Management of external ventricular drain: to wean or not to wean?

PURPOSE: External ventricular drain (EVD) is one of the most frequent procedures in neurosurgery and around 15 to 30% of these patients require a permanent cerebrospinal fluid (CSF) diversion. The optimal EVD weaning strategy is still unclear. Whether gradual weaning compared to rapid closure, reduces the rate of permanent CSF diversion remains controversial. The aim of this trial is to compare the rates of permanent CSF diversion between gradual weaning and rapid closure of an EVD. METHODS: This was a single-center, retrospective cohort study including patients between 2010 to 2020. Patients were divided into a weaning (WG) and non-weaning (NWG) group. The primary outcome was permanent CSF diversion rates, secondary outcomes included hospitalization time, EVD-related morbidity, and clinical outcome. RESULTS: Out of 412 patients, 123 (29.9%) patients were excluded due to early death or palliative treatment. We registered 178 (61.6%) patients in the WG and 111 (38.4%) in the NWG. Baseline characteristics were comparable between groups. The VPS rate was comparable in both groups (NWG 37.8%; WG 39.9%, p = 0.728). EVD related infection (13.5% vs 1.8%, p < 0.001), as well as non-EVD related infection rates (2.8% vs 0%, p < 0.001), were significantly higher in the WG. Hospitalization time was significantly shorter in the NWG (WG 24.93 ± 9.50 days; NWG 23.66 ± 14.51 days, p = 0.039). CONCLUSION: Gradual EVD weaning does not seem to reduce the need for permanent CSF diversion, while infection rates and hospitalization time were significantly higher/longer. Therefore, direct closure should be considered in the clinical setting.

Predictive Value of Sonographic Parameters on the Effects of Cranial Molding Helmet Therapy in Infants with Positional Plagiocephaly.

Positional plagiocephaly is a deformational cranial flattening frequently treated in pediatric neurosurgical practice. Positional maneuvers and orthotic helmet therapy are preferred therapeutic options for moderate-to-severe forms. Treatment response seems to be age-dependent. Nevertheless, predictive data are vague, and cost-efficiency might be a limiting factor for treatment. The purpose of this study was to investigate the early predictive value of sonographic parameters on the efficacy of orthotic helmet therapy through the assessment of changes in skull shape and correlation of the parameters with caliper cephalometry values and with age. A consecutive cohort of 49 patients < 10 months of age, undergoing orthotic helmet therapy for positional plagiocephaly, was recruited prospectively. The authors routinely assessed the patency of the lambdoid sutures by ultrasound and the following additional skull parameters were measured: suture width, adjacent full bone thickness, adjacent cortical bone thickness and occipital angle. Caliper cephalometric values, as well as demographic and clinical data were collected. Retrospective data analysis showed an inverse relation between both cortical and full skull bone thickness and early treatment efficacy, defined by a reduction in the occipital angle. The improvement of sonographic parameters correlated with the development of cranial caliper cephalometry values. In conclusion, the sonographic assessment of skull bone thickness is a safe and cost-effective tool to predict the early efficacy of orthotic helmet therapy in positional plagiocephaly and might, therefore, help the clinician to foresee the potential evolution of the deformity.

Palliative single-level selective dorsal rhizotomy for children with spastic cerebral palsy Gross Motor Function Classification System level IV and V: a case series and systematic review of the literature.

