iNPH Group Research Articles

A NOVEL 18F-FDG PET-CT PATTERN IN IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS

Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable neurologic syndrome in an aging population. Elucidating the pathophysiology and assessing biomarkers are an important area of research in diagnosing and treating iNPH. We retrospectively compared 18F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls (3:1). We also compared controls and iNPH to matched AD (2:1), DLB (2:1), and bvFTD (1:1). After partial volume correction, regional hypometabolism was assessed using voxel and region-level analyses in Statistical Parametric Mapping. The iNPH group compared to controls had significant regional hypometabolism in the dorsal striatum involving the caudate and putamen p < 0.05 (FWE corrected, height threshold 5.57). After partial volume correction peak t values were: 8.01 – left caudate, 7.19 – right caudate, 7.42 – left putamen, and 7.59 – right putamen. Results of FDG-PET patterns for AD, LBD, and bvFTD groups compared to controls were consistent with prior literature and distinct from iNPH. In this pilot study, we report a novel FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen. This pattern is consistent with prior cerebral blood flow pattern studies and the clinical presentation of iNPH.

Reversed aqueductal cerebrospinal fluid net flow in idiopathic normal pressure hydrocephalus.

The changes of CSF flow dynamics in idiopathic normal pressure hydrocephalus (iNPH) are not fully elucidated. Most previous studies took the whole cardiac cycle as a unit. In this work, it is divided into systole and diastole phase and compared between iNPH patients and normal elderly and paid special attention to the change of netflow direction. Twenty iNPH patients according to international guideline and twenty healthy volunteers were included in this study and examined by MRI. Three categories of CSF flow parameters were measured: peak velocity (Vpeak ), stroke volume (SV), and minute flow volume (MinV) covering the whole cycle; peak velocity (Vpeak-s , Vpeak-d ) and flow volume (Vols , Vold ) of the systole and diastole, respectively; net flow. Evans index (EI) was also measured and compared statistically between the two groups. EI, Vpeak , SV, MinV, Vols , Vold , and Vpeak-d significantly increased in iNPH group (P<0.05). Vpeak-s of the two groups were not significantly different (P>0.05). The net flow of 16 iNPH patients (16/20) was in the caudo-cranial direction, while 15 volunteers (15/20) were in the opposite direction, which showed statistically significant differences (P=.001). INPH patients present hyperdynamic flow with increased velocity and volume both in systole and diastole phase. Degree of rising in diastole phase exceeds that of systole phase. The resulting reversal of netflow direction may play a key role in the occurrence of ventriculomegaly in iNPH patients.

Trunk sway in idiopathic normal pressure hydrocephalus—Quantitative assessment in clinical practice

BackgroundIn diagnosis and treatment of patients with idiopathic normal pressure hydrocephalus (iNPH), there is need for clinically applicable, quantitative assessment of balance and gait. Using a body-worn gyroscopic system, the aim of this study was to assess postural stability of iNPH patients in standing, walking and during sensory deprivation before and after cerebrospinal fluid (CSF) drainage and surgery. A comparison was performed between healthy elderly (HE) and patients with various types of hydrocephalus (ventriculomegaly (VM)). MethodsTrunk sway was measured in 31 iNPH patients, 22 VM patients and 58 HE. Measurements were performed at baseline in all subjects, after CSF drainage in both patient groups and after shunt surgery in the iNPH group. ResultsPreoperatively, the iNPH patients had significantly higher trunk sway compared to HE, specifically for the standing tasks (p<0.001). Compared to VM, iNPH patients had significantly lower sway velocity during gait in three of four cases on firm support (p<0.05). Sway velocity improved after CSF drainage and in forward-backward direction after surgery (p<0.01). Compared to HE both patient groups demonstrated less reliance on visual input to maintain stable posture. ConclusionsINPH patients had reduced postural stability compared to HE, particularly during standing, and for differentiation between iNPH and VM patients sway velocity during gait is a promising parameter. A reversible reduction of visual incorporation during standing was also seen. Thus, the gyroscopic system quantitatively assessed postural deficits in iNPH, making it a potentially useful tool for aiding in future diagnoses, choices of treatment and clinical follow-up.

