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ObjectivesTo evaluate complex CSF movements and shear stress in patients with idiopathic normal pressure hydrocephalus (iNPH) on four-dimensional (4D) flow MRI.MethodsThree-dimensional velocities and volumes of the reciprocating CSF movements through 12 ROIs from the foramen of Monro to the upper cervical spine were measured in 41 patients with iNPH, 23 patients with co-occurrence of iNPH and Alzheimer’s disease (AD), and 9 age-matched controls, using 4D flow imaging and application. Stroke volume, reversed-flow rate, and shear stress were automatically calculated. Relationships between flow-related parameters and morphological measurements were also assessed.ResultsStroke volumes, reversed-flow rates, and shear stress at the cerebral aqueduct were significantly higher in patients with iNPH than in controls. Patients with pure iNPH had significantly higher shear stress at the ventral aspect of the cerebral aqueduct than those with co-occurrence of iNPH and AD. The stroke volume at the upper end of the cerebral aqueduct had the strongest association with the anteroposterior diameter of the lower end of the cerebral aqueduct (r = 0.52). The stroke volume at the foramen of Monro had significant associations with the indices specific to iNPH. The shear stress at the dorsal aspect of the cerebral aqueduct had the strongest association with the diameter of the foramen of Magendie (r = 0.52).ConclusionsStroke volumes, reversed-flow rates, and shear stress through the cerebral aqueduct on 4D flow MRI are useful parameters for iNPH diagnosis. These findings can aid in elucidating the mechanism of ventricular enlargement in iNPH.Key Points• The CSF stroke volume and bimodal shear stress at the cerebral aqueduct were considerably higher in patients with iNPH.• The patients with pure iNPH had significantly higher shear stress at the ventral aspect of the cerebral aqueduct than those with co-occurrence of iNPH and AD.• The shear stress at the cerebral aqueduct was significantly associated with the diameter of the foramen of Magendie.

ObjectiveThis study aimed to determine the prevalence and clinical features of Parkinson’s disease (PD)/PD dementia (PD/PDD) or dementia with Lewy bodies (DLB) in idiopathic normal pressure hydrocephalus (iNPH).MethodsPatients with iNPH who were admitted to the Department of Neurology, Juntendo University School of Medicine over the past 10 years have been retrospectively analyzed. The diagnosis of iNPH and concomitant PD/PDD or DLB was established using diagnostic criteria. Motor symptoms were assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III. 123I-ioflupane single-photon emission computed tomography (DaT-SPECT) and cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC)-based assay were performed for alpha synuclein aggregation.ResultsOverall, 79 patients met the criteria for iNPH, of which 34 developed iNPH without accompanying disorders (iNPHa; 43%), 23 developed iNPH with comorbid PD/PDD (iNPHc + PD/PDD; 29.1%), and 8 developed iNPH with comorbid DLB (iNPHc + DLB; 10.1%). Significant differences in facial expansion and upper-limb parkinsonism were observed with a comorbidity of either PD/PDD or DLB. The specific binding ratio (SBR) of DaTscan was reduced in iNPHa (p = 0.02), but it reduced further with comorbid PD/PDD (p < 0.01) or DLB (p < 0.01). RT-QuIC was positive for all 13 comorbid PD/PDD and negative for all 19 iNPHa.ConclusionThese results highlight that synucleinopathies coexist with iNPH. These can be differentiated by performing DaTscan and RT-QuIC, which can affect its clinical features.

The aims of the study are to evaluate idiopathic normal‐pressure hydrocephalus (INPH)‐related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface‐based early‐phase 18F‐florbetaben (E‐FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three‐dimensional volumetric images, for automated surface‐based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent 18F‐fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age‐ and gender‐matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients. The present study investigates cerebral blood flow (CBF) and cortical thickness using surface‐based analysis of early‐phase 18F‐florbetaben PET and MRI in patients with idiopathic normal‐pressure hydrocephalus (INPH). INPH patients had significantly increased CBF with a concomitant increase in cortical thickness in areas located in the high convexity of the frontal and parietal cortical regions, and significantly decreased CBF without a concomitant change in cortical thickness in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions in comparison to control subjects. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.

