Search Results (49)

Background/Objectives: Idiopathic normal pressure hydrocephalus (iNPH) is a potentially treatable syndrome, but biologically informative biomarkers remain limited. Progranulin (PGRN) constitutes a pleiotropic growth factor involved in neuroinflammation, lysosomal function, and tissue repair, which has not been adequately studied in iNPH. The purpose of this study was to examine the serum and cerebrospinal fluid (CSF) levels of PGRN in corresponding patients with suspected iNPH and its correlation with integrated clinical, functional, and neuroradiological parameters. Methods: Thirteen patients with probable iNPH underwent an evaluation protocol, including clinical assessment, neuroradiological evaluation, Tap-test with concomitant gait analysis, and paired serum/CSF sampling. PGRN concentrations in biofluids were measured by ELISA. Correlation analyses were performed. Composite Tap-test response variable derived from quantitative gait-improvement indices was modeled using ridge-logistic regression with leave-one-out cross-validation. Results: In the between-group analyses, serum and CSF concentrations of PGRN were not correlated (r = −0.10, p = 0.74), suggesting that peripheral and intrathecal PGRN behave as non-redundant, compartment-specific readouts rather than as interchangeable measures of the same biological process. Higher CSF concentration of PGRN was nominally associated with older age (r = 0.69, p = 0.009) and with poorer turning-time improvement after the Tap-test (r = −0.62, p = 0.025), while serum concentration of PGRN showed no meaningful associations with clinical or neuroradiological variables. In the model of logistic regression, inclusion of CSF concentration of PGRN substantially improved discrimination of Tap-test response. The full ridge-logistic regression model, including serum and CSF concentration of PGRN, symptom duration, and Kiefer score, achieved an accuracy of 0.923 and an AUC of 0.881. The CSF concentration of PGRN coefficient remained consistently negative across bootstrap resamples (penalized OR 0.434; 95% CI: 0.354–0.697), indicating that higher baseline CSF concentration of PGRN was associated with a lower probability of significant short-term Tap-test response, whereas serum PGRN contributed negligibly to the model. Conclusions: The observed changes in PGRN in CSF may reflect compartment-specific intrathecal inflammatory or tissue-stress processes and may help identify patients with lower short-term responsiveness to CSF drainage. These findings support further longitudinal evaluation of CSF concentration of PGRN for biological stratification and prognostic refinement in iNPH. Full article

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence; however, its diagnosis and prediction of shunt responsiveness remain challenging. This systematic review aimed to synthesize current evidence on cerebrospinal fluid (CSF) proteomic biomarkers in iNPH and to identify molecular patterns with diagnostic and prognostic relevance. A PRISMA-guided search of PubMed, Web of Science, and Google Scholar identified 14 eligible studies comprising 1171 iNPH patients. Proteomic analyses revealed substantial heterogeneity in study design and detected proteins; however, consistent patterns emerged. iNPH is associated with upregulation of inflammatory and extracellular matrix-related proteins and relative downregulation of synaptic and neuronal markers. Neurodegenerative proteins, including amyloid-β, tau, and neurofilament light chain, demonstrated value in differentiating iNPH from comorbid neurodegenerative diseases and in predicting response to ventriculoperitoneal shunting (VPS). These findings support a multifactorial model of iNPH involving impaired glymphatic clearance, neuroinflammation, blood–brain barrier dysfunction, and mechanical axonal stress. Multidimensional biomarker profiles, rather than single proteins, appear to provide the greatest clinical utility, highlighting the need for standardized proteomic panels and integrative predictive models. However, given the substantial heterogeneity of the included studies and the predominantly exploratory nature of current proteomic evidence, the identified proteins should be interpreted as candidate biomarkers rather than clinically validated diagnostic or prognostic tools. Multidimensional biomarker profiles appear biologically plausible and may offer greater explanatory value than single proteins, but their clinical utility requires validation in standardized prospective cohorts. The authors therefore propose a conceptual iNPH proteomic “Vulnerability Model” integrating CSF biomarkers to reflect the balance between reversible and irreversible pathology; this is currently a hypothetical model that requires rigorous statistical and clinical validation through large-scale prospective cohort studies before it can fulfill its potential for improving patient stratification and prediction of postoperative outcomes. Full article

