Paediatric pineal region cysts: enigma or impaired neurofluid system?

PURPOSE: Pineal region cysts (PCs) may affect the tectum and aqueduct and cause deep central vein congestion. Beside headaches, PC often causes a broad range of symptoms, leading to prolonged diagnosis and therapy. The aims of this study are to reveal parameters that might explain the ambiguity of the symptoms and to identify factors in association with the respiration-driven neurofluid system. METHODS: This retrospective study included 28 paediatric patients (mean age 11.6 years) who received surgical treatment and 18 patients (mean age 11.3 years) who were followed conservatively. Symptoms, time to diagnosis, cyst size, ventricular indices, head circumference and postoperative outcome, were analysed. Four patients were investigated for CSF dynamics with real-time MRI. The mean follow-up time was 1.6 years. RESULTS: The most common early onset symptoms were headaches (92%), blurred vision (42.8%), sleep disturbances (39.3%) and vertigo (32.1%). Tectum contact was observed in 82% of patients, and MRI examinations revealed that imaging flow void signals were absent in 32.1% of patients. The maximal cyst diameters were 13.7 × 15.6 mm (mean). Together with a postoperative flow void signal, 4 patients recovered their respiration-driven CSF aqueductal upward flow, which was not detectable preoperatively. After surgery the main symptoms improved. CONCLUSION: Despite proximity to the aqueduct with frequently absent flow void signals, hydrocephalus was never detected. Data from real-time MRI depicted a reduced preoperative filling of the ventricular CSF compartments, indicating a diminished fluid preload, which recovered postoperatively.

Deep breathing couples CSF and venous flow dynamics.

Venous system pathologies have increasingly been linked to clinically relevant disorders of CSF circulation whereas the exact coupling mechanisms still remain unknown. In this work, flow dynamics of both systems were studied using real-time phase-contrast flow MRI in 16 healthy subjects during normal and forced breathing. Flow evaluations in the aqueduct, at cervical level C3 and lumbar level L3 for both the CSF and venous fluid systems reveal temporal modulations by forced respiration. During normal breathing cardiac-related flow modulations prevailed, while forced breathing shifted the dominant frequency of both CSF and venous flow spectra towards the respiratory component and prompted a correlation between CSF and venous flow in the large vessels. The average of flow magnitude of CSF was increased during forced breathing at all spinal and intracranial positions. Venous flow in the large vessels of the upper body decreased and in the lower body increased during forced breathing. Deep respiration couples interdependent venous and brain fluid flow-most likely mediated by intrathoracic and intraabdominal pressure changes. Further insights into the driving forces of CSF and venous circulation and their correlation will facilitate our understanding how the venous system links to intracranial pressure regulation and of related forms of hydrocephalus.

Neurofluids-Deep inspiration, cilia and preloading of the astrocytic network.

With the advent of real-time MRI, the motion and passage of cerebrospinal fluid can be visualized without gating and exclusion of low-frequency waves. This imaging modality gives insights into low-volume, rapidly oscillating cardiac-driven movement as well as sustained, high-volume, slowly oscillating inspiration-driven movement. Inspiration means a spontaneous or artificial increase in the intrathoracic dimensions independent of body position. Alterations in thoracic diameter enable the thoracic and spinal epidural venous compartments to be emptied and filled, producing an upward surge of cerebrospinal fluid inside the spine during inspiration; this surge counterbalances the downward pooling of venous blood toward the heart. Real-time MRI, as a macroscale in vivo observation method, could expand our knowledge of neurofluid dynamics, including how astrocytic fluid preloading is adjusted and how brain buoyancy and turgor are maintained in different postures and zero gravity. Along with these macroscale findings, new microscale insights into aquaporin-mediated fluid transfer, its sensing by cilia, and its tuning by nitric oxide will be reviewed. By incorporating clinical knowledge spanning several disciplines, certain disorders-congenital hydrocephalus with Chiari malformation, idiopathic intracranial hypertension, and adult idiopathic hydrocephalus-are interpreted and reviewed according to current concepts, from the basics of the interrelated systems to their pathology.

