Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients.

AIMS: To document the type, location, extent, and complications of brain metastases in patients with breast cancer and identify associations with oestrogen receptor (ER) negative and human epidermal growth factor receptor 2 (HER-2) receptor expression. MATERIALS AND METHODS: Breast cancer patients with known brain metastases were included in this retrospective study, if cross-sectional imaging of the brain [computed tomography (CT)] was available to review and HER-2 and ER status was known. Two neuroradiologists, who were blinded to the receptor status, separately and for each patient, documented on a proforma the location, number, and dimensions of the deposits and the presence or absence of hydrocephalus. Adjudication was sought where there was discrepancy between the two reports. ER status, HER-2 receptor status, and patient age were also documented. The results were analysed using two-sided Fisher's exact tests with Lancaster's mid-P correction and associations were sought between the tumour characteristics and the pattern of brain disease. RESULTS: Sixty patients were included in the study. There was an association between young age (<40 years) and HER-2 positivity [10 of 24 (41.7%) versus three of 36 (8.3%); p = 0.002]. In ER-negative women, HER-2 positivity was found to be associated with a larger number (six or more) of metastases [11 of 18 (61%) versus nine of 25 (36%); p = 0.049], more brain stem metastases [11 of 18 (61%) versus three of 26 (11.5%); p = 0.035], more frequent occurrence of hydrocephalus [7 of 12 (36.8%) versus three of 26 (11.5%); p = 0.049], and a higher incidence of occipital metastases [12 of 18 (66.7%) versus eight of 26 (30.8%); p = 0.029]. CONCLUSION: ER-negative HER-2-positive women are more likely to present with a larger number of lesions, more brain stem/occipital metastases, and hydrocephalus, which may predispose them to unfavourable outcomes following treatment.

What neuroimaging should be performed in children in whom inflicted brain injury (iBI) is suspected? A systematic review.

AIMS: To investigate the optimal neuroradiological investigation strategy to identify inflicted brain injury (iBI). MATERIALS AND METHODS: A systematic review of studies published between 1970-2008 in any language was conducted, searching 20 databases and four websites, using over 100 keywords/phrases, supplemented by hand-searching of references. All studies underwent two independent reviews (with disagreements adjudicated by a third reviewer) by trained reviewers from paediatrics, paediatric neuroradiology and related disciplines, using standardized critical appraisal tools, and strict inclusion/exclusion criteria. We included primary studies that evaluated the diagnostic yield of magnetic resonance imaging (MRI), in addition to initial computed tomography (CT), or follow-up CT or ultrasound in children with suspected iBI. RESULTS: Of the 320 studies reviewed, 18 met the inclusion criteria, reflecting data on 367 children with iBI and 12 were published since 1998. When an MRI was conducted in addition to an abnormal early CT examination, additional information was found in 25% (95% CI: 18.3-33.16%) of children. The additional findings included further subdural haematoma, subarachnoid haemorrhage, shearing injury, ischaemia, and infarction; it also contributed to dating of injuries. Diffusion-weighted imaging (DWI) further enhanced the delineation of ischaemic changes, and assisted in prognosis. Repeat CT studies varied in timing and quality, and none were compared to the addition of an early MRI/DWI. CONCLUSIONS: In an acutely ill child, the optimal imaging strategy involves initial CT, followed by early MRI and DWI if early CT examination is abnormal, or there are ongoing clinical concerns. The role of repeat CT imaging, if early MRI is performed, is unclear, as is the place for MRI/DWI if initial CT examination is normal in an otherwise well child.

Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

BACKGROUND AND PURPOSE: HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non-brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY. MATERIALS AND METHODS: We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process. RESULTS: Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1). CONCLUSIONS: The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.

Intrathecal chemotherapy delivered by a lumbar-thecal catheter in metastatic medulloblastoma: a case illustration.

BACKGROUND: Medulloblastoma is the most common malignant brain tumour in children. Despite recent advances, the prognosis in high risk patients remains poor. Further improvement in survival is dependent upon the development of strategies to attack the tumour more effectively, but with less toxicity. Intrathecal chemotherapy, is an ideal but currently underused method of directly targeting residual tumour within the area of resection and the leptomeningeal disease commonly associated with this tumour. METHOD: We describe the case of a 12 yr old child with metastatic medulloblastoma, who received intrathecal topotecan via a spinal catheter. CONCLUSION: This method represents a simple, safe and effective method of delivering an even and widespread distribution of drug within the cerebrospinal fluid (CSF) of the neuroaxis. With new agents being identified and others in the early stages of development, intrathecal chemotherapy may emerge as an important therapeutic option to consider when faced with such challenging cases.

Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas.

Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.

PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m(2) on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B). Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans. RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy. Grade 3/4 thrombocytopenia was the most frequent toxic event (7% of cycles). Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively). Two toxic deaths were documented and were related to myelosuppression and sepsis in one patient and pneumonia in a second. The overall (best) response rate was 12% for arm A (95% confidence interval [CI], 3 to 28 in the study cohort, and 2 to 31 for eligible patients) and 5% and 6%, respectively, for arm B (95% CI, 0 to 26 in the study cohort, and 0 to 27 for eligible patients). Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication. CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.

Tamoxifen as an anti-tumour agent: oestrogen binding as a predictive test for tumour response.

Rats with growing 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary carcinomata were biopsied and oestrogen-binding capacity was measured using a Sephadex LH-20 chromatography method. Tumours were measured with calipers and animals were treated for 3 weeks with tamoxifen (50 mug/day, S.C.). Tumour response was determined by the size (cm2) before and after therapy. An increase in tumour regression (ten tumours) was seen with increasing oestrogen-binding sites determined by Scatchard analysis (P less than 0.01). Thirty tumours were used to determine oestrogen binding with a single dose of [3H]-oestradiol. The percentage tumour regression was linearly correlated with oestrogen-binding capacity (P less than 0.01), although some tumours with high oestrogen-binding capacities only partially regressed in response to tamoxifen therapy. The time of the oestrous cycle when biopsy occurred was not a critical factor in determining oestrogen binding for prediction of response. Oestrogen binding was reduced during tamoxifen therapy.

Delayed reconfiguration of a Guglielmi detachable coil mass associated with late occlusion of an adjacent aneurysm and parent vessel.

We present a case of asymptomatic, progressive, late occlusion of the left superior cerebellar artery (SCA) and an aneurysm arising from the junction of the SCA and basilar artery after embolization of an adjacent aneurysm arising between the left posterior cerebral artery and the left SCA. The delayed occlusion was associated with reconfiguration of the Guglielmi detachable coils at the neck of the treated aneurysm.

Intraventricular neurocytoma: a clinical and pathological study of three cases and review of the literature.

Three patients with a recently described tumor of neuronal origin, intraventricular neurocytoma, are presented. These tumors occur as intraventricular lesions in young patients, and the prognosis after surgical treatment is favorable. The initial pathological diagnosis of intraventricular neurocytoma may be difficult because of the striking resemblance of these tumors to oligodendroglioma and, to a lesser extent, ependymoma on light microscopic examination. Despite the use of wide-ranging panels of monoclonal antibodies, previous authors have not found any characteristic immunohistochemical staining patterns, but in our three patients, the use of synaptophysin, glial fibrillary acidic protein, and Leu-7 demonstrated staining patterns that may be useful in the diagnosis of this tumor. The monoclonal antibody Ki-67 was used to stain one tumor and showed a low cell proliferation rate. We have reviewed the clinical, radiological, and pathological features of these 3 patients and 17 previously described patients in an attempt to determine the important diagnostic features of intraventricular neurocytoma. Intraventricular neurocytoma should be considered in any young patient with symptoms of raised intracranial pressure and radiological evidence of an intraventricular lesion. Pathological diagnosis requires the use of electron microscopy to show features of neuronal differentiation; however, immunohistochemical demonstration of a neuronal phenotype is also a useful adjunct to diagnosis. Failure to use specialized techniques for pathological diagnosis will lead to misdiagnosis of these lesions as oligodendrogliomas, as was the initial diagnosis in 2 of our patients before review.

A simple simulation for the visualisation of CSF flow in infants with hydrocephalus.

Cerebrospinal fluid (CSF) flow was demonstrated incidentally in our unit during the routine cranial colour Doppler examination of infants with hydrocephalus. Pulsed Doppler analysis of the flow jets within CSF has shown that for each CSF flow jet there is a characteristic sinusoidal wave pattern that decreases in amplitude at the end of each jet episode. Any activity that transiently elevates the intracranial pressure, such as crying, increased the intensity of this signal. A study was subsequently carried out to investigate the origin of these clinical observations of CSF flow. Using a simple flow phantom, experiments with degassed water demonstrated the transient production of a Doppler signal at a stenosis in an otherwise uniform bore tube. We postulate that in infants with obstructive hydrocephalus, high CSF velocities in excess of 25 cm/s are produced as a result of the pressure caused by the excess cerebrospinal fluid. In some instances fluid jets may give rise to the production of microbubbles that act as transient but extremely efficient reflectors for the ultrasound, thus enabling the visualisation of CSF flow in these patients.

High resolution CISS imaging of the spine.

