Apparent diffusion coefficient for molecular subtyping of non-gadolinium-enhancing WHO grade II/III glioma: volumetric segmentation versus two-dimensional region of interest analysis.

OBJECTIVES: To investigate if quantitative apparent diffusion coefficient (ADC) measurements can predict genetic subtypes of non-gadolinium-enhancing gliomas, comparing whole tumour against single slice analysis. METHODS: Volumetric T2-derived masks of 44 gliomas were co-registered to ADC maps with ADC mean (ADCmean) calculated. For the slice analysis, two observers placed regions of interest in the largest tumour cross-section. The ratio (ADCratio) between ADCmean in the tumour and normal appearing white matter was calculated for both methods. RESULTS: Isocitrate dehydrogenase (IDH) wild-type gliomas showed the lowest ADC values throughout (p < 0.001). ADCmean in the IDH-mutant 1p19q intact group was significantly higher than in the IDH-mutant 1p19q co-deleted group (p < 0.01). A volumetric ADCmean threshold of 1201 × 10-6 mm2/s identified IDH wild-type with a sensitivity of 83% and a specificity of 86%; a volumetric ADCratio cut-off value of 1.65 provided a sensitivity of 80% and a specificity of 92% (area under the curve (AUC) 0.9-0.94). A slice ADCratio threshold for observer 1 (observer 2) of 1.76 (1.83) provided a sensitivity of 80% (86%), specificity of 91% (100%) and AUC of 0.95 (0.96). The intraclass correlation coefficient was excellent (0.98). CONCLUSIONS: ADC measurements can support the distinction of glioma subtypes. Volumetric and two-dimensional measurements yielded similar results in this study. KEY POINTS: • Diffusion-weighted MRI aids the identification of non-gadolinium-enhancing malignant gliomas • ADC measurements may permit non-gadolinium-enhancing glioma molecular subtyping • IDH wild-type gliomas have lower ADC values than IDH-mutant tumours • Single cross-section and volumetric ADC measurements yielded comparable results in this study.

Predicting outcomes of vocational rehabilitation in patients with brain tumours.

OBJECTIVE: The aim of this study was to examine the outcome of a vocational rehabilitation programme for patients with brain tumours and to determine whether the outcome could be predicted at point of referral to the service. METHODS: Data was collected for 34 patients with brain tumours referred to the Macmillan vocational rehabilitation service. Work status at baseline (time of referral) and at discharge was compared. Logistic regression analyses were computed to identify which variables (demographic, tumour and treatment, functional and vocational) predicted work status at discharge from the service. RESULTS: Significantly, more patients were working at discharge from the service than at baseline. Having at least some physical disability decreased the likelihood of being in work at discharge from the service. CONCLUSIONS: The vocational rehabilitation programme for brain tumour survivors showed significant improvement over time. Functional ability affected the likelihood of working to some extent. Vocational rehabilitation services should be available to patients with brain tumours and should focus on supporting patients wishing to return to or maintain their current work. However, more support for brain tumour patients with physical impairments is needed.

The new World Health Organization Classification of Central Nervous System Tumors: what can the neuroradiologist really say?

The WHO Classification of Tumors of the Central Nervous System has become the worldwide standard for classifying and grading brain neoplasms. The most recent edition (WHO 2007) introduced a number of significant changes that include both additions and redefinitions or clarifications of existing entities. Eight new neoplasms and 4 new variants were introduced. This article reviews these entities, summarizing both their histology and imaging appearance. Now with more than 3 years of clinical experience following publication of the newest revision, we also ask, "What can the neuroradiologist really say?" Are there imaging findings that could suggest the preoperative diagnosis of a new tumor entity or variant?

The concepts, diagnosis and management of early imaging changes after therapy for glioblastomas.

Since postoperative radiotherapy plus concomitant temozolomide followed by adjuvant temozolomide has become standard treatment for glioblastoma, the phenomenon of early post-treatment enlargement of the imaged tumour volume, usually without clinical deterioration, has become widely recognised. The term pseudoprogression has been used to describe a poorly understood pathophysiological process. In this review, the pathophysiological concepts, relevance, diagnosis and management of patients with 'pseudoprogression' and 'pseudoresponse' are discussed. Guidelines are given with respect to radiological imaging modality, mode and frequency. Further biological and clinical insights into these phenomena require carefully designed prospective studies.

