Demographics, presentation, and clinical outcomes after traumatic bifrontal contusions: a systematic review.

Traumatic bifrontal contusions (TBC) form a recognised clinical entity among patients with traumatic brain injury (TBI). This study aims to systematically review current literature on demographics, management, and predictors of outcomes of patients with TBC. A multi-database literature search (PubMed, Cochrane, OVID Medline/Embase) was performed using PRISMA as a search strategy. Studies were selected by predefined selection criteria (PROSPERO: CRD42018055390), and risk of bias was assessed using an adapted form of ROBINS-I tool. Of the 275 studies yielded by the literature search, seven articles met the criteria for inclusion, all of which were level III evidence. Total cohort consisted of 468 patients; predominantly male (n = 5; 303/417 patients) with average age 44.3 years (range, 7-81). Falls (44.9%) and road traffic accidents (46.6%) were the commonest mechanisms of injury with an average presentation GCS of 9.2 (n = 3, 119 patients). GCS on admission of ≤ 13.1 and contusion volume at day 2 post-injury of ≥ 62.9cm3 were associated with increased risk of deterioration needing surgical interventions (n = 1, 7 patients). The majority of patients underwent surgery; the average GOS was 4, at an average follow-up duration of 11.7 months (n = 6, 356 patients). The currently available evidence on the management of TBC is scarce. Larger multicentre well-designed studies are needed to further delineate the factors behind acute deterioration, the effectiveness of management options. Once in place, this can be used to develop and test an algorithmic approach to management of TBC resulting in consistently improved outcomes.

Integrated fundal assessment pathway for patients with suspected shunt malfunction via digital retinal images.

Introduction: Papilloedema is an important clinical sign in the assessment of neurosurgical patients presenting with suspected shunt malfunction.Methods: We describe our 18-month experience using a newly acquired nonmydriatic digital retinal camera to acquire fundal photographs for this purpose.Results: It was used to take digital photographs in 67 patients presenting with suspected shunt malfunction and 54% of these images were discussed with the on-call ophthalmology team for advice. Of these 81% had instant input provided by ophthalmology and the remainder were sent to the ophthalmology department for formal assessment. Of all shunt related regional referrals in the same time period, we found that only 13% of the referred patients were discussed with the on-call ophthalmology team. The rest had decisions made by the on-call neurosurgical team.Conclusions: We believe this new integrated pathway is clinically and cost-effective and recommend it as a useful tool in other neurosurgical units.

Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study.

INTRODUCTION: The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours. METHODS: A retrospective analysis was undertaken at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow transplant and metastases were excluded. Pre-operative full blood counts (FBC), collected before the diagnosis of intracranial pathology and before administration of steroids, were matched with histological diagnosis for each patient. Post-operative FBC was also recorded, together with survival data where applicable. RESULTS: A total of 116 patients (74 male, 42 female; mean age, 8 ± 0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC that could be matched to final histological grade. Pre-operative NC and NLCR were higher with increasing grade of tumour: grade 1 (NC 4.29 109/l, NLCR 2.26), grade 2 (NC 4.59 109/l, NLCR 2.38), grade 3 (NC 5.67 109/l, NLCR 2.72) and grade 4 (NC 6.59 109/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together had a lower NC (4.37 95% CI ± 0.67 109/l) compared to WHO grade 3 and 4 patients (6.41 95% CI ± 0.99 109/l, p = 0.0013). The NLCR was lower in grade 1 and 2 tumours (2.29 ± 0.59) (compared to grade 3 and 4 tumours; 3.20 ± 0.76) but this did not reach significance (p = 0.069). The subgroup of patients with pilocytic astrocytoma had a significantly lower NC when compared to patients with high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups had significantly higher NC compared to the low-grade group (p = 0.033, p = 0.002). Post-operative NC was significantly higher in the high-grade tumours (p = 0.034), but no difference was observed for NLCR (p = 0.28). CONCLUSIONS: No evidence exists to support the correlation of pre-operative NC or NLCR to histological diagnosis in paediatric intracranial tumours. Our results indicate that a higher pre-operative NC/NLCR correlates with a higher histological grade of tumour. This suggests that immunological mechanisms may be involved in the pathogenesis of paediatric brain tumours, and a further prospective study is required to substantiate and expand these findings.