Spatial resolution remains one of the major problems and goals in spinal imaging. The high spatial resolution afforded by a novel sequence, constructive interference in steady state (CISS), provides a further refinement to MRI, the modality of choice in the investigation of suspected intraspinal pathology. Both complex and subtle abnormalities are more fully elucidated using CISS. It is now used in our institution as an adjunct to conventional imaging sequences in the diagnostic evaluation of complex intraspinal pathology. The anatomical information provided by CISS is of particular value in planning surgical interventions, most notably in the management of intraaxial and extraaxial cystic abnormalities, dysraphic malformations and disturbances of cerebrospinal fluid circulation, including post-traumatic and post-surgical scarring.

The outcome of fetal ventriculomegaly.

Over a 5 year period 38 cases of fetal ventriculomegaly were diagnosed at Queen's Medical Centre, Nottingham. There were 12 cases of spina bifida and all patients opted for a termination of pregnancy. There were 15 cases of isolated ventriculomegaly comprising seven cases of aqueduct stenosis, four abnormalities of the corpus callosum, one cavum septum pellucidum cyst, one case of porencephaly and two cases of mild lateral ventricular dilatation. The fetuses in this group had a relatively good outcome with five babies showing normal development, three with mild development delay and one with moderate developmental delay. There was one stillbirth and five patients opted for a termination of pregnancy. Associated abnormalities were seen in seven cases and these carried a poor prognosis with one fetus stillborn, one neonatal death, and three patients opted for a termination of pregnancy. Two babies were liveborn, one has severe developmental delay and the other one is normal. The four remaining cases included two Dandy Walker syndrome, one brain tumour and one case of subdural haemorrhage. There were three terminations of pregnancy and one stillbirth in this group. The outcome of fetal ventriculomegaly depends on the presence of associated abnormalities which carry a poor prognosis. It also depends on the timing of the diagnosis as most patients will opt for a termination of pregnancy if the diagnosis is made before 24 weeks gestation. A review of the literature reveals that, excluding terminations, fetuses with isolated ventriculomegaly have an 80% chance of survival and a 50% chance of normal development.

A comparative study of magnetic resonance imaging and computed tomography-assisted myelography in spinal dysraphism.

Thirty-seven patients with a wide spectrum of spinal dysraphic lesions were studied by both magnetic resonance imaging (MRI) and myelography complemented by computed tomography (CT). Magnetic resonance imaging proved to be superior for tissue characterization, overall anatomical definition, topographical relationships of the cranio-cervical junction and demonstration of the presence and extent of hydrosyringomyelia. Demonstration by CT myelography of fine neural structures such as the filum terminale and nerve roots remains the superior technique; however, with constantly improving spatial resolution and thinner-slice imaging, MRI will become increasingly competitive in this respect. The osseous component of these lesions was best demonstrated by CT myelography. A high incidence of associated syrinx (8/15 cases) was found in the diastematomyelia group, with an overall incidence of 15 cases in all the dysraphic patients studied. The use of both T1- and T2-weighted sequences is required for tissue characterization. Whilst both imaging modalities proved complementary in the investigation of spinal dysraphism, we suggest that, with its superior tissue characterization and anatomical display of these lesions. MRI should be the primary imaging technique. Avoidance of an invasive procedure and use of ionizing radiation confers additional benefits upon MRI. The relative ease and shorter examination time of MRI makes this technique ideal for pre- and post-operative monitoring and assessment.

Magnetic resonance imaging of spinal trauma.

A retrospective series of 118 magnetic resonance examinations of 110 patients who had sustained previous spinal trauma is reported. Examinations performed within 3 weeks of trauma showed extraspinal soft tissue (including ligamentous) injury in 48% and intraspinal lesions in 61% (mostly consisting of extradural haematoma and spinal cord contusion). In examinations performed more than 3 weeks after injury intraspinal abnormalities were shown in 51% and these represented spinal cord compression, atrophy, myelomalacia and syringohydromyelia. Magnetic resonance imaging has the unique capability of displaying non-invasively the late sequelae of spinal trauma permitting simultaneous evaluation of the extra-spinal soft tissues, vertebral column and spinal cord. It is therefore recommended as the technique of choice in the investigation of patients who have sustained previous spinal injury, particularly those with neurological deficit. In the acute phase potentially remediable causes of neurological impairment such as disc herniation or extradural haematoma can be identified. Signal changes in the cord may allow the prognosis for neurological recovery to be established. In the later stages sequelae such as cord atrophy, myelomalacia and syringohydromyelia are accurately identified and surgical therapy may be guided, where appropriate.

Gadolinium-enhanced magnetic resonance imaging of spinal tumours.

