Donald Macarthur

Neuroendoscopic Third Ventriculostomy in Patients Less than 1 Year Old

A series of neuroendoscopic third ventriculostomies in children less than 1 year old is reported. Twenty-seven patients underwent the procedure with 21 (77%) failing within a mean of 1.36 months of the procedure. Nineteen were subsequently shunted. The presence or absence of flow through the ventriculostomy and the size of the lateral ventricles on post-operative imaging were not an indicator of success or failure. Only 4 (15%) had a complication of the procedure. Although the majority fail, approximately 1/3 are spared the added morbidity and mortality of having a shunt. With such a low morbidity and zero mortality the procedure has many benefits over shunting. Consequently, neuroendoscopic third ventriculostomy is used in this institution, where possible, rather than a shunt.

Neuroendoscopic third ventriculostomy for hydrocephalus in adults: report of a single unit’s experience with 63 cases

BACKGROUND Neuroendoscopic third ventriculostomy (NTV) is becoming a first line treatment for hydrocephalus in this center. Its use in a consecutive series of adults is reported. METHOD Initially a retrospective data collection after 7 months becoming prospective studying all patients who underwent NTV in this center. The adults (17 years or older) have been studied. RESULTS Sixty-three patients met the criteria for inclusion: 38 male, 25 female. Mean age at first NTV 37.5 years. There was an 80% success rate (i.e., no further therapy for the hydrocephalus required). Follow-up was for a mean of 3.1 years. The largest subgroup were patients with third ventricular tumours (35%), of whom 86% were successfully treated. Mean time to failure for the whole series was 8.5 months (range immediate--30 months). Complications occurred in 17.5%; those deemed serious in 11%. There were three deaths (4.7%) within 30 days of the procedure. There were six other deaths during follow-up, five because of tumour progression and one because of pneumonia. CONCLUSIONS This procedure lends itself to the treatment of hydrocephalus in adults and appears to be more successful than in young children. It is efficacious in both previously shunted and non shunted patients. It is now the first-line treatment for noncommunicating hydrocephalus in this center and also for patients with shunt failure who are anatomically suitable, having cerebrospinal fluid spaces large enough to admit the endoscope. The complication and mortality rates compare favorably with those for shunts.

Homozygous loss of ADAM3A revealed by genome-wide analysis of pediatric high-grade glioma and diffuse intrinsic pontine gliomas

Overall, pediatric high-grade glioma (pHGG) has a poor prognosis, in part due to the lack of understanding of the underlying biology. High-resolution 244 K oligo array comparative genomic hybridization (CGH) was used to analyze DNA from 38 formalin-fixed paraffin-embedded predominantly pretreatment pHGG samples, including 13 diffuse intrinsic pontine gliomas (DIPGs). The patterns of gains and losses were distinct from those seen in HGG arising in adults. In particular, we found 1q gain in up to 27% of our cohort compared with 9% reported in adults. A total of 13% had a balanced genetic profile with no large-scale copy number alterations. Homozygous loss at 8p12 was seen in 6 of 38 (16%) cases of pHGG. This novel deletion, which includes the ADAM3A gene, was confirmed by quantitative real-time PCR (qPCR). Loss of CDKN2A/CDKN2B in 4 of 38 (10%) samples by oligo array CGH was confirmed by fluorescent in situ hybridization on tissue microarrays and was restricted to supratentorial tumors. Only ∼50% of supratentorial tumors were positive for CDKN2B expression by immunohistochemistry (IHC), while ∼75% of infratentorial tumors were positive for CDKN2B expression (P = 0.03). Amplification of the 4q11-13 region was detected in 8% of cases and included PDGFRA and KIT, and subsequent qPCR analysis was consistent with the amplification of PDGFRA. MYCN amplification was seen in 5% of samples being significantly associated with anaplastic astrocytomas (P= 0.03). Overall, DIPG shared similar spectrum of changes to supratentorial HGG with some notable differences, including high-frequency loss of 17p and 14q and lack of CDKN2A/CDKN2B deletion. Informative genetic data providing insight into the underlying biology and potential therapeutic possibilities can be generated from archival tissue and typically small biopsies from DIPG. Our findings highlight the importance of obtaining pretreatment samples.

