Cerebrospinal Fluid Disorders Research Articles

Abstracts from Hydrocephalus 2015.

The 7th Annual Meeting of the International Society for hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) is being held in Banff, Alberta, Canada September 19th-21st, 2015. There are three satellite symposia accompanying the main Congress. On September 17th, the 1st Calgary Hydrocephalus Symposium will be hosted by the Cumming School of Medicine to provide an intimate opportunity to explore state-of-the-art hydrocephalus care. On September 18th, the satellite Normal Pressure Hydrocephalus (NPH) Symposium will be held in Banff, providing an opportunity to share and learn from the experience of international experts regarding this challenging hydrocephalus disorder. We also welcome our colleagues and members of the International Hydrocephalus Imaging Working Group (IHIWG). IHIWG members include Neurologists, Neurosurgeons, Neuroradiologists and Physicists who will have their autumn meeting on September 18th in Banff. Hydrocephalus 2015 will cover the full range of CSF disorders affecting both children and adults. The focus of work done in our field is the patient and to this end, the theme of three special sessions of this Congress will be “The Patient”. These special sessions will examine: 1) Quality Improvement and Safety in Hydrocephalus Care; 2) Transition and Adult Hydrocephalus Care; and 3) Ethics and Patient Involvement in Clinical Research. These sessions will provide a foundation for the research that will be presented during Hydrocephalus 2015 which will include sessions dealing with pediatric hydrocephalus, adult hydrocephalus, advanced Neuro-imaging techniques in hydrocephalus, CSF shunt design and technology and intracranial pressure. We will also have special sessions devoted to young investigators and will recognize those with the best oral presentations and best posters. We have a great social program to span the conference. We start with the Welcoming Reception on September 18th, party at a bar-be-que buffet barn dance on September 19th and then celebrate at the Denim and Diamonds Gala Dinner on September 20th. Our very special guest speaker for the Gala Dinner is Dr. Michael Bliss, renowned historian and author of “Harvey Cushing. A Life in Surgery”.

Ambulatory intracranial pressure monitoring in NPH with a miniaturized acquisition chain

Diagnosis of cerebrospinal fluid (CSF) disorders may require intracranial pressure (ICP) monitoring. Classically, recordings are performed with a cumbersome acquisition chain, requiring the patient to be bedridden in a specific environment. New solutions have recently been proposed to free patient of these constraints, by mean of telemetric technology. We report our first experience of the use of a miniaturized ambulatory acquisition chain.

Relationship between cerebrospinal fluid flow, ventricles morphology, and DTI properties in internal capsules: differences between Alzheimer's disease and normal-pressure hydrocephalus

Normal-pressure hydrocephalus (NPH) and Alzheimer's disease (AD) have some similar clinical features and both involve white matter and cerebrospinal fluid (CSF) disorders. To compare putative relationships between ventricular morphology, CSF flow, and white matter diffusion in AD and NPH. Thirty patients (18 with AD and 12 with suspected NPH) were included in the study. All patients underwent a 3-Tesla MRI scan, which included phase-contrast MRI of the aqueduct (to assess the aqueductal CSF stroke volume) and a DTI session (to calculate the fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) in the internal capsules). FA was correlated with ventricular volume in the suspected NPH population (P < 0.001; rs = 0.88), whereas the ADC was highly correlated with the aqueductal CSF stroke volume in AD (P < 0.001; rs = 0.79). Although AD and NPH both involve CSF disorders, the two diseases do not have the same impact on the internal capsules. The magnitude of the ADC is related to the aqueductal CSF stroke volume in AD, whereas FA is related to ventricular volume in NPH.

Cerebrospinal Fluid Disorders: A Multidisciplinary Approach to Diagnosis and Management for the Practicing Otolaryngologist

Program Description: This miniseminar will provide a multidisciplinary perspective (rhinology, neurotology, head and neck, and neurosurgery) on the pathophysiology and management of cerebrospinal fluid disorders encountered by the practicing otolaryngologist. The program will discuss epidemiologic, radiologic, medical, and surgical aspects of spontaneous and iatrogenic cerebrospinal fluid leaks of the anterior and lateral skull bases and will highlight important considerations in proper diagnosis, workup, and management. Educational Objectives: (1) Properly recognize, diagnose, and manage spontaneous and iatrogenic cerebrospinal fluid (CSF) leaks of both the anterior and lateral skull base. (2) Explain various medical and surgical interventions available for the treatment of CSF disorders encountered by the otolaryngologist.

Evaluation of hydrocephalus and other cerebrospinal fluid disorders with MRI: An update.

