Fetoscopic insufflation of heated-humidified carbon dioxide during simulated spina bifida repair is safe under controlled anesthesia in the fetal lamb.

OBJECTIVE: To assess the safety of Partial-Amniotic-Insufflation-of-heated-humidified-CO2 (hPACI) during fetoscopic spina bifida repair (fSB-repair). METHOD: A simulated fSB-repair through an exteriorized uterus under hPACI was performed in 100-day fetal lambs (term = 145 days) under a laboratory anesthesia protocol (n = 5; group 1) which is known to induce maternal-fetal acidosis and hypercapnia. Since these may not occur clinically, we applied a clinical anesthesia protocol (n = 5; group 2), keeping maternal parameters within physiological conditions, that is, controlled maternal arterial carbon dioxide (CO2) pressure (pCO2  = 30 mmHg), blood pressure (≥67 mmHg), and temperature (37.1-39.8°C). Our superiority study used fetal pH as the primary outcome. RESULTS: Compared to group 1, controlled anesthesia normalized fetal pH (7.23 ± 0.02 vs. 7.36 ± 0.02, p < 0.001), pCO2 (70.0 ± 9.1 vs. 43.0 ± 1.0 mmHg, p = 0.011) and bicarbonate (27.8 ± 1.1 vs. 24.0 ± 0.9 mmol/L, p = 0.071) at baseline. It kept them within clinically acceptable limits (pH ≥ 7.23, pCO2  ≤ 70 mmHg, bicarbonate ≤ 30 mm/L) for ≥120 min of hPACI as opposed to ≤30 min in group one. Fetal pO2 and lactate were comparable between groups and generally within normal range. Fetal brain histology demonstrated fewer apoptotic cells and higher neuronal density in the prefrontal cortex in group two. There was no difference in fetal membrane inflammation, which was mild. CONCLUSION: Fetoscopic insufflation of heated-humidified CO2 during simulated fSB-repair through an exteriorized uterus can be done safely under controlled anesthesia.

The incidence of postoperative cerebrospinal fluid leakage after elective cranial surgery: a systematic review.

Cerebrospinal fluid (CSF) leakage is a major complication after elective neurosurgical procedures. The aim of this systematic literature review is to summarize the incidence rates of postoperative cerebrospinal fluid leakage for neurosurgical procedures, classified by surgical approach. The Pubmed, Cochrane, Embase, and Web of Science databases were searched for studies reporting the outcome of patients undergoing elective neurosurgical procedures. The number of patients, surgical approach, and indication for surgery were recorded for each study. Outcomes related to CSF leakage such as clinical manifestation and treatment were reported as well. One hundred and thirteen studies were included, reporting 94,695 cases. Overall, CSF leaks were present in 3.8% of cases. Skull base surgery had the highest rate of CSF leakage with 6.2%. CSF leakage occurred in 5.9% of anterior skull base procedures, 6.4% of middle fossa, and 5.2% of transpetrosal surgeries. 5.8% of reported infratentorial procedures were complicated by CSF leakage versus 2.9% of supratentorial surgeries. CSF leakage remains a common serious adverse event after cranial surgery. There exists a need for standardized procedures to reduce the incidence of postoperative CSF leakage, as this serious adverse event may lead to increased health care costs.

Stroke rate after external fractionated radiotherapy for benign meningioma.

PURPOSE: Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long-term side effects are of considerable concern. A controversial long-term side effect of radiotherapy is stroke. Due to its severity, it is important to know the frequency of this side effect. The aim of this study was to assess the stroke incidence and risk factors among patients receiving radiotherapy for their benign meningioma. METHODS: We performed a retrospective database study of patients who underwent primary or adjuvant radiotherapy for their benign meningioma at University Hospitals Leuven from January 2003 to December 2017. RESULTS: We included 169 patients with a median age of 51 years (range 22-84). Every patient received fractionated radiotherapy using photons with a median dose of 56 Gy (range 54-56) in fractions of 2 Gy (range 1.8-2). The median follow-up was 5.3 years (range 0.1-14). The cumulative stroke incidence function showed an incidence of 11.6% after 9 years of follow-up, translating to a stroke incidence per year of 1.29%. We found two significant risk factors for stroke: medically treated arterial hypertension (p = 0.005) and history of previous stroke or transient ischemic attack (p < 0.001). 5-year local control and overall survival rates were respectively 97.4% and 91.2%. Other late grade III/IV toxicities occurred in 16.0% (27/169) of patients. CONCLUSION: Our study shows a higher incidence of stroke in patients who received radiotherapy for their benign meningioma compared to the general population.

