Development and Growth of Intracranial Meningiomas in Transgender Women Taking Cyproterone Acetate as Gender-Affirming Progestogen Therapy: A Systematic Review.

Background: Gender-affirming hormone therapy is critical to the management of transgender persons. Cyproterone acetate (CPA) is a synthetic, progesterone-like compound commonly used in high doses as gender-affirming progestogen therapy in transgender women. An association between high-dose CPA and the development and growth of intracranial meningioma, including case reports in transgender women, has been described. This systematic review summarizes these cases at the patient level and discusses their management. Methods: This systematic review was registered with PROSPERO (CRD42020191965). A detailed search of the PubMed, EMBASE, and Web of Science electronic bibliographic databases was performed (inception-December 20, 2020). Two review authors independently completed screening, data extraction, and risk of bias assessment in duplicate. Results: Nine records were included describing (n=12) individual case reports and (n=35) intracranial meningiomas. The median age at presentation was 48 years (interquartile range [IQR], 43-55 years), most frequent daily CPA doses were 50 mg/day (n=5) and 100 mg/day (n=5), and the median duration of CPA use was 9.5 years (IQR, 6.5-17.5 years). Multiple meningiomas were common (n=7). For most cases (n=10), surgical resection was the initial preferred management strategy, but two were successfully managed by CPA cessation. Conclusions: Transgender women receiving high doses of CPA may be at increased risk of intracranial meningioma development and/or growth, although this remains a rare disease. For presumed CPA-associated meningioma, drug cessation appears to be an appropriate management strategy when surgery is not imminently required to manage raised intracranial pressure or prevent neurological deterioration. Given the importance of gender-affirming hormone therapy to transgender persons, a suitable alternative hormone regimen should be offered, although the use of CPA in both high doses and for prolonged periods of time is now in decline.

Gender-affirming hormone therapy associated with multiple meningiomas and atypical histology in a transgender woman.

We present a 69-year-old transgender woman who underwent gender-affirming surgery in 1998 and gender-affirming hormone therapy (cyproterone acetate (CPA) and estradiol) since this time. Following an MRI scan to investigate tremor in 2013, an incidental left anterior clinoid and right petrous meningioma were identified. Subtotal surgical resection was achieved for the anterior clinoid meningioma (WHO grade 1, meningothelial subtype). At follow-up in 2016, an olfactory groove meningioma and left greater wing of sphenoid meningioma were identified. By 2017, both tumours, along with the petrous meningioma, demonstrated significant growth. In 2018, clinical decline was evident and MRI demonstrated further tumour growth. Surgery was scheduled and the olfactory groove meningioma was completely resected (WHO grade 2, chordoid subtype). Hormones were stopped, after which regression of the petrous meningioma was observed. This case demonstrates an association between high-dose CPA and estradiol and the development, growth and regression of meningiomas in a transgender woman.

Screening for cerebrovascular disorder on the basis of family history in asymptomatic children.

Background: Cerebrovascular disorders represent a group of uncommon, heterogeneous, and complex conditions in children. We reviewed the screening practice for the detection of cerebrovascular disorder in asymptomatic children referred to our neurovascular service on the basis of a positive family history and parental and/or treating physician concern.Methods: Retrospective case-note review of referrals to our neurovascular service (July 2008-April 2018). Patients were included if the referral was made for screening, on the basis of a positive family history of cerebrovascular disorder. Symptomatic children, those with previous cranial imaging, or children under the care of a clinical geneticist (i.e. due to the child or their relative having HHT or mutations in KRIT1) were not eligible for inclusion.Results: Forty-one children were reviewed, 22 males (Median age 10.7 years, range 0.6-15.6 years). This represented 22% of the total number of referrals over a 10-year period. Twenty-nine children had an MRI/MRA brain. Twenty-eight children were referred due to a family history of intracranial aneurysm and/or subarachnoid haemorrhage, but only two had two first-degree relatives affected. Ten children were referred due to a family history of arteriovenous malformation. Three children were referred due to a family history of stroke. No cerebrovascular disease was detected during the study period (n = 29).Conclusions: Parental and/or physician concern generated a substantial number of referrals but no pathology was detected after screening. Whilst general screening guidance exists for the detection of intracranial aneurysms, consensus guidelines for the screening of children with a positive family history do not, but are required both to guide clinical practice and to assuage parental and/or physician concerns.

Spontaneous and recurrent subdural haematoma in a patient with May-Hegglin anomaly.

