Search Results (46)

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

Pathological gait in patients with Hakim’s disease (HD, synonymous with idiopathic normal-pressure hydrocephalus; iNPH), Parkinson’s disease (PD), and cervical myelopathy (CM) has been subjectively evaluated in this study. We quantified the characteristics of upper and lower limb movements in patients with pathological gait. We analyzed 1491 measurements of 1 m diameter circular walking from 122, 12, and 93 patients with HD, PD, and CM, respectively, and 200 healthy volunteers using the Three-Dimensional Pose Tracker for Gait Test. Upper and lower limb movements of 2D coordinates projected onto body axis sections were derived from estimated 3D relative coordinates. The hip and knee joint angle ranges on the sagittal plane were significantly smaller in the following order: healthy > CM > PD > HD, whereas the shoulder and elbow joint angle ranges were significantly smaller, as follows: healthy > CM > HD > PD. The outward shift of the leg on the axial plane was significantly greater, as follows: healthy < CM < PD < HD, whereas the outward shift of the upper limb followed the order of healthy > CM > HD > PD. The strongest correlation between the upper and lower limb movements was identified in the angle ranges of the hip and elbow joints on the sagittal plane. The lower and upper limb movements during circular walking were correlated. Patients with HD and PD exhibited reduced back-and-forth swings of the upper and lower limbs. Full article

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. Full article

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. Full article

The aim of this study was to employ artificial intelligence (AI)-based magnetic resonance imaging (MRI) brain volumetry to potentially distinguish between idiopathic normal pressure hydrocephalus (iNPH), Alzheimer’s disease (AD), and age- and sex-matched healthy controls (CG) by evaluating cortical, subcortical, and ventricular volumes. Additionally, correlations between the measured brain and ventricle volumes and two established semi-quantitative radiologic markers for iNPH were examined. An IRB-approved retrospective analysis was conducted on 123 age- and sex-matched subjects (41 iNPH, 41 AD, and 41 controls), with all of the iNPH patients undergoing routine clinical brain MRI prior to ventriculoperitoneal shunt implantation. Automated AI-based determination of different cortical and subcortical brain and ventricular volumes in mL, as well as calculation of population-based normalized percentiles according to an embedded database, was performed; the CE-certified software mdbrain v4.4.1 or above was used with a standardized T1-weighted 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence. Measured brain volumes and percentiles were analyzed for between-group differences and correlated with semi-quantitative measurements of the Evans’ index and corpus callosal angle: iNPH patients exhibited ventricular enlargement and changes in gray and white matter compared to AD patients and controls, with the most significant differences observed in total ventricular volume (+67%) and the lateral (+68%), third (+38%), and fourth (+31%) ventricles compared to controls. Global ventriculomegaly and marked white matter reduction with concomitant preservation of gray matter compared to AD and CG were characteristic of iNPH, whereas global and frontoparietally accentuated gray matter reductions were characteristic of AD. Evans’ index and corpus callosal angle differed significantly between the three groups and moderately correlated with the lateral ventricular volumes in iNPH patients [Evans’ index (r > 0.83, p ≤ 0.001), corpus callosal angle (r < −0.74, p ≤ 0.001)]. AI-based MRI volumetry in iNPH patients revealed global ventricular enlargement and focal brain atrophy, which, in contrast to healthy controls and AD patients, primarily involved the supratentorial white matter and was marked temporomesially and in the midbrain, while largely preserving gray matter. Integrating AI volumetry in conjunction with traditional radiologic measures could enhance iNPH identification and differentiation, potentially improving patient management and therapy response assessment. Full article

Idiopathic obstruction of the outlets of the fourth ventricle (FVOO) is a rare cause of hydrocephalus, which can be misdiagnosed as communicating hydrocephalus due to the enlargement of all four ventricles. Different surgical approaches are discussed in the literature. We present a case report of a 25-year-old male admitted with headache, vertigo, and nystagmus. The MRI scan showed a tetraventricular hydrocephalus with a patent aqueduct. After endoscopic third ventriculostomy (ETV), symptoms resolved. We performed a systematic review of the literature, covering 26 years, with the aim to investigate the symptoms, therapy, and outcome of primary FVOO, according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. We found 9 case reports and 2 case series and could extract a total of 34 cases. After ETV all symptoms resolved in 10 of 23 cases (43.5%), and in 13 of 23 cases (56.5%) symptoms improved partially. Seven cases (30.4%) required additional surgery. A decrease in ventricular volume occurred in most cases. In the 10 patients who were operated via fenestration, all symptoms resolved in 6 cases. ETV seems to be an effective treatment option for patients with idiopathic FVOO in a majority of cases. In special cases, fenestration of the foramen of Magendie may be suitable. Full article

We aimed to capture the fluctuations in the dynamics of body positions and find the characteristics of them in patients with idiopathic normal pressure hydrocephalus (iNPH) and Parkinson’s disease (PD). With the motion-capture application (TDPT-GT) generating 30 Hz coordinates at 27 points on the body, walking in a circle 1 m in diameter was recorded for 23 of iNPH, 23 of PD, and 92 controls. For 128 frames of calculated distances from the navel to the other points, after the Fourier transforms, the slopes (the representatives of fractality) were obtained from the graph plotting the power spectral density against the frequency in log–log coordinates. Differences in the average slopes were tested by one-way ANOVA and multiple comparisons between every two groups. A decrease in the absolute slope value indicates a departure from the 1/f noise characteristic observed in healthy variations. Significant differences in the patient groups and controls were found in all body positions, where patients always showed smaller absolute values. Our system could measure the whole body’s movement and temporal variations during walking. The impaired fluctuations of body movement in the upper and lower body may contribute to gait and balance disorders in patients. Full article