Normal Pressure Hydrocephalus Research Articles

Neurocognitive change over the course of a multiday external lumbar drain trial in patients with suspected normal pressure hydrocephalus

Objective: To characterize neurocognitive response to cerebrospinal fluid (CSF) diversion during a multiday external lumbar drainage (ELD) trial in patients with suspected normal pressure hydrocephalus (NPH). Methods: Inpatients (N = 70) undergoing an ELD trial as part of NPH evaluation participated. Cognition and balance were assessed using standardized measures before and after a three-day ELD trial. Cognitive change pre- to post-ELD trial was assessed in relation to change in balance, baseline neuroimaging findings, NPH symptoms, demographics, and other disease-relevant clinical parameters. Results: Multiday ELD resulted in significant cognitive improvement (particularly on measures of memory and language). This improvement was independent of demographics, test-retest interval, number of medical and psychiatric comorbidities, NPH symptom duration, estimated premorbid intelligence, baseline level of cognitive impairment, cerebrovascular disease burden, degree of ventriculomegaly, or other NPH-related morphological brain alterations. Balance scores evidenced a greater magnitude of improvement than cognitive scores and were weakly, but positively correlated with cognitive change scores. Conclusions: Findings suggest that cognitive improvement associated with a multiday ELD trial can be sufficiently captured with bedside neurocognitive testing. These findings support the utility of neuropsychological consultation, along with balance assessment, in informing clinical decision-making regarding responsiveness to temporary CSF diversion for patients undergoing elective NPH evaluation. Implications for the understanding of neuroanatomical and cognitive underpinnings of NPH are discussed.

In vivo assessment of the ocular biomechanical properties in patients with idiopathic normal pressure hydrocephalus

PurposeIdiopathic normal pressure hydrocephalus (iNPH) is associated with an increased prevalence of open-angle glaucoma, attributed to variations of the pressure gradient between intraocular and intracranial compartments at the level of the lamina cribrosa (LC). As ocular biomechanics influence the behavior of the LC, and a lower corneal hysteresis (CH) has been associated to a higher risk of glaucomatous optic nerve damage, in this study we compared ocular biomechanics of iNPH patients with healthy subjects.Methods Twenty-four eyes of 24 non-shunted iNPH patients were prospectively recruited. Ocular biomechanical properties were investigated using the ocular response analyzer (Reichert Instruments) for the calculation of the CH, corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc). Results were compared with those of 25 eyes of 25 healthy subjects.Results In iNPH eyes, the median CH value and interquartile range (IQR) were 9.7 mmHg (7.8–10) and 10.6 mmHg (9.3–11.3) in healthy controls (p = 0.015). No significant differences were found in IOPcc [18.1 mmHg (14.72–19.92) vs. 16.4 mmHg (13.05–19.6)], IOPg [15.4 mmHg (12.82–19.7) vs. 15.3 mmHg (12.55–17.35)], and CRF [9.65 mmHg (8.07–11.65) vs. 10.3 mmHg (9.3–11.5)] between iNPH patients and controls.Conclusions In iNPH patients, the CH was significantly lower compared to healthy subjects. This result suggests that ocular biomechanical properties may potentially contribute to the risk of development of glaucomatous optic nerve damage in iNPH patients.

Preoperative Predictors of Outcomes of Cerebrospinal Fluid Shunt Surgery in Patients with Idiopathic Normal Pressure Hydrocephalus

The disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings on cranial images are useful to predict cerebrospinal fluid (CSF) shunt responsiveness to some extent in patients with idiopathic normal-pressure hydrocephalus (iNPH). However, recent studies show that patients with iNPH often have concomitant Alzheimer's or Lewy body disease regardless of DESH findings, which may be associated with poor outcomes of CSF shunt surgery. Moreover, long-term outcomes after CSF shunt surgery in patients with iNPH, which is one of the most important issues to be addressed for effective treatment of iNPH, remain unknown.

Symptomatology of Idiopathic Normal Pressure Hydrocephalus

Idiopathic normal pressure hydrocephalus causes a triad of gait disturbance, dementia, and urinary incontinence in the elderly. All these symptoms may manifest as age-related functional decline or from neurological and non-neurological diseases common in the elderly. In idiopathic normal pressure hydrocephalus, characterized by ataxic-ataxic gait, subcortical dementia, and urge urinary incontinence, it is clinically important to consider these characteristic features. This overview describes the symptomatology of idiopathic normal pressure hydrocephalus.

