Risk Analysis Index as a preoperative frailty tool for elective ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) predominantly occurs in older patients, and ventriculoperitoneal shunt (VPS) placement is the definitive surgical treatment. VPS surgery carries significant postoperative complication rates, which may tip the risk/benefit balance of this treatment option for frail, or higher-risk, patients. In this study, the authors investigated the use of frailty scoring for preoperative risk stratification for adverse event prediction in iNPH patients who underwent elective VPS placement. METHODS: The Nationwide Readmissions Database (NRD) was queried from 2018 to 2019 for iNPH patients aged ≥ 60 years who underwent VPS surgery. Risk Analysis Index (RAI) and modified 5-item Frailty Index (mFI-5) scores were calculated and RAI cross-tabulation was used to analyze trends in frailty scores by the following binary outcome measures: overall complications, nonhome discharge (NHD), extended length of stay (eLOS) (> 75th percentile), and mortality. Area under the receiver operating characteristic curve analysis was performed to assess the discriminatory accuracy of RAI and mFI-5 for primary outcomes. RESULTS: A total of 9319 iNPH patients underwent VPS surgery, and there were 685 readmissions (7.4%), 593 perioperative complications (6.4%), and 94 deaths (1.0%). Increasing RAI score was significantly associated with increasing rates of postoperative complications: RAI scores 11-15, 5.4% (n = 80); 16-20, 5.6% (n = 291); 21-25, 7.6% (n = 166); and ≥ 26, 11.6% (n = 56). The discriminatory accuracy of RAI was statistically superior (DeLong test, p < 0.05) to mFI-5 for the primary endpoints of mortality, NHD, and eLOS. All RAI C-statistics were > 0.60 for mortality within 30 days (C-statistic = 0.69, 95% CI 0.68-0.70). CONCLUSIONS: In a nationwide database analysis, increasing frailty, as measured by RAI, was associated with NHD, 30-day mortality, unplanned readmission, eLOS, and postoperative complications. Although the RAI outperformed the mFI-5, it is essential to account for the potentially reversible clinical issues related to the underlying disease process, as these factors may inflate frailty scores, assign undue risk, and diminish their utility. This knowledge may enhance provider understanding of the impact of frailty on postoperative outcomes for patients with iNPH, while highlighting the potential constraints associated with frailty assessment tools.

Comparison of decline in different cognitive domain in patients with normal pressure hydrocephalus.

We sought to describe the cognitive profile of patients with Idiopathic Normal Pressure Hydrocephalus (iNPH) using a comprehensive neuropsychological battery. Based on age and education correlated norms, we aimed to compare performance in each measured cognitive domain: executive functions (EFs), verbal memory (VM), non-verbal memory (nVM), visuoconstructional abilities (VA) and attention/psychomotor speed (A/PS). Patients diagnosed with iNPH underwent comprehensive neuropsychological evaluation before shunting. Their performance was compared to the age and education correlated norms. Correlation of different cognitive domains in iNPH profile was performed. A total of 53 iNPH patients (73.21 ± 5.48 years) were included in the study. All of the measured cognitive domains were significantly damaged. The most affected domains were EFs and VM (p<0.001 and p<0.001, respectively). A/PS domain was affected milder than EFs and VM (p<0.001). The least affected domains were nVM (p<0.001) and VA (p<0.001). Patients with iNPH are affected in all cognitive domains and the cognitive decline is uneven across these domains. The impairment of memory was shown to depend on the presented material. VM was shown to be much more severely affected than nVM and along with VM, EFs were shown to be the most affected. A/PS speed was shown to be less affected than VM and EFs and the least affected domains were nVM and VA.

Comparing the Long-Term Cardiovascular Outcomes of Lumbo-Peritoneal, Ventriculo-Peritoneal, or Non-Shunting Treatment after Idiopathic Normal Pressure Hydrocephalus: A Nationwide Retrospective Cohort Study.

Purpose: With advances in medical technology, the average lifespan has increased, leading to a growing significance of idiopathic normal pressure hydrocephalus (iNPH), particularly in the elderly population. Most patients with iNPH have been treated either with ventriculo-peritoneal shunts (VPS) or conservative measures. However, lumbo-peritoneal shunts (LPS) have emerged as an alternative treatment option for iNPH in recent decades, extensive research still lacks comparing outcomes with LPS to those with VPS or non-surgical treatment. The aim of the resent study is to disclose the long-term therapeutic outcomes of LPS, VPS, and non-shunting in patients with iNPH. Methods: We used the National Health Insurance Research Database in Taiwan to assess the long-term outcomes of these treatment options. We enrolled 5,537 iNPH patients who received shunting surgery, of which 5,254 were VPS and 283 were LPS. To compare the difference between each group, matching was conducted by propensity score matching using a 1:1 ratio based on LPS patients. Primary outcomes included death and major adverse cardiovascular events (MACEs) Results: Our findings show that VPS resulted in significantly more MACEs than non-surgical treatment (Odds ratio: 1.83, 95% confidence interval: 1.16-2.90). In addition, both VPS and LPS groups had significantly lower overall mortality rates than non-shunting group. Moreover, LPS had lower overall mortality but similar MACEs rates to VPS. Conclusions: Based on these findings, we propose that the LPS is preferable to the VPS, and surgical treatment should be considered the primary choice over conservative treatment unless contraindications are present.