Methylation-specific multiplex ligation-dependent probe amplification identifies promoter methylation events associated with survival in glioblastoma.

DNA methylation plays an important role in cancer biology and methylation events are important prognostic and predictive markers in many tumor types. We have used methylation-specific multiplex ligation-dependent probe amplification to survey the methylation status of MGMT and 25 tumor suppressor genes in 73 glioblastoma cases. The data obtained was correlated with overall survival and response to treatment. The study revealed that methylation of promoter regions in TP73 (seven patients), THBS1 (eight patients) and PYCARD (nine patients) was associated with improved outcome, whereas GATA5 (21 patients) and WT1 (24 patients) promoter methylation were associated with poor outcome. In patients treated with temozolomide and radiation MGMT and PYCARD promoter methylation events remained associated with improved survival whereas GATA5 was associated with a poor outcome. The identification of GATA5 promoter methylation in glioblastoma has not previously been reported. Furthermore, a cumulative methylation score separated patients into survival groups better than any single methylation event. In conclusion, we have identified specific methylation events associated with patient outcome and treatment response in glioblastoma, and these may be of functional and predictive/prognostic significance. This study therefore provides novel candidates and approaches for future prospective validation.

Occurrence and distribution of pilomyxoid astrocytoma.

PURPOSE: To know the occurrence and distribution of Pilomyxoid Astrocytomas amongst tumours previously diagnosed histologically as Pilocytic Astrocytoma and to assess the clinical impact of this new entity. METHODS: Retrospective Diagnostic review of all cases histologically diagnosed as WHO Grade I Astrocytoma at a single Neurosurgical unit between 1990 and 2003. RESULTS: Of a total of 91 cases identified, 9 were found to have Pilomyxoid histology. Of these, 8 were children (mean age 3.33 years) and 1 adult. 6 tumours were hypothalamochiasmatic in location. The clinical course of Pilomyxoid tumours was aggressive marked by maturation, multiple recurrences and disease control was rarely achieved with single treatment modality as opposed to typical pilocytics. The overall survival of the pilomyxoid group was not statistically different from the pilocytic tumours. CONCLUSIONS: Encompassing all age-groups and locations, Pilomyxoid Astrocytomas constitute about 10% of all tumours previously diagnosed as Pilocytic Astrocytoma. Nearly two-thirds are hypothalamo-chiasmatic in location. Knowledge of this entity is essential for appropriate aggressive treatment and follow-up.

Changes in the patterns of care of central nervous system tumours among 16-24 year olds and the effect on survival in Yorkshire between 1990 and 2009.

AIM: There is a paucity of work documenting the influence of patterns of care on survival for teenagers and young adults with primary central nervous system tumours. Therefore, the aim of this study was to undertake a detailed assessment examining any changes in the patterns of care over time and how these related to survival outcomes for 16-24 year olds diagnosed with a primary central nervous system tumour between 1990 and 2009. MATERIALS AND METHODS: We used high-quality data from one population-based cancer registry in Yorkshire, UK to describe primary central nervous system tumours in teenagers and young adults (16-24 years) diagnosed between 1990 and 2009. The Birch classification scheme was used to identify differences by tumour subgroup. Incidence, patterns of care and survival trends were described using Poisson and Cox regression. RESULTS: There were 163 cases comprising 98 astrocytomas, 17 'other gliomas', 14 ependymomas, 11 medulloblastomas and 23 'other intracranial and intraspinal neoplasms' yielding an overall incidence of 18.1 million person-years. Care varied significantly over time and by principal treatment centre (Leeds 77%, Hull 23%), co-ordinating specialty (neurosurgery 53%, clinical oncology 22%, paediatrics 17%, other adult services 8%) and treatment received. Cox regression showed no significant difference in survival by age, gender, treatment centre, level of deprivation, year of diagnosis or co-ordinating specialty, but a significant difference by tumour grade and diagnostic group. Survival improved for all diagnostic groups except astrocytoma, although only the medulloblastoma group showed a significant change over time. CONCLUSION: The lack of any significant improvement in survival over time in most diagnostic groups warrants further investigation and provides justification for a more collaborative regional approach to the care of central nervous system tumours, perhaps through the development of regional guidelines for this unique population. More detailed analysis of relapse patterns and prediagnostic symptoms would also be informative for this cohort.

