Abstracts from hydrocephalus 2018: the tenth meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders

s from hydrocephalus 2018: the tenth meeting of the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders Bologna, Italy. 19–22 October 2018 © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. I


Introduction:
The diagnosis of normal pressure hydrocephalus (NPH) can be quite challenging given the phenotypic overlap with other cognitive disorders. Moreover, knowledge about the pathophysiological mechanism leading to neurological dysfunction in NPH is limited.
Cerebrospinal fluid (CSF) biomarkers have been investigated to these aims, but the results appear discordant among studies. Methods: We measured CSF amyloid β (Aβ)42 and Aβ40, neurofilament light chain protein (NfL), total(t)-tau and phosphorylated(p)-tau in healthy controls (n = 38) and subjects with cognitive disorders including NPH (n = 66), Alzheimer's disease (AD) (n = 60), vascular dementia (n = 30), frontotemporal dementia spectrum (FTD) (n = 80), and dementia with Lewy bodies (n = 35). Results: NPH patients showed significantly lower levels of Aβ42 (p = 0.024) and Aβ40 (p = 0.006) than controls, whereas the concentration of both t-tau and p-tau were similar between the two groups. All disease groups showed a significant increase in NfL levels (p < 0.001), with FTD patients demonstrating the highest values. Within the NPH group, NfL levels did not significantly differ between those with or without vascular and/or AD comorbidities. Since the values of Aβ42/ Aβ40 ratio were significantly reduced only in AD cases, the Aβ42/Aβ40 ratio demonstrated a higher diagnostic accuracy than Aβ42 alone (AUC 0.955 ± 0.018 and 0.858 ± 0.035, respectively) in the discrimination between NPH and AD. Conclusion: CSF levels of Aβ peptides and NfL may reflect two distinct pathophysiological mechanisms in NPH, namely the down-regulation of β-amyloid production and the degeneration of periventricular myelinated axons. Our data also underline the clinical value of Aβ42/Aβ40 in the differential diagnosis between NPH and AD.
Introduction: Increase in optic nerve sheath diameter (ONSD) in trans-orbital sonography has been proven to be able to detect elevated intracranial pressure (ICP) in different scenarios, but little is known of conditions without increased ICP. From 2015 patients with a suspect of idiopathic Normal Pressure Hydrocephalus (iNPH) were prospectively evaluated by a multidisciplinary team at the Institute of Neurological Sciences of Bologna. In selected patients, we included the measurement of ONSD with MRI and ultrasound (US) technique, to identify a possible new follow-up modality after high volume spinal tap test (TT) and after ventriculo-peritoneal shunt (VPS). Methods: An experienced neuroradiologist measured the vertical and horizontal diameters of optic nerve sheath (ONS) bilaterally, calculated on a plane orthogonal to the optic nerve, in a three dimensional T2 weighted MRI sequence. After an informed consent of each patient was obtained, in a cohort of Fluids Barriers CNS 2018, 15(Suppl 2):35 terminus of a distal peritoneal catheter using 2-0 suture to prevent reflux and allow sub-zero pressure drainage via the distal slit valves, facilitating siphoning; (2) Division and attachment of the ventricular aspect of a ventricular catheter to a convertible reservoir; (3) Division of the peritoneal aspect of a convertible reservoir and connection to the proximal end of the peritoneal catheter using suture. Results: Our patient initially presented to us after spontaneous subarachnoid hemorrhage associated with hemangioblastomatosis. He was treated with a ventriculoperitoneal shunt and underwent resection of a Meckel's cave hemangioblastoma and whole brain irradiation. One month later, he presented to us again with worsening headaches and persistent hydrocephalus despite shunt interrogations and revisions revealing no malfunction. Ventriculostomy drainage at negative-pressure was required for resolution of symptoms and ventriculomegaly, leading us to a diagnosis of LPH. After insertion of the improvised negative-pressure shunt there has been maintained resolution for over 1 year. Conclusions: LPH can be successfully treated using a simple improvised negative-pressure ventriculoperitoneal shunt. Informed consent has been obtained from the patient. Introduction: Intravoxel incoherent motion (IVIM) is a technique which can measure diffusion of water molecules and blood perfusion volume in microvasculature, therefore can provide both information of blood flow and blood perfusion. Aim of the study was to compare IVIM-MRI derived parameters: slow diffusion coefficient (D), fast diffusion coefficient (D*) and perfusion fraction (f) among a group of patients affected by probable iNPH. Methods: A total of 12 patients with diagnosis of probable iNPH were submitted to a diagnostic MR examination including an IVIM multi b-value sequence on a 3.0 Tesla-Magnet before and immediately after a lumbar-infusion and a Tap-test. Seven subjects were positive to invasive tests (group 1) while five patients were negative (group 2). For each patient the IVIM multi b-value sequence was post-processed using a specific software (Olea Sphere, France). IVIM derived parameters D, D* and f were calculated from 20 different regions of interest (ROIs) that were placed in the basal ganglia region and in the periventricular-white-matter (PVWM) of both hemispheres. Comparison between D, D* and f distribution among the two different groups of patients and correlation with invasive test results was performed with non-parametric-Wilcoxon-Mann-Whitney-test. Results: Relevant differences although not yet significant were found in the distribution of D, D* and f in the basal ganglia region or in the PVWM among the two different groups of patients, both D* and f were lower in group 1 patients especially at basal evaluation. Conclusions: IVIM-MRI could be a promising non-invasive technique in the evaluation of patients affected by probable iNPH. Introduction: Phase Contrast sequence (PCMRI) is the unique technique to quantify in around 1-min blood and CSF in the cranium to provide a mean flow curve of the cardiac cycle. Using new MRI development (EPI-PCMRI) it is now possible to quantify flows curve in real-time! What is the EPI-PCMRI contribution to investigate cerebral blood flow? Methods: Cerebral blood flows of five hydrocephalus patients were investigated in a 3T MRI. Internal carotid, vertebral and jugular vein vessels were explored by PCMRI with a good spatial resolution, to acquire only one mean curve accurate flow of 32 points from the 2 min acquisition time. Epi-PCMRI was also done with a low spatial resolution but able to quantify directly flow every 0.1 s during 1 min. A dedicated post processing software quickly calculated all the key flow parameters. A spearman correlation test evaluated EPI-PCMRI in front of PCMRI. Frequential analysis evaluated respiratory component in the flows. Results: Blood flows were calculated in nine internal carotids arteries, six vertebral arteries and four jugular veins by the two techniques. The spearman correlation was pretty good (r = 0.94, p < 10-5). the Blood flow shape changed. Respiratory frequency amplitude was present in all the flows, its impact was more important in the jugular flows. Conclusions: By combining flow accuracy and high spatial resolution from PCMRI with the high temporal of EPI-PCMRI we have shown that arterial and venous blood flow change due to breathing. These new investigations applied to CSF should help to better understand the hydrocephalus mechanism.
Introduction: Urinary symptoms in idiopathic normal pressure hydrocephalus (iNPH) has received little attention from the scientific and medical community. Materials and methods: A literature review of MedLine publications concerning urinary incontinence in iNPH was conducted, including prospective and retrospective studies as well as previous reviews. Results: Pathophysiology: Urinary symptoms in iNPH are mainly represented by overactive bladder, explained by a dysregulation of the spino-bulbo-spinal micturition reflex, in relation with a right frontal hypoperfusion. Isolated overactive bladder is more frequent (64%) than urinary incontinence (57%). Detrusor overactivity is seen in 95.2% of the cases. Assessment: The International Society for Hydrocephalus and CSF Disorders recommends to realize a micturition calendar and a bladder ultrasonography to measure post void residual to all patients presenting iNPH. The interest of urodynamics analysis in this situation is considered low. Efficacy of surgical treatment: shunt surgery is efficient on urinary symptoms in 61.5% of the patients. This recovery could result from an increased perfusion and a functional restoration of the mid-cingulate, that normally inhibits the micturition reflex. Overall, this clinical improvement is considered higher than on the cognition aspect but lower than on gait disturbance. Medical options, added or not to surgery, they include specific anticholinergic drugs that do not pass through the blood-brain barrier, transcutaneous electrical nerve stimulation and sacral neuromodulation. Conclusion: This article highlights the importance of a harmonization of neuro-urological practices in the pre-therapeutic and follow-up evaluations of patients suffering from iNPH. Introduction: Effective pharmaceutical treatments for hydrocephalus represent a serious unmet need. Drug development has been hampered by a dearth of in vitro and in vivo models that accurately reflect the physiological disease presentation. Methods: We characterized a genetic rat model which is homologous to Meckel Gruber Syndrome III. The homozygous animals (TMEM67−/−) have severe hydrocephalus and survive to post-natal day 18-20. The heterozygous animals (TMEM67±) have a mild hydrocephalus present before weaning but not manifested as overt disease until 1 year of age. Animal studies are complemented by electrophysiological studies of ion transport in a choroid plexus epithelial cell line. Results: In cultured cells an agonist of the transient receptor potential, vanilloid 4 (TRPV4) cation channel (GSK1016790A) stimulates a transepithelial ion flux consistent with cation secretion. The ion flux is undoubtedly coupled to secondary water secretion. Agonist-stimulated ion flux is blocked by pre-treatment with either of two TRPV4 antagonists, RN1734 or HC06747. In the homozygous animals, treatment with RN1734, 4 mg/kg BW i.p. daily from day 7 to day 15 substantially reduces the degree of hydrocephalus measured by MRI quantification of cerebral ventricular volume. Conclusions: TRPV4, a channel that can be activated by inflammatory mediators or changes in pressure or osmotic balance, may be a hub protein in the choroid plexus epithelia allowing the cells to respond to various stimuli. Regulation of this transporter may be an important target for the development of pharmaceutical agents to treat all forms of hydrocephalus. Fluids Barriers CNS 2018, 15(Suppl 2):35 Methods: In our in vitro IVH model we assayed ADAM10's role in IVH-mediated VZ disruption by quantifying ADAM10-dependent cleavage of N-cadherin. Western Blot and immunohistochemistry was performed after three different treatments of mouse VZ cell cultures with; (1) Vehicle control (DMSO); (2) Syngeneic blood and (3) GI 254023X (inhibitor of ADAM 10) + syngeneic blood. N-cadherin immunohistochemistry on human IVH/PHH post-mortem brain specimens was performed to co-validate the in vitro experiments. Results: In vitro blood treatment was associated with significant disruption of N-cadherin expression (p < 0.05), reduction in the percentage of multiciliated ependymal cells, and increased astroglial activation (p < 0.01) when compared with controls. ADAM10 inhibition preserved the cytological structure of the blood-treated cells; i.e. N-cadherin expression was similar to controls. Examination of the human IVH/PHH tissue showed similar N-cadherin based VZ perturbations as was observed in vitro. Conclusions: These findings suggest that IVH causes VZ disruption via ADAM10-induced impairment of N-cadherin-based junctions and ADAM10 inhibition mitigates this cytopathological condition. Introduction: It has been suggested that intracranial dynamics play an important role in the pathogenesis of normal pressure hydrocephalus (NPH). To investigate this further, a real-time monitoring of dynamic ventricular enlargement with a bioimpedance sensor has been proposed. The relative conductivity difference between brain parenchyma and cerebrospinal fluid (CSF) makes it possible. A testbench is therefore necessary to perform in vitro validation of the bioimpedance prototypes. Methods: The electrical properties of various silicone gels to be implemented as brain phantoms have been tested. Initial impedance measurements have been performed on five cylindrical silicone gel probes with an artificial CSF-filled hollow cavity (saline water, conductivity = 17.9 mS/cm) of discrete volumes [20, 40, 60, 80, 100 mL] representing a single ventricle. Using an Agilent LCR meter E4980, a 250 uA current with a 50 kHz frequency is injected through a pair of ring electrodes integrated onto the surface of a drainage catheter. The electrical impedance is measured between the inner electrodes. Results: The measured impedance decreases linearly with increasing volume (58.8 O for a 20 mL ventricular cavity to 10.3 O for 100 mL). This trend is expected as observed in a finite element model (FEM) study. Conclusions: Initial static measurements of discrete volumes show that the validation of a bioimpedance sensor for ventricular size might be possible on a test-bench. Current work is the extension of the setup to an electronically controlled Hardware-in-the-Loop model which portrays intracranial dynamics, for which a Matlab/Simulink model of pulsatile CSF with cardiovascular coupling is available. Introduction: Ventricular dilation in severe acquired brain injured patients (SABIPs) remains a great challenge. Despite numerous efforts, it remains difficult to achieve a neuroradiological and clinical diagnosis of hydrocephalus; furthermore, these patients belong to a fragile group, with high comorbidities and risks. It is therefore difficult to estimate the impact of shunt surgery. Methods: We retrospectively reviewed 81 SABIPs admitted to our unit during a 9-year period (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017) and managed in partnership with neurosurgeons of the Institute for Neurological Sciences of Bologna, analyzing the impact of hydrocephalus treatment. All patients underwent shunt surgery. The diagnosis of hydrocephalus was based on serial CT examinations and on clinical characteristics (clinical stagnation with or without hydrocephalus symptoms, cognitive improvement after lumbar puncture). We assessed outcome improvement with LCF (Levels of Cognitive Functioning) and DRS (Disability Rating Scale) scales. Results: Patients showed an overall improvement after shunting. Hemorrhagic patients had shorter LOS (length of stay), early shunt implantation and higher LCF score. 12 patients had complications after shunt implantation; 9 out of 12 had severe complications and had worse outcomes in LCF scores. Fixed valves had a significant higher relative risk ratio (4.16 p < 0.05) of severe complications. A significant correlation with LOS was found: the longer the hospitalization, the worse the DRS score. Conclusions: We investigated hydrocephalus SABIPs who presented arrested or slow recovery or neurological and/or cognitive deterioration. A thorough multidisciplinary approach is critical for shunt surgery indication. We could observe good recovery following shunting even in this extremely fragile group of patients. Introduction: Existing shunts suffer from complications including mechanical malfunctions, obstructions, infections, blockage, breakage, overdrainage, and/or underdrainage. Some of these complications may be attributed to the shunts' physically large and lengthy course making them susceptible to external forces, siphoning effects, and risks of infection. Additionally, intracranial catheters artificially traverse the brain, and drain the ventricle rather than subarachnoid space. Methods: A MEMS (Micro-Electro-Mechanical-System) based hydrogel check valve offers an alternative treatment approach targeting restoration of near natural CSF dynamics. Reconstruction of this route may potentially offer greater reliability and safety to current failure-prone shunts. The valve, being made of hydrogel, was manufactured via MEMS technology, which aims to regulate the CSF flow between the sub-arachnoid space and the superior sagittal sinus, in essence substituting for the obstructed arachnoid granulations. Results: The benchtop measurements demonstrate the realization of targeted cracking pressures of 20-200 mmH 2 O and operation at − 800-600 mmH 2 O without observable degradation or reverse flow leakage, < − 10 μL/min. Hydrodynamic measurements and over-time tests under physically relevant conditions further demonstrate the valve's operationally-reproducible properties. Conclusions: The MEMS-based valve has been shown to operate with targeted hydro-static and dynamic specifications as a stand-alone passive unit for hydrocephalus treatment. Results of this work indicate the valve's potential application in treating hydrocephalus in a safer and more robust manner than current treatment methods. Future work to ensure its reliability and ability to drain CSF in sentient brains will entail in vivo testing in animal models.

