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.

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.

Normal pressure hydrocephalus, or Hakim syndrome: review and update.

This review makes the case that idiopathic normal pressure hydrocephalus (iNPH) is an outdated term because new information indicates that the syndrome is less idiopathic and that the cerebrospinal fluid (CSF) pressure of normal individuals is affected by several factors such as body mass index, age, and sex. Our review updates the epidemiology of iNPH and provides a clinical approach to the management of these patients. All the clinical features of iNPH are common in older individuals, and each has many causes, so the diagnosis is difficult. The first step in reaching an accurate diagnosis is to address the possible contributory factors to the gait abnormality and determine what if any role iNPH may be playing. The two best diagnostic tests are neuroimaging and cerebrospinal fluid (CSF) diversion (large volume lumbar puncture or external lumbar drainage) with pre/post gait evaluation. This review provides an update on the growing evidence that vascular disease, impaired CSF absorption, congenital, and genetic factors all contribute to the pathogenesis of iNPH. We suggest replacing the term iNPH with the term Hakim syndrome (HS) in acknowledgement of the first person to describe this syndrome. Lastly, we discuss the improvements in shunt technology and surgical techniques that have decreased the risks and long-term complications of shunt surgery.

10-year mortality, causes of death and cardiovascular comorbidities in idiopathic normal pressure hydrocephalus.

OBJECTIVE: The objective was to investigate 10-year mortality, causes of death and cardiovascular comorbidity in idiopathic normal pressure hydrocephalus (iNPH) and to evaluate their mutual associations. METHODS: This prospective cohort study included 176 CSF-shunted iNPH patients, and 368 age- and sex-matched controls. At inclusion, participants were medically examined, had blood analyzed and answered a questionnaire. The vascular comorbidities investigated were smoking, diabetes, body mass index, blood pressure (BP), hyperlipidemia, kidney function, atrial fibrillation and, cerebro- and cardiovascular disease. RESULTS: Survival was observed for a mean period of 10.3 ± 0.84 years. Shunted iNPH patients had an increased risk of death compared to controls (hazard ratio (HR) = 2.5, 95% CI 1.86-3.36; p < 0.001). After 10 years, 50% (n = 88) of iNPH patients and 24% (n = 88) of the controls were dead (p < 0.001). The risk of dying from cardiovascular disease, falls and neurological diseases were higher in iNPH (p < 0.05). The most common cause of death in iNPH was cardiovascular diseases (14% vs 7% for controls). Seven out of nine iNPH dying from falls had subdural hematomas. Systolic BP (HR = 0.985 95% CI 0.972-0.997, p = 0.018), atrial fibrillation (HR = 2.652, 95% CI 1.506-4.872, p < 0.001) and creatinine (HR = 1.018, 95% CI 1.010-1.027, p < 0.001) were independently associated with mortality for iNPH. DISCUSSION: This long-term and population-matched cohort study indicates that in spite of CSF-shunt treatment, iNPH has shorter life expectancy. It may be important to treat iNPH in supplementary ways to reduce mortality. Both cardiovascular comorbidities and lethal falls are contributing to the excess mortality in iNPH and reducing these preventable risks should be an established part of the treatment plan.

[Coincidence of normal pressure hydrocephalus and Alzheimer`s disease: therapeutic implications and open questions]. / Zur Koinzidenz von Normaldruckhydrocephalus und Alzheimer-Demenz: therapeutische Implikationen und offene Fragen.

Normal pressure hydrocephalus (NPH) is prevalent in aging patient populations. Despite its clinical relevance, many patients with NPH may not receive adequate treatment. Because of the frequency of Alzheimer`s disease in these patients, there could be overlapping pathophysiological mechanisms that are as yet incompletely understood. Cerebral comorbidities seem to have negative effects on therapeutic response to ventriculoperitoneal shunting. In order to avoid unnecessary and unsuccessful surgery in highly vulnerable elderly patients, they have to be taken into consideration in the diagnostic process.