OBJECTIVE: Single-level selective dorsal rhizotomy (SDR), typically indicated for ambulatory patients, is a controversial topic for severe spastic cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) level IV or V. The objective of this case series and systematic literature review was to outline the indication and outcome of palliative SDR for nonambulatory patients with CP and GMFCS level IV and V, focusing on improvement of spasticity and of patient and caregiver reported quality of life assessment. METHODS: A retrospective case series of patients with CP and GMFCS level IV or V who underwent single-level SDR at the authors' institution is presented. Furthermore, two databases (PubMed and Embase) were searched and a systematic review with a search string based on the terms "selective dorsal rhizotomy," "cerebral palsy," and "outcome" was conducted. The primary outcome was the reduction of spasticity based on the modified Ashworth scale (MAS). Secondary outcomes were change on the Gross Motor Function Measure-66 (GMFM-66), evaluation of patient-reported outcome measures (PROMs), surgical morbidity, and mortality. RESULTS: Eleven consecutive children under the age of 25 years undergoing palliative single-level SDR were included. All patients showed a reduction in MAS score (mean 1.09 ± 0.66 points) and no surgical morbidity and mortality occurred. For the systematic review results from our case series, in addition to 4 reports, 274 total patients were included. Reduction of spasticity based on MAS score was noted in all studies (mean range 1.09-3.2 points). Furthermore, in 2 studies spasticity of the upper extremities showed a MAS score reduction as well (range 1.7-2.8 points). The GMFM-66 score improved in 72% of the patients, while bladder function improved in 78% of the patients. Based on the PROMs, 92% of the patients/caregivers were satisfied with the outcome and their quality of life after the procedure. Two wound infections (2.7%) and one CSF leak (1.3%) occurred, while no surgery-related deaths were described. CONCLUSIONS: This analysis showed an improvement in spasticity, daily care, and comfort for patients with CP and GMFCS levels IV and V. Larger cohorts analyzing the outcome of palliative single-level SDR, based on the MAS, GMFM-66, and PROMs, are still needed and should be the focus of future studies. Systematic review registration no.: CRD42024495762 (https://www.crd.york.ac.uk/prospero/).

Pediatric neurosurgery training during residency in Switzerland and the need for dedicated subspecialization training.

INTRODUCTION: Pediatric Neurosurgery as a subspeciality started to emerge during the late 1950s, with only a few dedicated pediatric neurosurgeons in the Western world. Over the last few decades, the awareness that children require subspecialized care by dedicated pediatric neurosurgeons and an interdisciplinary team has been growing worldwide, leading to an increase in pediatric neurosurgeons. Several studies have shown that subspecialized care for pediatric patients improves outcomes and is cost-effective. This survey aims to assess the current setting of pediatric neurosurgery and training of neurosurgical residents in pediatric neurosurgery in Switzerland. METHODS: We conducted an online survey by sending e-mail invitations in 2021 to all neurosurgical residents in Switzerland. The survey included questions regarding the participants' demographics, current workplace structures, the care of specific pediatric neurosurgical pathologies, and participants' opinions of the Swiss training program for pediatric neurosurgery and possible improvement. We defined at the beginning of the survey that a pediatric neurosurgeon is a board-certified neurosurgeon with at least one year of dedicated pediatric neurosurgical fellowship training abroad. RESULTS: We received a total of 25 responses from residents, of which 20 (80%) were male. Twenty-two participants (88%) worked in one of seven major hospitals in Switzerland at the time of the survey, and four (16%) were interested in pursuing a fellowship in pediatric neurosurgery. Seven (35%) and five residents (25%) feel comfortable taking care on the ward of a craniosynostosis and hydrocephalus patient younger than 6 months, respectively. Twelve residents (60%) feel comfortable taking care of a pediatric brain tumor patient. The majority (n = 22, 88%) of all residents agree that a fellowship-trained pediatric neurosurgeon should treat children, while two (8%) residents state that any neurosurgeon with an interest in pediatric neurosurgery should be able to treat children. All residents (n = 25, 100%) agree that pediatric neurosurgery training and care in Switzerland needs to be improved. CONCLUSION: Pediatric neurosurgery training in Switzerland is rather heterogeneous and not very well structured, with varying frequencies of children-specific neurosurgical pathologies. Most residents agreed that a subspecialized pediatric neurosurgeon should oversee the care of children in neurosurgery, while all agree that pediatric neurosurgical training and care should be improved in Switzerland.

Patient- and Caregiver-Reported Outcome Measures after Single-Level Selective Dorsal Rhizotomy in Pediatric and Young Adult Patients with Spastic Cerebral Palsy.

