Normal Pressure Hydrocephalus Research Articles

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

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. 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. Survival was observed for a mean period of 10.3 ± 0.84years. 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 10years, 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. 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.

CSF CXCL13 is elevated in patients with CIDP and may reflect higher disease activity

To evaluate B-cell involvement in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 11 patients with CIDP, 8 patients with Guillain–Barré syndrome and 13 patients with idiopathic normal pressure hydrocephalus (iNPH) were studied. CSF cytokine and chemokine (IL-10, IL-15, TNF-α, TGF-β1, GM-CSF, BAFF, CXCL10, and CXCL13) levels were measured by ELISA. The CSF CXCL13 level was significantly higher in patients with CIDP than in those with iNPH. The CSF CXCL13 level was significantly higher in CIDP patients with higher annualized relapse rates and higher modified Rankin scale scores. The CSF CXCL13 level is elevated in CIDP, especially in those with higher disease activity.

96 The Proportion of Patients with Cerebrospinal Fluid Biomarkers Consistent with Alzheimer’s Disease in a Cohort with Suspected Normal Pressure Hydrocephalus

Objective:Normal pressure hydrocephalus (NPH) is characterized by pathologically enlarged ventricles without elevated cerebrospinal fluid (CSF) pressure along with a triad of clinical symptoms including gait disturbances, urinary incontinence, and cognitive impairment. NPH is evaluated with lumbar drain trials (LDTs) where CSF is removed over several days to determine if patients would benefit from ventricular shunting. Candidate selection and success for these surgeries remains challenging because other diseases such as Alzheimer’s disease (AD) share common features with NPH in cognitive impairment and enlarged ventricles. Prior research has found that 20%-40% of presumed NPH cases have AD pathology as determined by brain biopsy or autopsy. CSF biomarkers of AD can be altered in NPH and are not always conclusive, complicating the interpretation of results when formulating diagnoses and prognoses. Studies to refine the analyses of AD CSF biomarkers in NPH are needed. We aimed to examine the frequency of CSF biomarker results among patients presenting for NPH evaluations with LDTs.Participants and Methods:62 patients presented for LDTs upon physician recommendations. CSF specimens were sent to Mayo Clinic Laboratories for Alzheimer Disease Evaluation (ADEVL) that utilizes Elecsys (Lenexa, KS) CSF electrochemiluminescence immunoassays (Roche Diagnostics, Basel, Switzerland) to measure levels of amyloid-beta 42 (Aβ42), total tau (t-tau), and phosphorylatedtau (p-tau), and p-tau:Aβ42 ratio. Results were classified based on interpretation through the Amyloid/Tau/Neurodegeneration (ATN) framework1: 1) AD - biomarker profile consistent with AD pathologic change, 2) non-AD profile - biomarker levels normal or inconsistent with AD pathologic change, or 3) indeterminate - biomarkers were incongruous with only one or two abnormal levels of Aβ42, t-tau, p-tau, or ptau: Aβ42. Indeterminate cases may represent altered protein levels due to CSF dynamics or AD-related pathologic change. In reviewing recent research on CSF dynamics and AD biomarkers in NPH2 a p-tau threshold of 15 pg/mL was derived and implemented such that cases with Aß42 &lt;=1026 pg/mL and p-tau &lt;15 pg/mL were designated as suspected non-AD, and those with Aß42 &lt;=1026 pg/mL and p-tau &gt;15 pg/mL were designated suspected AD.Results:Of the 62 LDT cases, 12 (19.35%) were classified as AD, 31 (50%) were indeterminate and 22 (35.48%) were non-AD. Of the 31 indeterminate cases, 21 (33.87% of the overall sample) were suspected non-AD and 7 (11.29% of the full sample) were categorized as suspected AD.Conclusions:Our findings show that 20%-30% of patients presenting for LDT showed evidence for AD-type pathologic change, consistent with prior reports of AD pathology in cases of possible NPH. Half of all LDT cases had indeterminate AD CSF biomarker results, the interpretations of which were confounded by the potential alterations of CSF biomarkers levels due to NPH independent of AD. Our findings emphasize the need to establish better approaches to interpreting CSF AD biomarkers in evaluating NPH. Future research should examine the discriminative utility of CSF AD biomarkers and the selected p-tau threshold in indeterminate cases for predicting response to LDT and shunting.

