Rupture of a flow aneurysm secondary to spontaneous extracranial to intracranial revascularisation in the posterior fossa following radiation-induced vasculopathy for cerebellar tumour.

Paediatric patients receiving cranial irradiation therapy for brain tumours are at increased risk of cerebrovascular complications. Radiation-induced moyamoya syndrome (MMS) is a well-recognised complication of this. We present a case of an 8-year-old boy with a history of medulloblastoma, who underwent surgical excision followed by post-operative adjuvant oncological treatment. Six years later, he developed cerebellar/intraventricular haemorrhage. He underwent an emergency external ventricular drain (EVD) insertion followed by posterior fossa suboccipital craniotomy. On dural opening, an abnormal vessel was visualised on the surface of the right cerebellar hemisphere, which was not disturbed. No obvious abnormalities were identified intra-operatively. Cerebral catheter angiography confirmed the presence of a right-sided occipital artery (OA) to posterior inferior cerebellar artery (PICA) extracranial to intracranial (EC-IC) bypass with a zone of the distal PICA territory supplied by this EC-IC bypass. A presumed flow aneurysm originated from the bypass in the distal PICA, identified as cause for the haemorrhage. We highlight a rare cause for intracranial haemorrhage in this cohort of patients. Children who have undergone radiotherapy may have exquisitely sensitive cerebral vasculature and need careful vigilance and evaluation for vasculopathic complications following spontaneous haemorrhage.

Atypical teratoid rhabdoid tumours (ATRTs)-a 21-year institutional experience.

PURPOSE: Atypical teratoid/rhabdoid tumours (ATRTs) are malignant embryonal tumours of childhood that affect the central nervous system (CNS). We aim to determine which factors, including patient age, extent of resection (EOR), presence of distal metastasis and use of adjuvant therapies, affect overall survival in children with atypical teratoid/rhabdoid tumours (ATRTs) treated at this single centre. METHODS: Retrospective cohort review of patients with histological diagnosis of ATRT treated over 21 years (1999-2020) was conducted. Data on demographics, tumour location, presence of metastasis, use of adjuvant therapy, extent of resection (EOR), complications, neurological outcome post-surgery, and overall survival were collected. Kaplan-Meier survival analysis was performed. RESULTS: A total of 45 children (mean age 2 years) underwent 64 operations. 25 patients were <1 year of age. Gross-total resection (GTR) pre-adjuvant therapy was achieved in 15, near-total resection (NTR) in 15, subtotal resection (STR) in 9, and biopsy in 6 children. Most children had good neurological outcomes post-operatively (28/45 with GOS 5). Fourteen patients survived longer than 4 years. Survival analysis showed a significant difference in median survival in favour of GTR and localised disease. There was no significant difference in median survival between patients <1 year vs >1 year of age (p=0.84). CONCLUSION: We find that presence of metastasis was an important factor in poor survival in patients with ATRT. GTR, where possible, may confer significant survival benefit in ATRT. Children aged <1 year appear to have performed as well as those >1 year and therefore should still be considered for radical surgery.

Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery.

BACKGROUND AND PURPOSE: Pediatric posterior fossa tumors often present with hydrocephalus; postoperatively, up to 25% of patients develop cerebellar mutism syndrome. Arterial spin-labeling is a noninvasive means of quantifying CBF and bolus arrival time. The aim of this study was to investigate how changes in perfusion metrics in children with posterior fossa tumors are modulated by cerebellar mutism syndrome and hydrocephalus requiring pre-resection CSF diversion. MATERIALS AND METHODS: Forty-four patients were prospectively scanned at 3 time points (preoperatively, postoperatively, and at 3-month follow-up) with single- and multi-inflow time arterial spin-labeling sequences. Regional analyses of CBF and bolus arrival time were conducted using coregistered anatomic parcellations. ANOVA and multivariable, linear mixed-effects modeling analysis approaches were used. The study was registered at clinicaltrials.gov (NCT03471026). RESULTS: CBF increased after tumor resection and at follow-up scanning (P = .045). Bolus arrival time decreased after tumor resection and at follow-up scanning (P = .018). Bolus arrival time was prolonged (P = .058) following the midline approach, compared with cerebellar hemispheric surgical approaches to posterior fossa tumors. Multivariable linear mixed-effects modeling showed that regional perfusion changes were more pronounced in the 6 children who presented with symptomatic obstructive hydrocephalus requiring pre-resection CSF diversion, with hydrocephalus lowering the baseline mean CBF by 20.5 (standard error, 6.27) mL/100g/min. Children diagnosed with cerebellar mutism syndrome (8/44, 18.2%) had significantly higher CBF at follow-up imaging than those who were not (P = .040), but no differences in pre- or postoperative perfusion parameters were seen. CONCLUSIONS: Multi-inflow time arterial spin-labeling shows promise as a noninvasive tool to evaluate cerebral perfusion in the setting of pediatric obstructive hydrocephalus and demonstrates increased CBF following resolution of cerebellar mutism syndrome.