Neuropsychological Assessment in the Differential Diagnosis of Idiopathic Normal Pressure Hydrocephalus. An Important Tool for the Maintenance and Restoration of Neuronal and Neuropsychological Functions.

Idiopathic normal pressure hydrocephalus (iNPH) is a progressive clinical syndrome that includes gait disturbances, urinary incontinence, and cognitive impairment. iNPH shows similarities to other neurodegenerative disorders, primarily Alzheimer's Disease (AD). Definition of the neuropsychological profile of iNPH and the qualitative analysis of systematic mistakes made in cognitive tests could represent a valid method for systematizing possible specific markers of iNPH dementia and differentiating it from other dementias. To evaluate the role and the efficacy of a neuropsychological protocol, designed at our institution, based on psychometric analysis and qualitative assessment, in the differential diagnosis of iNPH from AD dementia, we prospectively enrolled 12 patients with suspected iNPH, 11 patients with AD, and 10 healthy controls (HC) who underwent neuropsychological assessment. The assessment was done with the Mini Mental State Examination (MMSE), Mental Deterioration Battery (MDB), Frontal Assessment Battery (FAB), and the Deux Barrage Test. Evaluation in the iNPH group was performed before extended lumbar drainage (ELD), 48 h after ELD, and 1 week and 3 months after the insertion of a ventriculoperitoneal shunt (VPS). Statistical analysis demonstrated the cognitive profile of iNPH, which was mainly characterized by executive function and immediate verbal memory impairment compared with AD. Additionally, the neuropsychological markers were different between the two groups. The qualitative analysis of systematic mistakes made on the tests demonstrated differences in cognitive performances between the iNPH, AD, and HC cohorts. Neuropsychological assessment and qualitative evaluation could represent a useful tool for achieving effective management and restoration of functions in patients with iNPH.

Fractional anisotropy in patients with disproportionately enlarged subarachnoid space hydrocephalus.

Disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings on MRI were described as a prognostic factor for responsiveness to the treatment of idiopathic normal pressure hydrocephalus (iNPH). Our premise is that DESH could be associated with compression of the cerebral white matter. Microstructural changes can be identified using diffusion tensor imaging (DTI), specifically fractional anisotropy (FA). The aim of this study is to compare FA in iNPH patients with and without DESH and healthy controls. We analysed 1.5-T MRI scans of patients fulfilling the criteria of probable or possible iNPH and positive supplementary tests before and after surgery (ventriculo-peritoneal shunt). FA was measured in the anterior and posterior limb of the internal capsule (PLIC) and in the corpus callosum. Patients were divided into the DESH and non-DESH group. These data were also compared to FA values in the control group. Twenty-seven patients and 24 healthy controls were enrolled. DESH was present in 15 patients and lacking in 12. Twenty-three iNPH patients were shunt responders (85.2%), and 4 were non-responders (14.8%). All patients in the DESH group were shunt responders. In the non-DESH group, eight patients were responders (66.7%). A significant difference between the DESH and non-DESH group was found in the FA of the PLIC. The mean value of FA in the PLIC was 0.72 in the DESH group and 0.66 in the non-DESH group. After the surgery FA decreased in both groups. In the DESH iNPH group FA PLIC decreased to 0.65 and in the non-DESH iNPH group to 0.60. In the healthy controls, the mean FA in the PLIC was 0.58. DESH on MRI scans is related to a higher FA in the PLIC with a decrease after the surgery. It reflects a more severe compression of the white matter than in non-DESH patients or healthy volunteers. DESH patients had better outcome than non-DESH patients. This study confirmed the importance of DESH as a supportive sign for iNPH.

Spectrum of cognitive disorders in idiopathic normal pressure hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by ventricular dilation accompanied by a progressive triad of a gait disturbance, "dementia" and incontinence. We retrospectively evaluated cognitive profile, and its relationship with disease variables, in 64 iNPH patients. The iNPH group performed significantly worse than the control group on all neuropsychological tests, except for verbal memory (within the normal range). The patients were subdivided into four groups: group 1 (42%: global cognitive impairment); group 2 (24%: frontosubcortical dysfunction); group 3 (17%: isolated deficit of a single cognitive domain); group 4 (17%: no cognitive impairment). Group 1 was older, with a significantly longer disease duration and more severe motor disease, while groups 3 and 4 were younger and presented milder motor impairment and a shorter disease duration. These data suggest parallel progression of cognitive and motor impairment in iNPH; early shunt surgery might prevent the development, in older age, of dementia in these patients.