Fixed versus Adjustable differential pressure valves in case of idiopathic normal pressure hydrocephalus treated with ventriculoperitoneal shunt. A systematic review and meta-analysis of proportion.

INTRODUCTION: Idiopathic normal pressure hydrocephalus is a common cause of communicating hydrocephalus in adult age, presenting with classic Hakim-Adam's triad. Ventriculoperitoneal shunting is the treatment of choice in these cases. The main objective of this study is to compare the complication rate of Adjustable differential pressure valves with fixed differential pressure valves in these cases. LITERATURE SEARCH: We systematically searched PubMed/Medline, Embase, LILACS, and ClinicalTrials.gov from their date of inception to 30th Jan 2023. We included observational studies, Randomized Controlled Trials (RCTs), and comparative and noncomparative studies in the search. The literature search resulted in 1394 studies, and only 22 studies were eligible to be included in the meta-analysis. We performed the meta-analysis of proportion to compare incidence rates by performing a Freeman-turkey double arcsine transformation. RESULTS: The summary of the proportions of the incidence rate of complications was less for Adjustable Differential Pressure Valves (ADPV) as compared to Fixed Differential Pressure Valves (FDVP) but the confidence intervals overlapped. The summary proportion of surgical revision of shunt in the case of ADPV was 0.081 (95% CI (0.047, 0.115)), and in the case of FDPV was 0.173 (95% CI (0.047, 0.299)). Similarly, the summary proportion of subdural fluid collection in the case of ADPV was 0.090 (0.058, 0.122), and in the case of FDPV was 0.204 (0.132, 0.277). The incidence of complication was low in population implanted with DPV along with gravitational or anti-siphon unit (GASU). CONCLUSION: Complication rates in the case of ADPV plus GASU were the lowest. Though the summary proportion of complication rate in the case of ADPV was low as compared to FDPV, the statistical significance of this difference is doubted due to overlapping confidence intervals.

Association between vascular risk factors and idiopathic normal pressure hydrocephalus: a Mendelian randomization study.

BACKGROUND AND OBJECTIVE: Patients with idiopathic normal pressure hydrocephalus (iNPH) have a higher prevalence of hypertension and diabetes. However, the causal effects of these vascular risk factors on iNPH remain unclear. This study aimed to explore the causal relationship between vascular risk factors (VRFs) and iNPH. METHODS: We conducted the Mendelian randomization (MR) analysis of iNPH. We included nineteen vascular risk factors related to hypertension, diabetes, lipids, obesity, smoking, alcohol consumption, exercise, sleep, and cardiovascular events as exposure factors. We used the inverse-variance weighted method for causal effect estimation and weighted median, maximum likelihood, and MR Egger regression methods for sensitivity analyses. RESULTS: We found that genetically predicting essential hypertension (OR = 1.608 (1.330-1.944), p = 0.013) and increased sleep duration (OR = 16.395 (5.624-47.799), p = 0.009) were associated with higher odds of iNPH. Type 1 diabetes (OR = 0.869 (0.828-0.913), p = 0.004) was associated with lower odds of iNPH. For the other 16 VRFs, there was no evidence that they were significantly associated with iNPH. Sensitivity analyses showed that essential hypertension and type 1 diabetes were significantly associated with iNPH. CONCLUSION: In our MR study on VRFs and iNPH, we found essential hypertension to be a causal risk factor for iNPH. This suggests that hypertension may be involved in the pathophysiological mechanism of iNPH.

Longitudinal post-shunt outcomes in idiopathic normal pressure hydrocephalus with and without comorbid Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity. METHODS: Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24-60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively. RESULTS: There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence. CONCLUSION: iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.