INTRODUCTION: The aim of this cohort study was to assess the outcome of single-level selective dorsal rhizotomy (SDR) in children and young adults with spastic cerebral palsy (CP) treated at our institution, focusing on patient-reported outcome measures (PROMs) and quality of life (QoL) of patients and their caregivers. METHODS: We included consecutive patients undergoing SDR from 2018 to 2020 at our institution. Subjective outcome was measured through PROMs, while functional outcome was measured through baseline characteristics, operative outcome, as well as short- and long-term follow-up. Furthermore, the effect of age at the time of surgery on patient/caregiver satisfaction was analyzed. RESULTS: Seven patients (3 female, 43%) with a median age at surgery of 11.9 years (IQR 8.7-15.5) were included. All patients had a Gross Motor Function Classification (GMFCS) score of at least IV before surgery. Five surgeries were palliative and two non-palliative. Based on PROMs, SDR showed very good QoL and health-related outcome measures for both palliative and non-palliative patients. Patient/caregiver satisfaction was higher for the early subgroup (age ≤11) than the late subgroup (age >11). Functional outcome showed reduced spasticity in both groups. Blood transfusions were never needed, while no cerebrospinal fluid leak, infection, or permanent morbidity was seen. CONCLUSION: Based on PROMs, SDR leads to high satisfaction and improved QoL, especially if done at an early age. Further studies with larger cohorts are necessary to underline and confirm our observations.

Surgical management of Chiari malformation type 1 associated to MCAP syndrome and study of cerebellar and adjacent tissues for PIK3CA mosaicism.

BACKGROUND: Subjects with Megalencephaly-Capillary Malformation-Polymicrogyria syndrome (MCAP) can present with a Chiari Malformation Type 1 and resulting alterations in cerebrospinal fluid (CSF) dynamics, which may require surgical treatment. The aim of this paper is to describe the features of children with MCAP who underwent surgical decompression for CM1, and to explore the PIK3CA variant allele frequency (VAF) identified in cerebellar parenchyma and other adjacent structures. METHODS: This study reviewed two cases of children with CM1 and MCAP who underwent surgical decompression treatment. These two cases were part of a national cohort of 12 MCAP patients who had CM1, due to their surgical eligibility. Tissue samples were obtained from the cerebellar tonsils and adjacent anatomical structures during the surgical procedures. Samples were then subsequently analyzed for PIK3CA postzygotic variants. RESULTS: In both cases, alterations in CSF dynamics, specifically hydrocephalus and syringomyelia, were observed and required surgical treatment. PIK3CA targeted sequencing determined the VAF of the postzygotic variant in both cerebellar and adjacent bone/connective tissues. DISCUSSION: The recognition of a CM1 comorbidity in MCAP patients is of paramount importance when considering personalized treatment options, especially because these patients are at higher risk of developing complications during surgical decompression surgery. The variable PIK3CA VAF identified in the different analyzed tissues might help explain the heterogeneous nature and severity of anomalies observed in the volume of the posterior fossa structures in MCAP patients and associated CSF and venous disorders.

Wound closure with a mesh and liquid tissue adhesive (Dermabond Prineo) system in pediatric spine surgery: a prospective single-center cohort study incorporating parent-reported outcome measures.

OBJECTIVE: Wound healing can be challenging in children undergoing spine surgery for neurological conditions due to a high risk of cerebrospinal fluid (CSF) leakage and wound infection. In adults, use of the Dermabond Prineo (DP) skin closure system, which consists of both tissue adhesive glue and a self-adhesive mesh, for wound closure of medium-length surgical incisions has been reported. The aim of this study was to investigate the efficiency and cosmetic outcome of DP for wound closure in extra- and intradural pediatric neurological spine surgery. METHODS: In this prospective cohort study, 47 children underwent 50 spine procedures using DP for wound closure between 2018 and 2022 at a single institution. Patient demographic and surgical data were collected. The primary outcome was revision surgery for wound healing disorders, while secondary outcomes were infections, minor wound healing disorders, and both physician and parental satisfaction (parent-reported outcome measures [PROMs]) at last follow-up. RESULTS: Among 50 spinal (45 intra- and 5 extradural) interventions, 1 patient (2%) underwent revision surgery for a cutaneous CSF fistula and pseudomeningocele. Minor wound healing disorders occurred after 16 surgeries, which did not require surgical wound revision and resolved completely. No allergic reactions to DP or surgical site infections within 30 days were observed. The parents and the medical team described wound care as significantly facilitated since wound dressing changes were not needed. Three families (6.4%) encountered difficulties in wound care, and 46 (97.9%) were satisfied with DP. The cosmetic outcome based on PROMs was excellent, with a mean score of 8 (IQR 2) on a scale from 1 to 10. At long-term follow-up, a mean of 11.3 ± 10.7 months after surgery, physicians rated the cosmetic outcome on the visual analog scale (median score 9, IQR 1) and Hollander scale (median score 6, IQR 1). The outcomes were similar among the different pathologies and age groups and did not differ in patients with and without syndromic malformations. CONCLUSIONS: The application of DP is simple, enables good patient comfort, facilitates both professional and parental wound care, and leads to excellent cosmetic results. DP possibly aids in the reduction of postoperative CSF leakage and infections after pediatric neurological spine surgery.