Movement Disorders and Rehabilitation in Idiopathic Normal Pressure Hydrocephalus

Movement disorders, particularly gait and balance disturbances can lead to falls and reduced daily activities in patients with idiopathic normal pressure hydrocephalus (iNPH). In this study, we investigate movement disorders from both the pathophysiological and kinematic perspectives in patients with iNPH. Additionally, we discuss essential factors that should be evaluated before and after cerebrospinal fluid tap tests and shunt surgeries and considerations for assessment of fall risk in patients with iNPH. Additionally, we describe the most recent findings on rehabilitation of iNPH patients.

Recent Developments in Diagnostic Imaging for Idiopathic Normal Pressure Hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH), a syndrome characterized by cognitive impairment, gait abnormalities, and urinary incontinence attributable to cerebrospinal fluid circulatory insufficiency, is associated with an obscure etiology. Several methodologies and imaging analysis techniques, including visualization of cerebral hemodynamics and diffusion tensor imaging have emerged in recent years to determine functional alterations in cases of iNPH. These advancements have led to more comprehensive understanding of the pathophysiological mechanisms underlying iNPH. In this article, we discuss the historical evolution of imaging modalities for iNPH and contemporaneous imaging techniques designed to acquire deeper insight into this disease.

Glymphatic System and Idiopathic Normal Pressure Hydrocephalus

The inflow channel of the glymphatic pathway is the basilar membrane formed by the pia matter and glial border membrane in the outermost layer of the artery. Cerebrospinal fluid from the subarachnoid space enters the brain parenchyma through this pathway, and its water component is pumped into the brain parenchyma through aquaporin 4. One of the driving forces is vascular pulsation, and if this pathway becomes inoperative, cerebrospinal fluid loses its normal dynamics and contributes to idiopathic normal pressure hydrocephalus. Future research is needed to determine the extent of this contribution to the development of idiopathic normal pressure hydrocephalus.

Challenges to Distinguish Idiopathic Normal Pressure Hydrocephalus from Progressive Supranuclear Palsy

Idiopathic normal pressure hydrocephalus (iNPH) is a clinical condition characterized by symptoms of gait disturbance, cognitive dysfunction, and urinary disturbance. In contrast, progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease characterized by supranuclear gaze palsy, akinetic rigidity, gait disturbance, and dementia. PSP manifests various clinical phenotypes that mimic other diseases and occasionally present iNPH-like presentations. Our previous publication showed that PSP develops iNPH-like magnetic resonance imaging (MRI) features more frequently than other neurodegenerative diseases. It is thus sometimes challenging to distinguish iNPH from PSP. Recently, we showed that patients with PSP, particularly those with iNPH-like MRI findings, often demonstrate amelioration of their gait disturbance following a spinal tap or shunt operation. Moreover, our study revealed that both patients with iNPH and PSP often manifest a placebo effect that can be evaluated by implementing a sham spinal tap. Therefore, although a positive response to a spinal tap has been thought of as a distinct feature of iNPH, it may not be useful in differentiating iNPH and PSP. However, in clinical practice, comparing the response to a spinal tap with that of a sham spinal tap may help accurately specify patients with iNPH or PSP who definitively respond to the shunt operation.

Improving access to pediatric hydrocephalus care for all: the role of maternal health literacy and socioeconomic status.

Limited research has addressed the barriers impeding access to surgical care for pediatric patients with hydrocephalus. To identify priorities for enhancing access to pediatric hydrocephalus surgical care and to address healthcare disparities, it is essential to understand the level of access to care and the influence of socioeconomic status (SES) and maternal health literacy. In this study, the authors aimed to assess the level of access to surgical care; determine the frequency of more than a 2-week delay in seeking, reaching, and receiving care; and investigate the influence of parental SES and maternal health literacy on these delays. This observational prospective cohort study involved data collection from a sample of 100 pediatric patients aged ≤ 5 years with hydrocephalus and their mothers, including information on family SES (education, occupational, and economic status). Maternal health literacy was assessed using the Brief Health Literacy Screen (BHLS) questionnaire. The Three Delays framework from the Lancet Commission on Global Surgery, categorizing delays in seeking care, reaching care, and definitive care, provided a structured approach for analyzing access delays. Statistical significance was set at p < 0.05. Among the pediatric patients, there was a male-to-female ratio of 1.7:1, with a median age of 1.5 months. None of the patients had insurance coverage that included surgical treatment. A significantly low number of patients accessed care within 2 weeks for seeking care duration (34%), reaching care duration (15%), and definitive care duration (1%). The median time to definitive surgical treatment for the entire study population was 14 weeks (upper SES: median 6.3 weeks, middle SES: median 9.8 weeks, lower SES: median 16.7 weeks). Through Cox proportional hazards regression, a hazard ratio of 0.046 (95% CI 0.010-0.210) was obtained. Multiple linear regression analysis identified BHLS Brief D (β = -0.335, p = 0.001) and SES (β = 0.389, p < 0.001) as predictor variables for delays in seeking care and definitive care, respectively. SES (β = 0.446, p < 0.001) and Evans index (β = 0.233, p = 0.010) were predictor variables for delays in reaching care. Maternal health literacy and SES were identified as factors associated with delays in accessing neurosurgical care for pediatric patients with hydrocephalus. To reduce disparities in pediatric hydrocephalus care, it is essential to implement strategies that promote education, improve healthcare infrastructure, and provide support to families encountering challenges related to low SES and limited maternal health literacy.