MRI is not only beneficial in the diagnosis of cerebrospinal fluid (CSF)-related diseases, but also aids in planning the management and post-surgery follow-up of the patients. With recent advances in MRI systems, there are many newly developed sequences and techniques that rapidly enable evaluation of CSF-related disorders with greater accuracy. For a better assessment of this group of disorders, radiologists should follow the developments closely and should be able to apply them when necessary. In this pictorial review, the role of MRI in the evaluation of hydrocephalus, CSF diversion techniques, and other CSF disorders is illustrated. Teaching Points • The 3D-SPACE seems to be most efficient technique for evaluation of hydrocephalus and ventriculostomy.• In complex cases, PC-MRI, 3D-heavily T2W, and/or CE-MRC images may prevent false results of 3D-SPACE.• MRI is beneficial in the diagnosis and management of hydrocephalus and other CSF-related diseases.

Influence of comorbidities in idiopathic normal pressure hydrocephalus — research and clinical care. A report of the ISHCSF task force on comorbidities in INPH

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome of ventriculomegaly, gait impairment, cognitive decline and incontinence that occurs in an elderly population prone to many types of comorbidities. Identification of the comorbidities is thus an important part of the clinical management of INPH patients. In 2011, a task force was appointed by the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) with the objective to compile an evidence-based expert analysis of what we know and what we need to know regarding comorbidities in INPH. This article is the final report of the task force. The expert panel conducted a comprehensive review of the literature. After weighing the evidence, the various proposals were discussed and the final document was approved by all the task force members and represents a consensus of expert opinions. Recommendations regarding the following topics are given: I. Musculoskeletal conditions; II. Urinary problems; III. Vascular disease including risk factors, Binswanger disease, and white matter hyperintensities; IV. Mild cognitive impairment and Alzheimer disease including biopsies; V. Other dementias (frontotemporal dementia, Lewy body, Parkinson); VI. Psychiatric and behavioral disorders; VII. Brain imaging; VIII. How to investigate and quantify. The task force concluded that comorbidity can be an important predictor of prognosis and post-operative outcome in INPH. Reported differences in outcomes among various INPH cohorts may be partly explained by variation in the rate and types of comorbidities at different hydrocephalus centers. Identification of comorbidities should thus be a central part of the clinical management of INPH where a detailed history, physical examination, and targeted investigations are the basis for diagnosis and grading. Future INPH research should focus on the contribution of comorbidity to overall morbidity, mortality and long-term outcomes.

Na+ dependent acid-base transporters in the choroid plexus; insights from slc4 and slc9 gene deletion studies

The choroid plexus epithelium (CPE) is located in the ventricular system of the brain, where it secretes the majority of the cerebrospinal fluid (CSF) that fills the ventricular system and surrounds the central nervous system. The CPE is a highly vascularized single layer of cuboidal cells with an unsurpassed transepithelial water and solute transport rate. Several members of the slc4a family of bicarbonate transporters are expressed in the CPE. In the basolateral membrane the electroneutral Na+ dependent Cl−/HCO3− exchanger, NCBE (slc4a10) is expressed. In the luminal membrane, the electrogenic Na+:HCO3− cotransporter, NBCe2 (slc4a5) is expressed. The electroneutral Na+:HCO3− cotransporter, NBCn1 (slc4a7), has been located in both membranes. In addition to the bicarbonate transporters, the Na+/H+ exchanger, NHE1 (slc9a1), is located in the luminal membrane of the CPE. Genetically modified mice targeting slc4a2, slc4a5, slc4a7, slc4a10, and slc9a1 have been generated. Deletion of slc4a5, 7 or 10, or slc9a1 has numerous impacts on CP function and structure in these mice. Removal of the transporters affects brain ventricle size (slc4a5 and slc4a10) and intracellular pH regulation (slc4a7 and slc4a10). In some instances, removal of the proteins from the CPE (slc4a5, 7, and 10) causes changes in abundance and localization of non-target transporters known to be involved in pH regulation and CSF secretion. The focus of this review is to combine the insights gathered from these knockout mice to highlight the impact of slc4 gene deletion on the CSF production and intracellular pH regulation resulting from the deletion of slc4a5, 7 and 10, and slc9a1. Furthermore, the review contains a comparison of the described human mutations of these genes to the findings in the knockout studies. Finally, the future perspective of utilizing these proteins as potential targets for the treatment of CSF disorders will be discussed.