Utilidad de la volumetría del tercer ventrículo en pacientes con hidrocefalia a presión normal

ObjectiveTo use third ventricle morphometric variables as a tool for the selection of patients with idiopathic normal pressure hydrocephalus (iNPH) who are candidates for ventriculoperitoneal shunts (VPS). Material and methodsRetrospective study enrolling patients with iNPH. Katzman infusion test was performed and a Rout>12mmHg/ml/min was considered a positive result. The transverse diameter and the volume of the third ventricle were measured in the preoperative MRI. Postoperative improvement was assessed with the NPH score. The results were analysed with SPSS software. ResultsFifty-two patients with a mean age of 76 years were analysed. There was no difference in the diameter of the third ventricle among patients with a positive result and those with a negative result in the infusion test (12.28mm vs. 11.68mm; p=0.14). Neither were difference detected in the ventricle volume of both groups (3.6cm3 vs. 3.5cm3; p=0.66). Those patients who improved after VPS had a smaller third ventricle compared to those who did not respond after surgery (11.85mm vs. 12.96mm; p=0.009). Diameter and volume of third ventricle present a significant strong correlation (Pearson correlation coefficient=0.72; p<0.0001). ConclusionMorphometric variables of third ventricle may be useful in predicting a good response to VPS in patients with idiopathic normal pressure hydrocephalus.

Case report of idiopathic normal pressure hydrocephalus: a challenging diagnosis

Introduction: This report concerns the case of a 70-year-old man with idiopathic normal pressure hydrocephalus (iNPH). The diagnosis in the current case took more than 2 years. iNPH is characterised by ventriculomegaly with a known triad of symptoms: gait disturbance, cognitive impairments and urinary incontinence. Although this is a difficult diagnosis and other conditions must be ruled out, several points in the process could lead to a correct diagnosis. The aim of the report is to identify several reasons why the diagnosis was delayed for such a long time, as well as lessons for the future. Case: This patient developed several symptoms over time. First, he presented with depressive mood and altered behaviour. He later developed gait difficulties and, finally, urinary incontinence. Multiple consultations and examinations failed to provide an exact explanation for all his symptoms. After 2 years, a new doctor at the hospital started from scratch and recognised the iNPH triad, and the diagnosis was confirmed by the radiologist. Conclusion: The diagnosis of iNPH is difficult, as symptoms may manifest over time. In this case, the delay of diagnosis exceeded estimations. A broader view through interdisciplinary consultation could provide new insights and lead to earlier diagnosis.

Idiopathic Normal Pressure Hydrocephalus: The Real Social and Economic Burden of a Possibly Enormous Underdiagnosis Problem.

Normal Pressure Hydrocephalus (iNPH) typically affects the elderly and can cause cognitive decline, resulting in its differential diagnosis with other neurodegenerative conditions. Moreover, it is probably underdiagnosed; such under- and misdiagnosis prevents the patient from receiving the right treatment and significantly affects the quality of life and life expectancy. This investigation is an in-depth analysis of the actual incidence of iNPH in the population of the province served by our hospital (circa 580,000 individuals). The first phase of this study was conducted by visualizing a total of 1232 brain CT scans performed in the Emergency Departments of the four hospitals of our network on patients who were admitted for different complaints yet screened as suspicious for iNPH. Subsequently, corresponding Emergency Department medical records were investigated to understand the medical history of each patient in search of elements attributable to an alteration of CSF dynamics. The cohort of positive CT scans, according to the radiological and clinical inclusion criteria, included 192 patients. Among the reasons to require acute medical care, "Fall" was the most common. The cumulative incidence of CT scans suggestive of iNPH among the patients undergoing CT scans was as high as 15.58%, and the period prevalence calculated for the total amount of patients accessing the Emergency Departments was 1.084%. The real incidence of iNPH in the population may be underestimated, and the social burden linked to the assistance of patients suffering from such untreated conditions could be significantly relieved.

