Abstracts from Hydrocephalus 2016

s from Hydrocephalus 2016 Cartagena, Colombia. 8–10 October 2016 © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/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://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. A1 Barriers to standardizing care for hydrocephalus in the Middle East A. Adam, J. Robison, J. Lu, R. Jose, N. Badran, T. Vivas‐Buitrago, D. Rigamonti Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia Correspondence: A. Adam Fluids and Barriers of the CNS 2017, 14(Suppl 1):A


Introduction:
The burden of the geriatric population within Saudi Arabia is increasing rapidly and there is poor understanding of the prevalence of normal pressure hydrocephalus (NPH). This is the first study in the Middle Eastern regions that aims at diagnosing and increasing awareness of NPH through a population based screening approach. Methods: The team implemented a nurse-based screening clinic within primary care at four clinic sites over 6 months. Patients were screened using standard gait assessment measures. Patients with symptomology indicative of Hydrocephalus were then sent for CT and then MRI, if necessary. Results: The team screened over 300 patients in the first 6 months, of which, 31 were referred for head CT to confirm ventriculomegaly and diagnosis of NPH. Patient reluctance was high given the association between their symptoms and the progression of natural aging. Infrastructure to support screening (ex. radiological services) was also limited. Conclusions: While the main focus of this study was in understanding the burden of NPH in the region, key areas were identified to encourage proactive screening of patients amongst primary care to raise awareness and further educate the country about hydrocephalus. Education was expanded on both the provider level as well as to the patient and family. From these screening measures, the team was able to train nurses to integrate screening for hydrocephalus within primary care. The team also raised awareness to physicians to refer patients with the triad to the new hydrocephalus clinic.
Introduction: Intracranial pressure (ICP) is an important clinical parameter for the proper functioning of the brain but this pressure is still difficult to measure in a non-invasive way and its regulation is quite hard to understand. Phase-contrast MRI (PC-MRI) provides arterial, venous and cerebrospinal fluid (CSF) cerebral flows in a noninvasive way that quantifies most of the fluid exchanges in the cranium. Fluid-structure interactions are numerous in the cerebrospinal system and difficult to understand in the rigid skull, so this study focussed on a numerical model of the cerebrospinal system taking into account CSF compartment, blood compartment and brain in fluid-structure interaction using PC-MRI measurements to approximate ICP. Methods: A fluid-structure interaction model was designed by coupling the fluid mechanics equations and the solid mechanics equations to obtain a global representation of the cerebrospinal system. The input of this model is the PC-MRI measured flows in arteries, in veins and in the CSF at the cervical level. This model allows quantification of velocity, pressure and displacement in the whole system. Different configurations of the model were tested to evaluate their impact on the system. Results: Ventricle stroke volume is widely impacted by heart rate and mechanical properties of the brain (Youngs modulus). Ventricles volume is modified under specific model configurations during a relatively short time (few minutes). Conclusions: The presented model allows a quantification of the system variables and highlights significant variations of the stroke volume in the ventricles under parameters variations that can be an origin of hydrocephalus.

A9
Assessment of the dynamic of the cerebrospinal fluid in the spinal canal of hydrocephalus patients O. Balédent 1 , A. Lokossou 1 , S. Garnotel 1 , G. Page 1 , L. Balardy 2 , Z. Czosnyka 3 , P. Payoux 4 , E. A. Schmidt 5,6 Introduction: During cardiac cycle (CC), the vascular brain expansion is quickly compensated by cerebrospinal fluid (CSF) volume flush, also called the stroke volume (SVcsf ), toward the spinal compartment. Change in this flush resulting from the modification of biomechanical properties of the spinal canal could alter the main compliance of the system. We aimed to calculate the SVcsf. Methods: 83 subjects (74 ± 7 years) suspected of hydrocephalus underwent an infusion test. The change in intracranial pressure (ICP) at rest over the CC (ΔP_rest) was assessed from ICP monitoring before infusion using ICM+. After infusion, resistance to CSF outflow (R out ) was calculated and was used to classify the patients in normal or pathological group. The day before the infusion, at the cervical level, the patients underwent a phase contrast MRI for the quantification of the spinal CSF flow oscillations. Then, SV CSF was calculated and represents the CSF volume moving outside and inside the cranium during CC. Results: 32 patients with a normal R out (9 ± 2 mmHg/ml/min) were included in the Normal_inf_group. 51 others whose R out was elevated (23 ± 14 mmHg/ml/min) were included in the Patho_inf_group. SVcsf was higher (p = 0.04) in the Normal_inf_group (0.62 ± 0.22 ml) than in the Patho_inf_group (0.52 ± 0.19 ml). ΔP_rest was smaller (p = 0.04) in the Normal_inf_group (1.92 ± 1.03 mmHg) than in the Patho_inf_ group (2.46 ± 1.34 mmHg). Conclusions: We found that the increase of R out is associated with a decrease of the SVcsf combined with an increase of ΔP_rest. This decrease of SVcsf could be explained by: a spinal canal compliance decrease, a vascular brain expansion decrease or an increase of subarachnoid space resistance to CSF flow.
Introduction: It is well documented that venous drainage modulates intracranial pressure. It is less known how changes in body posture affect the link between intracranial and extracranial venous dynamics. This study combines velocity encoding MRI and Doppler ultrasound to characterize the relationship between intracranial and extracranial venous dynamics and postural influence on the venous drainage dynamics. Methods: Ten volunteers underwent Phase Contrast MRI study to measure venous drainage through the sagittal sinus as well as the extracranial drainage through the internal jugular veins. Flow waveform dynamics and mean flow rates were assessed to determine pulsatility [(flow_max-flow_min)/mean_flow] differences between intra and extra cranial flows. Fluids Barriers CNS 2017, 14(Suppl 1):15 B-mode Ultrasound study were used to assess the change of the internal jugular veins in the cross sectional area and Doppler ultrasound was used to asses flow velocities waveforms and estimated the mean flow. Results: Ultrasound-derived measurements demonstrated a significant reduction in the extracranial drainage through the internal jugular veins in the upright posture compared with supine posture (130 ±60 vs. 20 ± 30 ml/min for the left side and 290 ± 380 vs. 60 ± 100 ml/min). Comparison between intracranial and extracranial venous flow dynamics demonstrated significantly larger magnitude of pulsatility in the internal jugular veins (0.41 ± 0.13) than in the sagittal sinus (0.27 ± 0.08). These differences were evident regardless of large interindividual variability. Conclusions: These results emphasize the complexity of the venous modulation of the intracranial physiology and a potential role for the right side of the heart and the jugular valves in the overall intracranial physiology and intracranial pressure dynamics. Introduction: Improvement in mobility is key aim of cerebrospinal fluid (CSF) diversion in idiopathic normal pressure hydrocephalus (INPH). However, there is little information on the estimated walking speed improvement expected after the insertion of a ventriculoperitoneal shunt (VP). In this study we measured actual improvement in walking speed, in miles per hour (MPH), after VP shunt insertion. Methods: Single centre analysis of patients with probable INPH. Preand post-operative (following ventriculoperitoneal shunt insertion) walking speeds over 10 m were recorded. The speed over 10 m was then converted into mph. Results: Seventeen patients (8 M:9 F), mean age 80 ± 7.4. For all 17 patients, mobility decline was a major symptom at the point of referral. The mean pre-operative walking speed was 0.8 mph. Post-operatively this increased to 1.2 mph on average, a 50% improvement in walking speed. Of the 17 patients, only one had a deterioration in the walking speed. Pre-op average for 10 m walking test was 36 steps, and post-op was 23. Conclusions: A mean improvement of 0.4 mph was observed after shunt insertion, providing further evidence that CSF diversion in INPH can effectively improve mobility.  (IIH). T-tau and Aβ-42 have been studied in neurodegenerative diseases. This study aimed to determine if these biomarkers levels are influenced after shunting in IIH. Methods: Single-centre retrospective case series of patients, who had CSF samples taken during either: ventriculoperitoneal (VP) shunt insertion or revision or during lumboperitoneal (LP) shunt insertion or revision. An unpaired T test was used to compare the CSF biomarker levels.