Convection-Enhanced Delivery in Children: Techniques and Applications.

Since its first description in 1994, convection-enhanced delivery (CED) has become a reliable method of administering drugs directly into the brain parenchyma. More predictable and effective than simple diffusion, CED bypasses the challenging boundary of the blood brain barrier, which has frustrated many attempts at delivering large molecules or polymers into the brain parenchyma. Although most of the clinical work with CED has been carried out on adults with incurable neoplasms, principally glioblastoma multiforme, an increasing number of studies have recognized its potential for paediatric applications, which now include treatment of currently incurable brain tumours such as diffuse intrinsic pontine glioma (DIPG), as well as metabolic and neurotransmitter diseases. The roadmap for the development of hardware and use of pharmacological agents in CED has been well-established, and some neurosurgical centres throughout the world have successfully undertaken clinical trials, admittedly mostly early phase, on the basis of in vitro, small animal and large animal pre-clinical foundations. However, the clinical efficacy of CED, although theoretically logical, has yet to be unequivocally demonstrated in a clinical trial; this applies particularly to neuro-oncology.This review aims to provide a broad description of the current knowledge of CED as applied to children. It reviews published studies of paediatric CED in the context of its wider history and developments and underlines the challenges related to the development of hardware, the selection of pharmacological agents, and gene therapy. It also reviews the difficulties related to the development of clinical trials involving CED and looks towards its potential disease-modifying opportunities in the future.

Postoperative speech impairment and cranial nerve deficits after secondary surgery of posterior fossa tumours in childhood: a prospective European multicentre study.

PURPOSE: Brain tumours constitute 25% of childhood neoplasms, and half of them are in the posterior fossa. Surgery is a fundamental component of therapy, because gross total resection is associated with a higher progression-free survival. Patients with residual tumour, progression of residual tumour or disease recurrence commonly require secondary surgery. We prospectively investigated the risk of postoperative speech impairment (POSI) and cranial nerve dysfunction (CND) following primary and secondary resection for posterior cranial fossa tumours. METHODS: In the Nordic-European study of the cerebellar mutism syndrome, we prospectively included children undergoing posterior fossa tumour resection or open biopsy in one of the 26 participating European centres. Neurological status was assessed preoperatively, and surgical details were noted post-operatively. Patients were followed up 2 weeks, 2 months and 1 year postoperatively. Here, we analyse the risk of postoperative speech impairment (POSI), defined as either mutism or reduced speech, and cranial nerve dysfunction (CND) following secondary, as compared to primary, surgery. RESULTS: We analysed 426 children undergoing primary and 78 undergoing secondary surgery between 2014 and 2020. The incidence of POSI was significantly lower after secondary (12%) compared with primary (28%, p = 0.0084) surgery. In a multivariate analysis adjusting for tumour histology, the odds ratio for developing POSI after secondary surgery was 0.23, compared with primary surgery (95% confidence interval: 0.08-0.65, p = 0.006). The frequency of postoperative CND did not differ significantly after primary vs. secondary surgery (p = 0.21). CONCLUSION: Children have a lower risk of POSI after secondary than after primary surgery for posterior fossa tumours but remain at significant risk of both POSI and CND. The present findings should be taken in account when weighing risks and benefits of secondary surgery for posterior fossa tumours.

Surgery for recurrent medulloblastoma: A review.