An adjustable gravitational valve for initial VP-shunt treatment in hydrocephalic preterm neonates and infants below 1 year of age.

OBJECTIVE: Shunt treatment for hydrocephalus in children should aim for sustainable flexibility in regard to optional, perspective pressure level adjustment during advancing physical and mental development. Gravitation-assisted shunt valves are designed to prevent hydrostatic over-drainage frequently observed in the long course of shunt-treated hydrocephalus. We prospectively studied and analyzed the implication, safety, and feasibility for an adjustable gravitational unit combined with a fixed differential-pressure (DP) valve for neonates and infants primary shunted within the first 12 months of life. METHODS: Clinical course of hydrocephalic neonates and infants who received initial VP-shunt insertion in the early post-natal phase were monitored prospectively on the basis of our digital institutional Hydrocephalus & Shunt Registry. All patients were equipped with a fixed DP valve combined with a programmable gravitational unit activated in upright body position. Patients with a minimum shunt follow-up of 24 months were considered for further statistical analysis regarding hydrocephalus etiology, surgical setting, pre- and post-operative ventricular enlargement, head circumference, valve pressure setting, implication for the adjustment option of the gravitational unit, type and number of shunt complications, and revision-free shunt and valve survival. RESULTS: Seventy-eight pediatric patients received primary VP-shunt insertion at a mean age of 10 weeks with age gestationally corrected for preterm neonates. Hydrocephalus was related to perinatal IVH (64%), CNS malformation (11%), spina bifida (9%), congenital aqueductal stenosis (9%), and idiopathic (4%) or post-infectious etiology (3%). Fifty-two patients (70%) presented with history of prematurity (gestational age 23-36 weeks). Regular follow-up carried out for a mean period of 63 months demonstrated that ventricular enlargement decreased significantly after applied treatment and excessive head growth could be counteracted effectively. At least one pressure level adjustment was performed in 31% of all patients after 12 months, in 42% after 24 months, and in 64% at the time of last clinical follow-up since initial shunt insertion. Pressure level adjustments were successful in cases of clinical or radiographic signs of under- or over-drainage for individual patients of various ages during entire clinical course. Mean pressure setting for upright position was 24.1 cm H2O at the time of initial shunt insertion and increased to 26.4 cmH2O at the time of last clinical follow-up. Revision-free shunt-survival rates after 12 and 24 months were 79% and 70% and valve-survival rates 91% and 90%, respectively. CONCLUSION: The combination of a fixed DP valve with an adjustable gravitational unit utilized as first-line shunt regimen was feasible and safe in a highly vulnerable subgroup of hydrocephalic infants. The adjustment option for the gravitational unit showed frequent and increasing implication over time and was beneficial even during the very early developmental stage of limited autonomous mobility. To our knowledge this is the first ever reported long-term investigation of an age-consistent pediatric patient collective primary shunted with an adjustable gravitational valve system.

Hydrocephalus Revisited: New Insights into Dynamics of Neurofluids on Macro- and Microscales.

New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time magnetic resonance imaging (MRI) evaluation of cerebrospinal fluid (CSF) flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids: (1) inspiration is a major driving force; (2) adequate filling of brain ventricles by balanced CSF upsurge is sensed by cilia; and (3) the perivascular glial network connects the ependymal surface to the pericapillary Virchow-Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework, improving knowledge and therapy for severe disorders of normal-pressure and posthemorrhagic hydrocephalus, spontaneous intracranial hypotension, and spaceflight disease.

Spinal Deformities after Childhood Tumors.