A12 Biomarkers in IIH: does CSF drainage influence T-tau and
Results: Between January 2013 to March 2016, 34 IIH patients (33 F:1 M) mean age 36.5 years, were included. The mean follow-up was 51.2 ± 23.1 months. Nineteen samples were from lumbar CSF of which 11 were primary samples and 8 during revision. Sixteen samples were ventricular CSF, of which 4 were taken during a primary VP shunt insertion and 12 were taken during a revision. The mean ventricular CSF levels were: T-tau 1240 ng/l, Aβ-42 1240 ng/l and T-tau/Aβ1-42 ratio 7.1. Mean lumbar CSF levels were: T-tau 377 ng/l, Aβ-42 1108 ng/l and T-tau/Aβ1-42 ratio 0.3. The mean ratio of T-tau/AB1-42 was significantly higher in CSF taken during shunt revision surgery compared to primary shunt insertion (p < 0.05). Conclusions: Patients with IIH appear to have normal lumbar CSF levels of T-tau and Aβ-42, suggesting neurodegeneration is not a major process in the pathophysiology of the disease. Samples taken during revision surgery had, on average, higher levels of neurodegenerative markers than those taken during primary surgery, suggesting the presence of the shunt may influence the levels.

A13
CSF outflow along all nerves: a widely unexplored aspect in the pathophysiology of neuroinflammation Karl Bechter Department Psychiatry II/Bezirkskliniken, Ulm University, Günzburg, Germany Correspondence: Karl Bechter Fluids and Barriers of the CNS 2017, 14(Suppl 1):A13 Introduction: Although first described by HI Quincke in 1872 (Bechter & Benveniste 2015 NPBR) the physiological outflow of CSF along all brain nerves and peripheral nerves remained unexplored with regard to a possible role in pathophysiology in general and specifically in neuroinflammation. Methods: Based on clinical observations during experimental treatments of therapy resistant psychiatric disorders with CSF filtration, shown effective for in autoimmune-neuroinflammatory disorder Guillain-Barre-syndrome, beyond the observed improvement of depression (associated with neuroinflammation) also minor peripheral neurological symptoms improved in parallel (Bechter et al. 2004, Bechter 2007. On this background and extensive literature the Peripheral CSF Outflow (PCOP)-Hypothesis was developed, suggesting a broad role for CSF signaling at the PCOP (Bechter 2011). Results: With MRI the CSF outflow at the PCOP can be easily visualized (Bechter &Schmitz Croat Med J 2014). With case analysis including histopathology after death from chronic leukemia, we for the first time demonstrated, that CSF cells follow the PCOP (Schmitt et al. Anticancer Res 2011). These findings match with recent knowledge about the afferent and efferent immunological pathways of the brain (Carare et al. BBI 2014). Beyond, CSF signaling at the PCOP may result in retrograde effects in neurons, e.g. synaptic stripping, but may also modulate neuronal guided immune responses (Bechter NPBR 2016). Conclusions: The predictions of the PCOP-Hypothesis remain yet poorly explored as far as investigated were confirmed. Further research in clinical and experimental approaches is required.

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Changes in brain tissue mechanical properties during hydrocephalus development in adult and young rats are different A. C. Pong 1,2 , L. Jugé 1,2 , L. E. Bilston 1,3 , S. Cheng 1,4 Fluids Barriers CNS 2017, 14(Suppl 1):15 a fused skull. The aims of this study are to determine how brain tissue stiffness changes in adult hydrocephalic rats with a fused skull, and how these changes are related to tissue deformation. Methods: Hydrocephalus was induced in nine adult Sprague-Dawley rats by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. Anatomical MR images and MR elastograms (800 Hz) were acquired 1 day before and 3 days post injection (9.4T, Bruker). Results were also compared with existing data from young hydrocephalic rats. Results: When the ventricles enlarged in adult hydrocephalic rats, brain tissue area decreased (GEE, p < 0.01) while the cranial area and cortical stiffness did not change (GEE, p = 0.40, p = 0.24, respectively). However, while the ventricles enlarged more in young hydrocephalic rats than in adult hydrocephalic rats (t test, p = 0.01), brain tissue area normalized to baseline was significantly lower (t test, p = 0.0002) in the adult hydrocephalic rats than in young hydrocephalic rats, suggesting higher brain compression in adults. Plotting stiffness against changes in normalised brain cross sectional area for both adult and young hydrocephalic rats, cortical stiffness was higher when normalized brain tissue area was lower (Spearman, p = 0.001).

Conclusions:
This study showed that brain stiffness was higher in the more compressed adult hydrocephalic brains than the less compressed juvenile brains. Introduction: While most aqueductal stenosis (AS) presents in infancy, some presents in late adulthood with a similar clinical triad as NPHplus chronic headaches. The goal of this study was to consider a possible mechanism for a late adult onset presentation. Specifically, we believe that AS forces some CSF to exit via the extracellular space (ECS) of the brain via the glymphatic system-similar to children with tectal gliomas. With aging comes deep white matter ischemia (DWMI) which consists of myelin pallor and greater attraction between the exiting polar water molecules and the bare myelin protein, increasing resistance to CSF outflow, leading to back up of CSF both in NPH and AS. Methods: Retrospective review of medical records revealed 15 elderly patients referred for possible NPH who had aqueductal webs on midsagittal, bright CSF, submillimeter CISS or FIESTA sequences. Routine MRI including DWI with ADC was performed. Age matched controls were imaged using the same routine technique. Results: The apparent diffusion coefficient (ADC) was significantly higher for a given degree of DWMI for the AS patients (p < 0.018 for mild DWMI; p < 0.001 for moderate to severe DWMI) than the controls implying a higher water content in the ECS of the former. Conclusions: The greater resistance to egress of CSF via the extracellular space of the brain (glymphatic system) due to DWMI may contribute to symptom onset in late adult onset AS.