Long-Term Outcomes of Patients with Hydrocephalus Secondary to Tectal Plate Glioma versus Idiopathic Aqueductal Stenosis: Results from a Single Center.

INTRODUCTION: Tectal plate gliomas (TPG) constitute a distinct entity of benign tumors of the brain stem which show an indolent clinical course. Adequate treatment of secondary hydrocephalus is undoubtedly a major factor in the outcome. However, little is known about to what degree the tumor itself determines the long-term outcome of these patients. METHODS: We retrospectively analyzed and compared the clinical and radiological data of 16 pediatric TPG patients with data of 12 pediatric idiopathic aqueductal stenosis (IAS) patients treated in our center from 1988 to 2018. For both groups, we assessed the long-term outcome in terms of hydrocephalus management, and for the TPG group, we assessed tumor growth during follow-up. In a separate prospective part of the study, we performed a neuropsychological evaluation in a subgroup of patients using a standardized testing battery, covering intelligence, learning, memory, executive functions, and an inventory on depression. RESULTS: In the TPG group, the mean clinical and radiological follow-up was 84 and 70 months, respectively. On average, the maximum diameter of the tumor increased by 11% (p = 0.031) and the estimated tumor volume with 35% (p = 0.026) on radiological follow-up. The fronto-occipital horn ratio (FOHR) decreased by 23% on average after treatment. In the IAS group, the mean clinical and radiological follow-up was 117 and 85 months, respectively. In this group, the FOHR decreased by 21% on average. Neurocognitive testing revealed significant higher scores in the TPG group on global intelligence (TPG = 109, IAS = 85.5, U = 3, p < 0.01, z = -2.71), performance (TPG= 100, IAS = 85, U = 7, p = 0.03, z = -2.2), and verbal intelligence (TPG = 122, IAS = 91.5, U = 2, p < 0.00, z = -2.87) as well as working memory (TPG = 109.5, IAS = 77, U = 0.5, p = 0.01, z = -2.46). CONCLUSION: Our results suggest that the long-term outcome in TPG patients is acceptable and that cognition is substantially better preserved than in patients with IAS. This puts the idea of a significant contribution of the tumoral mass to disease outcome on the long term in question. Adequate and prompt management of hydrocephalus is the most important factor in long-term cognitive outcome.

Outcome after surgery in supratentorial and infratentorial solitary brain metastasis.

BACKGROUND: The aim of this retrospective study was to investigate and compare the outcome after surgery in patients with a supratentorial solitary metastasis (SSM) and an infratentorial solitary metastasis (ISM). A worse prognosis has been reported in ISM. METHODS: Fifty-two patients with a newly diagnosed solitary brain metastasis on MRI were included to identify risk factors affecting the outcome. Key variables included tumor size, staging of the primary tumor, time span of presurgical work-up, and surgical technique. Outcome variables included postoperative complications, tumor recurrence, and mortality. Kaplan-Meier survival analysis was applied. RESULTS: Thirty patients with a SSM and 22 patients with an ISM underwent gross total resection. The tumor size did not have a statistical significant effect on survival. Presurgical work-up time was similar in SSM and ISM. Postoperative complications were more frequently encountered in ISM. Recurrence rate was comparable in SSM and ISM. Carcinomatous meningitis (CM) was more frequently seen in ISM, and CM was seen more often with the piecemeal resection technique. There was no statistical difference in overall survival between SSM and ISM. CONCLUSIONS: This study identified factors that play a role in the outcome after surgery in patients with ISM and SSM on MRI. Postoperative complications seemed to be higher in ISM and CM was more often seen in ISM, but the worse prognosis in patients with ISM compared with SSM could not be confirmed.