The role of neuroendoscopy in the management of brain tumours

Neuroendoscopy is increasingly used in the management of brain tumours and tumour related hydrocephalus and this study reviews the efficacy of neuroendoscopic interventions in this unit in patients with brain tumours. A series of 87 neuroendoscopic operations carried out in 77 patients with brain tumours over a 6-year period is reported. The age range of the patients was from 5 months to 70 years (median 13 years). In 56 cases (64%) presentation was with a newly-diagnosed tumour and hydrocephalus. The majority of the remaining patients had var ying degrees of worsening hydrocephalus on the background of a previously diagnosed tumour. Neuroendoscopic third ventriculostomy (NTV) was successful in relieving hydrocephalus in the short term in 63/66 cases (95%) and in the longer term in 55/66 cases (83%). Neuroendoscopic tumour biopsies were successful in providing a tissue diagnosis in 17/28 cases (61%) and four extensive and three partial resections of tumour were carried out. There were two deaths within 30 days of the procedure with only one of these, secondary to intraventricular haemorrhage, directly related to neuroendoscopy. Few significant complications were noted otherwise. For selected intraventricular and paraventricular tumours neuroendoscopy offers the opportunity to combine relief of hydrocephalus with tumour biopsy and sampling of CSF in a single procedure.

An artificial neural network system for diagnosis of acute myocardial infarction (AMI) in the accident and emergency department: evaluation and comparison with serum myoglobin measurements

Recent studies have confirmed that artificial neural networks (ANNs) are adept at recognising patterns in sets of clinical data. The diagnosis of acute myocardial infarction (AMI) in patients presenting with chest pain remains one of the greatest challenges in emergency medicine. The aim of this study was to evaluate the performance of an ANN trained to analyse clinical data from chest pain patients. The ANN was compared with serum myoglobin measurements--cardiac damage is associated with increased circulating myoglobin levels, and this is widely used as an early marker for evolving AMI. We used 39 items of clinical and ECG data from the time of presentation to derive 53 binary inputs to a back propagation network. On test data (200 cases), overall accuracy, sensitivity, specificity and positive predictive value (PPV) of the ANN were 91.8, 91.2, 90.2 and 84.9% respectively. Corresponding figures using linear discriminant analysis were 81.0, 77.9, 82.6 and 69.7% (P < 0.01). Using a further test set from a different centre (91 cases), the accuracy, sensitivity, specificity and PPV for the admitting physicians were 65.1, 28.5, 76.9 and 28.6% respectively compared with 73.6, 52.4, 80.0 and 44.0% for the ANN. Although myoglobin at presentation was highly specific, it was only 38.0% sensitive, compared with 85.7% at 3 h. Simple strategies to combine clinical opinion, ANN output and myoglobin at presentation could greatly improve sensitivity and specificity of AMI diagnosis. The ideal support for emergency room physicians may come from a combination of computer-aided analysis of clinical factors and biochemical markers such as myoglobin. This study demonstrates that the two approaches could be usefully combined, the major benefit of the decision support system being in the first 3 h before biochemical markers have become abnormal.

Neuroendoscopy in the premature population

Abstract The population born prematurely is particularly prone to hydrocephalus. Shunting techniques, whilst still the gold standard, have considerable failure rates and contribute significant morbidity and mortality. The role of neuroendoscopic techniques in the treatment of such patients is explored, and a series of 19 patients born prematurely and operated on neuroendoscopically before their 1st birthdays is described.

Neuroendoscopic third ventriculostomy for failed shunts.

BACKGROUND Neuroendoscopic third ventriculostomy has increased in frequency for the management of hydrocephalus. The objective of this paper is to study the outcome in patients with hydrocephalus whose shunt subsequently failed and who were treated with neuroendoscopic third ventriculostomy (NTV). METHOD The departmental prospectively acquired database, kept since 1994, was researched to identify those patients who underwent NTV, having presented with a failed shunt. Subsequent failure of the NTV occurs when further treatment for the hydrocephalus is required. RESULTS There were 88 patients identified, 45(51%) male and 43(49%) female. Median age at time of NTV was 14 years (range 1 day to 69 years). Median time from last shunt to NTV was 8 years (1 week to 35 years). Follow-up was for a median of 3 years (1 month to 6 years) after their NTV. Overall 42 (48%) failed and 46 (52%) were successful. In those with noncommunicating causes the success rate was 73%. Median time to failure was 1 month (immediate to 5 years) Median age of failed patients at time of NTV was 7 years. Serious complications occurred in 5 (5.6%). CONCLUSION NTV in patients having previously been shunted for their hydrocephalus is safe and as successful as in primary NTV. Failure can be expected to occur with greater frequency in communicating than noncommunicating types of hydrocephalus. The fact that they have a malfunctioning shunt in situ is not a contraindication to this procedure. In cases of infected shunts it is a useful adjunct to the treatment of the infection.