O22 MEMS (Micro-Electro-Mechanical-System) based passive hydrogel valve for hydrocephalus treatment
Introduction: CSF diversion with external ventricular (EVD) or lumbar drain (LD) is common following aneurysmal subarachnoid haemorrhage (aSAH). At this single centre, invasive tri-modal monitoring of ICP, temperature and direct brain tissue oxygen tension (PbtO2) is used to guide management for delayed cerebral ischaemia. In this study we observe the immediate effect of CSF drainage on PbtO2. Methods: Inclusion: Patients with aSAH who underwent over 24-h of multi-modal PbtO2, temperature and intracranial pressure (ICP) monitoring via a Raumedic NEUROVENT-PTO ® probe, during insertion of either EVD or LD. PbtO2 values are presented as mmHg (mean ± SD). Results: Seven patients underwent CSF diversion (2 LD and 4 EVD) inserted, with simultaneous tri-modal monitoring. LD or EVD insertion resulted in a significant decrease in ICP of 11.3 ± 2.75 mmHg over the first 5 min (p = 0.034). A simultaneous mean increase of 7.6 ± 2.94 mmHg in PbtO2 was observed over the same time period (p = 0.002). In all seven patients the global reduction in ICP and increase in PbtO2 was sustained. The greatest increase was observed in the two patients who underwent LD, whom had PbtO 2 increases of 17 mmHg and 16 mmHg respectively. Conclusions: CSF diversion following acute aSAH can reduce ICP and simultaneously increase PbtO2, potentially addressing both hydrocephalus and delayed cerebral ischemia. Further research into the effect of caudal vs. cranial diversion may demonstrate a superior modality. Introduction: Slit ventricles can be a challenging target during shunt catheter insertion. Traditionally, the frontal approach has been considered optimial. At this centre, routine use of electromagnetic (EM) stereotatic guidance (Stealth ™ , Medtronic) has enabled a parieto-occipital burr hole approach to the frontal horns. We compare shunt placement and revisions required for patients with slit ventricles who had shunts inserted via a parieto-occipital (P-O) approach vs. frontal shunt. Methods: Retrospective cohort of patients with slit ventricles and a ventricular shunt inserted using EM guidance between 2012 and 2018. Slit-like ventricles were defined as the widest point of the lateral ventricle < 3 mm. Outcome measures included placement accuracy and survival using Kaplan-Meier curve. Optimal final catheter tip location was considered to be the frontal horn of the ipsilateral lateral ventricle. Results: 82 patients (77F:5M) aged 34.9 ± 10.8 years (mean ± SD) had ventricular shunts inserted for IIH (n = 63), chiari/syrinx (n = 8), congenital (n = 10), pseudomeningocoele (n = 1). Of the those indentified, 35 had primary P-O shunts and 46 had frontal shunts. Overall, 94% of cases had the catheter tip sitting in the frontal horn. The P-O approach was just as accurate as the frontal approach. Eight P-O shunts and nine frontal shunts required revision over a 60-month periods. There was no significant different in shunt survival between the two approaches (p = 0.99). Conclusions: EM guided placement has enabled the P-O approach to be as safe and with equivalent survival to frontal approach. The accuracy of shunt placement between the two approaches was equivocal. Introduction: AQP4 present in ependymal cells, glia limiting membranes and pericapillary astrocytes foot processes; and AQP1 expressed in choroid plexus epithelial cells are believed to play an important role in the cerebrospinal fluid (CSF) production and may be involved in the pathophysiology of age-dependent hydrocephalus. The finding that brain AQPs expression is regulated by low oxygen tension and ageing led us to analyze how hypoxia and elevated levels of cerebral AQPs may increase the CSF production that could be associated with the hydrocephalus onset.

Methods:
Here we have explored in young and aged mice exposed to hypoxia whether expression levels of AQP4 and AQP1 were affected. Choroid plexus, striatum, cortex and ependymal tissue were analyzed separately both for mRNA and protein levels. Moreover, parameters such as intraventricular pressure (IVP), outflow rate of CSF and ventricular compliance measured by intra ventricular recordings in live animals, as well as total ventricular volume, measured by resonance magnetic images (RMI), were estimated. Experiments were done using WT, AQP4 −/− and AQP1 −/− mice. Results: Our data demonstrate that hypoxia participates in the origin of hydrocephalus by a process that depends on AQP4 as a main route for CSF movement. Significant increases in AQP4 expression that occur along animal's aging contribute to produce a considerably worse hydrocephalus situation related with hypoxic events, with impairment of the cognitive function.

Conclusions:
We propose that physiological events and/or pathological situations coursing with brain hypoxia/ischemia, along live span would contribute to development of chronic adult hydrocephalus.
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 versus programmable). Overall, gait improvement was observed in 75% of patients, cognitive function improvement in more than 60%, and incontinence improvement in 55%. Adjustable valves were associated with a reduction in revisions (12% vs 32%) and subdural collections (9% vs 22%) when 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.
There was also a significant change in the CC-splenium area (p = 0.01) between HI and iNPH (postop). Conclusion: Significant ADC-changes in the frontal periventricular area between HI and patients indicate possible disease-related pathology. The almost significant changes pre-postop suggest reversibility of this pathology. This could be of interest to study further with the aim to improving diagnostics in iNPH. Patients undergoing venous stenting responded well to treatment with 6/6 reporting an improvement in headache symptoms; in severity and/or duration affected. 4/8 of patients undergoing VP shunting noticed an improvement in headaches, as did the patient who underwent an LP shunt. These differences were not statistically significant. VP shunting was associated with higher rates of further intervention than venous stenting, during mean follow up of 29.6 ± 19.4 months (mean ± SD). Conclusions: Patients with IIH in the absence of papilloedema may benefit from surgical interventions and report an improvement in their symptoms. Venous stenting in particular was associated with improvements in symptoms and few further interventions needed. We included a total of 106 patients who met the inclusion criteria. 56 (58%) women and 50 (42%) men with an average age of 58.3 years. The dysfunction of the system was presented in 9 (8.5%) patients. 7 of these during the first year, all of them requiring reintervention. Infection was identified in 8 (7.6%) of the patients. 57.5% of patients completed at least 1 year of follow-up. Conclusions: Ventriculoatrial shunt is a valid option in the management of hydrocephalus, in our experience is a safe, reproducible and effective technique. We consider that a DVA shunt is more physiological than traditional technic and less shunt malfunction in the follow up. Introduction: Ventricular shunt infections pose a threat to patients with cerebrospinal fluid (CSF) disorders who rely on long-term functioning of implanted flow diversion hardware. To better understand mechanisms of shunt infection and prevention we adapted an existing canine model of ventricular shunting to induce ventriculitis. This model was used to evaluate a novel method of treating shunt catheters with a polymer-based antibiotic delivery system. Methods: Bilateral shunt catheters were introduced into the lateral ventricles of three dogs and then immediately inoculated with methicillin-susceptible Staphylococcus aureus (MSSA). Two animals were given catheters pretreated with a modified polymer that contained vancomycin-loaded chemical "pockets". The third animal's catheters were coated with a similar polymer yet without vancomycin. Subjects were closely monitored and, upon clinical decline, high-resolution MRI images were obtained, catheters explanted, and brain tissue harvested for histological analysis. Recovered catheters underwent microbiological culturing and scanning electron microscopy. Results: All animals underwent successful ventricular catheter implantation bilaterally without immediate neurological sequelae. By day 10 all animals began clinical deterioration with MRI evidence of ventriculitis and cerebral edema. Growth of MSSA following culture of sonicated catheters was limited to only one of the two implanted catheters among each of the experimental subjects, while both catheters in the control animal produced positive growth. Conclusion: This demonstrates a reliable canine ventriculitis model that can be verified clinically and radiologically, and evaluated microbiologically and histologically. This model has utility in the evaluation of future shunt catheter modifications including the polymer-based antibiotic-coated shunts described. Introduction: Periventricular white matter (PVWM) disruption is a dominant pathology in post-hemorrhagic hydrocephalus (PHH), and accounts for long-term morbidity. Diffusion Tensor Imaging (DTI), which is frequently used to assess PVWM integrity, is unable to differentiate complex cellular pathologies such as edema, inflammation and axonal loss. We used Diffusion Basis Spectrum Imaging (DBSI), which has been validated to be more effective for assessing complex WM pathologies in multiple sclerosis, spinal cord injury and brain tumors to address the PVWM pathology associated with PHH. Methods: PHH was induced in 20-day-old ferrets by intraventricular injection of autologous blood (n = 7). Controls (n = 6) received intraventricular PBS. About 50-days-old, their brains were harvested and fixed in 4% PFA, then scanned ex vivo in a Varian ® 4.7T MRI for T2-weighted, multi-echo, spin-echo, and diffusion weighted sequences in 99 directions (TR 3000 ms, TE 60 ms, maxb-value = 3000 s/mm 2 ). Regions of Interest and voxel intensities for corpus callosum (CC), anterior and (ALIC) posterior (PLIC) limbs of the internal capsule were statistically analyzed using Python v2.7 and R package v3.4.1 scripts. Immunohistochemistry was done to assess PVWM.

Results:
The PHH group had 68% (p < 0.005) proportional increase in hindered fraction: 120% (p < 0.005) and 51% (p < 0.005) in the CC and ALIC, respectively. CC and ALIC demonstrated proportionally decreased fiber density by 7% (p < 0.05) and 10% (p < 0.05), respectively. ALIC demonstrated axonal injury with decreased axial diffusivity of 8% (p < 0.05). While similar trends were observed in the PLIC, none were statistically significant. Immunohistochemistry demonstrated significantly higher PVWM in PHH than in controls. Discussion: DBSI demonstrated marked edema, neuroinflammation, axonal injury and axonal loss in the PVWM of the PHH cohort, as was seen on immunohistochemistry. DBSI is a versatile tool for differentiating and quantifying the different components of WM disruption, and can be used as a novel non-invasive biomarker for PVWM integrity in PHH.

O47
Gait analysis in idiopathic normal pressure hydrocephalus on timed-up-and-go-test using free smartphone application Masatsune Ishikawa 1,2 , ShigekiYamada 2,3 , Kazuo Yamamoto 3, Yukihio Aoyagi 4 , Rokuwa Villa Ilios 1 Fluids Barriers CNS 2018, 15(Suppl 2):35 assessment of quantitative measurement on six components of timedup-and-go test (TUG) was examined in iNPH using the free iPhone application (Senior Quality) (iTUG). Methods: Thirty-two patients with probable iNPH including 19 shunt responsive patients and 87 age-matched control subjects were enrolled. TUG was done twice. Data were automatically collected during iTUG, and the time for the six components were automatically segmented (Stand, Go, Turn1, Come, Turn2 and Sit). The item cluster analysis (ICLUST) was performed to explore underlying structures of iTUG.
Results: In the age-matched control, some components in the second session were shorter than the first one. There were no statistical differences in the NPH. The ICLUST revealed that pairs of the Go and Come, and the Turn1 and Turn2, were two major clusters in the control. This pattern was deranged in the NPH and a pair of the Turn1 and Come became the first cluster. At the tap test, a pair of the Go and Turn2 became the first cluster. After the shunt surgery, the pattern as in the control was regained.

Conclusions:
The iTUG enables quantitative assessment of six components on TUG. They showed that derangement of the relationship among the components of TUG in iNPH. This derangement was regained after the surgical treatment. This provides further insight into the patho-physiology of gait disturbances in various disorders.