In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome of elderly individuals likely sustained by different neurodegenerative changes as copathologies. Since iNPH is a potentially reversible condition, assessing neurodegenerative pathologies in vitam through CSF biomarkers and their influence on clinical features and surgical outcome represents crucial steps. METHODS: We measured α-synuclein seeding activity related to Lewy body (LB) pathology by the real-time quaking-induced conversion assay (RT-QuIC) and Alzheimer disease core biomarkers (proteins total-tau, phospho-tau, and amyloid-beta) by immunoassays in the cerebrospinal fluid (CSF) of 293 iNPH patients from two independent cohorts. To compare the prevalence of LB copathology between iNPH participants and a control group representative of the general population, we searched for α-synuclein seeding activity in 89 age-matched individuals who died of Creutzfeldt-Jakob disease (CJD). Finally, in one of the iNPH cohorts, we also measured the CSF levels of neurofilament light chain protein (NfL) and evaluated the association between all CSF biomarkers, baseline clinical features, and surgery outcome at 6 months. RESULTS: Sixty (20.5%) iNPH patients showed α-synuclein seeding activity with no significant difference between cohorts. In contrast, the prevalence observed in CJD was only 6.7% (p = 0.002). Overall, 24.0% of iNPH participants showed an amyloid-positive (A+) status, indicating a brain co-pathology related to Aß deposition. At baseline, in the Italian cohort, α-synuclein RT-QuIC positivity was associated with higher scores on axial and upper limb rigidity (p = 0.003 and p = 0.011, respectively) and lower MMSEc scores (p = 0.003). A+ patients showed lower scores on the MMSEc (p = 0.037) than A- patients. Higher NfL levels were also associated with lower scores on the MMSEc (rho = -0.213; p = 0.021). There were no significant associations between CSF biomarkers and surgical outcome at 6 months (i.e. responders defined by decrease of 1 point on the mRankin scale). CONCLUSIONS: Prevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined.

Management of patients with cervical myelopathy and normal pressure hydrocephalus: Epidemiology, medical and surgical complications.

OBJECTIVE: Normal pressure hydrocephalus (NPH) and degenerative cervical myelopathy (DCM) can each lead to gait dysfunction and urinary incontinence and may occur concurrently in some patients. In patients presenting with NPH and DCM, there is a paucity of literature describing the medical and surgical complications of treatment and the potential consequences of the sequence of surgical procedures. The aim of this study is to evaluate patients with DCM, NPH, and dual pathology to determine epidemiology and how the order of surgical intervention for both conditions may impact complications and patient outcomes. METHODS: The PearlDiver Mariner database was queried between 2010 and 2020 to identify patients by their diagnosis of NPH, DCM, or both. Additional groups were created to identify cohorts of patients who underwent ventriculoperitoneal (VP) shunting, DCM surgery, or both surgeries, as determined by the CPT, ICD9, and ICD10 codes included in the dataset. Overall demographics were reported for these cohorts of patients including age, gender, and region. Multivariable logistic regression, controlling for age, sex, and Charlson Comorbidity Index, was used to calculate odds ratios for the rates of perioperative complications within 1 year of initial ventriculoperitoneal (VP) shunt and/or DCM surgery. RESULTS: A total of 825,989 patients were identified with DCM and/or NPH: 725,433 (87.8%) had myelopathy alone, 96, 411 (11.7%), had NPH alone, and 4145 patients (0.5%) had both NPH and DCM. Of all patients with NPH, 4.8% underwent DCM surgery. Of all patients with DCM, 0.08% underwent VP shunting. Compared to NPH only patients who underwent VP shunting, patients with both pathologies undergoing VP shunting had higher odds of revision at 1-year (OR: 1.33, p-value: 0.04) and 5-years (OR: 1.36, p-value: 0.011), as well as spinal cord injury (OR: 7.77, p-value 0.016), dysphonia (OR: 2.88, p-value: 0.004), cervicalgia (OR: 2.95, p-value: 0.004), cervical kyphosis (OR: 17.49, p-value: 0.004), and limb paralysis (OR: 2.02, p-value: 0.002). Compared to DCM only patients who underwent DCM surgery, patients with both pathologies undergoing DCM surgery had higher odds of cardiac complications (OR: 1.12, p-value: 0.002), dural tear (OR: 1.66, p-value: 0.029), and dysphagia (OR: 1.28, p-value: <0.001). Patients who underwent VP shunting prior to DCM surgery had higher odds of revision shunting surgery at 1-year (OR:1.61, p-value:0.03) and 5- years (OR:2.16, p-value: <0.001). CONCLUSION: This is the largest study to date examining patients with dual cervical myelopathy and normal pressure hydrocephalus. Surgeons should carefully consider the order of VP shunting and DCM surgery, as complication rates differ depending on the order in which these surgeries are performed. Shunt revision is more common when VP shunting is performed prior to spinal decompression.

