Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature.

Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing's syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days-seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.

Comparing the accuracy of initial head CT reporting by radiologists, radiology trainees, neuroradiographers and emergency doctors.

OBJECTIVES: Demand for out-of-hours cranial CT imaging is increasing and some departments have considered addressing this shortfall by allowing non-radiologists to provisionally report imaging studies. The aim of this work was to assess whether it is appropriate for non-radiologists to report head CTs by comparing the misreporting rates of those who regularly report head CTs with two groups of non-radiologists who do not usually report them: neuroradiographers and emergency doctors. METHODS: 62 candidates were asked to report 30 head CTs, two-thirds of which were abnormal, and the results were compared by non-parametric statistical analysis. RESULTS: There was no evidence of a difference in the score between neuroradiographers, neuroradiologists and general consultant radiologists. Neuroradiographers scored significantly higher than senior radiology trainees, and the emergency doctors scored least well. CONCLUSION: The results of this preliminary study show that appropriately trained neuroradiographers are competent at reporting the range of abnormalities assessed with this test and that their misreporting rates are similar to those who already independently report these studies.

Does perfusion computed tomography facilitate clinical decision making for thrombolysis in unselected acute patients with suspected ischaemic stroke?

BACKGROUND: Despite use in clinical practice and major positive trials of thrombolysis, non-contrast computed tomography (NCCT) is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how physiological imaging using CT perfusion (CTP) could add to the diagnostic utility of an NCCT and inform clinical decisions regarding thrombolysis. METHODS: Forty imaging datasets containing NCCT and CTP were retrospectively identified from a cohort of consecutive acute stroke patients. Two sets of observers (n = 6) and a neuroradiologist evaluated the images without knowledge of clinical symptoms. Inter-observer agreement was calculated using the κ statistic for identifying acute ischaemic change on NCCT: perfusion abnormalities (namely cerebral blood volume, cerebral blood flow and time to peak), and penumbral tissue on perfusion maps obtained by two image processing algorithms. RESULTS: Inter-rater agreement was moderate (κ = 0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for cerebral blood volume (κ = 0.67) and to almost perfect for time to peak (κ = 0.87) and cerebral blood flow (κ = 0.87). The agreement for qualitative assessment of penumbral tissue was substantial to perfect for images obtained using the two different perfusion algorithms. Overall, there was a high rate of decision to thrombolyse based on NCCT (81.25%). CTP strengthened the decision to thrombolyse based on NCCT in 38.3% of cases. It negatively influenced the decision in 14.6% of cases, this being significantly more common in experienced observers (p = 0.02). CONCLUSIONS: We demonstrate that the qualitative evaluation of CTP produces near perfect inter-observer agreement, regardless of the post-processing method used. CTP is a reliable, accessible and practical imaging modality that improves confidence in reaching the appropriate diagnosis. It is particularly useful for less experienced clinicians, to arrive at a physiologically informed treatment decision.

Canal wall cholesteatoma following canalplasty.

INTRODUCTION: Bony canalplasty is a common otological procedure performed to widen a narrow ear canal. The aim of this report is to describe two unusual patients who presented with a canal wall cholesteatoma many years after bony canalplasty. CASES: Two patients, aged 28 and 52 years, are presented. Both underwent canalplasty, 14 and 17 years before re-presenting with cholesteatoma evident through posterior canal wall defects. Both patients underwent exploration of the mastoid cavities and cartilage reconstruction of the canal walls. There was no recurrence at 24 and three month follow-up examinations (variously), hearing was preserved in both cases, and the patients suffered no early complications. CONCLUSIONS: The most frequent long-term complication of canalplasty is re-stenosis of the external auditory canal. The importance of sealing any inadvertently opened mastoid air cells, in order to avoid the late complication reported, is emphasised.

Selective neuronal loss in rescued penumbra relates to initial hypoperfusion.