Minimal invasive interlaminar approach for untethering of fatty filum terminale in pediatric patients - how I do it.

BACKGROUND: Fatty filum terminale is a form of spinal dysraphism and a third of all patients develop symptoms such as sensory, motor, and urinary impairment. Early surgery at 6 months has the advantage that the bone density is still soft, and the patients are not ambulatory yet, promoting faster healing. METHOD: We present our minimal invasive surgical technique for FFT untethering. CONCLUSION: Due to the low complication rate and the potentially high benefit of surgery, prophylactic untethering is recommended.

Endoscopic and Endoscopically-Assisted Resection of Intraventricular Lesions Using a Neuroendoscopic Ultrasonic Aspirator.

The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) broadened the treatment spectrum of neuroendoscopy. We aim to describe our experience with the use of NUA for the resection of intraventricular lesions. Here, we present consecutive retrospective case series of adult and pediatric patients undergoing resection of an intraventricular lesion with a NUA (Endoscopic Neurosurgical Pen, Söring GmbH, Quickborn, Germany) between January 2019 and April 2020. Eight patients between the age of 0.5 and 73 years underwent surgery using NUA and were included in this study. In four patients, an endoscopic assisted (EA) resection of the lesion was undertaken, while in four patients, the lesion was removed using purely endoscopic (PE) resection. In all cases, gross/near total resection was achieved. The average blood loss was 142.5 ± 90.4 mL (range 50-300 mL). Transient morbidity was seen in four patients (50%), while permanent morbidity or mortality did not occur. The NUA seems to be a safe and valuable tool for the minimally invasive resection of intraventricular lesions in selected cases. The type, size, consistency, and vascularization of the lesion limit at times the purely endoscopic use of the NUA.

Fixed posterior cranial vault expansion technique.

BACKGROUND: Different techniques to reshape the posterior skull vault have been developed in the last decades, all sharing the same goals of increasing the skull volume, decreasing the intracranial pressure (ICP), correcting the cranial dysmorphy, and contributing to a better growth of the skull. Though over the last years most refinements in these techniques have focused on the use of hardware as distractors or springs, the fixed posterior vault expansion remains a valuable procedure for cranial remodeling. METHODS: We describe in details the technique used for fixed posterior vault expansion in children that is applied at the French Referral center for Craniosynostosis of Lyon, France. DISCUSSION: The fixed posterior vault expansion increases the risk of perioperative complications due to the elevation of the posterior bone flap from the dura but allows an immediate decompression and correction of the shape, simplifying the postoperative course.

CSF shunting in myelomeningocele-related hydrocephalus and the role of prenatal imaging.

OBJECTIVE: Hydrocephalus is commonly associated with myelomeningocele (MMC). Indication and timing of cerebrospinal fluid (CSF) shunting are still a topic of discussion. The aim of this study was to investigate whether the analysis of prenatal cerebral imaging studies could provide information that is predictive of the necessity of CSF shunting in the postnatal period. MATERIAL AND METHODS: Among 73 infants operated on because of MMC between January 2003 and June 2020, 50 had undergone prenatal and postnatal MRI studies and were considered for analysis. For each patient, frontal horn width, atrial ventricle diameter, third ventricle diameter, and subarachnoid spaces (sinocortical width, craniocortical width, and the interhemispheric width) have been measured on prenatal, postnatal, and a follow-up MRI study. The need of CSF shunting device placement in relation to prenatal and early postnatal MRI data was investigated. RESULTS: Of the 50 infants, 31 (62%) developed a progressive hydrocephalus. Of these, 30 needed a CSF shunt and the majority of them (n=29) was operated on within 28 days after birth. One patient needed CSF shunt implantation at 45 days after birth and one child developed a late progressive hydrocephalus, successfully treated by ETV alone, at 14.2 months of age. All patients with an atrial ventricle diameter greater than 1.9 cm and a 3rd ventricle diameter larger than 0.3 cm on antenatal third trimester imaging have undergone CSF shunting within 1 month after birth. Conversely, all the children that did not undergo a CSF shunt placement showed an atrial cerebral ventricle diameter inferior to 1.2 cm and a 3rd ventricle width < 0.3 cm on antenatal imaging. Frontal horn width and subarachnoid CSF spaces' evolution did not seem to play a role. CONCLUSION: The prenatal MRI assessment of the associated prenatal ventriculomegaly in MMC provides parameters that have a predictive value heralding the probability of a CSF diversion procedure after birth. In the same way, the analysis of intrauterine MRI studies may identify those subjects that are less at risk of developing a progressive hydrocephalus after birth, therefore encouraging a more cautious attitude towards the early implantation of CSF shunting devices in the current clinical practice.