O48 A panel of CSF biomarkers can distinguish between idiopathic normal pressure hydrocephalus and subcortical ischemic vascular dementia-pathophysiological implications?
Anne Introduction: Patients with subcortical ischemic vascular dementia (SIVaD) exhibit a similar subcortical cognitive impairment as patients with iNPH and can show similar gait, balance and urinary dysfunction. Further, white matter lesions on MRI and enlargement of the brain ventricular system may be present, probably due to brain atrophy. Hence, distinguishing between iNPH and SIVaD, which has a large impact on treatment options, constitutes a major clinical challenge. We aimed at comparatively examine the CSF biomarker expression in a group of iNPH-patients, one group of SIVaD patients and healthy individuals (HI) to enhance the differential diagnostic accuracy.

Methods:
The study included 52 patients with iNPH (aged 72 ± 7 years, 29 men and 23 women). 17 SIVaD (aged 71 ± 7 years, 5/12) and 28 HI (68 ± 4, 18/9). We analyzed a panel of APP-derived proteins, i.e. Aβ38, Aβ40, Aβ42 and soluble forms sAPPα, sAPPβ, as well as markers of white matter damage NFL, GFAP and MBP. Results: Patients with iNPH exhibited lowered levels of APP-derived proteins in comparison with SVD. Both groups had lowered levels in comparison with HI. NFL, GFAP and MBP was elevated in iNPH and SVD compared to HI. NFL was higher in SIVaD and levels of MBP and GFAP higher in iNPH.

Conclusions:
The biochemical changes in CSF of patients with iNPH and SIVaD seems to share common features but the levels could be used to differentiate between the conditions. This might implicate common pathological mechanisms in iNPH and SIVaD. This is a retrospective review of 100 consecutive lumbar infusion studies in patients being evaluated for the surgical treatment of symptoms consistent with normal pressure hydrocephalus. Initial evaluations of these patients consisted of a clinical assessment along with an abbreviated scoring system to provide a baseline measurement of symptoms falling within the NPH triad. Patients and their families were then offered further studies including bolus lumbar infusion studies as described by Marmarou, along with a family assessed CSF volume tap test, and other studies as indicated by the results of the LP studies. Follow up studies, including scoring, will be presented and correlated with preop measurements. While we are aware of the limitations of lumbar infusion studies and family-assessed CSF tap tests, we believe that they can be performed safely and efficiently in an outpatient setting and do provide additional valuable data that is useful in determining which of these patients will be successfully treated with CSF shunt surgery.

O50
Towards iNPH multimorbidity score system: do we need to exclude patients from surgical treatment? Linda D' Antona 1 , Sandra Blamey 2 , Simon D Introduction: Frail patients are known to have poor perioperative outcome. We hypothesized that our modified frailty index (mFI) may be a predictor of morbidity and mortality following shunt surgery in idiopathic normal pressure hydrocephalus (iNPH).
Methods: A retrospective cohort study was conducted among patients diagnosed with probable iNPH according to the 2004 Guideline for iNPH, who underwent shunt surgery, and were followed 3 years postoperatively between 2005 and 2014. Our mFI, ranging from 0 to 1, was calculated as the proportion of 15 possible risk factors (including dementia, movement disorder, neoplasm and depression). We examined the associations among mFI, Charlson comorbidity index, and 3-year morbidity, mortality, neurological and medical complications by mRS and iNPH grading scale using univariate and multivariable analyses and compared the index to established risk stratification methods.
Results: A total of 82 patients were identified. Morbidity, mortality and severe medical complications increased incrementally with increasing level of frailty. Severe neurological complications were highest in those with low frailty. Multivariate logistic regression analysis showed that increased frailty increased the odds of all adverse outcome, including neurological complication. The mFI enhanced the ability to predict 3-years outcomes beyond available indices and was a reliable predictor of neurological complications.

Conclusions:
This index may be a useful preoperative risk assessment method with implications for shared decision-making, perioperative planning, and risk adjusted outcomes measurement in iNPH patients. Introduction: Cerebrospinal fluid (CSF) movement is not a unidirectional circulation, but the permanent rhythmic systolic-diastolic pulsation of CSF volume. That kind of CSF movement represents the main force of substances distribution along the CSF system, and from CSF via peri-and paravascular routes into the central nervous system (CNS) parenchyma interstitial space. Methods: Distribution of various substances (radioactive water, organic acids, inulin etc.) has been investigated in CSF and interstitial space after their application into different CSF compartments in freely moving large animals (dogs and cats).

Results:
Our results suggest that the distribution of substances along the CSF system is observed in all directions (in the direction of imagined circulation from brain ventricles to subarachnoid space as well as in the opposite direction), and depends on the resident time of the substance, whereby longer resident time means longer path of distribution. Quick disappearance of organic anions from central CSF compartments, and very low concentrations of the tested substances in "peripheral" CSF compartments were observed in control condition. When active transport was blocked in animals by probenecid, the concentrations of monitored substances in CNS tissue and in "peripheral" CSF compartments were significantly increased in comparison to the control group. Conclusions: Obtained results suggest that transport at the capillary endothelium has the most important role in CNS homeostasis and in removal of potentially toxic metabolites from the CNS tissue into blood circulation, and not, as was previously conceived, the unidirectional CSF circulation and its absorption through the dural sinuses. Results: Interim data of the first 88 consecutive investigations show that there was a small but statistically significant increase in iNPH Radscale score, comparing baseline and follow up. The association between the symptom score at baseline and the difference in radiological score was nonsignificant. Conclusion: Radiological features of iNPH gently progress over time in elderly, independent symptom severity at baseline. The imaging findings need to be correlated to symptom progression to define its clinical relevance. Background: The presence of third ventricle deformation, otherwise known as 'bowing' , is an indicator of obstructive hydrocephalus and also the success of endoscopic third ventriculostomy (ETV). The aim of this study is to determine bowing's influence in ETV success in both pediatric and adult patients and is the first study to evaluate this relationship in patients younger than 6 months old. Method: 157 ETVs were performed on 157 patients with obstructive hydrocephalus between January 2008 and December 2016. The presence and extent of third ventricle floor bowing was determined by preoperative MR imaging. Only patients who had been followed up for at least 3 months or those in which it was possible to determine third ventricle bowing were included in the study. 135 patients (70 adults and 65 children of which 38 were younger than 6 months old) fulfilled the induction criteria. Additional factors were evaluated for their effects on ETV success. Results: In patients older than 6 months, The ETV success rate was 91% in those presenting with bowing and 47.6% in those without. Among patients younger than 6 months old, ETV was successful in 37% of those with bowing and 36.4% of those without. We confirmed that the presence of bowing strongly indicates ETV success in patients older than 6 months (p < 0.0005), including those of 7 months of age and older (p 0.001). However, this relationship was not confirmed in pediatric patients up to 6 months old (p 1.000). Additionally, there is a greater risk of failure among this group (p 0.002). The extent of bowing, as opposed to its presence, does not influence ETV success (p 0.559).

O54
Bowing correction strongly correlates with ETV success (p < 0.0005), being observed in 96% of patients who successfully underwent ETV. While bowing more frequently occurs in severely premature infants (p 0.049), prematurity in itself does not affect ETV outcome (p 0.262). We confirmed the relationship between intraventricular hemorrhage and ETV failure (p < 0.0005) but among patients older than 6 months, ETV success was not found to be affected by the etiology of hydrocephalus (p 0.527), clinical problems (p 0.115) or clinical duration (0.546). 90% of ETV failures occurred within 12 weeks post operation whereas just 3.4% of ETV failures occurred more than 1 year post operation; ETV failure is significantly more likely in the first 12 postoperative weeks (p < 0.0005).

Conclusions:
Our study is the largest published discussing bowing as an indicator of ETV success and is to date the only one to investigate this relationship in patients younger than 6 months old. While we confirmed significant correlation between bowing and ETV success in both adults and children over 6 months of age, this relationship was not determined in those younger than 6 months and therefore we do not recommend bowing as one of the ETV indication criteria for this patient cohort. Results: Baseline ICP in obstructed shunts was significantly above shunt operating pressure. CSF outflow resistance and ∆ICP plateau were significantly elevated (n = 0.001) in obstructed shunts, with cutoff thresholds being 5.9 mmHg/mL/min and 8.5 mmHg, respectively. All obstructed shunts were revised. In about 50% of cases the ventricular size decreased postoperatively, with 50% of patients showing an improvement on clinical investigation or according to parent's reports. Conclusions: SIS is a feasible, elegant and radiation free technique for quantitative shunt assessment to rule out or prove shunt malfunction. Dedicated software containing shunt hydrodynamic characteristics is necessary and small children will need short term sedation. Due to his clinical and inherent economic advantages, we postulate that SIS should become routine in neurosurgery units. We have previously investigated the negative predictive value of shunt infusion studies and their role in avoiding revisions of properly functioning shunts. With shunt infusion studies we can accurately detect blockage, over/underdrainage or normal function of shunts. We hypothesised that the positive predictive value of shunt infusion studies in detecting shunt obstruction is also high. Methods: We identified a cohort of patients who had their shunts tested right before revision surgery and compare the two findings. A first researcher collected the results of infusion tests showing blockage between January 2013 and December 2017. A second, independent researcher collected the results from the revision of the shunt. The second researcher was blinded to the infusion results. The findings were compared and contrasted. Results: A total of 47 patients (29female:18male) during this time period had undergone an infusion study confirming blockage with immediate revision afterwards and had a clear intraoperative note describing the patency of all the shunt elements. In 45 of these, the intraoperative finding was identical to the blockage detected during infusion. The two patients in whom there was a disagreement were scrutinised individually and the dispute could be identified in limitations in the intraoperative notes and clinical opinion. 46/47 patients also had confirmation that the other end of the shunt was patent. These correspond to 96% 98% positive predictive value for shunt obstruction and shunt patency identification respectively. Conclusions: Infusion studies are an objective, accurate method that can be used to identify shunt blockage and/or confirm shunt patency at their occurrence, as well as the exact site of the blockage (proximally or distally to the needle insertion). Introduction: Currently, non-invasive methods to evaluate the shunt effect at different shunt valve settings in hydrocephalus is lacking. A possible future method to evaluate shunt function could be volumetric measurement of brain ventricles. This study aimed to examine whether the ventricular volume changes in response to shunt treatment, and at different setting of the shunt valve. Methods: Consecutive patients undergoing shunt-surgery were invited to participate in the study. Exclusion criteria were severe cognitive impairment (Mini Mental State Examination < 15). Using MRI volumetry (SyntheticMR ® ) the effects of three different settings of strata shunts on ventricular volume were examined: low (1.0), intermediate (1.5) and high (2.5) valve setting. Each setting was tried in all patients, beginning with intermediate followed by a randomized and blinded order of low and high. MRI was performed 1 month after each shunt adjustment.

Results:
The four patients who have so far completed the study (men = 4, mean age = 78, SD = 5.5) showed a significant decrease in ventricular volume between preoperative and first as well as third post-operative MRI measurements with mean 139.8/125.5/119.8 mL, respectively (SD = 21.67/21.71/15.82, p < 0.05). Individual changes in volume in relation to different valve settings will be presented.

Conclusions:
The ventricular volume changed significantly after shunt surgery. Volumetry seems to be a promising future method for shunt function evaluation. Introduction: Current assessments of the progression of infant hydrocephalus and its treatment are crude, with little power for predicting neurodevelopmental impairment (NDI). We developed novel frequency-domain near-infrared (FDNIRS) and diffuse correlation spectroscopy (DCS) for quantitative measurement of cerebral blood flow (CBF) and oxygen metabolism (CMRO 2 ) non-invasively, at the bedside, in both the developed and developing worlds. We aim to test whether CBF and CMRO 2 can be new indicators of cerebral health for guiding hydrocephalus treatment and NDI prognosis. Methods: We are investigating post-hemorrhagic hydrocephalus (PHH) and spinal bifida at Boston Children's Hospital (BCH), and postinfectious hydrocephalus (PIH) infants at CURE Children's Hospital Uganda (CCHU). Primary study outcomes are CBF and CMRO 2 with secondary outcomes of cerebral hemoglobin concentrations, treatment outcomes (success or failed within 6 months), and brain growth in 6-month post-operative brain imaging scans. Results: In the BCH cohort (N = 17), we found successful hydrocephalus treatment immediately increases CBF and restores CMRO 2 , whereas there was no change after unsuccessful treatment. The CCHU cohort (N = 33) shows primary infectious injuries in PIH cause more severe damage to brain structure than in PHH. Decreases in brain optical scattering immediately post-surgery is highly predictive for treatment Fluids Barriers CNS 2018, 15(Suppl 2):35 failure to occur within 6 months. Most importantly, brain regions with higher CMRO 2 had better recovery of brain structure by CT scan 6 months after treatment. Conclusions: We have demonstrated our measurements of cerebral physiology are sensitive to the state of hydrocephalus and have potential as objective quantitative diagnostics for both high and low resource settings. Introduction: Diagnosis, treatment and follow-up of cerebrospinal fluid (CSF) disorders are often controversial and challenging. Ideally, they should be managed in dedicated expert centres and follow consensual guidelines. However, to date, expert centres and guidelines are scarce. In this collaborative work, we wanted to identify challenges in building a dedicated centre for CSF disorders. Our intention is to share our experience, in order to promote such project and rise awareness of the experts community on the compelling needs for producing consensual, updated and unified guidelines to manage CSF disorders.