Both acute and chronic subdural haematomas typically occur following trauma. Non-traumatic causes are less common, but aetiologies include arteriovenous malformation, intracranial aneurysm rupture, tumour-associated haemorrhage and coagulopathies. May-Hegglin anomaly is an example of a coagulopathy, which is caused by a mutation in the gene encoding non-muscle myosin heavy chain 9 (MYH9) and therefore falls into a group of diseases referred to as MYH9-related diseases (MYH9-RD). The symptomology of MYH9-RD is often mild, and patients tend to experience epistaxis, gingival bleeding and bruising. Life-threatening haemorrhage rarely occurs. In this short report, we describe a patient with known May-Hegglin anomaly who presented with a potentially life-threatening, spontaneous subdural haematoma requiring surgery on two occasions. This is only the second such report in the literature, and the first of spontaneous and recurrent haemorrhage in association with May-Hegglin anomaly.

Reporting morbidity associated with pediatric brain tumor surgery: are the available scoring systems sufficient?

OBJECTIVE: Complications in pediatric neurooncology surgery are seldom and inconsistently reported. This study quantifies surgical morbidity after pediatric brain tumor surgery from the last decade in a single center, using existing morbidity and outcome measures. METHODS: The authors identified all pediatric patients undergoing surgery for an intracranial tumor in a single tertiary pediatric neurosurgery center between January 2008 and December 2018. Complications between postoperative days 0 and 30 that had been recorded prospectively were graded using appropriate existing morbidity scales, i.e., the Clavien-Dindo (CD), Landriel, and Drake scales. The result of surgery with respect to the predetermined surgical aim was also recorded. RESULTS: There were 477 cases (364 craniotomies and 113 biopsies) performed on 335 patients (188 males, median age 9 years). The overall 30-day mortality rate was 1.26% (n = 6), and no deaths were a direct result of surgical complication. Morbidity on the CD scale was 0 in 55.14%, 1 in 10.69%, 2 in 18.66%, 3A in 1.47%, 3B in 11.74%, and 4 in 1.05% of cases. Morbidity using the Drake classification was observed in 139 cases (29.14%). Neurological deficit that remained at 30 days was noted in 8.39%; 78% of the returns to the operative theater were for CSF diversion. CONCLUSIONS: To the authors' knowledge, this is the largest series presenting outcomes and morbidity from pediatric brain tumor surgery. The mortality rate and morbidity on the Drake classification were comparable to those of published series. An improved tool to quantify morbidity from pediatric neurooncology surgery is necessary.

The role of early intra-operative MRI in partial resection of optic pathway/hypothalamic gliomas in children.

INTRODUCTION: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign but situated in an exquisitely sensitive brain region. They follow an unpredictable course and are usually impossible to resect completely. We present a case series of 10 patients who underwent surgery for OPHGs with the aid of intra-operative MRI (ioMRI). The impact of ioMRI on OPHG resection is presented, and a role for ioMRI in partial resection is discussed. METHODS: Ten patients with OPHGs managed surgically utilising ioMRI at Alder Hey Children's Hospital between 2010 and 2013 were retrospectively identified. Demographic and relevant clinical data were obtained. MRI was used to estimate tumour volume pre-operatively and post-resection. If ioMRI demonstrated that further resection was possible, second-look surgery, at the discretion of the operating surgeon, was performed, followed by post-operative imaging to establish the final status of resection. Tumour volume was estimated for each MR image using the MRIcron software package. RESULTS: Control of tumour progression was achieved in all patients. Seven patients had, on table, second-look surgery with significant further tumour resection following ioMRI without any surgically related mortality or morbidity. The median additional quantity of tumour removed following second-look surgery, as a percentage of the initial total volume, was 27.79% (range 11.2-59.2%). The final tumour volume remaining with second-look surgery was 23.96 vs. 33.21% without (p = 0.1). CONCLUSIONS: OPHGs are technically difficult to resect due to their eloquent location, making them suitable for debulking resection only. IoMRI allows surgical goals to be reassessed intra-operatively following primary resection. Second-look surgery can be performed if possible and necessary and allows significant quantities of extra tumour to be resected safely. Although the clinical significance of additional tumour resection is not yet clear, we suggest that ioMRI is a safe and useful additional tool, to be combined with advanced neuronavigation techniques for partial tumour resection.

Endoscopic Third Ventriculostomy in Children with Myelomeningocele: A Case Series.

Hydrocephalus develops in up to 80-90% of children with myelomeningocele (MM) after closure of the defect. Traditionally, ventriculoperitoneal shunts have been used to manage hydrocephalus in these patients. A role for endoscopic third ventriculostomy (ETV) in MM has provoked much debate, principally due to anatomical variants described, which may complicate the procedure. We present 7 cases of children with MM and hydrocephalus undergoing a total of 10 ETV procedures. All patients demonstrated clinical improvement (in acute/subacute cases) or stabilization (in chronic cases). Three patients requiring a second ETV have shown clinical stability and renewed radiological evidence of functioning ventriculostomies in follow-up since reintervention. ETV can be used, albeit cautiously, in selected cases of hydrocephalus associated with MM. However, the frequency with which anatomical variation is encountered and the difficulty of the assessment of success make the procedure more challenging than usual.