Atypical meningiomas: WHO moved the goalposts?

The histological grading of meningiomas underwent substantial revision and standardization in a WHO review of 2000. Prior to this the histological definition of atypical and malignant meningiomas was less tightly defined. We conducted a retrospective analysis of all meningiomas operated on between 1993 and 2003 in our unit (n = 565), to assess whether the WHO changes had altered the proportion of tumours diagnosed as atypical. The percentage of tumours graded WHO II (atypical meningiomas) has increased significantly since these changes were adopted (18.3 – 23.1%, p = 0.0408). We also examined the epidemiology of meningioma, finding that previous irradiation is associated with atypical meningiomas (p = 0.038) and surgeons find that complete excision is also more difficult with atypical tumours (p = 0.010), reporting poorer Simpson grades intraoperatively before the tumour grade is known. The increase in atypical lesions caused by the grading changes may lead to a corresponding increase in the numbers of patients referred for radiotherapy/radiosurgery, and we examine the evidence base for this strategy and whether our experience is replicated in other units.

Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome.

Relapsed ependymoma in children poses difficult dilemmas in management. Clinico-pathological and treatment data of 108 children with relapsed ependymoma in the United Kingdom (UK) treated between 1985 and 2002 were reviewed to identify prognostic factors affecting survival. The primary site was the most common site of relapse (84%). Overall 25% had metastatic relapse. Surgery at relapse was attempted in only 55%. Radiotherapy was delivered at relapse in 66% infants and 50% of older children were re-irradiated. Overall 5-year survival was 24% and 27% for children less than 3 years of age at initial diagnosis and older children, respectively. Multivariate analysis showed that, for infants, surgery (p=0.01) and radiotherapy (p=0.001) at relapse were independent predictors of survival. For older children regardless of the previous radiotherapy, repeat irradiation was associated with better outcome (p=0.05). Relapse was associated with poor outcome in both age groups. A survival advantage conferred by both radiotherapy and surgery at relapse is independently significant.

Can experimental models of rodent implantation glioma be improved? A study of pure and mixed glioma cell line tumours

To evaluate the hypothesis that co-implantation of different rodent glioma cell lines might result in experimental brain tumours that more closely resemble human gliomas the neuropathology and immunocytochemical features of implantation gliomas derived from single cell lines (C6, A15A5, F98), two cell lines admixed 50:50 prior to implantation (C6 + F98 and C6 + A15A5) and three cell lines equally admixed (C6 + A15A5 + F98) was studied in the adult Wistar rat. Tumours grew consistently following implantation of the single and the two admixed cell lines, however tumour growth following triple mix implantation was considerably and consistently impaired. The tumours derived from admixed cell lines showed regional heterogeneity with areas characteristic of both the primary cell lines. Foci of lymphocytic infiltrates, tumoural necrosis, often with pseudopallisading, and peritumoural edema were consistent features of all tumours. Limited parenchymal and more extensive perivascular tumoural invasion was seen predominantly in tumours containing the C6 cell line. There were no significant differences in GFAP, vimentin and HSP70 staining between the mixed tumours, although the pure F98 and A15A5 tumours were, unlike the pure C6 gliomas, S-100 negative. Using PCNA expression as a measure of the tumour proliferation all except the tumours derived from the three cell lines mix, which had a staining index of 7–10%, had focal staining indices in viable tumour of between 40–80%. There was focal positive staining in both perilesional brain and in regions of all tumours for the macrophage markers ED-1 and ED-2. None of the three cell lines stained in vitro for either ED1 and ED2 but all were constitutively positive in vitro for OX-6, a proposed marker for antigen presenting cells. The macrophage and lymphocytic response suggest a vigorous but largely ineffective immunological response had been mounted against all tumours. The consistent failure of the triple mix tumours to grow is unexplained. This work has shown the feasibility of producing ‘mixed’ cell line experimental gliomas by combining two cell lines at the time of innoculation. However, the relative failure to produce (i) mixed tumours that have properties not inherent to either parent cell line and (ii) implantation glioma with three cell lines suggest there are limits to this approach. Admixture of cell lines at the time of implantation therefore does not make experimental glioma models that more closely resemble natural gliomas, and also has some particular disadvantages. This experimental approach is therefore not recommended for use in the study of tumour biology and in evaluating the effectiveness of novel therapies.