Background: Lumboperitoneal (LP) shunt surgery is an established treatment for idiopathic normal pressure hydrocephalus (iNPH). In Japan, patients undergoing LP shunt surgery are often hospitalized for several days to more than one week after surgery, even in uncomplicated cases, reflecting concerns regarding early complications, cerebrospinal fluid overdrainage, and discharge readiness in older adults. This study evaluated the feasibility and short-term safety of a perioperative optimization pathway for planned short-stay hospitalization after LP shunt surgery. Methods: This single-center retrospective before-and-after cohort study included 15 consecutive patients who underwent elective LP shunt surgery. Six patients were managed using a conventional hospitalization pathway, whereas nine patients were treated under a short-stay pathway targeting discharge after one postoperative night. Key perioperative modifications included a uniform higher initial programmable valve pressure (level 7), structured discharge education, scheduled postoperative analgesia, waterproof wound sealing permitting early showering, and early outpatient follow-up with head computed tomography for staged valve pressure adjustment. The primary outcome was 30-day safety, defined as readmission, reoperation, or major postoperative complications. Results: Baseline characteristics were generally comparable between groups, although the short-stay group was slightly older and had more frequent antithrombotic therapy. Mean hospital length of stay was shorter in the short-stay group than in the conventional group (3.7 ± 2.0 vs. 9.7 ± 0.8 days; median, 3 vs. 9.5 days). Orthostatic headache requiring valve adjustment occurred in three conventional cases but in none of the short-stay patients. No patients in the short-stay group required readmission or reoperation within 30 days. Conclusions: In this pilot before-and-after study, a short-stay LP shunt pathway incorporating perioperative optimization and individualized discharge decision-making was feasible and was not associated with an apparent increase in early adverse events. These findings should be interpreted as exploratory and may support further evaluation of short-stay management strategies for selected patients undergoing LP shunt surgery in Japan. Full article

Background/Objectives: Hydrocephalus is defined as the symptomatic accumulation of excessive cerebrospinal fluid (CSF) within the ventricular system. It has an estimated incidence of 85 cases per 100,000 population annually in adults, making it one of the most common conditions managed by neurosurgeons globally. Many conditions may lead to ventricular dilation and hydrocephalus, such as hemorrhage, tumors, infection, trauma, and idiopathic normal-pressure hydrocephalus (iNPH). Regardless of the cause, the gold-standard treatment for hydrocephalus is CSF diversion, usually via a ventriculoperitoneal (VP) shunt. The goal of the present study is to present our experience regarding the etiology of hydrocephalus, management, and shunt failure characteristics over the last 11 years. Methods: A single-center retrospective cohort study was performed. Our cohort consisted of adult patients who were shunted or required revision surgery in our department over the last 11 years. Data regarding the etiology of hydrocephalus, management, shunt characteristics, revision status, and etiology of revision were collected and retrospectively analyzed. Univariable and multivariable logistic regression models were established in order to explore potential associations between the etiology of hydrocephalus and patient characteristics and risk of shunt revision. Revision-free survival probabilities were estimated using the Kaplan–Meier method, while shunt failure rates were also calculated. Results: Our cohort consisted of 114 patients, the median age was 59 (IQR = 26.5) years, and the male-to-female ratio was 1.04:1. The most common cause of hydrocephalus was iNPH (30.7%), followed by post-hemorrhagic (23.7%) and tumor-related hydrocephalus (21.1%). The 12-month revision rate was 13.6%, with overall revision-free survival of 86.4% at one year. Infection (43.2%) was the most common cause of shunt revision, followed by obstruction (16.2%), and mechanical disconnection and migration (18.9%). Younger age was associated with higher risk of revision, while etiology of hydrocephalus and patient sex were not. Conclusions: Our study adds to the pertinent literature data regarding hydrocephalus etiology, management strategies, and shunt failure rates across different hydrocephalus etiologies. Additionally, it serves as a foundation for future studies that could identify predictors of shunt failure, apart from the etiology of hydrocephalus, such as patient characteristics, surgical factors, or shunt types. Finally, we highlight the importance of comprehensive national and potentially continental registries, which will facilitate large-scale analyses. Full article

Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible cause of gait disturbance and cognitive impairment in older adults, yet its diagnosis remains challenging and controversial. The core difficulty lies in distinguishing true hydrocephalus from ventricular enlargement secondary to cerebral atrophy or neurodegenerative disease, a distinction now recognized as non-binary. In many patients, ventricular enlargement reflects a continuum ranging from predominantly hydrocephalic iNPH to mixed pathological states combining impaired cerebrospinal fluid (CSF) dynamics and neurodegeneration. Conventional neuroradiological markers, including the Evans Index, the callosal angle, and the disproportionately enlarged subarachnoid-space hydrocephalus (DESH) pattern, provide useful qualitative guidance but are limited by their two-dimensional nature, interobserver variability, and poor sensitivity for differential diagnosis and outcome prediction. Over the past decade, advances in artificial intelligence-based brain volumetry (AI-BrV) have introduced a new paradigm for quantitative structural assessment. By enabling automated, anatomically precise, and reproducible three-dimensional quantification of ventricular and extraventricular CSF, cortical and subcortical gray matter, deep gray matter nuclei, and periventricular white matter, AI-BrV addresses many limitations of traditional imaging approaches. Beyond absolute volume measurements, AI-BrV enables the derivation of composite indices and ratios that may capture disease-specific structural phenotypes and better reflect the underlying pathophysiology of ventricular enlargement. Importantly, AI-BrV pipelines can be applied retrospectively to large legacy neuroimaging datasets and compared with extensive publicly available repositories, facilitating normative modeling, cross-disease analyses, and external validation of volumetric biomarkers. When integrated with clinical data and multivariable statistical or machine-learning frameworks, these approaches hold promise for improving patient selection, refining disease categorization, and supporting more rational decision-making regarding CSF diversion. In this context, AI-BrV offers a unifying framework for reconciling divergent clinical perspectives and advancing iNPH toward a more precise, reproducible, and evidence-based diagnostic and therapeutic paradigm. Full article

Idiopathic normal-pressure hydrocephalus (iNPH) is clinically characterized by the Hakim–Adams triad: gait disturbance, cognitive decline, and urinary incontinence. Cognitive impairment in iNPH predominates as a subcortical syndrome, with deficits in executive functions, psychomotor slowing, and memory inefficiency. However, the cognitive profile is heterogeneous and often overlaps with other neurodegenerative conditions, complicating differential diagnosis. This study investigated the cognitive features of iNPH using the Rey Auditory Verbal Learning Test (RAVLT), comparing 29 iNPH patients to 28 healthy controls. Demographic and neuroimaging parameters—such as Evans Index and Callosal Angle—were assessed. Results indicated significantly lower Montreal Cognitive Assessment (MoCA) and RAVLT scores in iNPH patients compared to controls. Analysis of serial position effects revealed that, whereas healthy individuals exhibited typical primacy and recency effects in verbal memory, iNPH patients demonstrated a selective impairment of the primacy effect, likely reflecting hippocampal dysfunction. These findings underline the importance of detailed neuropsychological evaluation in differentiating iNPH from other dementias and suggest that damage to medial temporal lobe structures plays a prominent role in the verbal memory deficit observed in iNPH. Full article