Childhood tumors of the central nervous system (CNS) and other entities affecting the spine are rare. Treatment options vary from surgical biopsy to partial, subtotal, and total resection, to radiation, to chemotherapy. The aim of this study is to investigate spinal deformity and subsequent surgical interventions in this patient cohort. A retrospective review at our institution identified children with CNS tumors, spinal tumors, and juxta-spinal tumors, as well as spinal deformities. Tumor entity, treatment, mobilization, and radiographic images were analyzed relative to the spinal deformity, using curve angles in two planes. Conservative or surgical interventions such as orthotic braces, growth-friendly spinal implants, and spinal fusions were evaluated and analyzed with respect to treatment results. Tumor entities in the 76 patients of this study included CNS tumors (n = 41), neurofibromatosis with spinal or paraspinal tumors (n = 14), bone tumors (n = 12), embryonal tumors (n = 7), and others (n = 2). The initial treatment consisted of surgical biopsy (n = 5), partial, subtotal, or total surgical resection (n = 59), or none (n = 12), followed by chemotherapy, radiotherapy, or both (n = 40). Out of 65 evaluated patients, 25 revealed a moderate or severe scoliotic deformity of 71° (range 21-116°), pathological thoracic kyphosis of 66° (range 50-130°), and lordosis of 61° (range 41-97°). Surgical treatment was performed on 21 patients with implantation of growth-friendly spinal implants (n = 9) as well as twelve dorsal spinal fusions (two with prior halo distraction). Surgical interventions significantly improved spinal deformities without additional neurological impairment. With the increasing number of children surviving rare tumors, attention should be focused on long-term problems such as spinal deformities and consequent disabilities. A significant number of children with CNS tumors, spinal tumors or juxta-spinal tumors required surgical intervention. Early information about spinal deformities and a close follow-up are mandatory for this patient group.

Biological responses to individualized small titanium implants for the treatment of focal full-thickness knee cartilage defects in a sheep model.

BACKGROUND: The present study aimed to evaluate the functional, radiological and histological outcome of a customized focal implant for the treatment of focal full-thickness cartilage defects in sheep. METHODS: The study used magnetic resonance imaging data as the basis for construction of the titanium implant using a three-dimensional printing technique. This was then placed on the medial condyle of the knee joint in eight sheep and left in place in vivo over a period of six months. Following euthanasia, the local biological response was analyzed using micro-computed tomography, light microscopy and histological evaluation (International Cartilage Repair Society (ICRS) score). The variables were analyzed using a generalized linear mixed model. Odds ratios were given with 95% confidence intervals. RESULTS: The osseointegration rate was 62.1% (SD 3.9%). All implants were prone to the neighboring cartilage bed (4.4-1096.1 µm). Using the IRCS score, the elements 'surface', 'matrix', 'cell distribution' and 'cell population' all showed pathological changes on the operated side, although these did not correlate with implant elevation. On average, a difference of 0.7 mm (±2 mm) was found between the digitally planned implant and the real implant. CONCLUSIONS: As a result of imprecise segmentation and difficult preparation conditions at the prosthesis bed, as well as changes at the surface of the implant over the operational lifetime of the prosthesis, it must be stated that the approach implemented here of using a customized implant for the treatment of focal full-thickness cartilage defects at the knee did not meet our expectations.

[Coronavirus pandemic-Memories of the flu epidemic from 1918 from a gynecological and obstetric perspective]. / Coronavirus-Pandemie ­ Erinnerungen an die Grippe-Epidemie von 1918 aus gynäkologisch-geburtshilflicher Sicht.

From the medical reports on the flu epidemic in 1918, there is accordance with the present-day corona pandemic. The symptoms, course and outcome all seem to show parallels. Pregnant women in the last trimester are to be classified as being particularly vulnerable. Physicians in several disciplines, e.g. gynecology, general medicine and internal medicine are equally called upon to be particularly vigilant.

Spinal CSF flow in response to forced thoracic and abdominal respiration.

BACKGROUND: Respiration-induced pressure changes represent a powerful driving force of CSF dynamics as previously demonstrated using flow-sensitive real-time magnetic resonance imaging (MRI). The purpose of the present study was to elucidate the sensitivity of CSF flow along the spinal canal to forced thoracic versus abdominal respiration. METHODS: Eighteen subjects without known illness were studied using real-time phase-contrast flow MRI at 3 T in the aqueduct and along the spinal canal at levels C3, Th1, Th8 and L3. Subjects performed a protocol of forced breathing comprising four cycles of 2.5 s inspiration and 2.5 s expiration. RESULTS: The quantitative results for spinal CSF flow rates and volumes confirm previous findings of an upward movement during forced inspiration and reversed downward flow during subsequent exhalation-for both breathing types. However, the effects were more pronounced for abdominal than for thoracic breathing, in particular at spinal levels Th8 and L3. In general, CSF net flow volumes were very similar for both breathing conditions pointing upwards in all locations. CONCLUSIONS: Spinal CSF dynamics are sensitive to varying respiratory performances. The different CSF flow volumes in response to deep thoracic versus abdominal breathing reflect instantaneous adjustments of intrathoracic and intraabdominal pressure, respectively. Real-time MRI access to CSF flow in response to defined respiration patterns will be of clinical importance for patients with disturbed CSF circulation like hydrocephalus, pseudotumor cerebri and others.