An unusual presentation of inverted papilloma: case report and literature review.

OBJECTIVE: Inverted papilloma is a rare but locally aggressive tumour with the potential for malignant transformation. Intracranial extension or complications secondary to inverted papilloma are extremely rare. We report a case of inverted papilloma with a large frontal sinus mucocele eroding the frontal sinus, which presented with sudden neurological compromise. A literature review on intracranial extension of such tumours is also included. METHODS: A Medline search of articles, using the terms 'inverted papilloma', 'Ringertz tumour', 'intracranial extension' and 'complication'. Suitable references from the collected articles were also reviewed. Articles published in English were selected and reviewed. RESULTS: A total of 10 cases was identified. Intracranial spread was more commonly seen in recurrent cases, especially if the recurrence involved the cribriform plate, fovea ethmoidalis or orbits. Cases with extradural disease seemed to have a better prognosis than those with intradural spread. CONCLUSIONS: Intracranial involvement of inverted papilloma is extremely rare, and is usually seen in recurrent cases. This case report highlights an unusual but serious case of inverted papilloma presenting with acute neurological deterioration secondary to a large frontal sinus mucocele eroding the frontal sinus. A literature review on intracranial extension of inverted papilloma indicated that common sites of intracranial spread include the cribriform plate, fovea ethmoidalis and orbits. The prognosis for patients with such tumours depends on the type of dural involvement, with intradural extension carrying a poorer prognosis.

Construction of titanium cranioplasty plate using craniectomy bone flap as template.

In recent times a steady rise in cranioplasty operations has been noted because of increasing utilisation of decompressive craniectomy for trauma as well as stroke patients. A variety of techniques have been utilised for cranioplasty, with their own benefits and limitations. Titanium cranioplasty is one of the well-established and widely used techniques, with most centres utilising computer-assisted reconstruction for manufacture of titanium plates. In this paper we present a novel method for making titanium cranioplasty plates using the craniectomy bone flap as a template and the results of our experience. To date we have performed 51 cranioplasties using this method. The surgical results have been comparable to those obtained using the computer-assisted model technique. The construction cost for titanium cranioplasty plates using this method has been pound 360 cheaper per plate compared with the computer-assisted method. In addition, the CT workload and radiation exposure have been reduced.

Extradural haematomas in children: a 10-year review.

Extradural haematomas are a significant consequence of head injuries in children. The aim of this study was to evaluate the demographics, symptoms and signs, management and outcome of patients less than 18 years of age with extradural haematomas in our unit. We also specifically looked at repeat imaging performed, indications for this and its effect on further management. No previous reviews have included this. Fifty-six patients were identified from 01/01/1997 to 01/01/2007 for inclusion in this study. Their imaging was then reviewed as were the case notes. Of the patients studied, 70% were male. The average age was 10 years and 2 months with an average length of stay of one week. The commonest mechanisms of injury were a fall from height and an accident involving a bike. Presenting symptoms were documented in 40% of cases. 32% of patients had associated skull fractures. Six patients had other injuries, including long bone fractures and maxillofacial injuries. Glasgow Coma Scale was generally better on admission than pre-operatively and post-operatively was generally better than prior to surgery. Eight patients had neurological signs on admission, 11 had pre-operatively, and nine had post-operatively. 71% underwent a craniotomy with evacuation of the haematoma. Complications were reported in 16% with no mortality. 66% were seen in a neurosurgical clinic, with 46% seen in a Paediatric Head Injury Clinic after discharge. 66% had further imaging after their initial scan of which 52% had no clinical indication. Eight patients were operated on following re-imaging. Most extradural haematomas in children are caused by falls or vehicle accidents. The majority are treated surgically and do well. Indications for further scanning are often not present and in most, management is unchanged. The follow up of these patients also appears to be suboptimal.

Primitive neuroectodermal tumour arising within low grade astrocytoma: transformation, de novo or radiation induced? Report of three cases and review of literature.