Background and Objectives: Patients with idiopathic normal pressure hydrocephalus (INPH) present similar symptoms as other diseases, such as dementia (AD). However, while dementia is not reversible, INPH dementia can be treated through neurosurgery. This study aims to assess the Rorschach method as a valid tool to identify INPH patients. Materials and Methods: The perception characteristics of a small sample of patients (n = 19) were observed through the Rorschach Inblok test. Artificial neural network (ANN) models allowed us to analyze the correlations between patients’ cognitive functions and perception characteristics. Results: The results obtained revealed significant insights about the independent traits in patients’ patterns of response with INPH and AD. In performing the test, patients with INPH and AD concentrated more on the cards displayed and what they perceived, while other patients concentrated on reactions related to the image proposed. Conclusions: The Rorschach test is a valid predictor tool to identify INPH patients who could successfully be treated with neurosurgery. Hence, this methodology has potential in differential diagnosis applied to a clinical context. Full article

Background and Objectives: Idiopathic normal-pressure hydrocephalus (NPH) is a treatable, but diagnostically challenging condition in the elderly marked by gait disturbance, cognitive decline, and urinary incontinence. Ventriculoperitoneal (VP) shunting is effective, but the prognostic significance of symptom duration before surgery remains unclear. This systematic review evaluates symptom duration in NPH patients with postoperative outcomes. Methods: A systematic search of PubMed, Scopus, and Embase was conducted per PRISMA guidelines. Studies were included if they assessed clinical or radiological outcomes of VP shunting in adult NPH patients, reported symptom duration, and had a follow-up of at least one month. Clinical outcomes (MMSE, TUG, NPH score) were qualitatively analyzed due to study heterogeneity. Results: Twenty-four studies comprising 1169 patients were included (mean age: 72.45 years; mean symptom duration: 33.04 months). Most studies reported clinical improvement after VP shunting. However, few directly evaluated the effect of symptom duration, yielding inconsistent findings: some suggested better outcomes with shorter symptom duration, while others found no clear correlation. Larger studies often lacked conclusive data, and no randomized controlled trials were identified. Conclusions: VP shunting remains an effective intervention for NPH; however, evidence supporting the predictive value of preoperative symptom length is inconclusive. This review highlights the need for standardized diagnostic protocols and larger prospective studies to clarify this association and optimize surgical timing. Full article

Hydrocephalus is a complex neurological condition marked by abnormal cerebrospinal fluid (CSF) accumulation, often leading to elevated intracranial pressure and structural brain damage. Despite advances in surgical treatment, diagnostic precision and prognosis remain challenging, especially in idiopathic normal pressure hydrocephalus (iNPH). This narrative review aims to synthesize the current knowledge regarding molecular and neuroimaging biomarkers that hold diagnostic, prognostic, and therapeutic significance in hydrocephalus. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar. The inclusion criteria encompassed peer-reviewed studies involving congenital or acquired hydrocephalus and reporting on mechanistic, diagnostic, or monitoring biomarkers. Both established and emerging biomarkers were included, and preclinical findings were considered when translational relevance was apparent. The review highlights a broad spectrum of molecular markers including aquaporins, vascular endothelial growth factor, neurofilaments, glial fibrillary acidic protein, matrix metalloproteinases, and neuroinflammatory markers. The genetic markers associated with ciliogenesis also show promise in subtyping disease. Parallel to molecular advances, neuroimaging techniques, ranging from classic markers like Evans’ index to advanced modalities such as diffusion tensor imaging (DTI), arterial spin labeling (ASL), and glymphatic MRI, provide functional perspectives on hydrocephalus diagnosis and management, while artificial intelligence may further enhance diagnostic algorithms. Molecular and imaging markers could not only increase diagnostic confidence, but also provide information on disease causes and progression. As research progresses, merging various methodologies may result in more accurate diagnoses. Full article

Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients. Full article

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R_out) or the venous sinus pressure. Studies simultaneously measuring the ICP and sagittal sinus pressures in IIH suggest that there is either a reduction in the R_out and/or the CSF_fr. The latter suggests that the increased venous pressure can be the only variable causing this disease process. A study maintaining the ICP at zero showed a significantly elevated CSF_fr in this disease. The purpose of the current study is to define the most feasible explanation for these findings and to suggest a viable pathophysiology for IIH. Methods: A lumped parameter vascular model, originally developed to study normal pressure hydrocephalus, was extended to investigate IIH. The model used the simultaneously obtained ICP and sagittal sinus pressure measurements from five experiments published in the literature to estimate the CSF_fr and the capillary transmural pressure (TMP). The assumptions made during this study were those of a normal mean arterial pressure, a normal total R_out and a normal blood flow rate. Results: When the CSF formation rates were plotted against the estimated capillary transmural pressures, a straight line was returned, suggesting that the CSF_fr and capillary TMP are related. Conclusions: The novel findings of this study suggest that the CSF_fr in IIH varies with the capillary TMP. A reduced capillary TMP in IIH can moderate the ICP if there is net CSF absorption across the capillaries. This would require the blood–brain barrier (BBB) to be disrupted. The model suggests that drugs which stabilise the BBB may trigger IIH by blocking CSF absorption across the capillaries, increasing the apparent CSF formation rate back toward normal and increasing the ICP. Anaemia will promote IIH by increasing the cerebral blood flow, the capillary TMP and the CSF_fr. Full article

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cognitive decline, gait disturbances, and urinary incontinence. Surgical interventions such as ventriculoperitoneal shunt (VPS) and endoscopic third ventriculostomy (ETV) are the primary treatment options. While VPS is the standard of care, ETV offers a minimally invasive alternative with potentially fewer complications. However, comparative evidence regarding their impact on cognitive, motor, and structural outcomes remains limited. This study, titled ENVENTOR-iNPH (endoscopic ventriculostomy versus shunt on neuropsychological and motor performance in patients with iNPH), aims to address this gap through a rigorously designed comparative protocol. Methods: This protocol is designed as a multicenter, randomized, controlled trial (ENVENTOR-iNPH) to compare the effects of ETV and VPS in patients diagnosed with iNPH. The study will enroll 100 patients aged 60 years or older, randomly assigned to undergo ETV (n = 50) or VPS (n = 50). Preoperative and postoperative evaluations will include comprehensive cognitive and motor assessments, standardized quality-of-life instruments, and advanced neuroimaging techniques such as MRI with flowmetry and diffusion tensor imaging (DTI). Functional outcomes will also be evaluated using navigated transcranial magnetic stimulation (nTMS) and wearable motion analysis systems. The objective of this study is to compare the efficacy and safety of ETV versus VPS in restoring cognitive and motor performance in patients with iNPH. Results: Primary outcomes include cognitive and motor function improvements. Secondary endpoints are surgical complications, hospital stay duration, and changes in quality of life. Neuroimaging will assess changes in white matter integrity and cerebrospinal fluid dynamics, while nTMS will provide insights into neuroplasticity and motor pathway recovery. ETV is hypothesized to demonstrate clinical outcomes comparable or superior to VPS, particularly in terms of complication reduction and hospital recovery metrics. Conclusions: The ENVENTOR-iNPH protocol establishes the framework for a comprehensive, multicenter study comparing ETV and VPS in iNPH patients. The findings from this initial study will inform the design of larger-scale multicenter trials, guide clinical decision making, and potentially position ETV as a preferred treatment option for eligible patients. Full article