Craniocerebral birth injuries in term newborn infants: a retrospective series.

OBJECTIVE: In an attempt to further define the spectrum of cranial birth injuries, we analyzed 21 consecutive cranial birth injuries in term neonates presenting to the neurosurgical department of our institution over the period 1994-2015. METHODS: We performed a retrospective chart review from the medical records of the University Hospitals of the KU Leuven, from 1994 to 2015. We included 21 infants of 36-week gestational age or older with a diagnosis of cranial birth injury. The types and locations of injuries, the presenting signs, symptoms and their timing, and the required treatment(s) were recorded. Various maternal and neonatal factors and the mode of delivery were recorded. We recorded the different modes of delivery rates at our institution in the year 2013 and the rates in the Flemish community between 1995 and 2013, in order to compare the mode of delivery rates in the study group with current practice at our institution and with general practice over the years in the Flemish community. RESULTS: The most common clinical presentations were swelling (43% of cases) and seizures (19% of cases). Average Apgar scores were 6.57 at 1 min and 8.43 at 5 min; 48% of children had abnormally low Apgar scores at 1 min and 9.5% had abnormally low scores at 5 min. The most common intracranial lesion was skull fractures (33%). Operative treatment was required in 11 infants (52%). One infant died. Assisted mechanical delivery by either forceps and/or vacuum extraction occurred in 43% of infants. In comparison, in the year 2013, only 13.97% of deliveries at our institution were mechanically assisted. Over the period 1995-2013, the highest mechanically assisted delivery rates in the Flemish community were 14.1% in 1996. CONCLUSION: Although our series is too small to make firm conclusions, it is remarkable that the rates of assisted mechanical deliveries in our series far exceeded the assisted mechanical delivery rates at our institution in the year 2013 and even the highest vacuum and forceps delivery rates in the Flemish community over the period 1995-2013.

Maternal-fetal surgery for myelomeningocele: some thoughts on ethical, legal, and psychological issues in a Western European situation.

BACKGROUND: The results of the Management of Myelomeningocele Study (MOMS) randomized controlled trial have demonstrated that maternal-fetal surgery (MFS) for myelomeningocele (MMC) compared to postnatal MMC repair has clear neurological benefits for the child at 12 and 30 months of age. Level I evidence nevertheless does not provide answers to many questions in this delicate field. Since the beginning of 2012, our fetal center has been offering MFS for spina bifida aperta (SBA) to patients from different European and non-European countries, in a societal context where termination of pregnancy is the option chosen by most patients when being informed of this diagnosis. METHODS: We aim to explore in this text some of the ethical, legal, and psychological issues that we have encountered. RESULTS: For many of these questions, we do not have definite answers. A pregnant patient when diagnosed with a MMC fetus is a vulnerable subject. She needs to be referred to a highly specialized center with sufficient expertise in diagnosis and in all therapeutic options. Objective but compassionate counseling is of paramount importance. It is required that a multidisciplinary professional team obtains full voluntary consent from the mother after providing an appropriate information including diagnosis, short-, medium-, and long-term prognosis as well as benefits and harms of the fetal surgery. CONCLUSION: The latter should be offered with full respect for maternal choice and individual assessment and perception of potential risks taking into consideration legislation in the fetal center and the parents' country legislation.

10-year follow-up after implantation of the Bryan Cervical Disc Prosthesis.

