CSF formation rate-a potential glymphatic flow parameter in hydrocephalus?

BACKGROUND: Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort. METHODS: CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978. RESULTS: Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135). CONCLUSIONS: The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.

Improvement in gait velocity variability after cerebrospinal fluid elimination and its relationship to clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

AIM: This study aimed to investigate the improvement in gait velocity variability after cerebrospinal fluid (CSF) elimination, and the association between gait velocity variability and gait and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. METHODS: The gait velocity of 44 patients with idiopathic normal pressure hydrocephalus was measured using the Timed Up and Go Test (TUG) for a total of 10 times over 3 days each before and after CSF elimination. The coefficient of variation (CV) in the time required for the sequence of actions in TUG (TUG-CV) was calculated using 10 TUG data, and used for measuring intraindividual gait velocity variability. Gait quality was evaluated with the Gait Status Scale Revised (GSSR), and cognitive function was evaluated with the Mini-Mental State Examination and the Frontal Assessment Battery. RESULTS: The TUG, TUG-CV, GSSR and Frontal Assessment Battery results improved significantly after CSF elimination. The analyses using pre-CSF elimination results showed that the TUG-CV significantly and positively correlated with the TUG and GSSR results, and negatively with Mini-Mental State Examination results, but not with age and the Frontal Assessment Battery results. The stepwise multiple regression analysis indicates that the TUG, GSSR and Mini-Mental State Examination results were significant predictors of the TUG-CV. The analysis using data of change after CSF elimination showed that ΔTUG and ΔGSSR were significant predictors of ΔTUG-CV. CONCLUSIONS: Gait velocity variability improved after CSF elimination, and gait velocity variability was associated with gait disturbances and cognitive impairment in patients with idiopathic normal pressure hydrocephalus. Geriatr Gerontol Int 2024; 24: 693-699.

Normal pressure hydrocephalus and cognitive impairment: The gait phenotype matters too.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a chronic neurological disease resulting in progressive gait and cognitive disorders. We investigated whether the gait phenotype is associated with the severity of cognitive deficits in iNPH. METHODS: This retrospective study recruited 88 patients (mean age = 76.18 ± 7.21 years, 42% female). Patients were initially referred for suspicion of iNPH and underwent a comprehensive analysis, including gait analysis and cognitive evaluation. RESULTS: In this cohort (27% normal gait, 25% frontal gait, 16% parkinsonian gait, 27% other gait abnormalities), patients with parkinsonian and frontal gait had the lowest Mini-Mental State Examination (MMSE) scores and the slowest gait speed. Patients with normal gait had the highest MMSE scores and gait speed. Frontal gait was associated with lower MMSE score, even after adjusting for age, gender, comorbidities, white matter lesions, and education level (ß = -0.221 [95% confidence interval (CI) = -3.718 to -0.150], p = 0.034). Normal gait was associated with the best MMSE scores, even after adjusting for the abovementioned variables (ß = 0.231 [95% CI = 0.124-3.639], p = 0.036). CONCLUSIONS: Gait phenotypes among iNPH patients are linked to global cognition as assessed with MMSE.

Is there a spinal tap responder in progressive supranuclear palsy? The first prospective study.

OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease, and sometimes shows idiopathic normal pressure hydrocephalus (iNPH)-like presentations. We aimed to evaluate spinal tap responsiveness in patients with PSP, including the effect of sham spinal tap. METHODS: Eleven patients with PSP, ten with probable/definite iNPH, and eight control patients were prospectively enrolled. All participants underwent sham spinal tap and spinal tap procedures. Gait was evaluated using wearable inertial sensors. We defined "tap responders" as individuals with a 10% or more improvement from baseline in any of the gait parameters (timed up-and-go test total time, stride length, and velocity during straight walking under single-task and cognitive dual-task conditions). We compared the ratio of responders in patients with PSP to patients with iNPH and controls. RESULTS: The ratio of tap responders and the ratio of sham tap responders in patients with PSP were significantly higher than those in control patients, and not different from those in patients with iNPH. PSP patients with iNPH-like MRI features tended to respond to the spinal tap compared to those without such imaging features. Notably, one patient with PSP, who responded to the spinal tap beyond the effect of sham spinal tap, was treated by the shunt operation. CONCLUSION: This is the first prospective study to demonstrate tap and shunt responsiveness in patients with PSP while highlighting the placebo effects of the spinal tap in patients with PSP or iNPH. Our findings suggest that some PSP patients have impaired cerebrospinal fluid circulation, contributing to a distinct component of the clinical spectrum.

