Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid.

Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.

Metagenomic sequencing of the skin microbiota of the scalp predicting the risk of surgical site infections following surgery of traumatic brain injury in sub-Saharan Africa.

BACKGROUND: Surgical site infections (SSI) are a significant concern following traumatic brain injury (TBI) surgery and often stem from the skin's microbiota near the surgical site, allowing bacteria to penetrate deeper layers and potentially causing severe infections in the cranial cavity. This study investigated the relationship between scalp skin microbiota composition and the risk of SSI after TBI surgery in sub-Saharan Africa (SSA). METHODS: This was a prospective cohort study, enrolling patients scheduled for TBI surgery. Sterile skin swabs were taken from the surrounding normal skin of the head and stored for analysis at -80°Celcius. Patients were monitored postoperatively for up to three months to detect any occurrences of SSI. 16S rRNA sequencing was used to analyze the skin microbiota composition, identifying different taxonomic microorganisms at the genus level. The analysis compared two groups: those who developed SSI and those who did not. RESULTS: A total of 57 patients were included, mostly male (89.5%) with a mean age of 26.5 years, predominantly from urban areas in Uganda and victims of assault. Graphical visualization and metagenomic metrics analysis revealed differences in composition, richness, and evenness of skin microbiota within samples (α) or within the community (ß), and showed specific taxa (phylum and genera) associated with either the group of SSI or the No SSI. CONCLUSIONS: Metagenomic sequencing analysis uncovered several baseline findings and trends regarding the skin microbiome's relationship with SSI risk. There is an association between scalp microbiota composition (abundancy and diversity) and SSI occurrence following TBI surgery in SSA. We hypothesize under reserve that the scalp microbiota dysbiosis could potentially be an independent predictor of the occurrence of SSI; we advocate for further studies with larger cohorts.

Calvarial vault remodeling including pterional decompression for the treatment of nonsyndromic scaphocephaly patients: technical note and retrospective case series.

OBJECTIVE: Surgical techniques to correct scaphocephaly often rely on the implantation of foreign material and/or postoperative helmet therapy and possibly result in minimal correction of frontal bossing. Moreover, foreign material and helmet therapy are associated with extra medical care and financial costs. Frontal bossing is perceived as a prominent, disfiguring feature of scaphocephaly. Herein, authors present the results of a total cranial vault remodeling technique that corrects scaphocephaly features without relying on foreign material or postoperative helmet therapy. It includes frontal release and pterional decompression, which aim to correct frontal bossing. METHODS: All patients who had been operated on for isolated scaphocephaly at a single institution between January 2011 and December 2020 were included in this retrospective review. Operation time, transfusion volume, hospital stay, complications, cephalic index (CI), and bossing angle (BA) were analyzed. RESULTS: Sixty-five patients with nonsyndromic scaphocephaly were included in this analysis. Imaging to calculate the CI and BA preoperatively, immediately postoperatively, and 1 year postoperatively was available in 22 and 20 patients, respectively. The mean CI increased from 69.2% preoperatively to 74.6% postoperatively and 75.5% 1 year postoperatively. The mean BA decreased from 114.5° preoperatively to 111.6° postoperatively and 108.9° 1 year postoperatively. The mean operating time was 2 hours 4 minutes, and the median blood transfusion volume was 100 ml. There were no major complications or reoperations. CONCLUSIONS: The described total cranial vault remodeling technique is a safe procedure that mitigates total treatment burden, as no helmet therapy or implantation of foreign material is needed. It is effective in correcting CI and results in significant frontal bossing correction. The latter is attributed to a distinctive feature of the technique: frontal release and pterional decompression.

Spinal Syrinx Due to Lipiodol-Induced Arachnoiditis.

