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OBJECTIVE The objective of this study was to analyze the effect of concomitant Parkinson’s disease (PD) and PD dementia (PD/PDD) on the course of idiopathic normal pressure hydrocephalus (iNPH), especially as related to the outcome of lumboperitoneal shunt (LPS) surgery. METHODS The authors retrospectively analyzed patients with iNPH without accompanying disorders (iNPH alone [iNPHa]) and iNPH concomitant with PD/PDD (iNPHc+PD/PDD) who had presented to their department between 2010 and 2019. The diagnosis of iNPHc+PD/PDD was established using the diagnostic criteria of the Movement Disorder Society. The effect of LPS surgery on clinical symptoms and striatum volumes was evaluated. RESULTS Thirty-three patients with iNPHa and 23 patients with iNPHc+PD/PDD were identified. Comorbid PD/PDD significantly worsened clinical outcome as measured by the iNPH grading scale, modified Rankin Scale (mRS), and Hoehn and Yahr (HY) scale. LPS surgery improved the iNPH score including gait disturbance (p < 0.01), cognitive impairment (p = 0.02), and urinary disturbance (p < 0.01) in iNPHa and improved gait disturbance (p = 0.01) and urinary disturbance (p = 0.03) in iNPHc+PD/PDD for 1 year. Comorbid synucleinopathies maintained worse mRS scores and HY stages for 3 years, and LPS surgery extended overall survival (p = 0.003), as well as the period of sustained mRS scores (p = 0.04) and HY stages (p = 0.004) in iNPHc+PD/PDD. Both caudate and putamen volumes were reduced in iNPHa (p < 0.01) compared to those in controls and in patients with iNPHc+PD/PDD compared to those in patients with PD/PDD (p < 0.01), and LPS surgery restored caudate volumes in both groups. CONCLUSIONS These results revealed that comorbid PD/PDD deteriorates the clinical course of iNPH and that LPS surgery is recommended regardless of this comorbidity.

OBJECTIVE Tailored surgery to extensively resect epileptogenic lesions using intraoperative electrocorticography (ioECoG) may improve seizure outcomes. However, resection of large areas is associated with decreased memory function postoperatively. The authors assessed whether ioECoG could provide useful information on how to minimize the focus resection and obtain better seizure outcomes without memory deterioration. They examined the postoperative seizure-free period and memory alteration in a retrospective cohort of patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) in whom the extent of removal was determined using ioECoG findings. METHODS The authors enrolled 82 patients with TLE associated with HS who were treated surgically. Transsylvian amygdalohippocampectomy was indicated as the first step. When visual inspection identified interictal epileptic discharges from the lateral temporal lobe on ioECoG, anterior temporal lobectomy (ATL) was eventually performed. The patients were divided into the selective amygdalohippocampectomy (SA, n = 40) and ATL (n = 42) groups. Postoperative seizure outcomes were assessed at 1, 2, 3, 5, and 7 years postoperatively using the International League Against Epilepsy classification. The Kaplan-Meier survival analysis was applied to evaluate the period of seizure recurrence between the SA and ATL groups. Factors attributed to seizure recurrence were analyzed using the Cox proportional hazards model, and they were as follows: epileptic focal laterality; age at seizure onset (< 10 or ≥ 10 years old); seizure frequency (more than weekly or less than weekly seizures); history of focal to bilateral tonic-clonic seizure; infectious etiology; and surgical procedure. The Wechsler Memory Scale–Revised was used to evaluate memory function pre- and postoperatively. RESULTS Seizure outcomes were significantly worse in the SA group than in the ATL group at 2 years postoperatively (p = 0.045). The International League Against Epilepsy class 1 outcomes at 7 years postoperatively in the SA and ATL groups were 63% and 81%, respectively. Kaplan-Meier analysis showed that seizure recurred significantly earlier in the SA group than in the ATL group (p = 0.031). The 2-way ANOVA analysis was used to compare the SA and ATL groups in each memory category, and revealed that there was no significant difference regardless of the side of surgery. CONCLUSIONS Visual assessment of ioECoG cannot be used as an indicator to minimize epileptic focus resection in patients with TLE associated with HS. ATL is more effective in obtaining seizure-free outcomes; however, both ATL and SA can preserve memory function.

