Normal Pressure Hydrocephalus Group Research Articles

Lexical Retrieval Performance in Patients with Normal Pressure Hydrocephalus and Parkinson’s Disease

Objectives: This study aimed to investigate lexical retrieval performance in patients with similar patterns but different central nervous system degenerative diseases, specifically normal pressure hydrocephalus (NPH) and Parkinson’s disease (PD).Methods: A lexical retrieval task was performed on 14 patients with NPH, 14 patients with PD, and 14 healthy elderly subjects (HE) to compare their correct response scores, reaction times, and error types, and the Korean-Boston naming test (K-BNT) was additionally performed to determine the validity of the lexical retrieval task.Results: First, there was no significant difference in scores between the three groups on the K-BNT. Second, the scores of the NPH and PD groups were significantly lower than the HE group on the lexical retrieval task. Third, only the NPH group was significantly slower than the HE group in the reaction time on the lexical retrieval task. Fourth, the error type analysis showed that the NPH group made significantly more semantic and nonword errors and the PD group made significantly more semantic errors than the HE group. Fifth, the correlation analysis showed a significant static correlation between K-BNT and the lexical retrieval task scores with a correlation coefficient of .721.Conclusion: We suggest that the lexical retrieval task may be useful in the screening and differential diagnosis of patients with NPH and PD.

Evaluation of optic nerve sheath complex by magnetic resonance imaging in patients with idiopathic normal pressure hydrocephalus

Background: We aimed to evaluate the optic nerve and optic nerve sheath diameter of patients with idiopathic normal pressure hydrocephalus with magnetic resonance imaging and to compare with the normal population. Methods: Magnetic resonance images and clinical records of the patients were retrospectively evaluated between 01.01.2015 and 01.01.2020. Twenty one patients in the normal pressure hydrocephalus group and 47 patients in the control group were included. Measurements were performed from the images obtained by creating multiplanar reconstructions from thin-slice Fast Spin Echo T2-weighted images. Measurements were made of optic nerve from the 3 mm posterior to the optic globe, on the plane which is oriented perpendicular to the nerve. Results: There was no difference between the two groups in terms of optic nerve diameters. Optic nerve sheath diameters are significantly higher in the normal pressure hydrocephalus group (p<0.0001). Conclusion: Morphological analysis of the optic nerve sheath complex which contains cerebrospinal fluid will contribute to the diagnosis and understanding chronic effects of normal pressure hydrocephalus, a disease in which changes in brain compliance and cerebrospinal fluid absorption are suspected in its etiology.

Cerebrospinal Fluid Neurofilament Light as a Marker of Neuro-axonal Injury in Normal Pressure Hydrocephalus (P10-6.001)

<h3>Objective:</h3> To compare Cerebrospinal fluid (CSF) Neurofilament-light chain (NfL) and NfL/amyloid beta₄₂ (Abeta42) ratio levels in normal pressure hydrocephalus (NPH) patients with healthy controls (HC), Alzheimer’s disease (AD), and Frontotemporal lobar degeneration (FTLD). <h3>Background:</h3> Levels of CSF NfL have been shown to be a marker of neuro-axonal injury and are elevated in neurodegenerative disease. One putative etiology of NPH involves axonal injury; however, low CSF Abeta42 has been reported in NPH. To control for the higher volume of CSF in NPH, the NfL/Abeta42 ratio was used. <h3>Design/Methods:</h3> 120 patients with CSF analysis: (a) 46 NPH: ventriculomegaly on MRI or CT, negative AD biomarkers, clinical symptoms of NPH, improvement in gait after tap test; (b) 39 FTLD: 5 behavioural-variant frontotemporal dementia, 14 corticobasal syndrome, 4 frontotemporal dementia with motor neuron disease, 12 progressive supranuclear palsy, 2 semantic-variant primary progressive aphasia (PPA), and 2 non-fluent PPA; (c) 29 AD; and (d) 6 HC. Levels of CSF NfL were measured using single molecule array (Simoa) technology while Abeta42 was measured using a sandwich ELISA method (Innotest). All statistical analyses were corrected for multiple comparisons and age. <h3>Results:</h3> Log transformed NfL levels in the NPH group were significantly higher than HC (p &lt; 0.05), but lower than FTLD and AD group (p &lt;0 .001). Log transformed CSF NfL/Abeta42 ratio was significantly higher in the NPH group compared to HC (p&lt;0.05); but no significant difference with FTLD and AD groups. <h3>Conclusions:</h3> Intermediate CSF NfL levels in NPH patients suggest that there is some neuro-axonal injury present - although less than in FTLD and AD. Further investigations are warranted to determine whether the NfL normalizes after shunting or the neuroaxonal injury is irreversible. NfL in NPH may help elucidate the pathophysiology of the disease. <b>Disclosure:</b> Ms. Davenport has nothing to disclose. Dr. Taghdiri has nothing to disclose. Anna Vasilevskaya has nothing to disclose. Ms. Anastassiadis has received research support from Fonds de Recherche du Québec - Santé (FRQS). Dr. Thapa has nothing to disclose. Dr. Dimal has nothing to disclose. Namita Multani, 14039 has nothing to disclose. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbott. Dr. Fasano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Abbvie. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbott. Dr. Fasano has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medtronic. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sunovion. Dr. Fasano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ceregate. The institution of Dr. Fasano has received research support from Boston Scientific. The institution of Dr. Fasano has received research support from Medtronic. The institution of Dr. Fasano has received research support from Abbvie. Dr. Fasano has received publishing royalties from a publication relating to health care. Dr. Tang-Wai has nothing to disclose. Dr. Tartaglia has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Tartaglia has received research support from NIH. The institution of Dr. Tartaglia has received research support from University of Toronto.

