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.

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.

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.

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.

Inspiration is the major regulator of human CSF flow.

The mechanisms behind CSF flow in humans are still not fully known. CSF circulates from its primary production sites at the choroid plexus through the brain ventricles to reach the outer surface of the brain in the subarachnoid spaces from where it drains into venous bloodstream and cervical lymphatics. According to a recent concept of brain fluid transport, established in rodents, CSF from the brain surface also enters the brain tissue along para-arterial routes and exits through paravenous spaces again into subarachnoid compartments. This unidirectional flow is mainly driven by arterial pulsation. To investigate how CSF flow is regulated in humans, we applied a novel real-time magnetic resonance imaging technique at high spatial (0.75 mm) and temporal (50 ms) resolution in healthy human subjects. We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing, high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow in humans. Inspiratory thoracic pressure reduction is expected to directly modulate the hydrostatic pressure conditions for the low-resistance paravenous, venous, and lymphatic clearance routes of CSF. Furthermore, the experimental approach opens new clinical opportunities to study the pathophysiology of various forms of hydrocephalus and to design therapeutic strategies in relation to CSF flow alterations.

Safety and efficacy of gravitational shunt valves in patients with idiopathic normal pressure hydrocephalus: a pragmatic, randomised, open label, multicentre trial (SVASONA).

OBJECTIVES: To investigate whether gravitational valves reduce the risk of overdrainage complications compared with programmable valves in ventriculoperitoneal (VP) shunt surgery for idiopathic normal pressure hydrocephalus (iNPH). BACKGROUND: Patients with iNPH may benefit from VP shunting but are prone to overdrainage complications during posture changes. Gravitational valves with tantalum balls are considered to reduce the risk of overdrainage but their clinical effectiveness is unclear. METHODS: We conducted a pragmatic, randomised, multicentre trial comparing gravitational with non-gravitational programmable valves in patients with iNPH eligible for VP shunting. The primary endpoint was any clinical or radiological sign (headache, nausea, vomiting, subdural effusion or slit ventricle) of overdrainage 6 months after randomisation. We also assessed disease specific instruments (Black and Kiefer Scale) and Physical and Mental Component Scores of the Short Form 12 (SF-12) generic health questionnaire. RESULTS: We enrolled 145 patients (mean (SD) age 71.9 (6.9) years), 137 of whom were available for endpoint analysis. After 6 months, 29 patients in the standard and five patients in the gravitational shunt group developed overdrainage (risk difference -36%, 95% CI -49% to -23%; p<0.001). This difference exceeded predetermined stopping rules and resulted in premature discontinuation of patient recruitment. Disease specific outcome scales did not differ between the groups although there was a significant advantage of the gravitational device in the SF-12 Mental Component Scores at the 6 and 12 month visits. CONCLUSIONS: Implanting a gravitational rather than another type of valve will avoid one additional overdrainage complication in about every third patient undergoing VP shunting for iNPH.

On the method of a randomised comparison of programmable valves with and without gravitational units: the SVASONA study.

OBJECTIVE: The supremacy of low-pressure valves (LPV) in the therapy of patients with idiopathic normal pressure hydrocephalus (iNPH) has been proven by the Dutch NPH study. The downside of LPVs is the high rate of overdrainage complications. In the meantime gravitational units have been developed with the objective of minimising overdrainage complications. Do these gravitational units allow the same favourable outcomes as in the Dutch NPH study without overdrainage complications? The goal of this prospective randomised controlled multicentre trial is to compare the rate of overdrainage complications after shunt surgery with programmable valves with or without a gravitational unit. METHOD: Patients suspected with iNPH with gait ataxia and one or two other symptoms of Hakim's triad and enlarged ventricles on CT or MRI underwent a cerebrospinal fluid (CSF) infusion test, CSF tap test and/or continuous ICP measurement in seven experienced centres. If iNPH was diagnosed the patients were randomised to receive a ventriculoperitoneal shunt with a programmable valve with or without a gravitational unit. The patients were followed up for 3, 6 and 12 months after surgery. The primary hypothesis of the study was that programmable valves with gravitational units will reduce the rate of overdrainage from 25% to 10%. The outcome measured by iNPH-specific outcome scales (Kiefer score, Black grading scale) and the generic quality of life (short form 12, SF12) was defined as the secondary endpoint. To detect the hypothesised difference in the incidence of overdrainage with a type I error of 5% and a type II error of 20%, correcting for multiple testing and an anticipated drop-out rate of 10%, we planned to enrol 250 patients. To ensure safety and efficacy we performed a planned interim analysis halfway. RESULTS: The study design has been found to be effective with regard to the primary hypothesis. CONCLUSION: The design of the SVASONA study was developed to be able to confirm the primary hypothesis. Thus, the method of the study should solve the dilemma of the Dutch NPH study by the randomised comparison of LPVs with and without gravitational units.