Freezing of gait in idiopathic normal pressure hydrocephalus.

BACKGROUND: Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study's objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG's responsiveness to shunt surgery. METHODS: Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71-79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared. RESULTS: Twenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups. CONCLUSIONS: FoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom.

[Possibilities of dynamic phase contrast MRI of cerebrospinal fluid for performing a tap test in a patient with idiopathic normotensive hydrocephalus]. / Vozmozhnosti dinamicheskoi fazovo-kontrastnoi MR-likvorografii pri vypolnenii tap-testa u patsienta s idiopaticheskoi normotenzivnoi gidrotsefaliei.

Idiopathic normotensive hydrocephalus (iNH) is a widespread disease in elderly patients. The effectiveness of iNG treatment and the subsequent quality of patients' lives directly depends on timely and early diagnosis. The criteria for diagnosing iNG that are used in neuroimaging can also be found in patients without clinical manifestations of this disease, and the widely used tap-test is an invasive technique with a rather low sensitivity. The need for early diagnosis and initiation of treatment before the development of irreversible damage to brain structures determines the relevance of the search for an accessible, minimally invasive, accurate and safe diagnostic method. The article presents a clinical observation of the use of phase-contrast MRI of cerebrospinal fluid (CSF) in a female patient with a positive response to the tap test with a quantitative analysis of changes in CSF flow parameters and ALVI and Evans indices depending on the time after CSF evacuation. Phase-contrast MRI of CSF with a quantitative assessment of CSF flow parameters in combination with an assessment of the ALVI index has the potential to increase the accuracy of diagnosing iNH and is of scientific interest for further research.

Neuronal pentraxin 2 correlates with neurodegeneration but not cognition in idiopathic normal pressure hydrocephalus (iNPH).

AIM OF THE STUDY: Neuronal pentraxin-2 (NPTX2) is a synaptic protein responsible for modulating plasticity at excitatory synapses. While the role of NPTX2 as a novel synaptic biomarker in cognitive disorders has been elucidated recently, its role in idiopathic normal pressure hydrocephalus (iNPH) is not yet understood. CLINICAL RATIONALE FOR STUDY: To determine if NPTX2 predicts cognition in patients with iNPH, and whether it could serve as a predictive marker for shunt outcomes. MATERIAL AND METHODS: 354 iNPH patients underwent cerebrospinal fluid drainage (CSF) as part of the tap test or extended lumbar drainage. Demographic and clinical measures including age, Evans Index (EI), Montreal Cognitive Assessment (MoCA) score, Functional Activities Questionnaire (FAQ) score, and baseline and post-shunt surgery Timed Up and Go (TUG) test scores were ascertained. CSF NPTX2 concentrations were measured using an ELISA. CSF ß-amyloid 1-40 (Aß1-40), ß-amyloid 1-42 (Aß1-42), and phosphorylated tau-181 (pTau-181) were measured by chemiluminescent assays. Spearman's correlation was used to determine the correlation between CSF NPTX2 concentrations and age, EI, MoCA and FAQ, TUG, Aß1-40/Aß1-42 ratio, and pTau-181 concentrations. Logistic regression was used to determine if CSF NPTX2 values were a predictor of short-term improvement post-CSF drainage or long-term improvement post-shunt surgery. RESULTS: There were 225 males and 129 females with a mean age of 77.7 years (± 7.06). Average CSF NPTX2 level in all iNPH patients was 559.97 pg/mL (± 432.87). CSF NPTX2 level in those selected for shunt surgery was 505.61 pg/mL (± 322.38). NPTX2 showed modest correlations with pTau-181 (r = 0.44, p < 0.001) with a trend for Aß42/Aß40 ratio (r = -0.1, p = 0.053). NPTX2 concentrations did not correlate with age (r = -0.012, p = 0.83) or MoCA score (r = 0.001, p = 0.87), but correlated negatively with FAQ (r = -0.15, p = 0.019). CONCLUSIONS: While CSF NPTX2 values correlate with neurodegeneration, they do not correlate with cognitive or functional measures in iNPH. CSF NPTX2 cannot serve as a predictor of either short-term or long-term improvement after CSF drainage. CLINICAL IMPLICATIONS: These results suggest that synaptic degeneration is not a core feature of iNPH pathophysiology.

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

PURPOSE: Idiopathic 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.

[Overview of the Guidelines for Managing Idiopathic Normal Pressure Hydrocephalus].