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Atrophy or normal pressure hydrocephalus? F. Hakim 1 , J. F. Ramón 1 , M. F. Cárdenas 1 , J. S. Davidson 1 , C. García 1 , D. González 1 , S. Bermúdez 2 , N. Useche 2 Introduction: The proper diagnosis of normal pressure hydrocephalus has been a matter of debate since Dr. Hakim first described it in 1964. Along with the clinical triad and the tap test, the diagnostic confirmation has been achieved with radiological findings suggesting NPH. The current radiological tools, namely CT and MRI has permitted a clearer approximation to NPH, and enabled better differentiation from other disease processes coursing with ventriculomegaly, by showing a disproportionate ventricular system size, as compared to peripheral cortical subarachnoid space. NPH tends to be subdiagnosed, with an ensuing unfavorable management strategy. This is probably due to the shared clinical and imaging characteristics between NPH and dementias, principally of the Alzheimer's type. Methods: We compared pre-operative and post-operative head CT scan cuts of five patients with NPH, treated with ventriculo-atrial shunt placement, in order to determine changes in depth, antero-posterior segment length, and area of the Sylvian Fissure. Results: Analysis showed a bilateral, statistically significant reduction in the antero-posterior segment length and area of the Sylvian Fissure after shunt placement. Depth also decreased, but the difference was not statistically significant. Conclusions: These post-operative changes are an indirect index of parenchymal recuperation not previously measured in an objective manner. These findings support the hypothesis that at least a proportion of patients diagnosed with cerebral atrophy, could be coursing with reversible subarachnoid space augmentation associated with NPH. Summary: Despite normal pressure hydrocephalus (NPH) was described in 1964, its physiopathology has not yet been completely elucidated. Additionally, NPH diagnostic criteria and management clinical guidelines currently rely on epidemiological evidence and clinical experience. Unfortunately, epidemiological data display high variability due to the heterogeneity of diagnostic techniques and management approaches in different studies. This appears to lead to misdiagnosis and consequently to inaccurate treatment, as well as to underestimation of the number of NPH cases. There is as yet no consensus on the NPH patient´s interdisciplinary care protocol. In order to approach this limitation, a NPH Clinical Care Program was established at Hospital Universitario Fundación Santa Fe de Bogotá (FSFB) in 2014. The main objective of the program is to identify aspects that can be intervened in order to modify the course of the disease. This program consists as an interdisciplinary group of health care professionals, led by the Neurosurgery Department, and aims at designing and establishing of an assertive and early NPH detection for an optimal case management. The current approach of the FSB NPH-Program consists in offering early diagnosis; prompt treatment and initially a 1-year of patient's follow up The program has the final goal of improving the quality of NPH attention that may allow patients to be comfortable and confident in daily life with their families and in the community, and consequently a more effective health care. We will present the experience of the FSB NPH-Program and the importance of an accurate diagnose and treatment. Introduction: Idiopathic normal-pressure hydrocephalus (INPH) has no reliable biomarkers that assist in the selection of patients for a ventriculoperitoneal (VP) shunt. T-tau and Aβ-42 have been implicated as biomarkers in other neurodegenerative diseases and in INPH. The aim of this study was to review their ability to predict outcome after VP shunting. Methods: Single-centre retrospective analysis of probable INPH patients with ventricular CSF samples. Samples were sent for ELISA analysis. Clinical documentation was reviewed for outcome. An unpaired T test was used to compare the CSF biomarker levels. Negative and positive predictive values (NPV and PPV) for shunt-responsiveness were calculated. Results: August 2006 to July 2015, 78 (31 F:47 M) INPH patients, mean age 75.3 (R 55-94) had ventricular CSF analysed during shunt insertion or revision. Mean follow-up was 959 ± 657 days. Mean CSF levels for T-tau, Aβ-42 535 and T-tau/Aβ1-42 ratio were 669 ng/l, 471 ng/l and 2.00 respectively. There was no significant difference in levels between the shunt responsive and non-responsive group (p > 0.05). The markers demonstrated poor predictive value for shunt responsiveness (PPV 59% and NPV 41%). There was no significant difference in T-tau/Aβ1-42 ratio between those with INPH and a neurodegenerative diagnosis (mainly Alzheimer's and Parkinson's disease) compared to those with probable INPH alone. Eleven of fourteen with a neurodegenerative diagnosis were still shunt responsive.

Conclusions:
Neither T-tau nor Aβ-42 were effective at predicting shunt responsiveness in this group. Biomarkers more specific to INPH, with an ability to predict shunt responsiveness still need to be identified. Introduction: Idiopathic intracranial hypertension (IIH) is commonly associated with venous sinus stenosis and dural venous sinus stenting (DVSS) is becoming an increasingly used treatment option. Dural venous stenosis can be broadly classified into extrinsic (extra-luminal) or intrinsic (intra-luminal due to a thrombus or arachnoid granulation). We aimed to determine if morphological differences in sinus stenosis affected clinical or radiological outcome. Methods: A single centre case series. Clinical outcomes were assigned using degree of papilloedema on fundoscopy as a surrogate measure. Angiographic and manometry data before stenting and at 3 months after stent placement were reviewed. Differences in clinical outcomes, and development of re-stenosis in the two groups were assessed using Wilcoxon matched-pairs signed rank test and Fisher's exact test (Chi squared) respectively. Results: Between September 2010 and March 2016, 41 patients (2 M:39 F), mean age of 35.7 underwent DVSS, of whom 24 had an extrinsic and 17 had an intrinsic stenosis within the 3-month followup period. Sixteen of the 24 patients with an extrinsic stenosis developed a further morphological stenosis, compared to three within the intrinsic stenosis group (p < 0.05). There was no significant difference in development of re-stenosis with a significant pressure gradient (p = 0.12). Conclusions: Extrinsic venous sinus stenosis is more common radiologically and more likely to result in a re-stenosis post stenting. However there was no increase in re-stenosis with a significant pressure gradient, nor difference in outcome on fundoscopy. The high proportion of re-stenosis occurring those with extrinsic stenosis may provide further insight into the pathophysiology of IIH. Introduction: Acute hydrocephalus is a common complication of subarachnoid haemorrhage (SAH). Sampling of cerebrospinal fluid (CSF) from a pre-existing drain [external ventricular drain (EVD) or lumbar drain (LD)] is commonly performed to rule out infection prior to ventriculoperitoneal (VP) shunt insertion. Study aims to determine (1) if lumbar CSF infection markers reflects that of ventricular CSF (2) if abnormal WCC in LD correlated with a subsequent shunt infection. Methods: Single centre analysis of CSF from lumbar and ventricular CSF, sampled during the removal of LD and insertion of an EVD or VP shunt. Simultaneous CSF samples were sent for culture, WCC and biochemical analysis. A paired T test was performed to determine if levels were significantly different in lumbar and ventricular samples. An F-test compared the variances. Results: Five patients (4 M:1F), aged 67 ± 13.44 (mean ± SD), had hydrocephalus secondary to SAH. Lumbar CSF samples had a mean WCC of 939 ± 1894 cu/mm, ventricular CSF had a mean 57.0 ± 105 cu/ mm. Lumbar samples had a total protein of 3.80 ± 3.41 g/l, greater than ventricular samples level of 1.76 ± 2.09 g/l. Lumbar WCC levels had a significantly higher variance (p < 0.05). No patients developed a subsequent VP shunt infection. Conclusions: There is a rostral-caudal disparity in WCC and total protein levels, with lumbar CSF having greater WCC and total protein levels than ventricular CSF taken simultaneously. Decision to proceed to shunt insertion should be guided by clinical picture rather than cell count on thecal CSF. Introduction: Temporary cerebrospinal fluid (CSF) diversion through an external ventricular drain (EVD) comes with the risk of EVD-related infections (ERIs)-incidence varies from 0.8 to 22%. ERIs increase mortality, length of stay, costs, prolonged courses of antibiotics, and increase subsequent permanent CSF diversion. The rationale for this quality improvement project was therefore to reduce infection rates and improve placement via simulation training and a standardised perioperative care bundle. Methods: A best practice standardised perioperative approach and care bundle was peer-agreed amongst the senior neurosurgeons at the National Hospital for Neurology and Neurosurgery, Queen Square, London, and a standardised operation note was designed to improve documentation, and involve carers in positive decision-making. This was adapted from the bundle by Kubilay et al. Targeted simulation workshops included safe access, administration of intrathecal drugs, and demonstration of safe operative technique using a perpendicular trajectory using the Rowena head. Standardised aspects of care included choice of catheter, length of tunnelling, and method of securing the drain. Fluids Barriers CNS 2017, 14(Suppl 1):15