The grasp reflex in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.

Predicting post-surgical outcomes in idiopathic normal pressure hydrocephalus using clinically important changes from the cerebrospinal fluid tap test.

OBJECTIVE: Patients diagnosed with idiopathic Normal Pressure Hydrocephalus (iNPH) typically experience symptom improvements after undergoing a cerebrospinal fluid-tap test (CSF-TT), These improvements are recognized as indicative of potential improvements following surgical intervention. As gait disturbance is the most common iNPH symptom, gait improvements are of predominant interest. The purpose of this study was to examine if clinically important changes in gait and balance from CSF-TT predict meaningful changes following surgery. METHOD: The study involved analysis of data collected in a prospective observational study for 34 iNPH patients who underwent a CSF-TT and subsequent surgery. Linear regression, logistic regression and classification trees were used for predictive modelling comparing changes from CSF-TT with post-surgical changes in Tinetti, Timed Up and Go (TUG) and Berg Balance Scale (BBS) outcomes. RESULTS: Predictive models for minimal clinically important differences (MCIDs) from CSF-TT to surgery were significant for Tinetti (odds ratio = 1.42, p = 0.02) and BBS (odds ratio = 1.57, p < 0.01). Four items on Tinetti and two items on BBS were identified with a predictive accuracy of 79% and 76% respectively. BBS has the highest sensitivity (85%) and negative predictive value (77%). TUG had a 100% specificity and 100% positive predictive value. The predictive model using MCIDs for TUG was not significant (odds ratio = 1.13, p = 0.06). CONCLUSION: Clinically important changes from CSF-TT are useful in predicting post-surgical outcomes in iNPH patients. Tinetti and BBS, both have predictive value using MCID scores as cut off values, of which BBS is a stronger outcome measure for prediction.

Influence of interaction of cerebral fluids on ventricular deformation: A mathematical approach.

This paper describes the effects of the interaction of cerebral fluids (arterial, capillary and venous blood, cerebrospinal fluid) on ventricular wall displacement and periventricular pressure using a mathematical multiphase poroelasticity model for the cerebral parenchyma. The interaction of cerebral fluids is given by a set of four numerical coefficients. A multiple linear regression with interaction is constructed that allows us to quantify the effect of these coefficients on the average ventricular wall displacement. The prevailing influence of an arterial-liquor component was observed. The sets of coefficients associated with such pathological conditions were found: normal pressure hydrocephalus, intracranial hypertension, and replacement ventriculomegaly under a prolonged hypoperfusion.

Asymmetry and tuning shift of the cervical vestibular evoked myogenic potential indicate saccular dysfunction in idiopathic normal pressure hydrocephalus.

OBJECTIVE: The purpose of this study was to investigate the effects of excessive cerebrospinal fluid (CSF) retention on the peripheral vestibular function and the inner ear fluid in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: In 25 patients with iNPH (14 females, age 65-88 years), cervical vestibular evoked myogenic potential (cVEMP) was measured before the spinal tap test. The asymmetry ratios (ARs) and tuning properties in 500 Hz and 1,000 Hz short-tone burst stimuli of cVEMP were evaluated. Furthermore, cVEMP was measured in an age-matched control group of 12 non-iNPH patients. RESULTS: Seven (28%) iNPH patients exhibited a cVEMP asymmetry (AR > 33%). cVEMP tuning was significantly shifted to a higher frequency in the iNPH group than in the age-matched control group. CONCLUSIONS: One-fourth of patients with iNPH had obvious saccular dysfunction. A high rate of a shift in cVEMP tuning in the iNPH group indicated that excessive CSF accumulation propagated to the endolymph and perilymph. SIGNIFICANCE: Saccular dysfunction might be one of the possible causes of imbalance in iNPH, and the shift in cVEMP tuning may be a determining factor in the diagnosis and treatment strategy.