[Epidemiology of Idiopathic Normal Pressure Hydrocephalus and Hereditary Hydrocephalus].

Several cohort studies in Japan have revealed that the prevalence of idiopathic normal pressure hydrocephalus(iNPH)is around 1.6% among the elderly population(≧ 50 years old). The incidence of iNPH from the Yamagata(Takahata)cohort was 1.2/ 1,000 person-years in the elderly population. Although the Japanese guidelines for iNPH clearly describe the definition of "possible iNPH with MRI support," it is still difficult to find out not only patients with iNPH but also individuals in its preclinical stage with radiological findings of asymptomatic ventriculomegaly with features of iNPH on MRI(AVIM)or asymptomatic ventricular enlargement(AVE). It is assumed that only less than 10% of patients with iNPH were referred to hospitals in Japan. Several genes associated with congenital hydrocephalus have been found, including ciliopathy-related genes that directly affect the ependymal cilia in ventricles. Loss of the copy number of SFMBT1 was found to be a risk factor for iNPH. Knowledge about risk genes and their mechanisms in congenital and familial NPH may be a clue for the further understanding of the pathophysiology of iNPH.

Waiting time for surgery influences the outcome in idiopathic normal pressure hydrocephalus - a population-based study.

INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is a disease that comes with a great impact on the patient's life. The only treatment for iNPH, which is a progressive disease, is shunt surgery. It is previously indicated that early intervention might be of importance for the outcome. AIM: To investigate if a longer waiting time for surgery, negatively influences the clinical outcome. METHODS: Eligible for this study were all iNPH patients (n = 3007) registered in the Swedish Hydrocephalus Quality Registry (SHQR) during 1st of January 2004-12th of June 2019. Waiting time, defined as time between the decision to accept a patient for surgery and shunt surgery, was divided into the intervals ≤ 3, 3.1-5.9 and ≥ 6 months. Clinical outcome was assessed 3 and 12 months after surgery using the modified iNPH scale, the Timed Up and Go (TUG) test and the mini mental state examination (MMSE). RESULTS: Three months after surgery, 57% of the patients with ≤ 3 months waiting time showed an improvement in modified iNPH scale (≥ 5 points) whereas 52% and 46% of patients with 3.1-5.9 and ≥ 6 months waiting time respectively improved (p = 0.0115). At 12 months of follow-up, the corresponding numbers were 61%, 52% and 51% respectively (p = 0.0536). CONCLUSIONS: This population-based study showed that in patients with iNPH, shunt surgery should be performed within 3 months of decision to surgery, to attain the best outcome.

Comorbid alpha synucleinopathies in idiopathic normal pressure hydrocephalus.

OBJECTIVE: This study aimed to determine the prevalence and clinical features of Parkinson's disease (PD)/PD dementia (PD/PDD) or dementia with Lewy bodies (DLB) in idiopathic normal pressure hydrocephalus (iNPH). METHODS: Patients with iNPH who were admitted to the Department of Neurology, Juntendo University School of Medicine over the past 10 years have been retrospectively analyzed. The diagnosis of iNPH and concomitant PD/PDD or DLB was established using diagnostic criteria. Motor symptoms were assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III. 123I-ioflupane single-photon emission computed tomography (DaT-SPECT) and cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC)-based assay were performed for alpha synuclein aggregation. RESULTS: Overall, 79 patients met the criteria for iNPH, of which 34 developed iNPH without accompanying disorders (iNPHa; 43%), 23 developed iNPH with comorbid PD/PDD (iNPHc + PD/PDD; 29.1%), and 8 developed iNPH with comorbid DLB (iNPHc + DLB; 10.1%). Significant differences in facial expansion and upper-limb parkinsonism were observed with a comorbidity of either PD/PDD or DLB. The specific binding ratio (SBR) of DaTscan was reduced in iNPHa (p = 0.02), but it reduced further with comorbid PD/PDD (p < 0.01) or DLB (p < 0.01). RT-QuIC was positive for all 13 comorbid PD/PDD and negative for all 19 iNPHa. CONCLUSION: These results highlight that synucleinopathies coexist with iNPH. These can be differentiated by performing DaTscan and RT-QuIC, which can affect its clinical features.