Morphology of dural venous sinus stenosis in IIH
Results: The infection rate before implementation was 5% (n = 17), placement was satisfactory in 50% (n = 16), and mean length of drainage was 8 days. In the 6 months following the interventions, preliminary results suggest the infection rate was 1.4% (n = 70), placement was satisfactory in 86.7% (n = 60), and mean length of drainage was 9 days. Conclusions: This demonstrates that simulation training and standardising perioperative care of patients requiring EVDs dramatically reduces infection rates and accuracy of placement, resulting in improving patient outcomes and reducing length of stay. Introduction: Hydrocephalus (HC) treatment, related to myelomeningocele, through endoscopic third ventriculostomy (TVE) is controversial because of the fact that traditionally, ventriculoperitoneal shunt (VPS) represent a principal treatment for most of the patients. Consequently, our experience in the pathology treatment through TVE is presented. Materials and methods: A retrospective description was made for every patient, which was subjected to TVE to treat hydrocephalus related to Myelomeningocele (MMC) between January 2013 and May 2016. Results: 15/16 patients had previous VPS, debuted with symptoms and signs of system dysfunctions and one case with intracranial hypertension syndrome (IHS) anew. 15/16 patients showed clinical and radiological improvement post TVE and in just one case IHS symptoms recurred. Conclusions: Hydrocephalus is the principal problem for patients with MMC, which develops in up to 80-90%, after spinal defect closure. The VPS, at present the principal option for treatment, however, is related to high morbidity in this population. In spite of bad outcome a few years ago, and the difficulties TVE represents because of anatomical variations and neurological immaturity of the cerebrospinal fluid (CSF) system in these patients, highly qualified personnel recognize that in children after 6 months old, TVE is a valuable option for HC treatment associated with MMC. In our experience, the TVE in pediatric patients with MMC has a high level of success (93.7%) made in well-chosen patients. Methods: All children referred to a supra-regional paediatric neurosurgical centre with suspected CSF shunt failure over 6-month period were identified on a prospective database and a casenote review evaluating the diagnostic process was undertaken. Results: There were 100 emergency referrals for 61 children (mean age 6.4-years) with shunts, 46 of whom had never been revised, mean time since last shunt procedure was 3.3 years. 36 children required admission, 23 underwent revision (all requiring change of a part of the shunt at operation). 51% of referrals resulted in neurosurgical review, 9 required ventricular access and 6 required ICP monitoring. Five patients required multiple shunt operations.
A scale was developed to communicate the difficulty and level of invasiveness of investigation required to diagnose or exclude shunt failure, from 1 (not a query relating to potential blockage) to 5 (difficult to determine shunt issue requiring surgical exploration). Conclusions: The proposed scale can help clinicians understand the referral patterns of patients with shunts; and convey the increasing complexity of this population and need to undertake invasive investigations to diagnose shunt blockage. It can also aid longitudinal analysis of neurosurgery unit data and identify the subgroup of patients for whom imaging studies are of low diagnostic utility, and where ventricular access device placement may useful to facilitate more invasive evaluation of shunt function such as CSF infusion studies or ICP monitoring. Summary: Idiopathic normal pressure hydrocephalus (iNPH) is usually regarded as a sporadic disease with typical gait, cognitive and urinary symptoms caused by a disturbance of the cerebrospinal fluid dynamics. The pathophysiological mechanisms of iNPH are still poorly understood. In the literature there are a few reports of familial clustering of iNPH. We present the first case of iNPH in two adult identical twins. Both developed similar symptoms at approximately the same age. Their MRI showed enlargement of the ventricles, a disproportional narrowing of the subarachnoid space and cortical sulci at the high convexity of the cerebrum and sharp callosal angle. Both of them improved significantly after shunt surgery confirmed by a 3 monthpostoperative examination. This indicates a possible genetic component involved in the pathogenesis. Further genetic studies are needed in this poorly explored area.

A24 Identical twins with idiopathic normal pressure hydrocephalus
Introduction: Surgical management of idiopathic normal pressure hydrocephalus (iNPH) remains puzzling despite the wide clinical application of programmable CSF shunts. The shunt-associated complications, along with the increased cost of the shunt, constitute the major drawbacks for shunting as a treatment for iNPH patients. Endoscopic third ventriculostomy has been employed in several small series of selected iNPH patients with variable results. Materials and methods: Our prospective study included 23 patients (4 females, 19 males) with ages ranged between 63 and 76 years (mean 70.4), suffering iNPH. All participants underwent preoperatively conventional and cine-MRI study, 40-50 ml CSF drainage via a spinal tap, and neurocognitive evaluation by employing the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MOCA) tests. All patients underwent an endoscopic third ventriculostomy, while another MRI study and neuropsychological evaluations were obtained 6 months postoperatively, and then at 6 months interval for up to 2 years. The idiopathic normal pressure hydrocephalus grading system (INPHGS) was also employed pre-and post-operatively in all participants. The follow up time ranged in our cohort from 6 to 96 months (mean 40.2). Results: The mean postoperative INPHGS score was 5.2, while the preoperative one was 6.8 in our current series. The mean postoperative Fluids Barriers CNS 2017, 14(Suppl 1):15 FAB score was 14.3 from 12.5, while the mean postoperative MOCA score was 24.2 from 21.5 preoperatively. The mean postoperative CSF stroke volume was 33.2 μl from 47.0 μl preoperatively. Conclusions: Endoscopic third ventriculostomy seems to be a valid surgical alternative option in iNPH patients, with functional CSF obstruction. Introduction: One indication for the application of telemetric pressure monitoring (TPM) occurs in patients (with or without shunt) presenting with unclear clinical symptoms (e.g. headaches), not explained by imaging studies or the patients history. The question we wanted to answer is: Does this patient need treatment? Our second indication is the optimization/adjustment of a preexisting (adjustable) shunt. Here the task is: How can we adjust the valve in the best possible way. Methods: Between November 2012 and October 2015 a total of 15 patients (11 male, 4 female) underwent TPM. A Raumedic sensor was implanted in 13 patients and a Miethke sensor reservoir in two patients. Age was between 4 and 35 years (mean 14 a) and the Follow up between 6 and 32 months (mean 18 mo). Our algorithm was: Implantation-Measurement at the hospital-Training (patient/family)-Measurement at home (2-4 weeks)-Evaluation of data-Decision. Results: In all patients, pressure monitoring under daily conditions in the hospital and at home was helpful in guiding therapy decisions (implantation or revision of a shunt, decision against shunt/or any other surgery, valve adjustment, other surgeries like cranioplasty). We present several case examples. Conclusions: Telemetric pressure monitoring is a helpful tool to guide clinical decision making in complex or difficult cases. TPM adds pressure data to clinical judgment and imaging studies and it provides new insight in the correlation between symptoms (e.g. headaches) and normal or pathologic ICP. Introduction: IVH is the commonest neurosurgical presentation in preterm infants. In 2012, we introduced a new protocol for its management, using ventriculo-subgaleal shunts (VSGS) as the preferred temporising device. Methods: Retrospective case review on electronic records. All the preterm infants requiring VSGS between 01/12 and 01/14 were included. Results: During this period, 23 infants required VSGS; mean birthweight was 897 g. Nineteen (82.6%) presented with IVH Papile grade 3 or 4 IVH at the time of referral. At the time of VSGS insertion, mean gestational age was 31 + 1 weeks (range 26 + 4 to 36 + 4), and the weight was 1171 g (range 758-1600 g). Pre-and post-surgical ventricular indices (VI) demonstrated an average 7.6 mm reduction. Surgical complications occurred in 7 cases (30%), including 2 infections, 2 failures requiring revision, and 3 decompressive haemorrhages (managed conservatively). The mean follow up was 516 days (range 137-1056). Twenty-two infants (95.6%) underwent conversion to a permanent ventriculoperitoneal shunt, within a mean time of 79 days (range 24-349) after the VSGS insertion. Mortality was zero.

A26
Conclusions: VSGS is a safe therapeutic option for preterm IVH with an acceptable morbidity profile in these complex patients. Despite its conceptual use as temporising device, all, except one patient required insertion of a permanent shunt. This may relate to the severe Papilegrade in our population.