Comparative Assessment of Gait and Balance in Patients with Parkinson's Disease and Normal Pressure Hydrocephalus.

We aim to compare balance and gait parameters in patients diagnosed with Parkinson's disease (PD) and normal pressure hydrocephalus (NPH). A total of 13 patients with NPH, 20 with PD, and 13 healthy controls (HC) recruited in the study. Three IMU sensors (Ambulatory PD Monitoring Inc., OR, USA) were placed on the lumbar area and the feet of the participants. The balance evaluations comprised eight successive standing tasks; the modified clinical test of sensory interaction on balance test. These tasks involved standing with feet apart and eyes open as well as eyes closed on a firm and foam surface, standing with feet together and eyes open as well as eyes closed, and tandem stance with the right foot front and the left foot front. Functional evaluations of gait were conducted using the 10-M Walk Test (10 MWT), the 2 min-Walk Test (2 MWT), and the timed-up and go (TUG). Parameters of the gait and balance were analyzed and then compared. NPH patients displayed a notable decrease in both stride length and gait speed as compared with both PD patients and healthy participants. The balance tests revealed that the NPH group demonstrated significantly poorer performance, specifically in the feet-apart eyes-closed foam-surface test, and the tandem stance test. During the tasks while eyes were open on firm and foam surfaces, PD and NPH groups showed an increase in root mean square sway, range, and mean velocity (p<0.05) of sway in the anteroposterior plane. In addition, during the TUG test, the NPH group exhibited a significant prolongation in the time needed to complete the task and a decline in turning velocity as compared to PD, but no notable difference was seen in comparison to the HC group. Our study indicated that the patients with NPH exhibited notably worse gait and balance measurements in comparison to both the PD patients and HC groups. These findings emphasize the significance of monitoring and managing gait and balance impairments in NPH patients. Sensor-based technologies may offer objective parameters for a more precise and efficient follow-up of these patients in terms of gait and balance.

Neurofilament light as a marker of neuro‐axonal injury and potential biomarker of disease progression in normal pressure hydrocephalus