Abstract BackgroundPatients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) may improve clinically following cerebrospinal fluid (CSF) diversion (shunt) surgery, though the predictors of shunt response remain debated. Currently, radiological features play an important role in the diagnosis of iNPH, but it is not well established which radiological markers most precisely predict shunt responsive iNPH.ObjectiveTo conduct a systematic review and meta-analysis to identify radiological predictors of shunt responsiveness, evaluate their diagnostic effectiveness, and recommend the most predictive radiological features.MethodsEmbase, MEDLINE, Scopus, PubMed, Google Scholar, and JSTOR were searched for original studies investigating radiological predictors of shunt response in iNPH patients. Included studies were assessed using the ROBINS-1 tool, and eligible studies were evaluated using a univariate meta-analysis.ResultsOverall, 301 full-text papers were screened, of which 28 studies were included, and 26 different radiological features were identified, 5 of these met the inclusion criteria for the meta-analysis: disproportionately enlarged subarachnoid space (DESH), callosal angle, periventricular white matter changes, cerebral blood flow (CBF), and computerized tomography cisternography. The meta-analysis showed that only callosal angle and periventricular white matter changes significantly differentiated iNPH shunt responders from non-responders, though both markers had a low diagnostic odds ratio (DOR) of 1.88 and 1.01 respectively. None of the other radiological markers differentiated shunt responsive from shunt non-responsive iNPH.ConclusionCallosal angle and periventricular changes are the only diagnostically effective radiological predictors of shunt responsive iNPH patients. However, due to the DORs approximating 1, they are insufficient as sole predictors and are advised to be used only in combination with other diagnostic tests of shunt response. Future research must evaluate the combined use of multiple radiological predictors, as it may yield beneficial additive effects that may allow for more robust radiological shunt response prediction.

ABSTRACT Aims This study aimed to assess the glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) patients and its recovery post‐shunt surgery using diffusion tensor image analysis along perivascular spaces (DTI‐ALPS). Methods Thirty‐five iNPH patients and forty healthy controls (HC) underwent MRI scans and neuropsychological assessments at baseline. A follow‐up study, conducted three months post‐shunt surgery, included fifteen iNPH patients. The DTI‐ALPS index was calculated to assess the glymphatic system status. Group differences were evaluated using the Mann–Whitney U test, while the paired Wilcoxon signed‐rank test was employed to compare pre‐operative and post‐operative ALPS indices. Multiple linear regression was utilized to analyze the association between changes in the ALPS index (ΔALPS) and alterations in clinical scores. Results Baseline examinations disclosed iNPH patients had a lower ALPS index than HC (p < 0.0001). We found a significantly increased ALPS index at 3 months after surgery compared to baseline (p < 0.0001). Positive correlations between theΔALPS and the increments of MMSE score (ΔMMSE) were found in all iNPH patients. Baseline age and ΔALPS emerged as significant predictors of ΔMMSE, with the model explaining 68.13% of the variance (R2 = 0.6813). Conclusion Glymphatic function in iNPH was enhanced following shunt surgery, which positively impacted cognitive recovery. The DTI‐ALPS index may serve as a useful predictor of shunting efficacy in iNPH patients.

Objectives To explore the value of structural neuroimaging in predicting the prognosis of shunt surgery for idiopathic normal-pressure hydrocephalus (iNPH) using two different standard semi-quantitative imaging scales. Methods A total of 47 patients with iNPH who underwent shunt surgery at our hospital between 2018 and 2020 were included in this study. The modified Rankin Scale (mRS) and iNPH grading scale (iNPHGS) were used to evaluate and quantify the clinical symptoms before and after shunt surgery. The disproportionately enlarged subarachnoid space hydrocephalus (DESH) and iNPH Radscale scores were used to evaluate the preoperative MR images. The primary endpoint was improvement in the mRS score a year after surgery, and the secondary endpoint was the iNPHGS after 1 year. The preoperative imaging features of the improved and non-improved groups were compared. Results The rates of the primary and secondary outcomes were 59.6% and 61.7%, respectively, 1 year after surgery. There were no significant differences in preoperative DESH score, iNPH Radscale, Evans’ index (EI), or callosal angle (CA) between the improved and non-improved groups. Significant correlations were observed between the severity of gait disorder and EI and the CA. Conclusions The value of structural neuroimaging in predicting the prognosis of shunt surgery is limited, and screening for shunt surgery candidates should not rely only on preoperative imaging findings. Key Points • Early shunt surgery can significantly improve the clinical symptoms and prognosis of patients with idiopathic normal-pressure hydrocephalus (iNPH). • Structural imaging findings have limited predictiveness for the prognosis of patients with iNPH after shunt surgery. • Patients should not be selected for shunt surgery based on only structural imaging findings.

Normal Pressure Hydrocephalus (NPH) is a syndrome in predominantly older adults, differential diagnoses include primary neurodegenerative diseases. The key radiological finding is ventricular enlargement, different from increased ventricular size associated with cerebral atrophy. After definitive surgical cerebrospinal fluid (CSF) shunting there appears to be increased brain tissue volume in patients’ follow-up images which could indicate that imaging findings usually interpreted as cerebral atrophy may be reversible with appropriate treatment. A cross-sectional study was performed comparing pre and postoperative brain volume in magnetic resonance imaging (MRI) studies of NPH patients who underwent ventriculoatrial shunting at our institution between April 2016 and February 2022. Brain volumes were obtained using volBrain and vol2Brain software. 30 patients were included, and 60 MRI studies reviewed. The average age was 80.4 years (54–92 years). 20 patients (66.6%) were men and 10 women. Following CSF shunting, patients had a statistically significant increase in white matter ( p  = 0.043), gray matter ( p  = 0.002), and total brain parenchyma ( p  = 0.032). The brain volume increased in postoperative MRI. We call this finding cerebral pseudoatrophy, which has not been previously described. Further studies are required to confirm this finding, which poses relevance for the accurate diagnosis of NPH.