Biomarkers of Idiopathic Normal Pressure Hydrocephalus

Although the pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain largely unknown, it is well acknowledged that iNPH causes ventricular enlargement due to decreased cerebrospinal fluid (CSF) absorption. Pathophysiologically, it is supposed that the excretion of waste proteins is impaired along with CSF. Hence, they tend to aggregate, and in many neurodegenerative diseases, abnormal aggregation and accumulation of such proteins are deeply involved in the pathogenesis of disease. Biomarkers (BMs) contribute to diagnosis by identifying comorbid neurodegenerative diseases that may affect the prognosis of treatment, as well as exploring the pathogenetic mechanisms of iNPH. In addition, BMs can be an important prognostic test for shunt therapy.

Surgical Management of Idiopathic Normal Pressure Hydrocephalus

Cerebrospinal fluid shunting, including ventriculo-abdominal/atrial and lumbar-abdominal shunts, is the only treatment available for idiopathic normal pressure hydrocephalus (iNPH). Hybrid valves that combine a programmable pressure valve and an antisiphon device are being widely used for treatment of iNPH, which has significantly minimized surgical complications, such as shunt revision and subdural hematomas associated with overdrainage. Development of novel technologies that can maintain a more physiological intracranial environment after shunting presents a challenge for future research.

Epidemiology, Natural History, and Genetic Factors of Idiopathic Normal Pressure Hydrocephalus

According to a cohort study in a Japanese rural area, the prevalence of idiopathic normal pressure hydrocephalus (iNPH) in the 80s was 7.7% among the older inhabitants, despite only a small percentage of the population seeking consultation. The 16-year observation of the cohort revealed that people were in the state of asymptomatic ventriculomegaly with features of iNPH on magnetic resonance imaging or asymptomatic ventricular enlargement several years before presenting symptoms and intracranial changes of iNPH. SFMBT1 was found to be a risk gene for iNPH, and investigating these risk genes will further the study of iNPH pathophysiology.

Diagnosis and Treatment of Normal Pressure Hydrocephalus and Repeated Subdural Hematoma and Effusion after Ventriculoperitoneal Shunt in the Elderly: A Case Report

Idiopathic normal pressure hydrocephalus (iNPH) is a special type of hydrocephalus that is characterized by cognitive decline, gait disturbance, and urinary incontinence. It can lead to dementia and bedridden within 1-3 years. Without surgical treatment in time, the prognosis was bleak. We report an iNPH case misdiagnosed with Alzheimer’s disease, with a disease course of 3 years. The main manifestations of the patient were walking impairment, memory loss, urinary incontinence, repeated falls, and hallucinations, bedridden in the late stage, with a modified Rankin Scale (mRS):5. After undergoing the ventriculoperitoneal shunt, due to the low shunt pressure, the patient developed severe headache, repeated and severe subdural hemorrhage and effusion. After adjusting the shunt pressure in time, the patient recovered well with an mRS: 3, which was inconsistent with the previous belief that the operation was ineffective for patients with a disease course of more than 3 years. This case suggests that elderly patients with iNPH can still benefit from timely surgery even if the disease course of more than 3 years. Special attention should be paid after the operation, and the CSF shunt pressure should avoid setting too low, which may induce serious complications such as subdural hemorrhage or effusion.