Background: Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NAD + ) acts as a signaling molecule, and its levels were used to govern several biological pathways, for example, promoting angiogenesis by SIRT1 (sirtuin 1)-mediated inhibition of Notch signaling to rejuvenate capillary density of old-aged mice. NAD + modulation shows promise in the vascular remodeling of endothelial cells. However, NAD + distribution in atherosclerotic regions remains uncharacterized. Omega-3 polyunsaturated fatty acids consumption, such as docosahexaenoic acid and eicosapentaenoic acid, might increase the abundance of cofactors in blood vessels due to omega-3 polyunsaturated fatty acids metabolism. Methods: Apolipoprotein E-deficient ( ApoE −/− ) mice were fed a Western diet, and the omega-3 polyunsaturated fatty acids-treated groups were supplemented with docosahexaenoic acid (1%, w/w) or eicosapentaenoic acid (1%, w/w) for 3 weeks. Desorption electrospray ionization mass spectrometry imaging was exploited to detect exogenous and endogenous NAD + imaging. Results: NAD + , NADH, NADP + , NADPH, FAD + , FADH, and nicotinic acid adenine dinucleotide of the aortic arches were detected higher in the omega-3 polyunsaturated fatty acids-treated mice than the nontreated control. Comparing the distribution in the outer and inner layers of the arterial walls, only NADPH was detected slightly higher in the outer part in eicosapentaenoic acid-treated mice. Conclusions: Supplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD + , FAD + , and their metabolites in the aortic arch. Considering the pleiotropic roles of NAD + in biology, this result serves as a beneficial therapeutic strategy in the animal model counter to pathological conditions.

Background: The amyloid-β oligomers, consisting of 10–20 monomers (AβO10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. Objective: We hypothesized that cerebrospinal fluid (CSF) AβO10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. Methods: We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10–20 levels at baseline, 1 and 3 years after shunting. Results: Cohort-1 had higher CSF AβO10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10–20 decrease showed better cognitive outcome than those without. Conclusion: AβO10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10–20 can be an applicable diagnostic and prognostic biomarker.

Purpose Since a case of hydrocephalus in humans considered to be caused by ciliary dysfunction was first reported by Greenstone et al. in 1984, numerous papers on the correlation between ciliary function and hydrocephalus have been published. Methods We reviewed the published literature on primary ciliary dyskinesia in humans causing hydrocephalus, focusing on articles specifically examining the relation between ciliary function and hydrocephalus and its treatment. In addition, the authors’ experience is briefly discussed. Results Full texts of 16 articles reporting cases of human hydrocephalus (including ventriculomegaly) due to defects in ependymal ciliary function or primary ciliary dyskinesia observed in clinical practice were extracted. In recent years, studies on animal models, especially employing knockout mice, have revealed genetic mutations that cause hydrocephalus via ciliary dysfunction. However, a few reports on the onset of hydrocephalus in human patients with primary ciliary dyskinesia have confirmed that the incidence of this condition was extremely low compared to that in animal models. Conclusion In humans, it is rare for hydrocephalus to develop solely because of abnormalities in the cilia, and it is highly likely that other factors are also involved along with ciliary dysfunction.

Background Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM. Methods We enrolled 112 patients and classified them according to LCM distribution: (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS). Results The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups’ EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups. Conclusion Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.

Idiopathic normal pressure hydrocephalus (iNPH) is a condition resulting from impaired cerebrospinal fluid (CSF) absorption and excretion characterized by a triad of symptoms comprising dementia, gait disturbance (impaired trunk balance), and urinary incontinence. CSF biomarkers not only assist in diagnosis but are also important for analyzing the pathology and understanding appropriate treatment indications. As the neuropathological findings characteristic of iNPH have yet to be defined, there remains no method to diagnose iNPH with 100% sensitivity and specificity. Neurotoxic proteins are assumed to be involved in the neurological symptoms of iNPH, particularly the appearance of cognitive impairment. The symptoms of iNPH can be reversed by improving CSF turnover through shunting. However, early diagnosis is essential as once neurodegeneration has progressed, pathological changes become irreversible and symptom improvement is minimal, even after shunting. Combining a variety of diagnostic methods may lead to a more definitive diagnosis and accurate prediction of the prognosis following shunt treatment. Identifying comorbidities in iNPH using CSF biomarkers does not contraindicate shunting-based intervention, but does limit the improvement in symptoms it yields, and provides vital information for predicting post-treatment prognosis.

Spontaneous intracranial hypotension (SIH) is caused by cerebrospinal fluid (CSF) leakage. Patients with SIH experience postural headaches, nausea, etc., due to CSF hypovolemia. Imaging studies and clinical examinations, such as radioisotope (RI) scintigraphy, are useful for diagnosing SIH. However, 20-30% of patients do not show typical morphology and clinical test results. We previously reported that CSF contains transferrin (Tf) isoforms: “brain-type” Tf derived from the choroid plexus and “serum-type” Tf derived from blood. We showed that both isoforms increased in the CSF of patients with SIH by Western blotting. In the present study, we demonstrate that conventional ELISA for quantifying total Tf is useful for diagnosing SIH more accurately than Western blotting. In addition, SIH with chronic subdural hematoma (CSDH) was also accurately diagnosed. Total Tf in the CSF can serve as a useful biomarker for diagnosing SIH with or without CSDH.

