Novel therapeutic approaches for pediatric diencephalic tumors: improving functional outcomes.

Pediatric diencephalic tumors represent a histopathologically and molecularly diverse group of neoplasms arising in the central part of the brain and involving eloquent structures, including the hypothalamic-pituitary axis (HPA), optic pathway, thalamus, and pineal gland. Presenting symptoms can include significant neurological, endocrine, or visual manifestations which may be exacerbated by injudicious intervention. Upfront multidisciplinary assessment and coordinated management is crucial from the outset to ensure best short- and long-term functional outcomes. In this review we discuss the clinical and pathological features of the neoplastic entities arising in this location, and their management. We emphasize a clear move towards 'function preserving' diagnostic and therapeutic approaches with novel toxicity-sparing strategies, including targeted therapies.

Paraganglioma of the cauda equina: a tertiary centre experience and scoping review of the current literature.

Cauda equina paragangliomas are rare benign extra-adrenal neuroendocrine tumours arising from the neural crest cells associated with autonomic ganglia. These tumours are often mistaken preoperatively for ependymomas or schwannomas. Patients present with axial or radicular pain with or without neurological deficits. Recurrence, secretory features and length of follow-up are controversial. We conducted a retrospective cohort study of paraganglioma through searching a prospectively maintained histopathology database. Patient demographics, presentation, surgery, complications, recurrence, follow-up and outcome between 2004 and 2016 were studied. The primary aim was to collate and describe the current evidence base for recurrence and secretory features of the tumour. The secondary objective was to report outcome and follow-up strategy. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Ten patients were diagnosed (M:F 7:3) with a mean age of 53.6 ± 5.1 (range 34-71 years). MRI scans revealed intradural lumbar enhancing lesions. All patients had complete microsurgical excisions without adjuvant therapy with no recurrence with a mean follow-up of 5.1 ± 1.4 years. Tumours were attached to the filum terminale. Electron microscopic images demonstrated abundant neurosecretory granules with no evidence of catecholamine production. A total of 620 articles were screened and 65 papers (including ours) combining 121 patients (mean age 48.8 and M:F 71:50) were included. The mean follow-up was 3.48 ± 0.46 (range 0.15-23 years). Back pain was the most common symptom (94%). Cure following surgery was achieved in 93% of the patients whilst 7% had recurrence. Total resection likely results in cure without the need for adjuvant therapy or prolonged follow-up. However, in certain situations, the length of follow-up should be determined by the treating surgeon.

High grade gliomas in young children: The South Thames Neuro-Oncology unit experience and recent advances in molecular biology and targeted therapies.

High grade gliomas (HGG) have a dismal prognosis with survival rates of 15-35%. Approximately 10-12% of pediatric HGG occur in young children and their molecular biology and clinical outcomes differ from those arising at older ages. We report on four children aged <5 years newly diagnosed with non-brainstem HGG between 2011 and 2018 who were treated with surgery and BBSFOP chemotherapy. Two died of tumor progression. The other two are still alive without radiotherapy at 3.8 and 3.9 years from diagnosis: one of whom remains disease-free off treatment; and the other one, whose tumor harbored a KCTD16:NTRK2 fusion, went on to receive larotrectinib. Additionally we review the general management, outcomes and latest updates in molecular biology and targeted therapies for young children with HGG. Infant gliomas can be stratified in molecular subgroups with clinically actionable oncogenic drivers. Chemotherapy-based strategies can avoid or delay the need for radiotherapy in young children with HGG. Harnessing the potential of NTRK, ALK, ROS1 and MET inhibitors offers the opportunity to optimize the therapeutic armamentarium to improve current outcomes for these children.

Scalp Cirsoid Aneurysms: Case Illustration and Systematic Review of Literature.

