Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging

J Neurosurg 140:612–620, 2024

Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)—by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space—has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity.

METHODS Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool.

RESULTS: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00–1.15] vs 1.49 [1.36–1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47–1.67] vs 1.33 [1.14–1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = −0.644, p < 0.001), number of steps to complete TUG (r = −0.571, p < 0.001), 10-m walk time (r = −0.637, p < 0.001), and 10-m walk steps (r = −0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = −0.39, p < 0.001, R 2 = 0.459), female sex (B = 0.232, p = 0.002, R 2 = 0.157), and Evans index (B = −4.151, p < 0.001, R 2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R 2 = 0.626) than analysis of each of these factors alone.

CONCLUSIONS The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.

 

Treatment for secondary deterioration in idiopathic normal pressure hydrocephalus in the later course of the disease

Acta Neurochirurgica (2020) 162:2431–2439

Cerebrospinal fluid (CSF) shunting is a highly effective treatment for idiopathic normal pressure hydrocephalus (iNPH). However, secondary deterioration can occur at a later time. Thus, the current study aimed to evaluate the incidence rate and causes of secondary deterioration.

Methods A retrospective analysis was conducted on all patients with iNPH who were treated with implantation of a CSF shunt since 1993. A meticulous shunt workup was recommended to all patients who presented to our department with secondary deterioration during their follow-up visits. Data about the proportion of patients with such deterioration and its causes, subsequent treatment, and clinical outcome were obtained.

Results A total of 169 patients were included, and the mean follow-up time was 69.2 months. In total, 119 (70.4%) patients presented with a total of 153 secondary deteriorations. In 9 cases (5.9%), the deterioration was caused by delayed subdural hematoma and in 27 (22.1%) cases, by shunt dysfunction. Invasive shunt testing was commonly required to validate shunt failure. Moreover, 19 of 27 patients experienced a satisfactory improvement after revision surgery. In total, 86 deteriorations were attributed to nonsurgical causes, and the valve pressure was decreased in 79 patients, with only 16.5% presenting with a satisfactory improvement after lowering of valve pressure.

Conclusions Most patients with shunted iNPH presented with deterioration in the later course of the disease. Shunt dysfunction was considered a cause of secondary deterioration. Moreover, shunt revision surgery was a highly effective treatment, and patients with deterioration should undergo screening procedures for shunt dysfunction, including invasive shunt testing.

Mechanisms behind altered pulsatile intracranial pressure in idiopathic normal pressure hydrocephalus

Acta Neurochirurgica (2020) 162:1803–1813

The dementia subtype idiopathic normal pressure hydrocephalus (iNPH) has unknown etiology, but one characteristic is elevated intracranial pressure (ICP) wave amplitudes in those individuals who respond with clinical improvement following cerebrospinal fluid (CSF) diversion. To explore the mechanisms behind altered ICP wave amplitudes, we correlated central aortic blood pressure (BP) and ICP waveform amplitudes (intracranial aortic amplitude correlation) and examined how this correlation relates to ICP wave amplitude levels and systemic hemodynamic parameters.

Methods The study included 29 patients with probable iNPH who underwent continuous multi-hour measurement of ICP, radial artery BP, and systemic hemodynamic parameters. The radial artery BP waveforms were used to estimate central aortic BP waveforms, and the intracranial aortic amplitude correlation was determined over consecutive 4-min periods.

Results The average intracranial aortic amplitude correlation was 0.28 ± 0.16 at the group level. In the majority of iNPH patients, the intracranial aortic amplitude correlation was low, while in about 1/5 patients, the correlation was rather high (average Pearson correlation coefficient > 0.4). The degree of correlation was hardly influenced by systemic hemodynamic parameters.