INTRODUCTION: Medulloblastoma (MB) is the most common malignant brain tumour in children. Despite significant progress in its management, a proportion of children relapse; tumour recurrence still carries a poor prognosis. While surgery is a mainstay of the management of primary MB, its role in recurrent MB is unclear. The objective of this literature review is to explore current practice and potential benefits of surgery in recurrent MB. MATERIAL AND METHODS: We reviewed all articles published in PubMed and Scholar from 1990 to 2018 with the following terms: "medulloblastoma" AND "recurrence" AND "neurosurgical procedures". Among 69 articles, 12 were directly relevant. RESULTS: A total of 581 cases of recurrent MB were identified from published series. Median time from diagnosis to relapse was 20.4months. The majority of relapses involved disseminated craniospinal disease and only one-fifth relapses was located in the posterior fossa. The outcome was consistently poor, with a median survival of 12.4% and a median survival time after relapse of 18.5months. In the HIP-SIOP-PNET4 study, surgery at relapse was performed in 25% of cases and was associated with improved prognosis in solitary posterior fossa recurrence. CONCLUSION: Recurrent medulloblastoma is often fatal in children who have previously received radiotherapy. The role of surgery in improving survival is unclear, but there is some evidence that resection of a focal single posterior fossa recurrence can bring survival benefit. The value of biopsy lies in the optimisation and selection of appropriate targeted therapy and in excluding a second malignancy.

A pilot study of glioblastoma multiforme in elderly patients: treatments, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and survival.

OBJECTIVES: Elderly Glioblastoma multiforme (GBM) patients have a worse prognosis and receive variable treatments. MGMT gene promoter methylation is linked with improved survival in GBM. We examined treatments administered and survival including in relation to MGMT methylation status in elderly GBM patients. PATIENTS AND METHODS: Patients ≥65 years with diagnosed GBM between 1/01/2007 and 30/04/2009 and undergoing either a biopsy, subtotal (STR) or gross total resection (GTR) were included. The collected information included MGMT status [methylated (ME) vs. unmethylated (UN)] and survival data. p<0.05 was considered significant. RESULTS: 59 patients were identified with median age at diagnosis being 72.68 years (65.72-85.04). Treatment included surgery (25 GTR, 8 STR, 26 biopsy), chemoradiation (22) and radiotherapy alone (20). Overall median overall survival (MOS) was 219 days. MOS with chemoradiation was 316 days vs. 143 days without it (p=0.011). 47 patients had definite MGMT status (28 ME, 19 UN). In ME patients, 9/28 received temozolamide compared to 10/19 in UN category. Temozolamide administration in patients with definite MGMT status was based on WHO performance status (p=0.007). MOS in UN group was 308 days vs. 167 days in ME group (p=0.068). In a multivariate Cox model including use of temozolamide, WHO score and methylation status, only temozolamide use was significantly associated with a reduced risk for death (HR 0.443, 95% CI 0.200-0.982, p=0.045). CONCLUSIONS: In this small cohort of patients, chemoradiation in suitable elderly GBM patients seemed to afford a survival benefit. MGMT methylation was not associated with an improved survival with temozolamide being the only factor leading to a better survival. Temozolamide use should be considered irrespective of MGMT status in this population with future large prospective studies needed to elucidate this further.

Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood.

AIMS: post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Its management is important in determining outcome. Although rodent hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not been studied in a small animal model surviving to adulthood. Our objective is to evaluate survival, to adulthood, in our immature (7-day-old, P7) neonatal rat model, and to analyse early motor reflexes and fine motor and cognitive function, and neuropathology, at 8-12 weeks. METHODS: sixty-six rats underwent sequential bilateral stereotactic intraventricular haemorrhage (IVH); 36 more acted as controls. Staircase and radial maze evaluations were carried out at 7-11 weeks; animals were sacrificed at 12 weeks. Post mortem ventricular size and corpus callosum thickness were determined. RESULTS: seventy-six per cent of IVH animals developed PHVD; median (interquartile range) composite ventricular area was 3.46 mm(2) (2.32-5.24). Sixteen (24%) animals demonstrated severe ventricular dilatation (area > 5 mm(2) ). IVH animals failed to improve on the negative geotaxis test at 2 weeks. The staircase test did not identify any significant difference. On the radial maze, animals with severe PHVD made more reference errors. Histopathology confirmed PHVD, ependymal disruption and periventricular white matter injury. Median anterior corpus callosum thickness was significantly lower in IVH animals (0.35 mm) than in those not undergoing IVH (0.43 mm). CONCLUSION: our P7 neonatal rat IVH model is suitable for long-term survival and replicates many of the morphological and some of the behavioural features seen in human PHVD.