BACKGROUND: Scalp cirsoid aneurysms are rare subcutaneous arteriovenous fistulae affecting the scalp. They can be easily misdiagnosed and mistreated. OBJECTIVE: To review reported cases of scalp cirsoid aneurysms for their incidence, etiology, clinical presentation, treatment, and outcomes using an illustrative case. METHODS: We conducted a PUBMED, SCOPUS, OVID SP, SciELO, and INFORMA search using the keywords; "cirsoid," "aneurysm," "arteriovenous," "malformation," "scalp," "vascular," and "fistula." We identified 74 pertinent papers, reporting 242 cases in addition to our reported index case. RESULTS: Median age at presentation was 25 yr (range 1-72 yr); male to female ratio was 2.5:1. The most common symptoms were a pulsatile mass (94% of patients), headaches (25%), and tinnitus (20%). The median duration of symptoms was 3 yr (6 d to 31 yr), with 60.2% occurring spontaneously, 32.23% traumatic, and the rest iatrogenic. A total of 58.5% of cases were managed with surgical excision only, 21.6% with endovascular embolization only, and 14.5% with a combination of both methods. The complication rate observed in the endovascular embolization treatment cohort (55.8%) was significantly higher than that observed in the surgical excision only cohort (9.9%) (P < .00001) and in the combined therapy cohort (0%) (P < .00001). There is a low recurrence rate after treatment irrespective of modality: surgical excision only (6.3%), endovascular embolization only (8.3%), and combined therapy (0%). CONCLUSION: Scalp cirsoid aneurysms are associated with good prognoses when recognized and managed appropriately. We suggest combining surgery with endovascular embolization as the optimum treatment modality.

Cavum Septum Pellucidum Causing Obstructive Hydrocephalus in a Toddler.

Cavum septi pellucidi (CSP) are benign developmental cystic midline cavities that are located between the lateral ventricles through the foramina of Monro. CSP are usually asymptomatic and have no cerebrospinal fluid (CSF) flow. Although their incidence is increased in association with head trauma, as well as psychiatric and behavioural disorders, this increase seldom causes disease. Herein, we discuss the case of a toddler who presented with episodic headaches for 6 weeks with associated vomiting triggered by strenuous activity. His neurological examination was normal. His MRI brain scan revealed large cavum septum pellucidum with obstructive hydrocephalus. He underwent endoscopic fenestration of the cyst with resolution of both hydrocephalus and the symptoms. Although CSP are generally asymptomatic, in rare situations, as in our illustrative case, they may cause obstructive hydrocephalus that requires urgent attention. CSF flow studies are helpful in confirming the diagnosis.

Leukoencephalopathy, Intracranial Calcifications, Cysts, and SNORD118 Mutation (Labrune Syndrome) with Obstructive Hydrocephalus.

Labrune syndrome is a neurologic disorder that manifests as a progressive cerebral degeneration characterized by a radiologic triad of cerebral white matter disease (leukoencephalopathy), intracranial calcification, and cysts. The associated novel genetic mutation in SNORD118 has been recently identified. However, its significance in relation to the progression and severity of the disease is yet to be clarified. We present a 12-year-old boy with a 3-month history of headache that worsened 1 week before admission and was associated with nausea and vomiting, ataxia, and motor developmental delay. His head scans demonstrated widespread intracranial calcifications, cysts, leukoencephalopathy, and obstructive hydrocephalus. He had urgent endoscopic-assisted aspiration of the cerebellar cyst with insertion of a reservoir with resolution of the hydrocephalus and raised intracranial pressure symptoms. His genetic testing revealed a rare biallelic mutation with 2 variants in the gene SNORD118. The progressive form of this disease will be challenging for neurosurgeons.

Disco vertebral osteomyelitis causing intradural spinal abscess with cauda equina compression.

Intradural extramedullary spinal infections causing cauda equina compression are uncommon. We report an Escherichia coli bacteraemia causing lumbar discitis and an intracanalicular collection compressing the cauda equina: initially thought to be an epidural empyema, however microsurgery revealed an intradural location. Decompression, drainage, antibiotics, and neuropathy treatment are essential management.

Currarino syndrome: repair of the dysraphic anomalies and resection of the presacral mass in a combined neurosurgical and general surgical approach.