ObjectiveBecause of the lack of highly skilled experts, automated technologies that support electroencephalogram (EEG)-based in epilepsy diagnosis are advancing. Deep convolutional neural network-based models have been used successfully for detecting epileptic spikes, one of the biomarkers, from EEG. However, a sizeable number of supervised EEG records are required for training.ApproachThis study introduces the Satelight model, which uses the self-attention (SA) mechanism. The model was trained using a clinical EEG dataset labeled by five specialists, including 16,008 epileptic spikes and 15,478 artifacts from 50 children. The SA mechanism is expected to reduce the number of parameters and efficiently extract features from a small amount of EEG data. To validate the effectiveness, we compared various spike detection approaches with the clinical EEG data.Main resultsThe experimental results showed that the proposed method detected epileptic spikes more effectively than other models (accuracy = 0.876 and false positive rate = 0.133).SignificanceThe proposed model had only one-tenth the number of parameters as the other effective model, despite having such a high detection performance. Further exploration of the hidden parameters revealed that the model automatically attended to the EEG’s characteristic waveform locations of interest.

Epileptic seizure is the common symptom associated with lipomas in the Sylvian fissure (Sylvian lipomas). Removal of these lipomas carries risks of hemorrhage and brain damage. We report a surgical strategy of not removing the lipoma in a case of intractable temporal lobe epilepsy associated with Sylvian lipoma. We performed anterior temporal lobectomy with preservation of the pia mater of the Sylvian fissure and achieved seizure freedom. Focal cortical dysplasia type 1 of the epileptic neocortex adjacent to the Sylvian lipoma was pathologically diagnosed. We recommend our surgical procedure in similar cases to avoid complications and achieve adequate seizure control.

In aging societies, idiopathic normal-pressure hydrocephalus(iNPH)has emerged as an important disease that can negatively affect the activities of daily living among the elderly. Evidence supporting diagnosis and treatment has accumulated and, in Japan, the third edition of the iNPH treatment guideline was published in 2020. Through the promotion of multi-facility research efforts in Japan, diagnosis of iNPH has been based on characteristic phenomena including gait disturbance, overactive bladder, cognitive impairment, and disproportionately enlarged subarachnoid space hydrocephalus(DESH). In supplementary examinations, brain transformations associated with iNPH have been evaluated using modified magnetic resonance imaging methods. Moreover, studies aimed at elucidating the disease state in combination with biological information obtained from cerebrospinal fluid findings are in progress. However, the outcome prediction of shunt treatment for atypical iNPH(i.e., non-DESH iNPH)and coexisting nervous system abnormalities is also important. In these cases, determining indications for surgery is a particular challenge.

Objectives Comorbidities of idiopathic normal pressure hydrocephalus (iNPH), such as Alzheimer's disease (AD) and Parkinson's spectrum (PS) disorder, can affect the long-term prognosis of cerebrospinal fluid (CSF) shunting. Therefore, it is important to be able to predict comorbidities in the early stage of the disease. This study aimed to predict the comorbidities of iNPH using neuropsychological tests and cognitive performance evaluation. Materials & methods Forty-nine patients with possible iNPH were divided into three groups: iNPH without AD or PS comorbidity (group-1), iNPH with AD comorbidity (group-2), and iNPH with PS comorbidity (group-3), according to CSF biomarkers such as phosphorylated tau and dopamine transporter imaging. Scores on the new EU-iNPH-scale, which is based on 4 neuropsychological tests (Rey Auditory Verbal Learning Test, Grooved Pegboard test, Stroop colour-naming test and interference test), were compared for each group. In addition, the scores before and 12 months after CSF shunting for each group were compared. Results EU-iNPH-scale using 4 neuropsychological tests could distinguish group-1 from group-2 or group-3 by area under the curve values of 0.787 and 0.851, respectively. Patients in group-1 showed a remarkable increase in memory and learning ability after surgery. Group-2 performed significantly poorer than group-1 patients on memory testing, but otherwise showed improvements in most of the neuropsychological tests. Group-3 performed significantly worse than group-1 patients-especially on Stroop tests-but showed post-surgery improvement on only the Stroop colour-naming test. Conclusions The 4 neuropsychological tests of the EU-iNPH-scale can help predict iNPH comorbidities and evaluate the prognosis of CSF shunting.

Background and purpose The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) has not been completely clarified. We investigated the brain structure in iNPH using automatic ventricular volumetry, single-tensor diffusion tensor imaging (DTI) and bi-tensor free-water (FW) imaging analyses while focusing on cognitive impairments before and after lumboperitoneal shunt surgery. Materials and methods This retrospective study included 12 iNPH patients with structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) on a 3T-MRI scanner who underwent neuropsychological assessments before and after shunting and 8 healthy controls. Ventricular volumetry was conducted on structural MRI datasets using FreeSurfer. Ventricular volume was compared pre- and postoperatively. Correlation analyses were performed between ventricular volume or volume change and neuropsychological scores or score change. Tract-based spatial statistics were performed using dMRI datasets for group analyses between iNPH and controls and between pre- and post-surgery iNPH patients and for correlation analyses using neuropsychological scores. Tract-specific analyses were performed in the anterior thalamic radiation (ATR), followed by comparison and correlation analyses. Results The third ventricular volume was significantly decreased after shunting; its volume reduction negatively correlated with a neuropsychological improvement. Compared with controls, iNPH patients had lower fractional anisotropy and higher axial, radial, and mean diffusivities, and FW in the periventricular white matter including ATR, resulting in no difference in FW-corrected indices. Single-tensor DTI indices partially correlated with neuropsychological improvements, while FW-corrected indices had no correlations. Conclusion Third ventricle enlargement is possibly linked to cognitive impairment and FW imaging possibly provides better white matter characterization in iNPH.