Diagnosis and treatment in neuro-oncology: an oncological perspective.

Although brain tumours are rare compared with other malignancies, they are responsible, in many cases, for severe physical and cognitive disability and have a high case fatality rate (13% overall survival at 5 years). Gliomas account for over 60% of primary brain tumours and usually present with one or more symptoms of raised intracranial pressure, progressive neurological deficit, seizures, focal or global cognitive decline. The diagnosis is made by a combination of imaging and histological examination of tumour specimen. Contrast-enhanced MRI is the gold standard imaging modality and provides highly sensitive anatomical information about the tumour. Advanced imaging modalities provide complementary information about brain tumour metabolism, blood flow and ultrastructure and are being increasingly incorporated into routine clinical sequences. Imaging is essential for guiding surgery and radiotherapy treatments and for monitoring response to, and progression of, therapy. However, changes in imaging over time may be misinterpreted and lead to incorrect assumptions about the effectiveness of treatments. Thus, the disappearance of contrast enhancement and resolution of oedema after anti-angiogenesis treatments is seen early while conventional T(2) weighted/FLAIR sequences demonstrate continual tumour growth (pseudoregression). Conversely imaging may suggest lack of efficacy of treatment e.g. increasing tumour size and contrast enhancement following chemoradiation for malignant gliomas (pseudoprogression), which then stabilise or resolve after a few months of continued treatment and that paradoxically may be associated with a better outcome. These factors have led to a re-evaluation of the role of standard sequences in the assessment of treatment response spurning interest in the development of quantitative biomarkers.

Post-streptococcal opsoclonus-myoclonus syndrome associated with anti-neuroleukin antibodies.

BACKGROUND: Adult opsoclonus-myoclonus (OM), a disorder of eye movements accompanied by myoclonus affecting the trunk, limbs, or head, is commonly associated with an underlying malignancy or precipitated by viral infection. METHODS: We present the first two reports of post-streptococcal OM associated with antibodies against a 56 kDa protein. Two young girls presented with opsoclonus and myoclonus following a febrile illness and pharyngitis. Protein purification techniques were employed. Amino acid sequences of human neuroleukin (NLK) and streptococcal proteins were compared using the protein-protein BLAST application. RESULTS: The antigen was identified as NLK (glucose-6-phosphate isomerase, GPI). GPI is present on the cell surface of streptococcus making the protein a candidate target for molecular mimicry. CONCLUSIONS: We have identified NLK as an antigenic target in two patients with post-streptococcal OM. The pathogenicity of the antibodies is uncertain. The potential role of anti-neuroleukin antibodies in the pathogenesis of OM is discussed. We propose that OM may represent a further syndrome in the growing spectrum of post-streptococcal neurological disorders. The role of streptococcus in OM and the frequency with which anti-NLK responses occur in both post-infectious and paraneoplastic OM should be investigated further.

Fatal radiation myelopathy after high-dose busulfan and melphalan chemotherapy and radiotherapy for Ewing's sarcoma: a review of the literature and implications for practice.

Radiation myelopathy is a rare, devastating, late effect of radiotherapy to the spinal cord. Spinal cord tolerance is currently accepted as about 50 Gy in 1.8-2 Gy fractions. However, the effect of chemotherapy on cord tolerance is unclear. This issue is important, given the increasing use of chemotherapy in combination with radiotherapy. We describe the case of a 17-year-old boy with a right apical paraspinal Ewing's tumour in the neck treated with induction chemotherapy, high-dose chemotherapy (busulfan and melphalan) with peripheral stem-cell rescue and, 4 months later, radiotherapy to the primary tumour site (cervical cord received 50 Gy in 30 fractions). After a latent period of 4 months, he developed a progressive, severe and ultimately fatal radiation myelopathy, which we suggest was due to a synergistic interaction between the high-dose chemotherapy and the radiotherapy. The use of such chemotherapy regimens in Ewing's tumours should be carefully considered, particularly when radiotherapy encompassing the spinal cord is an essential component of management.

A follow up study of patients with paraneoplastic neurological disease in the United Kingdom.

