Undiagnosed sagittal synostosis as cause of "idiopathic" intracranial hypertension.

PURPOSE: Idiopathic intracranial hypertension (IIH) is a rare condition in children, but if diagnosed needs to be promptly treated to avoid clinical sequalae. The main purpose of this paper was to test our clinical experience with a cohort of normocephalic children with craniosynostosis who do not present in the routine way to craniofacial services, due to the normal head shape and age, diagnosed with IIH. METHODS: We retrospectively reviewed all children who were referred to neurosurgery from 2012 to 2022 for management of IIH on our prospectively kept database. We determined what treatments were offered and if there was an associated craniosynostosis. RESULTS: In total, 19 children were identified with an average age at referral of 11.5 years (st dev 4.0 years) with 11 male and 8 female. The most common presenting symptoms and signs were papilloedema (18/19), headaches (15/19), visual deterioration (9/19), nausea and vomiting (7/19) and diplopia (4/19). Five out of 19 children (26.3%) had a sagittal suture fused that was not identified at the time of treatment and all children were normocephalic. CONCLUSION: There is a cohort of children with IIH who will have concomitant craniosynostosis and ideally would benefit from cranial vault expansion as primary surgery rather than cerebrospinal fluid (CSF) diversion. We suggest all children with IIH requiring neurosurgical intervention have cross-sectional imaging to look for occult craniosynostosis prior to intervention.

Prevalence and severity of lower urinary tract symptoms in the third trimester of pregnancy.

INTRODUCTION AND HYPOTHESIS: Pregnancy is a risk factor for urinary disorders, mainly in the third trimester. Lower urinary tract symptoms (LUTS) are often underreported by health care professionals and significantly impact the quality of life of pregnant women. Our objective is to analyse lower urinary tract function during the third trimester of pregnancy and assess the impact of traditional risk factors for pelvic floor dysfunctions on bladder health in pregnant women. METHODS: This is a secondary analysis of a multicentre cross-sectional study. Third-trimester pregnant women aged 18 years or older anonymously filled in the "Italian Pelvic Floor Questionnaire for pregnant and postpartum women" questionnaire, validated for pelvic floor disorders in pregnancy and postpartum. RESULTS: A total of 927 pregnant patients completed the questionnaire. Among them, 97.3% complained of at least one urinary disorder. Frequency was the symptom reported most often (77.3%), whereas nocturnal enuresis was the least reported (17%). Despite the high prevalence of LUTS in our sample, only 13.4% reported that they negatively impact their quality of life. Overweight and obesity, advanced maternal age, smoking, family history of pelvic floor disorders and poor pelvic floor contraction capacity were confirmed to be risk factors for the onset of LUTS, even in our population. CONCLUSIONS: Urinary symptoms are extremely common in the third trimester and significantly affect the quality of life of pregnant women. Since overweight, obesity, smoking and reduced pelvic floor contractility emerged as modifiable risk factors for the development of these symptoms, prevention and adequate counselling are cornerstones of pregnancy care.

Trapped Fourth Ventricle: Pathophysiology, History and Treatment Strategies.

Trapped fourth ventricle is a clinic-radiological entity characterised by progressive neurological symptoms due to enlargement and dilatation of fourth ventricle secondary to obstruction to its outflow. There are several causative mechanisms for the development of trapped fourth ventricle, including previous haemorrhage, infection or inflammatory processes. However, this condition is most commonly observed in ex preterm paediatric patients shunted for a post-haemorrhagic or post-infective hydrocephalus. Until the introduction of endoscopic aqueductoplasty and stent placement, treatment of trapped fourth ventricle was associated with high rates of reoperation and complications resulting in morbidity. With the advent of new endoscopic techniques, supratentorial and infratentorial approaches for aqueductoplasty and stent insertion have revolutionised the treatment of trapped fourth ventricle. Fourth ventricular fenestration and direct shunting remain viable options in cases where aqueduct anatomy and length of obstruction is not surgically favourable for endoscopic approaches. In this book chapter, we explore the background, historical developments,$ and surgical treatment strategies in the management of this challenging condition.