The transformation from low grade to aggressive astrocytoma is well known. However, the development of a completely different tumour such as a primitive neuroectodermal tumour (PNET) within a low grade astrocytoma (LGA) is rare. Only two cases have been reported to date. We present three cases and review the literature. One case was identified at presentation. A subsequent review of our histopathology database revealed two further cases. All three patients had histologically proven low-grade astrocytoma and received radiotherapy following biopsy. The tumour location was infratentorial in one and supratentorial in two. The mean age at presentation with initial tumour was 20 years. Two patients underwent partial resection for recurrence, one at five and the other ten years later with histological confirmation of low-grade astrocytoma. At subsequent recurrence eight and thirty years following original presentation and eleven years later for the third patient, further tumour debulking was performed. Histology now revealed high grade PNET. Cytogenetics showed a complex karyotype with multiple chromosomal abnormalities in all three patients. All patients died within 1 year of final surgery. Among the six reported cases of PNET arising following prophylactic radiation therapy to low grade astrocytomas, only two occurred within the original tumour. Whether these cases represent transformation of low-grade astrocytoma, de novo formation of new tumour or radiation induced neoplasm is uncertain.

Gorham's disease of skull base and cervical spine--confusing picture in a two year old.

The unusual presentation of Gorham's disease of skull base and cervical spine in a two-year-old female child with radiological signs mimicking those of raised intracranial pressure is discussed. The differential diagnosis consists of skull base tumours, meningitis, osteomyelitis of the base of skull, congenital hydrocephalaus and congenital syndromes involving the skull base. Pathologically it can be very difficult to differentiate it from lymphangioma of the bone. Difficulty in establishing the diagnosis is discussed along with failure of radiotherapy and palmidronate therapy to cause arrest of the disease process and failure of surgery to provide stabilisation. We describe the course of the disease in this child over the period of last eight years. To the best of our knowledge this is the youngest case of Gorham's described so far.

Pre- and postoperative developmental attainment in sagittal synostosis.

AIMS: To investigate whether sagittal synostosis (SS) has consequences for children's mental and psychomotor development, and whether surgery has any impact on this. METHODS: The study involved 28 children with SS who underwent corrective surgery at a mean age of 8.0 (SD 7.16) months, and 28 normal controls. All the children with SS were assessed pre- and postoperatively using the Griffiths Mental Development Scales. The controls were assessed on one occasion, at an age matched with individuals in the patient group at the time of the preoperative assessment. A further control group consisted of 13 children with SS, who had received developmental assessment on two or more occasions without surgical intervention. RESULTS: The data indicated that children with SS have significantly poorer gross locomotor function than the normal controls. Following surgical intervention the deficit was shown to have resolved; consistent with this a lesser improvement in eye-hand coordination and performance skills was shown. Overall developmental attainment also improved postoperatively. The children with SS who did not receive surgery did not show any improvement in development. CONCLUSIONS: The study shows improved developmental attainment following surgical correction of SS, which may therefore be more than a cosmetic procedure.

Cauda equina syndrome following traction for acute sciatica.

A case report of a patient who developed cauda equina syndrome following pelvic traction for acute sciatica is presented. A good outcome was obtained with prompt surgical decompression. This case illustrates the potential dangers of traction, which is frequently employed in the management of acute back pain.

Investigations on a clinically and functionally unusual and novel germline p53 mutation.

This report describes an individual with a rare choroid plexus papilloma in adulthood (age 29) after earlier having an osteosarcoma (age 22). The results from this study, and others, suggest that it may be advisable to consider the possibility of a germline p53 mutation in adults presenting with choroid plexus tumours. In the current study automated DNA sequencing of genomic DNA detected a novel germline 7 base pair insertion in exon 5 of the p53 gene in this patient. The alteration in frame would produce amino acid substitutions beginning with alanine to glycine at position 161 and a stop codon at position 182 in the mutated protein. Surprisingly two assays of p53 function gave apparently wild-type results on peripheral blood lymphocytes from this individual. These results led us to carry out more detailed functional tests on the mutant protein. The mutant allele was expressed either at very low levels or not at all in phytohaemagglutinin stimulated lymphocytes. Further, the mutant protein was completely non-functional in terms of its ability to transactivate a series of p53-responsive genes (p21(WAF1), bax, PIG3), to transrepress a target gene and to inhibit colony growth in transfected Saos-2 cells. However, surprisingly, data from irradiated peripheral blood lymphocytes and transfected Saos-2 cells, suggested that this truncated, mutant protein retains significant ability to induce apoptosis.