We present a case of a progressive symptomatic intramedullary cyst, diagnosed decades after Lipiodol injection. Lipiodol was originally administered intrathecally for the radiologic diagnosis of spinal masses. A link between the lesion and the history of Lipiodol injection was never suspected. Surgical exploration revealed a membrane above the lesion, separating the intradural space in a cranial and caudal compartment. On the level of the cyst, we identified glassy pearls containing a fatty liquid, compatible with Lipiodol deposits. We hypothesize that the syrinx is secondary to the impact of cerebrospinal fluid pulsations on the reactive membrane and that this membrane originated from an arachnoiditis caused by Lipiodol deposits. Lipiodol was indeed abandoned after it was found to cause arachnoiditis and neurologic sequelae. Despite the cessation of its usage, the causal role of Lipiodol in arachnoiditis and spinal cyst formation should still be considered, as symptoms may arise many years after Lipiodol administration.

A new dynamic model for in vitro evaluation of intravascular devices.

INTRODUCTION:: A dynamic model to evaluate thrombus formation on intravascular catheters in vitro is presented. The model enables fluid infusion, variation in the catheter orientation, and variable flow conditions. It was applied on a catheter used to shunt cerebrospinal fluid to a vein, a dural venous sinus, for the treatment of hydrocephalus. METHODS:: Fresh human blood-filled circuits were circulated in a non-occlusive roller pump. A catheter infused either with cerebrospinal fluid, Ringer's lactate, or no fluid (control) was inserted through each circuit's wall. Sixteen circuits (six cerebrospinal fluid, six Ringer's lactate, four control) ran for 60 min. Qualitative assessment was performed by measuring viscoelastic properties of blood at the start and end of the experiment; quantitative evaluation of clot formation by scanning electron microscope. RESULTS:: Average blood velocity was 79 mm/s, with a pressure wave between 5 and 15 mm Hg. At the experiment's end, the infused fluid represented 5.88% of the blood/infusion volume in the circuit. The control circuits showed no statistical difference between the start and end for viscoelastic testing, whereas both Ringer's lactate and cerebrospinal fluid enhanced coagulation, most pronounced for the latter. Most thrombus material was observed on catheters in the cerebrospinal fluid group. Clot formation was less pronounced on the surface of the catheter facing the blood flow. DISCUSSION:: A dynamic model for intravascular catheter testing mimics better clinical conditions when evaluating blood-material interaction. Catheter position, blood flow around the catheter, and infusion fluid all have a potential impact on the hemocompatibility of a given catheter.

Treating Hydrocephalus with Retrograde Ventriculosinus Shunt: Prospective Clinical Study.

BACKGROUND: Since the 1950s, hydrocephalus has been be treated with cerebrospinal fluid (CSF) shunts, usually to the peritoneal cavity or to the right cardiac atrium. However, because of their siphoning effect, these shunts lead to nonphysiologic CSF drainage, with possible comorbidity and high revision rates. More sophisticated shunt valve systems significantly increase costs and technical complexity and remain unsuccessful in a subgroup of patients. In an attempt to obtain physiologic CSF shunting, many neurosurgical pioneers shunted towards the dural sinuses, taking advantage of the physiologic antisiphoning effect of the internal jugular veins. Despite several promising reports, the ventriculosinus shunts have not yet become standard neurosurgical practice. METHODS: In this single-center prospective clinical study, we implanted the retrograde ventriculosinus shunt, as advocated by El-Shafei, in 10 patients. This article reports on our operation technique and long-term outcome, including 4 patients in whom this shunt was implanted as a rescue operation. RESULTS: Implantation of a ventriculosinus shunt proved to be feasible, warranting physiologic drainage of CSF. However, in only 3 of 14 patients, functionality of the retrograde ventriculosinus shunt was maintained during more than 6 years of follow-up. In our opinion, these shunts fail because present venous access devices are difficult to implant correctly and become too easily obstructed. After discussion of possible causes of this frequent obstruction, a new dural venous sinus access device is presented. CONCLUSION: An easy-to-implant and thrombogenic-resistant dural venous sinus access device needs to be developed before ventriculosinus shunting can become general practice.