Conclusions In about 1/5 iNPH patients of this study, the intracranial aortic amplitude correlation (IAACAORTIC) was rather high (average Pearson correlation coefficient > 0.4), suggesting that cerebrovascular factors to some extent may affect the ICP wave amplitudes in a subset of patients. However, in 14/19 (74%) iNPH patients with elevated ICP wave amplitudes, the intracranial aortic amplitude correlation was low, indicating that the ICP pulse amplitude in most iNPH patients is independent of central vascular excitation, ergo it is modulated by local cerebrospinal physiology. In support of this assumption, the intracranial aortic amplitude correlation was not related to most systemic hemodynamic variables. An exception was found for a subgroup of the patients with high systemic vascular resistance, where there was a correlation.

Outcomes and complications of different surgical treatments for idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis

J Neurosurg 131:1024–1036, 2019

Different CSF diversion procedures (ventriculoperitoneal, ventriculoatrial, and lumboperitoneal shunting) have been utilized for the treatment of idiopathic normal pressure hydrocephalus. More recently, endoscopic third ventriculostomy has been suggested as a reasonable alternative in some studies. The purpose of this study was to perform a systematic review and meta-analysis to assess overall rates of favorable outcomes and adverse events for each of these treatments. An additional objective was to determine the outcomes and complication rates in relation to the type of valve utilized (fixed vs programmable).

METHODS Multiple databases (PubMed, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus) were searched for studies involving patients with idiopathic ventriculomegaly, no secondary cause of hydrocephalus, opening pressure < 25 mm Hg on high-volume tap or drainage trial, and age > 60 years. Outcomes included the proportion of patients who showed improvement in gait, cognition, and bladder function. Adverse events considered in the analysis included postoperative ischemic/hemorrhagic complications, subdural fluid collections, seizures, need for revision surgery, and infection.

RESULTS A total of 33 studies, encompassing 2461 patients, were identified. More than 75% of patients experienced improvement after shunting, without significant differences among the different techniques utilized. Overall, gait improvement was observed in 75% of patients, cognitive function improvement in more than 60%, and improvement of incontinence in 55%. Adjustable valves were associated with a reduction in revisions (12% vs 32%) and subdural collections (9% vs 22%) as compared to fixed valves.

CONCLUSIONS Outcomes did not differ significantly among different CSF diversion techniques, and overall improvement was reported in more than 75% of patients. The use of programmable valves decreased the incidence of revision surgery and of subdural collections after surgery, potentially justifying the higher initial cost associated with these valves.

Accuracy and safety of 1-day external lumbar drainage of CSF for shunt selection in patients with idiopathic normal pressure hydrocephalus

J Neurosurg 131:1011–1017, 2019

Three to five days of external lumbar drainage (ELD) of CSF is a test for ventriculoperitoneal shunt (VPS) selection in idiopathic normal pressure hydrocephalus (iNPH). The accuracy and complication rates of a shorter (1-day) ELD procedure were analyzed.

METHODS Data of patients with iNPH who underwent 1-day ELD to be selected to undergo VPS placement with a programmable valve in the period from 2005 to 2015 were reviewed. Patients experiencing VPS complications, valve malfunctioning, or with less than 1 year of follow-up were excluded. The ability of 1-day ELD to predict VPS outcome at 1- and 12-month follow-up was assessed by calculating sensitivity, specificity, and positive and negative predictive values.

RESULTS Of 93 patients who underwent 1-day ELD, 3 did not complete the procedure. Of the remaining 90 patients, 2 experienced transient nerve root irritation. Twenty-four patients had negative test outcomes and 66 had positive test out- comes. Nine negative-outcome patients had intraprocedural headache, which showed 37.5% sensitivity (95% confidence interval [CI] 19.5%–59.2%) and 100% specificity (95% CI 93.1%–100%) as predictors of negative 1-day ELD outcome. Sixty-eight patients (6 with negative and 62 with positive outcomes) underwent VPS insertion, which was successful in
0 and 58 patients, respectively, at 1-month follow-up. Test sensitivity and specificity in predicting surgical outcome at 1-month follow-up were 100% (95% CI 92.3%–100%) and 60% (95% CI 27.4%–86.3%), respectively, with 94.1% accu- racy (95% CI 85.6–98.4%). Among the 1-day ELD–positive patients, 2 showed no clinical benefit at 12 months follow-up. Test sensitivity and specificity in predicting surgical outcome at 12-month follow-up was 100% (95% CI 92.5%–100%) and 75.0% (95% CI 35.6%–95.5%), respectively, with 97.1% (95% CI 89.8%–99.6%) accuracy.