Background: Lee Silverman Voice Treatment-BIG (LB) was developed for Parkinson’s disease patients to improve patients’ movement amplitude and accuracy through large movements and enhance movements through self-awareness and recalibration. This study aimed to review studies on LB for neurological diseases other than Parkinson’s disease and examine its potential as an intervention tool. Method: The main search databases included Google Scholar, PubMed, and ScienceDirect. ‘Neurological disease’, ‘LSVT-BIG’, ‘Treatment or Rehabilitation’, ‘Intervention’, and ‘Therapy’ were used as search keywords until December 2024, and eight articles were finally selected. Results: As a result of analyzing eight studies, there were four studies on stroke (all conducted by occupational therapists) and four studies on other diseases, including two studies on progressive supranuclear palsy, one study on idiopathic normal pressure hydrocephalus, and one study on Huntington’s disease (all conducted by physical therapists). Conclusions: LB had a positive effect on improving physical function and overall motor control in patients with neurological diseases other than Parkinson’s disease, indicating its potential as an intervention tool. In the future, studies that have high-level evidence-based study designs and complement small sample sizes are needed to demonstrate the effectiveness of LB. Full article

Background/Objectives: Ventriculoperitoneal shunting is a validated procedure for the treatment of idiopathic normal-pressure hydrocephalus. To select shunt-responsive patients, infusion and tap tests can be used. Only gait is evaluated after the procedure to establish a potential improvement. In this study, we present our Hydro-Real-Time Neuropsychological Testing protocol to assess the feasibility of performing an ultra-fast assessment of patients during the infusion and tap test. Methods: We tested 57 patients during the infusion and tap test to obtain real-time feedback on their cognitive status. Data were obtained immediately before the infusion phase (T0), when the pressure plateau was reached (T1), and immediately after cerebrospinal fluid subtraction (T2). Based on cerebrospinal fluid dynamics, 63.15% of the patients presented a resistance to outflow > 12 mmHg/mL/min, while 88% had a positive tap test response. Results: Compared to T0, cerebrospinal fluid removal significantly improved performance on tasks exploring executive functions (counting backward, p < 0.001; verbal fluency, p < 0.001). Patients were significantly faster at counting backward at T2 vs. T1 (p < 0.05) and at T2 vs. T0 (p < 0.001) and were significantly faster at counting forward at T2 vs. T1 (p < 0.005), suggesting an improvement in speed at T2. There was a significantly smaller index at T1 vs. T0 (p = 0.005) and at T2 vs. T0 (p < 0.001), suggesting a more marked improvement in patients’ executive abilities at T2 and a smaller improvement at T1. Regarding verbal fluency, patients were worse at T1 vs. T0 (p < 0.001) and at T2 vs. T0 (p < 0.001). Conclusions: Patients’ performance can be monitored during the infusion and tap test as significant changes in executive functions are observable. In future, this protocol might help improve patients’ selection for surgery. Full article

In this prospective observational cohort study, we provide preliminary findings from a same-day multidisciplinary fast-tracked normal pressure hydrocephalus (NPH) clinic; incorporating the expertise of movement disorders neurologists, emphasizing the clinical characteristics, consensus classification, and management of patients referred for suspected NPH. We evaluated 111 patients (male/female: 67/44) from April 2022 to May 2023. Based on the multidisciplinary team consensus, 52 (46.8%) were classified as “probable” idiopathic NPH (iNPH), 14 (12.6%) as “possible” NPH, 42 (37.8%) as “unlikely” NPH, and three (2.7%) as secondary NPH. While parkinsonian syndromes were recognized in 19.2% of “probable” iNPH patients (vs. 7.1% in “possible” and 26.2% in “unlikely” NPH), no significant group differences were noted in the scores of the UPDRS-III scale. Degenerative spine pathologies were prevalent across all NPH categories, affecting at least 50% of patients. In the “probable” iNPH group, 78.8% received programmable ventriculoperitoneal shunts, with clinical improvement identified in 87.8% at 12-month follow-up. Our findings underscore the high prevalence of overlapping and competing movement and spinal disorders in patients with suspected NPH. Further, our novel approach, incorporating movement disorder neurologists in NPH multidisciplinary evaluation, improved diagnostic precision and streamlined personalized plans, including further neurological workups, necessary spinal interventions, and medical management or rehabilitation. Full article