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.

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.

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.

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.

Evaluation of carotid endarterectomy with sequential MR perfusion imaging: a preliminary report.

BACKGROUND AND PURPOSE: Current indications for carotid endarterectomy are determined by balancing the relative risks of surgery with the benefits of reduced risk of subsequent stroke. Our purpose was to use MR perfusion imaging to assess patients being considered for carotid endarterectomy and to monitor sequential changes in MR perfusion characteristics after surgery. In particular, we wished to determine whether this technique could be used to detect changes that might be related to post-carotid endarterectomy hyperemia. METHODS: We used a single-section gradient-recalled echo sequence to investigate 14 patients being examined before possible surgery for carotid artery disease. In the 12 patients in whom carotid endarterectomy was performed, sequential studies were performed 3 to 5 days after surgery and at 3 months. Analysis of bolus-arrival-time (BAT) images was performed. RESULTS: Significant delays in preoperative BAT images of 0.89 seconds (range, 0.05 to 3.22 seconds) were apparent between hemispheres. Excluding the two patients with contralateral internal carotid artery (ICA) occlusion, early arrival, possibly indicating postoperative hyperemia, was seen in five patients immediately after carotid endarterectomy but resolved within 3 to 5 months after surgery. CONCLUSION: MR perfusion imaging shows differences in BAT between hemispheres in patients with ICA stenosis. Changes in perfusion characteristics after carotid endarterectomy are complex, and early BAT on the operative side can occur soon after endarterectomy in over half those patients without an occluded contralateral vessel. The significance of these findings with regard to patient outcome and risk of postoperative hyperemia requires further investigation.

Assessment of quantitative computed tomographic cerebral perfusion imaging with H2(15)O positron emission tomography.

Assessment of quantitative cerebral blood flow on a conventional fast CT machine without the use of specialized equipment may be valuable in the investigation of acute stroke and head injury. We aimed to compare a single slice CT perfusion sequence with H2(15)O positron emission tomography using the sagittal sinus as an input function, a method that avoids unnecessary orbital irradiation. Eight patients were studied, two patients with gliomas, and six with arteriovenous malformations. The dynamic CT perfusion sequence was performed by acquiring the same 10 mm slice 10 times over 30 sec during a 50 ml bolus of intravenous contrast medium given at a rate of 7.5 ml sec-1 using a power injector. The CT perfusion studies were completed without complication. Co-registration was sub-optimal in one patient. Overall the correlation between the two methodologies was encouraging with an average r2 value of 0.524 for individual analyses. When two patients with high flow arteriovenous malformations were excluded the average r2 value increased to 0.640. The results of this CT perfusion methodology are encouraging. Having shown its feasibility, further studies in conditions with lower rates of cerebral blood flow are warranted.

Supportive cushions produce no practical reduction in lumbar lordosis.

It is common practice to place a pillow or bolster under the knees of patients undergoing lumbar spine CT or MRI. The use of such supportive cushions leads to gentle hip flexion that is thought to ease pain and "reduce lumbar lordosis". It is also thought to facilitate axial imaging through the discs. Observations in seven subjects who underwent lumbar spine MRI with and without such hip flexion showed no appreciable change in the degree of lordosis. As the use of such devices does not produce a practical reduction of lumbar lordosis, the decision to employ them should be made entirely with respect to patient comfort.

Reproducibility of quantitative CT perfusion imaging.

The ability to demonstrate regions of abnormal cerebral blood flow in the setting of acute stroke is of diagnostic and prognostic importance. It may also influence therapeutic strategies. The advantage of CT perfusion imaging is its ability to give quantifiable measurements of cerebral blood flow on any modern CT machine without the need to buy specialized equipment. The aim was to assess day-to-day variability of values of cerebral blood volume obtained with this technique. Seven patients with cerebral gliomas were studied using dynamic CT perfusion imaging on two occasions, approximately 24 h apart to reduce variability from diurnal variations. Regions of interest were produced in predominately middle cerebral artery locations in both hemispheres on the first and second CT perfusion studies. Absolute values for cerebral blood flow were produced for these regions and were correlated with flows obtained in the same regions of interest on the follow-up study. The Pearson correlation coefficient obtained was 0.884. CT perfusion imaging is easily performed on conventional modern CT equipment and demonstrates little variability in measures of absolute cerebral blood flow within individuals when studied on two occasions within 24 h.

Magnetic resonance imaging of acoustic neuromas: the role of gadolinium-DTPA.