Retrospective observational comparative study of Hemilaminectomy versus Laminectomy for intraspinal tumour resection; Shorter Stays, Lower Analgesic Usage and Less Kyphotic Deformity.

INTRODUCTION: Intraspinal tumours are rare and principally managed surgically. Laminectomy, employed for access to the spinal canal, destroys the posterior tension band leading to a risk of kyphosis. Hemilaminectomy as an alternative may be less destructive, potentially reducing the risk of deformity and causing less post-operative pain. METHOD: We investigated this hypothesis by retrospectively reviewing a case series of 56 surgeries for a disparate and unselected group of intraspinal tumours utilizing a laminectomy or hemilaminectomy approach. RESULTS: No difference was found in length of operation, completeness of resection, complication rate and Frankel-score improvements. Hemilaminectomy (n = 22) is associated with reduced hospital stay (post-op days) 4.5 (2-6) versus 6 (3-8), (p = 0.026, Mann-Whitney), and a reduction in post-operative morphine use (mg) 10 (3.5-28) versus 30 (10-90), (p = 0.005, Mann-Whitney). Post-operative kyphosis was measured with the Harrison posterior tangent method on T2-weighted sagittal MR images. The average change in kyphosis angle was greater in the laminectomy group compared with the hemilaminectomy group, 3.6 (0.8-6.2) versus 0.4 (-0.2-1.2), statistically significant (p = 0.004, Mann-Whitney). CONCLUSION: Hemilaminectomy is as effective an access procedure for the resection of unselected intraspinal tumours as laminectomy, but is associated with shorter post-operative stays, lower analgesic requirements and less post-operative kyphosis.

Extradural abscess secondary to Salmonella enteritidis in a child following fronto-orbital facial advancement and remodeling surgery.

Intracranial infections caused by Salmonella are rare. We describe the first case of a child undergoing craniofacial surgery for trigonocephaly and subsequently developing an extradural abscess secondary to likely community-acquired Salmonella enteritidis. He underwent surgical washout but returned to theater for a further 2, alongside a prolonged course of intravenous ciprofloxacin. We observed extensive anterior skull bone loss at 78 days postoperatively. At 1 year 11 months, extensive anterior skull bone remodeling had taken place, and the child is currently well.

MRI findings of intracranial anomalies associated with cephalocele--a case series.

INTRODUCTION: Cephalocele is a relatively rare cranial dysraphism characterised by herniation of intracranial structures through the skull. Surgical management is primarily necessary where a risk of infection through communication of the lesion with the intracranial space exists, a risk of rupture, or for cosmetic purposes. Cephalocele is often associated with venous anomalies such as vertical embryonic positioning of the straight sinus, splitting of the superior sagittal sinus, vein of Galen elongation, along with tenting of the tentorium [Morioka et al. Childs Nerv Syst 25:309-315, 2009] PATIENTS: Here, we report four cases of cephalocele with pre-operative MRI imaging retrospectively studied, demonstrating associated venous anomalies. Three of these patients went on to have uncomplicated, corrective surgery, while one was managed conservatively. RESULTS: All four cases demonstrated the main venous drainage going through a persistent falcine sinus to drain into the superior sagittal sinus. Upward tenting of the tentorium was observed in three cases (cases 1, 3 and 4). Two of our cases demonstrated other venous anomalies frequently reported in the literature, namely splitting of the superior sagittal sinus and absence of the transverse sinus (case 1) and communication of the cephalocele with the superior sagittal sinus and absence of the straight sinus (case 2). CONCLUSION: The association between cephalocele and venous anomalies suggests that pre-operative MRI should be mandatory for a full evaluation of a suspicious midline cranial lesion in order to evaluate the safety of corrective surgery.

Foreign body granuloma secondary to ventriculo-peritoneal shunt: a rare scenario with a new insight.

Ventriculo-peritoneal shunts are used extensively for the management of hydrocephalus and frequently present with complications such as shunt blockage and infection. Cerebrospinal fluid (CSF) eosinophilia and allergic responses to the shunt itself are rare, poorly understood but increasingly recognised complications. Here, the authors describe a child who required multiple shunt revision surgeries due to extensive scalp tenderness overlying the shunt tubing and persistent severe headaches despite having a normal working shunt and no CSF infection or eosinophilia. Histological investigation of excised tissue during the last shunt revision demonstrated fibrosis with scar tissue and chronic inflammatory infiltrate with foreign body giant cells and few abortive granulomata. This was felt to represent a foreign body reaction to the shunt. A hypoallergenic 'extracted' shunt was trialled (extracted Delta® valve and extracted ventricular and peritoneal catheters; Medtronic) and the child has had no further shunt revisions and is currently asymptomatic 1 year after the insertion.