Structural Olfactory Nerve Changes in Patients Suffering from Idiopathic Intracranial Hypertension

BackgroundComplications of idiopathic intracranial hypertension (IIH) are usually caused by elevated intracranial pressure (ICP). In a similar way as in the optic nerve, elevated ICP could also compromise the olfactory nerve system. On the other side, there is growing evidence that an extensive lymphatic network system around the olfactory nerves could be disturbed in cerebrospinal fluid disorders like IIH. The hypothesis that patients with IIH suffer from hyposmia has been suggested in the past. However, this has not been proven in clinical studies yet. This pilot study investigates whether structural changes of the olfactory nerve system can be detected in patients with IIH.Methodology/Principal FindingsTwenty-three patients with IIH and 23 matched controls were included. Olfactory bulb volume (OBV) and sulcus olfactorius (OS) depth were calculated by magnetic resonance techniques. While mean values of total OBV (128.7±38.4 vs. 130.0±32.6 mm3, p=0.90) and mean OS depth (8.5±1.2 vs. 8.6±1.1 mm, p=0.91) were similar in both groups, Pearson correlation showed that patients with a shorter medical history IIH revealed a smaller OBV (r=0.53, p<0.01). In untreated symptomatic patients (n=7), the effect was greater (r=0.76, p<0.05). Patients who suffered from IIH for less than one year (n=8), total OBV was significantly smaller than in matched controls (116.6±24.3 vs. 149.3±22.2 mm3, p=0.01). IIH patients with visual disturbances (n=21) revealed a lower OS depth than patients without (8.3±0.9 vs. 10.8±1.0 mm, p<0.01).Conclusions/SignificanceThe results suggest that morphological changes of the olfactory nerve system could be present in IIH patients at an early stage of disease.

Recurrent Intrahepatic Dislocation of Ventriculoperitoneal Shunt

Dislocation of ventriculoperitoneal (VP) shunt catheters is a well known complication after treatment of cerebrospinal fluid disorders; however, secondary perforation of the liver capsule by the catheter is exceptional. The literature on VP shunt complications involving the liver, their possible pathomechanisms and minimally invasive recovery strategies in reference to our own experience is reviewed. We present a patient who suffered penetration of the liver by the peritoneal catheter of her VP shunt. Causing intermittent epigastric pain, the shunt tip was found to have progressively dislocated into the liver, as documented by CT scans. A laparoscopic approach was indicated to recover the shunt. The peritoneal catheter was found to be covered by widespread adhesions, consistent with peritoneal fibrosis. After local adhesiolysis, it was successfully recovered without shunt dysfunction, hemorrhage of the liver, or biliary fistula. After 4 months, dislocation recurred with formation of a subdiaphragmatic pseudocapsule. Early formation of fibrosis was detected during laparoscopic revision surgery. Although bacterial smears from both laparoscopic surgeries did not show any pathological findings, the patient presented with an abscess in the Douglas pouch 4 months later. Coagulase-negative staphylococci were found on ultrasound-guided insertion of a pigtail catheter. The VP shunt had to be replaced by a ventriculoatrial shunt. The infection was treated successfully with piperacillin. The subsequent 6 months follow-up period was without adverse events. The treatment of choice in this exceptional case of intrahepatic shunt dislocation was laparoscopic recovery of the catheter. Laparoscopy allowed good visualization during adhesiolysis, immediate exclusion of hemorrhage or bile fistula at the puncture site, as well as function control and safe deposition of the shunt tip. Chronic infection as an underlying cause of peritoneal fibrosis has to be ruled out.

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

BackgroundThe 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.MethodsHydrocephalus 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.ResultsLateral 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.ConclusionsAQP4 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.

Report on BrainChild hydrocephalus conference

A report of a meeting sponsored by the BrainChild Foundation on the challenges for hydrocephalus researchers to provide the information required for better management of cerebrospinal fluid disorders.

Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats

A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport, 125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of 125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport.

Early combined cranioplasty and programmable shunt in patients with skull bone defects and CSF-circulation disorders

Objective: This study assesses the clinical outcome after early combined cranioplasty (own frozen bone) and shunt implantation (Codman-Medos programmable VP shunt) in patients with skull bone defects and cerebrospinal fluid (CSF) circulation disorders.Method: Medical records were reviewed retrospectively for the last 100 patients with CSF disorders after trauma or subarachnoid hemorrhage (SAH), who previously underwent decompressive craniotomy owing to therapy-resistant brain swelling. Patients treated with early (5 to 7 weeks after injury) combined cranioplasty and shunt implantation were analysed and a follow-up for the survivors was obtained.Results: In 60 patients with a daily CSF external drainage over 150 ml and dilated ventricles in CT scan, a programmable VP shunt was implanted simultaneously with the cranioplasty within 5.1 weeks after decompression. The neurological condition 6 months later was good (independent patients) in 39 cases (65%); 12 patients (20%) survived with a severe disability; three patients (5%) remained in a persistent vegetative state and only six patients (10%) died. There were few complications: bone or shunt infection (three cases), post-operative intracranial bleeding (one case), transitory neurological impairment after bone reimplantation (two cases), bone resorption (two cases) and shunt dysfunction (three cases).Conclusion: The early reimplantation of the patient's own skull bone combined to the employment of a programmable shunt system allowed us a dynamic adjustment of the intracranial pressure (ICP) changes. The combined treatment reduced the number of required surgical procedures, complications and unsatisfactory patient outcomes.