Selective neuronal loss (SNL) in the rescued penumbra could account for suboptimal clinical recovery despite effective early reperfusion. Previous studies of SNL used single-photon emission tomography (SPECT), did not account for potential volume loss secondary to collapse of the infarct cavity, and failed to show a relationship with initial hypoperfusion. Here, we obtained acute-stage computerized tomography (CT) perfusion and follow-up quantitative (11)C-flumazenil (FMZ)-PET to map SNL in the non-infarcted tissue and assess its relationship with acute-stage hypoperfusion. We prospectively recruited seven patients with evidence of (i) acute (<6 h) extensive middle cerebral artery territory ischaemia based on clinical deficit (National Institutes of Health stroke scale, NIHSS score range: 8-23) and CT Perfusion (CTp) findings and (ii) early recanalization (spontaneous or following thrombolysis) based on spectacular clinical recovery (DeltaNIHSS > or =6 at 24 h), good clinical outcome (NIHSS < or =5) and small final infarct (6/7 subcortical) on late-stage MRI. Ten age-matched controls were also studied. FMZ image analysis took into account potential post-stroke volume loss. Across patients, clusters of significantly reduced FMZ binding were more prevalent and extensive in the non-infarcted middle cerebral artery cortical areas than in the non-affected hemisphere (P = 0.028, Wilcoxon sign rank test). Voxel-based between-group comparisons revealed several large clusters of significantly reduced FMZ binding in the affected peri-insular, superior temporal and prefrontal cortices (FDR P < 0.05), as compared with no cluster on the unaffected side. Finally, comparing CTp and PET data revealed a significant negative correlation between FMZ binding and initial hypoperfusion. Applying correction for volume loss did not substantially alter the significance of these results. Although based on a small patient sample sometimes studied late after the index stroke, and as such preliminary, our results establish the presence and distribution of FMZ binding loss in ultimately non-infarcted brain areas after stroke. In addition, the data suggest that this binding loss is proportional to initial hypoperfusion, in keeping with the hypothesis that the rescued penumbra is affected by SNL. Although its clinical counterparts remain uncertain, it is tempting to speculate that peri-infarct SNL could represent a new therapeutic target.

A second biopsy?--Tandem lesion.

This is a rare case of synchronous pituitary adenoma and PNET in an adult and first of this sort in the literature. The MR appearances suggest a single pathological entity causing the changes in the different anatomical location which can occur in cases of germ cell tumours, PNET and glioblastoma. In certain cases, histological confirmation may be warranted for the different lesions. Both pathologies have different treatment strategy and outlook depending on the age, extent of the disease and Karnofsky score.

Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI.

BACKGROUND AND PURPOSE: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. METHODS: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. RESULTS: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm(2) vs 50 mm(2); p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. CONCLUSIONS: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

Reproducibility of volume measurements of vestibular schwannomas - a preliminary study.

OBJECTIVE: A preliminary study to investigate the intra-observer and inter-observer variability of measurements of vestibular schwannoma volume using an area-tracing and linear dimension measurement method. DESIGN: Prospective blinded measurements by two observers (one a consultant and one a sub-specialty trainee in neuroradiology). SETTING: Ambulatory patients with known vestibular schwannoma attending a tertiary referral centre. PARTICIPANTS: Twenty-three patients with 26 vestibular schwannomas aged 29-80 years old. MAIN OUTCOME MEASURE: Quantification of the variability in measured volume due to intra- and inter-observer measurement differences, expressed as reliability coefficients within which 95% of repeated measurements are calculated to lie from each other in relative percentage terms. RESULTS: For the linear measurement method, intraobserver variability was calculated to have a reliability coefficient of 65% and for interobserver variability this was 155%. For the area tracing method, the corresponding coefficients were 26% for intraobserver variability and 44% for interobserver variability. CONCLUSIONS: Volume measurements in vestibular schwannoma are variable even when the measurements are made by the same observer on identical images. The area tracing method, commonly regarded as the gold standard, is less variable than a linear method but still introduces more variability than commonly realized (for 95% of patients, repeated measurements by the same observer lie within around 25% of each other). Manual area tracing is not widely used in practice because it is time consuming and reliable automated methods are eagerly awaited.

Perfusion CT helps decision making for thrombolysis when there is no clear time of onset.

Current guidelines on thrombolysis post stroke with recombinant tissue plasminogen activator (rt-PA) exclude its use where time of onset is unknown, thus denying some patients potentially beneficial treatment. Contrast enhanced perfusion computed tomography (pCT) imaging can be used together with plain CT and information on clinical deficits to decide whether or not thrombolysis should be initiated even though the exact time of stroke onset is unknown. Based on the results of pCT and CT, rt-PA was administered to two patients with unknown time of stroke onset; one of the patients also underwent suction thrombectomy. Results in both cases were excellent.

Utility of an ultrafast magnetic resonance imaging protocol in recent and semi-recent strokes.