OBJECTIVEIt is well established that Currarino syndrome (CS) may be associated with spinal dysraphism. Here, the authors report on 10 CS patients with dysraphic anomalies who had undergone a combined neurosurgical and general surgical approach to repair the dysraphic anomalies and resect the presacral mass in a single operation. They discuss the spectrum of spinal dysraphism that may coexist in CS in the context of its developmental etiology.METHODSChildren with a confirmed CS diagnosis who had undergone the combined operative approach were identified from a departmental database. Presenting features were recorded and preoperative imaging was analyzed to record features of the presacral mass and the dysraphic anomalies. The histopathological nature of the resected presacral mass and the outcomes postoperatively and at the last follow-up were reviewed.RESULTSBetween 2008 and 2015, 10 patients presented with CS, 9 with constipation. Median age at the time of surgery was 1.3 years. Six of the 10 patients had anorectal malformation consisting of anal stenosis, rectal stenosis, or imperforate anus. Spinal anomalies included anterior meningocele (5 cases), low-lying conus (8), terminal syrinx (4), fatty filum (5), caudal lipoma (3), and intraspinal cyst (1). In all cases, the lumbosacral spinal canal was accessed via a midline approach with laminoplasty, allowing spinal cord untethering and repair of the dysraphic anomalies. Following dural closure, the incision was extended inferiorly to incorporate a posterior sagittal approach to resect the presacral mass. The histopathological nature of the mass was mature teratoma (8 cases), complex hamartomatous malformation (1), or neurenteric cyst (1). There were no new instances of neurological deterioration, with most instances of persisting morbidity related to constipation (6 cases) or neurogenic bladder dysfunction (8). There were no infective complications, no instances of cerebrospinal fluid fistula, no recurrences of the presacral mass, and no cases of retethering of the spinal cord.CONCLUSIONSAlthough not part of the original triad, spinal dysraphic anomalies are common in CS and in keeping with a disorder of secondary neurulation. Lumbosacral MRI is an essential investigation when CS is suspected. Children are at risk of sphincter impairment due to the anorectal malformation; however, both spinal cord tethering and compression from the presacral mass may further compromise long-term continence. A combined operative approach to repair the dysraphic anomalies and resect the presacral mass is described with good postoperative and long-term outcomes.

Post-operative paediatric cerebellar mutism syndrome: time to move beyond structural MRI.

PURPOSE: To determine the value of structural magnetic resonance imaging (MRI) in predicting post-operative paediatric cerebellar mutism syndrome (pCMS) in children undergoing surgical treatment for medulloblastoma. METHODS: Retrospective cohort study design. Electronic/paper case note review of all children with medulloblastoma presenting to Great Ormond Street Hospital between 2003 and 2013. The diagnosis of pCMS was established through a scoring system incorporating mutism, ataxia, behavioural disturbance and cranial nerve deficits. MRI scans performed at three time points were assessed by neuroradiologists blinded to the diagnosis of pCMS. RESULTS: Of 56 children included, 12 (21.4%) developed pCMS as judged by a core symptom of mutism. pCMS was more common in those aged 5 or younger. There was no statistically significant difference in pre-operative distortion or signal change of the dentate or red nuclei or superior cerebellar peduncles (SCPs) between those who did and did not develop pCMS. In both early (median 5 days) and late (median 31 months) post-operative scans, T2-weighted signal change in SCPs was more common in the pCMS group (p = 0.040 and 0.046 respectively). Late scans also showed statistically significant signal change in the dentate nuclei (p = 0.024). CONCLUSIONS: The development of pCMS could not be linked to any observable changes on pre-operative structural MRI scans. Post-operative T2-weighted signal change in the SCPs and dentate nuclei underlines the role of cerebellar efferent injury in pCMS. Further research using advanced quantitative MRI sequences is warranted given the inability of conventional pre-surgical MRI to predict pCMS.

Intracranial Hypotension Following Traumatic Brain Injury: A Diagnostic and Therapeutic Challenge.