Materials and methods:
The study consisted in three steps: (I) Listing the difficulties we encountered when starting to create a centre dedicated to CSF disorders; (II) Reviewing published clinical guidelines; (III) Visiting renowned European expert centres to evaluate their structural organization. Results: (I) When starting to create our centre for CSF disorders, we encountered difficulties in: motivating busy colleagues to create a multidisciplinary team, dealing with patients hosting in a financially stressed system, getting access to neuropsychological assessment, standardizing patients evaluation, proving medico-financial interest to the administration of our institution. (II) Three different clinical guidelines have been published concerning normal pressure hydrocephalus (NPH). To date, no guidelines have been published concerning other CSF disorders. (III) We described the modalities we adopted from the different European expert centres we visited. Conclusions: Creating an expert centre dedicated to CSF disorders is probably valuable but remains challenging.
Introduction: Idiopathic aqueductal stenosis (IAS) of the adult is an obstruction of cerebrospinal fluid outflow causing triventricular hydrocephalus. Clinical presentation mostly includes chronic neurological symptoms and cognitive inefficiencies. Endoscopic third ventriculostomy (ETV) represents the treatment of choice of this condition. Postoperative neurocognitive outcome has been poorely investigated. Methods: All patients affected by IAS and submitted to ETV were prospectively included in this study. Partecipants were administered a tailored neuropsychological testing battery to assess intellectual functioning, visual and verbal memory, language skills, and executive functioning pre and post operatively. All patients were clinically evaluated both pre and post operatively. Pre and post operative MRI findings were matched with neurocognitive outcome. Results: Between 2015 and 2017 eleven patients met the inclusion criteria. Median age of the patients was 59 (23 min-73 max). In two patients clinical presentation was headache, in one case papilledema without other symptoms and eight patients presented the typical symptoms of chronic hydrocephalus. All patients but one clinically improved after ETV. Postoperative neurocognitive evaluation compared to the preoperative one evidenced that 8 patients improved in different domains, one patient didn't obtain any benefit from the procedure and two patients worsened in visuospatial memory domains. No patient died and no case of severe morbidity occurred. Conclusions: In our series ETV has confirmed to be a safe and effective treatment leading to neurological improvement almost in all cases. Also cognitive inefficiencies seem to benefit from surgical treatment however these results are more variable and difficult to be interpreted and further studies are warrented. Introduction: Visualization of microscopic CSF motion called "bulk flow" may lead us to explicate clearance activity of neural wastes in the brain. In this work, we examined a quantitative visualization of microscopic motion based on q-space imaging (QSI) obtained with MRI. Methods: A phantom with microscopic circulation of physiological saline through a tube of 6 mm in inner diameter was placed in a vertical 9.4-T MR scanner. Flow rate of the pump was set at 0.1-0.5 mL/ min with 0.1 mL/min steps. Strength of motion probing gradient (MPG) was changed from − 43.4 to + 43.4 mT/m with 6.2 mT/m steps. The direction of MPG was foot-head direction. This resulted in a q-space of 32 points at each voxel in an axial section. The q-space was then Fourier-transformed into a probability density function (PDF) of proton displacement. The peak of PDF indicated the proton flow. The spatial distribution of the flow velocity was obtained by dividing the displacement by the MPG interval at all voxels. Results: The resultant flow velocities were from 57.80 to 300.72 µm/s, and were highly correlated (r = 0.99, p < 0.01) with the velocities generated by the pump. Regardless of the presence or absence of flow, the diffusion coefficient was about 1.6 × 10 −9 m 2 at each flow rate. Conclusions: Microscopic flow of the order of several 10 µm/s was sufficiently quantified by the present technique, even when the selfdiffusion exists. Our experimental work to observe the CSF bulk flow in mouse brain is in progress.

O66
Turnover of water molecules in brain, ventricles and subarachnoid spaces in normal volunteers and patients with idiopathic NPH: dynamic pet study using H 2

Results:
The maximum peak radio activities of GM, WM and BG were at 22.5, 50.0 and 22.5 s after the peak in ICA, respectively. The activities in the whole brain structures decreased gradually. On the contrary, the activity of LV, FS and PPC increased gradually until the end of the measurement {13.6, 27.4, and 50.9% of the whole brain parenchyma (GM + WM + BG) activity at 9.5 min, respectively}. The RRA of LV, FS and PPC in iNPH tended to be lower compared to the normal control. After L-P shunt surgery, RRA of these subarachnoid spaces tend to increase compared to the preoperative values.

Conclusions:
The present study showed very fast movement of water molecules from artery to brain parenchyma and ventricular and subarachnoid CSF. Water movements into the subarachnoid spaces may delay in iNPH patients, which may be normalized after shunt surgery. and over the surface of the brain, and is eventually absorbed by the arachnoid granulations and villi near the venous sinuses, returning to the bloodstream. However, through subsequent magnetic resonance imaging (MRI) studies in humans and in animals, many researchers have raised questions regarding this "CSF circulation theory" of CSF flowing unidirectionally and circulating through the ventricles and subarachnoid space in a downward or upward fashion. Methods: In this manuscript, we describe observations of CSF motion using three different MRI techniques, extract findings that are common among these techniques, and discuss CSF motion, as we currently understand it based on the results from the quantitative analysis of CSF motion. Results: CSF moves in various directions in the ventricles and subarachnoid space (CSF space), and the velocity of CSF motion differs depending on the CSF space. Conclusion: It is necessary to revise the currently held concept that CSF flows unidirectionally.

O68 Preliminary results on the effects of a cell junction inhibitor in experimental post-hemorrhagic hydrocephalus
Introduction: Our previous observations on human neuropathology specimens and cell cultures correlate well with our finding in infant ferrets of ventricular zone (VZ) disruption following intraventricular hemorrhage and post-hemorrhagic hydrocephalus (PHH). Impairments of ependymal cell (adherens) junctions appear to be a common feature of this disruption, which is mediated in part by ADAM10 modulation of N-cadherin cell junctions. Building on promising in vitro data, we sought to determine if an ADAM10 inhibitor could ameliorate VZ disruption and ventriculomegaly in our infant ferret model of PHH. Methods: PHH was induced in 20-day old ferrets by intraventricular injections of heparinized autologous or syngeneic lysed blood; sham controls received sterile saline. The ADAM10 inhibitor was given daily for 11 days post-induction. Anatomic and diffusion MRI evaluations were conducted biweekly until approximately 70 days post-induction. Fixed tissue was analyzed using immunohistochemistry for ependymal cells, neural progenitors, multiciliated ependymal cells, astrocytes, cell-adhesion molecules, N-cadherin, and ADAM10. Results: To date, 24 PHH and five control ferrets were analyzed. Within 1-2 weeks after PHH induction, mild-moderate ventriculomegaly occurred predominantly in the occipital and inferior horns. PHH animals, exhibited intermittent patches of disrupted VZ, increased expression of ADAM10, decreased expression of N-cadherin, and astrocytosis in periventricular white matter (PVWM). Diffusion MRI, especially diffusion basis spectrum imaging (DBSI) revealed myelin disruption, edema, axon loss and neuroinflammation in PVWM. Most importantly, no ventriculomegaly occurred during ADAM10-inhibitor treatments. Conclusions: VZ disruption and periventricular white matter astrocytosis occur in PHH and may be prevented by treatment with cell junction inhibitors. Introduction: Since occlusion of ventriculoperitoneal shunt (VPS) catheters continues to be a major cause of treatment failure in hydrocephalus patients, Microbot Medical, Inc. has designed the self-cleaning ventricular catheter (SCS) to resist catheter obstruction. Following promising in vitro and ex situ studies, preclinical evaluations of the SCS are needed, with an initial focus on biocompatibility. Methods: Hydrocephalus was induced in 30-day old piglets by percutaneous intracisternal injection of 25% kaolin. After ventriculomegaly had developed for 3-44 days, standard VPS (n = 1) and SCS (n = 4) catheters were implanted using routine surgical procedures. The Microbot activation coil was placed into a subcutaneous pocket behind the left ear and distal catheters were tunneled subcutaneously and inserted into the peritoneal cavity. Animals were monitored for neurological deficits, ventriculomegaly, and sacrificed at 5-49 days post-shunt (median 15d). Fixed tissue blocks containing the catheter path were processed for histopathology and immunohistochemistry. Results: Preliminary observations indicate that unactivated Microbot catheters exhibit the same neural tissue reaction as the standard commercial catheter in current clinical practice, although ventriculomegaly increased somewhat after shunting (ventricular volume 2774 mm 3 vs 4051 mm 3 ). Both types of catheters were ensheathed by a very thin capsule of collagenous and astrocytic tissue as they passed through brain tissue or contacted the ependyma. Adjacent white matter exhibited a mild inflammatory reaction that extended only 0.2-1.0 mm beyond the surface of the catheter.

Conclusions:
The inflammatory reaction to the Microbot catheter appeared to be no different than the reaction to the standard catheter. . ETV was performed successfully using standard neurosurgical procedures; i.e. frontal approach, visualization of the foramen of Monro (FoM), and opening the floor of the 3rd ventricle with balloon expansion. The piglet survived the procedure and after brain fixation via cardiac perfusion the path through the FoM and the ETV could be confirmed grossly with minimal damage to adjacent tissue. Conclusions: The juvenile piglet represents a good, clinically-relevant large animal model of hydrocephalus that is amenable to ventricular shunting and ETV. Cauterization of the choroid plexus also seems feasible. Of the studies with syrinx and normal flow (n = 16), all patients who had no intervention had an unchanged or improved clinical outcome. 40% of patients who had foramen magnum decompression reported a deterioration in symptoms. For studies with syrinx and abnormal flow (n = 23), clinical outcomes were similar after no surgery or foramen magnum decompression (36% and 33% showed clinical improvement respectively). Conclusions: Patients with normal CSF flow at the CVJ and syrinx did not clinically deteriorate if no surgery was performed, however, patients did experience worsening of symptoms after foramen magnum decompression. This study suggests that CSF MRI flow studies may be a useful assessment tool before deciding to operate in patients with Chiari Malformation. Introduction: iNPH's gait apraxia can often be associated with vascular encephalopathy (VE). The use of TUGT to evaluate gait's modification after cerebrospinal fluid tap test (CSFtt) is controversial. We instrumentally analyzed changes of Spatial-Temporal (ST) parameters during TUGT and compared data between pure iNPH and iNPH associated with VE. Methods: Using MRI, 64 iNPH patients were divided into two groups: 29 without (A) and 35 with (B) VE. Groups did not differ in sex and age. Patients performed an instrumented TUGT, by means of three wearable inertial sensors. A smartphone app was used to collect data. 3 repetitions per test were recorded before and after (24-72 h) CSFtt. Comparisons were made with the Wilcoxon signed rank test. Testretest reliability was assessed by ICC 1.1 Results: Test-retest reliability was excellent (ICC > 0.89). Stride length and cadence increased only in A: median values, respectively, from 73 to 77 (24 h) and 79 (72 h) cm (p < 0.001), and from 47 to 51 (24 h) and 52 (72 h) strides/min (p < 0.01). In A, speed progressively increased up to 72 h: from 55 to 59 (24 h) and 67 (72 h) cm/s (p < 0.001), whereas in B there was no significant improvement beyond 24 h. TUGT's total time decreased at 72 in both groups (p < 0.001), but was constantly lower in A. Conclusions: Instrumented TUGT is useful to detect possible improvements of ST parameters after CSFtt. In the presence of VE, gait apraxia modifiability after the tap test is less evident than in pure iNPH patients. Introduction: Endoscopic third ventriculostomy (ETV) is effective for non-communicating hydrocephalus, but in some cases, it is necessary to shunt early after ETV. We investigated the factors and pathology. Methods: In 52 consecutive cases of initial ETV since 2000, four cases of non-communicating hydrocephalus were investigated requiring shunt within 1 month after ETV. Their average age was 34.0 years. In three cases, a contrast medium was injected into the ventricle intraoperatively, and the effectiveness of ETV and the postoperative cerebrospinal fluid absorption ability were evaluated. Results: The primary disease was a brain stem tumor, spinal cord tumor, vertebral aneurysm after open surgery, and acoustic tumor after gamma knife. The average period from ETV to shunt was 18.8 (1-29) days. In the images, all cases showed obstruction of the outlet of fourth ventricle. Two cases of contrast injection were wash out within 24 h, but in one case, stagnation of the contrast agent was observed after 16 h, and ventricular dilatation was exacerbated, and the shunt was immediately performed. No findings that suspected early stoma occlusion after ETV. After the shunt, all cases progressed well. Conclusions: The early shunt requirement cases after ETV is associated with absorption disorder in addition to adhesion of the posterior cranial fossa due to inflammation, local infection, bleeding component. It can be said that so-called communicating and noncommunicating hydrocephalus were mixed clinically. Furthermore, subcutaneous fluid retained in the occipital region after surgery induce subclinical infection/inflammation, which may be the cause of ETV early failure. Fluids Barriers CNS 2018, 15(Suppl 2):35 prostaglandin D synthase (L-PGDS), soluble amyloid precursor protein (sAPP) and brain-type Tf by ELISA or Western blotting. We also examined correlations between radioisotope (RI) residual activity rate or CSF opening pressure and the quantification data of six proteins. Results: Comparing with non-SIH patients, SIH patients showed significant increase of brain-derived CSF glycoproteins such as L-PGDS, sAPP and brain-type Tf. Brain-type Tf was demonstrated to be produced in choroid plexus. Serum-derived proteins such as albumin, IgG, and serum-type Tf were also increased. A combination of L-PGDS and brain-type Tf differentiated SIH from non-SIH with sensitivity 94.7% and specificity 72.6%. Significant correlation were observed between clinical tests and L-PGDS or brain-type Tf. Decrease of RI residual activity rate was inversely correlated with increases of L-PGDS and brain-type Tf. Decrease of intracranial pressure was also inversely correlated with increases of L-PGDS and brain-type Tf. No other proteins were correlated with intracranial pressure or RI residual activity rate. Conclusions: L-PGDS and brain-type Tf can be biomarkers for diagnosing SIH. Introduction: CSF drainage in every-day neurosurgical care is very common, both in an emergency and a routine setting. Access to the CSF is gained via LP, shunt or reservoir, either for diagnostic or therapeutic reasons. Drainage is often arbitrarily determined by volume. However, the effects of excessive drainage are widely known and can be insignificant, or cause severe discomfort to the patient. Particularly in shunted patients, uncontrolled CSF drainage from the ventricular space can have long-term effects. We propose a short protocol for pressure-control CSF withdrawal in neurosurgical patients, using practical CSF dynamics and ICP monitoring. Materials and methods: A reliable baseline ICP can be obtained via connection with fluid-filled manometer lines to a pressure amplifier connected to a computer, with a software to record the ICP and calculate parameters such as the compensatory reserve. ICP is monitored for a few minutes (10-20), then drainage is started, rechecking every 5-10 mls in order to avoid overdrainage. When the compensatory reserve is depleted, smaller changes in volume provoke steeper drops in ICP which can be avoided. Results: Such a setting gives the advantage of a reliable baseline reading of the pressure and avoiding overdrainage by (1) checking the pressure (2) possessing knowledge of the compensatory reserves, which can warn about abrupt drops in ICP. Readings can be correlated and combined with clinical symptoms and clinical needs (diagnostic and therapeutic). Conclusions: Short-term ICP monitoring using an appropriate software can be a useful tool to support clinical practice in certain patients. ICP manometry can be unreliable and overdrainage can be prevented in many cases. Introduction: Measurements of preoperative cerebrospinal fluid (CSF) biomarkers using the xMAP ® platform were able to predict the long-term functional prognosis in iNPH patients after shunt treatment for the first time. Methods: Preoperative CSF biomarkers were measured in iNPH patients (n = 42), creating two groups based on a p-tau cut off value of 30 pg/mL Patents' clinical progress was recorded for 3 years following lumboperitoneal shunt treatment. The relationships among functional prognosis and the modified Rankin Scale (mRS), Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and the iNPH Grading Scale (iNPHGS) were analyzed and compared between an age-adjusted low (n = 24, aged 75.7 ± SD 5.3 years) and a high p-tau groups (n = 11, aged 76 ± 5.6 years). Informed consent to publish has been obtained from the patients. Results: The use of a p-tau cut-off value indicated that although it did not correlate with the preoperative MMSE score, it exhibited a significant negative correlation with the MMSE score at 1-year postoperatively (p = 0.02). This correlation strengthened with the extension of the postoperative period (2 years, p = 0.01, 3 years, p < 0.001, r 2 = 0.352). Cognitive function improved in the early postoperative period in the low p-tau group and was maintained thereafter. In contrast the high p-tau group, after early postoperative (3-6 months) improvement, gradual decline to baseline levels by the 2nd and 3rd postoperative year occurred (p < 0.001). Furthermore, both p-tau groups had initial mRS improvement, although the high p-tau group had some decline 3rd years after surgery. Conclusions: High p-tau is indicative of concomitant Alzheimer's pathology, and therapeutic effects of iNPH shunt treatment with coexisting Alzheimer's disease were limited to a shorter time period. Introduction: The purpose of this study was to test the hypothesis that the 'Callosal Arch Ratio' (CAR), described as the ratio of the greatest distances of the corpus callosum and the cortex to the Anterior Commissure-Posterior Commissure Line (ACPCL) as measured at 90° to the ACPCL, correctly predicts shunt responsiveness of Normal Pressure Hydrocephalus (NPH). Methods: Callosal Arch Ratio values were determined on preoperative magnetic resonance images (MRI) of 27 patients with presumed NPH undergoing VPS surgery between 2014 and 2016. Patients with an improvement of one point in the Normal Pressure Hydrocephalus Grading Scale (NPHGS) at 6 months postoperatively were considered shunt responders (Group 1) and those that did not show this improvement as non-responders (Group 2). The CAR results of these two groups were compared, as well as those of a control group (CG).