Endoscopic third ventriculostomy for hydrocephalus after craniovertebral decompression for Chiari malformation type I: technical nuances and surgical pitfalls.

PURPOSE: Hydrocephalus after craniovertebral decompression (CVD) for Chiari I malformation (CM-1) is a well-recognised complication. The mainstay of management involves medical management with high-dose steroids and/or acetazolamide, repeated lumbar punctures, external ventricular drainage (EVD) or insertion of a ventriculoperitoneal shunt (VPS). Endoscopic third ventriculostomy (ETV) has only been used a handful of times to treat this type of hydrocephalus with controversial outcomes. Not much is known about this or the technical nuances of this procedure. We report our experience. METHODS: All children who underwent ETV to treat hydrocephalus post CVD done for CM-1 were identified from a prospectively kept database. RESULTS: Three children were identified (13F, 11F, 13F). The average time to presentation of hydrocephalus was 8 days after craniovertebral decompression. Two were successfully treated with ETV with brain imaging showing a reduction in the size of the ventricles post-operatively and not requiring any further cerebrospinal fluid drainage. In one patient, the procedure had to be abandoned after the peel away catheter was introduced into the right ventricle because CSF egressed under high pressure with ventricle walls collapse resulting in an obstructed view. This child ultimately required a VPS. CONCLUSION: ETV can be used to successfully treat post CVD hydrocephalus in CM-1 patients depending on the aetiology of the hydrocephalus. There are technical and anatomical commonalities between these cases which make it more challenging than an ETV performed in "typical" obstructive hydrocephalus. We describe our experience and review the cases previously reported in the literature.

Endoscopic fenestration of the superior medullary velum for the treatment of a trapped fourth ventricle-technical note.

A trapped fourth ventricle is a clinic-radiological entity characterised by progressive neurological symptoms due to an enlargement of the fourth ventricle secondary to obstruction to its outflow. This condition is most commonly observed in ex-preterm patients shunted for a post-haemorrhagic or post-infective hydrocephalus. Until the introduction of endoscopic aqueductoplasty and stent placement, through a supratentorial or an infratentorial approach, treatment of trapped fourth ventricle entailed high rates of complications, repeated procedures and consequent morbidity. We describe the first case of successful treatment of trapped fourth ventricle by fenestration of superior medullary velum through an infratentorial approach in a 20-month-old child with a functional supratentorial ventriculoperitoneal shunt and an aqueductal anatomy not favourable for stenting. To the best of our knowledge, this is the first reported case of utilisation of this technique in a patient with a trapped fourth ventricle, and we wish to highlight this new alternative approach in cases where conventional aqueductoplasty and stenting may not be feasible.

The role of surgery in relieving calcified shunt site-related pain in patients with functioning VP shunt.

PURPOSE: Shunt calcification is a known late sequela of ventriculoperitoneal (VP) shunt insertion and is associated with shunt malfunction. However, in some patients, while shunt functionality is preserved despite calcification of the catheters, they experience nociceptive symptoms. In this paper, the authors present their surgical experience in managing patients with a functional VP shunt and experiencing pain secondary to shunt calcification. METHODS: We analysed outcomes of patients presenting with pain at the level of a calcified shunt who underwent surgical untethering of the calcified catheter from the soft tissues. This procedure was commenced by the senior author in 2015. Patients were collected prospectively from the databases of two institutions. Evidence of shunt calcification was confirmed on neuroimaging. RESULTS: Seven patients, two male and five female, were included. The mean age at untethering was 13.5 years. The mean time interval between primary shunt surgery and symptom onset was 12 years (range 6-16 years). The commonest site of tethering was the neck (50%) followed by abdomen and chest (both 25%). Six patients underwent untethering of the catheter from soft tissues. One patient had removal of a redundant segment of calcified shunt left in situ during a previous revision. All patients experienced pain relief following shunt untethering. CONCLUSION: Untethering of calcified VP shunt catheters from soft tissue can be considered an effective treatment of shunt site pain and offered to patients presenting with a functional VP shunt.

ERF-related craniosynostosis and surgical management in the paediatric cohort.