Upward movement of cerebrospinal fluid in obstructive hydrocephalus-revision of an old concept.

PURPOSE: The specific pathophysiological processes in many forms of obstructive hydrocephalus (HC) are still unclear. Current concepts of cerebrospinal fluid (CSF) dynamics presume a constant downward flow from the lateral ventricles towards subarachnoid spaces, which are in contrast to neurosurgical observations and findings of MRI flow studies. The aim of our study was to analyze CSF movements in patients with obstructive HC by neuroendoscopic video recordings, X-ray studies, and MRI. METHODS: One hundred seventeen pediatric patients with obstructive HC who underwent neuroendoscopy in our center were included. Video recordings were analyzed in 85 patients. Contrast-enhanced X-rays were conducted during surgery prior to intervention in 75 patients, and flow void signals on pre-operative MRI could be evaluated in 110 patients. RESULTS: In 83.5% of the video recordings, CSF moved upwards synchronous to inspiration superimposed by cardiac pulsation. Application of contrast medium revealed a flow delay in 52% of the X-ray studies prior to neurosurgery, indicating hindered CSF circulation. The appearances and shapes of flow void signals in 88.2% of the pre-operative MRI studies suggested valve-like mechanisms and entrapment of CSF. CONCLUSIONS: Neuroendoscopic observations in patients with obstructive HC revealed upward CSF movements and the corresponding MRI signs of trapped CSF in brain cavities. These observations are in contrast to the current pathophysiological concept of obstructive HC. However, recent real-time flow MRI studies demonstrated upward movement of CSF, hence support our clinical findings. The knowledge of cranial-directed CSF flow expands our understanding of pathophysiological mechanisms in HC and is the key to effective treatment.

Two-Micron Continuous-Wave Laser-Assisted Neuroendoscopy: Clinical Experience of Two Institutions in 524 Procedures.

OBJECTIVE: To present the clinical experience of 2 neurosurgical centers with the use of a 2-micron continuous-wave laser (2µ-cwL) system as standard tool in neuroendoscopic procedures and to discuss the safety and efficacy of this system. METHODS: In total, 469 patients underwent neuroendoscopic procedures using 2µ-cwL between September 2009 and January 2015. All patient data were retrospectively reviewed. In total, 241 (51%) patients were children and 228 (49%) adults. Mean age was 27.5 years (range: 3 days to 83 years). Intraoperative ultrasonography or neuronavigation were used to guide ventricular or cyst puncture and for intraventricular or intracystic orientation if necessary. RESULTS: A total of 524 neuroendoscopic procedures using 2µ-cwL were performed. Laser-assisted endoscopic third ventriculostomy was the most common procedure in 302 (64%) patients. Cyst fenestration was performed in 124 (26%), septostomy in 45, tumor biopsy in 41, tumor resection in 8, and choroid plexus coagulation in 3 patients. There was no intraoperative complication directly attributable to the use of laser and an overall procedural complication rate of 4.8%. CONCLUSIONS: This large series of 2µ-cwL as a routine tool in neuroendoscopic procedures demonstrates that 2µ-cwL is safe for endoscopic third ventriculostomy, septostomy, cyst fenestration, and intraventricular tumor biopsy or resection. As a cutting and coagulation tool, it combines the action of mechanical tools like forceps, balloons, and scissors plus those of electric tools. It therefore renders neuroendoscopic procedures more straightforward with a minimum need to change tools.