O79 Early stage p-tau measurement of cerebrospinal fluid can predict cognitive function 3 years after shunt surgery in patients with idiopathic normal pressure hydrocephalus
Results: There were 22 responders and 5 non-responders to shunt surgery. There was no difference between the two groups and the control group regarding demographical data (p > 0.05). The mean value of CAR was 0.66 (± 0.01) for Group 1 (responders to VPS), 0.60 (± 0.01) for Group 2 (non-responders to VPS) and 0.38 (± 0.01) for the control group. The difference between groups 1, 2 and CG was statistically significant (p = 0.000), and the difference between groups 1 and 2 was statistically significant (p = 0.001). Conclusion: These preliminary results suggest that CAR may be a valuable prognostic tool in selecting patients for shunt surgery. Studies with a higher number of patients are needed to obtain more reliable results. We previously reported a novel form of hydrocephalus termed essential tremor-idiopathic normal pressure hydrocephalus (ETINPH) identified in a large five-generation pedigree and mapped ETINPH locus to a 17-cM interval between 19q12-13.31 on chromosome 19 (chr19). In this report, we employed Whole Exome Sequencing (WES) to sequence three ETINPH patients and three normals from this pedigree. WES was performed with approximately 60× coverage and 100 bp paired-end (PE) reads and mapped to human genome GRCh38 to generate genetic variant files: SNPs and INDELs. We found that unique SNPs and INDELs shared by patients on chr19 is much higher than that on other chromosomes. Compared with normals, SNPs shared by patients on chr19 is fivefold higher than on other chromosomes and INDELs shared by patients on chr19 is nearly eightfold higher than on other chromosomes. This strongly reverberates our linkage result. By analyzing WES data with exome data parsing and novel variants extraction, we narrowed down ETINPH gene to 25 genes on chr19. Narrowing our focus to the 17-cM critical interval on 19q12-13.31, the ETINPH gene has been further narrowed down to mutations on 8 genes. These 8 non-synonymous mutations are currently analyzed with functional prediction assays (SIFT, PolyPhen2, etc.). A second ETINPH pedigree has been identified and sample has been collected for WES (100× coverage), which will lead to ETINPH gene identification. Idiopathic normal pressure hydrocephalus (iNPH) is a type of hydrocephalus affecting the elderly, characterized by unexplained symmetric gait disturbance, dementia, and/or urinary incontinence without elevated CSF pressure and other causative disorders. It has been hypothesized that genetic factors play an important role in the pathogenesis of iNPH. However, iNPH is a complex and multifactorial disorder which frequently overlaps with other neurological disorders, such as Alzheimer's and Parkinson's Diseases (AD/PD), therefore the genetics and molecular pathogenesis of human iNPH remain unknown.

O82 Unravelling the genetics of hydrocephalus
In this pilot study, we hypothesize that there are some common genetic variants among iNPH patients. To identify these novel biomarkers related to iNPH, using Illumina Human Omin1-Quad v.1 single nuclear polymorphism (SNP) microarrays which contain 450,000 SNPs spanning the whole genome, we performed the whole genome genotyping scan for 71 patients of iNPH recruited from our Hopkins clinics and 71 controls matched for sex, age, and race from the current NCBI database. Using a case control methodology such as logistic regression, random forest models, and other rigorous statistical methods to account for the multiple comparisons made, we are performing a pilot small-scale genome-wide association study to try to identify "relatively significant" SNPs or CNVs associated with the iNPH. At the same time, we will try to build a statistical model with these markers that can be used for prognosis and diagnosis of iNPH. Finally, we will perform pathway analysis by utilizing all identified genetic variants corresponding to this pilot biomarker search to extract more biological information related to iNPH. Introduction: Hydrocephalus is not excessive CSF accumulation under pressure. Although this condition has been recognized for several centuries, we still do not have a comprehensive understanding of the complex pathophysiology involved. The condition can occur in the fetus and is now more frequently recognized in older individuals. This continuum and the multiple "faces" of hydrocephalus make it a very interesting and almost indefinable situation. Over the past several years, recent advances in neuroradiologic techniques, genetic and molecular biology of hydrocephalus provide the opportunity to revisit the initial hypotheses. Excessive CSF accumulation within the CNS may be the result of a complex mechanism gone awry, or the primary causative pathology in an otherwise wellbalanced system. The numerous causes of hydrocephalus, and the varied manifestations of this condition beg the need for a more unified theory. Methods: Causative factors of hydrocephalus can be considered in many different ways: (1) restriction of blood flow, (2) blockage of normal CSF flow, (3) irregularities in normal brain pulsations, (4) loss of vascular integrity, (5) volume transmission abnormalities, (6) asynchrony of arterial/venous pressure waves, (7) extracellular matrix disfiguration (7) abnormal CSF absorption, (8) inadequate toxin removal, (9) "poisoning", (10) abnormal "brain turgor", (11) excessive reactionary responses, (12) inadequate activation of reparative mechanisms, and (13) abnormal expression of growth factors/cytokines. Results: Given these various theoretical approaches, it seems natural to attempt a unified approach to the "cause" of hydrocephalus. Such an approach is absolutely crucial in hopes of identifying therapeutic targets at various stages of this complex condition. Conversely, a multi-directional attack also seems appropriate, if a logical progression can be established, or an appropriate sequence of events can be ascertained. However, given the various ages and etiologies involved, there may be a simple, yet unrecognized basic pathophysiological mechanism that integrates our understanding. In this presentation, we will review the current philosophies of thought and attempt to unify them into similar avenues for discussion. These plausible and recognized theories may serve as a model of "pattern" recognition, and may have relevance to the currently available treatment options. This attempt will assist in our understanding, and allow reconsideration of accepted pathophysiological models of hydrocephalus. It will also allow us to consider several plausible and simultaneously applicable avenues of research. The basic question 'why CSF?' is still not clearly defined in our thinking! Fluids Barriers CNS 2018, 15(Suppl 2):35

Materials and methods:
We report our experience on 9 patients with NPH diagnosis that underwent also a diagnostic LIT. A different CSF dynamic parameters were determined. Only the patient with intracranial elastance (IE) ≥ 0.3 underwent to implant a VP shunt. Every patient has carried out two neuropsychological evaluations (MMSE, FAB, MOCA) and of 3D-gait analysis, pre-(30 days pre-surgery) and 3 months post-surgical intervention. Results: Three months post-intervention the patients increased the FAB (t7 = − 3.870; p = 0.006) and MOCA (t7 = − 3.564; p = 0.009) scores. Moreover, patients presented improvements in the gait spatiotemporal parameters. In particular, they decreased the support phase and double support phase percentage, and increased the balance phase percentage. They increased the cadence, gait mean velocity and stride length also. Conclusions: Although in our study there is no control group of patients treated with IE < 0.3, all patients in our group improve their cognitive and motor condition after the shunt implantation. On the basis of our previous experience, our data suggest that the evaluation of IE is very useful in predicting a successful prognosis of the derivative intervention in NPH patients. Introduction: An unchecked increase of intracranial pressure (ICP) causes a brain tamponade (BT). It is generally accepted that BT occurs when ICP is the same as values of systemic blood pressure (SBP). Method: Six sheeps were intubated, anesthetized and put in extracorporeal brachiocephalic circulation (EBC). Through a subdural needle, in which Ringer Lactate was infused, we produced BT. We recorded: Electrocardiogram, SBP, Carotid arterial blood pressure (CABP), Cerebral blood flow (CBF), ICP. In each animal we performed three different types of procedures.