Feasibility of radiological markers in idiopathic normal pressure hydrocephalus.

Various radiological markers have been proposed for diagnostics in idiopathic normal pressure hydrocephalus (iNPH). We examined the usefulness of radiological markers in the diagnostics and prediction of shunt response in iNPH. In this retrospective cohort study, we evaluated brain CT or MRI scans of 390 patients with suspected iNPH. Based on a 24-h intraventricular pressure monitoring session, patients were classified into a non-NPH (n = 161) or probable iNPH (n = 229) group. Volumes of cerebrospinal fluid compartments (lateral ventricles, sylvian and suprasylvian subarachnoid spaces and basal cisterns) were visually assessed. Disproportionally enlarged subarachnoid spaces, flow void, white matter changes, medial temporal lobe atrophy and focally dilated sulci were evaluated. Moreover, we measured quantitative markers: Evans' index (EI), the modified cella media index, mean width of the temporal horns and callosal angle. iNPH was more likely in patients with severe volumetric disproportion between the suprasylvian and sylvian subarachnoid spaces than in those without disproportion (OR 7.5, CI 95 % 4.0-14.1, P < 0.0001). Mild disproportion (OR 2.6, CI 95 % 1.4-4.6, P = 0.001) and narrow temporal horns (OR per 1 mm 0.91, CI 95 % 0.84-0.98, P = 0.014) were also associated with an iNPH diagnosis. Other radiological markers had little association with the iNPH diagnosis in the final combined multivariate model. Interestingly, EI was higher in non-NPH than iNPH patients (0.40 vs. 0.38, P = 0.039). Preoperative radiological markers were not associated with shunt response. Visually evaluated disproportion was the most useful radiological marker in iNPH diagnostics. Narrower temporal horns also supported an iNPH diagnosis, possibly since atrophy was more pronounced in the non-NPH than iNPH group.

Voxel‐Based Morphometry of Disproportionate Cerebrospinal Fluid Space Distribution for the Differential Diagnosis of Idiopathic Normal Pressure Hydrocephalus

To determine whether voxel-based morphometry of the cerebrospinal fluid (CSF) space can accurately differentiate iNPH from other related neurological disorders. Nineteen patients with surgically proven iNPH and 24 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease (PD), and 14 healthy elderlies were examined. Regions of interest (ROIs) in the ventricular/sylvian (VS) and high convexity/midline (HCM) areas were used in VBM, and differences in CSF volume within these ROIs among the 4 groups were examined. The relative CSF volume in the VS-ROI in the iNPH group (.64) was significantly higher than that in the AD, PD, and healthy control groups (.26, .29, and .17, respectively; P < .001), whereas the relative CSF volume in the HCM-ROI was significantly reduced in the iNPH (.10) than in the other (.17, .16, and .16, respectively) groups (P < .001). Furthermore, the ratio of the 2 areas (VS/HCM) was markedly higher in the iNPH (6.87) than in the other (1.65, 1.74, .97, respectively) groups (P < .001), with sensitivity and specificity of .89 and 1.00, respectively. The VBM-based CSF space analysis can detect disproportionate changes in CSF space and differentiate iNPH patients from those with AD or PD and healthy elderlies accurately.