Comparison of comfortable and maximum walking speed in the 10-meter walk test during the cerebrospinal fluid tap test in iNPH patients: A retrospective study.

BACKGROUND: The 10-meter walking test (10 MWT) is widely used during a cerebrospinal fluid tap test (CSFTT) for idiopathic normal-pressure hydrocephalus (iNPH). However, various previous studies and guidelines do not specify whether to adopt a comfortable walking speed or maximum walking speed when implementing the 10 MWT. In this study, we analyzed the values of comfortable and maximum walking speeds during the CSFTT in patients who underwent shunt surgery to determine which walking form is desirable for evaluation. METHODS: The patients were 29 consecutive cases in which a CSFTT was performed, followed by shunting, between October 2012 and April 2019. Data on the 10 MWT comfortable walking speed and maximum walking speed were collected, as were data on the timed up and go (TUG) test and Mini-Mental State Examination (MMSE). We analyzed the rate of change in comfortable walking speed and maximum walking speed before CSFTT and on the first day after CSFTT, and the amount of improvement compared to baseline ability. In addition, diagnostic performance was compared using a receiver operating characteristic (ROC) analysis. RESULTS: Twenty-eight patients who underwent shunt surgery improved their symptoms and were designated as shunt responders. The remaining patient who underwent surgery was considered a non-responder with no improvement in symptoms. The parameters of the shunt responders that changed were muscle strength, the 10 MWT, and the TUG test, and there was no significant change in cognitive function. The rate of change, amount of change, and sensitivity were large at a comfortable walking speed, but ROC analysis showed that the maximum walking speed had a large area under the curve and excellent specificity. The higher the preoperative gait function, the lower the improvement rate of gait function. DISCUSSION: The comfortable walking speed is easy to measure, but its specificity is inferior to the maximum walking speed. However, the maximum walking speed may be affected by the ceiling effect and measurement errors. Despite this, we concluded that the maximum walking speed had a better diagnostic performance. Because the causes of gait disturbance in iNPH include decreased muscle output, postural instability, and gait rhythm disorder, and maximum walking speed is strongly related to each of these factors, this accounts for the changes in maximum walking speed. CONCLUSION: In conclusion, although comfortable walking speed was easy to measure in terms of changes and had high sensitivity, the maximum walking speed had the highest specificity and comprehensive diagnostic performance. It is recommended that maximum walking speed be evaluated when making a definitive diagnosis of iNPH.

Cerebral ventriculomegaly in myotonic dystrophy type 1: normal pressure hydrocephalus-like appearances on magnetic resonance imaging.

BACKGROUND: Cerebral ventriculomegaly is an abnormal feature characteristic of myotonic dystrophy type 1 (DM1). This retrospective study investigated the morphologic changes accompanied by ventriculomegaly in DM1 on brain MRI. METHODS: One hundred and twelve adult patients with DM1 and 50 sex- and age-matched controls were assessed. The imaging characteristics for evaluations included the z-Evans Index (ventriculomegaly), callosal angle (CA), enlarged perivascular spaces in the centrum semiovale (CS-EPVS), temporo-polar white matter lesion (WML) on 3D fluid-attenuated inversion recovery (FLAIR), disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and pathological brain atrophy. The "z-Evans Index" was defined as the maximum z-axial length of the frontal horns to the maximum cranial z-axial length. To determine the imaging characteristics and genetic information (CTG repeat numbers) that were associated with the z-Evans Index, we used binominal logistic regression analyses. RESULTS: The z-Evans Index was significantly larger in the patients than in the controls (0.30 ± 0.05 vs. 0.24 ± 0.02; p < 0.01). The z-Evans Index was independently associated with the callosal angle (p < 0.01) and pathological brain atrophy (p < 0.01) but not with age, gender, CTG repeat numbers, or CS-EPVS. Of the 34 patients older than 49 years, 7 (20.6%) were considered to have DESH. CONCLUSIONS: Our MRI study revealed a normal pressure hydrocephalus (NPH)-like appearance as a morphologic finding accompanied by ventriculomegaly in DM1 that tends to occur in elderly patients.