CONCLUSIONS One-day ELD is a reliable tool in iNPH management, with low complication risk and short trial duration. The test is very consistent in predicting who will have a positive outcome with VPS placement, given the high chance of successful outcome at 1- and 12-month follow-up; negative-outcome patients have a high risk of unsuccessful surgery. Intraprocedural headache is prognostic of 1-day ELD negative outcome.

Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus

Acta Neurochir (2017) 159: 51-61

It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH).

Method

In this study, we retrospectively analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy.

Results

The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer’s disease (AD)-related proteins (amyloid-β, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (P = 0.014). High mean ICP was associated with Evans’ index (EI; P = 0.025), disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were associated with less atrophy of the medial temporal lobe (P = 0.018) and more severe disproportionality between the sylvian and suprasylvian subarachnoid spaces (P = 0.001).

Conclusions

The EI and disproportional sylvian and suprasylvian subarachnoid spaces were associated with mean ICP. Disproportionality was also associated with ICP B waves. These associations, although rather weak, with elevated ICP in 24-h measurements, support their value in iNPH diagnostics and suggest that these radiological markers are potentially related to the pathogenesis of iNPH. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation.

Comparison of elevated intracranial pressure pulse amplitude and disproportionately enlarged subarachnoid space (DESH) for prediction of surgical results in suspected idiopathic normal pressure hydrocephalus

External lumbar drain- A pragmatic test for prediction of shunt outcomes in idiopathic normal pressure hydrocephalus

Acta Neurochir (2016) 158:2207–2213

To compare the prognostic value of pulse amplitude on intracranial pressure (ICP) monitoring and disproportionately enlarged subarachnoid space hydrocephalus (DESH) on magnetic resonance imaging (MRI) for predicting surgical benefit after shunt placement in idiopathic normal pressure hydrocephalus (iNPH).

Method Patients with suspected iNPH were prospectively recruited from a single centre. All patients received preoperative MRI and ICP monitoring. Patients were classified as shunt responders if they had an improvement of one point or more on the NPH score at 1 year post-surgery. The sensitivity, specificity, Youden index, and positive and negative predictive values of the two diagnostic methods were calculated.

Results Sixty-four of 89 patients clinically improved at 1 year post-surgery and were classed as shunt responders. Positive DESH findings had a sensitivity of 79.4 % and specificity of 80.8 % for predicting shunt responders. Fifty-five of 89 patients had positive DESH findings: 50 of these responded to VP shunt, giving a positive and negative predictive value of 90.9 % and 61.8 %, respectively. Fifty-seven of 89 patients had high ICP pulse amplitude. High ICP pulse amplitude had a sensitivity of 84.4 %, specificity of 88 %, positive predictive value of 94.7 % and negative predictive value of 61.8 % for predicting shunt responders.

Conclusions Both positive DESH findings and high ICP pulse amplitude support the diagnosis of iNPH and provide additional diagnostic value for predicting shunt-responsive patients; however, high ICP amplitude was more accurate than positive DESH findings, although it is an invasive test.

Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus

iNPH

J Neurosurg 124:350–358, 2016

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient’s clinical symptoms.

Methods Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients’ clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)–based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis.

Results Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxelbased analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus.

Conclusions This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.

Clinical effect of different shunt valve settings in iNPH

Hydrocephalus

J Neurosurg 124:359–367, 2016

The study aim was to examine the effect of gradually reducing the opening pressure on symptoms and signs in the shunt treatment of idiopathic normal pressure hydrocephalus (iNPH).