Background Intracranial hypotension is a disorder characterized by low cerebrospinal fluid (CSF) pressure typically caused by loss of CSF. Although some mechanisms account for the CSF leakage have been elucidated, spinal canal stenosis has never been reported as a pathological cause of intracranial hypotension. C1-C2 sign is a characteristic imaging feature, which indicates CSF collection between the spinous processes of C1 and C2, occasionally observed on magnetic resonance imaging (MRI) in patients with intracranial hypotension. Case presentation A 58-year-old man was presented to our institute with complaints of posterior cervical pain persisting for 3 months, along with numbness and muscle weakness of extremities. A fat suppression T2-weighted image of MRI illustrated fluid collection in the retrospinal region at C1-C2 level, and an 111In-DTPA cisternoscintigram clearly revealed the presence of CSF leakage into the same region. The MRI also showed stenosis in spinal canal at C3/4 level, and a computed tomography (CT) myelogram suggested a blockage at the same level. We gave a diagnosis as intracranial hypotension due to the CSF leakage, which might be caused by the spinal canal stenosis at C3/4 level. Despite 72 h of conservative therapy, a brain CT showed the development of bilateral subdural hematomas. We, therefore, performed burr-hole drainage of the subdural hematoma, blood-patch therapy at C1/2 level, and laminoplasty at C3–4 at the same time. Improvement of symptoms and imaging features which suggested the CSF leak and subdural hematoma were obtained post-operatively. Conclusion The present case suggested the mechanism where the CSF leakage was revealed as fluid collection in the retrospinal region at C1-C2 level. Increased intradural pressure due to the spinal canal stenosis resulted in dural tear. CSF leaked into the epidural space and subsequently to the retrospinal region at C1-C2 level, due to the presence of spinal canal stenosis caudally as well as the vulnerability of the tissue structure in the retrospinal region at C1-C2 level. Thus, our theory supports the mechanisms of previously reported CSF dynamics associated to C1-C2 sign, and also, we suggest spinal canal stenosis as a novel etiology of intracranial hypotension.

Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NADApolipoprotein E-deficient (NADSupplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD

BackgroundCongenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus.MethodsComparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. ResultsCGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats, encompassing the Ptpn20 gene, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20-/-) mice were generated and found to develop ventriculomegaly. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20. ConclusionsThe high level of pNKCC1 in CP epithelium may cause the overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20-/- mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.

Background Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus. Methods Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus. Results CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20−/−) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks. Conclusions This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20−/− mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.

We assessed the diagnostic utility of the occurrence rate of high-frequency oscillations and modulation index (MI) from intraoperative electrocorticography (ioECoG) in determining the extent of epileptogenicity in mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS).We enrolled 17 patients who underwent selective amygdalohippocampectomy (SelAH) for TLE due to HS. We analyzed the occurrence rate of ripples (80-200 Hz) and fast ripples (200-300 Hz); and MI between ripples and 3-4 Hz (MIIn the poor seizure outcome group, an increase in the occurrence rate of ripples was seen in the hippocampus and LTL pre-SelAH and the LTL post-SelAH. The MIHigh occurrence rate of ripples and MI

Treatment for idiopathic normal pressure hydrocephalus (iNPH) continues to develop. Although ventriculoperitoneal shunt surgery has a long history and is one of the most established neurosurgeries, in the 1970s, the improvement rate of iNPH triad symptoms was poor and the risks related to shunt implantation were high. This led experts to question the surgical indication for iNPH and, over the next 20 years, cerebrospinal fluid (CSF) shunt surgery for iNPH fell out of favor and was rarely performed. However, the development of programmable-pressure shunt valve devices has reduced the major complications associated with the CSF drainage volume and appears to have increased shunt effectiveness. In addition, the development of support devices for the placement of ventricular catheters including preoperative virtual simulation and navigation systems has increased the certainty of ventriculoperitoneal shunt surgery. Secure shunt implantation is the most important prognostic indicator, but ensuring optimal initial valve pressure is also important. Since over-drainage is most likely to occur in the month after shunting, it is generally believed that a high initial setting of shunt valve pressure is the safest option. However, this does not always result in sufficient improvement of the symptoms in the early period after shunting. In fact, evidence suggests that setting the optimal valve pressure early after shunting may cause symptoms to improve earlier. This leads to improved quality of life and better long-term independent living expectations. However, in iNPH patients, the remaining symptoms may worsen again after several years, even when there is initial improvement due to setting the optimal valve pressure early after shunting. Because of the possibility of insufficient CSF drainage, the valve pressure should be reduced by one step (2–4 cmH2O) after 6 months to a year after shunting to maximize symptom improvement. After the valve pressure is reduced, a head CT scan is advised a month later.