Early surgical management and long-term surgical outcome for intraventricular hemorrhage-related posthemorrhagic hydrocephalus in shunt-treated premature infants.

OBJECTIVE Perinatal intraventricular hemorrhage (IVH) in premature neonates may lead to severe neurological disability and lifelong treatment requirement for consecutive posthemorrhagic hydrocephalus (PHHC). Early CSF diversion as a temporizing measure, or a permanent ventriculoperitoneal shunt (VPS), is the treatment of choice. Preterm neonates are not only at high risk for different perinatal but also for treatment-related complications. The authors reviewed their institutional neurosurgical management for preterm neonates with IVH-related PHHC and evaluated shunt-related surgical outcome for this particular hydrocephalus etiology after completion of a defined follow-up period of 5 years after initial shunt insertion. METHODS The authors retrospectively analyzed early surgical management for preterm newborns who presented with IVH and PHHC between 1995 and 2015. According to the guidelines, patients received implantation of a ventricular access device (VAD) for temporizing measures or direct VPS insertion as first-line surgical treatment. Surgical outcome was evaluated for a subgroup of 72 patients regarding time to first shunt revision and the mean number of shunt revisions during a time span of 5 years after initial shunt insertion. Gestational age (GA), extent of IVH, and timing and modality of initial surgical intervention were analyzed for potential impact on corresponding surgical outcome. RESULTS A total cohort of 99 preterm newborns with GAs ranging from 22 to 36 weeks (mean 28.3 weeks) with perinatal IVH-related PHHC and a median follow-up duration of 9.9 years postpartum could be selected for further investigation. Extent of perinatal IVH was defined as grade III or as periventricular hemorrhagic infarction in 75% of the patient cohort. Seventy-six patients (77%) underwent VAD insertion and temporizing measures as initial surgical treatment; for 72 (95%) of these a later conversion to permanent ventriculoperitoneal shunting was performed, and 23 patients received direct VPS insertion. Etiological and treatment-related variables revealed no significant impact on revision-free shunt survival but increased the mean numbers of shunt revisions after 5 years for low GA, higher-order IVH in the long term. CONCLUSIONS Low GA and higher-order IVH in preterm neonates with PHHC who are treated with VPSs show no significant impact on time to first shunt revision (i.e., revision-free shunt survival), but marked differences in mean revision rates evaluated after completion of 5 years of follow-up. Temporizing measures via a VAD represent a rational strategy to gain time and decision guidance in preterm patients with PHHC before permanent VPS insertion.

Respiration and the watershed of spinal CSF flow in humans.

The dynamics of human CSF in brain and upper spinal canal are regulated by inspiration and connected to the venous system through associated pressure changes. Upward CSF flow into the head during inspiration counterbalances venous flow out of the brain. Here, we investigated CSF motion along the spinal canal by real-time phase-contrast flow MRI at high spatial and temporal resolution. Results reveal a watershed of spinal CSF dynamics which divides flow behavior at about the level of the heart. While forced inspiration prompts upward surge of CSF flow volumes in the entire spinal canal, ensuing expiration leads to pronounced downward CSF flow, but only in the lower canal. The resulting pattern of net flow volumes during forced respiration yields upward CSF motion in the upper and downward flow in the lower spinal canal. These observations most likely reflect closely coupled CSF and venous systems as both large caval veins and their anastomosing vertebral plexus react to respiration-induced pressure changes.

Implementing a digital real-time Hydrocephalus and Shunt Registry to evaluate contemporary pattern of care and surgical outcome in pediatric hydrocephalus.