A28
Modelling of posture-related changes in cerebrospinal fluid dynamics M. Gehlen 1,2 , V. Kurtcuoglu 2,3 , M. Schmid Daners 1 Introduction: Postural changes lead to changes in intracranial pressure, but also to a shift in the cranio-spinal compliance distribution of the cerebrospinal fluid (CSF) system. We hypothesize that this shift is caused by the collapse of the jugular veins and aim to test the hypothesis with a lumped-parameter model of CSF dynamics. Methods: An exponential function was used to describe the relationship between CSF pressure-relative to venous pressure-and volume. 63% of this CSF-to-venous compliance was assumed to be located spinally. The hydrostatic pressure column in the CSF system was assumed to be uninterrupted in upright posture, while the one in the veins was assumed to be interrupted at the jugular veins. The venous pressure at the spinal level was modelled as posture independent. Results: Reaching the same overall compliance in supine and upright equilibrium required 22% of the CSF absorption to be located spinally. With this, the overall CSF volume in upright equilibrium was increased by 1.6 ml. Sitting up caused an immediate caudal CSF shift of 2.5 ml and a spinal compliance decrease from 63 to 22% of the overall value. Due to this shift in compliance, the ability to compensate for cerebral arterial volume pulsations was reduced and the cranio-spinal CSF flow pulsations decreased from 328 to 61 ml/min peak-to-peak amplitude.

Conclusions:
The good accordance of the here modelled changes with values observed in vivo lead us to the conclusion that the jugular collapse is a major contributor to the posture-related changes in CSF dynamics.

A29
In vitro comparison of anti-siphon mechanisms under postural changes M. Gehlen 1,2 , A. Eklund 3 , V. Kurtcuoglu 2,4 , J. Malm 5 , M. Introduction: Flow-regulated, gravitational, and membrane-controlled anti-siphon devices (ASD) have been developed to counteract siphoning-induced overdrainage in upright posture through cerebrospinal fluid (CSF) shunts. We aimed to elucidate how these three types of ASDs interact with the CSF system under postural changes. Methods: Three shunts each of Codman Hakim with SiphonGuard (flow-regulated), Miethke miniNAV with proSA (gravitational), and Medtronic Delta (membrane-controlled) were tested. The pressureflow characteristic of each shunt was quantified in terms of opening pressure, closing pressure, and resistance. CSF drainage rates, resulting CSF volume change and intracranial pressure (ICP) were measured in supine, sitting, and standing posture. The measurements Fluids Barriers CNS 2017, 14(Suppl 1):15 were performed on a robotic test bench that models the in vivo environment of the shunt based on a mathematical description of CSF dynamics. Results: The flow-regulated ASDs avoided increased drainage in sitting posture, but reopening of the ASD was observed while standing. This reopening may be problematic for short patients and patients with increased IPP. The gravitational ASDs allowed setting the opening pressures in horizontal and vertical orientation independently. However, as their drainage rate changes with IPP, uniform drainage in upright posture is impossible and adaptation to the patient is critical. The membrane-controlled ASDs eliminated overdrainage by stopping drainage in upright posture at the expense of CSF accumulation. Conclusions: All tested ASDs reduced overdrainage, but their effects on CSF dynamics varied greatly: While membrane-controlled ASDs are a robust means of siphon-prevention, flow-controlled devices provide continuous drainage, and gravitational ASDs allow patient-specific adaptation, but precise adjustment is required. Introduction: Ventricular shunts represent the axis of treatment of disorders of the cerebrospinal fluid (CSF). The literature shows that the preferred technique around the world is the ventricular peritoneal shunt (VP), which is technically more simple, reproducible and represents a permanent and lasting CSF drainage. In our institution ventriculoatrial derivation is the first choice in the treatment of hydrocephalus in adults, results are equivalent to the technique of choice or even better. Methods: A retrospective review of patients with hydrocephalus who were treated with ventriculoatrial shunting at a single institution, from 2007 to 2015, was performed. Results: The results will be shown at the meeting. Conclusion: 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 techniques and less shunt malfunction in the follow up. Introduction: Prenatal and adult neurogenesis is impaired in hydrocephalus. The aim of the present investigation was to encapsulate cells of the subcommissural organ (SCO) in order to develop a neurotrophic therapy for hydrocephalic children. SCO cells secrete SCO-spondin, transthyretin, fibroblast growth factor, and S100β. These compounds have neurotrophic, neuroprotective and immunomodulatory functions [1]. Methods: SCO explants from bovine were maintained in organ culture for 30 days, a time when they become secretory ependymospheres. These spheres were encapsulated by using different polymeric semipermeable membranes. Encapsulated ependymospheres were cultured for 6 months with complete culture medium containing DMEM/ F12HAM supplemented with 10% fetal calf serum and 5% bovine serum. Double immunofluorescence was used to analyze the phenotype of SCO-cells after encapsulation and a long term in culture. Western blotting analyses were performed to study the presence of SCO-secretory compounds in the conditioned medium. Culture of rat neural stem cells (NSC) or human SH-SY5Y cells in the presence of encapsulated ependymospheres or of their condition medium was used as an assay to evaluate neurogenetic properties of SCO. Results: (I) SCO-encapsulated cells maintained their phenotype and they keep on secreting neurotrophic factors to the conditioned media for at least 6 months; (II) SCO-spondin was detected in the conditioned media of encapsulated cells; (III) In the differentiation assay, NSCs and SH-SY5Y cells differentiated into neurons. Conclusions: Encapsulated-SCO may become a useful tool to promote neuronal differentiation in the brain. Since xenografting of encapsulated tissue does not trigger a host-versus-graft reaction, grafting of encapsulated bovine SCO into the hydrocephalic cerebrospinal fluid may become a fruitful clinical tool. This would provide an opportunity for the early treatment of the neurological impairment associated with the onset fetal hydrocephalus.  Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a disorder of gait, cognition and urination in the aged population. Cerebrospinal fluid (CSF) tap test is useful for diagnosis of iNPH, but its diagnostic accuracy was relatively low. To improve the accuracy, we performed early and delayed quantitative assessments for gait on day 1 and day 4. Methods: Fifty-seven patients who were treated with CSF shunt surgery were subjected in this study. Assessments included 3-m timed up and go test (TUG) and 10-m walk by time and step. The values of area under the curve (AUC), sensitivity, specificity and cutoff were computed using receiver-operating curves.

A31 Encapsulation of subcommissural organ (SCO) cells to promote neurogenesis in foetal onset hydrocephalus
Results: On all three examinations, improvement of gait on day 4 was same as or more frequent than that on day 1. High AUC values above 0.75 were noted in TUG and TUG (%) on day 1, and 10-m walk (step) and 10-m walk (% time) on day 4. Among them, percent change of TUG on day 1 showed highest AUC of 0.784 and cutoff was 9.3% (sensitivity 83%, specificity 78%). On day 4, AUC values on TUG and 10-m walk were comparable to those on day 1, but statistical differences were not noted. We made a subgroup of better values of variables between day 1 and day 4. They showed high AUC values, but no statistical differences were noted. Conclusions: Percent change of TUG on day 1 would be favorable for predicting the effectiveness of shunt surgery.

A34
Health Results: White matter changes in brain stem (p < 0.001), periventricular area (p < 0.001) and deep white matter (p = 0.001) were associated with high mortality. Wide temporal horns (p < 0.001) and high Scheltens scores (p < 0.001) were also associated with high mortality. The disproportional Sylvian and supraSylvian subarachnoid spaces (p = 0.026) and decreased superior medial subarachnoid spaces (p = 0.048) were associated with better prognosis. Evans' index, focally dilated sulci, superior convexity subarachnoid spaces, lateral ventricles, Sylvian fissures, basal cisterns, flow void, callosal angle and modified cella media index were not associated with mortality. In shunted patients the disproportional Sylvian and supraSylvian subarachnoid spaces and decreased superior medial subarachnoid spaces were no longer associated with mortality, while the other associations remained similar. Conclusions: Radiological findings related to Alzheimer's disease and vascular degeneration were associated with high mortality. However, iNPH related markers were only weakly associated with better survival. Our findings suggest that in the treatment of iNPH patients, we should focus more on vascular degeneration.