Association of gait and cognition after surgery in patients with idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable disease in older adults. The association between gait and cognition has recently become a topic of interest. Sequential changes in this association were investigated in patients with iNPH using a newly developed statistical method. Data were extracted from the SINPHONI-2 multicenter study on iNPH. Fifty patients who underwent shunt surgery were included in this study. Gait and cognition were assessed using the Timed Up and Go (TUG) and Mini-Mental State Examination (MMSE) tests. In addition to the MMSE total score, changes in the sub-item scores were examined. The ordinal sub-items of the MMSE are usually treated as continuous or categorical; however, both are unsuitable. An ordinal smoothing penalty with a generalized additive model enables precise statistical inference of ordinal and binary predictors. The TUG time improved significantly at 3, 6, and 12 months after surgery. The MMSE total scores increased without statistical significance. Preoperatively, there was no association between TUG time and MMSE sub-items. At 3 months, the “Registration,” ”3-step command,” “Read,” and “Copy” sub-items were statistically significant. The number of significant sub-items increased after 12 months. Thus, the association between gait and cognition gradually increased after surgery in patients with iNPH.

Association between ventricular CSF biomarkers and outcome after shunt surgery in idiopathic normal pressure hydrocephalus

IntroductionThe relationship between neurochemical changes and outcome after shunt surgery in idiopathic normal pressure hydrocephalus (iNPH), a treatable dementia and gait disorder, is unclear. We used baseline ventricular CSF to explore associations to outcome, after shunting, of biomarkers selected to reflect a range of pathophysiological processes.MethodsIn 119 consecutive patients with iNPH, the iNPH scale was used before and after shunt surgery to quantify outcome. Ventricular CSF was collected perioperatively and analyzed for biomarkers of astrogliosis, axonal, amyloid and tau pathology, and synaptic dysfunction: glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL40/CHI3L1), monocyte chemoattractant protein-1 (MCP-1) neurofilament light (NfL), amyloid beta 38 (Aβ38), Aβ40, Aβ42, amyloid beta 42/40 ratio (Aβ42/40), soluble amyloid precursor protein alfa (sAPPα), sAPPβ, total tau (T-tau), phosphorylated tau (P-tau), growth-associated protein 43 (GAP43), and neurogranin.ResultsThe neurogranin concentration was higher in improved (68%) compared to unimproved patients (median 365 ng/L (IQR 186–544) vs 330 (205–456); p = 0.046). A linear regression model controlled for age, sex and vascular risk factors including neurogranin, T-tau, and GFAP, resulted in adjusted R2 = 0.06, p = 0.047. The Aβ42/40 ratio was bimodally distributed across all samples, as well as in the subgroups of improved and unimproved patients but did not contribute to outcome prediction. The preoperative MMSE score was lower within the low Aβ ratio group (median 25, IQR 23–28) compared to the high subgroup (26, 24–29) (p = 0.028). The T-Tau x Aβ40/42 ratio and P-tau x Aβ40/42 ratio did not contribute to shunt response prediction. The prevalence of vascular risk factors did not affect shunt response.DiscussionA higher preoperative ventricular CSF level of neurogranin, which is a postsynaptic marker, may signal a favorable postoperative outcome. Concentrations of a panel of ventricular CSF biomarkers explained only 6% of the variability in outcome. Evidence of amyloid or tau pathology did not affect the outcome.

Idiopathic Intracranial Hypertension with Disproportionately Enlarged Subarachnoid Space Hydrocephalus on Imaging: A Case Report.