BackgroundThe aim of this study was to evaluate the water diffusivity changes along the perivascular space after lumboperitoneal shunt (LPS) surgery in idiopathic normal pressure hydrocephalus.MethodsNine patients diagnosed with idiopathic normal pressure hydrocephalus (iNPH; three men and six women, mean age ± SD = 75.22 ± 5.12 years) according to the guidelines for iNPH in Japan were included in the study. Post-LPS surgery, six patients with iNPH who exhibited improvement in symptoms were defined as responder subjects, while three patients with iNPH who did not were defined as non-responder subjects. We calculated the mean analysis along the perivascular space (ALPS) index of the left and right hemispheres and compared the differences between pre- and post-LPS surgery mean ALPS indices in iNPH patients. In the responder or non-responder subjects, the mean ALPS indices in the pre- and post-operative iNPH groups were compared using Wilcoxon signed-rank tests. Next, correlation analyses between pre- and post-operation changes in the mean ALPS index and clinical characteristics were conducted.ResultsThe mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.021). In responder subjects, the mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.046). On the other hand, in the non-responder subjects, the mean ALPS index of the post-operative iNPH group was not significantly different compared to the pre-operative iNPH group (p = 0.285). The mean ALPS index change was not significantly correlated with changes in the Mini-Mental State Examination (MMSE) score (r = −0.218, p = 0.574), Frontal Assessment Battery (FAB) score (r = 0.185, p = 0.634), Trail Making Test A (TMTA) score (r = 0.250, p = 0.516), and Evans' index (r = 0.109, p = 0.780). In responder subjects, the mean ALPS index change was significantly correlated with Evans' index in pre-operative patients with iNPH (r = 0.841, p = 0.036).ConclusionThis study demonstrates the improved water diffusivity along perivascular space in patients with iNPH after LPS surgery. This could be indicative of glymphatic function recovery following LPS surgery.

Background: We analyzed the predictive value of the tap test (TT) on the outcome of cerebrospinal fluid (CSF) shunting in patients with idiopathic normal pressure hydrocephalus (iNPH) and cognitive impairment up to 12 months postoperatively.Methods: We analyzed the data of two prospective multicenter studies on ventriculoperitoneal shunt (VPS) and lumboperitoneal shunt (LPS) use in iNPH patients. We selected patients with Mini-Mental State Examination (MMSE) scores ≤ 26 points as study subjects. We used a multivariate logistic regression model to obtain the optimal threshold of MMSE scores after TT to predict the score improvement at 12 months following shunting and that helped to control for confounding factors such as age and MMSE scores before TT. We used logistic regression models to identify variables with age-adjusted odds ratio (A-OR) and multivariate-adjusted OR (M-OR).Results: For an improvement of ≥3 points in the MMSE score cutoff 7 days following TT in VPS and LPS cohort studies, the MMSE scores improved by 6 points after 12 months. The VPS cohort had sensitivity, specificity, and area under the curve (AUC) of 69.2, 73.7, and 0.771%, respectively; however, for the LPS cohort, they were 86.2, 90.9, and 0.906%, respectively. For MMSE scores that improved by ≥3 points in patients after the TT, the possibility of an improvement by 6 points at 12 months following CSF shunt had A-OR 7.77 and M-OR 6.3 times for the VPS, and A-OR 62.3 and M-OR 59.6 times for the LPS cohort.Conclusion: CSF shunting contributes to improved cognitive function in iNPH patients. Furthermore, MMSE score evaluation at the TT can sensitively predict improvement in postoperative MMSE scores following LPS intervention.Clinical Trial Registration: SINPHONI-1 (ClinicalTrials.gov, no. NCT00221091), first posted: September 22, 2005.SINPHONI-2 [University Hospital Medical Information Network (UMIN) Clinical Trials no. UMIN000002730], the posted: February 1, 2010.

Background In many brain volumetry reports, data from both controls and patients have been used to create the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) templates for spatial normalization, whereas some studies used data from only the control group. Purpose To investigate the association between lesion detection and the processes used in creating DARTEL template in group comparisons with voxel-based morphometry. Material and Methods Three-dimensional T1-weighted MRI data of 31 healthy controls, 31 patients with Alzheimer’s disease, and 31 patients with idiopathic normal pressure hydrocephalus were obtained using a 3-T magnetic resonance scanner. Segmented gray matter images were then deformed into three types of DARTEL templates using the Statistical Parametric Mapping 12 software. Results Processes 1 (DARTEL template with all individuals) and 2 (DARTEL template with healthy controls) showed significant lesions, as observed in previous reports, whereas process 3 (DARTEL template with individuals divided into two groups) showed significantly larger lesions than those noted with processes 1 and 2. Conclusion The present study demonstrated that lesion detection depends on the processes used in the creation of the DARTEL template.