A38
Associations of intracranial pressure with brain biopsy, radiological findings, and shunt surgery outcome in idiopathic normal pressure hydrocephalus M. Introduction: It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH). Methods: We analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy.

Results:
The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer's disease (AD) related proteins (amyloid-β, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (p = 0.014). High mean ICP was associated with Evans' index (EI; p = 0.025), disproportional Sylvian and supraSylvian subarachnoid spaces (p = 0.014), and focally dilated sulci (p = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (p = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes.

Conclusions:
The EI and disproportional Sylvian and Suprasylvian subarachnoid spaces were associated with mean ICP. Their ability, although limited, to predict elevated ICP in 24-h measurements, underlined their value in iNPH diagnostics. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation. Results: NME8 AG-genotype was more common in iNPH-patients than no demented controls (p = 0.044). With respect to other SNP:s, no other significant differences were discovered between groups. Conclusions: Our findings support iNPH to have independent genetic and pathophysiological mechanisms independent from Alzheimer's disease. Considering the fact NME8 plays a role in ciliary function and has SNP-related diversity in MRI-volumetry and CSF-biomarkers, the plausible ciliopathic dimension of iNPH as well as further genetic studies are required. Introduction: Chiari malformation 1 is defined as a herniation of the cerebellar tonsils below the foramen magnum and into the spinal canal. Although initially considered a congenital malformation it is increasingly understood as a CSF dynamic disorder where fluid differential pressures and cardiac pulsation may play a role in the pathophysiology. While the degree of descent of the tonsils into the spinal canal has been used as an index of symptom likelihood and candidacy for surgical decompression it has been found to unreliable and fluid dynamic parameters are being investigated. Methods: In this study we investigate the measurement of fluid impedance in the area of the cervicomedullary junction (longitudinal impedance, LI) using quantified phase-contrast MRI imaging in fifteen adult Chiari patients and eight normal controls. Results: Longitudinal Impedance was found to be increased in Chiari patients compared to normal controls and was variably decreased by decompressive surgery. The effect of this increased impedance on pulsatile brain tissue movement will also be discussed. Conclusions: Chiari pathophysiology demonstrates an increased impedance to flow at the cervicomedullary junction that may be related to pathophysiology and symptoms, and that is variably reduced in surgery. The assessment of the cardiac-dynamic fluid-brain interaction in Chiari malformation may provide insights into the pathophysiology, symptom generation, and appropriate surgical treatment.

A43
The Introduction: IIH is more common in patients with a raised BMI. Increased intra-peritoneal pressure is likely to affect the functioning of CSF shunts. We aimed to investigate the relationship between intraabdominal pressure and outcomes in patients with IIH. Idiopathic intracranial hypertension (IIH) is a difficult to treat condition. In a subset of patients, this condition results from venous stenosis. Stenosis can be primary or secondary to another cause. One theory is increased abdominal mass compresses the IVC giving rise to increased venous pressures resulting in a similar picture to IIH. We aimed to investigate the relationship between BMI and outcomes in patients with IIH. Methods: Case notes and radiological reports were reviewed. BMI for each patient was recorded as well as what interventions each patient had. Inferior vena cava pressure (IVCP) measured during venography was recorded. The outcome in clinic was also recorded. Results: We identified 27 patients who had undergone venography as part of their assessment for IIH. IVCP ranged from 3 to 19 mmHg (10.7 ± 5.04). 21/27 patients had IVCP >8 mmHg. BMI ranged from 25.9 to 63.4. Mean follow up was 9.4 months. Of these 27 patients 15 had undergone CSF drainage into the peritoneum. 60% of these patients had a BMI >30. We found a positive correlation between BMI and need to re-operate. These patients were advised to have bariatric surgery or pleural shunts. Conclusions: Outcome was less likely to resolve symptoms in patients with an increased BMI. For patients with CSF drainage into the peritoneum the need for re-intervention was higher and the outcome in clinic was worse. Therefore patients with a raised BMI and evidence of IIH should be considered for atrial or pleural shunt or be considered for bariatric intervention. Introduction: Venous sinus stenting is increasingly being used as a treatment option in patients with idiopathic intracranial hypertension. Venous hypertension is frequently observed in patients with IIH, and the pathophysiology behind this remains poorly understood. Pressure gradients across focal points of stenosis in the venous sinuses have been demonstrated and this pressure gradient has been shown to be obliterated once a stent is inserted. Furthermore we have been able to demonstrate a significant reduction in the ICP within 24 h after stenting. We aim to present the follow up findings for these difficult to treat patients from our unit. Methods: A case note review was carried out for all patients with idiopathic intracranial hypertension that had undergone venous sinus stenting. Length of follow up was recorded and clinical outcome as well as ICP was noted. Results: 40 patients who had undergone venous sinus stenting were identified. Mean length of follow up was 24.1 months (range 8-60 months). 1 patient had a clinically silent intracerebral bleed during the stent insertion. 95% (38/40) of our patient cohort were female. On follow up venography 97.5% (39/40) of our patients demonstrated a significant reduction in their pressure gradient. Mean intracranial pressure was recorded following stenting in 27 patients, and of these 27 patients a significant reduction in ICP was recorded in 23 patients. Clinical improvement was recorded in 42.5% (17/40) of patients. Conclusions: Venous sinus stenting is associated with a significant reduction in intracranial pressure and is effective in obliterating a pressure gradient across the venous sinus. This however does not correlate with clinical improvement, particularly with regards to improving symptoms of headache.
Introduction: Patients presenting with idiopathic normal pressure hydrocephalus (iNPH) triad often show some additional symptoms from the Parkinsonian spectrum (PS) including progressive supranuclear palsy (PSP), or symptoms typical for Alzheimer's disease (AD).
Making the correct initial diagnosis is challenging, but it also strongly influences the long-term outcome of shunting procedures. The aim of this study was to find potential cerebrospinal fluid (CSF) microRNA biomarkers to distinguish patients with iNPH from PS and AD. Methods: Records of 55 patients with iNPH that were treated between the year 2011 and 2014 were retrospectively reviewed. CSF samples were obtained from patients clinically diagnosed with definite iNPH (n = 21), possible iNPH with PS (n = 18), and possible iNPH with AD (n = 16). A two-step qRT-PCR analysis of the CSF samples was done to detect miRNAs that were differently expressed in the definite iNPH group.
Results: From 1008 miRNAs, miR-1280 and miR-4274 showed most promising results, both distinguishing definite iNPH versus possible iNPH with PS (AUC = 0.997 and 0.913), and miR-1280 distinguishing definite iNPH versus possible iNPH with AD (AUC = 0.949) with high accuracy. Furthermore, the combination of these microRNA biomarkers and p-Tau clearly separated iNPH from PS and AD patients. Conclusions: Potential microRNA biomarkers were identified in CSF of definite iNPH patients that could differentiate them from patients presenting with symptoms that are overlapping with other neurodegenerative disorders. Further investigations on larger number of patients would be useful to confirm these preliminary results. Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a disease of the elderly, and there is a possibility that a number of complications coexist. Shunt surgery if it is properly indicated and performed improves the patient's QOL, but it might increase the risk of subdural hematoma (SDH). So we examined the effects of antithrombotic drugs or neurological comorbidities on the outcome. Methods: From July 2002 to May 2015, 290 cases of iNPH were diagnosed. In the 171 patients who underwent shunt surgery, comorbidities, preoperative cognitive function and the effects of antithrombotic drugs on SDH were examined. Results: Of the 171 patients subjected to surgery, neurological comorbidities with dementia coexisted in 45 patients (26%), oral antithrombotic drugs were taken in 59 cases (34%). A median observation period was 3 years and 10 months. Chronic subdural hematoma was observed in 29 patients (17%, 4% per year), with non-surgical treatments the surgery was needed in only 7 patients (4.1%, 0.96% per year). Antithrombotic agents have the trend to increase the incidence, but it was not significant. There was no correlation between the outcome and preoperative cognitive function. Even if there is coexistence of other neurological disorders, most cases had some better period before deterioration.