INTRODUCTION: ERF mutation is one of the most recently identified genetic aberrations associated with syndromic craniosynostosis. Data on the pattern of craniosynostosis, surgical management of ERF-related craniosynostosis and outcomes is limited. We report on our single-centre experience in paediatric cohort of patients with syndromic craniosynostosis secondary to ERF mutation. METHODS: A retrospective review of all paediatric craniofacial cases was performed over an 8-year period (2014-2022). All patients with genetically confirm ERF-related craniosynostosis were identified, and clinical parameters including, age, sex, pattern of craniosynostosis, associated tonsillar herniation and follow-up period were further analysed from electronic clinical and imaging systems. All patients were selected and discussed in multidisciplinary craniofacial meeting (composed of neurosurgical, maxillofacial, plastics and genetics teams) prior to any surgical intervention. RESULTS: Overall, 10 patients with ERF-related craniosynostosis were identified with a male-to-female ratio of 4:1 with mean age at the time of surgery of 21.6 months with a mean follow-up period of 5.2 years. ERF-confirmed cases led to variable craniosynostosis pattern with multi-sutural synostosis with concurrent sagittal and bilateral lambdoid involvement as the most common pattern (7/10). No patient pre-operatively had evidence of papilloedema on ophthalmological assessment. Eight out of 10 patients had associated low-lying tonsils/hind brain hernia pre-operatively. Eight out of 10 patients required surgery which included 2 fronto-orbital advancement, 3 calvarial remodelling, 2 posterior calvarial remodelling/release and 1 insertion of ventriculoperitoneal shunt. CONCLUSION: Involvement of sagittal and lambdoid sutures is the most common pattern of craniosynostosis. ERF-related craniosynostosis can have variable pattern of suture fusion, and management of each patient requires unique surgical planning and execution based on clinical needs for the optimal outcomes.

The Management of Idiopathic and Refractory Syringomyelia.

Idiopathic syringomyelia (IS) and refractory syringomyelia (RS) are types of syringomyelia that often pose a management challenge and are associated with long-term clinical sequela. They are usually an epiphenomenon reflecting an underlying pathology where the treatment of the primary cause should be the aim for any surgical intervention. In the case of IS, the initial step is agreeing on the definition of the terms idiopathic and syringomyelia. After a rigorous exhaustive clinic-radiological workup, only IS patients with progressive neurology are treated, usually unblocking subarachnoid cerebrospinal fluid (CSF) pathway obstruction somewhere in the thoracic spinal canal and reserving shunting techniques to nonresponsive cases. Similar to IS, also RS is multifactorial, and its management varies based on the initial pathology, strongly supported by radiological and clinical features. We aim to address this topic focusing on the etiopathology, investigation paradigm, and surgical pathway, formulating algorithms of management with available evidence in literature. Surgical techniques are discussed in detail.

A 10-year retrospective observational study on the utility and prescription standards of dexamethasone in pediatric neuro-oncosurgery in a tertiary care center.

OBJECT: This study aimed to retrospectively assess dexamethasone utility in pediatric CNS tumor patients over a 10-year period, to better understand dosing variability, and highlight optimal practice. METHODS: All pediatric CNS tumor cases managed operatively for a 10-year period at a single center were reviewed. Information was gathered on demographics, dexamethasone doses, course durations, weaning regimes, PPI co-prescription, adverse events, and route of administration. Comparison within these groups was analyzed through use of statistical testing. RESULTS: One hundred twenty-seven patients received 193 dexamethasone courses. Median age was 7 years, with a median weight of 27.9 kg. Most common tumor type was astrocytoma (24.8%). Median daily dose was 8 mg, with twice-daily dosing most common. Median course duration was 8 days, ranging from 1 to 1103 days. Median weaning duration was 11.5 days. Daily dose was not correlated with patient weight and the median daily dose per kg was 0.2319 mg/kg. Incidence of adverse effects was 14.5% across all course lengths, with weight gain most common. The short-term course duration (<14 days) had the lowest adverse event incidence, with direct correlation between course length and adverse effect incidence. Dexamethasone dose per kg was not significantly different between patients with and without adverse effects. No relationship was noted between adverse effects incidence and administration route (intravenous compared to oral). 64.2% of patients received concurrent PPI with 35.8% receiving no PPI, with 1 gastrointestinal side effect noted in the PPI-receiving population. CONCLUSIONS: Large variation was seen in practice, with prescriptions appearing based on clinician preference and symptom severity rather than patient age or weight. Future guidelines should consider lower dose regimens than are currently presented with less frequent dosing as these may benefit quality of life. Weaning period can be relatively rapid for most patients, taking place in 2-3 days. PPI co-prescription does not seem to add significant benefit. We recommend using a standardized guideline of 0.2 mg/kg/day (max 8 mg/day) given OD or BD, with PPI cover where necessary. For acute presentations, we recommend limiting dexamethasone treatment to <14 days. These recommendations can be adjusted for individual cases to yield optimal results.