Background Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. Objective The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. Methods We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. Results An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). Conclusions The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

Numerous studies have been conducted on indoor and outdoor seamless positioning and indoor&ndash, outdoor detection methods. However, the classification of real space into two types, outdoor space and indoor space, is difficult. One type of space that is difficult to classify is top-bounded space, which can be observed in commercial facilities, logistics facilities, and street-facing sidewalks. In this study, we designed a method for detecting stays in three spatial contexts: Outdoor, top-bounded space, and indoor. This method considers elongated top-bounded spaces covered with a roof and open on one of the sides. Specifically, we selected Global Positioning System (GPS) satellites for stay detection based on the simple extraction of the spatial characteristics of a top-bounded space and designed a decision flow using fuzzy inference based on the signal-to-noise ratio (SNR) of the selected GPS satellites. Moreover, we conducted an evaluation experiment to verify the effectiveness of the proposed method and confirmed that it could correctly detect the stay in three spatial contexts, outdoor, top-bounded space, and indoor, with a high probability of 93.1%.

With the widespread use of indoor positioning technology, various services based on this technology are beginning to be offered to consumers and industrial applications. In the case of logistics facilities, in addition to indoor and outdoor spaces, there are top-bounded spaces (TBSs): elongated areas that are covered with roofs or eaves on the upper parts of buildings. The sides of such spaces are open, and workers and forklifts work in these areas. Only a few studies have been conducted on positioning methods for this unusual environment, and the way by which Signal-to-Noise Ratio (SNR) of Global Positioning System (GPS) changes with the stay in TBSs is unclear. Therefore, we conducted preliminary experiments and confirmed that TBS dwellings are difficult to stably detect with existing methods due to the combination of satellites with variable and unchanged SNRs. In this study, we designed a simple processing flow for selecting satellites with high probabilities of changing SNRs by using the spatial characteristics of TBSs as parameters (height, depth, and side opening orientation). We propose a method to detect the stay in TBSs using the SNR change rates of the selected satellites. As a result of evaluation experiments with three TBSs, we successfully detected the stay in TBSs with about 30% higher probability than those of an existing method.

To cope with the lack of highly skilled professionals, machine learning with proper signal processing is key for establishing automated diagnostic-aid technologies with which to conduct epileptic electroencephalogram (EEG) testing. In particular, frequency filtering with the appropriate passbands is essential for enhancing the biomarkers—such as epileptic spike waves—that are noted in the EEG. This paper introduces a novel class of neural networks (NNs) that have a bank of linear-phase finite impulse response filters at the first layer as a preprocessor that can behave as bandpass filters that extract biomarkers without destroying waveforms because of a linear-phase condition. Besides, the parameters of the filters are also data-driven. The proposed NNs were trained with a large amount of clinical EEG data, including 15,833 epileptic spike waveforms recorded from 50 patients, and their labels were annotated by specialists. In the experiments, we compared three scenarios for the first layer: no preprocessing, discrete wavelet transform, and the proposed data-driven filters. The experimental results show that the trained data-driven filter bank with supervised learning behaves like multiple bandpass filters. In particular, the trained filter passed a frequency band of approximately 10–30 Hz. Moreover, the proposed method detected epileptic spikes, with the area under the receiver operating characteristic curve of 0.967 in the mean of 50 intersubject validations.

Ependymoma is the most common primary intramedullary tumor of the spinal cord, accounting for a quarter of these tumors. We experienced a case of 'ependymoma of the spinal cord with a cystic lesion that presented as an intradural extramedullary tumor extending from the thoracic to lumbar vertebrae. In review of past literature on reports of spinal intradural extramedullary ependymoma, lesions spanning three or more vertebrae with cystic lesions were frequent, and about half were World Health Organization grade II or higher. Dissemination or recurrence of these tumors may occur after surgery. There is no consensus on postoperative adjuvant therapy for intradural extramedullary spinal ependymoma, but careful consideration should be given to the intraoperative findings and the characteristics of the tumor.

Introduction Our previous community-based study demonstrated that some individuals with AVIM [asymptomatic ventriculomegaly with features of idiopathic normal pressure hydrocephalus (iNPH) on magnetic resonance imaging (MRI)] progressed to iNPH in several years. In this hospital-based study, we investigated the progression rate from AVIM to iNPH and its possible predictors. Methods We conducted a prospective study of participants with AVIM from several medical institutions/hospitals in Japan. AVIM is defined as “asymptomatic ventriculomegaly with features of iNPH on MRI”; in the present study, asymptomatic was defined as “0 (no symptoms) or 1 (presence of only subjective, but not objective, symptoms) on the iNPH Grading Scale (iNPH-GS).” We also measured possible predicting factors for AVIM-to-iNPH progression, including age, sex, body weight, blood pressure, diabetes mellitus, dyslipidemia, history of mental disease/head injury/sinusitis/smoking/alcohol-intake, Evans index, and the presence of DESH (disproportionately enlarged subarachnoid-space hydrocephalus) findings on brain MRI, and analyzed these potential predictive values. Results In 2012, 93 participants with AVIM were registered and enrolled in the study. Of these, 52 participants were able to be tracked for three years (until 2015). Of the 52 participants, 27 (52%) developed iNPH during the follow-up period (11 definite, 6 probable, and 10 possible iNPH), whereas 25 participants remained asymptomatic in 2015. Among the possible predictive factors examined, the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression. Conclusions The multicenter prospective study demonstrated that the progression rate from AVIM to iNPH was ~17% per year, and the baseline scores of iNPH-GS predicted the AVIM-to-iNPH progression.

Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.

Background Alzheimer's disease (AD) pathology in idiopathic normal pressure hydrocephalus (iNPH) contributes to poor shunt responses. Amyloid-β 1- 42 (Aβ42) toxic conformer was recently identified with features of rapid oligomerization, strong neurotoxicity and synaptotoxicity. Objective This observational study points to Aβ42 toxic conformer as a biomarker for AD pathology and for poor postoperative prognosis in patients with iNPH. Methods The first cohort consisted of patients with AD (n = 17) and iNPH (n = 17), and cognitively normal individuals (CN, n = 12). The second cohort, consisted of 51 patients with iNPH, was divided into two groups according to phosphorylated Tau (pTau) level (low- and high-pTau groups); the low-pTau group was further subdivided according to one-year postoperative change in Aβ42 toxic conformer ratio (%) [Aβ42 toxic conformer/Aβ42×100] (decreased- and increased-conformer subgroups). Enzyme-linked immunosorbent assay was used to measure pTau, Aβ42, and Aβ42 toxic conformer in cerebrospinal fluid. Outcomes were evaluated using neuropsychological tests one- and two-years postoperatively. Results In the first cohort, Aβ42 toxic conformer ratio in the iNPH group (10.8%) was significantly higher than that in the CN group (6.3%) and significantly lower than that in the AD group (17.2%). In the second cohort, the high-pTau group showed cognitive decline two-years postoperatively compared to baseline. However, the low-pTau group showed favorable outcomes one-year postoperatively; furthermore, the increased-conformer subgroup showed cognitive decline two-years postoperatively while the decreased-conformer subgroup maintained the improvement. Conclusions Change in Aβ42 toxic conformer ratio predicts long-term cognitive outcome in iNPH, even in the low-pTau group.

Precise control is a key factor in enabling Unmanned Underwater Vehicles (UUVs) to complete various underwater activities. The development of UUV control rules is mostly based on UUV dynamic models. However, such dynamic models contain unknown hydrodynamic parameters that need to be identified. This paper presents a new method, Laser Line Scanning for Hydrodynamic Parameter Identification (LSHPI), which integrates laser line scanning, decoupled dynamics, and evolutionary optimisation to identify the hydrodynamic parameters of an Autonomous Underwater Vehicle (AUV). In this research, laser images, seen from an on board camera's perspective and created using Open Graphics Library (OpenGL), were used to validate LSHPI's feasibility. The accuracy of the AUV positions and Euler angles obtained by the laser image-based methods were investigated for each decoupled One-Dimensional (1D) motion and the influence of other motion disturbances on the accuracy of the obtained AUV positions or Euler angles was also evaluated. In addition, the accuracy of the surge-related hydrodynamic parameters obtained by LSHPI was investigated under different motion disturbances. Based on the hydrodynamic parameter identification results under different motion disturbances, LSHPI's feasibility was successfully validated.

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity. The prognosis for cognitive improvement after shunt surgery has been difficult to predict. We therefore investigated various CSF proteins, hoping to find a biomarker predictive of cognitive performance one to two years after shunt surgery. CSF proteins of 34 iNPH and 15 non-iNPH patients were analysed by Western blotting, revealing two glycan isoforms of transferrin (Tf); 'brain-type' Tf with N-acetylglucosaminylated glycans and 'serum-type' Tf with α2, 6-sialylated glycans. Brain-type Tf levels decreased in iNPH but rapidly returned to normal levels within 1-3 months after shunt surgery. This change was positively correlated with recovery from dementia, per Mini-Mental State Examination and Frontal Assessment Battery scores at 11.8 ± 7.7 months post-operation, suggesting that brain-type Tf is a prognostic marker for recovery from dementia after shunt surgery for iNPH. Histochemical staining with anti-Tf antibody and an N-acetylglucosamine-binding lectin suggests that brain-type Tf is secreted from choroid plexus, CSF-producing tissue.

Background Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage. Objective To investigate whether LPSs, including gravitational "add-on" and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes. Methods We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated. Results Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group. Conclusion This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.