O88 Brain tamponade mechanical parameters and its treatment by extracorporeal brachiocephalic selective circulation
Introduction: Patients who never clinically improve or improve and then worsen after CSF shunting constitute a difficult group to manage. The difficulty partially depends on establishing whether their clinical condition is due to shunt. We report our experience using infusion test with two different type of software (ICM+ Cambridge University, NEMO Catholic University) to estimate shunt patency. Method: Normal saline or Ringer lactate was infused at a constant rate into the shunt prechamber or previously implanted Ommaya reservoir. With ICM+ we analyzed retrospectively 312 tests, performed in 197 patients, to investigate the parameters describing CSF dynamics that correlate with the clinical finding of shunt malfunction. With Nemo we analyzed 15 NPH patients with suspect of malfunction. Results: In 161 of the 312 infusion tests results indicated under-draining shunts. Patients in the under-draining group had higher baseline (p = 5 * 10 − 9) and plateau CSF pressures (p = 0), higher resistance to CSF outflow (p = 0) and higher levels of baseline pulse amplitude waveform (p = 0.044) compared to patients with a properly performing shunt. During the test a significantly greater vasogenic waves (p = 5.8 * 10 − 7) and lower compensatory reserve (p = 0.0027) was noticed in patients with blocked shunts. In 10 of the 15 patients we found a higher baseline and plateau CSF pressure comparing with the opening pressure of the valve. All the patients with altered parameters underwent operative revision of the shunt with an improvement in symptoms. Conclusions: Infusion test is easy, safe and clinically useful, aiding decision in difficult clinical situations, where shunt malfunction is suspected but not certain.
Introduction: Tap Test (TT) can predict the clinical response to shunt. The objective of this study was to determine a correlation between the initial and final pressure difference (50 mL CSF removal) with clinical outcome after 12 months of shunt surgery in NPH patients. Methods: 42 NPH patients, who presented positive TT, were enrolled in the study. Of these, 14 were excluded because they did not have complete TT pressure data or they were not submitted to shunt. After surgery, the patients were followed for 12 months. Japanese NPH scale, BERG, DGI and TUG were compared and related to the difference between the initial and final TT pressure. Results: 28 NPH patients were included in the study. The mean values of the initial and final TT pressure and the difference between them were 17.3, 4.8 and 12.5 cmH 2 O. The preoperative and post-12 months of shunt surgery scores on the Japanese NPH scale, BERG, DGI and TUG were, respectively, 5.6 and 3.3, 33.2 and 41.6, 8.7 and 14.0, 38.2 and 43.8 s. Eighteen patients improved the TUG and the Japanese NPH scale, 8 worsened. In the statistical analysis, the t-test showed a difference between preoperative and after 12 months of surgery scores, but the Pearson correlation coefficient did not show a correlation between the difference of TT initial and final pressures and the clinical outcome. Conclusion: TT showed a positive predictive value of 64.3%, but the initial and final pressure difference did not present a relationship with the clinical outcome after shunt. Introduction: Programmable valve is the first choice for the treatment of NPH patients and it is also indicated for arachnoid cyst (AC) and idiopathic intracranial hypertension (IIH). The aim of this study was to confirm the safety and clinical performance of the Sphera Pro ™ programmable valve. Methods: 9 NPH, 1 temporal AC and 1 IIH patients were included sequentially in the study from July 2017 to February 2018. After shunt surgery, the postoperative evaluations took place at 10 days, 3 months, 6 months and 1 year. Primary outcomes: frequency and severity of complications or side effects. Secondary outcomes: clinical improvement after shunt. Results: Seven patients had idiopathic NPH, 2 secondary NPH and the mean age was 73.6. In all of them the valve was initially set at 3 cmH 2 O with antigravitacional device of 15 cmH 2 O. Two NPH patients required 1 adjustment for pressure reduction to 1 cmH 2 O. All patients improved on the Japanese NPH scale (mean pre = 5, mean post 3 months = 2). There was no overdrainage, spontaneous or after 3 T MRI valve deprogramming or infections. In the AC patient, the valve was set at 3 cmH 2 O and symptoms improved. In the IIH patient, the valve was initially set at 10 cmH 2 O and partial improvement of the symptoms were observed after 3 adjustments down to 1 cmH 2 O. Conclusion: Despite the small sample and the short follow-up period, preliminary data from this pilot study show that Sphera Pro ™ programmable valve is safe when used in NPH, IHH or arachnoid cyst adult patients. In this pilot study, the objective was to evaluate the performance of noninvasive intracranial pressure monitoring (niICP) in adult patients with idiopathic intracranial hypertension (IIH), arachnoid cyst or hydrocephalus with inadequately functioning shunt. Methods: During routine outpatient care, 10 patients with cerebral hydrodynamic disorder (6 IIH, 3 arachnoid cyst, 1 hydrocephalus with inadequately functioning shunt) underwent niICP, which detects the nanoscale variation of the skull for 5 min in the positions: dorsal decubitus, sitting, standing and valsalva maneuver. Results: Seven of the ten patients had focal neurological symptoms or clinical signs of intracranial hypertension. In these patients there was abnormal ICP curves and positive correlation with the data obtained in niICP. Five patients with IIH presented curves with P2 > P1, one patient with frontal arachnoid cyst had P1 = P2 and one patient with hydrocephalus with inadequately functioning shunt had horizontal P3. These patients received a shunt implant indication for the treatment of cerebral hydrodynamic disorders. Conclusion: Noninvasive monitoring of intracranial pressure is a practical, fast and efficient tool for the evaluation of patients with hydrocephalus, HII and arachnoid cyst. Index (CCI), already validated in the elderly; the American Society of Anesthesiologists (ASA) classification as part of the preoperative evaluation before shunt surgery. Methods: From 2015 to 2018 a multidisciplinary team selected 38 patients for shunt surgery after diagnosis of "probable iNPH" and exclusion of very severe comorbidities. Baseline demographic, cognitive, functional, and pathological characteristics were recorded and converted into the four scores. A ventriculoperitoneal shunt was positioned in all patients. Postoperative complications were registered during a 2 months period. Results: Each score pointed out different aspects of concomitant diseases. All patients had at least two CIRS-G "level 2" items. The scores median values (ranges) were: CIRS-G 9 (4-16), Charlson 1 (0-3), Kiefer 3 (0-6), ASA 3 (2-3). Symptomatic and asymptomatic postoperative complications were registered in 10 patients (subdural hygroma/ hematoma, seizures, shunt dysfunction, respiratory failure) and the statistical correlation with comorbidity scores, calculated at different cut-off values, was significant (p < 0.05) for CIRS-G > 9 and Charlson > 1. Conclusions: Concomitant diseases were always present in this study population: each score described them in a different way. CIRS-G > 9 and Charlson > 1 were associated with an increased risk of postoperative complications. patients for shunt surgery after diagnosis of "probable iNPH" and exclusion of very severe comorbidities. Baseline demographic, cognitive, functional and pathological characteristics were recorded and converted into the "four scores". A ventriculoperitoneal shunt was positioned in all patients. Outcome evaluation was carried out 6 months later. "Good outcome" was defined by the improvement of modified Rankin Scale (mRS) > 0 and/or iNPH grading scale (INPHGS) > 1 (or return to INPHGS = 0). Results: The "four scores" median values (ranges) were: CIRS-G 9 (4-14); Charlson 0.5 (0-3); Kiefer 2.5 (0-6); ASA 3 (2-3). Good outcome was reported in 23 cases (76.6%); this "good outcome" group generally had lower values of comorbidity scores than the other one, with fewer and/or less severe concomitant diseases, but only for the ASA classification the difference was statistically significant (p < 0.05); ASA 2 was associated with good outcome. Conclusions: In this study population of selected iNPH patients the preoperative ASA physical status classification 2 (mild systemic diseases) was significantly associated to good outcome; a similar trend, but not significant, was observed for CIRS-G, Charlson CI and Kiefer CMI. Purpose: The incidence of suprasellar cysts is approximately 9-21% in children with arachnoid cysts. It is generally believed that the occupying effect of suprasellar cysts is an important cause of hydrocephalus. We have investigated the endoscopic treatment of hydrocephalus with small suprasellar cyst and insignificant mass effect. Methods: Neurosurgery in our hospital performed between August 2016 and August 2017 for 10 patients with 3 months to 15 months. There were 6 males and 4 females. Their bregma tension increased and development was delayed. MRI of the head revealed dilatation of the ventricles, no obstruction in the aqueduct of sylvius, and flat or slightly raised bulges at the base of the third ventricle. ETV were given, and the midbrain lobe and pontine lobe of lilliequist membrane were fistulized at the same time. Results: Postoperative fontanelle tension decreased in 9 patients. Magnetic resonance imaging revealed a decrease in ventricular volume. One patient's symptoms did not improve significantly and he was treated with ventriculoperitoneal shunt. Conclusion: For patients with imaging findings suggesting that there is no clear obstruction in the ventricular system, the basal cisterna matrices and the morphology of the basement of the third ventricle should be carefully observed. If the basal cistern is full, the flat or microvolume of the third ventricle may indicate the possibility of suprasellar cysts. Endoscopic treatment can relieve the basal cistern obstruction, relieve hydrocephalus, and reduce shunt dependence. Keywords: Hydrocephalus, Arachnoid cyst, Suprasellar cistern, Neuroendoscopy Introduction: There is limited information on the effect of frontal versus parietal shunt placement on complication and revision rates after shunting for normal pressure hydrocephalus (NPH). Methods: Patients with NPH receiving shunts between 2001 and 2017 were included for analysis. The effect of frontal versus parietal shunt placement on the incidence of complications and revision surgery was assessed using the Pearson's Chi squared or Fisher's exact test and logistic regression analysis. Results: There were 348 patients included for analysis, with 266 (76.4%) and 82 (23.6%) patients receiving a frontal and parietal shunt, respectively. The incidence of intracerebral hemorrhage (ICH), subdural (SD) fluid collections, and SD fluid collections requiring surgical evacuation was 1.7%, 19.9%, and 5.7%, respectively. The rate of revision surgery was 21.0%, with a rate of proximal catheter malpositioning or obstruction of 1.7% and an infection rate of 3.7%. There were no differences in the rate of ICH (1.1% vs 3.7%; p = 0.146), SD fluid collection formation (17.7% vs 26.8%; p = 0.071), and SD collection requiring evacuation (5.6% vs 6.1%; p = 0.877) between patients with frontal versus parietal shunts. There was no difference in the rate of revision surgery (21.8% vs 18.3%; p = 0.495), either due to proximal Fluids Barriers CNS 2018, 15(Suppl 2):35 obstruction/malpositioning (1.1% vs 3.7%; p = 0.146) or infection (3.8% vs 3.7%; p = 0.966), between frontal versus parietal shunts. Conclusions: We did not observe differences in complication or shunt revision rates between shunts placed through a frontal versus parietal approach in our institutional series. were included for analysis. The incidence of shunt revision was noted and risk factors for revision were identified using a Cox proportional hazards model. Results: There were 348 patients included for analysis, with 98 patients (28.1%) receiving a PV. Shunt revision occurred in 73 patients (21.0%), with 12 patients (3.4%) undergoing multiple revisions. Overall revision rates were lower in patients receiving a PV (13.3% vs 24.0%; p = 0.027), and all patients undergoing multiple revisions initially received a FSV. Patients with a PV were less likely to undergo revision due to persistent symptoms without obstruction (2.0% vs 8.8%; p = 0.032). On multivariate analysis, increasing age (Unit RR 0.93, 95% CI 0.90-0.96; p = 0.001) and PVs (RR 0.18, 95% CI 0.01-0.90; p = 0.035) were associated with reduced risk of distal obstruction, and PVs were associated with reduced risk of revision due to persistent symptoms without obstruction (RR 0.26, 95% CI 0.04-0.91; p = 0.032). PVs were associated with more frequent shunt series during follow-up (4.1 vs 1.0 x-rays/follow-up year; p < 0.001), but not more frequent head CT scans (4.8 vs 3.9 CTs/follow-up year; p = 0.260). Conclusion: Our results suggest that programmable valves lead to reduced rates of shunt revision in patients with NPH. Despite the increased cost of PVs, they may be cost-effective. Methods: Records of patients with NPH treated with VPS between 2001 and 2017 were reviewed. The incidence of revision surgery due to distal obstruction was noted. Risk factors for distal obstruction were identified using a stepwise Cox proportional hazards model. Results: There were 341 patients included for analysis. Assistance from a general surgeon in placement of the peritoneal catheter was provided in 55 patients (16.1%). Shunt revision was necessary in 69 patients (20.2%), with 17 patients (5.0%) found to have a distal obstruction. On univariate analysis, increasing age was associated with reduced risk of distal obstruction (Unit RR 0.92, 95% CI 0.89-0.96; p < 0.001). BMI ≥ 38.9 (RR 6.60, 95% CI 1.84-19.00), prior abdominal surgery (RR 2.95, 95% CI 1.11-7.70; p = 0.032), and fixed-setting valve (RR 6.24, 95% CI 1.27-112.72; p = 0.020) were associated with increased odds of distal obstruction. General surgery involvement had no effect on distal obstruction rates (OR 0.89, 95% CI 0.25-3.21; p = 0.862). On multivariate analysis, increasing age (Unit RR 0.92, 95% CI 0.89-0.95; p < 0.001) and prior abdominal surgery (RR 3.30, 95% CI 1.23-8.71; p = 0.019) were independently associated with decreased and increased risk of distal obstruction, respectively. Conclusions: We identify multiple factors associated with distal shunt obstruction. These data may aid in the risk-stratification of patients undergoing VPS for NPH.