The use of gadolinium diethylenetriamine-penta-acetic acid (Gd-DTPA) (Magnevist) enhanced magnetic resonance imaging (0.15 T) in the assessment of spinal tumours is described. Thirty-five patients were entered into the study and a total of 39 examinations were performed. The information obtained from unenhanced T1- and T2-weighted spin-echo sequences was compared with the Gd-DTPA-enhanced T1 images. Thirty patients had intradural lesions and five had extradural lesions. A variable pattern of enhancement of intramedullary tumours was found, which in part reflected differences in the cystic component of the lesions. Extramedullary intra- and extradural lesions generally showed marked enhancement. The greatest contribution to management decisions was in the evaluation of intramedullary tumours where the use of contrast enhancement facilitated the precise localization of active tumour, differentiation of cystic and solid components of tumour, separation of tumour from peritumoral oedema and, in cases of suspected recurrence, aided distinction between tumour and both post-operative scarring and radiation damage.

Magnetic resonance imaging with even-echo rephasing sequences in the assessment and management of giant intracranial aneurysms.

The role of magnetic resonance imaging in the assessment of giant intracranial aneurysms was compared with angiography and contrast-enhanced computed tomography (CT) in 18 patients. The use of T1- and T2-weighted spin-echo (SE) sequences demonstrated both the presence and the evolution of thrombus within these lesions. High-velocity flow within the parent vessels and still-patent lumen could be defined as an area of absent signal. The use of even-echo rephasing (EER) sequences provided a rapid technique for demonstrating and confirming the presence of luminal flow, which is shown as areas of high signal. The combination of SE and EER techniques proved superior to CT in the assessment of thrombus and flow patterns in these lesions, as well as enabling superior demonstration of the patency of the parent vessel following surgical ligation. Computed tomography remains the most accurate method of defining the presence and location of associated calcification.

Review article: computed tomography and magnetic resonance in the diagnosis of intraventricular cerebral masses.

We describe a series of 60 cases of patients with masses arising within the cerebral ventricles. The site and relative frequency is noted for each histological type. The differential diagnosis depends on patient age and sex, site, morphology and number of masses, presence and type of hydrocephalus and the characteristics of the mass on computed tomography (CT) and magnetic resonance (MR) images. A review of the literature has been performed and this information collated with our own experience to give detailed descriptions of the typical features of each intraventricular mass. Attention is drawn to intraventricular neurocytoma, a recently described tumour that may be mistaken histologically for intraventricular oligodendroglioma or ependymoma. A comparison is made of the value of CT and MR in the diagnosis of intraventricular masses.

Brown-Sequard syndrome after management of vertebral hemangioma with intralesional alcohol. A case report.

STUDY DESIGN: This report describes Brown-Sequard syndrome after intralesional injection of absolute alcohol into vertebral hemangioma. OBJECTIVE: To discuss whether the described technique is safe in the management of vertebral hemangiomas. SUMMARY OF BACKGROUND DATA: The management of vertebral hemangiomas remains controversial. There have been reports of successful management using intralesional absolute alcohol. METHODS: The clinical and radiologic features of the reported complication are detailed. RESULTS: Intralesional injection of absolute alcohol caused Brown-Sequard syndrome. CONCLUSION: This case shows that intralesional alcohol injection cannot be considered a safe technique for management of vertebral hemangiomas with spinal cord compression.

Cerebellar encephalomalacia on magnetic resonance imaging after removal of acoustic tumor.

MRI is widely used for postoperative surveillance of patients undergoing surgery for removal of acoustic neuroma. The purpose of this study was to investigate the frequency and pattern of postoperative changes in the cerebellum and brain stem on MRI after removal of acoustic neuroma. A retrospective study was conducted in 30 consecutive patients who underwent postoperative MRI between 1994 and 1995. The timing of the scans after surgery ranged from 12 months to 10 years. T2 -weighted turbo spin-echo images revealed cerebellar encephalomalacia in 17 of 30 cases. Cerebellar encephalomalacia was found more consistently in patients who had large tumors and was more frequent after the suboccipital approach. Encephalomalacia is largely caused by gliotic changes in the adjacent cerebellar tissues after tumor removal.

Idiopathic diffuse erosion of the skull base presenting as cerebrospinal fluid rhinorrhoea.

We present an unusual case of generalized erosion of the skull base. We have not found a similar case reported in the world literature. The presenting symptom was spontaneous cerebrospinal fluid (CSF) rhinorrhoea which arose from a bony defect associated with herniation of the right temporal lobe into the sphenoid sinus. We discuss the management of such a case including imaging of the skull base and the endoscopic repair of the bony defect.