Conclusions:
(1) In case of coexistence with dementia, we recommend doing tap test even if the MRI image is typical and informing and negotiating well with the patients and their family.
(2) The use of antithrombotic drugs did not appear to be a contraindication for shunt surgery. Introduction: Cerebrospinal fluid (CSF) shunt also has a role of improving clearance of CSF in addition to the role of adjusting intracranial pressure. Neurotoxic proteins in CSF are removed from the brain by shunt treatment. For lumboperitoneal shunt (LPS) that is used for treatment of iNPH, complications arising from CSF over-drainage (OD) are perceived as problematic.
The objective of treatment is to avoid complications caused by OD, while maintaining the amount of CSF drained. For that it is necessary to create a shunt system that can avoid OD and also safely facilitate removal of neurotoxic proteins such as Aβ42. We aimed to establish whether LPS by a shunt system that has gravitational add-on valves (GV) installed in tandem with programmable pressure valve could reduce complications arising from OD due to iNPH and improve the condition of patients.

Methods:
The peritoneal catheter has a small (0.7 mm) inner lumen (SL) to preserve distal shunt resistance. GV, enables the surgeon to use different opening pressure for supine and standing positions, managing over drainage complications and patient discomfort. We compared two settings of Strata NSC valve shunt systems: one with attached GV and one with SL, under different performance levels.
We analyzed 62 cases of iNPH patients (average age of 75.0 years) to whom LPS was implanted using GV + programmable pressure valves in tandem from March 2013 through June 2015, and 54 cases (74.7 years) of treatment of iNPH from July 2010 through April 2012. By shunt systems with programmable pressure valves + SL with regard to OD complications 1 year after commencement of treatment, evaluating mRS, Japan NPH grading scale score, MMSE and CSF biomarkers; amyloid beta (Aβ) 42, p-tau. Results: As for complications due to OD, on the other hand, the rate of postoperative headache was 13.2% and that of chronic subdural hematoma that required surgery was 2.2%, showing a decreasing trend. mRS scores improved from 2.8 to 2.2, total JNPHGS decreased from 5.9 to 4.5. MMSE scores improved from 21.9 to 24.8. Aβ42, p-tau concentration were changed from 483 to 480 (pg/ml), 31.3 to 71.9 (pg/ ml) respectively. Conclusions: It was found that the complications of low CSF pressure syndrome peculiar to LP shunt tended to be decreased by the use of the add-on valve system. In the case where GV was used in tandem, the effect of insufficient removal of CSF was assumed.  Introduction: Obesity is a risk factor for both idiopathic intracranial hypertension syndrome (IIHS) and sleep apnea (SA). Studies have demonstrated the relationship between elevations in intracerebral pressure and sleep apnea as well as shown a relationship between papilledema and OSA. In our sample 39% of patients with IIHS were shown to have SA. Thus far, there are no human studies on neurochemical factor that may play a role in the susceptibility of this population to sleep disordered breathing. Current literature has shown low leptin levels in obese patients with SA. In addition leptin is well known for its adipogenic properties. Animal studies have demonstrated a role for the adipocytokines especially Leptin which is deficient in the cerebrospinal fluid (CSF) leptin in obese animals, a phenomenon is known as of "leptin resistance". However, this has not been tested in patients with IIHS. Our hypothesis is that patients with IIHS are more susceptible to OSA due to obesity and/or leptin resistance. Through this study we plan to explore further the anthropometric characteristics that make subjects with IIHS more susceptible to sleep disordered breathing. We also plan to analyze the CSF from these subjects for evidence of leptin resistance as well as other possible neurohumoral factors which may play a role in the pathophysiology. Higher opening pressures were found in subjects with higher BMI (p = 0.03) and SA (p = 0.05). Leptin concentrations in CSF were not correlated to the plasma level (r = 0.5; p = 0.216). CSF leptin levels were not correlated to body mass index (r = 0.14; p = 0.567). Opening pressure did not correlate with CSF leptin levels (r = 0.96; p = 0.732) Conclusions: Obesity is a risk factor for both PTC and OSA and is characterised by leptin resistance due to poor penetration through the blood-brain barrier. Leptin has been shown to be protective against OSA (5). Our pilot data demonstrates that in subjects with IIHS those with higher BMI and SA had higher opening pressures. Our analysis of leptin levels in subjects with IIHS and SA did not demonstrate a correlation between CSF and serum leptin as is seen in obesity and SA, i.e. "leptin resistance". There was also no correlation with BMI which was a surprising finding. This suggests that the neurochemical pathways associated with leptin in IIHS are unique and distinct from its role in adiposity. Summary: Stress of caring for an elderly person can have a negative impact on a caregiver's health and well-being. Lack of functional independence in the elderly has been shown to increase caregiver's burden, both in the quantity of time and resources needed as well as changes in personal health relationships of the caregiver in charge. But establishing associations in caregiver's burden across different culture and regions in the world is unclear and less studied. Given the lack of knowledge on the caregiver-patient structures seen within Johns Hopkins Aramco Healthcare (JHAH), the primary aims of this exploratory study are to (1) define caregiver-patient demographics for the region and (2) identify the relationship between aspects of caring context and caregiver health as measured by quality of life. This study involves prospective data collection of geriatric patients seen at JHAH who will be assessed on their ability to carry out their activities of daily living Fluids Barriers CNS 2017, 14(Suppl 1):15 by administering the Barthel Index. Eligible patients and their primary caregivers will be asked to participate in the voluntary survey. The caregivers will be assessed on their quality of life (SF-36) and burden from caregiving role (Zarit burden questionnaire). The patients will be assessed on their quality of life . This study clarifies the type of caregiver and caregiver duties specific to JHAH, the effect of the burden on the caregiver and ways to improve caregiver well-being. Introduction: Transverse sinus stenosis is seen in the majority of patients with idiopathic intra-cranial hypertension (IIH). In case of a significant pressure gradient, transverse sinus is stented to reduce cerebral venous pressure, improve CSF resorption, reduce ICP and papilledema. However the pathogenesis of sinus stenosis and its effect on the cerebral venous system remains controversial. We hypothesize that transverse sinus stenosis stenting modifies the dynamic component of venous pressure. Methods: Ten IIH patients were prospectively enrolled. Under general anesthesia, a microcatheter was navigated into cerebral veins and sinuses. Intra sinus pressure was measured and recorded upstream and downstream from the stenosis with a pressure transducer connected to the micro catheter. A stent was placed if a significant pressure gradient (>10 mmHg) was found across the stenosis. Finally pressure was measured upstream and downstream from the stented stenosis. Off line mean venous pressure (VP) was calculated and waveform analyses were performed to extract fundamental harmonic A1 (heart-rate), second harmonic A2 (2 * heart-rate), and respiratory component (Resp). Parameters are presented before and after stenting (mean ± SD) upstream and downstream the stenosis with p value (Kruskal-Wallis test). Results: Stenting significantly reduces mean venous pressure upstream from the stenosis, which is expected. Stenting also significantly reduces fundamental harmonic A1 upstream with a trend in A1 decrease downstream the stenosis (Table 1). Introduction: Diabetes mellitus (DM) represents a major cause of morbidity and mortality worldwide. DM is an independent risk factor for cerebrovascular disease. DM is associated with an increase in the risk of brain atrophy and dementia. The WHO diagnostic criteria for DM is fasting plasma glucose ≥7.0 mmol/l. As well, glycated haemoglobin (HbA1c) reflects average plasma glucose over the previous 2-3 months. An HbA1c of 6.5% is recommended as the cut off point for diagnosing diabetes. DM is considered as a co morbidity of normal pressure hydrocephalus (NPH). We hypothesize that DM has an influence on ICP, CSF circulation and brain biophysical characteristics.