Metopic triangle osteotomy in trigonocephaly Piezosurgery: a technical variant to control metopic emissary veins.

Premature fusion of the metopic suture results in trigonocephaly with variable degrees of anterior cranial fossa dysmorphia and craniofacial deformity. Different surgical corrective techniques that aim to reshape the forehead and enlarge the cranial volume have been described. Typical variations of the standard fronto-orbitary advancement carry the risk of relevant blood loss during frontal osteotomy, where paired emissary metopic veins are disrupted. The authors present a technical variant that preserves a bony triangle over the glabella to optimize control of these veins, which represent the major source of bleeding, and applies Piezosurgery to perform the osteotomies to minimize bone substance loss. The video can be found here: https://vimeo.com/511536423.

Development and validation of a synthetic 3D-printed simulator for training in neuroendoscopic ventricular lesion removal.

OBJECTIVE: Neuroendoscopic surgery using an ultrasonic aspirator represents a valid tool with which to perform the safe resection of deep-seated ventricular lesions, but the handling of neuroendoscopic instruments is technically challenging, requiring extensive training to achieve a steep learning curve. Simulation-based methods are increasingly used to improve surgical skills, allowing neurosurgical trainees to practice in a risk-free, reproducible environment. The authors introduce a synthetic, patient-specific simulator that enables trainees to develop skills for endoscopic ventricular tumor removal, and they evaluate the model's validity as a training instrument with regard to realism, mechanical proprieties, procedural content, and handling. METHODS: The authors developed a synthetic simulator based on a patient-specific CT data set. The anatomical features were segmented, and several realistic 1:1 skull models with all relevant ventricular structures were fabricated by a 3D printer. Vascular structures and the choroid plexus were included. A tumor model, composed of polyvinyl alcohol, mimicking a soft-consistency lesion, was secured in different spots of the frontal horn and within the third ventricle. Neurosurgical trainees participating in a neuroendoscopic workshop qualitatively assessed, by means of a feedback survey, the properties of the simulator as a training model that teaches neuroendoscopic ultrasonic ventricular tumor surgery; the trainees rated 10 items according to a 5-point Likert scale. RESULTS: Participants appreciated the model as a valid hands-on training tool for neuroendoscopic ultrasonic aspirator tumor removal, highly rating the procedural content. Furthermore, they mostly agreed on its comparably realistic anatomical and mechanical properties. By the model's first application, the authors were able to recognize possible improvement measures, such as the development of different tumor model textures and the possibility, for the user, of creating a realistic surgical skull approach and neuroendoscopic trajectory. CONCLUSIONS: A low-cost, patient-specific, reusable 3D-printed simulator for the training of neuroendoscopic ultrasonic aspirator tumor removal was successfully developed. The simulator is a useful tool for teaching neuroendoscopic techniques and provides support in the development of the required surgical skills.

Maternal and obstetric complications in fetal surgery for prenatal myelomeningocele repair: a systematic review.