Gait characteristics and effects of the cerebrospinal fluid tap test in probable idiopathic normal pressure hydrocephalus.

OBJECTIVES: To evaluate gait characteristics and investigate changes pre- and post- cerebrospinal fluid tap test (CSF TT) in gait parameters in patients with probable idiopathic normal pressure hydrocephalus (iNPH). METHODS: Sixty patients were sequential circuited and diagnosed with possible iNPH according to Japanese second iNPH guidelines at our hospital from December 2016 to March 2021. All patients underwent the CSF TT. Gait parameters, cognitive and urinary function were assessed pre- and post-CSF TT. Patients who were unable to ambulate to take the tests or could not walk independently or walked normally were excluded. RESULTS: Twenty-six patients were diagnosed with probable iNPH using the CSF TT. After CSF TT, the Boon sum score improved from 20.0 ± 7.7-16.6 ± 8.0 (p < 0.001), the Boon walking score improved from 8.9 ± 3.5-7.8 ± 4.4 (p = 0.008), the Boon step score improved from 6.3 ± 2.3-5.2 ± 2.1 (p < 0.001), the Boon time score improved from 4.9 ± 2.4-3.7 ± 2.3 (p < 0.001), tandem walking disturbance improved from 1.7 ± 0.7-1.4 ± 0.9 (p = 0.043), tendency toward falling improved from 1.7 ± 0.7-1.3 ± 1(p = 0.022), 3-meter timed up and go test (3-mTUG) improved from 21.9 ± 7.1-17.6 ± 5.1( p < 0.001), 10-meter walking (10-MWT) step improved from 31.1 ± 13.1-24.6 ± 7.5 (p < 0.001), velocity improved from 0.7 ± 0.2-0.8 ± 0.3 (p < 0.001) and stride length improved from 0.4 ± 0.1-0.46 ± 0.1(p < 0.001), compared with before the CSF TT. CONCLUSION: These results suggest that many parameters in the Boon gait test were responsive to the CSF TT, and the Boon gait test may help objectify response to the CSF TT by combining the 10-MWT and 3-mTUG gait assessments.

Assessment of neurological symptoms in adult hydrocephalus occlusus. A pilot study.

BACKGROUND: Comprehensively describe and compare (pre/postoperatively) the clinical symptomatology in adult non-communicated hydrocephalus. Associated hydrocephalus signs were analyzed with the idiopathic Normal Pressure Hydrocephalus Scale (iNPH Scale). A standardized clinical scale for non-communicated hydrocephalus is currently not in use. METHODS: Ten patients with hydrocephalus occlusus (HO) were analyzed. Hydrocephalus signs were examined with the iNPH Scale in gait, neuropsychology, continence, and balance before and three months after treatment with shunt operation or third endoscopic ventriculostomy. RESULTS: Patients significantly improved in iNPH total score (25.8%) and gait score (35.4%) three months after neurosurgical intervention. Domain scores in neuropsychology, continence, and balance reached statistical trends (p ≤ 0.066). Most clinical symptoms and signs at baseline improved after surgery (dizziness, lapse of concentration, gait instability, and headache). CONCLUSION: Patients with non-communicated HO also showed classical hydrocephalus symptoms as communicated in iNPH patients. The iNPH Scale allows a structured neurological assessment over the disease's progress and surgical intervention. Further studies with a larger patient samples are necessary to support our results.

Quantitative gait analysis of idiopathic normal pressure hydrocephalus using deep learning algorithms on monocular videos.