Association of intracranial hypertension without ventriculomegaly and Chiari malformation: a dangerous combination.

With the increased use of MRI, tonsillar ectopia, the hallmark of the adult Chiari malformation (ACM) is being more frequently recognized. However, in some cases, the patient's symptoms do not fit with the classical presentation for ACM, but are similar to intracranial hypertension (IH). The latter may be difficult to diagnose in absence of ventricular enlargement. We report a case of ACM and IHWV due to carcinomatous meningitis.

Telemetric implantable pressure sensor for short- and long-term monitoring of intracranial pressure.

Patients with hydrocephalus, idiopathic intracranial hypertension and head injury frequently require monitoring of intracranial pressure (ICP) and may need repeated episodes of monitoring months or years apart. The gold standard for measurement of ICP remains the external ventricular catheter. This is a fluid-filled catheter transducer system that allows regular recalibration and correction of zero drift by its position relative to a fixed anatomical reference. It also allows drainage of cerebrospinal fluid (CSF), providing a means of lowering the ICP. Several catheter tip transducer systems are currently in clinical use, including using strain gauges or fiber-optical pressure sensing techniques. In these devices, zero drift and calibration cannot be checked in vivo. All the ICP monitoring devices in current clinical use require a physical connection between the brain and the external environment. This is a source of infection and limits the duration of monitoring. A number of telemetric monitoring devices, in which data is in some way transmitted transcutaneously, have been developed over the last twenty years, but significant technical problems have precluded their use in routine clinical practice. All current ICP monitors are temporary percutaneous implanted devices. Placement of these devices carries significant morbidity, particularly infection. Patients undergoing repeated monitoring require multiple surgical procedures. Apart from decreasing the risk of infection in patients with severe head injury, the clinical value of an accurate telemetric ICP monitoring system which maintains its reliability over a long period of implantation is high.

Granular cell tumour of the neurohypophysis: a rare sellar tumour with specific radiological and operative features.

Symptomatic granular cell tumours of the neurohypophysis are rare sellar lesions. Preoperative prediction of the diagnosis on the basis of radiological appearance is useful as these tumours carry specific surgical difficulties. This is possible when the tumour arises from the pituitary stalk, rostral to a normal pituitary gland. This has not been emphasized previously.

Subdural haemorrhage following endoscopic third ventriculostomy. A rare complication.

Subdural collections or hematomas are frequently observed after shunt placement [7-9, 13], but rarely after ETV [6]. A review of literature revealed 7 cases [1, 5, 6, 10, 12], of which only 1 was symptomatic [5]. We will discuss the causes, management, and methods of prevention of this complication and we will present a case of symptomatic subdural haematoma, following endoscopic third ventriculostomy for illustration.

Garré's chronic diffuse sclerosing osteomyelitis of the sacrum: a rare condition mimicking malignancy.

Garré's chronic diffuse sclerosing osteomyelitis (DSOM) is a rare disease that occurs most commonly in the mandible. We present a case of sacral DSOM that simulated an expanding destructive sacral tumour. Treatment was conducted on the basis of the available experience with the mandibular form of the disease, with partial symptomatic relief, but progressive sclerosis of the sacral lesion. To the best of our knowledge, this is the first case initially presenting in the sacrum. As an osteolytic expanding lesion simulating malignancy, it is important to recognize this entity in the sacrum.

Pseudoaneurysm of the occipital artery: an unusual cause of persisting headache after minor head injury.

Post-traumatic pseudoaneurysms of the extracranial arteries in the scalp are uncommon sequelae of head injury. We report on a patient who presented four weeks after a minor head injury with a tender, pulsating and enlarging mass in the course of the left occipital artery. There was associated headache radiating to the vertex. Computed tomographic angiography confirmed the lesion to be a pseudoaneurysm of the occipital artery. The lump was resected with complete resolution of symptoms.