PURPOSE: Cervical arthroplasty is being used as an alternative for cervical fusion, but long-term follow-up results have rarely been reported. In this paper, we present 10-year follow-up results after implantation of the Bryan Cervical Disc Prosthesis in a single center. METHODS: 89 patients underwent implantation of a single-level Bryan Cervical Disc Prosthesis to treat radiculopathy and/or myelopathy. Clinical (Neurological Success, Neck Disability Index (NDI), Neck- and Arm-Pain, and SF-36) and radiological follow-up was prospectively organized up to 10 years after surgery. Adverse events and second surgeries were recorded and evaluated. RESULTS: Ten-year follow-up data were available for 72 (81%) patients. Maintenance or improvement of the neurological state was seen in 89% of patients after 10-year follow-up. SF-36 PCS scores improved significantly at all follow-up points. SF-36 MCS improvement was significant at 4 and 6 year, but not at 8- and 10-year follow-up. Significant improvement for NDI, and Neck- and Arm-Pain scores was found for the subgroup of patients in whom these data were available. Mean angular motion of the prosthesis at 10-year follow-up was 8.6°. Mobility of the device, defined as >2° of angular motion, was reached in 81% of patients. During the study period, 21 patients (24%) developed new or recurrent radiculopathy or myelopathy, the majority of these being treated conservatively. Seven patients (8%) required 8 additional spine surgeries to treat persistent or recurrent symptoms. Of these, 2 patients (2%) were reoperated at the index level and at 5 (6%) an adjacent level. CONCLUSION: In this study, favorable long-term clinical outcome after implantation of the Bryan Cervical Disc Prosthesis was seen, with the majority of prostheses remaining mobile after 10-year follow-up. However, still 6% of patients required adjacent level surgery.

Complications of skull reconstruction after decompressive craniectomy.

INTRODUCTION: Decompressive craniectomy can be a life-saving procedure. Later reconstruction of the skull using the stored bone flap ("cranioplasty") is often associated with complications. These complications require new procedures and often result in the reconstruction of the skull using an expensive patient-specific cranial implant. PATIENTS & METHODS: All adult patients who underwent cranioplasty after decompressive craniectomy in the last 10 years in our center were included (74 patients). Bone flap size, duration of the procedure, age, and other clinical parameters were included in our analysis. RESULTS: 29.7% of our patients who received in the first place an autologous cranioplasty developed a complication which necessitated removal of the bone flap and the implantation of a custom-made implant. Descriptive statistics demonstrate a significantly higher amount of complications in younger patients (20-40 years, p = 0.027). We also saw a trend toward lower complications when bone flaps were stored according to a biobank protocol (p = 0.075). CONCLUSIONS: Cranioplasty using the stored bone flap after decompressive craniectomy is associated with a high percentage of complications. Selecting patients at risk could possibly indicate cases where an immediate custom-made implant technique would be required.

Left atrial appendage occlusion with the Amplatzer Cardiac Plug could improve survival and prevent thrombo-embolic and major bleeding events in atrial fibrillation patients with increased bleeding risk.

AIMS: Literature suggests a beneficial effect of percutaneous left atrial appendage occlusion (LAAO) to prevent thrombo-embolic events in patients with non-rheumatic atrial fibrillation (AF). We compared outcome of LAAO versus 'suboptimal standard' treatment in AF patients with high bleeding risk. METHODS AND RESULTS: Patients with sufficient follow-up data (n = 125) who underwent LAAO with the Amplatzer Cardiac Plug (ACP) were selected from the Belgian ACP database. AF patients who survived intracranial haemorrhage were recruited from the Leuven Neurosurgical Registry (LNR, n = 113). After propensity score adjustment, the outcome of both groups was compared for the combined end point (death, stroke, transient ischaemic attack, systemic emboli, and major bleeding event). The LAAO group did not differ from the LNR group for mean age and gender (74 ± 7 versus 75 ± 10 years, P = 0.29; female 39% versus 48%, P = 0.18). However, the CHA2DS2-VASc and HAS-BLED scores were both higher in the LAAO group (4.8 ± 1.7 versus 3.9 ± 1.7, P = 0.0001; 3.5 ± 1.4 versus 3.2 ± 1.4, P = 0.036). After propensity score adjustment, the risk for the primary end point was significantly higher for the LNR group (HR 2.012, 95% CI 1.113-3.638). CONCLUSION: LAAO with ACP seems to improve the combination of survival and the prevention of thrombo-embolic and major bleeding events in patients with atrial fibrillation and increased bleeding risk.