AbstractBackgroundThe etiology of normal pressure hydrocephalus (NPH) is unknown. Patients worsen but the cause of the progression is unclear. A prognostic biomarker in NPH is required for selecting the best candidates for shunt surgery. Neurofilament‐light chain (NfL) is a marker of neuro‐axonal injury and is elevated in neurodegenerative disease, traumatic brain injury, stroke and encephalitis. The aim of this study was: (1) To compare cerebrospinal fluid (CSF) NfL of NPH patients with healthy controls (HC), and other neurodegenerative diseases: Alzheimer’s disease (AD), and Frontotemporal lobar degeneration (FTLD); and (2) To evaluate CSF NfL levels as a potential biomarker of disease progression in NPH.Method108 patients with CSF analysis: (a) NPH group (39 patients): ventriculomegaly on MRI or CT, negative AD biomarkers, clinical symptoms of NPH, improvement in gait after removal of a large amount of CSF. 14 patients of the unshunted NPH group had a 1‐year follow‐up scan. EVANS index was calculated for these participants; (b) FTLD group (45 patients): 5 behavioural‐variant frontotemporal‐dementia, 19 corticobasal syndrome, 3 frontotemporal dementia with motor neuron disease, 13 progressive supranuclear palsy, 3 semantic‐variant primary progressive aphasia (PPA), and 2 non‐fluent PPA; (c) AD group (19 patients): CSF biomarkers and cognitive symptoms consistent with AD; and (d) HC group (5 participants): cognitively and functionally normal. Levels of NfL in CSF were measured using single molecule array (Simoa) technology. All statistical analyses were corrected for multiple comparisons and age.ResultNfL levels in patients with NPH were significantly higher than HC (1504.7±520 vs 702.5±170pg/ml, p &lt; 0.001), and lower than FTLD group (1504.7±520 vs 3071.7±2830pg/ml, p=0.005). There was a trend for lower NfL in NPH compared to AD, (1504.7±520 vs 2305.4±1179.7pg/ml, p=0.056). There was a significant correlation between baseline NfL levels and increase in EVANS index (r=0.784, p=0.002) in the 14 NPH patients with longitudinal brain imaging.ConclusionCSF NfL levels in NPH patients suggests there is neuro‐axonal injury but is lower than some other neurodegenerative diseases (i.e., FTLD and AD). NfL may be a biomarker for neuro‐axonal injury and disease progression in NPH.

Clinical Outcomes After Ventriculo-Peritoneal Shunting in Patients With Classic vs. Complex NPH

ObjectiveNormal pressure hydrocephalus (NPH) is a neurological condition characterized by a clinical triad of gait disturbance, cognitive impairment, and urinary incontinence in conjunction with ventriculomegaly. Other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and vascular dementia share some overlapping clinical features. However, there is evidence that patients with comorbid NPH and Alzheimer's or Parkinson's disease may still exhibit good clinical response after CSF diversion. This study aims to evaluate clinical responses after ventriculo-peritoneal shunt (VPS) in a cohort of patients with coexisting NPH and neurodegenerative disease.MethodsThe study has two components; (i) a pilot study was performed that specifically focused upon patients with Complex NPH and following the inclusion of the Complex NPH subtype into consideration for the clinical NPH programme, (ii) a retrospective snapshot study was performed to confirm and characterize differences between Classic and Complex NPH patients being seen consecutively over the course of 1 year within a working subspecialist NPH clinic. We studied the characteristics of patients with Complex NPH, utilizing clinical risk stratification and multimodal biomarkers.ResultsThere was no significant difference between responders and non-responders to CSF diversion on comorbidity scales. After VPS insertion, significantly more Classic NPH patients had improved cognition compared to Complex NPH patients (p = 0.005). Improvement in gait and urinary symptoms did not differ between the groups. 26% of the Classic NPH group showed global improvement of the triad, and 42% improved in two domains. Although only 8% showed global improvement of the triad, all Complex NPH patients improved in gait.ConclusionsOur study has demonstrated that the presence of neurodegenerative disorders co-existing with NPH should not be the sole barrier to the consideration of high-volume tap test or lumbar drainage via a specialist NPH programme. Further characterization of distinct cohorts of NPH with differing degrees of CSF responsiveness due to overlay from neurodegenerative or comorbidity risk burden may aid toward more precise prognostication and treatment strategies. We propose a simplistic conceptual framework to describe NPH by its Classic vs. Complex subtypes to promote the clinical paradigm shift toward subspecialist geriatric neurosurgery by addressing needs for rapid screening tools at the clinical-research interface.