Japanese guidelines for idiopathic normal pressure hydrocephalus (iNPH) (iNPHGL) are the first and only guidelines in the world that were revised following subsequent developments in iNPH research. We first discuss the virtuous cycle in which the development and revision of the iNPHGL and how the implementation of two consecutive multicenter prospective studies conducted in Japan, SINPHONIs, have worked together to advance iNPH practices. Subsequently, we explained the most characteristic features of the iNPHGL, such as "Positioning of iNPH," "Diagnostic Criteria," and "Algorithms for Diagnosis and Treatment." To classify iNPH, we categorized chronic adult-onset normal pressure hydrocephalus (NPH) as iNPH, secondary NPH, Congenital/Developmental NPH, and Familial NPH. In the diagnostic criteria and algorithm, we classified iNPH into four categories: Suspected iNPH, Possible iNPH, Probable iNPH, and Definite iNPH, depending on the certainty of the diagnosis. In addition, a positioned disproportionately enlarged subarachnoid space hydrocephalus (DESH) on head computed tomography and magnetic resonance imaging is an important finding for the diagnosis of iNPH. Finally, we presented the results of a survey on the treatment status of patients with suspected iNPH, awareness of DESH, and use of this iNPHGL among medical centers for dementia in Japan.

[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.

[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.

[Neuropathology of Idiopathic Normal Pressure Hydrocephalus: A Study of Three Autopsy Cases and a Literature Review].

We present neuropathological findings in three autopsy brains from patients diagnosed clinically with idiopathic normal pressure hydrocephalus (iNPH) in Japan; still, specific findings of iNPH remain unclear. Comorbid atherosclerosis and hypertensive microvascular diseases, including arterio- and arteriolosclerosis and ischemic changes in the brain parenchyma, are frequently (65%) observed in autopsy brain tissue from patients with iNPH, which has drawn attention to the clinicopathological similarities and differences between iNPH and Binswanger's disease. Additionally, Aß protein deposition and phosphorylated tau-positive neurofibrillary tangles and neuropil threads are observed in cerebral cortical biopsy specimens obtained during intracranial pressure monitoring or shunt surgery among a subset of patients with iNPH. These findings are as frequent as those reported in autopsy data of the age-matched general population. Alterations in aquaporin-4 expression in the cerebral cortex have also been reported, suggestive of a possible association with altered volume or composition of the interstitial fluid in the microenvironment, particularly in the vicinity of capillaries, or glymphatic system dysfunction and consequent altered interstitial fluid drainage. Greater understanding of the normal anatomical structures and pathways involved in cerebrospinal fluid circulation, particularly in absorption and drainage, in the craniospinal region is essential for better clarity regarding iNPH neuropathology.

[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.

[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.

[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.

[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.

[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.

[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.

Cerebrospinal fluid shunt surgery reduces the risk of developing dementia and Alzheimer's disease in patients with idiopathic normal pressure hydrocephalus: a nationwide population-based propensity-weighted cohort study.

BACKGROUND: Patients with idiopathic normal-pressure hydrocephalus (iNPH) are predisposed to developing dementing disorders. Cerebrospinal fluid (CSF) shunt implantation is a treatment used to improve the motor and cognitive disabilities of these patients; however, its effect on the risk of developing dementing disorders remains unclear. We conducted a population-based propensity-weighted cohort study to investigate whether CSF shunt surgery may reduce the risk of subsequently developing dementia, Alzheimer's disease (AD), and vascular dementia in iNPH patients. METHODS: Patients aged ≥ 60 years who were diagnosed with iNPH (n = 2053) between January 2001 and June 2018 were identified from the Taiwan National Health Insurance Research Database. Various demographic characteristics (age, sex, and monthly income) and clinical data (incidence year, comorbidities, and Charlson comorbidity index) were collected and divided into the shunt surgery group (SSG) and the non-shunt surgery group (NSSG). Stabilized inverse probability of treatment weighting by using the propensity score was performed to achieve a balanced distribution of confounders across the two study groups. The cumulative incidence rate and risk of dementing disorders were estimated during a 16-year follow-up period. RESULTS: After weighting, the data of 375.0 patients in SSG and 1677.4 patients in NSSG were analyzed. Kaplan-Meier curve analysis indicated that the cumulative incidence rate of AD (p = 0.009), but not dementia (p = 0.241) and vascular dementia (p = 0.761), in SSG was significantly lower than that in NSSG over the 16-year follow-up period. Cox proportional hazards regression analysis revealed that SSG had a reduced hazard ratio (HR) for developing AD [HR (95% CI) 0.17 (0.04-0.69)], but not for dementia [HR (95% CI) 0.83 (0.61-1.12)] and vascular dementia [HR (95% CI) 1.18 (0.44-3.16)], compared with NSSG. Further Fine-Gray hazard regression analysis with death as a competing event demonstrated that SSG had a reduced subdistribution HR (sHR) for developing dementia [sHR (95% CI) 0.74 (0.55-0.99)] and AD [sHR (95% CI) 0.15 (0.04-0.61)], but not for vascular dementia [sHR (95% CI) 1.07 (0.40-2.86)]. CONCLUSION: CSF shunt surgery is associated with reduced risks of the subsequent development of dementia and AD in iNPH patients. Our findings may provide valuable information for assessing the benefit-to-risk profile of CSF shunt surgery.