The Role of Simultaneous Medical Conditions in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a chronic neurologic syndrome that affects the elderly population in a context of concomitant medical conditions. The aim of this study was to understand the significance of comorbidities using 4 validated and specific clinical scores: Cumulative Illness Rating Scale (CIRS), American Society of Anesthesiologists (ASA) score, Comorbidity Index (CMI), and Charlson Comorbidity Index (CCI). METHODS: From 2015 until 2019, the Bologna PRO-Hydro multidisciplinary team selected 63 patients for shunt surgery. All comorbidity scores were collected during preoperative anesthesia evaluation. Positive shunt response was defined as an improvement in overall disability (assessed with modified Rankin Scale [mRS]), in risk of fall (assessed with Tinetti Permormance Orientated Mobility Assessment, Tinetti) and in INPH specific symptoms (assessed with INPH Grading Scale, INPHGS). RESULTS: Patients with elevated values of CIRS had worse performance in gait and balance at Tinetti scale, both before (P = 0.039) and after surgery (P = 0.005); patients with high values of CMI had inferior values of Tinetti at baseline (P = 0.027) and higher mRS after surgery (P = 0.009); ASA 2 patients had better postoperative Tinetti scores than ASA 3 patients (P = 0.027). A positive or negative shunt response was not significantly correlated with patients' preoperative comorbidity scores. CONCLUSIONS: Patients with multiple comorbidities have a worse preoperative condition compared to patients with less concomitant diseases, and the proposed comorbidity scores, CIRS in particular, are useful clinical tools for the anesthesiologist. Comorbidities, though, do not impact overall postoperative outcome.

Parkinsonism and cerebrospinal fluid disorders.

BACKGROUND: Although various motor manifestations can be seen in patients with cerebrospinal fluid (CSF) disorders, such as hydrocephalus or intracranial hypotension, the clinical presentation with parkinsonism is not clearly elucidated. METHODS: We searched the literature for studies describing the occurrence of parkinsonism in subjects with normal pressure hydrocephalus (NPH), obstructive hydrocephalus, and intracranial hypotension. We analyzed the clinical presentation (particularly with respect to bradykinesia, rigidity, rest tremor, and gait disturbance/postural instability) as well as the response to treatment. RESULTS: Parkinsonism was most commonly reported in NPH patients. Although gait disturbance/postural instability is a well-known motor symptom of NPH, other cardinal signs include upper limb involvement or asymmetric presentation. As for obstructive hydrocephalus, parkinsonism was mainly observed in subjects with aqueductal stenosis and more often after shunt surgery. Patients with NPH or obstructive hydrocephalus rarely improved with levodopa therapy, while most subjects only improved with shunt surgery. Although the mechanism is still controversial, a functional involvement of nigrostriatal pathway has been hypothesized based on imaging studies and case reports. Brain imaging is also helpful for atypical cases of intracranial hypotension presenting with parkinsonism. Parkinsonism improved after treatment in such cases as well. CONCLUSIONS: Studies exploring the relationship between CSF disorders and parkinsonism are mainly descriptive and their quality is generally poor. However, considering that these disorders can be treated, clinicians' awareness of the differential diagnosis is important and future studies better exploring the underlying pathophysiological mechanisms are warranted. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

Clinical comorbidities correlated with a response to the cerebrospinal fluid tap test in idiopathic normal-pressure hydrocephalus.