A vision-based gait analysis method using monocular videos was proposed to estimate temporo-spatial gait parameters by leveraging deep learning algorithms. This study aimed to validate vision-based gait analysis using GAITRite as the reference system and analyze relationships between Frontal Assessment Battery (FAB) scores and gait variability measured by vision-based gait analysis in idiopathic normal pressure hydrocephalus (INPH) patients. Gait data from 46 patients were simultaneously collected from the vision-based system utilizing deep learning algorithms and the GAITRite system. There was a strong correlation in 11 gait parameters between our vision-based gait analysis method and the GAITRite gait analysis system. Our results also demonstrated excellent agreement between the two measurement systems for all parameters except stride time variability after the cerebrospinal fluid tap test. Our data showed that stride time and stride length variability measured by the vision-based gait analysis system were correlated with FAB scores. Vision-based gait analysis utilizing deep learning algorithms can provide comparable data to GAITRite when assessing gait dysfunction in INPH. Frontal lobe functions may be associated with gait variability measurements using vision-based gait analysis for INPH patients.

Intracranial pressure waveform characteristics in idiopathic normal pressure hydrocephalus and late-onset idiopathic aqueductal stenosis.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) and late-onset idiopathic aqueductal stenosis (LIAS) are two forms of chronic adult hydrocephalus of different aetiology. We analysed overnight intracranial pressure (ICP) monitoring to elucidate ICP waveform changes characteristic for iNPH and LIAS to better understand pathophysiological processes of both diseases. METHODS: 98 patients with iNPH and 14 patients with LIAS from two neurosurgical centres were included. All patients underwent diagnostic overnight computerised ICP monitoring with calculation of mean ICP, ICP heartbeat related pulse wave amplitude calculated in the frequency domain (AMP) and the time domain (MWA), index of cerebrospinal compensatory reserve (RAP) and power of slow vasogenic waves (SLOW). RESULTS: ICP was higher in LIAS than iNPH patients (9.3 ± 3.0 mmHg versus 5.4 ± 4.2 mmHg, p = 0.001). AMP and MWA were higher in iNPH versus LIAS (2.36 ± 0.91 mmHg versus 1.81 ± 0.59 mmHg for AMP, p = 0.012; 6.0 ± 2.0 mmHg versus 4.9 ± 1.2 mmHg for MWA, p = 0.049). RAP and SLOW indicated impaired reserve capacity and compliance in both diseases, but did not differ between groups. INPH patients were older than LIAS patients (77 ± 6 years versus 54 ± 14 years, p < 0.001). CONCLUSIONS: ICP is higher in LIAS than in iNPH patients, likely due to the chronically obstructed CSF flow through the aqueduct, but still in a range considered normal. Interestingly, AMP/MWA was higher in iNPH patients, suggesting a possible role of high ICP pulse pressure amplitudes in iNPH pathophysiology. Cerebrospinal reserve capacity and intracranial compliance is impaired in both groups and the pressure-volume relationship might be shifted towards lower ICP values in iNPH. The physiological influence of age on ICP and AMP/MWA requires further research.

Exploring mechanisms of ventricular enlargement in idiopathic normal pressure hydrocephalus: a role of cerebrospinal fluid dynamics and motile cilia.

Idiopathic normal pressure hydrocephalus (iNPH) is considered an age-dependent chronic communicating hydrocephalus associated with cerebrospinal fluid (CSF) malabsorption; however, the aetiology of ventricular enlargement in iNPH has not yet been elucidated. There is accumulating evidence that support the hypothesis that various alterations in CSF dynamics contribute to ventricle dilatation in iNPH. This review focuses on CSF dynamics associated with ventriculomegaly and summarises the current literature based on three potential aetiology factors: genetic, environmental and hydrodynamic. The majority of gene mutations that cause communicating hydrocephalus were associated with an abnormal structure or dysfunction of motile cilia on the ventricular ependymal cells. Aging, alcohol consumption, sleep apnoea, diabetes and hypertension are candidates for the risk of developing iNPH, although there is no prospective cohort study to investigate the risk factors for iNPH. Alcohol intake may be associated with the dysfunction of ependymal cilia and sustained high CSF sugar concentration due to uncontrolled diabetes increases the fluid viscosity which in turn increases the shear stress on the ventricular wall surface. Sleep apnoea, diabetes and hypertension are known to be associated with the impairment of CSF and interstitial fluid exchange. Oscillatory shear stress to the ventricle wall surfaces is considerably increased by reciprocating bidirectional CSF movements in iNPH. Increased oscillatory shear stress impedes normal cilia beating, leading to motile cilia shedding from the ependymal cells. At the lack of ciliary protection, the ventricular wall is directly exposed to increased oscillatory shear stress. Additionally, increased oscillatory shear stress may be involved in activating the flow-mediated dilation signalling of the ventricular wall. In conclusion, as the CSF stroke volume at the cerebral aqueduct increases, the oscillatory shear stress increases, promoting motor cilia shedding and loss of ependymal cell coverage. These are considered to be the leading causes of ventricular enlargement in iNPH.

