephalus.

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

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

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

Changes in Callosal Angle and Evans Index After Shunt Surgery in Patients with Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is a disease characterized by gait disturbance, cognitive impairment, and urinary incontinence. For those patients who do not respond to shunt surgery, it lacks objective radiologic findings for the diagnosis of shunt malfunction. Here we aimed to evaluate whether the Evans index and callosal angle change during a prospective long-term follow-up of patients with iNPH submitted to shunt surgery. METHODS: Clinical (NPH Japanese Scale) and radiologic (Evans index and callosal angle) data were collected pre- and postoperatively (3, 6, 12 and months) in 19 patients with iNPH. Imaging tests were evaluated by the same neuroradiologist during the follow-up. RESULTS: Patients had lower scores on the NPH Japanese Scale over time (P < 0.001). There was no significant difference among Evans index values during the follow-up (P = 0.24). Preoperative average callosal angle was 72 ± 15, which increased to 91 ± 18 in 6 months (P = 0.003). CONCLUSIONS: In this sample, patients with iNPH submitted to a programmable valve shunt had an increase in callosal angle concomitant to neurologic improvement. The Evans index did not change during follow-up.

Methodological challenges of measuring brain volumes and cortical thickness in idiopathic normal pressure hydrocephalus with a surface-based approach.

Identifying disease-specific imaging features of idiopathic Normal Pressure Hydrocephalus (iNPH) is crucial to develop accurate diagnoses, although the abnormal brain anatomy of patients with iNPH creates challenges in neuroimaging analysis. We quantified cortical thickness and volume using FreeSurfer 7.3.2 in 19 patients with iNPH, 28 patients with Alzheimer's disease (AD), and 30 healthy controls (HC). We noted the frequent need for manual correction of the automated segmentation in iNPH and examined the effect of correction on the results. We identified statistically significant higher proportion of volume changes associated with manual edits in individuals with iNPH compared to both HC and patients with AD. Changes in cortical thickness and volume related to manual correction were also partly correlated with the severity of radiological features of iNPH. We highlight the challenges posed by the abnormal anatomy in iNPH when conducting neuroimaging analysis and emphasise the importance of quality checking and correction in this clinical population.

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

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

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

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

Deep learning assisted quantitative analysis of Aß and microglia in patients with idiopathic normal pressure hydrocephalus in relation to cognitive outcome.

Neuropathologic changes of Alzheimer disease (AD) including Aß accumulation and neuroinflammation are frequently observed in the cerebral cortex of patients with idiopathic normal pressure hydrocephalus (iNPH). We created an automated analysis platform to quantify Aß load and reactive microglia in the vicinity of Aß plaques and to evaluate their association with cognitive outcome in cortical biopsies of patients with iNPH obtained at the time of shunting. Aiforia Create deep learning software was used on whole slide images of Iba1/4G8 double immunostained frontal cortical biopsies of 120 shunted iNPH patients to identify Iba1-positive microglia somas and Aß areas, respectively. Dementia, AD clinical syndrome (ACS), and Clinical Dementia Rating Global score (CDR-GS) were evaluated retrospectively after a median follow-up of 4.4 years. Deep learning artificial intelligence yielded excellent (>95%) precision for tissue, Aß, and microglia somas. Using an age-adjusted model, higher Aß coverage predicted the development of dementia, the diagnosis of ACS, and more severe memory impairment by CDR-GS whereas measured microglial densities and Aß-related microglia did not correlate with cognitive outcome in these patients. Therefore, cognitive outcome seems to be hampered by higher Aß coverage in cortical biopsies in shunted iNPH patients but is not correlated with densities of surrounding microglia.

Neurosarcoidosis as a rapidly progressive dementia associated with normal pressure hydrocephalus.

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.

La neurosarcoidosis es un subtipo raro de sarcoidosis con mal pronóstico y diversas presentaciones clínicas que a menudo plantea un reto diagnóstico y terapéutico. Describimos el caso de un varón de 53 años con diagnóstico inicial de sarcoidosis lingual, que posteriormente desarrolló ataxia y deterioro cognitivo de rápida evolución. Una punción lumbar reveló hipoglucorraquia, hiperproteinorraquia, pleocitosis linfocítica y niveles elevados de IL-6 (600 pg/ml). La citometría de flujo del líquido cefalorraquídeo mostró una concentración elevada de linfocitos CD4 y un cociente CD4+/CD8+ de 3.91, indicativo de neurosarcoidosis. La RM cerebral evidenció lesiones hiperintensas periventriculares y subcorticales en FLAIR/T2 que se asemejaban a una leucoencefalopatía multifocal progresiva (LMP), aunque la PCR negativa para el virus JC descartó el diagnóstico diferencial. Tras un curso evolutivo favorable con pulsos de corticoides, el paciente recayó con hidrocefalia normotensiva, tratada con inmunosupresores y derivación ventriculoperitoneal con buena respuesta hasta la fecha. Este caso subraya la importancia de mantener un alto índice de sospecha de neurosarcoidosis en individuos con sarcoidosis y síntomas neurológicos. En estos casos, los biomarcadores del líquido cefalorraquídeo tales como la IL-6 y el cociente CD4+/CD8+ son esenciales para orientar el diagnóstico. Además, destaca que la hidrocefalia es una complicación poco frecuente y requiere un abordaje multidisciplinario, que incluya tratamiento médico y neuroquirúrgico.