Paradigm shift in hydrocephalus research in legacy of Dandy’s pioneering work: rationale for third ventriculostomy in communicating hydrocephalus

OBJECTIVE: This study aims to question the generally accepted cerebrospinal fluid (CSF) bulk flow theory suggesting that the CSF is exclusively absorbed by the arachnoid villi and that the cause of hydrocephalus is a CSF absorption deficit. In addition, this study aims to briefly describe the new hydrodynamic concept of hydrocephalus and the rationale for endoscopic third ventriculostomy (ETV) in communicating hydrocephalus. CRITIQUE: The bulk flow theory has proven incapable of explaining the pivotal mechanisms behind communicating hydrocephalus. Thus, the theory is unable to explain why the ventricles enlarge, why the CSF pressure remains normal and why some patients improve after ETV. HYDRODYNAMIC CONCEPT OF HYDROCEPHALUS: Communicating hydrocephalus is caused by decreased intracranial compliance increasing the systolic pressure transmission into the brain parenchyma. The increased systolic pressure in the brain distends the brain towards the skull and simultaneously compresses the periventricular region of the brain against the ventricles. The final result is the predominant enlargement of the ventricles and narrowing of the subarachnoid space. The ETV reduces the increased systolic pressure in the brain simply by venting ventricular CSF through the stoma. The patent aqueduct in communicating hydrocephalus is too narrow to vent the CSF sufficiently

Three-dimensional (p,q) AdS superspaces and matter couplings

We introduce N-extended (p,q) AdS superspaces in three space-time dimensions, with p+q=N and p>=q, and analyse their geometry. We show that all (p,q) AdS superspaces with X^{IJKL}=0 are conformally flat. Nonlinear sigma-models with (p,q) AdS supersymmetry exist for p+q4 the target space geometries are highly restricted). Here we concentrate on studying off-shell N=3 supersymmetric sigma-models in AdS_3. For each of the cases (3,0) and (2,1), we give three different realisations of the supersymmetric action. We show that (3,0) AdS supersymmetry requires the sigma-model to be superconformal, and hence the corresponding target space is a hyperkahler cone. In the case of (2,1) AdS supersymmetry, the sigma-model target space must be a non-compact hyperkahler manifold endowed with a Killing vector field which generates an SO(2) group of rotations of the two-sphere of complex structures.Comment: 52 pages; V3: minor corrections, version published in JHE

ICP curve morphology and intracranial flow-volume changes: a simultaneous ICP and cine phase contrast MRI study in humans

Background: The intracranial pressure (ICP) curve with its different peaks has been extensively studied, but the exact physiological mechanisms behind its morphology are still not fully understood. Both intracranial volume change (ΔICV) and transmission of the arterial blood pressure have been proposed to shape the ICP curve. This study tested the hypothesis that the ICP curve correlates to intracranial volume changes. Methods: Cine phase contrast magnetic resonance imaging (MRI) examinations were performed in neuro-intensive care patients with simultaneous ICP monitoring. The MRI was set to examine cerebral arterial inflow and venous cerebral outflow as well as flow of cerebrospinal fluid over the foramen magnum. The difference in total flow into and out from the cranial cavity (Flowtot) over time provides the ΔICV. The ICP curve was compared to the Flowtot and the ΔICV. Correlations were calculated through linear and logarithmic regression. Student’s t test was used to test the null hypothesis between paired samples. Results: Excluding the initial ICP wave, P1, the mean R2 for the correlation between the ΔICV and the ICP was 0.75 for the exponential expression, which had a higher correlation than the linear (p = 0.005). The first ICP peaks correlated to the initial peaks of Flowtot with a mean R2 = 0.88. Conclusion: The first part, or the P1, of the ICP curve seems to be created by the first rapid net inflow seen in Flowtot while the rest of the ICP curve seem to correlate to the ΔICV

Health promoting settings in primary health care - "hälsotorg": an implementation analysis

Background Sweden, like many other western countries, faces increasing rates of lifestyle related diseases and corresponding rise in costs for health care. To meet these challenges, a number of efforts have been introduced at different societal levels. One such effort is "Hälsotorg" (HS). HS is a new health promotion setting that emerged in collaboration between the Swedish County Councils and Apoteket AB, a state-owned pharmacy company. HS's overall aim was to improve population health and facilitate inhabitants' responsibility for self-care. A new National Public Health Policy, introduced in 2008, emphasizes more focus on individual's needs and responsibility as well as strong need for county councils to provide supportive environment for individual-centred health services and increased health literacy among the population. In light of this policy, there is a need to examine existing settings that can provide supportive environment for individuals at community level. The aim of this study was to explore HS's policy implementation at local level and analyse HS's activities, in order to provide a deeper understanding of HS's potential as a health promoting setting. Methods Materials included a survey and key documents related to the development and nature of HS on local and national levels. A policy analysis inspired by Walt and Gilson was used in data analysis. In addition, an analysis using the principles of health promotion in relation to HS policy process and activities was also carried out. Results The analysis illuminated strengths and weaknesses in the policy process, its actors, contextual factors and activities. The health communication approach in the analysed documents contained health promoting intentions but the health promoting approach corresponding to a health promoting setting was neither apparent nor shared among the stakeholders. This influenced the interpretation and implementation of HS negatively. Conclusions The analysis indicates that HS has potential to be a valuable health promotion setting for both population and individuals, given the strong intentions for a health and empowerment building approach that is expressed in the documents. However, for a more sustainable implementation of HS, there is need for an in- depth understanding of the health promotion approach among HS stakeholders

Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF) induced by shunt surgery and the relationship between these changes and clinical improvement.</p> <p>Methods</p> <p>We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17) and idiopathic NPH (INPH, n = 18) before and 3 months after shunt surgery. Patients were divided into groups according to whether or not there was improvement in clinical symptoms after surgery.</p> <p>Results</p> <p>Preoperatively, the only pathological findings were elevated neurofilament protein (NFL), significantly more so in the SNPH patients than in the INPH patients, and elevated albumin content. Higher levels of NFL correlated with worse gait, balance, wakefulness and neuropsychological performance. Preoperatively, no differences were seen in any of the CSF biomarkers between patients that improved after surgery and those that did not improve. Postoperatively, a greater improvement in gait and balance performance correlated with a more pronounced reduction in NFL. Levels of albumin, albumin ratio, neuropeptide Y, vasoactive intestinal peptide and ganglioside GD3 increased significantly after shunting in both groups. In addition, Gamma amino butyric acid increased significantly in SNPH and tau in INPH.</p> <p>Conclusion</p> <p>We conclude that a number of biochemical changes occur after shunt surgery, but there are no marked differences between the SNPH and INPH patients. The results indicate that NFL may be a marker that can predict a surgically reversible state in NPH.</p

Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

<p>Abstract</p> <p>Background</p> <p>The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.</p> <p>Methods</p> <p>Hydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.</p> <p>Results</p> <p>Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.</p> <p>Conclusions</p> <p>AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.</p