Benedetta Pettorini

Endoscopic third ventriculostomy for the treatment of osteopetrosis-related hydrocephalus: a case-based update

BackgroundOsteopetrosis is a heterogenous group of disorders characterised by a failure of normal bone maturation and abnormal bone sclerosis secondary to the failure of osteoclasts to resorb bone. The most serious consequences of this disorder affect the nervous system. Patients with infantile osteopetrosis (also called malignant osteopetrosis) can develop a gradual occlusion of, or narrowing of the skull foramina at the skull base, resulting in the compression of vital nerves and vessels. Hydrocephalus has been identified in these patients, particularly those with the autosomal recessive variety of osteopetrosis. Although the exact aetiology is uncertain, it is possible that venous outflow obstruction at the cranial foramina along with a reduced intracranial space for cerebrospinal fluid (CSF) to flow around the hemispheres could be contributing factors. There are few reports in the literature on the management of this unusual association, hydrocephalus secondary to osteopetrosis. The authors report one such case where this association has been successfully surgically treated with endoscopic third ventriculostomy as a form of CSF diversion.Case reportWe successfully treated a 9-month-old girl with osteopetrosis and symptomatic hydrocephalus with an endoscopic third ventriculostomy (ETV). She later went on to have stem cell transplantation to treat the osteopetrosis.ConclusionsMost reports in the literature have identified ventriculoperitoneal (or other distal site) shunting as the treatment of choice for hydrocephalus in this setting. We would like to highlight that ETV is another effective and often very suitable method of CSF diversion in these patients.

Spontaneous spinal epidural haematoma mimicking meningitis in a 2-year-old child—a case report and literature review

IntroductionWe report the case of a 2-year-old boy with suspected meningitis who presented with acute onset neck pain and stiffness associated with right-sided weakness and ataxia.ManagementDespite intravenous antibiotics and antiviral treatment, his condition deteriorated. Magnetic resonance imaging demonstrated spontaneous cervical epidural haematoma (C4–C7) extending down to thoracic (T7) level with associated compression of the spinal cord. He was treated successfully by neurosurgical decompression and made a complete recovery.DiscussionSpinal epidural haematoma is a neurosurgical emergency characterised by extravasation of blood in the spinal epidural space. The clinical presentation particularly in young children can masquerade other conditions such as meningitis. In this article, we discuss our case and review the literature on spontaneous spinal epidural hematoma with an aim to improve awareness of this condition which if not recognised and treated early can lead to significant lifelong morbidity.

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities by revealing the activation of the MAPK/ERK and inflammasome pathways in human ACP.

Neonatal post-haemorrhagic hydrocephalus in the UK: a survey of current practice

Abstract Objectives: The management of neonatal post-haemorrhagic hydrocephalus (nPHH) varies considerably between centres and even between neurosurgeons in the same centre. We performed a nationwide survey to evaluate current practice in the UK and reviewed the evidence for each intervention. Methods: An online semi-structured questionnaire was emailed to all units registered on the British Paediatric Neurosurgery Group Mailing List. The survey consisted of 18 questions designed to establish the status quo in the management of nPHH, including preferred temporising procedure, factors guiding the timing of intervention and willingness to participate in a prospective study. Results: A total of 24 consultants responded to the survey. Ventricular access device (VAD), trans-fontanelle tap, ventriculosubgaleal shunt (VSGS) and lumbar puncture (LP) were used by 33, 25, 17 and 17%, respectively, as the first temporising measure. Almost all reported that the timing of this intervention was guided by increasing head circumference and tense fontanelle. If the first temporising procedure fails, VAD, external ventricular drainage (EVD), trans-fontanelle tap, VSGS and other procedures (including ventriculoperitoneal (VP) shunting and endoscopic third ventriculostomy (ETV)) were performed by 42, 17, 13, 8 and 21%, respectively. Almost all respondents reported that VP shunting would be their preferred method of definitive cerebrospinal fluid (CSF) diversion. Almost all responded that they would be willing to participate in a prospective study in the future to determine best practice. Conclusion: As expected there was a significant heterogeneity between respondents in the initial management of nPHH in the UK. VAD was the most popular first and second choice temporising measure. On reviewing the literature, it is clear that more work still needs to be done to establish which temporising measure is best. There is willingness in the UK to participate in a study to help determine this.

Neurofibroma of the cervical spine in infants

Dear Editor-In-Chief, We would like to draw your attention to this case of a 3month old girl with an intra-extradural neurofibroma. This patient came to the attention of our paediatric neurosurgical team presenting with macrocrania and failure to thrive. An MRI of the head and spine revealed an intra-extradural tumour compressing the cervical spine at levels C3–C4, with soft tissue involvement at the base of the skull and extending into the soft tissue of the neck through the right C2–C3 root foramina (Fig. 1). We came to the decision that the cord required decompression and a specimen obtained to achieve a diagnosis. We performed a laminoplas ty f rom C1–C4 and debulking of the tumour. After a midline dural opening, the tumour was obvious and easily visualised with a yellow-grey appearance distorting the cord to the left. At least one nerve root was involved intradurally and macroscopically had the appearance of a nerve sheath tumour. The involved upper cervical nerve root was cut proximally, allowing further mobilisation of the intradural component. The extradural component of the tumour was followed out through the cervical root canal and radical excision was achieved. The small portion of the tumour extending into the neck became difficult to visualise, and hence, it was decided to stop the procedure at that stage with a near-total excision achieved. Smear results were indicative of a nerve sheath tumour. We left the soft tissue abnormalities around the skull base undisturbed, and immediately after surgery, we placed the patient in a Papoose brace due to the extent of her laminoplasty. The definitive histopathology came back as neurofibroma and genetic NF1 testing was suggestive of NF1 (Figs. 2 and 3). The patient had a post-op MRI 6 weeks after surgery which showed a kyphotic deformity for which she is now in a laser cut brace and receiving regular follow up (Fig. 4). From an oncological perspective, no adjuvant therapies were used and it was decided that regular radiological monitoring was the most appropriate way to proceed. In a paediatric setting, such an invasive and large neoplasm in a patient with NF1 carries several post-operative complications of which we should be mindful. Bone deformity is the most prominent as was the case with our patient as she had developed a kyphosis at her 6-week post-operative MRI. This

Neonatal Brain Tumours

Neonatal brain tumours (NBT) are a rare but important group of neoplasms within the field of paediatric neuro-oncology as they present particular technical and physiological challenges to the neuro-surgical team. Contemporary management requires the application of appropriate multimodal individualised therapeutic approaches.

Neurofibroma of the cervical spine in infants: a case-based update.

Reply to comment: We read the comments of Mr. Lavrador with great interest. He shares his experience of managing an infant with high cervical neurofibroma. The significant difference between the two cases is the size of the intradural component of the tumour. In our patient, the intradural tumour was the predominant component causing significant cord compression and we had significant concerns with regard to her respiration and lower cranial nerve function. Pre-operatively, our patient was showing initial signs of respiratory distress and swallowing function disorders. We felt in view of the severe cord compression that radical decompression of the intradural component of the tumour was warranted. The extraspinal component of the tumour was left behind and will be monitored long term. In addition, there were no red flags for a diagnosis of NF1 pre-operatively and we felt a histopathological diagnosis via open surgery biopsy was mandatory. We did perform a laminoplasty to avoid long-term neck deformity which unfortunately did set in but luckily at the moment is under control. Our case represents a rather unusual first presentation of NF1 with significant spinal cord compression and hence the report.