OBJECTIVE: Treatment monitoring and outcome evaluation in pediatric hydrocephalus require gapless documentation regarding surgical and clinical follow-up data beginning from day 1 of treatment in order to apply high quality of care. Endoscopic procedures, shunt insertion and revision surgeries, and individual modifications of valve hardware or pressure settings during follow-up as well as established outcome measurements are highly relevant for complete illustration of the patient's hydrocephalus histories. A digital tool to capture, organize, and analyze comprehensive treatment-related data was estimated long overdue, consequentially developed, and implemented in daily pediatric neurosurgical routine. METHODS: We established a self-contained, network-capable database application to supply and back up clinical information of complete surgical treatment history with implant status and follow up for all institutional pediatric hydrocephalus patients from 1995 to date. The application content has been prospectively complemented since 2012 during daily pediatric neurosurgical routine. Beside surgical data, neurological outcome and quality of life assessment were integrated according to validated scales to be recordable 2, 3, and 5 years after initial surgical intervention for prospective administration. The application is in continuous and problem-free use since implementation offering homogeneous and structured real-time information of surgical and corresponding neurological hydrocephalus-related data. By using an automatized data extraction tool, an exemplary surgical outcome evaluation reviewing institutional ventriculo-peritoneal shunt (VPS) treatment in infants over a period of more than 20 years was performed. To validate applicability, the Registry was successfully implemented in an external institution under identical conditions continuously serving for the same purpose until today. RESULTS: Upon completion of the developing process, the application was successfully implemented into routine clinical workflow of our institution. In total, 579 pediatric hydrocephalus patients entered into the Registry with collectively 1874 corresponding hydrocephalus-related surgeries (9% neuro-endoscopic procedures, 18% temporary CSF-diversions, 73% shunt surgeries) so far. For exemplary surgical outcome analysis, the total volume of complex data sets could easily be reduced stepwise in regard to requested inclusion criteria. The selection process generated conclusive data of 256 institutional pediatric VPS patients providing a median follow-up of 8.5 years. Surgical outcome was evaluated in regard to hydrocephalus etiology, applied valve design, valve augmentation, cause of initial malfunction, time to initial shunt revision, and number of total revisions. CONCLUSION: The pediatric hydrocephalus registry application delivers easy access to contemporary and up-to-date clinical information during daily clinical routine and proves comprehensive value for various scientific purposes. Institutional hydrocephalus etiologies, treatment modalities, and surgical outcome could be reviewed for a selected pediatric patient collective during an interval of more than 20 years and confirmed initial shunt treatment within the first year of age, communicating hydrocephalus and a history of prematurity as significant variables for unfavorable shunt survival and long-term revision rate. At our institution, the Registry emerged to an essential and sustainable tool to capture, organize, and analyze patterns of care in pediatric hydrocephalus patients of all etiologies and treatment modalities. Because of its adaptable and reliable predicate, a prospective multi-center utilization is currently in preparation.

Identification of the Upward Movement of Human CSF In Vivo and its Relation to the Brain Venous System.

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension.SIGNIFICANCE STATEMENT Effective disposal of brain cellular waste products via CSF has been demonstrated repeatedly in animal models. However, CSF dynamics in humans are still poorly understood. A novel quantitative real-time MRI technique yielded in vivo CSF flow directions, velocities, and volumes in the human brain and upper spinal canal. CSF moved upward toward the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated that CSF and venous flux act as closely communicating systems. The finding of a human CSF-venous network with upward CSF net movement opens new clinical concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension.

Contrast-enhanced shunt series ("shuntography") compare favorably to other shunt imaging modalities in detecting shunt occlusion.

BACKGROUND: Obstruction is a common cause of ventriculo-peritoneal shunt failure. Head computed tomography and plain x-ray examinations of shunt tubing ("shunt series") are routinely used in patients readmitted for reemerging symptoms but are of limited value. The validity of shunt series can be improved by applying contrast agent into the system (contrast-enhanced shunt series, a.k.a. a "shuntogram" or "shuntography"). We hypothesized that contrast-enhanced shunt series have a high predictive value for shunt revision surgeries. METHODS: We retrospectively re-evaluated 107 contrast-enhanced shunt series and reviewed the patient histories. We defined outcome parameters for calculating the utility of a pathological contrast-enhanced shunt series in predicting revision surgery. RESULTS: Of 107 contrast-enhanced shunt series, 41 examinations were positive for obstruction, mainly of the ventricular (36.5 %) and the peritoneal catheter (48.8 %). Within 30 days, 35 successful revision surgeries and 3 revision surgeries without resolution of symptoms were performed. In two cases the shunt tubing was found to be patent. Sixty-six negative examinations resulted in two revision surgeries, in addition to ten surgeries not attempting to restore patency. After 30 days, the specificity of contrast-enhanced shunt series for shunt failure identification was calculated at 92.8 %, the sensitivity at 94.7 %, the positive predictive value at 87.8 %, and the negative predictive value at 97.0 %. CONCLUSIONS: The contrast-enhanced shunt series method is a highly specific examination with a negative predictive value exceeding that of head computed tomography and plain shunt series. Compared to radionuclide marker studies, contrast-enhanced shunt series demonstrate better spatiotemporal resolution, enabling focused local surgical repair.

Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease: increased NPY levels and differential degradation of the NPY1-30 fragment.

Huntington's disease (HD) is an inherited and fatal polyglutamine neurodegenerative disorder caused by an expansion of the CAG triplet repeat coding region within the HD gene. Progressive dysfunction and loss of striatal GABAergic medium spiny neurons (MSNs) may account for some of the characteristic symptoms in HD patients. Interestingly, in HD, MSNs expressing neuropeptide Y (NPY) are spared and their numbers is even up-regulated in HD patients. Consistent with this, we report here on increased immuno-linked NPY (IL-NPY) levels in human cerebrospinal fluid (hCSF) from HD patients (Control n = 10; early HD n = 9; mid HD n = 11). As this antibody-based detection of NPY may provide false positive differences as a result of the antibody-based detections of only fragments of NPY, the initial finding was validated by investigating the proteolytic stability of NPY in hCSF using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and selective inhibitors. A comparison between resulting NPY-fragments and detailed epitope analysis verified significant differences in IL-NPY1-36/3-36 and NPY1-30 levels between HD patients and control subjects with no significant differences between early vs mid HD cases. Ex vivo degradomics analysis demonstrated that NPY is initially degraded to NPY1-30 by cathepsin D in both HD patients and control subjects. Yet, NPY1-30 is then further differentially hydrolyzed by thimet oligopeptidase (TOP) in HD patients and by neprilysin (NEP) in control subjects. Furthermore, altered hCSF TOP-inhibitor Dynorphin A1-13 (Dyn-A1-13 ) and TOP-substrate Dyn-A1-8 levels indicate an impaired Dyn-A-TOP network in HD patients. Thus, we conclude that elevated IL-NPY-levels in conjunction with TOP-/NEP-activity/protein as well as Dyn-A1-13 -peptide levels may serve as a potential biomarker in human CSF of HD. Huntington's disease (HD) patients' cerebrospinal fluid (CSF) exhibits higher neuropeptide Y (NPY) levels. Further degradomics studies show that CSF-NPY is initially degraded to NPY1-30 by Cathepsin D. The NPY1-30 fragment is then differentially degraded in HD vs control involving Neprilysin (NEP), Thimet Oligopeptidase (TOP), and TOP-Dynorphin-A network. Together, these findings may help in search for HD biomarkers.

Common molecularcytogenetic alterations in tumors originating from the pineal region.

Tumors of the pineal region (PR) are rare and can be subdivided into four main histomorphological groups: Pineal-parenchymal tumors (PPT), germ cell tumors (GCT), glial tumors and miscellaneous tumors. The appropriate pathological classification and grading of these malignancies is essential for determining the clinical management and prognosis. However, an early diagnosis is often delayed due to unspecific clinical symptoms, and histological support is not always decisive to identify the diversity of tumors of the PR. The present study aimed to characterize 18 tumors of the PR using comparative genomic hybridization. All the tumors were primarily surgically resected without any previous irradiation or chemotherapy. In addition to chromosomal aberrations in PPT and different GCTs of the PR, the present study described, for the first time, the chromosomal changes in a few rare entities (solitary-fibrous and neuroendocrine tumors) of the PR. The tumors in the study, regardless of histology and World Health Organization grade, were characterized by frequent gains at 7, 9q, 12q, 16p, 17 and 22q, and losses at 13q. While the detection of chromosomal aberrations in these tumors appears not to be indicative enough of histological entities and their grade of malignancy, the present data may be of use to select genes of interest for higher resolution genomic analyses.