OBJECTIVES: To examine the range of clinical phenotypes, tumour associations, relevant investigations, response to therapy and outcome in a large series of non-selected patients with paraneoplastic neurological disease (PND) affecting the central nervous system (CNS) in the United Kingdom. METHODS: Data were obtained on patients either through direct referral or through the British Neurological Surveillance Unit (BNSU) from February 2000 to January 2001. Physicians were asked to supply information about age and sex of patients, presenting neurological syndromes, the basis of the diagnosis of PND, any associated malignancy, and treatment. Case notes were reviewed and follow up data obtained where possible one year after notification. RESULTS: A total of 63 patients (48 females, 15 males) were identified, 48 through the BNSU and 15 through direct referral. Of these 52 were diagnosed as having definite PND, 10 probable PND, and 1 possible PND. The median age of onset of PND was 66 years (range 30-80 years) and only 7 patients (11%) were less than 50 years at presentation. In 53 patients (84%) the PND preceded the diagnosis of cancer. Paraneoplastic sensory neuronopathy, paraneoplastic encephalomyelitis, and paraneoplastic cerebellar degeneration (PCD) were the most common syndromes reported. The benefit of magnetic resonance imaging in the diagnosis of the disease was limited, while fluorodeoxyglucose positron emission tomography was shown to be useful for the detection of an occult malignancy in 10 out of 14 patients. Antineuronal antibodies were positive in 44/57 (77%) of cases. The following tumours were diagnosed: small cell lung cancer (30%), breast cancer (14%), ovarian cancer (8%), non-small cell lung cancer (8%), Hodgkin's lymphoma (6%), other (16%). With the exception of PCD associated with mesothelioma all other tumours diagnosed in these patients had been previously documented as being associated with PND. Only treatment of the tumour was found to be associated with a stable or improved neurological outcome at last follow up (Fisher's exact test = 4.7, p<0.03). Median survival time was 43 months (95% CI 28 to 57) from onset of neurological disease as calculated using the Kaplan-Meier survival analysis. CONCLUSIONS: PND has a striking female preponderance usually affecting patients in their sixth decade and above. The median survival in our study was 43 months. The majority of patients with PND are not known to have cancer at the time of diagnosis. Our study confirms the importance of diagnosing and treating the underlying tumour.

MRI of the brain with ultra-short echo-time pulse sequences.

As well as the long-T2 relaxation components normally detected with conventional imaging techniques, the brain has short-T2 components. We wished to use ultra-short (0.08 ms) echo time (UTE) pulse sequences to assess the feasibility of imaging these in normal subjects and patients. UTE sequences were employed, with or without fat suppression, 90 degree long-T2 suppression pulses, and selective nulling of long-T2 components using an inversion pulse. Subtraction of later echoes from the first was also used to reduce the signal from long-T2 components. We studied dive normal subjects and 15 patients with various diseases. Short-T2 components were demonstrated in grey and white matter. Increased signal from these components was seen in meningeal disease, probable calcification, presumed cavernomas, melanoma metastases and probable gliosis. Reduced signal was seen in some tumours, infarcts, mild multifocal vascular disease and vasogenic oedema. Further development and evaluation of these pulse sequences is warranted.

Apolipoprotein E genotypes and clinical outcome in Guillain-Barré syndrome.

BACKGROUND: Polymorphism of the gene encoding the cholesterol transport protein apolipoprotein E (APOE, gene; apoE, protein), known to be involved in axonal regeneration and remyelination, influences outcome after a variety of central nervous system disorders. Apolipoprotein E gene polymorphisms could affect recovery from Guillain-Barré syndrome. OBJECTIVE: To correlate APOE genotypes with residual disability and degree of improvement in Guillain-Barré syndrome, assessed one year after presentation METHODS: 91 patients with the syndrome were recruited from southeast England and their APOE genotypes were determined. RESULTS: There were no clear differences in APOE genotype or allele frequencies when comparing the 91 patients with controls, nor when comparing 81 patients with good outcome and 10 with poor outcome. CONCLUSIONS: APOE genotype did not influence susceptibility to Guillain-Barré syndrome or recovery from it. This may be because our sample size of 91 was not sufficiently large to detect small differences in recovery associated with different APOE genotypes, or because cholesterol transportation is not a crucial rate limiting step in peripheral nerve regeneration.

A model for evaluating radiological impacts on organisms other than man for use in post-closure assessments of geological repositories for radioactive wastes.