Posterior Calvarial Distraction in older paediatric population: single centre paediatric neurosurgery craniofacial unit outcomes.

PURPOSE: Posterior calvarial distraction (PCD) is a safe and effective technique used to increase cranial vault volume and therefore reduce intracranial pressure in children with complex craniosynostosis. Optimal timing and method used for PCD is controversial. This procedure is usually performed in children younger than 2 years. Literature regarding calvarial distraction in older children is sparse and limited. We report our single-centre experience with PCD in children aged 6 and above to outline the applications, benefits and challenges of employing this technique in an older paediatric population. METHODS: A retrospective analysis of a database on craniofacial cases from 2006 to 2021 was performed. Patients undergoing PCD were identified and children aged 6 and above at the time of operation were included. Data on demographics and clinical outcomes were obtained from electronic records and relevant imaging was reviewed. All cases were reviewed prior to a decision for surgery by the multidisciplinary craniofacial team (composed of neurosurgery, maxillofacial and plastics teams) and underwent surgery in our paediatric craniofacial centre. RESULTS: Overall, 98 PCD cases were identified during the study period, of which 20 cases were identified as having undergone PCD at age 6 or above with mean age of 8.8 years (range 6-18). The most common indication was pansynostosis associated with raised intracranial pressure. Four cases had calvarial remodelling previously and represented with symptoms of raised intracranial pressure sometime after their initial surgery requiring PCD as rescue procedure. Average duration of inpatient stay was 5.85 days. The average duration of follow-up was 3.5 years (0.3 to 11 years). Mean distraction distance achieved was 22.5 mm (18-29 mm). Five patients experienced complications related to wound infection or distractor. Follow-up assessment in all patients demonstrated evidence of vault expansion and symptomatic improvement and resolution of intracranial pressure signs. Comparison with younger cohort did not reveal any difference in any parameters except lower rate of transfusion in the older cohort compared to young cohort (5% vs 38%). CONCLUSION: Posterior calvarial distraction in older children is safe and effective for vault expansion and treatment of raised intracranial pressure in selected cases. A multidisciplinary craniofacial team approach is crucial for appropriate case selection and management in order to optimise outcomes.

DelCFHR3-1 influences graft survival in transplant patients with IgA nephropathy via complement-mediated cellular senescence.

IgA nephropathy (IgAN) is a frequent cause of chronic kidney disease (CKD) and progressive renal impairment. A native renal biopsy diagnosis of IgAN is a predictor of graft loss, with a relative risk of 47% but it is difficult to predict graft survival and progressive allograft dysfunction in these patients. Deletion of complement factor H-related genes 1 and 3 (delCFHR3-1) has been associated with a decreased risk of developing IgAN on native kidneys, but the impact on the graft in IgAN-transplanted patients is unknown. We hypothesized that delCFHR3-1 is also associated with the processes that influence graft survival in transplant recipients with IgAN and tested whether cellular senescence is involved in mediating graft damage. We found that patients carrying two copies of CFHR1-3 had a worse outcome (P = .000321) and presented increased FHR1 deposits at glomerular and tubulointerstitial level associated with higher expression of the senescence marker p16INK4a (P = .001) and tubulointerstitial fibrosis (P = .005). Interestingly, FHR1 deposits were associated with increased complement activation as demonstrated by C5b-9 deposits. These data support both the role of FHR1 in mediating complement activation and tubular senescence, and suggest the possibility of genotyping delCFHR3-1 to predict graft survival in IgAN-transplanted patients.