The pathophysiology of idiopathic intracranial hypertension (IIH) and idiopathic normal-pressure hydrocephalus (iNPH) differs in terms of cerebrospinal fluid (CSF) pressure and imaging-related characteristics. A 51-year-old man presented with optic nerve papillary edema, visual disturbance, bilateral abducens nerve palsy, and a wide-based gait. Imaging showed characteristic findings of IIH and disproportionately enlarged subarachnoid space hydrocephalus (DESH)-characteristic of iNPH. A CSF examination revealed marked CSF hypertension. IIH with iNPH-like imaging features (DESH) was diagnosed, and ventriculoperitoneal shunt surgery was performed. Postoperatively, the visual acuity and visual field improved. This report also describes the distinct and overlapping pathophysiological mechanisms of IIH and iNPH.

Evaluation of a Fully Automated Method for Ventricular Volume Segmentation Before and After Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus

Determination of the ventricle size in idiopathic normal pressure hydrocephalus (iNPH) is essential for diagnosis and follow-up of shunt results. Fully automated segmentation methods are anticipated to optimize the accuracy and time efficiency of ventricular volume measurements. We evaluated the accuracy of preoperative and postoperative ventricular volume measurements in iNPH by a magnetic resonance imaging (MRI)-based licensed software for fully automated quantitative assessment. Forty-eight patients diagnosed with iNPH were retrospectively analyzed. All patients received a ventriculoperitoneal shunt and had symptom grading and routine MRI preoperatively and 3-6 months postoperatively. Ventricular volumes, generated by fully automated T1-weighted imaging volume sequence segmentation, were compared with semiautomatic measurements and routine radiologic reports. The relation of postoperative ventricular size change to clinical response was evaluated. Fully automated segmentation was achieved in 95% of the MRIs, but showed various rates of 8 minor segmentation errors. The correlation between both segmentation methods was very strong (r >0.9) and the agreement very good using Bland-Altman analyses. The ventricular volumes differed significantly between semiautomated and fully automated segmentations and between preoperative and postoperative MRI. The fully automated method systematically overestimated the ventricles by a median 15 mL preoperatively and 14 mL postoperatively; hence, the magnitudes of volume changes were equivalent. Routine radiologic reports of ventricular size changes were inaccurate in 51% and lacked association with treatment response. Objectively measured ventricular volume changes correlated moderately with postoperative clinical improvement. A fully automated volumetric method permits reliable evaluation of preoperative ventriculomegaly and postoperative ventricular volume change in idiopathic normal pressure hydrocephalus.

Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases

BackgroundNeuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH.MethodsLumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer’s disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number.ResultsThree proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91.ConclusionsThe inflammatory cytokines MCP-1 and CCL4 are present at higher—and PD-L1 at lower—levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH.

Letter to Our Colleagues Family Practitioners, Geriatricians, and Radiologists to Increase Awareness Regarding Idiopathic Normal Pressure Hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) affects elderly individuals and is characterized by a progressive deterioration of gait, urinary continence, and cognition. In most cases, it is reversible with treatment. INPH is not uncommonly an unrecognized cause of dementia. We wish to raise awareness of iNPH among primary care providers who are seeing these patients first. We reviewed the current epidemiological data regarding iNPH as well as epidemiological data regarding Alzheimer disease. We searched for the most sensitive radiological screening test for iNPH. Alzheimer disease comprises 60%-70% of all dementia cases, in 2023 is affecting 6.7 million Americans, about 10.7% of people 65 and older. Epidemiological data from the Scandinavian countries confirmed that 3.7% of people older than 65 have iNPH. Surgical studies confirmed the presence of early Alzheimer's pathology in about 25% of operated patients with iNPH. Useful radiological findings of iNPH include an Evans Index greater than 0.30, and a disproportionally enlarged subarachnoid space hydrocephalus (DESH). However, the callosal angle is thought to represent the best tool to discriminate iNPH from its mimics. According to the available epidemiological data iNPH is underdiagnosed. We strongly encourage the primary care physicians and geriatricians to ask the radiologist to measure the callosal angle on the initial brain computed tomography (or magnetic resonance) image. If the callosal angle is ≤71°, it is appropriate to refer the patient to neurosurgery for further diagnostic work-up.