BACKGROUND: Intracranial hypotension (IH) is a recognized cause of coma; however, the diagnosis is often challenging, especially in patients with superimposed traumatic brain injury. CASE DESCRIPTION: A 67-year-old woman became comatose following evacuation of bilateral acute subdural hematomas with concurrent respiratory failure. Imaging and intraparenchymal intracranial pressure monitoring confirmed secondary IH. She was managed with an epidural blood patch and a 72-hour period in the Trendelenburg position guided by intracranial pressure monitoring and clinical assessment. She subsequently made an excellent neurologic recovery from an initial Glasgow Coma Scale score of 3 to a score of 15. CONCLUSIONS: Secondary IH can easily be missed in patients who have sustained a primary brain injury. In patients with a poor neurologic recovery, clinicians should rule out secondary IH as a potential cause, as immediate treatment can lead to profound clinical improvement.

Oesophageal pleural fistula presenting with Parvimonas micra infection causing cervical and brain abscesses.

Parvimonas micra (P. micra) infections causing spinal cord compression are extremely rare. We report an occult oesophageal pleural fistula presenting with spinal epidural and brain abscesses resulting in severe neurological deficits caused by P. micra. Molecular detection proved to be instrumental in identifying the causative pathogen. Essential management with decompression, drainage, antibiotics and fistula repair lead to a good outcome.

Unusual Intraparenchymal Pontomedullary Epidermoid Cyst in a 2-Year-Old Child: A Case Report and Review of the Literature.

BACKGROUND: Intrinsic brainstem epidermoid cysts are rare, benign, slow-growing lesions. Their eloquence precludes complete excision; however, subtotal resection often will result in prolonged or sometimes permanent relief of presenting symptoms and signs. We describe an unusual case and review the literature of this pathology in the pediatric population. CASE DESCRIPTION: We report an intra-axial pontine epidermoid cyst in a 2-year-old girl who presented with developmental delay, multiple cranial nerve palsies, and pneumonia. Magnetic resonance imaging demonstrated an intrinsic pontine lesion with partial restricted diffusion and an enhancing plaque, the latter not typically seen in congenital lesions like epidermoid. However, gross surgical inspection and histopathology confirmed an epidermoid. CONCLUSIONS: Our case, supported by the literature, shows that brain stem epidermoid cysts may have atypical radiologic characteristics and that near-total resection remains safe and can improve outcome.

Posterior fossa syndrome-a narrative review.

Posterior fossa syndrome (PFS), or cerebellar mutism syndrome (CMS), is a collection of neurological symptoms that occur following surgical resection of a posterior fossa tumour, and is characterised by either a reduction or an absence of speech. Some authors suggest that CM is only one symptom of the CMS complex that also includes ataxia, hypotonia and irritability as well as cranial nerve deficits, neurobehavioral changes and urinary retention or incontinence. It is seen almost exclusively in children. In 1985 Rekate et al. published the first work describing CM as a clinical entity, occurring as a consequence of bilateral cerebellar injury. Other associated symptoms include visual impairment, altered mood, impaired swallowing and significant gross and fine motor deficits. The effects of this can have a devastating impact on both the patient and their carers, posing a significant clinical challenge to neurorehabilitation services. The reported incidence was between 8% and 31% of children undergoing surgery for posterior fossa tumour. The underlying pathologies include vasospasm, oedema, and axonal/neuronal injury. Neuroimaging has contributed to a better understanding of the anatomical location of postoperative injury. There have been a number of suggestions for treatment interventions for PFS. However, apart from some individual reports, there have been no clinical trials indicating possible benefit. Occupational therapy, speech and language therapy, as well as neurocognitive support, contribute to the recovery of these patients.

A review of spontaneous intracranial extradural hematoma in sickle-cell disease.