Superficial siderosis of the central nervous system following cervical nerve root avulsion: the importance of early diagnosis and surgery.

Superficial siderosis (SS) of the central nervous system is an insidious, progressive, irreversible and debilitating neurological disorder caused by recurrent haemorrhage within the subarachnoid space. The subsequent deposition of haemorrhagic breakdown products in the spinal cord and nervous tissues leads to the loss of neurones and myelin, and to the development of a neurological deficit. In a small number of patients, the source of haemorrhage is related to traumatic cervical nerve root avulsion occurring several years prior to the onset of symptoms. Surgical ablation of the source has been shown to halt the progression of the disease, at least in the short term. We review the literature on SS secondary to cervical nerve root avulsion and report a further case in which surgical management was successful in halting disease progression. We emphasize that early detection and recognition of the initial non-progressive symptoms related to this poorly known disease, coupled with timely surgical management, minimizes the degree of neurological disability.

Intramedullary capillary haemangioma.

Intramedullary capillary haemangioma is extremely rare and only four cases have been previously reported. We describe a further case, outlining the clinical, radiological, surgical and pathological features.

Idiopathic spinal cord hernia.

Idiopathic spinal cord hernia (ISCH) is a rare cause of slowly progressive spinal cord dysfunction. It is readily diagnosed on magnetic resonance imaging of the spine. The neurological deficit related to ISCH is often reversible once surgical exploration and reduction of the hernia is achieved. We present the case of a 37 year-old lady with a ventral ISCH at the T4 level. There was a significant post-operative improvement in her myelopathy post-operatively. ISCH should be considered in the differential diagnosis of progressive spinal cord neurological deficit.

Diffuse primary non-Hodgkin's lymphoma of the cranial vault.

Primary non-Hodgkin's lymphoma of the skull vault is a rare disease. We describe a case occurring in a 72-year-old woman presenting with generalized tonic clonic seizures on a background of a 1-year history of headaches and progressively enlarging scalp masses. Imaging showed diffuse infiltration of the skull vault with multifocal intra- and extracranial soft tissue masses, causing compression and probably infiltration of the cerebral cortex. Further investigation failed to identify any other evidence of systemic lymphoma. Biopsy of one of the scalp masses showed a small to intermediate cell B cell lymphoma. The other nine reported cases of primary skull vault lymphoma are reviewed. The diffuse vault infiltration as well as the multiple intracranial, scalp and temporalis muscle masses renders this case unique.

How accurate is magnetic resonance angiography in predicting neurovascular compression in patients with trigeminal neuralgia? A prospective, single-blinded comparative study.

Ninety-two patients with trigeminal neuralgia (TGN) were investigated prior to posterior fossa surgery with magnetic resonance imaging (MRI) and contrast-enhanced magnetic resonance angiography (MRA). The preoperative investigation was matched to one consultant neuroradiologist (co-author) who was blinded to the side of symptomotology. The imaging results were compared with the operative findings in all patients. In 76 patients MRA showed present neurovascular compression in accordance with surgical findings. Eight cases had no compression either on MRA or intraoperatively. Eight predictions of no compression were false and there was no false positive. Based on surgical findings, the sensitivity of MRA was 90.5% and the specificity 100%. In 19 cases MRA predicted bilateral compression of the trigeminal nerves. Only two cases had clinically bilateral TGN. We conclude that MRA with gadolinium enhancement is an extremely sensitive and specific method for demonstrating compression in TGN. As a result posterior fossa surgery can be recommended with confidence, and microvascular decompression remains the treatment of choice for TGN at the authors' centre.

Endoscopic methods of hydrocephalus treatment.

This article discusses the use of the endoscope in treatment of hydrocephalus without shunting. The selection of candidates for third ventriculostomy and choroid plexus coagulation are described together with the overall published rates of success with each technique. A summary of the nature and frequency of complications of third ventriculostomy are given after reviewing published data on over a thousand patients who have had the operation to date. The role of other endoscopic techniques, such as septal fenestration and decompression of obstructing cysts, also are discussed.