A - 20 Do Alzheimer's Disease Biomarkers Impact Normal Pressure Hydrocephalus Lumbar Drain Trial Outcomes.

Distinguishing normal pressure hydrocephalus (NPH) from Alzheimer's disease (ad) would aid patient selection for lumbar drain trials (LDT). Cerebrospinal fluid (CSF) ad biomarkers are altered in NPH, limiting interpretation. This study examines the utility of CSF ad biomarkers in predicting gait and cognitive outcomes in patients undergoing LDT. 127 patients underwent LDT. CSF ad biomarkers from Mayo Clinic Laboratories (MCL) or Athena Diagnostics were used to classify patients as ad, non-ad, or indeterminate. MCL indeterminate results were further classified as suspected ad, non-ad, or suspected NPH (sNPH) using a derived p-tau threshold (>15pg/mL & Aß42 &lt;=1026pg/mL)1. Cognitive improvement was determined using reliable change indices for Trail Making Test A&B and Hopkins Verbal Learning Test-Revised. Physical therapists (PT) utilized the Berg Balance Scale and/or the Timed Up and Go to determine gait improvements. Chi-square tests investigated relationships between diagnostic groups, PT and cognitive improvements, and eventual shunting for the whole sample and then stratified by the two laboratory assays. The sNPH group had the highest percentage of PT (63%-70%) and cognitive (9% -11%) improvement (see Table 1), while the ad group had the lowest (50% and 3%, respectively). The sNPH group underwent shunting more (56%-68%) compared to the ad and non-ad groups (47%). Relationships, however, were not statistically significant (p > 0.05). Patients with sNPH CSF ad biomarker profiles demonstrated clinically meaningful physical improvements and underwent shunting more frequently than those with ad or non-ad biomarker profiles. This highlights the potential for CSF ad biomarkers in predicting NPH treatment response.

A - 99 Older Adult Male with Idiopathic Normal Pressure Hydrocephalus (iNPH): Neuropsychological Case Study.

Idiopathic normal pressure hydrocephalous (iNPH) is a potentially reversible syndrome characterized by ventriculomegaly. Parkinsonism is an often-overlooked clinical feature of iNPH. Mostile et al. (2022) argued that the diagnostic iNPH "triad" should be reconsidered as a "tetrad" including parkinsonism. This case will discuss iNPH presenting with parkinsonism. Patient is an 81-year-old male with a history of iNPH with Hakim's triad. His medical history includes hyperlipidemia, hypertension, deep vein thrombosis, benign prostatic hyperplasia, total knee replacement, and chronic depression. Presenting concerns were continued cognitive and gait impairments. Patient was referred from his physiatrist for evaluation of his cognitive functioning and assistance with discharge planning in an acute inpatient rehabilitation hospital. Patient was neuropsychologically evaluated to clarify the etiology of his cognitive presentation. Patient's cognitive profile was impaired in areas of attention, executive functioning, processing speed, visuoperception, and displayed a subcortical memory profile. Patient had intact functioning in areas of oral reading, naming, and working memory. Motor examination was evident for apraxia, task-specific tremor, and micrographia. This case report provides additive findings for common presentation of iNPH including parkinsonism presenting with comorbid psychiatric and medical confounders, highlighting the need for further research on neuropsychological profile of iNPH post shunt procedure. It also accentuates the need to accept parkinsonism as one of the common presentations of iNPH. Akinesia has been reported in nearly 70% of iNPH cases (Krauss et al, 1997), with bradykinesia and postural instability being the main parkinsonian features. Asymmetry and resting tremor were seen to be uncommon (Molde et al., 2017).