Olfactory bulb volume in patients with normal-pressure hydrocephalus: an MRI evaluation

To investigate changes in olfactory bulb (OB) volume in patients with idiopathic normal-pressure hydrocephalus (NPH). This multicentric retrospective study included a test group of 23 patients with NPH (10 male and 13 female patients) and a control group of 27 healthy participants without hydrocephalus. The OB volume in all participants had been measured using cranial magnetic resonance imaging (MRI). In the NPH group, positivity for disproportionately enlarged subarachnoid space hydrocephalus (DESH) was also evaluated. The OB volumes of the NPH group (R 38.29±9.34 mm3 and L37.52±9.59 mm3) were significantly lower than those of the control group (R 45.87±7.33 mm3 and L48.41±7.62 mm3) bilaterally. There were no significant differences between right and left OB volumes in the NPH group. Nine of the 23 patients were DESH positive and 14 were DESH negative. There were no significant differences between OB volumes of the DESH positive and DESH vpatients in the NPH group. In both groups, there was a positive correlation between right and left OB volumes. There were no significant correlations between OB volumes and age or gender. In the NPH group, there were no significant correlations between DESH positivity and OB volumes. OB volume decrease and olfactory problems should be taken into account in idiopathic NPH patients. When expanded ventricles and decreased OB volume are observed at cranial MRI, a diagnosis of idiopathic NPH should be considered.

Quantification of Oscillatory Shear Stress from Reciprocating CSF Motion on 4D Flow Imaging.

Oscillatory shear stress could not be directly measured in consideration of direction, although cerebrospinal fluid has repetitive movements synchronized with heartbeat. Our aim was to evaluate the important of oscillatory shear stress in the cerebral aqueduct and foramen magnum in idiopathic normal pressure hydrocephalus by comparing it with wall shear stress and the oscillatory shear index in patients with idiopathic normal pressure hydrocephalus. By means of the 4D flow application, oscillatory shear stress, wall shear stress, and the oscillatory shear index were measured in 41 patients with idiopathic normal pressure hydrocephalus, 23 with co-occurrence of idiopathic normal pressure hydrocephalus and Alzheimer-type dementia, and 9 age-matched controls. These shear stress parameters at the cerebral aqueduct were compared with apertures and stroke volumes at the foramen of Magendie and cerebral aqueduct. Two wall shear stress magnitude peaks during a heartbeat were changed to periodic oscillation by converting oscillatory shear stress. The mean oscillatory shear stress amplitude and time-averaged wall shear stress values at the dorsal and ventral regions of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus groups were significantly higher than those in controls. Furthermore, those at the ventral region of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus group were also significantly higher than those in the co-occurrence of idiopathic normal pressure hydrocephalus with Alzheimer-type dementia group. The oscillatory shear stress amplitude at the dorsal region of the cerebral aqueduct was significantly associated with foramen of Magendie diameters, whereas it was strongly associated with the stroke volume at the upper end of the cerebral aqueduct rather than that at the foramen of Magendie. Oscillatory shear stress, which reflects wall shear stress vector changes better than the conventional wall shear stress magnitude and the oscillatory shear index, can be directly measured on 4D flow MR imaging. Oscillatory shear stress at the cerebral aqueduct was considerably higher in patients with idiopathic normal pressure hydrocephalus.

Dementia with Lewy bodies: A differential diagnosis of normal pressure hydrocephalus

AbstractBackgroundThe diagnosis of idiopathic normal pressure hydrocephalus (NPH) is challenging and remains overestimated because of the absence of specific clinical, imaging or biological features. It relies on association of classical triad of symptoms (gait disturbance, cognition impairment, urinary symptoms) associated to a ventricular enlargement. Several differential diagnoses should be considered with an initial presentation suggestive of NPH, such as dementia with Lewy bodies (DLB), Alzheimer disease (AD) and vascular dementia (VD). The aim of this study was to identify NPH differential diagnosis as well as to highlight clinical and radiological features that could help questioning this diagnosis, before performing invasive procedures.MethodIn this monocentric retrospective study, we included 42 patients fulfilling the criteria of possible NPH on initial presentation. At the end of the follow‐up, we classified the sample into patients with probable NPH (NPH group ; n = 13), differential diagnosis of NPH (NPH‐ group; n = 21) and dual pathology with criteria of probable NPH (NPH+; n = 8), depending on their outcome after cerebrospinal fluid (CSF) drainage. We collected clinical data, including results of cognitive assessment, as well as results of CSF biomarkers, EEG, functional and morphological neuroimaging. Ventricular enlargement profile was analyzed using different visual measures on MRI.ResultThe main differential diagnosis of NPH was DLB (21/21), mixed with vascular dementia in four cases. None of the patient had a CSF profile suggestive of AD. Regarding clinical features, asymmetric parkinsonism, fluctuations, agitation during sleep, visual hallucinations and visuospatial impairment were significantly more frequent in NPH‐ patients, compared to NPH patients (p=0.033). The callosal angle was significantly more acute (&lt;104° ; p &lt;0.01) and fourth ventricular dilatation greater (&gt;17 mm ; p&lt;0.01) in NPH patients than in NPH‐ patients, while there was no significant difference in the dilatation of lateral ventricles and third ventricle.ConclusionDLB appeared as the main differential diagnosis of NPH. Our results indicate that the existence of asymmetric parkinsonism, fluctuations, agitation during sleep, visual hallucinations or visuospatial impairment, as well as the absence of acute callosal angle or fourth ventricular dilatation should lead to consider DLB as a differential diagnosis of NPH.