The influence of cerebrospinal fluid on blood coagulation and the implications for ventriculovenous shunting.

OBJECTIVE: The effect of CSF on blood coagulation is not known. Enhanced coagulation by CSF may be an issue in thrombotic complications of ventriculoatrial and ventriculosinus shunts. This study aimed to assess the effect of CSF on coagulation and its potential effect on thrombotic events affecting ventriculovenous shunts. METHODS: Two complementary experiments were performed. In a static experiment, the effect on coagulation of different CSF mixtures was evaluated using a viscoelastic coagulation monitor. A dynamic experiment confirmed the amount of clot formation on the shunt surface in a roller pump model. RESULTS: CSF concentrations of 9% and higher significantly decreased the activated clotting time (ACT; 164.9 seconds at 0% CSF, 155.6 seconds at 9% CSF, and 145.1 seconds at 32% CSF). Increased clot rates (CRs) were observed starting at a concentration of 5% (29.3 U/min at 0% CSF, 31.6 U/min at 5% CSF, and 35.3 U/min at 32% CSF). The roller pump model showed a significantly greater percentage of shunt surface covered with deposits when the shunts were infused with CSF rather than Ringer's lactate solution (90% vs 63%). The amount of clot formation at the side facing the blood flow (impact side) tended to be lower than that at the side facing away from the blood flow (wake side; 71% vs 86%). CONCLUSIONS: Addition of CSF to blood accelerates coagulation. The CSF-blood-foreign material interaction promotes clot formation, which might result in thrombotic shunt complications. Further development of the ventriculovenous shunt technique should focus on preventing CSF-blood-foreign material interaction and stagnation of CSF in wake zones.

A non-hydrocephalic goat experimental model to evaluate a ventriculosinus shunt.

The ventriculosinus shunt is a promising treatment for hydrocephalus. Currently, different shunt techniques exist, and it is not clear whether one is preferable. This pilot study reports on a non-hydrocephalic goat model (Saanen breed) that provides opportunities to evaluate and optimize several aspects of the ventriculosinus shunt technique. Analysis of the coagulation properties of 14 goats by a viscoelastic coagulation monitor showed that goats have a hypercoagulable state compared to humans. This property can be partially counteracted by antiplatelet drugs. During implantation of a ventriculosinus shunt, a pulsatile reflux of blood was observed. After implantation, the animals recovered to their preoperative state, and none of them developed a superior sagittal sinus thrombosis. Evaluation of the shunts after 16 days showed an obstructing luminal clot. Several model-related factors may have promoted this obstruction: the absence of hydrocephalus, the hypercoagulability of caprine blood and the smaller dimensions of the caprine superior sagittal sinus. However, the pulsatile reflux of blood, which is caused by the compliance of the shunt system distal to the valve, may have been an important factor as well. In conclusion, the non-hydrocephalic goat model limits animal suffering and simplifies the study protocol. This model allows researchers to evaluate their implantation technique and shunt hardware but not the efficacy of the treatment or shunt survival.

Delayed intravenous thrombolysis based on MRI mismatch in posterior circulation stroke.

The current time-based approach for patient selection for intravenous (IV) thrombolysis in an acute stroke setting neglects the individual variation of cerebral blood flow impairment. This approach restricts the eligible patient population. In the last decade, advanced imaging and especially MRI diffusion- and perfusion-weighted imaging (DWI-PWI) techniques have been used to select patients for IV thrombolysis outside the current 4.5 h time window. Most of these studies focus on the anterior (carotid artery) cerebral circulation only. We report the case of an acute ischemic stroke due to a dissection of the right vertebral artery and occlusion of the posterior inferior cerebellar artery with good clinical outcome. The patient received IV thrombolysis far beyond the current established time window. This decision was based upon a marked MRI DWI-PWI mismatch zone in the posterior circulation territory.