Assessment of Evan’s Index in North-Western Nigeria using Computerised Tomography

Aim: To determine the Evan’s Index of Nigerians using computerized tomography in Sokoto North-Western Nigeria.&#x0D; Study Design: Retrospective cross- sectional.&#x0D; Place and duration of study: Department of Anatomy Usmanu Danfodiyo University Sokoto and Department of Radiology Usmanu Danfodiyo University Teaching Hospital Sokoto, between January, 2020 and January, 2022.&#x0D; Methodology: Normal brain CT scans of one hundred and seventy-eight subjects from the Radiology Department of the Usmanu Danfodiyo University Teaching Hospital, whose ages ranged from 1 to 70 year. The Evans index was determined by the ratio of the measured distance between the tips of the frontal horns of lateral ventricles and the inner skull tables at the midpoint of the cranium in axial plane.&#x0D; Results: The Evan’s indexes were larger in male than the females and these differences were not statically significant except in the age group 51-60years where statistically significant difference was observed between male and female (p=0.042). The minimum Evan’s index was 0.02cm in male and 0.01 females and the maximum bi-frontal index was 0.40cm in male and 0.38cm in females.&#x0D; Conclusion: The Evan’s indexes and it relation with sex and age in our environment was determined.

Predictive value of spinal CSF volume in the preoperative assessment of patients with idiopathic normal-pressure hydrocephalus.

The pathophysiology, diagnosis, and management of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Although some prognostic tests recommended in iNPH guidelines should have high sensitivity and high predictive value, there is often no positive clinical response to surgical treatment. In our study, 19 patients with clinical and neuroradiological signs of iNPH were selected for preoperative evaluation and possible further surgical treatment according to the guidelines. MR volumetry of the intracranial and spinal space was performed. Patients were exposed to prolonged external lumbar drainage in excess of 10 ml per hour during 3 days. Clinical response to lumbar drainage was assessed by a walk test and a mini-mental test. Twelve of 19 patients showed a positive clinical response and underwent a shunting procedure. Volumetric values of intracranial space content in responders and non-responders showed no statistically significant difference. Total CSF volume (sum of cranial and spinal CSF volumes) was higher than previously published. No correlation was found between spinal canal length, CSF pressure, and CSF spinal volume. The results show that there is a significantly higher CSF volume in the spinal space in the responder group (n = 12) (120.5 ± 14.9 ml) compared with the non-responder group (103.1 ± 27.4 ml; n = 7). This study demonstrates for the first time that CSF volume in the spinal space may have predictive value in the preoperative assessment of iNPH patients. The results suggest that patients with increased spinal CSF volume have decreased compliance. Additional prospective randomized clinical trials are needed to confirm our results.

Brain positron emission tomography in idiopathic normal-pressure hydrocephalus: new 18F-fluorodeoxyglucose pattern in a long-known syndrome.

Patients with idiopathic normal-pressure hydrocephalus (iNPH) can show a global reduction in cerebral glucose metabolism at [18F]Fluorodeoxyglucose (FDG) PET. The presence of caudate hypometabolism has been identified as a potential biomarker in iNPH, yet there is limited evidence of hypermetabolic findings in patients with iNPH so far. We retrieved retrospectively patients with iNPH and normal cognitive assessment, evaluated before surgery undergoing brain [18F]FDG-PET. The 18F-FDG-PET brain scans were compared to those of a control group of healthy subjects, matched for age and sex, by statistical parametric mapping (SPM) to identify areas of relative hypo- and hypermetabolism. Furthermore, the existence of a correlation between areas of hypo- and hypermetabolism in the patient group was tested. Seven iNPH patients (mean age 74 ± 6 years) were found in the hospital database. SPM group analysis revealed clusters of significant hypometabolism (P = 0.001) in the iNPH group in the dorsal striatum, involving caudate and putamen bilaterally. Clusters of significant hypermetabolism (P = 0.001) were revealed in the bilateral superior and precentral frontal gyrus (BA 4, 6). A significant inverse correlation between striatal hypometabolism and bilateral superior and precentral frontal gyrus hypermetabolism was revealed (P < 0.001 corrected for multiple comparisons). In this cohort, patients with iNPH showed subcortical hypometabolism, including bilateral dorsal striatum. To the best of our knowledge, this is the first report demonstrating a hypermetabolic pattern in the primary motor and premotor areas, and showing an inverse correlation between the striatum and motor cortex in patients with iNPH.