Fetoscopic versus Open Repair for Spina Bifida Aperta: A Systematic Review of Outcomes.

OBJECTIVE: To compare outcomes of fetoscopic spina bifida aperta repair (FSBAR) with the results of the open approach (OSBAR) as in the Management Of Myelomeningocele Study (MOMS). METHODS: This was a systematic comparison of reports on FSBAR with data from the MOMS (n = 78). Inclusion criteria were studies of spina bifida aperta patients who underwent FSBAR and were followed for ≥12 months. Primary outcome was perinatal mortality. Secondary outcomes included operative, maternal, fetal, neonatal and infant outcomes. RESULTS: Out of 16 reports, we included 5 from 2 centers. Due to bias and heterogeneity, analysis was restricted to two overlapping case series (n = 51 and 71). In those, FSBAR was technically different from OSBAR, had comparable perinatal mortality (7.8 vs. 2.6%, p = 0.212) and shunt rate at 12 months (45 vs. 40%, p = 0.619), longer operation time (223 vs. 105 min, p < 0.001), higher preterm prelabor membrane rupture rate (84 vs. 46%, p < 0.001), earlier gestational age at birth (32.9 vs. 34.1 weeks, p = 0.03), higher postnatal reoperation rate (28 vs. 2.56%, p < 0.001) and absence of uterine thinning or dehiscence (0 vs. 36%, p < 0.001). Functional outcomes were not available. CONCLUSION: FSBAR utilizes a different neurosurgical technique, takes longer to complete, induces more prematurity, requires additional postnatal procedures, yet has a comparable shunt rate and is not associated with uterine thinning or dehiscence. Long-term functional data are awaited.

Cutaneous reflex modulation and self-induced reflex attenuation in cerebellar patients.

Modulation of cutaneous reflexes is important in the neural control of walking, yet knowledge about underlying neural pathways is still incomplete. Recent studies have suggested that the cerebellum is involved. Here we evaluated the possible roles of the cerebellum in cutaneous reflex modulation and in attenuation of self-induced reflexes. First we checked whether leg muscle activity during walking was similar in patients with focal cerebellar lesions and in healthy control subjects. We then recorded cutaneous reflex activity in leg muscles during walking. Additionally, we compared reflexes after standard (computer triggered) stimuli with reflexes after self-induced stimuli for both groups. Biceps femoris and gastrocnemius medialis muscle activity was increased in the patient group compared with the control subjects, suggesting a coactivation strategy to reduce instability of gait. Cutaneous reflex modulation was similar between healthy control subjects and cerebellar patients, but the latter appeared less able to attenuate reflexes to self-induced stimuli. This suggests that the cerebellum is not primarily involved in cutaneous reflex modulation but that it could act in attenuation of self-induced reflex responses. The latter role in locomotion would be consistent with the common view that the cerebellum predicts sensory consequences of movement.

Gait asymmetry during early split-belt walking is related to perception of belt speed difference.

Gait adaptation is essential for humans to walk according to the different demands of the environment. Although locomotor adaptation has been studied in different contexts and in various patient populations, the mechanisms behind locomotor adaptation are still not fully understood. The aim of the present study was to test two opposing hypotheses about the control of split-belt walking, one based on avoidance of limping and the other on avoiding limb excursion asymmetry. We assessed how well cerebellar patients with focal lesions and healthy control participants could sense differences between belt speeds during split-belt treadmill walking and correlated this to split-belt adaptation parameters. The ability to perceive differences between belt speeds was similar between the cerebellar patients and the healthy controls. After combining all participants, we observed a significant inverse correlation between stance time symmetry and limb excursion symmetry during the early phase of split-belt walking. Participants who were better able to perceive belt speed differences (e.g., they had a lower threshold and hence were able to detect a smaller speed difference) walked with the smallest asymmetry in stance time and the largest asymmetry in limb excursion. Our data support the hypothesis that humans aim to minimize (temporal) limping rather than (spatial) limb excursion asymmetry when using their perception of belt speed differences in the early phase of adaptation to split-belt walking.