Sickle-cell disease is common among patients of Afro-Caribbean origin. Though it can precipitate neurological conditions, it only rarely causes neurosurgical problems, with very few reported cases. We describe the case of a 7-year-old girl with a background of sickle-cell disease (SCD) brought into an acute neurosurgical unit in extremis, signs of a raised ICP, and with no history of recent trauma. Following further investigations, an acute drop in the hemoglobin and hematocrit levels were noted, with the cause of her presentation being attributed to a sickling crisis causing skull convexity infarction and resulting in spontaneous bilateral extradural hematomas requiring emergency evacuation. We review the current literature and propose the pathophysiological mechanism behind this phenomenon.

Malignant transformation in craniopharyngiomas.

BACKGROUND: Craniopharyngiomas are successfully managed with surgery and/or adjuvant chemoradiotherapy but have been documented to undergo malignant transformation (MT), albeit very rarely, with only 23 reported cases. The exact cause and pathogenesis of this MT are unknown, although the literature has suggested a possible correlation with radiotherapy. OBJECTIVE: To review the reported cases of malignancy, in particular looking at the incidence, tumor characteristics, previous treatment modalities, and median survival. METHODS: We conducted a PUBMED, SCOPUS, OVID SP, and INFORMA search with a combination of key words: craniopharyngioma, malignancy, transformation, neoplasm, radiation therapy, and anaplastic. We identified 23 cases relevant to our study. RESULTS: Median age at the time of diagnosis of malignant craniopharyngiomas was 31 years (range, 10-66 years); 52.6% of the patients were female. Histologically, the most common tumor types were squamous cell carcinoma (80.96%), with adamantinomatous cell type being the most common morphology (89.47%). We found that 21.7% of the cases were diagnosed as malignant craniopharyngioma at first biopsy. Of the rest, the median time from initial benign diagnosis to MT was 8.5 years (range, 3-55 years). Median overall survival after MT was 6 months (range, 2 weeks-5 years). Using the Spearman rank correlation, we found no correlation between the use of radiation therapy (correlation coefficient, -0.25; P < .05) or its dosage (correlation coefficient, -0.26; P < .05) and MT. CONCLUSION: Malignant craniopharyngiomas are rare and are associated with a poor prognosis. MTs occur years after the initial benign craniopharyngioma diagnosis and are associated with multiple benign craniopharyngioma recurrence. Results also show that, contrary to widespread belief, there is a poor correlation between radiotherapy and MT.

Complications of titanium cranioplasty--a retrospective analysis of 174 patients.

BACKGROUND: Titanium cranioplasty (TC) has been associated with high complication rates, but abundant data are lacking. We aimed to determine the incidence and type of complications following TC and risk factors for complications. METHODS: A retrospective review was performed on 174 patients who underwent TC at two London units over a seven year period. Data were collected on demographics, primary pathology, perioperative details, complications and functional outcome. Skull defect size was estimated using 3-dimensional computed tomographic reconstructions. RESULTS: The overall complication rate was 26.4 % (46/174), and plate removal rate10.3 % (18/174). The commonest complication was infection, which accounted for 69 % of plate removals. Patients who had undergone craniectomy for trauma had a higher complication rate (35 vs 21 %; p = 0.043) and plate removal rate (16 vs 7 %; p = 0.049) than others. There was a non-significant trend towards the association of craniectomy-to-cranioplasty interval of 4-8 months with the lowest complication rate and shortest postoperative hospital stay. Patients with a skull defect larger than 100 cm(2) had the highest complication rate (p < 0.001), highest plate removal rate (p = 0.039), and longest postoperative hospital stay (p = 0.019). Bifrontal versus unilateral cranioplasty was associated with a significantly higher complication rate (40 vs 14 %) and length of hospital stay (5.0 vs 2.9 days). There was no perioperative mortality and no change between pre-operative and post-operative functional outcome. CONCLUSION: In the largest UK study on cranioplasty to date, we have demonstrated that size of defect, traumatic aetiology and bifrontal insertion are risk factors for complications. Our results suggest that the timing of cranioplasty may be important with late (> 12 months) TC associated with a higher rate of complications, although further prospective studies on the optimal timing of TC are required to establish the observed trend. Our data can help clinicians stratify risk to inform the consent process and aid pre-operative planning.