Altered glymphatic system in idiopathic normal pressure hydrocephalus

ObjectiveTo assess the glymphatic activity in patients with idiopathic normal pressure hydrocephalus (NPH) using the “Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS)” method, and determine the feasibility of non-invasive MRI for the evaluation of the glymphatic function. MethodsBetween April 2017 and March 2019, 16 patients diagnosed with NPH and 16 age- and sex-matched controls were included. On 3T DTI-MRI, the diffusivities along x-, y-, and z-axes were measured, and the ALPS-index – a ratio that accentuated water diffusion along the perivascular space – was calculated by two independent readers. The inter-observer agreement was tested using the interclass correlation coefficient. The differences in the diffusivities and the ALPS-index between the NPH and control groups were compared using the Mann-Whitney test. The values were also compared according to the treatment response to the cerebrospinal fluid drainage and correlated with the callosal angle using a correlation coefficient. ResultsThe inter-observer agreements were excellent for the diffusivities and the ALPS-index. The diffusivity along the x-axis in the projection fibers area and the ALPS-index were significantly lower in patients with NPH (median, 0.556/1.181) than in the controls (0.610/1.540), respectively (P = 0.032/< 0.0001). The ALPS-index was significantly lower in the NPH group who did not show treatment response than those who showed symptomatic relief (0.987/1.329; P < 0.0001). The ALPS-index showed a significant positive correlation with the callosal angle (r = 0.82, P = 0.0001). ConclusionsThe DTI-ALPS method can be a useful imaging tool for identifying glymphatic dysfunction and for individually quantifying glymphatic activity in patients with NPH.

Structural volumetry in NPH diagnostics and treatment-future or dead end?

To assess automated volumetric analysis as a potential presurgical diagnostic tool or as a method to potentially shed light on normal pressure hydrocephalus (NPH) pathophysiology. MRI imaging according to our protocol was performed in 29 NPH patients, 45 non-NPH (but suspected) patients and 15 controls. Twenty patients underwent a second MRI 3months after ventriculoperitoneal (VP) shunt surgery. All structures relevant to NPH diagnosis were automatically segmented using commercial software. The results were subsequently tested using ANOVA analysis. Significant differences in the volumes of the corpus callosum, left hippocampus, internal globus pallidus, grey and white matter and ventricular volumes were observed between NPH group and healthy controls. However, the differences between NPH and non-NPH groups were non-significant. Three months after, VP shunt insertion decreased ventricular volume was the only clearly significant result (p value 0.0001). Even though a detailed volumetric study shows several significant differences, volumetric analysis as a standalone method does not provide a simple diagnostic biomarker, nor does it shed a light on an unknown NPH aetiology.

Diffusion tensor imaging in idiopathic normal pressure hydrocephalus: clinical and CSF flowmetry correlations.