Gait Analysis in Idiopathic Normal Pressure Hydrocephalus: A Meta-Analysis.

Gait analysis objectively quantifies gait impairment in idiopathic normal pressure hydrocephalus (iNPH), may improve diagnosis and evaluation for surgical candidacy. This meta-analysis aims to understand which objective gait parameters improve after tap-test (TT) and CSF shunt surgery (CSS), also comparing responders (R) with non-responders (NR) and to assess if gait restores within the range of healthy controls after procedures. Studies enrolling iNPH with at least one instrumented gait measure were selected. Three time points of gait assessment were defined: PRE, POST-TT, and POST-CSS. Gait velocity, cadence, step length, stride length, and double limb support time were evaluated. Patients were categorized based on responsiveness to CSF diversion procedures. Seventeen studies including 527 patients were selected. iNPH improved significantly in almost all gait parameters POST-TT, and to a greater extent POST-CSS. Gait parameters consistently discriminated iNPH from healthy controls. Despite the aforementioned improvements, iNPH's gait did not completely normalize after CSF diversion procedures. Meta-regression analysis also revealed that TT's effect on gait velocity plateaus after 24-48 hr and returns to baseline in 90-100 hr. Gait analysis is a reliable quantitative instrument to assess gait impairment in iNPH, demarking a net differentiation from healthy controls, according to the notion that the iNPH CSF dynamic alteration also leads to an irreversible damage. Specific gait parameters improve among TT-R, providing an opportunity to select patients that will respond to CSS. Future studies validating a standardized reporting method including criteria of responsiveness, specific gait parameters, and timeframe of assessment are needed.

Correction: Coincidence of normal pressure hydrocephalus and Alzheimer`s disease: therapeutic implications and open questions

Correction: Coincidence of normal pressure hydrocephalus and Alzheimer`s disease: therapeutic implications and open questions

Choroidal morphology and microvascular structure in eyes of patients with idiopathic normal pressure hydrocephalus before and after ventriculo-peritoneal shunt surgery

The present study aims to investigate the choroidal morphology and microvascular structure in eyes of patients with idiopathic normal pressure hydrocephalus (iNPH) compared with the eyes of healthy age-matched individuals, and to assess the choroidal structure in eyes of iNPH patients before and after shunt surgery using Optical Coherence Tomography (OCT). The primary objective was to assess the choroidal morphology in eyes of iNPH patients before and after ventriculo-peritoneal (VP) surgery compared to age and sex-matched healthy individuals. The secondary objective was to compare the choroidal morphology of iNPH patients before and after a mean of 56 days from shunt surgery. Eighteen consecutive patients diagnosed with iNPH and 18 healthy controls were prospectively recruited between November 2021 and October 2022. Spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) was conducted before and within 4 months after shunt surgery. Images were binarized using the ImageJ software, and the choroidal vascular index (CVI) was calculated. Sub-foveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were significantly increased in iNPH patients before surgery compared to the control group (p < 0.05). SFCT, TCA, and SCA were significantly increased in iNPH patients after surgery compared to the control group (p < 0.05). There were no differences in the CVI between iNPH patients and controls. No statistical differences in the choroidal structure were observed before and after VP shunt surgery (p > 0.05). In conclusion, the choroid was thicker in iNPH patients before and after VP shunt compared to age-matched healthy individuals. However, there were no difference in the choroidal microstructure in the eyes of iNPH patients before and after a mean of 3 months from VP shunt surgery.