OBJECTIVE: Comparing prenatal and postnatal surgical repair techniques for myelomeningocele (MMC), in utero fetal surgery has increasingly gained acceptance and is considered by many specialized centers the first choice of treatment. Despite its benefits, as demonstrated in the Management of Myelomeningocele Study (MOMS), including reduced need for CSF shunting in neonates and improved motor outcomes at 30 months, there is still an ongoing debate on fetal and maternal risks associated with the procedure. Prenatal open hysterotomy, fetoscopic MMC repair techniques, and subsequent delivery by cesarean section are associated with maternal complications. The aim of this systematic review is to assess the available literature on maternal and obstetric complication rates and perinatal maternal outcomes related to fetal MMC repair. METHODS: The authors identified references for inclusion in this review by searching PubMed and MEDLINE, with restrictions to English language, case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews. The rate of maternal and obstetric complications was analyzed based on studies focusing on this issue and presenting clear results on the matter. RESULTS: Of 1264 articles screened, 36 were included in this systemic review, whereof 11 were eligible for data analysis and comparison. The average overall rate of maternal and obstetric complications corresponds to 78.6%. The majority of the described events are obstetric complications, varying from chorioamniotic membrane separation in 65.6% of cases, oligohydramnios in 13.0% of cases, placental abruption in 5.0% of cases, spontaneous or preterm premature membrane rupture in 42.0% of cases, and early preterm delivery in 11.3% of cases due to uterine dehiscence, occurring in 0.9% of cases. The most common medical complications are development of pulmonary edema occurring in 2.8%, gestational diabetes in 3.7%, gestational hypertension/preeclampsia in 3.7%, and need for blood transfusions in 3.2% of cases. Limitations of the review arise from the lack of data in the current literature, with maternal and obstetric complications being underreported. CONCLUSIONS: Although the efforts of further advancement of intrauterine prenatal MMC repair aim to increase neonatal outcomes, maternal health hazard will continue to be an issue of crucial importance and further studies are required.

Neuronal Mitochondrial Dysfunction Activates the Integrated Stress Response to Induce Fibroblast Growth Factor 21.

Stress adaptation is essential for neuronal health. While the fundamental role of mitochondria in neuronal development has been demonstrated, it is still not clear how adult neurons respond to alterations in mitochondrial function and how neurons sense, signal, and respond to dysfunction of mitochondria and their interacting organelles. Here, we show that neuron-specific, inducible in vivo ablation of the mitochondrial fission protein Drp1 causes ER stress, resulting in activation of the integrated stress response to culminate in neuronal expression of the cytokine Fgf21. Neuron-derived Fgf21 induction occurs also in murine models of tauopathy and prion disease, highlighting the potential of this cytokine as an early biomarker for latent neurodegenerative conditions.

Frontoethmoidal Osteoma with Secondary Intradural Mucocele Extension Causing Frontal Lobe Syndrome and Pneumocephalus: Case Report and Review of Literature.

BACKGROUND: Paranasal sinus osteoma is a common, asymptomatic, histologically benign, slow-growing tumor. However, it can give rise to secondary pathologies such as a mucocele in about 50% of the cases. Rarely, intracranial and orbital extension is present, leading to rhinoliquorrhea, pneumocephalus, or neurologic and visual impairment, which might be potentially life-threatening. CASE DESCRIPTION: A 49-year-old man presented with an acute frontal lobe syndrome and rhinoliquorrhea. Cranial magnetic resonance tomography showed a suspected frontoethmoidal osteoma with a mucocele expanding intradurally into the left frontal lobe. It was accompanied by pneumocephalus and showed communication with the left lateral ventricle. Through a bifrontal craniotomy, in toto resection of the frontoethmoidal bony tumor and the intradural mucocele was performed, while thereafter the frontal sinus was cranialized using a pedunculated periosteal flap. Postoperative recovery was uneventful with complete resolution of the tension pneumocephalus and rhinoliquorrhea and led to an improvement of the frontal lobe syndrome. CONCLUSIONS: We present a rare case of pneumocephalus caused by a frontoethmoidal osteoma associated with an intradural mucocele. A review of the literature, focusing on the surgical strategies in such cases, is provided.

Influence of Postoperative Thrombosis Prophylaxis on the Recurrence of Chronic Subdural Hematoma After Burr-Hole Drainage.