Microstructural changes of the corticospinal tract in idiopathic normal pressure hydrocephalus: a comparison of diffusion tensor and diffusional kurtosis imaging

The goals of this study were to examine the usefulness of diffusional kurtosis imaging (DKI) for assessing microstructural changes in the compressed corticospinal tract (CST) among patients with idiopathic normal pressure hydrocephalus (iNPH). Eleven patients with iNPH (mean age: 73.6 years, range: 65-84), who underwent 3-T magnetic resonance imaging, including DKI before surgery, were recruited. Six age-matched, healthy subjects (mean age: 69.8 years, range: 60-75) served as the control group. DKI and diffusion tensor imaging parameters were calculated and compared between the iNPH and the control groups using tract-specific analysis of the CST at the level of the lateral ventricle. Mean diffusional kurtosis (DK) and axial diffusion kurtosis were significantly lower in iNPH patients. However, apparent diffusion coefficient, fractional anisotropy, and axial eigenvalue (λ₁) were significantly higher in the iNPH group than in the control group. The mechanical pressure caused by ventricular enlargement in iNPH patients might induce formation of well-aligned fiber tracts and increased fiber density in the CST, resulting in decreased DK. DKI is able to depict both the altered microstructure and water molecule movement within neural axons and intra- or extracellular space. In addition, the investigated DKI parameters provide different information about white matter relative to conventional diffusional metrics for iNPH.

Dual-task related gait changes after CSF tapping: a new way to identify idiopathic normal pressure hydrocephalus

BackgroundGait disturbances found in patients with idiopathic normal pressure hydrocephalus (iNPH) are unspecific to the diagnosis and commonly occur in neurodegenerative or vascular conditions (iNPH-like conditions). This current retrospective pre-post intervention study aims to determine whether changes in quantitative gait parameters during dual task condition differed between iNPH and iNPH-like conditions before and after cerebrospinal fluid (CSF) tapping.Methods49 patients assessed before and after CSF tapping were included in this study (27 with iNPH and 22 with iNPH-like conditions). Gait analysis during single and dual task conditions (walking and backward counting) was performed before and after a CSF spinal tap of 40 ml. Gait parameters were compared between iNPH and iNPH-like conditions patients. Logistic regressions were used to examine the association between iNPH and gait parameters.ResultsImprovements of step width (−9.03 (20.75)% for iNPH group; +0.28 (21.76)% for iNPH-like conditions group), stride length (+7.82 (20.71)% for iNPH group; -0.62 (19.22)% for iNPH-like conditions group), walking speed (+12.20 (29.79)% for iNPH group; +2.38 (32.50)% for iNPH-like conditions group) and stance duration (−1.23 (4.03)% for iNPH group; +0.49 (5.12)% for iNPH-like conditions group) during dual task, after CSF spinal tapping, were significant in patients with iNPH compared to patients with iNPH-like conditions. No between group difference was observed for the single walking task evaluation. The multiple logistic regression revealed that among these four gait parameters, only the improvement in step width was associated with the diagnosis of iNPH.ConclusionDual-task related changes in spatio-temporal gait parameters before and after CSF tapping might be a novel and discriminative method of identifying iNPH patients from other similar conditions.

Differential Diagnosis of Idiopathic Normal Pressure Hydrocephalus from Other Dementias Using Diffusion Tensor Imaging

Because DTI can provide good markers of white matter pathology, it could be useful in differentiating white matter changes of INPH from those of other dementias. The aim of this study was, by using DTI, to compare the characteristic white matter changes in INPH with those in AD, subcortical vascular dementia, and healthy control subjects. Sixteen patients with presurgical INPH, 10 with AD, 10 with subcortical vascular dementia, and 20 healthy control subjects underwent DTI. All patients with INPH showed clinical improvement after shunt surgery, and 9 of them also underwent postshunting DTI. Regions of interest were selected at the periventricular white matter, the anterior limb of the internal capsule, the posterior limb of the internal capsule, the genu and the splenium of the corpus callosum, the superior longitudinal fasciculus, and the inferior longitudinal fasciculus. FA and MD were obtained from each region of interest and were compared among the groups. Presurgical INPH showed significantly higher FA than all the other groups in the posterior limb of the internal capsule, which was decreased after shunt surgery. Presurgical MD of the INPH group was higher than that in the AD and healthy control groups but lower than that in the subcortical vascular dementia group in the anterior periventricular white matter, the anterior limb of the internal capsule, and the superior longitudinal fasciculus. In differentiating INPH, the sensitivity and specificity of FA in the posterior limb of the internal capsule was 87.5% and 95.0%, respectively. Patients with shunt-responsive INPH showed higher FA in the posterior limb of the internal capsule compared with healthy controls and those in other groups of dementia that was reversible with shunt surgery. With this parameter, shunt-responsive INPH could be distinguished from AD, subcortical vascular dementia, and healthy conditions with high diagnostic accuracy.