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.

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.

CNS tumor 22 years after spinal neuroblastoma IV: diagnostic dilemma between recurrence and secondary malignancy.

We present the very unusual case of a young woman suffering from a brain tumor 22 years after a stage IV spinal neuroblastoma as an infant, demonstrating the difficulties of differentiating late neuroblastoma relapse from secondary supratentorial primitive neuroectodermal tumor (sPNET). Lacking specific immunohistochemical features, the first cerebral tumor at the age of 21 was regarded as sPNET, and we pursued a therapeutic approach consisting of neurosurgical resection as well as irradiation and high-dose alkylator-based chemotherapy according to the HIT2000 protocol. Two years later the patient suffered from a diffusely infiltrating local recurrence, changing its imaging appearance as well as its immunohistochemical characteristics, now revealing disseminated positivity for neuron-specific enolase and neural cell adhesion molecule. Moreover, the lack of PNET-specific translocations (EWS/FLI1 gene fusion) in both brain tumors as well as the development of hepatic metastases was more compatible with the diagnosis of a very late relapse 22 years after initial stage IV spinal neuroblastoma.

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.

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.

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.

Piezoelectric osteotomies in craniofacial procedures: a series of 15 pediatric patients. Technical note.

Frontoorbital advancement has become a standard method both to increase intracranial volume and to improve facial appearance in patients with syndromal or nonsyndromal craniosynostosis. Relevant complications of this procedure include severe hemorrhage and trauma to intracranial, orbital, or facial soft tissues, which mostly arise during the process of bone exposure or osteotomy. To minimize the risk of soft tissue injury and to increase the precision of the osteotomy, the authors applied a piezoelectric osteotome for frontoorbital advancement in 15 patients with craniosynostosis seen consecutively (mean age 11.3 months). They demonstrated that this new device can cut cranial bones using ultrasonic microvibrations created by piezoelectric effects. In all patients, this instrument allowed an easy and precise handling during osteotomy with a reduced amount of trauma to adjacent soft tissues and with no complications. Although the time required for piezoelectric osteotomy was longer compared with conventional techniques, the total operation time remained approximately the same because the preparation requirements are less extensive. Postoperatively, bone regeneration was uneventful. The authors conclude that this new technique of piezoelectric osteotomy is a valuable tool for craniofacial reconstructive surgery in pediatric patients.

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.

Predictors of subsequent overdrainage and clinical outcomes after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus.

BACKGROUND: Little is known about variables associated with overdrainage complications and neurofunctional and health-related quality of life outcomes in idiopathic normal-pressure hydrocephalus (iNPH) patients after shunt surgery. OBJECTIVE: To identify candidate demographic and disease-specific predictors of overdrainage and patient-related outcomes, allowing for more personalized care of patients with iNPH. METHODS: This was a secondary analysis of the dataset of the SVASONA study, a multicenter randomized trial comparing gravitational and conventional gravitational valves for treating iNPH. We evaluated the association between baseline items and the incidence of overdrainage, using different endpoint definitions. RESULTS: We identified only a few variables associated with a possible increased risk of overdrainage. Apart from using conventional rather than gravitational valves, longer duration of surgery and female sex were associated with a higher risk of clinical signs and symptoms suggestive of overdrainage (hazard ratio: 1.02, 95% confidence interval: 1.01-1.04 and 1.84, 95% confidence interval: 0.81-4.16). The occurrence of clinical symptoms of overdrainage, and the need for exchanging a programmable by a gravitational valve may adversely affect disease-specific outcomes like the Kiefer score. CONCLUSION: Few, if any, baseline and treatment characteristics may be helpful in estimating the individual risk of complications and clinical outcomes after shunt surgery for iNPH. Patients should be informed that longer surgery for any reason may increase the risk of later overdrainage. Also, women should be counseled about a sex-associated increased risk of the development of clinical symptoms of overdrainage, although the latter cannot be distinguished from a generally higher prevalence of headaches in the female population.