AIMS: The mainstay of treatment for idiopathic normal-pressure hydrocephalus (iNPH) is spinal fluid shunting. A tap test (TT) is recommended as an indication of shunting. Patients with iNPH are often elderly and have multiple comorbidities affecting the shunting outcome. We investigated the factors affecting TT in patients with iNPH. METHODS: Seventy-five patients with iNPH were admitted to our department for a TT from April 2010 to May 2021. The patients were divided into a responsive group and an unresponsive group according to the clinical outcomes after TT on the Timed Up and Go Test (TUG), Mini-Mental State Examination (MMSE), or iNPH grading scale. Factors affecting the TT were compared between the responders and nonresponders. RESULTS: There were 38 patients (50.7%) in the TT responder group, and the prevalence of improvement was 82.9% in the TUG, 27.6% in the MMSE, and 76.3% in the iNPH grading scale. There were no significant differences in the vascular risk factors between the two groups. The prevalence of lumbar spondylosis, compression fracture, severe periventricular hyperintensity, deep and subcortical white matter hyperintensity (DSWMH), and old cerebral infarcts was significantly higher among the TT nonresponders. The logistic regression analysis showed that severe DSWMH and lumbar spondylosis were associated with a TT nonresponse (p < 0.001 and p = 0.003, respectively). Shunting was performed in 22 patients, 19 of whom were TT responders. CONCLUSION: Severe DSWMH and lumbar spondylosis were associated with a poor response to the TT in iNPH patients. We should consider risk factors when selecting candidates for shunt surgery.

Improvement in the long-term care burden after surgical treatment of patients with idiopathic normal pressure hydrocephalus: a supplementary study.

Idiopathic normal pressure hydrocephalus (iNPH) is a surgically treatable syndrome commonly observed in older adults. However, it is unclear whether clinical improvements after surgery can effectively reduce the long-term care burden (LTCB). In this study, we determined whether shunt surgery was effective in decreasing LTCB. We also investigated the degree of variability in patients and hospitals, using data from the iNPH multicenter study. This study involved 69 participants who underwent lumboperitoneal shunt surgery with follow-up for 12 months. A generalized linear mixed model was applied to analyze the fixed and random effects simultaneously. Regarding LTCB, the disability grades improved significantly. Although the dementia grades also improved, it was not statistically significant. The differences in the LTCB grades in most patients were within the range of the 95% confidence intervals, while in the case of hospitals, some were often out of the range. Further studies are needed to improve dementia in patients with iNPH. The incorporation of random variables, such as hospitals, is important for the analysis of data from multicenter studies.

Patient Risk Factors Associated With 30- and 90-Day Readmission After Ventriculoperitoneal Shunt Placement for Idiopathic Normal Pressure Hydrocephalus in Elderly Patients: A Nationwide Readmission Study.

OBJECTIVE: For idiopathic normal pressure hydrocephalus (iNPH), risk stratifying patients and identifying those who are likely to fare well after ventriculoperitoneal shunt (VP) surgery may help improve quality of care and reduce unplanned readmissions. The aim of this study was to investigate the drivers of 30- and 90-day readmissions after VP shunt surgery for iNPH in elderly patients. METHODS: The Nationwide Readmission Database, years 2013 to 2015, was queried. Elderly patients (≥65 years old) undergoing VP shunt surgery were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Unique patient linkage numbers were used to follow patients and identify 30- and 31- to 90-day readmission rates. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31 to 90 days (90-R). RESULTS: We identified 7199 elderly patients undergoing VP shunt surgery for iNPH. A total of 1413 (19.6%) patients were readmitted (30-R: n = 812 [11.3%] vs. 90-R: n = 601 [8.3%] vs. Non-R: n = 5786). The most prevalent 30- and 90-day complications seen among the readmitted cohort were mechanical complication of nervous system device implant (30-R: 16.1%, 90-R: 12.4%), extracranial postoperative infection (30-R: 10.4%, 90-R: 7.0%), and subdural hemorrhage (30-R: 6.0%, 90-R: 16.4%). On multivariate regression analysis, age, diabetes, and renal failure were independently associated with 30-day readmission; female sex, and 26th to 50th household income percentile were independently associated with reduced likelihood of 90-day readmission. Having any complication during the index admission independently associated with both 30- and 90-day readmission. CONCLUSIONS: In this study, we identify the most common drivers for readmission for elderly patients with iNPH undergoing VP shunt surgery.