Postshunt Cognitive and Functional Improvement in Idiopathic Normal Pressure Hydrocephalus

Improvement in gait after shunt placement has been well documented in idiopathic normal pressure hydrocephalus (iNPH); however, controversy remains regarding the extent and pattern of postsurgical cognitive changes. Conflicting findings may be explained by variability in both test selection and follow-up intervals across studies. Furthermore, most investigations lack a control group, making it difficult to disentangle practice effects from a true treatment effect. To examine postshunt changes in a sample of well-characterized iNPH participants compared with a group of age- and education-matched healthy control subjects. We identified 12 participants with iNPH undergoing shunt placement and 9 control participants. All participants were evaluated with comprehensive neuropsychological testing and standardized gait assessment at baseline and were followed up for 6 months. Repeated-measures analysis of variance revealed a significant group- (iNPH and control) by-time (baseline and 6 months) interaction for Trailmaking Test B: (P < .003) and Symbol Digit Modalities (P < .02), with greater improvement in iNPH participants relative to control subjects. In addition, the iNPH group showed greater improvement in gait (P < .001) and caregivers reported improved activities of daily living (P < .01) and reduced caregiver distress (P < .01). This study demonstrates improvements in mental tracking speed and sustained attention 6 months after shunt placement in iNPH. The present investigation is the first study to use a controlled design to show that cognitive improvement in iNPH is independent of practice effects. Furthermore, these findings indicate functional and quality-of-life improvements for both the shunt responder and their caregiver.

Retrograde jugular flow associated with idiopathic normal pressure hydrocephalus

To clarify the relation between the drainage pathway of cerebrospinal fluid and the development of idiopathic normal pressure hydrocephalus (iNPH), we examined flow patterns of internal jugular veins in 20 patients with iNPH and 13 control patients using air-contrast ultrasound venography during the Valsalva maneuver. The iNPH group had a significantly greater frequency of retrograde jugular venous flow (19/20, 95%) than the control group (3/13, 23%) (chi(2) test, p < 0.001). Our results suggest that retrograde jugular venous flow may be associated with the development of iNPH; therefore, the analysis of retrograde jugular venous flow could be a useful element in the diagnosis of iNPH.

Caudate structural abnormalities in idiopathic normal pressure hydrocephalus

BACKGROUND - Idiopathic normal pressure hydrocephalus (iNPH) is a reversible dementia in which fronto-striatal cognitive deficits and apathy may be present. OBJECTIVES - The study investigated structural volumetric changes in iNPH, apart from ventriculomegaly. MATERIALS AND METHODS - A full-brain voxel-based morphometric analysis between 11 iNPH patients and 14 healthy controls identified regions of interest (ROIs) for manual volumetric analyses. RESULTS - Caudate and corpus callosum ROI measurements revealed diminished caudate nuclei volume in the iNPH group. CONCLUSIONS - The role of the caudate nucleus in cognitive and affective changes in iNPH should now be explored.

Cognitive Impairment in Patients with Idiopathic Normal Pressure Hydrocephalus

Cognitive impairment in patients with idiopathic normal pressure hydrocephalous (iNPH) has not been clearly documented. We performed standardized neuropsychological assessments of 21 patients with iNPH and of 42 patients with Alzheimer’s disease (AD) matched to the patients with iNPH 2:1 by age, sex, and Mini-Mental State Examination score. Compared with the AD group, the iNPH group scored significantly higher on the orientation subtest of the Alzheimer’s Disease Assessment Scale and on the general memory and delayed recall subtests of the Wechsler Memory Scale-Revised (WMS-R), and significantly lower on the attention/concentration subtest of the WMS-R and on the digit span, arithmetic, block design and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised. The impairment of frontal lobe functions is disproportionately severe and memory impairment is disproportionately mild in patients with iNPH compared with AD. Recognition of these features contributes to an early diagnosis, which can lead to a better prognosis.