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

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

Efficacy and safety of cysto-ventricular catheter implantation for space-occupying cysts arising from glioma and brain metastasis: a retrospective study

BackgroundCysto-ventricular catheters (CVC) have emerged as promising treatment option for cystic craniopharyngioma and arachnoid cysts, but their effectiveness in treating cysts originating from glioma or brain metastasis (BM) remains limited. This study aimed to analyze the efficacy of CVC in patients with glioma and BM as well as procedure-associated morbidity.MethodsThis single-center retrospective study included all patients treated with CVC placement for acquired space-occupying cysts deriving from previously treated glioma or BMs between 1/2010 and 12/2021.ResultsA total of 57 patients with a median age of 47 years (IQR 38–63) were identified. Focal neurological deficits were the predominant symptoms in 60% of patients (n = 34), followed by cephalgia in 14% (n = 8), and epileptic seizures in 21.1% (n = 12). Accurate CVC placement was achieved in all but one case requiring revision surgery due to malposition. Three months after CVC implantation, 70% of patients showed symptomatic improvement. Multivariate logistic regression analysis identified the development of space-occupying cysts later in the course of the disease (OR 1.014; p = 0.04) and a higher reduction of cyst-volume postoperatively (OR 1.055; p = 0.05) were significant predictors of postoperative symptomatic improvement following CVC placement. Local cyst recurrence was observed in three cases during follow-up MRI after an average time of 5 months (range 3–9 months). Further complications included secondary malresorptive hydrocephalus in three cases and meningeosis neoplastica in one patient.ConclusionsStereotactic implantation of CVC is an efficient treatment option for patients suffering from symptomatic space-occupying cysts from BMs or glioma, independently from their CNS WHO grade. However, a vigilant approach is crucial regarding potential complications and treatment failures.

Prediction of Surgical Outcomes in Normal Pressure Hydrocephalus by MR Elastography.

Normal pressure hydrocephalus is a treatable cause of dementia associated with distinct mechanical property signatures in the brain as measured by MR elastography. In this study, we tested the hypothesis that specific anatomic features of normal pressure hydrocephalus are associated with unique mechanical property alterations. Then, we tested the hypothesis that summary measures of these mechanical signatures can be used to predict clinical outcomes. MR elastography and structural imaging were performed in 128 patients with suspected normal pressure hydrocephalus and 44 control participants. Patients were categorized into 4 subgroups based on their anatomic features. Surgery outcome was acquired for 68 patients. Voxelwise modeling was performed to detect regions with significantly different mechanical properties between each group. Mechanical signatures were summarized using pattern analysis and were used as features to train classification models and predict shunt outcomes for 2 sets of feature spaces: a limited 2D feature space that included the most common features found in normal pressure hydrocephalus and an expanded 20-dimensional (20D) feature space that included features from all 4 morphologic subgroups. Both the 2D and 20D classifiers performed significantly better than chance for predicting clinical outcomes with estimated areas under the receiver operating characteristic curve of 0.66 and 0.77, respectively (P < .05, permutation test). The 20D classifier significantly improved the diagnostic OR and positive predictive value compared with the 2D classifier (P < .05, permutation test). MR elastography provides further insight into mechanical alterations in the normal pressure hydrocephalus brain and is a promising, noninvasive method for predicting surgical outcomes in patients with normal pressure hydrocephalus.

Upper extremity motor function before and after the cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus: A retrospective study.

Upper extremity motor function before and after the cerebrospinal fluid tap test in patients with idiopathic normal pressure hydrocephalus: A retrospective study.

Prevalence of Possible Idiopathic Normal Pressure Hydrocephalus in Sweden: A Population-Based MRI Study in 791 70-Year-Old Participants

Very divergent prevalence rates for idiopathic normal pressure hydrocephalus (iNPH) are reported, probably due to differences in study sample selection and diagnostic criteria. This MRI-based study aimed to determine the prevalence of iNPH and iNPH-specific radiologic changes and their association with clinical symptoms in a large, 70-year-old population-based cohort (Gothenburg H70). In this cross-sectional study, disturbances in gait and balance, cognition, and urinary continence were assessed using clinical examination and self-report. MRI was evaluated for iNPH-specific imaging markers. iNPH was diagnosed according to International Guidelines (I.G.). Based on radiologic findings, participants were allocated to 1 of 4 groups: (A) Evans index (EI) ≤0.3 (reference), (B) EI >0.3 without other iNPH-typical radiologic findings, (C) radiologically probable iNPH according to I.G., and (D) radiologically holistically probable (h-probable) iNPH fulfilling radiologic criteria according to I.G. plus highly iNPH-specific changes according to an experienced neuroradiologist. The Gothenburg H70 Studies include 791 individuals (377 men, 414 women) born in 1944 who underwent brain MRI. The prevalence of iNPH was 1.5% (2.1% for men, 0.96% for women) according to I.G. Ninety participants (11%) had EI >0.3 without other iNPH-typical radiologic findings, 29 (3.7%) fulfilled the I.G. radiologic probable iNPH criteria alone, and 11 (1.4%) were classified as radiologically h-probable iNPH. Forty participants (5.1%) had I.G. radiologic features of iNPH (70% men vs 30% women, p = 0.005). Gait disturbances were more common in participants with EI >0.3 without other radiologic iNPH features (B) (33%) compared with the reference group (A) (19%) (p = 0.006). All clinical symptoms were more common in participants with I.G. radiologic features of iNPH (C + D) than they were in the reference group (A) (p < 0.03). The iNPH prevalence of 1.5% among 70-year-olds, which is considerably higher than earlier reported in this age group, suggests that iNPH may be more common than previously assumed. This is supported by the 5.1% total prevalence of imaging signs of iNPH. Ventriculomegaly without other iNPH-typical radiologic findings may be an early sign of developing iNPH in some patients.