Methods:
In a prospective cohort of 91 patients suspected of NPH, we performed lumbar infusion tests and measured at the same time plasma glucose and HbA1C. To understand the influence of DM on ICP and CSF/brain characteristics we dichotomized our cohort into two sub-groups: one diabetic and one non-diabetic. According the WHO, we characterized our two sub-groups with glycemia and HbA1C: patients with normal glycemia (i.e. <7.0 mmol/l) or high glycemia (i.e. ≥7.0 mmol/l) and patients with normal HbA1c (i.e. <6.5%) or high HbA1c (i.e. ≥6.5%). Then we compared the data in the diabetic and non-diabetic subgroups with Student test. Results: The figure below gives mean ± SD values of various parameters in each diabetic and non-diabetic subgroup (Table 2). Conclusions: Our data suggest that patients with DM have stiffer brain with less CSF production rate and more resistive CSF outflow. Introduction: The subcommissural organ has been implicated in the development of congenital hydrocephalus, and some genetic models of hydrocephalus involve disrupting the development or function of this structure located along the ependyma of the caudal third ventricular at the posterior commissure. Ocular motor pathways important in vertical gaze traverse the posterior commissure; deficits in downward saccadic eye movement is a hallmark of Niemann-Pick Type C (NPC), an autosomal recessive neurodegenerative condition that interferes with trafficking and transport of cholesterol and glycolipids. Methods: EM first manifest ataxia in her teens, with progressive neurologic symptoms of dysarthria, psychosis, inability to voluntarily initiate downward eye movements and hepatosplenomegaly. Results: MRI brain showed atrophy, low signal abnormality in the thalamus, globus pallidus, putamen and external capsule bilaterally. Postmortem examination showed glial plaque displacing the posterior commissure anteriorly, originating in the subcommissural organ (SCO, also called the subnucleus dorsalis or nucleus subcommissuralis of Carpenter). This structure is composed mainly of glia with fenestrated capillaries abutting the ventricle. Conclusions: Alterations in secretory function, blood brain barrier and or glycoproteins (Reisner's fiber) may contribute to hydrocephalus during development and metabolic neurodegeneration in adulthood. Methods: Human CSF is collected and stored from patients in Johns Hopkins Neuroscience Critical Care Unit with an IVC following intraventricular or subarachnoid hemorrhage. Red blood cell count is reduced <1000 cc by freezing and centrifugation. Pooled CSF preserved with sodium azide (0.08%) is analyzed daily for desired protein concentration (5 g/l) and adjusted using sediment or dilution. Fluid, intraventricular catheters and shunts are maintained at body temperature (37 °C) in a shaking, thermal controlled water bath. Collection chamber height re: shunt valve is changed to mimic daily upright and recumbent postures. Gravitational flow is used, and physiological pulsatility mimicked by shaking water bath oscillations at 1 Hz. Testing lasts 30 days, after which valves will be pressure-flow tested per ISO-7197. Results: Initial flow studies are currently underway; results will be available at the time of presentation.

Conclusions:
We present an in vitro method for testing shunt survival in patients requiring CSF diversion after subarachnoid or intraventricular hemorrhage, taking into account effects of abnormal CSF contents, orthostatic postural changes and concomitant use of anti-siphoning devices with programmable shunt valves. Findings should help with the selection and timing of shunt systems in survivors of intracranial hemorrhage.

A62
Two-year outcome of VA shunt for iNPH evaluated by modified Rankin scale K. Takagi  Introduction: Shunt surgery is the only treatment for iNPH. Although VA shunt has been almost abandoned, it has many advantages. We have selected VA shunt as a first choice surgery for iNPH. The purpose of this study is to report the 2-year outcome of VA shunt evaluate by mRS.
Methods: Between January 2012 to December 2013, 137 VA shunts were performed for NPH. From these patients, those less than 60 year, with secondary NPH, and with advanced Alzheimer's disease were excluded. Patients with Evans Index less than 0.3 were included. Eighty-nine cases were the candidates for this study. The mRS was evaluated before the surgery (pre), 6 months (6 m), 1 year (1 y), and 2 years (2 y) after the surgery. The data was shown in mean (SD). The outcome at each time point was compared with preoperative condition. Statistical analysis was carried out with Dunnett's multiple comparison test. Statistic significant level was set at p < 0.05.  Introduction: The NPH population is elderly, commonly suffering from multi-morbidities and are frail. Current practice at our hospital involves several out-patient appointments pre surgical admission, including initial surgeon review, anaesthetic assessment and baseline neuropsychological testing. We have commenced a one-stop polyclinic where patients can see all specialties in 1 day as well as being reviewed by an occupational therapist. Methods: iNPH patients traveling from long distances to central London has proved difficult for some of these elderly patients. Therefore we have developed a one-stop NPH polyclinic, allowing patients to see neurosurgeons, specialist nursing, occupational therapy, anaesthetics and neuropsychology in 1 day. Here we undertake a prospective cohort observational study to review its impact. Results: In the trial group, patients who attended the clinic were discharged, on average, day 4. This is compared against an average of day 5.6 for patients that did not pass through the clinic over the same period.

Conclusions:
The one-stop clinic allowed for patients to be screened appropriately prior to admission. The input from occupational therapists assessing patients and putting adequate resources in place where needed pre admission, proved essential in reducing the length of admission for these patients.
Introduction: Intraventricular hemorrhage (IVH) is a complication of prematurity often associated with ventricular dilatation, which may resolve over time or progress to post-hemorrhagic hydrocephalus (PHH). We investigated anatomic factors that could predispose infants with IVH to PHH. Methods: We analyzed a cohort of premature infants diagnosed with Grade III-IV IVH between 2004 and 2014. Using ultrasounds and MRIs, we determined CSF obstruction pattern, skull shape and brain:skull ratios, comparing children with PHH to those with resolved ventricular dilatation (RVD), and comparing both groups to a set of healthy controls. Results: Among 110 premature infants with grade III-IV IVH, 65 (59%) developed PHH. Infants with PHH had more severe ventricular dilatation compared to those with RVD, though ranges overlapped. Intraventricular CSF obstruction was observed in 36/42 infants (86%) with PHH and 0/18 (0%) with RVD (p < 0.001). The distribution of skull shapes found among infants with PHH was similar to that of infants with RVD, though markedly different from controls. No significant differences in supratentorial brain:skull ratio were observed; however, the mean infratentorial brain:skull ratio of infants with PHH was 5% greater (more crowded) than controls (p = 0.006), whereas the mean infratentorial brain:skull ratio of infants with RVD was 8% smaller (less crowded) than controls (p = 0.004). Conclusions: Among premature infants with IVH, intraventricular obstruction and infratentorial crowding are strongly associated with PHH. Prospective studies are required to determine how these anatomic factors relate to the disease process and whether they can be used to predict the need for surgical intervention.