Diffusion tensor imaging is a magnetic resonance technique that provides information about the orientation and anisotropy of the white matter tracts. The aim of this study was to analyse diffusion tensor imaging quantitative parameters in idiopathic normal pressure hydrocephalus patients, in order to determine whether this method could correlate to clinical scores and cerebrospinal fluid flowmetry data. Fifteen consecutive patients with idiopathic normal pressure hydrocephalus and 15 age-matched controls underwent cerebrospinal fluid flowmetry and diffusion tensor imaging using a 1.5 Tesla system. Fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity values were calculated using region of interest atlas-based tract-mapping in nine cerebral areas and compared among the two groups. In addition, for idiopathic normal pressure hydrocephalus patients, diffusion tensor imaging parameters were correlated to clinical scores (mini mental state examination and frontal assessment battery) and cerebrospinal fluid flowmetry data. Mean fractional anisotropy was significantly lower for the idiopathic normal pressure hydrocephalus group than for the control group in the forceps minor and motor cortex; the idiopathic normal pressure hydrocephalus group had significantly higher mean axial diffusivity for the genu of the corpus callosum and forceps minor. We did not find significant correlation between diffusion tensor imaging parameters and cerebrospinal fluid flowmetry and mini mental state examination, while we observed a correlation between forceps minor fractional anisotropy and frontal assessment battery; no correlation between flowmetry and clinical scores was found. Our findings suggest that diffusion tensor imaging provides a non-invasive biomarker of white matter changes in idiopathic normal pressure hydrocephalus patients. Forceps minor is the best site to analyse. As diffusion tensor imaging offers a better correlation to clinical status than cerebrospinal fluid flowmetry, it should be included in the routine idiopathic normal pressure hydrocephalus protocol.

Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage.

In patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration. In this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures. Twenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119). Preliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

Dynamics of extracellular matrix proteins in cerebrospinal fluid and serum and their relation to clinical outcome in human traumatic brain injury.

Background Brevican, neurocan, tenascin-C and tenascin-R are extracellular matrix proteins present in brain that show increased expression in experimental animal models of brain injury. However, little is known about the dynamics of these proteins in human body fluids, such as cerebrospinal fluid (CSF) and serum, after traumatic brain injury (TBI). The aims of this study were to investigate if matrix proteins in CSF and serum are associated with functional outcome following traumatic brain injury, if their concentrations change over time and to compare their levels between brain injured patients to controls. Methods In total, 42 traumatic brain injury patients, nine healthy controls and a contrast group consisting of 38 idiopathic normal pressure hydrocephalus patients were included. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the concentrations of proteins. Results Increased concentrations of brevican, tenascin-C and tenascin-R in CSF correlated with unfavourable outcome, with stronger outcome prediction ability compared to other biomarkers of brain tissue injury. CSF brevican, tenascin-R and serum neurocan gradually decreased with time (p = 0.04, p = 0.008, p = 0.005, respectively), while serum tenascin-C (p = 0.01) increased. CSF concentrations of brevican, neurocan and tenascin-R (only in time point 3) after TBI were lower than in the idiopathic normal pressure hydrocephalus group (p < 0.0001, p < 0.0001, and p = 0.0008, respectively). In serum, tenascin-C concentration was higher and neurocan lower compared to healthy controls (p = 0.02 and p = 0.0009). Conclusions These findings indicate that levels of extracellular matrix proteins are associated with clinical outcome following TBI and may act as markers for different pathophysiology than currently used protein biomarkers.

Opposing CSF hydrodynamic trends found in the cerebral aqueduct and prepontine cistern following shunt treatment in patients with normal pressure hydrocephalus

BackgroundThis study investigated cerebrospinal fluid (CSF) hydrodynamics using cine phase-contrast MRI in the cerebral aqueduct and the prepontine cistern between three distinct groups: pre-shunt normal pressure hydrocephalus (NPH) patients, post-shunt NPH patients, and controls. We hypothesized that the hyperdynamic flow of CSF through the cerebral aqueduct seen in NPH patients was due to a reduction in cisternal CSF volume buffering. Both hydrodynamic (velocity, flow, stroke volume) and peak flow latency (PFL) parameters were investigated.MethodsScans were conducted on 30 pre-treatment patients ranging in age from 58 to 88 years along with an additional 12 controls. Twelve patients also received scans following either ventriculoatrial (VA) or ventriculoperitoneal (VP) shunt treatment (9 VP, 3 VA), ranging in age from 74 to 89 years with a mean follow up time of 6 months.ResultsSignificant differences in area, velocity, flow, and stroke volume for the cerebral aqueduct were found between the pre-treatment NPH group and the healthy controls. Shunting caused a significant decrease in both caudal and cranial mean flow and stroke volume in the cerebral aqueduct. No significant changes were found in the prepontine cistern between the pre-treatment group and healthy controls. For the PFL, no significant differences were seen in the cerebral aqueduct between any of the three groups; however, the prepontine cistern PFL was significantly decreased in the pre-treatment NPH group when compared to the control group.ConclusionsAlthough several studies have quantified the changes in aqueductal flow between hydrocephalic groups and controls, few studies have investigated prepontine cistern flow. Our study was the first to investigate both regions in the same patients for NPH pre- and post- treatment. Following shunt treatment, the aqueductal CSF metrics decreased toward control values, while the prepontine cistern metrics trended up (not significantly) from the normal values established in this study. The opposing trend of the two locations suggests a redistribution of CSF pulsatility in NPH patients. Furthermore, the significantly decreased latency of the prepontine cisternal CSF flow suggests additional evidence for CSF pulsatility dysfunction.