Evaluating the cerebrospinal fluid tap test with the Hellström iNPH scale for patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: The cerebrospinal fluid tap test (CSF TT) is used for selecting shunt surgery candidates among patients with idiopathic normal pressure hydrocephalus (iNPH). We aimed to evaluate the predictive value of the CSF TT, by using the Hellström iNPH scale for shunted iNPH patients with a standardized method. METHODS: One hundred and sixteen shunt-operated iNPH patients were retrospectively included in this study. The gait and balance domains in the iNPH scale were used as outcome measures for the CSF TT and the total iNPH scale score as the postoperative outcome. A positive response to CSF TT was defined as a change of ≥ 5 points in the gait domain and ≥ 16 points in the balance domain. Differences between CSF TT responders and non-responders, sensitivity, specificity, positive and negative predictive values, accuracy, and correlations between changes from baseline to post CSF TT and from baseline to the postoperative follow-up, were calculated. RESULTS: In the CSF TT there were 63.8% responders in the gait domain and correspondingly 44.3% in the balance domain. CSF TT responders had a significantly better postoperative outcome in the total scale score (gait P ≤ 0.001, balance P ≤ 0.012) and gait CSF TT responders improved more in gait (P ≤ 0.001) and balance CSF TT responders in balance (P ≤ 0.001). No differences between CSF TT gait or balance responders could be found in neuropsychological or urinary continence assessments postoperatively. The sensitivity and specificity of the CSF TT and the outcome of the total iNPH scale score postoperatively were 68.1% and 52.0% for gait and 47.8% and 68.0% for balance, respectively. CONCLUSIONS: The CSF TT, with the Hellström iNPH scale as the outcome measure, has clear limitations in predicting postoperative results. The gait domain may be used to predict outcomes for gait, but the balance domain is too insensitive.

Perceived and actual changes in gait balance after CSF shunting in idiopathic normal pressure hydrocephalus.

OBJECTIVES: We evaluated the perceived and actual changes in gait and balance function immediately after cerebrospinal fluid (CSF) shunting in patients with idiopathic normal pressure hydrocephalus (iNPH), including those with mild cases. MATERIALS AND METHODS: Ninety-nine iNPH patients were assessed using the timed Up and Go (TUG) and Functional Gait Assessment (FGA) before and 1-week after CSF shunting and their perceived changes were assessed on a Global Rate of Change (GRC) scale. Minimal clinically important differences (MCIDs) were calculated using a receiver operating characteristic (ROC) curve method using GRC scores. RESULTS: In all patients (n = 99), the TUG value postoperatively was significantly faster than the preoperative value (difference; 3.1 ± 4.6 s, p < 0.001), and the postoperative FGA score was significantly better than the preoperative score (difference; 3.8 ± 3.3 points, p < 0.001). In the TUG <15 s group (n = 51), the postoperative FGA score was significantly improved (difference; 3.3 ± 2.9 points, p < 0.001), whereas the TUG value was only slightly improved (difference; 0.6 ± 1.6 s, p = 0.008). The ROC curve MCIDs of GRC ≥2 points, which is the recommended level of improvement, were 1.7 s (16.5%) for the TUG and 4 points (20.0%) for the FGA in all patients (n = 99) and the TUG <15 s group (n = 51). CONCLUSIONS: FGA can be used to confirm treatment effects, including perceived and actual changes after CSF shunting, in patients with mild iNPH. Our results can help clinicians to determine the clinical significance of improvements in gait and balance function immediately after CSF shunting in individual patients with iNPH.