Transcranial Doppler in infantile cerebrospinal fluid disorders: clinical validity

The present study was designed to investigate a possible relationship between transcranial Doppler sonography (TCD) parameters with infantile hydrocephalus and other types of cerebrospinal fluid (CSF) abnonnalities, i.e. arrested hydrocephalus and essential ventriculomegaly. TCD parameters in the major arteries of the circle of Willis were studied in hydrocephalic children (n = 12) before and after insertion of a ventricular shunt device. It was correlated with TCD parameters of children with CSF disorders (n = 13), in whom no surgery was performed. Also, TCD parameters were assessed in control cases (n = 10). Mean values for medial cerebral artery (MCA) flow velocities were higher in the essential ventriculomegaly (75.38 ± 4.1) and in the control group (73.93 ± 3.4) compared with hydrocephalic children (64.13 ± 5.3). All hydrocephalic children had a higher mean MCA pulsatility index (RI) (1.08 ± 0.13) and resistance index (RI) (0.64 ± 0.17) values than the essential ventriculomegaly group (PI: 1.03 ± 0.48; RI: 0.63 ± 0.13) and the control group (PI: 0.84 ± 0.32; RI: 0.57 ± 0.23). Analysis of all TCD parameters disclosed its usefulness only after a particular and thorough evaluation of the TCD results with special emphasis in the clinical correlation of every case.

Evidence of the subcommissural organ in humans and its association with hydrocephalus.

A group of structures in the human central nervous system (CNS) represents a noteworthy dilemma for the neuroscientist, particularly to the neuroanatomist. In this paper an attempt is made by extensive review of the literature to give an account of the significance of the subcommissural organ (SCO) in humans and its possible relationship with cerebrospinal fluid (CSF) disorders. The subcommissural organ is a gland located in the diencephalic plate caudal to the pineal organ that covers the anterior part of the posterior commissure. Histologically, it is a highly differentiated ependyma. After birth, the SCO undergoes regressive changes, and in the adult human only remnants of the specialized SCO cells can be found. The Reissner's fiber (RF) may be regarded as a pure secretory product of the SCO. Only a few vertebrate species have been reported to lack an RF, namely the bat, camel, chimpanzee, and man. Nonetheless, a successful immunoreaction against a proteinaceous compound of the fetal human SCO has been performed. Recently, new interest was elicited regarding SCO and its possible implication in the pathogenesis of hydrocephalus. The objective of this review is to bring into consideration the relevance of the SCO to the neurosurgical scenario.

Multifocal dural arteriovenous shunts in children

The authors present four consecutive cases of multiple dural arteriovenous (AV) shunts in children. This entity represents a rare but severe clinical situation. The etiology of the shunts is not known. There is clinical and radiological evidence that they are evolutionary lesions. The clinical presentation in this series was usually by cardiac manifestations (one case), cerebrospinal fluid disorders (two cases), neurological symptoms (three cases), including intracranial hemorrhage (two cases), and cranial bruits (four cases). No radical treatment leading to anatomical cure of all dural AV shunts was thought to be possible using current methods, including modern endovascular and surgical techniques, in any of the four cases. Therefore, treatment was only symptomatic and directed at some of the AV shunts. Targeted arterial embolization with permanent embolic agents represents the most rational technique for symptomatic relief in these patients. However, clinical recurrence often happens without evidence of recanalization. Secondary multifocal pial AV shunts opening into the abnormal sinus occurred in two of the cases; they may have been induced by venous sump from the sinus draining the dural AV shunts. Mechanical occlusion (or excision) in multiple dural AV shunts in children does not represent a satisfactory goal, as the shunts can be the expression of a more complex and yet unknown disease.

Cisternoatrial, ventriculocisternal, and other cisternal shunts simplified. A percutaneous technique.

✓ The authors describe a shunt inserted by a percutaneous route to the cisterna magna for the treatment of various cerebrospinal fluid disorders.