A review of the cytogenetics of 58 pediatric brain tumors.

We describe the cytogenetic results of 58 pediatric central nervous system (CNS) tumors of variable histology, investigated between 1992 and 2000. Successful cytogenetics were obtained for 53 patients, with clonal chromosome abnormalities demonstrated in 25. Notable findings included (1) 2p abnormality in four primitive neuroectodermal tumors (PNET); (2) 1p loss in four low-grade gliomas and two PNET; (3) telomeric associations in one pilocytic astrocytoma; (4) chromosome 7 gain in four astrocytomas and two PNET; (5) 17p loss in four PNET; (6) double minutes in one PNET and three glioblastomas; and (7) chromosome 10 loss in four PNET. Higher grade tumors demonstrated greater karyotype complexity. Low-grade tumors showed either minimal simple chromosome changes or a normal karyotype. Chromosome abnormalities were more frequent in supratentorial tumors than their infratentorial counterparts. Our results add weight to the limited existing body of cytogenetic documentation for pediatric CNS tumors and provide further evidence that 2p loss is a consistent region of chromosome involvement in PNET. We advocate further studies of CNS tumors, in particular, to evaluate the importance of 2p changes and to compare cytogenetic results for supratentorial tumors and their infratentorial counterparts.

Management of hydrocephalus in pediatric patients with posterior fossa tumors: the role of endoscopic third ventriculostomy.

OBJECT: The authors undertook a study to evaluate the effectiveness of endoscopic third ventriculostomy in the management of hydrocephalus before and after surgical intervention for posterior fossa tumors in children. METHODS: Between October 1, 1993, and December 31, 1997, a total of 206 consecutive children with posterior fossa tumors underwent surgery at Hjpital Necker-Enfants Malades in Paris. Excluded were 10 patients in whom shunts had been placed at the referring hospital. The medical records and neuroimaging studies of the remaining 196 patients were reviewed and categorized into three groups: Group A, 67 patients with hydrocephalus present on admission in whom endoscopic third ventriculostomy was performed prior to tumor removal; Group B, 82 patients with hydrocephalus who did not undergo preliminary third ventriculostomy but instead received conventional treatment; and Group C, 47 patients in whom no ventricular dilation was present on admission. There were no significant differences between patients in Group A or B with respect to the following variables: age at presentation, evidence of metastatic disease, extent of tumor resection, or follow-up duration. In patients in Group A, however, more severe hydrocephalus was demonstrated (p < 0.01): the patients in Group C were in this respect different from those in the other two groups. Ultimately, there were only four patients (6%) in Group A compared with 22 patients (26.8%) in Group B (p = 0.001) in whom progressive hydrocephalus required treatment following removal of the posterior fossa tumor. Sixteen patients (20%) in Group B underwent insertion of a ventriculoperitoneal shunt, which is similar to the incidence reported in the literature and significantly different from that demonstrated in Group A (p < 0.016). The other six patients (7.3%) were treated by endoscopic third ventriculostomy after tumor resection. In Group C, two patients (4.3%) with postoperative hydrocephalus underwent endoscopic third ventriculostomy. In three patients who required placement of CSF shunts several episodes of shunt malfunction occurred that were ultimately managed by endoscopic third ventriculostomy and definitive removal of the shunt. There were no deaths; however, there were four cases of transient morbidity associated with third ventriculostomy. CONCLUSIONS: Third ventriculostomy is feasible even in the presence of posterior fossa tumors (including brainstem tumors). When performed prior to posterior fossa surgery, it significantly reduces the incidence of postoperative hydrocephalus. The procedure provides a valid alternative to placement of a permanent shunt in cases in which hydrocephalus develops following posterior fossa surgery, and it may negate the need for the shunt in cases in which the shunt malfunctions. Furthermore, in patients in whom CSF has caused spread of the tumor at presentation, third ventriculostomy allows chemotherapy to be undertaken prior to tumor excision by controlling hydrocephalus. Although the authors acknowledge that the routine application of third ventriculostomy in selected patients results in a proportion of patients undergoing an "unnecessary" procedure, they believe that because patients' postoperative courses are less complicated and because the incidence of morbidity is low and the success rate is high in those patients with severe hydrocephalus that further investigation of this protocol is warranted.