Structural correlates of cognitive impairment in normal pressure hydrocephalus.

ObjectivesThe pathological bases for the cognitive and neuropsychiatric symptoms in normal pressure hydrocephalus (NPH) have not been elucidated. However, the symptoms may indicate dysfunction of subcortical regions. Previously, volume reductions of subcortical deep grey matter (SDGM) structures have been observed in NPH patients. The present study used automated segmentation methods to investigate whether SDGM structure volumes are associated with cognitive and neuropsychiatric measures.MethodsFourteen NPH patients and eight healthy controls were included in the study. Patients completed neuropsychological tests of general cognition, verbal learning and memory, verbal fluency and measures of apathy and depression pre‐ and postshunt surgery. Additionally, patients underwent 3 Tesla T1‐weighted magnetic resonance imaging at baseline and 6 months postoperatively. Controls were scanned once. SDGM structure volumes were estimated using automated segmentation (FSL FIRST). Since displacement of the caudate nuclei occurred for some patients due to ventriculomegaly, patient caudate volumes were also estimated using manual tracing. Group differences in SDGM structure volumes were investigated, as well as associations between volumes and cognitive and neuropsychiatric measures in patients.ResultsVolumes of the caudate, thalamus, putamen, pallidum, hippocampus and nucleus accumbens (NAcc) were significantly reduced in the NPH patients compared to controls. In the NPH group, smaller caudate and NAcc volumes were associated with poorer performance on neuropsychological tests and increased severity of neuropsychiatric symptoms, while reduced volume of the pallidum was associated with better performance on the MMSE and reduced apathy.ConclusionsStriatal volume loss appears to be associated with cognitive and neuropsychiatric changes in NPH.

Cerebrospinal fluid flowmetry using phase-contrast MRI technique and its clinical applications

Background and aim and aim Cine phase-contrast (PC) MRI is a useful noninvasive imaging technique in evaluating the dynamics of cerebrospinal fluid (CSF) in the evaluation, follow-up, surgical decision, and postoperative survey of certain disease processes, such as normal pressure hydrocephalus, aqueduct stenosis (AS), postendoscopic third ventriculostomy, and arachnoid cysts cases. The aim of this study was to determine the value of cardiac-gated cine-PC-MRI in characterizing CSF flow in patients with CSF flow disorders. Patients and methods The study included 30 patients with 10 persons as the control group and 20 patients who were suspected to have CSF flow abnormalities. Two imaging techniques were applied: the axial plane for flow quantification and the sagittal plane for a qualitative assessment. Results Among the 30 patients, quantitative analysis revealed the mean value to be 22 μl as the average aqueductal stroke volume in the control group. In the normal pressure hydrocephalus group, systolic velocities as well as stroke volume values were higher than those of the controls. In the AS group, lack of significant aqueductal CSF flow was noticeable. Both peak systolic and diastolic velocities were found to be statistically significantly lower in patients with AS than in the control group. In arachnoid cyst cases, CSF flow study with cine PC-MRI enables visualization of flow communication between cysts and neighboring CSF compartments. Two cases were assigned as communicating cysts and four cases were noncommunicating. Conclusion Assessment of CSF flow indicates the potentials of using PC-MRI adjunct to routine MR for the clinical study of CSF-related diseases.

Cerebrospinal fluid dynamics study in communicating hydrocephalus.