Falls and Fear of Falling in Shunted Idiopathic Normal Pressure Hydrocephalus-The Idiopathic Normal Pressure Hydrocephalus Comorbidity and Risk Factors Associated With Hydrocephalus Study.

BACKGROUND: Gait and balance impairment are typical symptoms of idiopathic normal pressure hydrocephalus (INPH), implicating that falls may afflict these patients. OBJECTIVE: To investigate falls, related injuries, and associated psychological features, before and after shunt surgery for INPH and compared to the general population. METHODS: The study included 176 patients shunted for INPH and 368 age- and sex-matched controls. Falls, fear of falling (FOF), fall-related injuries (mild-severe), confidence in avoiding falls (Swedish Falls Efficacy Scale (FES(S)), quality of life (QoL; EuroQoL 5-dimension 5 level instrument), and symptoms of depression (Geriatric Depression Scale 15) were investigated. Pre- and postoperative observational times were 12 mo before surgery and 21 mo after (mean). Recurrent fallers fell ≥2 times. RESULTS: More INPH patients than controls were recurrent fallers (67% vs 11%; P < .001). They feared falling more often (FOF, mean ± standard deviation: 3.3 ± 1.1 vs 1.6 ± 0.9; P < .001) and had lower confidence in avoiding falls (FES(S) 78 ± 40 vs 126 ± 14; P < .001). After surgery, INPH patients improved in all parameters but they did not reach the levels of the controls. Among fallers there was no difference between patients and controls in the severity of injuries suffered. Low QoL and symptoms of depression were more common among recurrent fallers than one-time or nonfallers in both shunted patients and controls (P ≤ .001). CONCLUSION: Falls, FOF, and low confidence in avoiding falls are considerable problems in INPH that may be reduced by shunt surgery. We suggest that remaining risk of falling and preventative measures are routinely considered in postoperative follow-ups and rehabilitation planning.

Prevalence and Trends in Management of Idiopathic Normal Pressure Hydrocephalus in the United States: Insights from the National Inpatient Sample.

BACKGROUND: Over the past 2 decades, management of idiopathic normal pressure hydrocephalus (iNPH) has evolved significantly. In the current study, we sought to evaluate the national prevalence and management trends of iNPH in the United States using a national database. METHODS: The National Inpatient Sample was queried for patients with an International Classification of Diseases diagnosis code for iNPH from 2007 to 2017. Trends in prevalence and procedure type were evaluated per 100,000 discharges and as a percentage of discharges, using weighted discharges. Utilization of procedure type across U.S. regions and hospital types was also compared. RESULTS: From 2007 to 2017, 302,460 weighted discharges with any diagnosis code for iNPH, aged ≥60 years, were identified. Prevalence ranged from 0.04% to 0.20% (41/100,000 to 202/100,000) among admitted patients ≥60 years old, giving an average prevalence during the study duration of 0.18% (179/100,000). Of 66,759 weighted discharges with a primary diagnosis code of iNPH undergoing surgical management, ventriculoperitoneal shunt (72.0% of discharges, n = 48,977) was most commonly used; of these, 9.3% (n = 4567) were performed laparoscopically. This result was followed by lumbar peritoneal shunt (15.1% of discharges, n = 10,441). Up to 15.1% (n = 9990) of discharges reported only a lumbar puncture, assumed to be only diagnostic, for screening, or part of serial cerebrospinal fluid removal procedures. Significant discrepancies in procedure utilization were also identified among hospitals in the Western, Southern, Northeast and Midwest regions, as well as between urban and rural hospitals (P < 0.05). CONCLUSIONS: We have summarized the national prevalence of iNPH, trends in its management over the previous decade and trends by region and hospital type.