Methods In this prospective double-blinded, randomized, controlled, double-center study on patients with iNPH, a ventriculoperitoneal shunt with an adjustable Codman Medos Valve was implanted in 68 patients randomized into 2 groups. In 1 group (the 20–4 group) the valve setting was initially set to 20 cm H2O and gradually reduced to 4 cm H2O over the course of the 6-month study period. In the other group (the 12 group), the valve was kept at a medium level of 12 cm H2O during the whole study period. All patients were clinically evaluated using 4 tests preoperatively as well as postoperatively at 1, 2, 3, 4, and 6 months. The test scores between the 2 groups (20–4 and 12) were compared for each clinical evaluation.

Results Fifty-five patients (81%) were able to complete the study. There were no significant differences between the 2 groups (20–4 and 12) preoperatively or at any time postoperatively. Both groups exhibited significant clinical improvement after shunt insertion at all valve settings compared with the preoperative score, with the greatest improvement observed at the first postoperative evaluation. The clinical improvement was significant within the first 3 months, and thereafter no significant improvement was seen in either group.

Conclusions Gradual reduction of the valve setting from 20 to 4 cm H2O did not improve outcome compared with a fixed valve setting of 12 cm H2O. Improvement after shunt surgery in iNPH patients was evident within 3 months, irrespective of valve setting.

Feasibility of radiological markers in idiopathic normal pressure hydrocephalus

Feasibility of radiological markers in idiopathic normal pressure hydrocephalus

Acta Neurochir (2015) 157:1709–1719

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.

Method In this retrospective cohort study, we evaluated brain CTor 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.

Results 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 1mm0.91, 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.

Conclusions 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.

Improvement in social function and health-related quality of life after shunt surgery for idiopathic normal-pressure hydrocephalus

HRQOL in iNPH

J Neurosurg 121:776–784, 2014

Object. To investigate the impact of shunt surgery on the activity, participation, autonomy, and health-related quality of life (HRQOL) of patients with idiopathic normal-pressure hydrocephalus (iNPH) as well as the effect on caregiver burden.

Methods. Thirty-seven patients (median age 70 years, range 50–89 years) with iNPH were evaluated before and 6 months after surgery. Symptoms and signs were assessed by the iNPH scale, activities of daily living (ADL) with the Functional Independence Measure (FIM) and Assessment of Motor and Process Skills (AMPS), autonomy and participation with Impact on Participation and Autonomy (IPA), and caregiver burden with the Caregiver Burden Scale (CBS). HRQOL was evaluated with the EQ-5D (EuroQol Group–5 Dimension health survey).

Results. Twenty-four patients (65%) improved clinically (iNPH scale score) and 31 (86%) improved their HRQOL after surgery, almost to the same level as found in the normal population. The patients became more independent in physical and cognitive activities, and participation and autonomy improved. The caregiver burden was decreased among caregivers to male patients but remained unchanged on the overall group level.

Conclusions. After shunt surgery, patients with iNPH showed improvement in most aspects of social life, they became more independent, and their quality of life returned to nearly normal.

Role of Endoscopic Third Ventriculostomy and Ventriculoperitoneal Shunt in Idiopathic Normal Pressure Hydrocephalus: Preliminary Results of a Randomized Clinical Trial

Role_of_Endoscopic_Third_Ventriculostomy_and

Neurosurgery 72:845–854, 2013

Currently, the most common treatment for idiopathic normal pressure hydrocephalus (INPH) is a ventriculoperitoneal shunt (VPS), generally with programmable valve implantation. Endoscopic third ventriculostomy (ETV) is another treatment option, and it does not require prosthesis implantation.

OBJECTIVE: To compare the functional neurological outcome in patients after 12 months of treatment with INPH by using 2 different techniques: ETV or VPS.