Context:Communicating hydrocephalus often poses a challenge in diagnosis and management decisions.Aims:The objective of this study is to measure the opening pressure (Po), pressure volume index (PVI), and cerebrospinal fluid outflow resistance (Rout), in patients with communicating hydrocephalus using bolus lumbar injection method and to evaluate its diagnostic and prognostic value.Materials and Methods:The study was conducted in 50 patients with communicating hydrocephalus, including normal pressure hydrocephalus (NPH) (19), post-meningitic hydrocephalus (23) and post-traumatic hydrocephalus (8). An improvised bolus lumbar injection method [the Madras Institute of Neurology (MIN) method] was used.Results:In the NPH Group, the CSF dynamics studies correlated well with the clinico-radiological classification. The prediction of shunt responsiveness by CSF dynamics studies correlated with good outcome in 87.5%. In the post-meningitic hydrocephalus group, the value of CSF dynamics studies in predicting patients needing shunt was 89.5%. The CSF dynamics studies detected patients who needed shunt earlier than clinical or radiological indications. In the post-traumatic hydrocephalus group, 62.5% of patients improved with the treatment based on CSF dynamics studies.Conclusions:The improvised bolus lumbar injection method (MIN method) is a very simple test with fairly reliable and reproducible results. Study of CSF dynamics is a valuable tool in communicating hydrocephalus for confirmation of diagnosis and predicting shunt responsiveness. This is the first time that the value of CSF dynamics has been studied in patients with post-meningitic hydrocephalus. It was also useful for early selection of cases for shunting and for identifying patients with atrophic ventriculomegaly, thereby avoiding unnecessary shunt.

Phase-Contrast MRI CSF Flow Measurements for the Diagnosis of Normal-Pressure Hydrocephalus: Observer Agreement of Velocity Versus Volume Parameters.

Manual segmentation of the aqueduct for CSF flow analysis may induce measurement variability. The aim of our study was to assess observer agreement of manual segmentation and to compare the repeatability and accuracy of different flow parameters in differentiating normal-pressure hydrocephalus (NPH) from brain atrophy. Thirty-two subjects were included and were divided into three groups: control, NPH, and brain atrophy. Subjects underwent phase-contrast MRI. Quantitative analysis of aqueductal CSF flow using manual ROI placement was performed by two independent readers. Reader 1 repeated measurements 3 months after the first session to assess interobserver and intraobserver agreement. Intraclass correlation coefficients (ICCs), within-subject SD, and repeatability were calculated. Peak systolic velocity (PSV), peak mean velocity, and aqueductal CSF stroke volume, which we refer to as "stroke volume," were recorded and compared between the three patient groups. The ROC curves of diagnostic accuracy for NPH were compared. PSV was ROI-independent, so only one measurement was obtained. The NPH group had significantly higher PSV, peak mean velocity, and stroke volume values in all readings than both the control and brain atrophy groups. The accuracy of PSV for the diagnosis of NPH was 82.7%, and the accuracy of peak mean velocity was 92.5-93.3% for the three readings. Stroke volume had perfect accuracy of 100% for the three readings. The stroke volume had higher ICCs (0.97 and 0.98) than the peak mean velocity (0.88). The intraobserver repeatability and interobserver repeatability of peak mean velocity were 1.9 cm/s, and the intraobserver repeatability and interobserver repeatability of stroke volume were 27.4 and 19.6 µL/cycle, respectively. Stroke volume had better agreement and repeatability and was more accurate than peak mean velocity for the diagnosis of NPH. PSV lacks variability but was the least accurate.

MR Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus.

Normal pressure hydrocephalus is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality, and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, multiple overlapping symptoms often make it difficult to differentiate normal pressure hydrocephalus from other types of dementia, and improved diagnostic techniques would help patient management. MR elastography is a novel diagnostic tool that could potentially identify patients with normal pressure hydrocephalus. The purpose of this study was to assess brain stiffness changes in patients with normal pressure hydrocephalus compared with age- and sex-matched cognitively healthy individuals. MR elastography was performed on 10 patients with normal pressure hydrocephalus and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MR imaging scanner. Shear waves with 60-Hz vibration frequency were transmitted into the brain by a pillowlike passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. A significant increase in stiffness was observed in the cerebrum (P = .001), occipital lobe (P < .001), parietal lobe (P = .001), and the temporal lobe (P = .02) in the normal pressure hydrocephalus group compared with healthy controls. However, no significant difference was noted in other regions of the brain, including the frontal lobe (P = .07), deep gray and white matter (P = .43), or cerebellum (P = .20). This study demonstrates increased brain stiffness in patients with normal pressure hydrocephalus compared with age- and sex-matched healthy controls; these findings should motivate future studies investigating the use of MR elastography for this condition and the efficacy of shunt therapy.