O95 "Four scores" comorbidity evaluation and outcome prediction in iNPH
Introduction: Idiopathic normal pressure hydrocephalus (iNPH) share some clinical features with Parkinson's disease (PD). Physical activity can promote positive effects on motor symptoms as well as cognitive functions in PD. In a previous study we used actigraphy for long-time evaluation of physical activity in iNPH patients. In spite of improved motor functions, measured with Timed up and go test (TUG) and 10-m walk test, the patients did not improve in motor parameters collected by actigraphy. The hypothesis is that adding a structured physical exercise program for iNPH-patients with goal setting after shunt surgery, an increased benefit for the patients regarding different aspects of motor function, cognition, quality of life and activities of daily living (ADL) can be achieved. Methods: Two Swedish centers have included patients from 2016 until 2018: 128 patients were needed according to sample analysis. Consecutive inclusion and randomisation into (1) written advice for physical self-exercise or (2) additional rehabilitation program for 12 weeks, 2 times 60 min a week postoperatively. Primary outcomes: changes in iNPH scale and Goal Attainment Scaling (GAS) before surgery, 3 and 6 months postoperatively. Secondary outcomes: changes in 6-min walk test, TUG, 30-s chair stand test, EQ5D-5L, LiSat11, Beck´s Depression Inventory, Actigraphy, ADL-taxonomy. The examiner is blinded. Results: Inclusion has ended. We are now finishing the intervention and completing the follow up data collections. Final results are expected in 2019. Conclusions: Hopefully this study will provide evidence for an additive effect of physical exercise after shunt surgery in iNPH. Introduction: The SINPHONI-2 study (a group of Japanese prospective multicenter cohort studies of the treatment of idiopathic normal pressure hydrocephalus [iNPH]) was carried out and showed the safety and efficacy of LP shunt surgery for iNPH. The LP shunt has recently become widely used in the treatment of iNPH in Japan. Although our high level of success with surgery may be considered to be a minor point, it is worth reporting, as minor differences in technique and know-how can markedly affect the efficacy of shunt surgery. We show a video of our LP shunt procedure. Methods: A total of 429 probable iNPH patients underwent LP shunt surgery at our NPH center between April 2009 and December 2016 (mean age of 78.1 ± 6.5 years). Aspects of our surgical technique Fluids Barriers CNS 2018, 15(Suppl 2):35 include: (1) general anesthesia, (2) use of the original drape, (3) upward insertion of the spinal tube through L2/3 via a paramedian puncture for highly deformed lumbar spine patients, (4) placement of a Codman-Hakim programmable valve with Siphonguard ™ in the back, (5) inclination of the table at 35° angle without position change and resterilization, (6) laparotomy via rectal muscle splitting, and (7) running the peritoneal tube obliquely from the upper lateral to lower medial (which is different from the route used for catheter installation and for abdominal entry to eliminate the space permitting catheter expulsion). Results: The LP shunt could be placed in all 429 cases without changing its route to the VP shunt. Of the 394 patients followed up at the NPH Center for 1 year after LP shunt surgery, 260 (66%; 95% CI 60-71) showed a favorable outcome, defined as improvement of at least one point on the modified Rankin scale. During the first year after surgery, 37 of 394 patients (9.4%) developed postoperative complications including chronic subdural hematoma requiring evacuation in 13 patients (3.2%), tube occlusion in 7, lower limb numbness in 5, migration of the abdominal tube in 5, rupture of the spinal tube in 2, and shunt infection in 2. Conclusions: Our LP shunt procedure generally seems to be acceptable from the viewpoint of complications. The low-invasive LP shunt that does not require ventricular puncture is preferred and has become the first-line procedure for iNPH in Japan. We would like to popularize the use of this surgical procedure worldwide in the future. Introduction: Normal pressure hydrocephalus (NPH) is frequently treated with ventriculoperitoneal (VP) shunt surgery. However, VP shunt implantation can lead to overdrainage and complications such as headaches, hygroma and subdural hematoma due to a siphon effect in upright position. Gravitational valves were designed to prevent overdrainage through position-dependent adjustment of valve resistance. Unfortunately, in our experience, gravitational valves occasionally cause underdrainage, requiring subsequent valve explantation. Flow-regulated valves, which increase flow resistance in presence of a high transvalvular pressure gradient, are an alternative to gravitational valves that may provide similar protection against overdrainage without causing underdrainage. Methods: We retrospectively compared gravitational valves with flowresistance valves in patients with NPH. The primary endpoint was the occurrence of hygroma or subdural hematoma. Secondary endpoints were response to shunt therapy (Black Grading Scale ≥ 5) and frequency of valve adjustments and reoperations. Results: Seventy three patients were included in this interim analysis. No significant difference in the postoperative occurrence of hygroma and subdural hematoma (5.7% for gravitational valves vs 10% for flow-regulated valves, p = 0.51) or the response to treatment (81.1% vs 85%, p = 0.7) was found. There was a significant difference in the average number of valve adjustments per patient between both groups (2 vs 0.7, p < 0.001) and a trend towards a lower rate of surgical revisions in the flow-regulated valve group (0.26 vs 0.05, p = 0.1). Conclusion: Our results suggest that implanting a flow-regulated valve instead of a gravitational valve may lead to fewer valve adjustments and reoperations in patients undergoing VP shunt implantation for NPH. In submitting an abstract to the to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders I warrant, on behalf of myself and any co-authors, that: Introduction: Idiopathic Normal Pressure Hydrocephalus (iNPH) patients have known cognitive deficits in addition to gait disturbances and urinary incontinence. Improvement in cognitive tests after lumbar drainage of cerebrospinal fluid is part of the diagnostic evaluation for possible iNPH patients. We review scores in cognitive subtests of a routinely used cognitive battery, to determine which were the most sensitive for iNPH. Methods: Retrospective analysis of iNPH cohort of 52 patients who underwent Wechsler Adult Memory Scale-Third Edition (WAIS-III). Scores are assessed against published normal values for Alzheimer's disease and intact patients [1]. Subjects: Fifty two patients with iNPH who undertook the WAIS-III Results: Median test scores in the WAIS-III facial memory subtest was 5.0 (n = 52, test result range 0-90). Facial memory deficit was the most consistent finding in the test battery, and was lower than median scores published for intact patients (32.3, n = 98) and Alzheimer's disease (26.9, n = 46). Word recall and pneumonic fluency were also found to be impaired, concurring with data already published on neurocognitive profile in iNPH2. Conclusion: Facial recognition scores in cognitive tests may be a sensitive tool to differentiate NPH patient. Facial recognition could be useful addition to cognitive test batteries used to predict shunt responsiveness. Fluids Barriers CNS 2018, 15(Suppl 2):35

O101 LP shunt for iNPH patients: surgical technique
Neither location of drain insertion (ITU/HDU n = 14, theatre n = 7, angiography suite n = 3), seniority of operator (resident n = 18; consultant n = 6) or drain material (Silverline ® Spiegelberg n = 16; bariumimpregnated EDM Medtronic n = 8) had any significant impact on infection rate. White cell count was raised in 23 of the 24 lumbar samples (411 ± 844 WCC/μL; 1009 ± 1590 RBC/μL). In 7 patients who underwent subsequent ventricular CSF diversion following LD removal (EVD n = 1, VP shunt n = 6), a rostro-caudal WCC gradient of 29.33 ± 37.44 to 163 ± 217 WCC/μL was observed. None of the 7 patients developed an intracranial infection. Conclusion: Lumbar drains can be safely inserted on ITU by residents without increasing infection risk. Lumbar white cell count is not a useful marker of infection following SAH. Antibiotic's should be used only in patients with clear organism growth.
review of the literature on ETV for adult hydrocephalus and discuss the need for an adult ETVSS. Methods: Publications on adult ETV were identified in MEDLINE and EMBASE, and selected for the review based on pre-specified inclusion and exclusion criteria. Meta-analysis was conducted for complications as well as for success rates grouped by aetiology and shunt history. Results: Twenty nine papers were included in the review. The best outcomes were seen for non-communicating hydrocephalus with success rates ranging from 79.8 to 83.1%, followed by haemorrhagic aetiology at 75.7%. Normal pressure hydrocephalus and infection showed success rates of 49.1% and 45.6% respectively. Previously shunted patients fared significantly worse than those without prior treatment (64.5% vs. 78.9%). The overall complication rate was 5.4% and procedure-related mortality 0.4%. Conclusions: While certain patient groups are treated effectively with ETV, low success rates are seen for others; and, although rare, serious complications occur. Proper patient selection is therefore paramount, and we believe that an adult ETVSS should be created. More research is required to determine appropriate outcome factors, but a meta-analytical approach serves as a good background for future studies. Introduction: Acetazolamide has frequently been used as a first-line treatment for idiopathic Intracranial Hypertension (IIH) and other disorders leading to raised intracranial pressure (ICP). The effect of Acetazolamide has been observed through lumbar puncture, however the effect of Acetazolamide on ICP has not been studied in continuous ICP measurement. Methods: A retrospective study of a prospectively built ICP database was undertaken. All patients with continuous ICP monitoring demonstrating 24 h on and 24 h off Acetazolamide were included in the study. Patients median ICP and median pulse amplitude over 24 h monitoring period on and off Diamox was assessed. Results: 12 patients (9F, 3M) underwent ICP monitoring with data collected during the same admission. 8 patients had IIH, 1 Chiari Malformation, 3 new diagnostic ICP procedures. Seven patients were started on Acetazolamide following raised ICP on primary monitoring, 5 were on Acetazolamide during the first period of monitoring and subsequently stopped and more data collected. 10 patients saw a reduction in ICP while on Acetazolamide. Overall, patients experienced a Median reduction of 1.14 mmHg (mean 1.16 mmHg, range 4.24 to − 4.445 mmHg). Patients (n9) who were on ≥ 1 g of Acetazolamide per day experienced a median reduction of 1.595 mmHg (mean 1.91 mmHg, range 4.24-0.5 mmHg). Conclusion: Our data suggests Acetazolamide can reduce ICP quickly following commencement, however this reduction was relatively small. The effect seems greater with a higher dose. Larger numbers of patients are required to gain a greater understanding into the significance of acetazolamide on ICP, particularly the affect at larger doses.  [3 males (38, 74, and 76 yo), 2 females (14 and 70 yo)] were examined under the following conditions: TR, 6.0 ms; TE, 3.9 ms; flip angle, 10 degrees; slice thickness, 7 mm; acquisition matrix, 256 × 256; SENSE factor, 4; velocity encode direction, FH; and velocity encoding (VENC), 10 cm/s. The time resolution was 217 ms. STFT was performed with 8-s long hamming window. Window length of ST was changed adaptively with the frequency component. Results: Cardiac-driven components were detected between 1 Hz and 1.5 Hz in most of the subjects. In 2 patients, the cardiac frequency was higher than the others by 0.3-0.6 Hz. One of them had tumor in anterior horn and the other had obstruction of Sylvian aqueduct. Respiratory components, which are likely between 0 and 0.5 Hz, were not clearly recognized in most of the subjects.

Conclusions:
The cardiac components of CSF motions were separately detected by STFT and ST under free breathing. The cardiac component had different frequency bands in each patient. In order to detect the weak respiratory components spreading over the low frequency bands, optimization of parameters for the transformation techniques is necessary. Introduction: Pediatric hydrocephalus is reputedly associated with high mortality, but the extent to which death is due to hydrocephalus as opposed to other medical comorbidities is unclear. Methods: We systematically assessed a cohort of children treated for hydrocephalus at a regional medical center between 2009 and 2018, using existing clinical data supplemented by official state death records. We assessed causes of death, calculated mortality rates, and compared hazard ratios (HRs) in various subgroups. Results: Among 2154 individuals with childhood-onset hydrocephalus, 159 (7.4%) were deceased, with an overall mortality rate of 9.1 per 1000 person-years (95% CI 7.8, 10.1). Mortality rates were more than 6 times higher in children diagnosed after their first birthday compared to those diagnosed before (32.6 vs 4.9 per 1000 person-years (95% CIs: 26.1, 40.6; 3.8, 6.2, respectively), primarily reflecting the preponderance of fatal brain tumors in the older age group. Among 1420 children diagnosed with hydrocephalus during infancy, 68 (4.8%) were deceased, and cause of death could be determined in 65. Death was primarily attributable to medical comorbidities such as complications of prematurity in 54 (83%). Among the 14 deaths associated with elevated intracranial pressure, 6 involved catastrophic shunt failure. The remaining 8 deaths were attributable to a decision not to pursue surgical treatment due to perceived futility. Conclusions: Death among children with hydrocephalus is primarily due to medical comorbidities rather than hydrocephalus itself. Among individuals diagnosed during infancy who died of elevated intracranial pressure, death was attributable to shunt failure and to decisions to forgo surgical treatment. Methods: A total of 12 consecutive patients with diagnosis of probable iNPH were submitted to a diagnostic MR examination before and immediately after a lumbar infusion test and tap test. 7 subjects were positive to lumbar infusion test (group 1) while 5 patients were negative (group 2). All the MR examinations included a T1w-mprage and a rsMRI SS-EPI (200 vol). Functional data were processed by FSL using MELODIC-ICA and analysis was performed with GLM by dualregression, p < 0.05. The ICA-component-dataset was inspected to identify the classical functional pattern. Differences in rsMRI data were assessed within and between group 1 and 2 and in a cohort of healthy volunteers. Results: In group 1 we found a significant positive difference from pre and post tap-test for motor network (p < 0.043, Z = 5.4), language network (p < 0.052, Z = 4.5) and DMN (p < 0.048, Z = 8.7). The analysis performed within group 2 pre and post tap-test don't show any improvement. The analysis of only the post tap-test-rsMRI acquisition in both groups showed an improvement in the motor network (p < 0.058, Z = 4.5), language network (p < 0.06, Z = 4.1) and DMN (p < 0.057, Z = 3.5). Conclusions: Since the trend of rsMRI agreed with invasive test results this could be a promising method to be considered for the management of iNPH patients candidates for shunt surgery. Introduction: Lung-brain interactions are partly already known, such as the oxygen delivery process, partly matter of recent studies, such as the cognitive impairment in chronic obstructive pulmonary diseases or the brain-lung cross-talk in neurocritically ill ventilated patients. The aim of this study was to test the relationship between chronic pulmonary diseases and outcome in patients with idiopathic Normal Pressure Hydrocephalus (iNPH). Methods: From 2015 to 2017 a multidisciplinary team selected 30 patients for shunt surgery after diagnosis of "probable iNPH". Baseline demographic, cognitive, physical and pathological characteristics were recorded. Very severe comorbidities were considered as exclusion criteria. Diagnosis of pulmonary disease was done considering history, symptoms and chest x-ray. A ventriculoperitoneal shunt was positioned in all patients. Outcome evaluation was carried out 6 months later, considering one generic scale, the modified Rankin Scale (mRS) and one specific scale, the iNPH grading scale (INPHGS). Good outcome was defined by improvement of mRS > 0 and/or INPHGS > 1 (or return of INPHGS to 0). Results: Chronic pneumopathies were present in 11 patients (36.6%). Overall "good outcome" was reported in 23 cases (76.6%). The absence of a pulmonary disease was significantly associated with improvement of mRS (p < 0.05), while the association with INPHGS was not significant. The relation between outcome and other comorbidities (cardiac, vascular, musculoskeletal, urinary, endocrine-metabolic, neurological, psychiatric) was not significant (p > 0.1). Conclusions: In this study pulmonary diseases were associated with the outcome described by the modified Rankin Scale. Pulmonary comorbidities should be considered in future studies on the outcome of iNPH shunted patients. Introduction: Brain aging is a natural process that can become pathological leading to neuronal loss and neurodegenerative diseases. In link with CSF related disorders, intracranial physical constrains like stress, strain or shear should participate to the pathophysiology of neurodegenerative diseases. We propose to explore the frail zone that is the transition region from normal to pathological brain aging with a biomechanical approach. Methods: A statistical analysis was performed on a database that included 100 patients suspected of normal pressure hydrocephalus with enlarged ventricles or parenchymal atrophy, gait disturbance, modest cognitive decline or urinary incontinence. The frailty was evaluated using the SEGA score, based on cognitive status, nutritional status, risk of depression, level of independence and fall risk. The cerebrospinal fluid (CSF) dynamics was explored using an infusion test. The intra cranial pressure was recorded while a saline fluid was injected at constant rate through a lumbar puncture. The intracranial fluids (blood and CSF) dynamics were also quantified (at baseline) with phase contrast MRI. A model of the blood and CSF circuit system was fitted on the clinical measurements in order to obtain the brain mechanical properties.