Guideline for the management of long tunnelled external ventricular drains in chronic hydrocephalus.

This article reports on the journey of a child with an inoperable hypothalamic-origin pilocytic astrocytoma causing hydrocephalus, which was refractory to treatment with shunts, and required a new approach. With multidisciplinary support, excellent nursing care and parental education, the child's hydrocephalus was managed long term in the community with bilateral long-tunnelled external ventricular drains (LTEVDs). This article describes the patient's journey and highlights the treatment protocols that were created to achieve this feat. Despite the difficulties in initially setting up these protocols, they proved successful and thus the team managing the patient proposed that LTEVDs are a viable treatment option for children with hydrocephalus in the context of inoperable tumours to help maximise quality of life.

Custom-Made Three-Dimensional Models for Craniosynostosis.

The use of computer-aided design and computer-aided manufacturing in oral and maxillofacial surgery is an ever-growing field.The availability of 3D models, cutting guides, and customised surgical instruments gives surgeons the opportunity to modify and improve their surgical procedures.Here, we discuss the use of computer-aided design-computer-aided manufacturing to improve the management of a case of nonsyndromic metopic synostosis through the construction of: A cutting guide for the cranium, custom-made orbital protectors, a 3D model of the predicted postoperative meninges to allow off the table bone recontouring, and a template frontal bar to allow more specific recontouring of the frontal bar.

De novo distal middle cerebral artery aneurysm post-excision of intracerebral arteriovenous malformation in an 8-year old.

Cerebral arteriovenous malformations (AVMs) are frequently associated with concurrent aneurysms. These aneurysms are commonly haemodynamically related to the AVM and can be classified into extranidal or intranidal in reference to the AVM nidus. An aneurysm arising from an artery that does not angiographically contribute to the blood flow to the AVM is uncommon. A distal middle cerebral artery (dMCA) aneurysm itself is also a rare presentation, especially in paediatric population. We present a rare case of dMCA aneurysm that was noted after successful surgical management of a ruptured AVM in an 8-year-old child and its management. BACKGROUND: About 10-30% of patients with cerebral arteriovenous malformation (AVM) have an associated artery aneurysm. The majority of these aneurysms are flow-related to the malformation. These aneurysms can be classified into extranidal or intranidal in reference to the AVM nidus Rammos et al Am J Neuroradiol 37:1966-1971, [1]. An aneurysm arising from a different artery that does not angiographically contribute to the blood flow associated with the AVM is less common and would generally be regarded as unrelated to the AVM. Distal cerebral artery aneurysm itself is also a rare presentation, comprising of 1-7% of all middle cerebral artery aneurysm. In children, mycotic infection and dissection are the two most common causes for aneurysm in this location. Unlike in adults, berry aneurysms are uncommon in children. We describe a young patient who was found to have distal middle cerebral artery (dMCA) aneurysm in follow-up DSA (Digital Subtraction Angiogram) after the initial successful surgical treatment for a cerebral frontal AVM. In this particular case, endovascular repair is thought to be the best strategy to treat the aneurysm. However, there still remains a lack of consensus of the best management strategy (surgery or endovascular) in treating flow-related aneurysms in general. This is usually based on an individual case scenario and the treatment is tailored depending on various factors including the expertise of the treating team.

Hot topic: Bisphenol A in cow milk and dietary exposure at the farm level.