OBJECTIVE: To evaluate the technical feasibility of an integrated ultrafast head magnetic resonance (MR) protocol using a sensitivity encoding (SENSE) technique for depicting parenchymal ischaemia and vascular compromise in patients with suspected recent stroke. METHODS: 23 patients were evaluated with the ultrafast MR protocol using T2, T1, fluid attenuated inversion recovery (FLAIR), 3D time of flight magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI) sequences. These were compared with routine conventional MR sequences. RESULTS: One patient could not tolerate conventional imaging, although imaging using the three minute head SENSE protocol was diagnostic. Both conventional and ultrafast protocols were of similar diagnostic yield in the remaining patients. There were no significant differences in clinical diagnostic quality for the T1, T2, FLAIR, and DWI sequences. One MRA examination was of better quality when SENSE was used, owing to reduced motion artefacts and shorter imaging time. CONCLUSIONS: It is possible to undertake a comprehensive MR examination in stroke patients in approximately three to five minutes. Ultrafast imaging may become a useful triage tool before thrombolytic therapy. It may be of particular benefit in patients unable to tolerate longer sequences. Further work is necessary to confirm these findings in hyperacute stroke.

Detection and evaluation of intracranial aneurysms with 16-row multislice CT angiography.

AIM: The aim of this study was to assess the usefulness of 16-row multislice CT angiography (CTA) in evaluating intracranial aneurysms, by comparison with conventional digital subtraction angiography (DSA) and intraoperative findings. METHODS: A consecutive series of 57 patients, scheduled for DSA for suspected intracranial aneurysm, was prospectively recruited to have CTA. This was performed with a 16-detector row machine, detector interval 0.75 mm, 0.5 rotation/s, table speed 10mm/rotation and reconstruction interval 0.40 mm. CTA studies were independently and randomly assessed by two neuroradiologists and a vascular neurosurgeon blinded to the DSA and surgical findings. Review of CTA was performed on workstations with an interactive 3D volume-rendered algorithm. RESULTS: DSA or intraoperative findings or both confirmed 53 aneurysms in 44 patients. For both independent readers, sensitivity and specificity per aneurysm of DSA were 96.2% and 100%, respectively. Sensitivity and specificity of CTA were also 96.2% and 100%, respectively. Mean diameter of aneurysms was 6.3mm (range 1.9 to 28.1 mm, SD 5.2 mm). For aneurysms of less than 3 mm, CTA had a sensitivity of 91.7% for each reader. Although the neurosurgeon would have been happy to proceed to surgery on the basis of CTA alone in all cases, he judged that DSA might have provided helpful additional anatomical information in 5 patients. CONCLUSION: The diagnostic accuracy of 16-slice CTA is promising and appears equivalent to that of DSA for detection and evaluation of intracranial aneurysms. A strategy of using CTA as the primary imaging method, with DSA reserved for cases of uncertainty, appears to be practical and safe.

Application of the Canadian CT head rules in managing minor head injuries in a UK emergency department: implications for the implementation of the NICE guidelines.

OBJECTIVE: In 2002 a new protocol was introduced based on the Canadian CT rules. Before this the Royal College of Surgeons "Galasko" report guidelines had been followed. This study evaluates the effects of the protocol and discusses the impact of the implementation of the NICE head injury guidelines-also based on the Canadian CT rules. METHODS: A "before and after" study was undertaken, using data from accident and emergency cards and hospital notes of adult patients with head injuries presenting to the emergency department over seven months in 2001 and nine months in 2002. The two groups were compared to see how rates of computed tomography (CT), admission for observation, discharge, and skull radiography had changed after introduction of the protocol. RESULTS: Head CT rates in patients with minor head injuries (MHI) increased significantly from 47 of 330 (14%) to 58 of 267 (20%) (p<0.05). There were also significantly increased rates of admission for observation, from 111 (34%) to 119 (45%). Skull radiography rates fell considerably from 33% of all patients with head injuries in 2001 to 1.6% in 2002, without any adverse effect. CONCLUSIONS: This study shows that it is possible to replace the current practice in the UK of risk stratification of adult MHI based on skull radiography, with slightly modified versions of the Canadian CT rule/NICE guidelines. This will result in a large reduction in skull radiography and will be associated with modest increases in CT and admissions rates. If introduction of the NICE guideline is to be realistic, the study suggests that it will not be cost neutral.

Contrast-enhanced MR angiography for carotid disease: diagnostic and potential clinical impact.