Aqueductal CSF stroke volume measurements may drive management of shunted idiopathic normal pressure hydrocephalus patients.

CSF shunting with adjustable valve is the treatment of idiopathic normal pressure hydrocephalus. The opening pressure valve setting is left to the neurosurgeon's experience. Aqueductal CSF stroke volume by phase-contrast magnetic resonance measures the CSF passing through the Sylvian aqueduct and it changes with intracranial hydrodynamics. We sought to identify a window of stroke volume differences associated with the best clinical outcome and lowest rate of complications. The records of 69 patients were reviewed. At every clinical check, stroke volume, opening pressure valve, clinical outcome, and CSF overdrainage were analyzed. The correlation between stroke volume differences and negative outcome was also analyzed. The median follow-up was 2.3 years (range 0.3-10.4 years). The odds of negative outcome between two consecutive checks significantly increased by 16% (95%CI 4-28%, p = 0.006). Taking the lowest risk group as reference, the odds ratio of negative outcome was 1.16 (95%CI 0.51-2.63, p = 0.726) for SV differences less than - 37.6 µL, while it was 1.96 (95%CI 0.97-3.98, p = 0.062) for stroke volume changes above + 23.1 µL. Maintaining stroke volume values within a definite range might help maximize clinical benefit and avoid the risk of CSF overdrainage.

The Pathogenesis Based on the Glymphatic System, Diagnosis, and Treatment of Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a rare neurological disorder with no clear prevalence factors and is a significant danger to the elderly. The intracranial glymphatic system is the internal environment that maintains brain survival and metabolism, and thus fluid exchange changes in the glymphatic system under various pathological conditions can provide important insights into the pathogenesis and differential diagnosis of many neurodegenerative diseases such as iNPH. iNPH can be diagnosed using a combination of clinical symptoms, imaging findings and history, and cerebrospinal fluid biomarkers due to the glymphatic system disorder. However, only few researchers have linked the two. Shunt surgery can improve the glymphatic system disorders in iNPH patients, and the surgical approach is determined using a combination of clinical diagnosis and trials. Therefore, we have composed this review to provide a future opportunity for elucidating the pathogenesis of iNPH based on the glymphatic system, and link the glymphatic system to the diagnosis and treatment of iNPH. The review will provide new insights into the medical research of iNPH.

Dynamic functional networks in idiopathic normal pressure hydrocephalus: Alterations and reversibility by CSF tap test.

Idiopathic Normal Pressure Hydrocephalus (iNPH)-the leading cause of reversible dementia in aging-is characterized by ventriculomegaly and gait, cognitive and urinary impairments. Despite its high prevalence estimated at 6% among the elderlies, iNPH remains underdiagnosed and undertreated due to the lack of iNPH-specific diagnostic markers and limited understanding of pathophysiological mechanisms. INPH diagnosis is also complicated by the frequent occurrence of comorbidities, the most common one being Alzheimer's disease (AD). Here we investigate the resting-state functional magnetic resonance imaging dynamics of 26 iNPH patients before and after a CSF tap test, and of 48 normal older adults. Alzheimer's pathology was evaluated by CSF biomarkers. We show that the interactions between the default mode, and the executive-control, salience and attention networks are impaired in iNPH, explain gait and executive disturbances in patients, and are not driven by AD-pathology. In particular, AD molecular biomarkers are associated with functional changes distinct from iNPH functional alterations. Finally, we demonstrate a partial normalization of brain dynamics 24 hr after a CSF tap test, indicating functional plasticity mechanisms. We conclude that functional changes involving the default mode cross-network interactions reflect iNPH pathophysiological mechanisms and track treatment response, possibly contributing to iNPH differential diagnosis and better clinical management.