Chemical hazards may enter the milk chain during primary production. The study, for the first time, investigated the occurrence of bisphenol A (BPA) levels in cow milk samples collected on the farm following manual or mechanical milking and from the cooling tank. We applied a new monitoring model based on the identification of the hazards at each stage of the milk chain to identify potential pathways for contamination along the milk chain. We evaluated exposure to BPA through milk consumption based on detected contamination levels and the temporary tolerable daily intake established by the European Food Safety Authority (EFSA). Milk samples (n = 72) were analyzed using liquid chromatography with fluorescence detection. The mean BPA concentrations were 0.757 µg/L in manually milked samples, 0.580 µg/L in mechanically milked samples, and 0.797 µg/L in milk from the cooling tank. Bisphenol A occurred in the milk chain as a result of different stages of milking, and reached the highest levels at the end of the milk chain. Although the dietary intake of BPA was below the EFSA's temporary tolerable daily intake, exposure to BPA, even at low doses, through milk consumption represents a public health concern. Therefore, to ensure milk safety, new monitoring plans should be applied based on the identification of hazards at each stage of the milk chain.

A rapid method to determine nine natural cannabinoids in beverages and food derived from Cannabis sativa by liquid chromatography coupled to tandem mass spectrometry on a QTRAP 4000.

RATIONALE: Phytocannabinoids are natural compounds produced by Cannabis spp. Some of these compounds show psychotropic effects on humans and are therefore used as drugs of abuse. These compounds are present in food and beverages containing ingredients from hemp, and thus can reach consumers. The Italian Ministry of Health planned to evaluate the intake of cannabinoids from food containing hemp ingredients. Thus, we were asked to develop and validate a multi-residue test method to determine nine phytocannabinoids in beverages and food. METHODS: Nine natural phytocannabinoids, hereafter called cannabinoids, were cleaned up from food by solid-liquid extraction, while beverages were simply diluted prior to analysis. The cannabinoids were separated by reversed-phase high-performance liquid chromatography, and on-line determination was carried out by tandem mass spectrometry using a 4000 QTRAP mass spectrometer with a TurboIonSpray source, in multiple-reaction monitoring mode, using both positive and negative ionization. RESULTS: Each compound was determined down to 0.25 ng/mL in solvent. In-house validation was carried out; the mean recoveries ranged from 83.4% to 101.2% in food, and from 84.5% to 104.5% in beverages. The limits of quantification were 20 µg/kg for food and 2 µg/L for beverages. CONCLUSIONS: A reliable and rapid method for the identification and quantification of the psychotropic Δ9 -tetrahydrocannabinol, its non-psychoactive precursor Δ9 -tetrahydrocannabinolic acid A, and seven other cannabinoids was developed and validated, to monitor the content of these substances in food and beverages produced using hemp seeds, flour and oil as ingredients.

Multi-drug ultraperformance liquid chromatography/tandem mass spectrometry method to quantify antimicrobials in feeding stuffs at carry-over level.

RATIONALE: Carry-over is an undesirable contamination from medicated to non-medicated during the production of feedingstuffs. In 2014 the European Parliament and the Council started working to produce a new regulatory act that will fix tolerable levels of drugs by carry-over in non-target feed to have a harmonized practice to evaluate this contamination by veterinary drugs. METHODS: We developed a rapid and effective multi-analyte method coupling ultraperformance liquid chromatography to tandem mass spectrometry (UPLC/MS/MS) for the detection of 37 drugs belonging to different classes of antimicrobials (sulfonamides, tetracyclines, macrolides, quinolones, pleuromutilins and streptogramins) in feeds at carry-over levels. The method was in-house validated in the concentration range 0.25-2.0 mg kg-1 , according to the Regulation (UE) 2017/625 requirements and the guideline included in the Commission Decision 2002/657/EC for official methods. RESULTS: The UPLC/MS/MS method allows the determination of the antimicrobials in 15 min, by providing results compliant to the criteria established by the European Commission legislation. All the analytes showed a limit of detection (LOD) in the range 2.0-5.0 µg kg-1 and a limit of quantification (LOQ) at 10.0 µg kg-1 ; oxytetracycline, doxycycline, spiramycin and virginiamycin have a higher LOD and LOQ (15.0 µg kg-1 ; 30.0 µg kg-1 , respectively). Recoveries were satisfactory ranging from 90.4% to 103.1%. CONCLUSIONS: The method is characterized by an effective clean-up of all drugs without the use of large sample size and organic solvent extraction.