METHODS: Randomized, parallel, open-label trial involving the study of 42 patients with INPH and a positive response to the tap test, from January 2009 to January 2012. ETV was performed with a rigid endoscope with a 30 lens (Minop, Aesculap), and VPS was performed with a fixed-pressure valve (PS Medical, Medtronic). The outcome was assessed 12 months after surgery. The neurological function outcomes were based on the results of 6 clinical scales: mini-mental, Berg balance, dynamic gait index, functional independence measure, timed up and go, and normal pressure hydrocephalus.

RESULTS: There was a statistically significant difference between the 2 groups after 12 months of follow-ups, and the VPS group showed better improvement results (ETV = 50%, VPS = 76.9%).

CONCLUSION: Compared with ETV, VPS is a superior method because it had better functional neurological outcomes 12 months after surgery.

Assessment of a Quick Reference Table Algorithm for Determining Initial Postoperative Pressure Settings of Programmable Pressure Valves in Patients With Idiopathic Normal Pressure Hydrocephalus: SINPHONI Subanalysis

Neurosurgery 71:722–728, 2012 

Management of overdrainage complications in shunted patients with idiopathic normal pressure hydrocephalus (INPH) remains a difficult task despite the use of programmable pressure valves.

OBJECTIVE: To assess the usefulness of a quick reference table (QRT) algorithm for achieving a suitable initial programmable pressure valve setting in INPH patients who participated in the Study for INPH on Neurological Improvement (SINPHONI).

METHODS: One hundred registered patients diagnosed with probable INPH were treated with ventriculoperitoneal shunts using Codman-Hakim programmable valves (CHPVs). In this series, the initial CHPV setting was decided prospectively according to the QRT algorithm. Shunt effectiveness, complications, and the number of CHPV readjustments during follow-up periods were investigated.

RESULTS: Eighty patients were considered better than shunt responders (more than 1 point improvement in modified Rankin Scale at any follow-up period). Readjustments of CHPVs within 3 months after treatment with ventriculoperitoneal shunt were performed 56 times in 44 cases (44%, 0.56 times/patient). Low-pressure headache occurred in 9 patients, all of whom improved by readjustment alone. Nontraumatic subdural fluid collections and chronic subdural hematomas occurred in 15 cases (15%); however, most of the cases were subclinical and improved after CHPV readjustments alone. Burr hole irrigation was necessary in only 1 case.

CONCLUSION: Use of the QRT algorithm was associated with a decrease in postoperative CHPV readjustments and serious overdrainage complications during the followup period. The QRT algorithm is an easy, safe, and effective method for determining the initial CHPV pressure setting in INPH patients.

Detection of changes in cerebrospinal fluid space in idiopathic normal pressure hydrocephalus using voxel-based morphometry

Neuroradiology DOI 10.1007/s00234-009-0610-z

We attempted to detect alterations in the cerebrospinal fluid (CSF) space in patients with idiopathic normal pressure hydrocephalus (iNPH) using voxel-based morphometry (VBM).

Methods. We obtained sagittal volume images of the entire head by three-dimensional T1-weighted magnetic resonance imaging and compared the regional distribution of CSF in 12 patients with iNPH, 14 patients with Alzheimer’s disease (AD), and 17 healthy individuals using VBM with automatically extracted CSF objects.

Results. VBM demonstrated significant widening at the lateral ventricles and Sylvian fissures and narrowing of the CSF space at the high convexity/midline areas in iNPH patients, compared to the AD patients and healthy controls (p<0.05, after correction with a false-discovery rate). In addition, the ratio of the CSF volume in the lateral ventricle/Sylvian fissure area to that in the high convexity/midline area in iNPH patients (3.9 ± 1.2) was remarkably greater than that in AD patients (1.2 ± 0.3) ANOVA, p < 0.001; post hoc Tukey’s test, p < 0.001); we could discriminate iNPH patients from those in the other two groups without any overlap, when using a cutoff level of 1.9.

Conclusion. VBM using CSF objects can be used to delineate the characteristic alteration of the CSF space in iNPH patients, which has been evaluated by visual interpretation.