Bioaccumulation and dosimetric models have been developed that allow the computation of dose rates to a wide variety of plants and animals in the context of the deep geological disposal of solid radioactive wastes. These dose rates can be compared with the threshold dose rates at which significant deleterious effects have been observed in field and laboratory observations. This provides a general indication of whether effects on ecosystems could be observable, but does not quantify the level of those effects. To address this latter issue, two indicator organisms were identified and exposure-response relationships were developed for endpoints of potential interest (mortality in conifers and the induction of skeletal malformations in rodents irradiated in utero). The bioaccumulation, dosimetry and exposure-response models were implemented and used to evaluate the potential significance of radionuclide releases from a proposed deep geological repository for radioactive wastes in France. This evaluation was undertaken in the context of a programme of assessment studies being performed by the Agence nationale pour la gestion des déchets radioactifs (ANDRA).

Intravenous immunoglobulin in neurological disease: a specialist review.

Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2).

The role of [18F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders.

The detection of an occult tumour in a patient with a suspected paraneoplastic neurological disorder (PND) may be difficult because of the limitations of conventional imaging techniques. [(18)F]fluoro-2-deoxyglucose-PET (FDG-PET) can visualize a small tumour anywhere within the body. We retrospectively reviewed the case notes of 43 unselected patients with suspected PND referred for FDG-PET scanning to determine how useful this technique was when conventional imaging was negative. All patients had undergone standard radiological investigations and bronchoscopy (where appropriate) prior to PET scanning. There were discrete areas of hypermetabolism suggestive of malignancy (positive) in 16 patients (37%). A tissue diagnosis of cancer was subsequently made in seven patients (two at post-mortem), further radiological studies were suggestive of cancer in one patient, one patient subsequently presented with a metastatic deposit which was biopsied, and four patients died shortly afterwards without a post-mortem. In three patients, subsequent investigations were negative for cancer. Serum anti-neuronal antibodies were present in 43% and CSF oligoclonal bands were present in 46% of patients with positive PET scans compared with 16 and 26%, respectively, in PET-negative patients, but this was not significant. Only one patient with a negative scan has been diagnosed subsequently as having malignancy on prolonged follow-up. These findings confirm that FDG-PET scanning is a useful technique in the detection of small tumours in patients with suspected PND. False positives and false negatives do occur, but at a sufficiently low frequency to justify the clinical usefulness of this technique.

Primary diffuse leptomeningeal gliomatosis simulating tuberculous meningitis.

Three patients are reported on who presented with communicating hydrocephalus due to presumed tuberculous meningitis. Subsequent clinical deterioration despite antituberculous chemotherapy prompted reassessment with FDG-PET scanning and meningeal biopsy in one case and repeat CSF cytology with special staining in the second. The third patient died and postmortem confirmed a diagnosis of primary diffuse leptomeningeal gliomatosis. In the first two patients, MRI of the entire neuraxis showed no evidence of a primary intraparenchymal tumour. These cases emphasise the need for repeated reassessment in patients with culture negative lymphocytic meningitis. In addition, this is the first report of FDG-PET scanning in leptomeningeal gliomatosis.

Cerebral haemangiopericytoma treated with conservative surgery and radiotherapy.

Cerebral haemangiopericytomas are rare tumours that resemble meningiomas but behave more aggressively, with a tendency to metastasize. We report two patients with haemangiopericytoma who had limited surgical resections owing to perioperative blood loss but who had massive tumour shrinkage after a course of radical radiotherapy. We suggest a more conservative surgical approach to the management of these tumours.

High-grade glioma mimicking acute viral encephalitis--three case reports.

The clinical features of viral encephalitis consist of headache, fever, seizures and encephalopathy. We report three patients with high-grade gliomas presenting with encephalitic illnesses. The diagnosis of brain tumour should always be borne in mind if definite evidence for a viral infection is not obtained.

Aminoglycoside-associated hypomagnesaemia in children with cystic fibrosis.

Hypomagnesaemia in children with cystic fibrosis (CF) is under-recognized. We report a child with CF who developed significant hypomagnesaemia following intravenous (i.v.) treatment with aminoglycosides for exacerbations of Pseudomonas aeruginosa infection. Three additional cases have also been observed. Investigations in two patients have revealed excessive renal loss of magnesium. It is postulated that renal tubular damage secondary to the cumulative effects of repeated courses of aminoglycosides resulted in hypomagnesaemia, and we suggest screening for this problem by monitoring serum magnesium regularly in all patients with CF receiving multiple courses of aminoglycosides.