OBJECTIVES: Chronic subdural hematoma is a commonly encountered disease in neurosurgic practice, whereas its increasing prevalence is compatible with the ageing population. Recommendations concerning postoperative thrombosis prophylaxis after burr-hole drainage of chronic subdural hematoma are lacking. The aim of this study was to analyze the correlation between recurrence of chronic subdural hematoma and postoperative application of thrombosis prophylaxis. DESIGN: Retrospective, consecutive sample of patients undergoing burr-hole drainage for chronic subdural hematoma over 3 years. SETTING: Single, academic medical center. PATIENTS: All patients undergoing surgical evacuation of a chronic subdural hematoma with burr-hole drainage. Exclusion: patients under the age of 18 years, who presented with an acute subdural hematoma and those who underwent a craniotomy. INTERVENTIONS: We compared patients receiving thrombosis prophylaxis treatment after burr-hole drainage of chronic subdural hematoma with those who were not treated. Primary outcome measure was reoperation of chronic subdural hematoma due to recurrence. Secondary outcome measures were thromboembolic and cardiovascular events, hematologic findings, morbidity, and mortality. In addition, a subanalysis comparing recurrence rate dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) was undertaken. MEASUREMENTS AND MAIN RESULTS: Overall recurrence rate of chronic subdural hematoma was 12.7%. Out of the 234 analyzed patients, 135 (57.3%) received postoperative thrombosis prophylaxis (low-molecular-weight heparin) applied subcutaneously. Recurrence of chronic subdural hematoma occurred in the thrombosis prophylaxis group and control group in 12 patients (8.9%) and 17 patients (17.2%), respectively, showing no significant difference (odds ratio, 0.47 [95% CI, 0.21 - 1.04]). A subanalysis comparing recurrence rate of chronic subdural hematoma dependent on the application time of thrombosis prophylaxis (< 48 vs > 48 hr) showed no significant difference either (odds ratio, 2.80 [95% CI, 0.83-9.36]). Higher dosage of thrombosis prophylaxis correlated with recurrence rates of chronic subdural hematoma, both in univariate and multivariate analyses. CONCLUSIONS: Our data suggest that the application of postoperative thrombosis prophylaxis after burr-hole drainage for chronic subdural hematoma does not result in higher recurrence rates of chronic subdural hematoma. In addition, it seems that early administration of thrombosis prophylaxis (< 48 hr) has no influence on recurrence rates; however, high dosage seems to increase recurrence rates.

DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress.

During apoptosis mitochondria undergo cristae remodeling and fragmentation, but how the latter relates to outer membrane permeabilization and downstream caspase activation is unclear. Here we show that the mitochondrial fission protein Dynamin Related Protein (Drp) 1 participates in cytochrome c release by selected intrinsic death stimuli. While Bax, Bak double deficient (DKO) and Apaf1(-/-) mouse embryonic fibroblasts (MEFs) were less susceptible to apoptosis by Bcl-2 family member BID, H(2)O(2), staurosporine and thapsigargin, Drp1(-/-) MEFs were protected only from BID and H(2)O(2). Resistance to cell death of Drp1(-/-) and DKO MEFs correlated with blunted cytochrome c release, whereas mitochondrial fragmentation occurred in all cell lines in response to all tested stimuli, indicating that other mechanisms accounted for the reduced cytochrome c release. Indeed, cristae remodeling was reduced in Drp1(-/-) cells, potentially explaining their resistance to apoptosis. Our results indicate that caspase-independent mitochondrial fission and Drp1-dependent cristae remodeling amplify apoptosis. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

Less than perfect divorces: dysregulated mitochondrial fission and neurodegeneration.

Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) proteins such as Fis1, Mff, and Mief1. It is also generally accepted that organelle fusion depends on the action of three large GTPases: mitofusins (Mfn1, Mfn2) mediating membrane fusion on the OMM level, and Opa1 which is essential for inner mitochondrial membrane fusion. Significantly, mutations in Drp1, Mfn2, and Opa1 have causally been linked to neurodegenerative conditions. Despite this knowledge, crucial questions such as to how fission of the inner and outer mitochondrial membranes are coordinated and how these processes are integrated into basic physiological processes such as apoptosis and autophagy remain to be answered in detail. In this review, we will focus on what is currently known about the mechanism of mitochondrial fission and explore the pathophysiological consequences of dysregulated organelle fission with a special focus on neurodegenerative conditions, including Alzheimer's, Huntington's and Parkinson's disease, as well as ischemic brain damage.