Results:
The statistical analysis showed a significant correlation (r = 0.34, p = 0.01) between brain elastance, which describes the brain ability to accommodate to volume changes, and frailty index SEGA. Conclusion: Our results support the hypothesis that biomechanical characterization of the brain could be valid to identify the transition from normal to pathological aging. Introduction: It is not fully recognized how symptoms and intracranial CSF distribution change after shunt surgery in iNPH. To reduce the misunderstanding that shunt surgery is ineffective for iNPH, we should objectively and quantitatively evaluate the improvement of symptoms and CSF imaging after shunting. Therefore, we quantitatively assessed the change of gait disturbance and CSF distribution in the patients with iNPH. Methods: Eighty-five patients (mean age, 76 years) with iNPH who underwent 3-T T2-weighted 3D-MRI before and after shunting. We measured Evans index, z-Evans index, brain/ventricle ratios (BVR) and callosal angle, and the volumes of total ventricle, convexity-SAS, Sylvian fissure and basal cistern and posterior fossa-SAS. Additionally, we measured the time and score on instrumented timed up-and-go test (iTUG) before and after shunting by using the newly released free iPhone application "hacaro iTUG".

Results:
The mean time on iTUG was shortened by > 5 s and the mean iTUG score was increased by > 20 points 2-4 weeks after shunting.

Conclusions:
The iTUG score rather than iTUG time measured by hacaro iTUG is a universally applicable measurement for the quantitative assessment of gait disturbance in iNPH. CSF distribution specific to iNPH gradually normalized around 6 months after shunting. The most distinct morphological change was increase in the volume of convexity-SAS. Introduction: Optimal treatment of hydrocephalus affecting ELBW newborns is still debated: although an early treatment correlates with better neurological outcome, the choice of surgical strategy must take into account the frailty of these patients. We present a safe, quick and well tolerated bedside procedure that can achieve this purpose. Methods: Fourteen cases of posthemorrhagic hydrocephalus (PHH) in ELBW infants (7 cases < 700 g, range 550-1000 g) were treated with a PTTEVD that was implanted at bedside as the first measure in a stepwise approach. Cognitive and motor outcome according to Griffith scales at 12 and 24 months of follow/up will be discussed.

Results:
The average duration of the procedure was 7 min, and there was no blood loss. The drain remained in place for an average of 24 days (range 8-45 days). In all cases early control of the hydrocephalus was achieved. One patient had a single episode of CSF leakage (due to insufficient CSF removal). In another patient Enterococcus in the CSF sample was detected the day after abdominal surgery with ileostomy (infection resolved with intrathecal vancomycin). One patient died of Streptococcus sepsis, a systemic infection existing prior to drain placement that never resolved. Once a patient reached 1 kg in weight, when necessary, a ventriculoperitoneal shunt was implanted and the PTTEVD was removed.

Conclusions:
The introduction of PTTEVD placement in our standard protocol for the management of PHH has proved to be a wise temporary option for small patients that could impact over the long-term outcome. Introduction: Shunt malfunction still represents a common problem for the pediatric and general neurosurgeon. In any case the choice between replacing the shunt, performing a secondary third ventriculostomy (sETV) with removal of the shunt or implanting a new catheter should aim to resolution of symptoms entailing the lowest operative risks. Methods: We applied to 122 cases of shunt malfunction a simple protocol taking into account the age of the patient, the presence of ventricular enlargement compared with the previous neuroradiological examinations and the technical feasibility of a sETV. Forty seven patients underwent sETV and 75 shunt revision. We employed another treatment protocol in the latter group with the use of intraluminal coagulation, endoscopic release of the adherent catheter, and the placement of a new catheter with neuronavigation as ultimate strategy.

Results:
The overall success rate of sETV was 74% (shunt free patients with normalized intracranial pressure and resolution of symptoms) also in patients with a long shunting duration (up to 30 years). The number of previous shunt revision procedures (p = 0.026) and lower age (p = 0.017) correlates with the likelihood of secondary ETV failure, a score of 80 in ETV success score correlates with secondary ETV success (p = 0.014).
None of the cases case of the group was complicated by postoperative intracranial hemorrhage Conclusion: The application of our treatment protocol to patients with CSF shunt malfunction allowed, in a large number of cases, shunt removal by performing sETV; when it didn't seem feasible, the endoscopic management of the intraventricular catheter avoided significant operative complications. were demented (CDR ≧ 1), in which 7 (6.7%) subjects were diagnosed as having possible or provable iNPH based on the Japanese Guidelines of iNPH; however, any of them had not consulted hospitals by themselves or their family. The longitudinal observation detected that; 3 subjects developed iNPH from AVIM, one became AVIM newly, one remained in AVIM for more than 16 years. Four were non-DESH ventriculomegaly at the age of 70 and became possible iNPH at 86.

Conclusions:
In the community-dwelling octogenarians, iNPH seems to be common but was underdiagnosed. retrospective study of our experience using this kind of shunt with a virtual off mode. Methods: A retrospective study was performed on ninety-five iNPH patient series underwent LPS surgery using Certas Plus valve (Codman ® ) from July 2016 to February 2018 at one hospital. Initial valve pressure of all cases was set at the seven level. Results: After LPS surgery, nine cases (9.4%) presented the symptoms, such as postural headache, subdural effusion, and subdural hematoma. We set the level of programmable valve in the virtual off mode, as soon as the appearance of symptoms. Six cases had improved their headache promptly. Three cases have not improved their symptoms, and we underwent shunt catheter ligation and one was required for hematoma irrigation surgery.

Conclusions:
The virtual off mode of LPS is useful for the management intracranial hypotension after LPS surgery. However, the symptoms of some cases were not completely resolved, even at the virtual off mode Introduction: The involvement of cerebral venous system in hydrocephalus condition is still debated. We determined the impact of hydrocephalus on venous vessels morphometry and their flow. Methods: We included 15 hydrocephalic patients (HY, 76 ± 6 years). They were age-matched to 13 Elderly Controls (EC, 74 ± 4 years). Both groups underwent PC-MRI for quantification of right (RJ) and left (LJ) jugular flows and sagittal (SS) and straight (Str.S) sinuses venous flow using Flow software. The circularities of these vessels were evaluated with ImageJ software. Considering anatomical aspects, we expect sinuses circularity equal to 0.6 which corresponds to a perfect equilateral triangle. For jugular veins, we expect a circularity between 1 (perfect circle circularity) and 0.6. Below these values, the vessel was deformed.
Results: For each vessel: Str.S, SS, RJ and LJ venous flow was significantly (p < 0.0005) decreased in HY compared to EC. SS circularity of HY was significantly decreased (p < 0.05) compared to EC (respectively 0.49 ± 0.2, 0.62 ± 0.1). SS of HY patients is deformed while EC exhibited normal SS circularity. There was no difference in the Str.S (0.46 ± 0.2; 0.55 ± 0.2) and RJ (0.29 ± 0.1; 042 ± 0.2) circularity between HY and EC. Str.S morphometry was normal in both groups while RJ was deformed in both groups. LJ circularity of HY was significantly decreased (p < 0.0005) compared to EC (0.35 ± 0.2; 0.61 ± 0.1, respectively). LJ of HY patients was deformed while EC exhibited normal SS morphometry.

Conclusions:
There is an impact of hydrocephalus on venous flow and morphometry which is reflected by a decrease of flow and vessels deformation.

P14
Post-traumatic CSF disorders: a comprehensive review Romain Manet 1 , Laurent Gergelé 2,3 , Marek Czosnyka 3 , Zofia H Czosnyka 3 , Angelos Kolias 3 , Jacques Luauté 4 , Emmanuel Jouanneau 1 pathology, we seek to objectify gait pattern analysis by quantitatively determining gait pattern differences with respect to baseline. Methods: We will perform a case-control study including 234 cases with a 1:1 ratio of controls. We will use the programme Kinovea version 0.8.15 to obtain measurements of the following gait parameters: speed, cadence, step length and stride length; each of which will be compared between the two groups. Statistical analysis will include absolute and relative frequencies, as well as central tendencies and dispersion measures. Numerical variables will be compared using parametric t-student or non-parametric U Mann-Whitney tests, according to their normal distribution determined with Shapiro-Wilk test. Results: We expect to find a significant difference between gait parameters obtained in patients versus those encountered in normal subjects.
Conclusions: By determining quantifiable measures and differences in gait parameters, we expect to be able to establish specific and characteristic patterns which would allow for better characterisation of the disease. We hope to be able to use these findings to build a diagnostic test which will permit an earlier diagnosis. Background: Intracerebral pressure (ICP) monitoring is widely used in the intensive care setting for the management of traumatic brain injury. There are also elective uses of ICP monitoring when objective measurement of cerebrospinal fluid (CSF) pressure is required to make informed decisions about management whether it be CSF leak repairs, blood patches or adjustments in shunted patients. Postural orthostatic tachycardia syndrome (POTS) is a disorder of the autonomic nervous system primarily affecting the control blood pressure and heart rate regulation. The hallmark of the disorder is the development of symptoms in the upright position and are relieved in the supine position which is similar to and can mimic cerebrospinal fluid (CSF) hypotension. The latter is a common indication for continuous intracerebral pressure (ICP) monitoring. Objective: To determine the percentage of patients who are admitted for continuous intracerebral pressure monitoring that have normal intracerebral pressure monitoring but abnormal positional tachycardia consistent with positional orthostatic tachycardia syndrome or POTS. Methods: This was a retrospective study in patients who were admitted for continuous ICP monitoring. We reviewed the charts of 130 patients admitted for continuous ICP monitoring between the years of 2015 and 2017. We measured ICP using Codman ICP express monitor which measures ICP using a strain gauge microchip located at the tip of the catheter. The micro sensor in inserted via a skull bolt by the neurosurgeon. ICP is transmitted as electrical voltage from the proximal end through nylon encapsulated copper wires which are connected to the Codman express monitor which displays the ICP measurement. We connect the Codman Express to a bedside monitor to obtain pressure waveforms using We converted the raw monitoring data into digital output format in order to analyze it. We converted the raw monitoring data into digital output format in order to analyze it. ICP is recorded in 60 s intervals and reported in mm of mercury (Hg). Other parameters are recorded using finger plethysmography include heart rate in beats per minute, blood pressure in mm of hg, oxygen saturation in percentage. ICP and heart rate was measured in supine position, sitting and standing position with the range of ICP reported as minimum, maximum and average values. Each position was maintained for a minimum of 10 min and average of 30 min before measurements were recorded. The average heart rate measurement was recorded in the same manner. Results: Data from a total of 130 patients was collected. 83 were female, ages ranged from 16 to 68 years. Indication for ICP monitoring was presumed CSF hypotension in 60 patients (46%), presumed CSF hypertension in 49 patients (37%) and other indications including congenital hydrocephalus, shunt malfunction made up the rest. Of the CSF hypotension group 13/60 (21%) had normal intracerebral pressures but positional tachycardia of 30 beat increase in heart rate from supine to standing position consistent with POTS. Conclusion: Our study demonstrates that obtaining objective measurement of continuous ICP with contiguous measurement of heart rate is important in diagnosing other causes of positional neurological symptoms that could mimic CSF hypotension. In our sample we were able to identify 21% of patients of POTS which were mistakenly thought to have CSF hypotension. This is an important distinction as the course of treatment for these two conditions is very different and could have valuable impact on patient care.