Adaptation and aftereffects of split-belt walking in cerebellar lesion patients.

To walk efficiently and stably on different surfaces under various constrained conditions, humans need to adapt their gait pattern substantially. Although the mechanisms behind locomotor adaptation are still not fully understood, the cerebellum is thought to play an important role. In this study we aimed to address the specific localization of cerebellar involvement in split-belt adaptation by comparing performance in patients with stable focal lesions after cerebellar tumor resection and in healthy controls. We observed that changes in symmetry of those parameters that were most closely related to interlimb coordination (such as step length and relative double stance time) were similar between healthy controls and cerebellar patients during and after split-belt walking. In contrast, relative stance times (proportions of stance in the gait cycle) were more asymmetric for the patient group than for the control group during the early phase of the post-split-belt condition. Patients who walked with more asymmetric relative stance times were more likely to demonstrate lesions in vermal lobules VI and Crus II. These results confirm that deficits in gait adaptation vary with ataxia severity and between patients with different types of cerebellar damage.

Prenatal diagnosis and patient preferences in patients with neural tube defects around the advent of fetal surgery in Belgium and Holland.

INTRODUCTION: We review the characteristics and prenatal choices of patients recently evaluated for neural tube defects (NTD) at two tertiary units. The prenatal diagnosis of NTD allows parents to consider all prenatal options. In selected cases of spina bifida aperta this also includes fetal surgery, which we started offering after combined 'in-house' and 'exported' training. MATERIAL AND METHODS: This is a retrospective review of prospectively collected data on NTD diagnosed over the last 8 years and recent fetal surgery referrals. RESULTS: A total of 167 patients were referred for assessment at a median of 19 weeks. Cranial lesions were diagnosed significantly earlier than spinal lesions. Of the open spinal lesions, 77% were isolated. Of these, 22% were managed expectantly and 1 (1%) had fetal surgery. There was no correlation between parental decisions on prenatal management with disease-specific severity markers. We had 14 fetal surgery referrals, all but 1 from beyond our typical referral area; 6 of the assessed patients were operated on, 4 were expectantly managed and 4 requested termination of pregnancy (TOP). These pregnancy outcomes were in the expected range. DISCUSSION: Open spina bifida is mainly diagnosed in the second trimester and 76% of subjects request TOP, irrespective of the severity indicators. The number of local patients considering fetal surgery is low.

Leukocyte- and platelet-rich fibrin in cranial surgery: a single-blinded, prospective, randomized controlled noninferiority trial.

OBJECTIVE: CSF leakage is a major complication after cranial surgery, and although fibrin sealants are widely used for reinforcing dural closure, concerns exist regarding their safety, efficacy, and cost. Leukocyte- and platelet-rich fibrin (L-PRF), an autologous platelet concentrate, is readily available and inexpensive, making it a cost-effective alternative for commercially available fibrin sealants. This study aimed to demonstrate the noninferiority of L-PRF compared with commercially available fibrin sealants in preventing postoperative CSF leakage in supra- and infratentorial cranial surgery, with secondary outcomes focused on CSF leakage risk factors and adverse events. METHODS: In a single-blinded, prospective, randomized controlled interventional trial conducted at a neurosurgery department of a tertiary care center (UZ Leuven, Belgium), patients undergoing elective cranial neurosurgery were randomly assigned to receive either L-PRF (active treatment) or commercially available fibrin sealants (control) for dural closure in a 1:1 ratio. RESULTS: Among 350 included patients, 328 were analyzed for the primary endpoint (44.5% male, mean age 52.3 ± 15.1 years). Six patients (5 in the control group, 1 in the L-PRF group) presented with CSF leakage requiring any intervention (relative risk [RR] 0.20, one-sided 95% CI -∞ to 1.02, p = 0.11), confirming noninferiority. Of these 6 patients, 1 (in the control group) presented with CSF leakage requiring revision surgery. No risk factors for reconstruction failure in combination with L-PRF were identified. RRs for adverse events such as infection (0.72, 95% CI -∞ to 1.96) and meningitis (0.36, 95% CI -∞ to 1.25) favored L-PRF treatment, although L-PRF treatment showed slightly more bleeding events (1.44, 95% CI -∞ to 4.66). CONCLUSIONS: Dural reinforcement with L-PRF proved noninferior to commercially available fibrin sealants, with no safety issues. Introducing L-PRF to standard clinical practice could result in important cost savings due to accessibility and lower cost. Clinical trial registration no.: NCT03812120 (ClinicalTrials.gov).