OBJECTIVE: To compare contrast-enhanced MR angiography (CEMRA) with intra-arterial digital subtraction angiography (DSA) for evaluating carotid stenosis. METHODS: A total of 167 consecutive symptomatic patients, scheduled for DSA following screening duplex ultrasound (DUS), were prospectively recruited to have CEMRA. Three independent readers reported on each examination in a blinded and random manner. Agreement was assessed using the Bland-Altman method. Diagnostic and potential clinical impact of CEMRA was evaluated, singly and in combination with DUS. RESULTS: CEMRA tended to overestimate stenosis by a mean bias ranging from 2.4 to 3.8%. A significant part of the disagreement between CEMRA and DSA was directly caused by interobserver variability. For detection of severe stenosis, CEMRA alone had a sensitivity of 93.0% and specificity of 80.6%, with a diagnostic misclassification rate of 15.0% (n = 30). More importantly, clinical decision-making would, however, have been potentially altered only in 6.0% of cases (n = 12). The combination of concordant DUS and CEMRA reduced diagnostic misclassification rate to 10.1% (n = 19) at the expense of 47 (24.9%) discordant cases needing to proceed to DSA. An intermediate approach of selective DUS review resulted in a marginally worse diagnostic misclassification rate of 11.6% (n = 22) but with only 6.8% of discordant cases (n = 13). CONCLUSIONS: DSA remains the gold standard for carotid imaging. The clinical misclassification rate with CEMRA, however, is acceptably low to support its safe use instead of DSA. The appropriateness of combination strategies depends on institutional choice and cost-effectiveness issues.

Conventional digital subtraction x-ray angiography versus magnetic resonance angiography in the evaluation of carotid disease: patient satisfaction and preferences.

AIM: To compare conventional digital subtraction x-ray angiography (DSA) and contrast-enhanced magnetic resonance angiography (MRA) of the carotid arteries in terms of patient satisfaction and preferences. METHODS: One hundred and sixty-seven patients with symptomatic carotid artery disease, who underwent both DSA and MRA, were prospectively recruited in this study. Patients' perceptions of each method were assessed by the use of a questionnaire after each procedure. Main outcome measures were anxiety, pain, satisfaction rate and patient preferences. RESULTS: DSA generated more anxiety and pain during the procedure, but the severity of these ill-effects was mild. Satisfaction rates for each method were similar. More patients were, however, willing to have a repeat MRA compared with DSA (67 versus 41%). The majority of patients (62%) preferred MRA over DSA (31%). The shorter MRA imaging time was found to be a significant factor in patients' acceptance of the technique. The main reasons cited by patients for their dislike of a particular procedure was noise and claustrophobia for MRA and invasiveness, pain and post-procedural bed rest for DSA. CONCLUSIONS: MRA is the method that is preferred by the majority of patients, although the actual disutility of DSA may be small. Assuming equal diagnostic accuracy, our data supports replacement of DSA by MRA for routine carotid imaging.

Evaluation of an MRI-based protocol for cell implantation in four patients with Huntington's disease.

The purpose of this study was to evaluate our surgical protocol for the preparation and delivery of suspensions of fetal tissue into the diseased human brain. We implanted suspensions of human fetal striatal anlage into the right caudate and putamen of four patients with Huntington's disease. Postoperative 3 tesla MR imaging confirmed accurate graft placement. Variability in graft survival was noted and the MR signal changes over 6 months revealed persistent hyperintense signal on T2-weighted images. Our results are consistent with those described by other groups and indicate that our surgical protocol is safe, accurate, and reproducible.

Diffusion tensor imaging of brain tumours at 3T: a potential tool for assessing white matter tract invasion?

AIM: To determine whether diffusion tensor imaging (DTI) of brain tumours can demonstrate abnormalities distal to hyperintensities on T2-weighted images, and possibly relate these to tumour grade. MATERIALS AND METHODS: Twenty patients with histologically confirmed supratentorial tumours, both gliomas (high and low grade) and metastases, were imaged at 3T using T2-weighted and DTI sequences. Regions of interest (ROI) were drawn within the tumour, in white matter at various distances from the tumour and in areas of abnormality on DTI that appeared normal on T2-weighted images. The relative anisotropy index (RAI)-a measure of white matter organization, was calculated for these ROI. RESULTS: The abnormality on DTI was larger than that seen on T2-weighted images in 10/13 patients (77%) with high-grade gliomas. New abnormalities were seen in the contralateral white matter in 4/13 (30%) of these cases. In these high-grade tumours the RAI in areas of white matter disruption with normal appearance on T2-weighted images was reduced (0.19+/-0.04). Even excluding patients with previous radiotherapy this difference remains significant. In all non high-grade tumours (WHO grade II gliomas and metastases) the tumour extent on DTI was identical to the abnormalities shown on T2-weighted imaging and RAI measurements were not reduced (0.3+/-0.04). CONCLUSIONS: Subtle white matter disruption can be identified using DTI in patients with high-grade gliomas. Such disruption is not identified in association with metastases or low-grade gliomas despite these tumours producing significant mass effect and oedema. We suggest the changes in DTI may be due to tumour infiltration and that the DTI may provide a useful method of detecting occult white matter invasion by gliomas.