Patients with normal pressure hydrocephalus have fewer enlarged perivascular spaces in the centrum semiovale compared to cognitively unimpaired individuals

IntroductionEnlarged perivascular spaces (ePVS) may be an indicator of glymphatic dysfunction. Limited studies have evaluated the role of ePVS in idiopathic normal pressure hydrocephalus (iNPH). We aimed to characterize the distribution and number of ePVS in iNPH compared to controls. MethodsThirty-eight patients with iNPH and a pre-shunt MRI were identified through clinical practice. Age- and sex-matched controls who had negative MRIs screening for intracranial metastases were identified through a medical record linkage system. The number of ePVS were counted in the basal nuclei (BN) and centrum semiovale (CS) using the Wardlaw method blinded to clinical diagnosis. Imaging features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), callosal angle, Fazekas white matter hyperintensity (WMH) grade, and the presence of microbleeds and lacunes were also evaluated. ResultsBoth iNPH patients and controls had a mean age of 74 ± 7 years and were 34% female with equal distributions of hypertension, dyslipidemia, diabetes, stroke, and history of smoking. There were fewer ePVS in the CS of patients with iNPH compared to controls (12.66 vs. 20.39, p < 0.001) but the same in the BN (8.95 vs. 11.11, p = 0.08). This remained significant in models accounting for vascular risk factors (p = 0.002) and MRI features of DESH and WMH grade (p = 0.03). ConclusionsFewer centrum semiovale ePVS may be a biomarker for iNPH. This pattern may be caused by mechanical obstruction due to upward displacement of the brain leading to reduced glymphatic clearance.

Kinematic movement and balance parameter analysis in neurological gait disorders

BackgroundNeurological gait disorders are mainly classified based on clinical observation, and therefore difficult to objectify or quantify. Movement analysis systems provide objective parameters, which may increase diagnostic accuracy and may aid in monitoring the disease course. Despite the increasing wealth of kinematic movement and balance parameter data, the discriminative value for the differentiation of neurological gait disorders is still unclear. We hypothesized that kinematic motion and balance parameter metrics would be differently altered across neurological gait disorders when compared to healthy controls.MethodsThirty one patients (9 normal pressure hydrocephalus < NPH > , 16 cervical myelopathy < CM > , 6 lumbar stenosis < LST >) and 14 healthy participants were investigated preoperatively in an outpatient setting using an inertial measurement system (MyoMotion) during 3 different walking tasks (normal walking, dual-task walking with simultaneous backward counting, fast walking). In addition, the natural postural sway of participants was measured by pedobarography, with the eyes opened and closed. The range of motion (ROM) in different joint angles, stride time, as well as sway were compared between different groups (between-subject factor), and different task conditions (within-subject factor) by a mixed model ANOVA.ResultsKinematic metrics and balance parameters were differently altered across different gait disorders compared to healthy controls. Overall, NPH patients significantly differed from controls in all movement parameters except for stride time, while they differed in balance parameters only with regard to AP movement. LST patients had significantly reduced ROMs of the shoulders, hips, and ankles, with significantly altered balance parameters regarding AP movement and passed center-of-pressure (COP) distance. CM patients differed from controls only in the ROM of the hip and ankle, but were affected in nearly all balance parameters, except for force distribution.ConclusionThe application of inertial measurement systems and pedobarography is feasible in an outpatient setting in patients with different neurological gait disorders. Rather than defining singular discriminative values, kinematic gait and balance metrics may provide characteristic profiles of movement parameter alterations in the sense of specific ´gait signatures´ for different pathologies, which could improve diagnostic accuracy by defining objective and quantifiable measures for the discrimination of different neurological gait disorders.Trial registrationThe study was retrospectively registered on the 27th of March 2023 in the ‘Deutsches Register für Klinische Studien’ under the number DRKS00031555.