Leukocyte- and platelet-rich fibrin in cranial surgery: study protocol for a prospective, parallel-group, single-blinded randomized controlled non-inferiority trial {1}.

BACKGROUND: CSF leakage is a major complication after cranial surgery, thus, adequate dural closure must be performed. Commercially available fibrin sealants are currently considered the gold standard for dural closure, but problems have been reported regarding safety, efficacy, and costs. This trial aims to investigate autologous leukocyte- and platelet-rich fibrin (L-PRF) as an alternative to commercially available fibrin sealants. METHODS/DESIGN: This single-blinded, prospective randomized controlled interventional trial aims to demonstrate the non-inferiority of L-PRF compared to commercially available fibrin sealants for dural closure. This trial will include patients undergoing cranial neurosurgery (supratentorial and infratentorial) with intentional opening of the dura. Patients are randomized in a 1:1 fashion comparing L-PRF to commercially available fibrin sealants. The primary endpoint is postoperative CSF leakage within 12 weeks after surgery. Secondary endpoints are complications such as bleeding or wound infections. Additionally, a cost-effectiveness analysis is performed. DISCUSSION: With this trial, we will evaluate the safety and efficiency of L-PRF compared to commercially available fibrin sealants. TRIAL REGISTRATION: ClinicalTrials.gov NCT03812120. Registered on 22 January 2019.

NID1-related autosomal dominant Dandy-Walker malformation with occipital cephalocele in three generations.

The combination of Dandy-Walker malformation and occipital cephalocele is a rare autosomal dominant condition, known as ADDWOC, and caused by mutations in NID1 or LAMC1. We present a three-generation family with variable manifestations of Dandy-Walker malformation and occipital cephalocele. They all have normal psychomotor development and lack neurological manifestations. Mutation analysis revealed a likely pathogenic missense variant in NID1 (c.3336T > G, p.Asn1112Lys), affecting an amino acid residue crucial in the nidogen/laminin interaction.

Stratification according to HGG-IMMUNO RPA model predicts outcome in a large group of patients with relapsed malignant glioma treated by adjuvant postoperative dendritic cell vaccination.

PURPOSE: Adult patients with relapsed high-grade glioma are a very heterogenous group with, however, an invariably dismal prognosis. We stratified patients with relapsed high-grade glioma treated with re-operation and postoperative dendritic cell (DC) vaccination according to a simple recursive partitioning analysis (RPA) model to predict outcome. PATIENTS AND METHODS: Based on age, pathology, Karnofsky performance score, and mental status, 117 adult patients with relapsed malignant glioma, undergoing re-operation, and postoperative adjuvant dendritic cell (DC) vaccination were stratified into 4 classes. Kaplan-Meier survival estimates were generated for each class of this HGG-IMMUNO RPA model. Extent of resection was documented but not included in the prognostic model. RESULTS: Kaplan-Meier overall survival estimates revealed significant (p < 0.0001) differences among the 4 HGG-IMMUNO RPA classes. Long-term survivors, surviving more than 24 months after the re-operation and vaccination, are seen in 54.5, 26.7, 11.5, and 0 % for the classes I, II, III, and IV respectively. CONCLUSION: This HGG-IMMUNO RPA classification is able to predict overall survival in a large group of adult patients with a relapsed malignant glioma, treated with re-operation and postoperative adjuvant DC vaccination in the HGG-IMMUNO-2003 cohort comparison trial. The model appears useful for prognostic patient counseling for patients participating in DC vaccination trials. A substantial number of long-term survivors after relapse are seen in class I to III, but not in class IV patients.