Magnetic resonance imaging (MRI) was performed in 20 patients with evidence on computed tomography (CT) of 21 acoustic neuromas before and after intravenous administration (0.1-0.2 mmol/kg body weight) of gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA). Multi-section spin-echo (SE) sequences of varying repetition (TR) and echo (TE) times were performed in the transverse and coronal planes with a section thickness of 10 mm. All acoustic neuromas displayed marked enhancement on the T1-weighted (short TR/TE) SE sequence post-Gd-DTPA. The intrameatal component was particularly well demonstrated compared with non-enhanced magnetic resonance (MR) images and contrast-enhanced CT. Identification of intrameatal tumour was difficult on T2-weighted SE images and one tumour was not identified on the T1-weighted SE sequence prior to Gd-DTPA. Four of five intrameatal tumours measuring less than 8 mm could only be demonstrated on CT by using CT air meatography. Extrameatal tumour extension was demonstrated on contrast-enhanced CT, although the assessment of brain-stem involvement and displacement was not as clearly seen as on coronal MR images. In two patients with large acoustic neuromas and a cyst, the true relationship of the cyst to the tumour could only be identified on the post-Gd-DTPA scan. Magnetic resonance imaging with gadolinium-DTPA is a relatively quick, safe, well tolerated and effective method for the diagnosis of acoustic neuroma.

MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T.

Recent advances in MR diffusion weighted imaging (DWI) enable the identification of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed to use a novel DTI technique to safely study patients with recent stroke in a high field (3 T) MR machine with its intrinsically higher spatial resolution and signal-to-noise ratio. Of ten patients studied, six had disruption of white matter tracts as determined by DTI. A further patient had distortion of white matter tracts around an infarct rather than actual disruption of the tracts themselves. The lack of tract destruction may imply a beneficial prognosis, information that is not available with conventional DWI.

Helical computed tomography and three-dimensional reconstruction of a bipedicular developmental anomaly of the C2 vertebra.

STUDY DESIGN: A case of bilateral failure of fusion of the C2 neural arch resembling a bipedicular fracture in a 9-year-old boy involved in a motor vehicle accident. OBJECTIVES: To describe the use of helical computed tomography and three-dimensional reconstruction images to identify the defect as congenital. SUMMARY OF BACKGROUND DATA: Congenital defects in the C2 neural arch are rare. Diagnostic difficulties arise when they are discovered during the assessment of patients after trauma, when they may resemble C2 arch fractures. METHODS: Lateral cervical spine radiograph, transverse section computed tomography, and three-dimensional reconstruction images were used to delineate the anatomy of the defect. RESULTS: The three-dimensional reconstruction views showed that normal alignment of the vertebrae was maintained, despite the pedicle defects. CONCLUSIONS: Differentiation of a C2 fracture from a congenital defect may be difficult. Reconstruction in three dimensions from helical computed tomography is a useful adjunct to conventional computed tomography in the evaluation of such patients.

The natural history of a recurrent central neurocytoma-like tumor.

The central neurocytoma was first recognized as a distinct entity in 1982. The original description was of a low grade, intraventricular neoplasm composed of uniform cells showing neuronal differentiation, and having a very favorable prognosis after surgery. Subsequently rare cases have been described showing malignant histological features but retaining the morphological characteristics that justify inclusion in this category. The behavior of such cases has yet to be determined. We report a case of a longstanding intraventricular tumor showing neuronal differentiation in which repeated recurrences following surgery have revealed evidence of increasing nuclear pleomorphism, mitotic activity and glial differentiation. We suggest that this tumor broadens further the clinical and pathological spectrum of central neurocytoma.

Chondrosarcoma of the petrous apex. Dilemmas in diagnosis and treatment.

A case of chrondrosarcoma of the petrous temporal bone is presented. Chondrosarcomas rarely occur intracranially and typically present apex mass. The dilemmas faced in the diagnosis and treatment of petrous apex chondrosarcomas are discussed. This case also gives interesting insight into the natural history of this tumour.

Value of computed tomography and magnetic resonance imaging in the treatment of a calcifying epithelial odontogenic (Pindborg) tumour.

The calcifying epithelial odontogenic (Pindborg) tumour is a rare primary tumour of the jaw with a characteristic histological appearance. We describe here its appearance on computed tomography (an expanding, multilocular lesion that is thinning both plates of the mandible, is well-defined and contains scattered radio-opaque areas) and magnetic resonance imaging (predominantly hypointense on T1-weighted images and of mixed hyperintensity on T2-weighted images; the extent of the tumour including involvement of the mandibular canal was clear).

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.

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.