We report the case of a young woman who received intrathecal baclofen therapy (ITB) and subsequently became pregnant and had a normal delivery. A 28-year-old woman with flexion myelopathy had anterior decompression with fusion at C4/5 and C5/6 levels. Clinical symptoms improved after surgery. However, when she was 29 years old, her symptoms steadily advanced to Modified Ashworth Scale 3 spasticity level in the lower legs, with pain in both of them and urinary retention tendency. Since a 25 μg intrathecal baclofen injection improved her symptoms, an ITB pump system was implanted. After surgery, lower limb spasticity and urinary retention improved. Two years after ITB pump implantation, the patient married and became pregnant. The patient intended to have normal delivery but the induction of labor was ineffective and childbirth was completed by Cesarean section with lumbar anesthesia. The infant’s Apgar score was 8 at 1 min and 9 at 5 min, and birth-weight was 2,704 g. We measured the baclofen concentration in the patient’s breast milk using high-performance liquid chromatography/tandem mass spectrometry. The level of baclofen in the breast milk was very low (0.617 ng/ml) and the predicted pharmacological effect on the infant was judged to be negligible. No withdrawal symptoms or muscle tone abnormalities were found after birth. Our findings indicate that ITB therapy could be considered for young women with severe spasticity, even if they plan to have children.

This study used location and physical-activity data to test hypothesis that Tokyo’s residents exercise more because they walk to and from public transit stations for daily trips. An activity tracker and a mobile app were used by ten subjects over 48 days to collect data. Analysis of the dataset showed that on an average, all subjects walked over 10,000 steps per day and ∼40% of trips were taken in outdoor urban environments. Results also revealed that the subjects did not always take the shortest path between the origin and destination of a walking trip. These results suggest that urban residents choose routes of travel based on both internal and external factors, including the subjective effects of street design and personal preference.

In the event of a large-scale disaster, the dissemination of audible disaster warning information via sirens is effective in ensuring a rapid response. Sirens can be installed not only on fixed towers, but also on public transport and other vehicles passing through residential areas, and at spots where residents congregate, to increase area coverage. Although models to calculate the spatial coverage of audible information delivered from fixed sirens have been constructed, no general-purpose model has been developed to assess the delivery from vehicles. In this study, we focused on the General Transit Feed Specification (GTFS), which is an open format for geospatial information on public transport. We conducted a spatial analysis using a geographic information system (GIS) on the basis of the acquired bus location information. We developed a model to calculate the spatial coverage of the audible information delivery for overlapping hazard maps and population. Assuming a flood occurred in the vicinity of Brisbane Central Station, Queensland, Australia, we confirmed that the developed model was capable of characterizing the time-series changes in the exposed population in the target area. Since the GTFS format is currently distributed across various countries, this assessment model is considered to be highly versatile and widely applicable.

We performed a safety evaluation using the procedure devised by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) of the following four flavouring substances that belong to the class of ‘aliphatic primary alcohols, aldehydes, carboxylic acids, acetals, and esters containing additional oxygenated functional groups’ and are uniquely used in Japan: butyl butyrylacetate, ethyl 2-hydroxy-4-methylpentanoate, 3-hydroxyhexanoic acid and methyl hydroxyacetate. Although no genotoxicity study data were found in the published literature, none of the four substances had chemical structural alerts predicting genotoxicity. All four substances were categorised as class I by using Cramer’s classification. The estimated daily intake of each of the four substances was determined to be 0.007–2.9 μg/person/day by using the maximised survey-derived intake method and based on the annual production data in Japan in 2001, 2005 and 2010, and was determined to be 0.250–600.0 μg/person/day by using the single-portion exposure technique and based on average-use levels in standard portion sizes of flavoured foods. Both of these estimated daily intake ranges were below the threshold of toxicological concern for class I substances, which is 1800 μg/person/day. Although no information from in vitro and in vivo toxicity studies for the four substances was available, these substances were judged to raise no safety concerns at the current levels of intake.

The symptoms of idiopathic normal pressure hydrocephalus (iNPH) can be improved by shunt surgery, but prediction of treatment outcome is not established. We investigated changes of the corticospinal tract (CST) in iNPH before and after shunt surgery by using diffusion microstructural imaging, which infers more specific tissue properties than conventional diffusion tensor imaging. Two biophysical models were used: neurite orientation dispersion and density imaging (NODDI) and white matter tract integrity (WMTI). In both methods, the orientational coherence within the CSTs was higher in patients than in controls, and some normalization occurred after the surgery in patients, indicating axon stretching and recovery. The estimated axon density was lower in patients than in controls but remained unchanged after the surgery, suggesting its potential as a marker for irreversible neuronal damage. In a Monte-Carlo simulation that represented model axons as undulating cylinders, both NODDI and WMTI separated the effects of axon density and undulation. Thus, diffusion MRI may distinguish between reversible and irreversible microstructural changes in iNPH. Our findings constitute a step towards a quantitative image biomarker that reflects pathological process and treatment outcomes of iNPH., Highlights • NODDI and WMTI provide markers of reversible and irreversible changes in iNPH. • Measures of axon orientation indicated recovery from stretching after surgery. • Axon density remained low after surgery, suggesting chronic neuronal damage. • Axon stretching in simulations differentially affected diffusion metrics.