PurposeThe potential relationship between mastication ability and cognitive function in idiopathic normal pressure hydrocephalus (iNPH) patients is unclear. This report investigated the association between mastication and cognitive function in iNPH patients using the gray level of the co-occurrence matrix on the lateral pterygoid muscle.MethodsWe analyzed data from 96 unoperated iNPH patients who underwent magnetic resonance imaging (MRI) between December 2016 and February 2023. Radiomic features were extracted from T2 MRI scans of the lateral pterygoid muscle, and muscle texture parameters were correlated with the iNPH grading scale. Subgroup analysis compared the texture parameters of patients with normal cognitive function with those of patients with cognitive impairment.ResultsThe mini-mental state examination score correlated positively with the angular second moment (P < 0.05) and negatively with entropy (P < 0.05). The dementia scale (Eide’s classification) correlated negatively with gray values (P < 0.05). Gray values were higher in the cognitive impairment group (64.7 ± 16.6) when compared with the non-cognitive impairment group (57.4 ± 13.3) (P = 0.005). Entropy was higher in the cognitive impairment group (8.2 ± 0.3) than in the non-cognitive impairment group (8.0 ± 0.3) (P < 0.001). The area under the receiver operating characteristic curve was 0.681 (P = 0.003) and 0.701 (P < 0.001) for gray value and entropy, respectively.ConclusionOur findings suggest an association between heterogeneity of mastication and impaired cognitive function in iNPH patients and highlight muscle texture analysis as a potential tool for predicting cognitive impairment in these patients.

Periventricular white matter changes are common in patients with idiopathic normal pressure hydrocephalus (iNPH) and considered to represent focally elevated interstitial fluid. We compared diffusion measures in periventricular hyperintensities in patients with imaging features of iNPH to patients without. The hypothesis is that periventricular hyperintensities in patients with presumed iNPH show higher water content than in patients without imaging features of iNPH. 21 patients with iNPH Radscale 7–12 (“high probability of iNPH”) and 10 patients with iNPH Radscale 2–4 (“low probability of iNPH”) were examined with a neurodegeneration imaging protocol including a diffusion microstructure imaging sequence. Periventricular hyperintensities and deep white matter hyperintensities were segmented and diffusion measures were compared. In patients with imaging features of iNPH, the free water content in periventricular hyperintensities was significantly higher compared to the control group ( p  = 0.005). This effect was also detectable in deep white matter hyperintensities ( p  = 0.024). Total brain volumes and total gray or white matter volumes did not differ between the groups. Periventricular cap free water fraction was highly discriminative regarding patients with presumed iNPH and controls with an ROC AUC of 0.933. Quantitative diffusion microstructure imaging shows elevated water content in periventricular hyperintensities in patients with imaging features of iNPH, which could be the imaging correlate for pathologic fluid accumulation and may be used as an imaging biomarker in the future.

Abstract BACKGROUND Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of gait and cognitive impairment. iNPH should be differentiated from ventriculomegaly secondary to brain atrophy to choose the best therapeutic option (ventriculoperitoneal shunt vs medical management). OBJECTIVE To determine the diagnostic accuracy of automated sulcal morphometry to differentiate patients with iNPH from patients with ventriculomegaly of neurodegenerative origin. METHODS Thirty-eight consecutive patients with iNPH (shunt responsive n = 31, nonresponsive n = 7), 35 with vascular cognitive disorder, and 25 age- and sex-matched healthy controls were prospectively included and underwent cognitive evaluation and 3T brain magnetic resonance imaging. Sulcal opening of 10 sulci of interest was retrospectively measured using an automated surface-based approach from the 3-dimensional T1-weighted images. Receiver-operating characteristic curve analyses determined the best parameter to identify iNPH patients. RESULTS The best parameter to discriminate shunt-responsive iNPH from patients with vascular cognitive disorder and healthy controls was the ratio between calcarine sulcus and cingulate sulcus opening with an area under the curve of 0.94 (95% CI: 0.89, 0.99). A cut-off value of 0.95 provided the highest sensitivity (96.8%) and specificity (83.3%). CONCLUSION This preliminary study showed that automated sulcal morphometry may help the neurosurgeon to identify iNPH patients and to exclude other causes of ventriculomegaly.